key: cord-0017905-p9vt7wp4 authors: Signore, Alberto; Casali, Massimiliano; Lauri, Chiara title: An easy and practical guide for imaging infection/inflammation by [(18)F]FDG PET/CT date: 2021-06-01 journal: Clin Transl Imaging DOI: 10.1007/s40336-021-00435-y sha: e48a5697f5cf8b06592169b4e3056066a08b9c4f doc_id: 17905 cord_uid: p9vt7wp4 AIM: The aim of this mini-review was to summarize the role of positron emission tomography/computed tomography (PET/CT) with (18)Fluorine-fluorodeoxyglucose ([(18)F]FDG) in inflammatory and infective processes, based on the published scientific evidence. METHODS: We analysed clinical indications, patient preparation, image acquisition protocols, image interpretation, pitfalls and how to make the report of cardio-vascular diseases, musculoskeletal diseases and other inflammatory and infective systemic diseases. Results of this analysis are shown in practical tables, easy to understand for daily routine consultation. CONCLUSIONS: Despite [(18)F]FDG is currently used in several inflammatory and infective diseases, standardized interpretation criteria are still needed in most cases. It is, therefore, foreseen the execution of multicentre clinical studies that, by adopting the same acquisition and interpretation criteria, may contribute to the standardization of this imaging modality. The diagnosis of an infection by means of imaging modalities mainly relies on the possibility to exclude aseptic inflammation due to degenerative process, or autoimmune/allergic reactions or simply irritative causes. Several radiological and Nuclear Medicine procedures are, therefore, involved, in the search of which modality is more accurate in which clinical setting. From the Nuclear Medicine point-of-view, this challenge to differentiate an infection from a sterile inflammation, has led to the production of hundreds of different radiopharmaceuticals that have open new ways to the possibility to specifically image the underlying process from a molecular point of view [1, 2] . Radiolabelled antibiotics [3, 4] or glucose derived sugars [5] [6] [7] [8] have shown the potential to image bacteria, and, on the other hand, radiolabelled cytokines [9] or monoclonal antibodies [10] open the possibility to image different white blood cell subsets for histopathological characterization in vivo of the inflammatory/infective process. Despite this enthusiastic output of new radiopharmaceuticals, the scintigraphy with radiolabelled white blood cells (WBCs), developed in early 1970 [11, 12] , remains the Nuclear Medicine modality of choice for routine and accurate diagnosis of infection. Over the years, we learned that this technique strictly relies on the application of precise labelling modalities, image acquisition protocol and interpretation criteria that have been published as guidelines by the European Association of Nuclear Medicine (EANM) [13] [14] [15] [16] [17] [18] . In the last two decades, given the increasing availability and application of positron emission tomography/computed tomography (PET/CT) with 18 Fluorine-fluorodeoxyglucose ([ 18 F]FDG) in several clinical contexts, infection and inflammation have also been extensively studied [19] . The great sensitivity of [ 18 F]FDG, together with the high quality of images provided by new generation tomographs, suggest the use of this modality for both diagnostic and follow-up purposes [19] . Nevertheless, well-standardized interpretation criteria, as it has been done for radiolabelled WBC scintigraphy, still do not exist for many infective or inflammatory disorders, thus resulting in different approaches adopted by each centre, and, most important, in a wide variability of reported accuracies of this modality that do not allow to make a direct comparison of different studies. The need of well standardized protocols for acquisition and interpretation of [ 18 F]FDG PET/CT images in this field, has become essential amongst the Nuclear Medicine community, as demonstrated by the increasing number of consensus documents and proposed interpretation criteria that have been published, for example, for imaging of prosthetic joint infections [20] [21] [22] [23] [24] , diabetic foot osteomyelitis [25] [26] [27] , cardiovascular inflammations and infections [18, [28] [29] [30] [31] [32] [33] [34] , spondylodiscitis [35] , inflammatory bowel diseases [36] and, more recently, for imaging with [ 18 F]FDG by PET/ Magnetic Resonance Imaging (MRI) [37, 38] . Nonetheless, the proposed interpretation criteria for [ 18 F] FDG PET/CT imaging in many clinical indications still need to be universally validated. This mini-review aims at providing an overview on the state of art of [ 18 F]FDG PET/CT imaging in musculoskeletal infections, cardiovascular infections and inflammations, and systemic inflammatory and infective diseases with particular emphasis on image acquisition protocols and interpretation criteria. In this mini-review, we summarize the available procedural recommendations for [ 18 quently observed pitfalls and artefacts that need to be considered for a correct interpretation of the scan. -Final report: describes how to report the exam (in addition to demographic data and technical information of the scan, type of tomograph, body weight and administered dose) with a focus on essential parts of the report. Time between injection and image acquisition should always be included in the report since it could be particularly useful for both long-term follow-up and therapy evaluation studies when SUV max are compared. Results are summarized in easy to read tables, aiming at proving a useful tool in daily practice (Tables 1, 2, 3, and 4). It emerges that standardized protocols for patient preparation, image acquisition and interpretation criteria exist only for very limited clinical indications in the field of infection and inflammation and, in particular, for infective endocarditis, cardiac implantable devices infections, left ventricular assist device-associated infections, cardiac sarcoidosis, large vessel vasculitis and spondylodiscitis. For all other clinical indications, the recommendations for patient preparation and the acquisition protocols, commonly adopted for oncologic studies, are currently applied. As far as image interpretation is concerned, several criteria have been proposed for vascular graft infections, osteomyelitis, diabetic foot infections, Qualitative analysis Description of lymph nodes (lambda sign), pulmonary, pleural, lacrimal and a salivary glands, brain, musculoskeletal and brain involvement; For assessing myocardial involvement, see Table 1 Semi-quantitative analysis prosthetic joint infections, and systemic infections/inflammations, but they still need to be validated in larger multicentre studies being the reported diagnostic accuracy of single centre studies, extremely variable and generally lower than the diagnostic accuracy of WBC scintigraphy [20, 27] . In summary, this article and the following, published in this journal, provide a useful tool for identifying several patterns of [ 18 F]FDG uptake able to discriminate between an infection and a sterile inflammation aiming at increasing the specificity and the accuracy of this radiopharmaceutical. This may have a great clinical impact on the management of each specific disease, may help to smooth the wide heterogeneity that is still evident in literature and will lay the basis for future comparative studies. The definition of disease-specific acquisition protocols is warranted to increase the specificity and accuracy of this imaging modality. Moreover, it is mandatory, that the definition of precise and standardized interpretation criteria for [ 18 F]FDG PET/CT imaging in different infective or inflammatory disorders need to be adopted and shared by several institutions and validated in large, possibly multicentre, studies. Conflicts of interest Alberto Signore, Chiara Lauri and Massimiliano Casali have nothing to declare. This article does not contain any studies with human or animal subjects performed by any of the authors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. Current status of molecular imaging in infections Current status of molecular imaging in inflammatory and autoimmune disorders Imaging bacteria with radiolabelled quinolones, cephalosporins and siderophores for imaging infection: a systematic review PET radiopharmaceuticals for specific bacteria imaging: a systematic review Validation of 2-18F-fluorodeoxysorbitol as a potential radiopharmaceutical for imaging bacterial infection in the lung Biodistribution and radiation dosimetry of the enterobacteriaceae-specific imaging probe [(18)F]fluorodeoxysorbitol determined by PET/CT in healthy human volunteers Infection imaging with (18)F-FDS and first-in-human evaluation Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography SPECT radiopharmaceuticals for imaging chronic inflammatory diseases in the last decade Antibody-based tracers for PET/SPECT imaging of chronic inflammatory diseases Bone accumulation of 99mTc-labeled leucocytes Survey of radioactive agents for in vitro labeling of phagocytic leukocytes. I Soluble agents Guidelines for the labelling of leucocytes with 99mTc-HMPAO. Inflammation/ infection taskgroup of the European Association of Nuclear Medicine Guidelines for the labelling of leucocytes with 111In-oxine. Inflammation/infection taskgroup of the European Association of Nuclear Medicine Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline Consensus document for the diagnosis of peripheral bone infection in adults: a joint paper by the EANM, EBJIS, and ESR (with ESC-MID endorsement) Consensus document for the diagnosis of prosthetic joint infections: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement) Recommendations on nuclear and multimodality imaging in ie and cied infections EANM/SNMMI guideline for 18F-FDG use in inflammation and infection The role of imaging techniques to define a peri-prosthetic hip and knee joint infection: multidisciplinary consensus statements FDG-PET in patients with painful hip and knee arthroplasty: technical breakthrough or just more of the same The importance of the location of fluorodeoxyglucose uptake in periprosthetic infection in painful hip prostheses Diagnosing infection in the failed joint replacement: a comparison of coincidence detection 18 F-FDG and 111 In-labeled leukocyte/ 99m Tc-sulfur colloid marrow imaging FDG PET for differentiation of infection and aseptic loosening in total hip replacements: comparison with conventional radiography and threephase bone scintigraphy Can sequential 18 F-FDG PET/CT replace WBC imaging in the diabetic foot? Diabetic foot infections: the diagnostic challenges Comparison of white blood cell scintigraphy, FDG PET/CT and MRI in suspected diabetic foot infection: results of a large retrospective multicenter study Multimodality imaging in the diagnostic work-up of endocarditis and cardiac implantable electronic device (CIED) infection Imaging modalities for the diagnosis of vascular graft infections: a consensus paper amongst different specialists Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation-(4Is) related cardiovascular diseases: a joint collaboration of the EACVI and the EANM: summary Diagnostic performance of 18F-FDG-PET/CT in vascular graft infections SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 1 of 2-evidence base and standardized methods of imaging Reviewer group; Members of EANM Cardiovascular; Members of EANM Infection & Inflammation; Members of Committees, SNMMI Cardiovascular; Members of Council, PET Interest Group; Members of ASNC; EANM Committee Coordinator. FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC Distribution patterns of 18F-fluorodeoxyglucose in large vessels of Takayasu's and giant cell arteritis using positron emission tomography Joint EANM/ESNR and ESCMID-endorsed consensus document for the diagnosis of spine infection (spondylodiscitis) in adults Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines Hybrid imaging in Crohn's disease: from SPECT/CT to PET/MR and new image interpretation criteria PET/MRI in Infection and Inflammation Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations