key: cord-0811693-xntgvujx authors: Flood, Ann Barry; Swarts, Steven G.; Krishna, Murali C.; Gallez, Bernard title: Special Issues of AMR on the Occasion of the 85th Birthday of Harold M. Swartz (HMS): Overview of Part 2 Articles and HMS’ Citations on Magnetic Resonance date: 2022-01-05 journal: Appl Magn Reson DOI: 10.1007/s00723-021-01459-3 sha: 390e74774bcf4db481a55905ad9815e8f9271b7d doc_id: 811693 cord_uid: xntgvujx nan I am especially grateful to the editors of this issue, Ann Flood, Steve Swarts, Murali Krishna, and Bernard Gallez who have worked so hard and diligently. And, of course, I am especially grateful to Ann who has had the leading role in conceptualizing this special issue and guiding it through to its completion, including untold hours of effort to improve the clarity of each manuscript. Most of all, I am grateful to Ann because of the many ways that she has made my personal and professional life so satisfying, including her change in career, after she became emerita as a leading health services researcher, to become an outstanding collaborator for advancing so many of what started as my professional interests and making them our interests. I also thank the tremendous help and tolerance of Kev Salikhov and Laila Mosina who have gone way beyond the responsibilities of the editorial guidance for having these issues as part of the AMR, facilitating and guiding at every step of the way to successfully herd the contributors (cat-like) into completing the manuscripts while not departing from rigorous peer review of each manuscript (except for the editorials and my histories which, in the tradition of the Journal, are not peer-reviewed). Part 2 of the special issue starts with four manuscripts which present historical overviews of Harold M. Swartz' (HMS') contributions to magnetic resonance. The initial histories are authored by HMS and present a detailed overview of his laboratories' efforts in three areas of magnetic resonance: (1) free radicals and paramagnetic metals in biological systems and associated EPR instrumental developments advancing in vivo measurements, (2) biodosimetry, particularly focused on using EPR to assess dose in large-scale emergencies, and (3) oximetry, particularly focusing on improving medical decision-making where hypoxia plays a key role in therapeutic success. The fourth historical overview/review is authored by Tadeusz Sarna and colleagues, and focuses on the contributions of EPR and its important implications for understanding melanins and their biological interactions. It particularly focuses on the important and complex area of the interactions of melanin with metals and how these impact the potential cytotoxic effects of metal ions. The next four articles present recent developments in in vivo EPR instrumental developments. Wilson Schreiber et al. describe the major modifications that were made to in vivo EPR to make the instruments better suited to the needs of both the intended end-use (for in vivo dosimetry and oximetry) and the end-users (who need to have reliable and clinically relevant data available quickly and well integrated into clinical workflow including being operated by available technicians). Sergei Petryakov et al. report on the development of surface resonators used with lowfrequency continuous wave in vivo EPR. These resonators have the flexible cables needed to conveniently attach the detection loop to the skin surface and the high sensitivity needed to avoid SRN problems associated with subject motion during in vivo measurements. Hiroshi Hirata and Harold Swartz review resonator developments in three contexts: preclinical oximetry and free radical measurements in small rodents, clinical (human) oximetry, and human dosimetry. They discuss guidelines for developing and optimizing resonators for each of these specific preclinical and clinical applications. Finally, Jim Hyde and his colleagues discuss their hypothesis that, with low Q-value sample resonators, dispersion EPR can provide better signal to noise. To achieve this, high microwave power is needed, and this is problematic for these samples. They found that the primary source of noise is phase noise at the receiver from leakage of microwave through the circulator. Their paper then focuses on the design of reflector bridges with the goal of minimizing this source of noise. The next group of articles discusses the physical underpinnings for advancing EPR, especially in vivo EPR. Jerzy Koziol and Wojciech Froncisz lead off with an analysis of influence of spurious signals on automatic frequency control (AFC) in EPR spectrometers. While the primary source of spurious signals is leakage across the circulator in the microwave bridge, the signals reflected from the connectors in the line between the circulator and resonator further modify that signal. They discuss two ways to overcome the potential degradation in performance of the AFC from these spurious signals. Joseph Kao and colleagues at U. of Maryland in Baltimore and the Eatons' lab at U. of Denver report on the use of EPR lineshapes of nitroxide diradicals and their relationship to spin relaxation because of their importance of their use in structural studies. It had been suggested that the usual maximum distance of 5-6 Å, for their use as a measure of interactions for relaxation enhancement, might be extended to a distance as long as 9 Å if the linker in the diradical were more flexible. Using carefully developed synthetic pathways, they made two dinitroxides with interspin distances of about 9 Å and J > > AN, but with more flexible amide and ethylenediamine linkers. They then showed that modulation of dipolar interactions at distances of about 9 Å is not an effective electron spin relaxation mechanism, even for dinitroxides with relatively flexible linkers. Jay Zweier and colleagues report on methods to increase the speed of EPR imaging with nitroxides. They developed and evaluated the use of fast millisecond scan EPR projection acquisition along with a novel reconstruction algorithm optimized for 3D spatial EPR image reconstruction from a high number of noisy projections. This reconstruction method utilizes the raw image projection data and zero gradient spectrum to account for EPR line shape and hyperfine structure of any given paramagnetic probe, without the need for deconvolution that is poorly suited for high noise data. Using fast-scan EPR imaging with this reconstruction method, they found that, while the approach seems effective, excess noise due to technical limitations of currently available instrumentation limited the gains achievable with the new approach. It is likely that future developments of EPR instrumentation will overcome the problems with noise, and image resolutions approaching 100 μm should be possible. Alex Smirnov and colleagues present an experimental verification of a prevailing but not yet verified assumption of the use of nitroxides to measure oxygen levels. They measured the effects of molecular oxygen in air and pure oxygen at atmospheric pressure on continuous wave EPR spectra of six structurally different nitroxides. Overall, the data further establish nitroxides as robust EPR molecular probes to measure the product of local oxygen concentration and its translational diffusion coefficient under a wide range of conditions such as pH and electrolyte concentrations. The last set of articles in this special issue deal with EPR and biodosimetry, focusing on its clinical uses for retrospective biodosimetry after unplanned exposures to ionizing radiation. Beinke and colleagues review the value of biological biodosimetry and EPR spectroscopy for medical management of people experiencing acute radiation syndrome. They conclude that biological biodosimetry (based on molecular biomarkers, especially gene expression analysis) and in vivo EPR represent very promising screening tools for rapid triage dosimetry in early phase diagnostics. They also note that biological biodosimetry can be employed to estimate whole-body dose, while EPR dosimetry on nails, bone, or teeth could be used to determine partial body doses which in combination is very useful for medical management. Vijay Singh et al. summarize the current state of development of drugs that could be given after exposures to ameliorate the damaging effects of radiation. This paper discusses the importance of determining who has actually received a life-threatening exposure, so that the drugs can be given to the people who need them. It concludes that EPR biodosimetry based on measurements in vivo of fingernails and toenails could be especially valuable, because it provides information about the heterogeneity of the dose as well as its magnitude. Continuing a long-standing collaboration between groups in Japan and Dartmouth, Nakai et al. show that the often-expressed concern about exposure to sunlight potentially compromising EPR tooth dosimetry is not really limiting. They carefully measured the effect of plausible levels of exposure from sunlight and found that this would not result in a large enough effect to perturb the utility of EPR tooth dosimetry. The final paper is from a leading group of EPR biodosimetry experts from France and the US reporting on the feasibility of using clipped nails for biodosimetry. Tkatchenko et al. investigated the well-known problem that the EPR signal induced by clipping overlaps with the signal induced by radiation, thereby confounding the interpretation of source of the signal. While other techniques like soaking nails have been investigated to try to overcome this problem, this team analyzed the EPR Effects of Nitroxides on the Magnetic Field and Temperature Dependence of 1/T1 of Solvent Water Protons Further Evidence that the Pigment in the Dubin-Johnson Syndrome is not Melanin Measurement of Intracellular Oxygen. In Handbook of Biomedicine of Free Radicals and Antioxidants Influence of Metabolic Inhibitors on the Nitroxide Reduction in the Cells Oxygen Dependent Metabolism of Potential MR Contrast Agents Modification of Relaxation of Lipid Protons by Molecular Oxygen and Nitroxides Cellular Metabolism of Water-Soluble Nitroxides: Effect on Rate of Reduction of Cell/Nitroxide Ratio, Oxygen Concentrations, and Permeability of Nitroxides Use of Nitroxides to Measure Redox Metabolism in Cells and Tissues Identification and Characterization of a Tetracycline Semiquinone Formed During the Oxidation of Minocycline Interactions Between Cells and Nitroxides and Their Implications for Their Uses as Biophysical Probes and as Metabolically Responsive Contrast Agents for Use of Field Gradient EPR to Measure Diffusion of Nitroxides in Tissues Contrast Enhancement in ESR Imaging: Role of Oxygen Detection of Diffusion of Oxygen by Fast Scan EPR Imaging Measurement of Pertinent Oxygen Concentrations in Biological Systems The Effect of Melanin on Iron Associated Decomposition of Hydrogen Peroxide. Free Rad Spin Trapping Studies on the Metabolic Activation of Carbon tetrachloride in Rat Liver Microsomes Incubated Under Steady-State Oxygen Pressures Metabolically Responsive Contrast Agents Evaluation of Dibromo Nitrosobenzene Sulfonate as a Spin Trap in Biological Systems. Free Rad The Cellular-Induced Decay of DMPO Spin Adducts of ·OH and ·O2. Free Rad Oxygen Gradients in CHO Cells: Measurement and Characterization by Electron Spin Resonance Modulation of Water Proton Relaxation Rates by Liposomes Containing Paramagnetic Materials Sources of Longitudinal Relaxation Rates Observed in Melanotic Melanoma: An In vitro Study of Synthetic Melanins Oxidation of Hydroxylamines to Nitroxide Spin Labels in Living Cells Delivery of Nitroxide Spin Labels to Cultured Cells by Liposomes Electron Spin Resonance Imaging of Tissues with Lipid-Rich Areas Distribution of 5-Doxylstearic Acid in the Membranes of Mammalian Cells Kinetics of Enzyme-Mediated Reduction of Lipid Soluble Nitroxide Spin Labels by Living Cells Reduction Mechanism of the Spin Probe Tempol in Liver Microsomes. In Medical, Biomedical and Chemical Aspects of Free Radicals Reduction of Doxyl Stearates by Ascorbate in Unilamellar Liposomes Rapid Assessment of Liposomal Stability in Blood by an Aqueous Nitroxide Spin Label Effects of Oxygen on the Metabolism of Nitroxide Spin Labels in Cells Three Dimensional Electron Spin Resonance Imaging Metabolism of Aqueous Soluble Nitroxides in Hepatocytes: Effects of Cell Integrity, Oxygen and Structure of Nitroxides Measurement of Time-Resolved Oxygen Concentration Changes in Photosynthetic Systems by Nitroxide-Based EPR Oximetry Interactions of Nitroxides with Plasma and Blood: Effect on 1/T1 of Water Protons Development of Nitroxides for Selective Localization Inside Cells Cellular Metabolism of Proxyl Nitroxides and Hydroxylamines Electron Spin Resonance Microscopy of an In vitro Tumor Model Metabolism in Rat Liver Microsomes of the Nitroxide Spin Probe Dextran Magnetite as a Liver Contrast Agent Exchange and Shuttling of Electrons by Nitroxide Spin Labels Synthesis of Nitroxyl (Aminoxyl) Labeled Probes for Studies of Intracellular Environment by EPR and MRI Blood Clearance of Dextran Magnetite Particles Determined by a Non-Invasive In Vivo ESR Method The Products of the Reduction of Doxyl Stearates in Cells are Hydroxylamines as Shown by Oxidation by 15 N-Perdeuterated Tempone The Use of In Vivo EPR to Follow the Pharmacokinetics of Drugs Analysis of the Reduction of Nitroxides by Flavin Mononucleotide Chemical and Electrochemical Reduction Rates of Cyclic Nitroxides (Nitroxyls) Spectral-Spatial ESR Imaging as a Method of Noninvasive Biological Oximetry Nonperturbing Test for Cytotoxicity in Isolated Cells and Spheroids Using Electron Paramagnetic Resonance Potential of Albumin Labeled with Nitroxides as a Contrast Agent for Magnetic Resonance Imaging and Spectroscopy Reduction of Nitroxides in Whole Blood, Erythrocytes, and Plasma Oximetry in Cells and Tissues Using a Nitroxide-Liposome System Measurements of the Concentration of Oxygen in Biological Systems Using EPR Techniques 1 GHz In Vivo ESR Spectrometer Operating with a Surface Probe Metabolism of Nitroxide Spin Labels in Subcellular Fractions of Rat Liver, I. Reduction by Microsomes Liposome Encapsulated MnCl2 as a Liver Specific Contrast Agent for Magnetic Resonance Imaging Measurement of Oxygen by EPRI and EPRS Principles of the Metabolism of Nitroxides and Their Implications for Spin Trapping Metabolism of Nitroxide Spin Labels in Subcellular Fractions of Rat Liver. II. Reduction in the Cytosol The Use of ESR to Measure Oxygen in Extended Biological Samples Mapping Oxygen Concentrations with 4D Electron Spin Resonance Spectral-Spatial Imaging Interactions of Melanin with Oxygen (and Related Species) Selective Suppression of Lipid Resonances by Lipid-Soluble Nitroxides in NMR Spectroscopy Thermal Tomography Using Electron Spin Resonance (ESR) Techniques The Use of Nitroxides in Viable Biological Systems: An Opportunity and Challenge for Chemists and Biochemists Measurements of Pertinent Concentrations of Oxygen In Vivo Blue Light Photoreception in Higher Plants Studied with ESR Spectrometry In Vivo Oximetry Using a Nitroxide-Liposome System The Importance of Measuring the Concentration of Oxygen Appropriately and How This Might Be Done Development of EPR Method for Measurement of Cellular Sulfhydryl Groups Contrast Agents for Magnetic Resonance Spectroscopy: A Method to Obtain Increased Information in In Vivo and In vitro Spectroscopy In Vivo EPR Oximetry Using Two Novel Probes: Fusinite and Lithium Phthalocyanine Simultaneous Measurement of Intra-and Extra-Cellular [O2] in Viable Cells Simultaneous Measurement of Intracellular and Extracellular Oxygen Concentrations Using a Nitroxide-Liposome System Measurement of the Intracellular Concentration of Oxygen in a Cell Perfusion System The Use of EPR for the Measurement of the Concentration of Oxygen In Vivo In Tissues Under Physiologically Pertinent Conditions and Concentrations DNA Synthesis Inhibition of Nitroxide Radicals on Leukemia Cells The Minocycline-Induced Thyroid Pigment and Several Synthetic Models: Identification and Characterization by Electron Paramagnetic Resonance (EPR) Spectroscopy Evaluation of the Potential Cytotoxicity of Paramagnetic Materials Used in Measurements of the Concentration of Oxygen Measurements of Intracellular Concentrations of Oxygen: Experimental Results and Conceptual Implications of an Observed Gradient Between Intracellular and Extracellular Concentrations of Oxygen Sonochemical Activation of Hematoporhyrin: An ESR Study Oxygen Tension in a Murine Tumor: A Combined EPR and MRI Study Characterization of Redox Activity in Resting and Activated Mast Cells by Reduction and Reoxidation of Lipophilic Nitroxides Reduction of Lipid-Soluble Nitroxides in CHO Cells and Macrophage Tumor Cells. Free Rad India Ink: A Potential Clinically Applicable EPR Oximetry Probe The Effects of Endotoxin on Oxygen Consumption of Various Cell Types In vitro: An EPR Oximetry Study. Free Rad The Concentration of Oxygen is Too Important of a Variable to be Ignored in Experiments Studying Oxidative Damage! In The Oxygen Paradox Effect of Repetitive Ischemia on Local Myocardial Oxygen Tension in Isolated Perfused and Hypoperfused Rat Hearts The Relationship between pO 2 and Perfusion in Two Murine Tumors After X-ray Irradiation: A Combined Gd-DTPA Dynamic MRI and In Vivo EPR Oximetry Study The Measurement of Temperature with Electron Paramagnetic Resonance Spectroscopy Measurement of pO 2 In Vivo, Including Human Subjects by Electron Paramagnetic Resonance Myocardial Oxygen Tension in Isolated Erythrocyte-Perfused Rat Hearts and Comparison with Crystalloid Media The Application of EPR Spectroscopy in the Field of Pharmacy Myocardial Oxygen Tension and Relative Capillary Density in Isolated Perfused Rat Hearts EPR and In Vivo EPR: Roles for Experimental and Clinical NMR Studies An Analysis of the Effects of Eddy Currents on L-Band EPR Spectra Low Frequency Electron Paramagnetic Resonance Investigation on Metabolism of Chromium (VI) by Whole Live Mice Free Radicals in Aging: Theories, Facts, and Artifacts. Dahlem Konferenzen EPR Studies of Living Animals and Related Model Systems (In Vivo EPR) Interaction in Situ of Neuromelanin with Paramagnetic Metals in Substantia Nigra: An EPR study The Binding of Iron to Neuromelanin of Human Substantia Nigra and Synthetic Melanin: An Electron Resonance Spectroscopy Study. Free Rad In Vivo Measurement of Oxygen Concentration Using Sonochemically Synthesized Microspheres Interaction of Neuromelanin and Iron in Substantia Nigra and Other Areas of Human Brain Vivo EPR Oximetry Using EPR and India Ink Low Frequency EPR Investigation on Chromium (VI) Reduction in Whole Mice Applications of Reactions of Nitroxides in Biophysics Biochemical Basis of Reduction of Nitroxides in Membranes In Nitroxide Spin Labels, Reactions in Biology and Chemistry Metabolism of Nitroxides and Their Products in Cells Metabolism and Distribution of Nitroxides in Tissues and Organs Metabolism and Distribution of Nitroxides In Vivo In Nitroxide Spin Labels Toxicity and the Use of Nitroxides as Drugs Metabolism, Toxicity, and Distribution of Spin Traps MRI Contrast Enhanced Study of Cartilage Proteoglycan Degradation in the Rabbit Knee Myocardial Oxygen Tension and Capillary Density in the Isolated Perfused Rat Heart During Pharmacological Intervention Detection of Free Radical Metabolite Formation Using EPR Spectroscopy: Evidence of Rat Hemoglobin Thiyl Radical In Vivo Formation Following Administration of Phenylhydrazine Can NMR Diffusion-Weighted Imaging Provide Quantitative Information on Tumor Interstitial pO 2 ? Pharmacokinetics of the Nitroxide PCA Measured by An Overview of Considerations and Approaches for Developing In Vivo EPR for Clinical Applications Microencapsulation of Carbon Particles Used as Oxygen Sensors in EPR Oximetry to Stabilize Their Responsiveness to Oxygen In vitro and In Vivo Changes in Oxygenation of Intracranial Tumors with Carbogen: A BOLD MRI and EPR Oximetry Study Estimation of Oxygen Distribution in RIF-1 Tumors by Diffusion Model-Based Interpretation of Pimonidazole Hypoxia and Eppendorf Measurements Firefly Flashing is Controlled by Gating Oxygen to Light Emitting Cells Development of Biocompatible Oxygen-Permeable Films Holding Paramagnetic Carbon Particles: Evaluation of their Performance and Stability in EPR Oximetry EPR Oximetry In Vivo in the Mouse Skin Modeling of Tumor Oxygen Micro-Heterogeneity for Photodynamic Therapy Dosimetry Electron Paramagnetic Resonance (EPR) Assessment of Brain Tissue Oxygen Tension in Anesthetized Rats Anti-Bacterial Peptide PR-39 Affects Local Nitric Oxide and Preserves Tissue Oxygenation in the Liver During Septic Shock Reduced Blood Flow and Oxygenation in SA-1 Tumors after Electrochemotherapy with Cisplatin Reduced Tumor Oxygenation by Treatment with Vinblastine Tumor pO 2 Changes During Photodynamic Therapy Depend upon Photosensitizer Type and Time After Injection High Spatial Resolution Multi-Site EPR Oximetry: The Use of a Convolution-Based Fitting Method Development of Isoindoline Nitroxides for EPR Oximetry in Viable Systems The Effects of Ketamine-Xylazine Anesthesia on Cerebral Blood Flow and Oxygenation Observed Using Nuclear Magnetic Resonance Perfusion Imaging and Electron Paramagnetic Resonance Oximetry The Evolution of Bioluminescent Oxygen Consumption as an Ancient Oxygen Detoxification Mechanism Applications of EPR (ESR or EMR) in Medicine and Biology In Vivo Assessment of Nodularin-Induced Hepatotoxicity in the Rat Using Magnetic Resonance Techniques (MRI, MRS and EPR Oximetry) Oxygen Consumption Rates and Oxygen Concentration in Molt-4 Cells and their mtDNA Depleted (rho0) Mutants Plasma Membrane Cholesterol: A Possible Barrier to Intracellular Oxygen in Normal and Mutant CHO Cells Defective in Cholesterol Metabolism Measuring Real Levels of Oxygen In Vivo: Opportunities and Challenges Measurements of In Vivo Parameters Pertinent to ROS/ RNS Using EPR Spectroscopy Simultaneous detection of pO 2 and NO by electron paramagnetic resonance In Vivo Electron Paramagnetic Resonance Oximetry with Particulate Materials EPR Oximetry in Biological and Model Samples EPR Spectroscopy of Function In Vivo: Origins, Achievements, and Future Possibilities Spin Traps: In vitro Toxicity and Stability of Radical Adducts. Free Rad Tumor Causes Enhanced Radiation Sensitivity An Improved External Loop Resonator for In Vivo L-band EPR Spectroscopy Using EPR to Measure a Critical but Often Unmeasured Component of Oxidative Damage: Oxygen The Difficulties in Comparing In Vivo Oxygen Measurements -Turning the Problems into Benefits Axial Oxygen Diffusion in the Krogh Model: Modifications to Account for Myocardial Oxygen Tension in Isolated Perfused Rat Hearts Measured by EPR Oximetry Effect of RSR13, an Allosteric Hemoglobin Modifier. on Oxygenation in Murine Tumors: An In Vivo EPR Oximetry and BOLD MRI Study Modeling of the Response of ptO2 in Rat Brain to Changes in Physiological Parameters Black Magic and EPR Oximetry: From Lab to Initial Clinical Trials Simultaneous NIR-EPR Spectroscopy of Rat Brain Oxygenation Cerebral PtO2, Acute Hypoxia, and Volatile Anesthetics in the Rat Brain Use of Electron Paramagnetic Resonance Spectroscopy to Evaluate the Redox State In Vivo Comparison of EPR Oximetry and Eppendorf Polarographic Electrode Assessments of Rat Brain PtO 2 Practical Experimental Conditions and Limitations for High Spatial Resolution Multi-Site EPR Oximetry Free Radicals and Medicine pO 2 and Regional Blood Flow in a Rabbit Model of Limb Ischemia Differentiation of the Observed Low Frequency Increased Oxygenation of Intracranial Tumors by EFAPROXYN (Efaproxiral) an Allosteric Hemoglobin Modifier: An In Vivo EPR Oximetry Study Cerebral Tissue Oxygenation in Reversible Focal Ischemia in Rats: EPR Oximetry Measurements Distant Spin Trapping: A Method for Expanding the Availability of Spin Trapping Measurement L-Band EPR Spectrometer for the Use In Vivo and in the Studies of Aqueous Biological Samples Implantable Resonators -A New Direction for In Vivo Application of EPR Spectroscopy. Working Document of the EPR Center Simultaneous Measurement of Rat Brain Cortex PtO 2 Using EPR Oximetry and a Fluorescence Fiber-Optic Sensor During Normoxia and Hyperoxia Measurement of Specific Absorption Rate for Clinical EPR at 1200 MHz EPR Spectrometer for Clinical Applications In Vivo EPR: When, How and Why? Clinical Applications of EPR: Overview and Perspectives Electron Paramagnetic Resonance (EPR) in Medical Dosimetry Spectrum File Size Optimization for EPR Tooth Dosimetry Measurements of Clinically Significant Doses of Ionizing Radiation Using Non-Invasive In Vivo EPR Spectroscopy of Teeth In Situ In Vivo EPR Dosimetry to Quantify Exposures to Clinically Significant Doses of Ionizing Radiation Impact of Mouse Strain Differences in Innate Hindlimb Collateral Vasculature Seeing is Believing -Visualizing Drug Delivery In Vitro and In Vivo Development and Evaluation of Biocompatible Films of Polytetrafluoroethylene Polymers Holding Lithium Phthalocyanine for their Use in EPR Oximetry Influence of Different Anesthetics on Skin Oxygenation Studied by Electron Paramagnetic Resonance In Vivo High Spatial Resolution Multi-Site EPR Oximetry of Transient Focal Cerebral Ischemia in the Rat Hypoxia: Importance in Tumor Biology, Noninvasive Measurement by Imaging, and Value of its Measurement in the Management of Cancer Therapy What is the Actual Heterogeneity to be Expected in Tumors -and How Can We Resolve It? in Hypoxia: Importance in Tumor Biology, Noninvasive Measurement by Imaging, and Value of Its Measurement in the Management of Cancer Therapy Noninvasive Measurement by Imaging, and Value of Its Measurement in the Management of Cancer Therapy EPR Dosimetry in Chemically Treated Fingernails Protocol for Emergency EPR Dosimetry in Fingernails Experimental Procedures for Sensitive and Reproducible In Situ EPR Tooth Dosimetry Radiation Dose Reconstruction from L-Band In Vivo EPR Spectroscopy of Intact Teeth: Comparison of Methods Implementing EPR Dosimetry for Life-Threatening Incidents: Factors Beyond Technical Performance Q-band EPR Biodosimetry in Tooth Enamel Microsamples: Feasibility Test and Comparison with X-band Oxygen Effects on the EPR Signals from Wood Charcoals: Experimental Results and the Development of a Model The Effects of EFAPROXYN™ (efaproxiral) on Subcutaneous RIF-1 Tumor Oxygenation and Enhancement of Radiotherapy Mediated Tumor Growth Inhibition in Mice Effect of Oxygen Therapy on Brain Damage and Cerebral pO 2 in Transient Focal Cerebral Ischemia in the Rat Measurements of Oxygen In Vivo: Overview and Perspectives on Methods to Measure Oxygen within Cells and Tissues. Antioxid Repetitive Tissue pO 2 Measurements by Electron Paramagnetic Resonance: Current Status and Future Potential for Experimental and Clinical Studies On Tissue Oxygen and Hypoxia: An Editorial, Introduction to the Forum Issue Biodose-EPR-2006 Meeting: Acute Dosimetry Consensus Committee Recommendations on Biodosimetry Applicants in Events Involving Uses of Radiation by Terrorists and Radiation Accidents Quinoid Radio-Toxin (QRT) Induced Metabolic Changes in Mice: An Ex Vivo and In Vivo EPR Investigation Tissue Oxygenation in a Murine SCC VII Tumor after X-Ray Irradiation as Determined by EPR Spectroscopy Seizure-Induced Formation of Isofurans: Novel Products of Lipid Peroxidation Whose Formation is Positively Modulated by Oxygen Tension Electron Paramagnetic Resonance in Human Fingernails: The Sponge Model Implication Tibial Fracture Decreases Oxygen Levels at the Site of Injury Methods for Tissue pO 2 Redox, pH and Glutathione Measurements by EPR Spectroscopy Electron Paramagnetic Resonance Radiation Dosimetry in Fingernails Repeated Tumor pO 2 Measurements by Multi-Site EPR Oximetry as a Prognostic Marker for Enhanced Therapeutic Efficacy of Fractionated Radiotherapy Burn Trauma in Skeletal Muscle Results in Oxidative Stress as Assessed by In Vivo Electron Paramagnetic Resonance Tissue pO 2 of Orthotopic 9L and C6 Gliomas and Tumor Specific Response to Radiotherapy and Hyperoxygenation Radiotherapy in Conjunction with 7-Hydroxystaurosporine: A Multimodal Approach with Tumor pO 2 as a Prognostic Marker of Therapeutic Response Implantable Resonators: A Technique for Repeated Measurement of Oxygen at Multiple Deep Sites with In Vivo EPR Oxygen Sensitivity and Biocompatibility of an Implantable Paramagnetic Probe for Repeated Measurements of Tissue Oxygenation Modulation of Tumor Hypoxia by Topical Formulations with Vasodilators for Enhancing Therapy A Critical Assessment of Biodosimetry Methods for Large Scale Incidents Increased Tumor Oxygenation and Drug Uptake During Anti-Angiogenic Weekly Low Dose Cyclophosphamide Enhances the Anti-Tumor Effect of Weekly Tirapazamine Physically-Based Biodosimetry Using In Vivo EPR of Teeth in Patients Undergoing Total Body Irradiation Opening of the MitoKATP Channel and Decoupling of Mitochondrial Complex II and III Contribute to the Suppression of Myocardial Reperfusion Hyperoxygenation Late Phase Ischemic Preconditioning Attenuates Hyperoxygenation in the Post-Ischemic Mouse Heart: An In Vivo EPR Oximetry Study Proposed Triage Categories for Large-Scale Radiation Incidents Using High-Accuracy Biodosimetry Methods The View from the Trenches Part 1: Emergency Medical Response Plans and the Need for EPR Screening Dosimetry Based on EPR Spectral Analysis of Fingernail Clippings Development of In Vivo Tooth EPR for Individual Radiation Dose Estimation and Screening Surface Loop Resonator Design for In Vivo EPR Tooth Dosimetry Using Finite Element Analysis The View from The Trenches: Part 2-Technical Considerations for EPR Screening Development of a Compact Electron Spin Resonance System for Measuring ESR Signals of Irradiated Fingernails Radiation Dose Prediction Using Data on Time to Emesis in the Case of Nuclear Terrorism Clinical Applications of In Vivo EPR: EPR Oximetry Use of EPR for Dosimetry After the Potential Exposure of Large Numbers of People to Doses of Radiation that are Potentially Life Threatening Clinical Electron Paramagnetic Resonance (EPR) Oximetry Using India Ink Effect of a Topical Vasodilator on Tumor Hypoxia and Tumor Oxygen Guided Radiotherapy using EPR Oximetry Endothelial NOS Activity and Myocardial Oxygen Metabolism Define the Salvageable Ischemic Time Window for Ischemic Postconditioning A Framework for Comparative Evaluation of Dosimetric Methods to Triage a Large Population Following a Radiological Event Overview of Biodosimetry for Management of Unplanned Exposures to Ionizing Radiation A Deployable In Vivo EPR Tooth Dosimeter for Triage After a Radiation Event Involving Large Populations Advances Towards Using Finger/Toenail Dosimetry to Triage a Large Population After Potential Exposure to Ionizing Radiation Cerebral Oxygenation in Awake Rats during Acclimation and Deacclimation to Hypoxia: An In Vivo Electron Paramagnetic Resonance Study Cerebral Oxygenation of the Cortex and Caudate Putamen Following Normobaric Hyperoxia and Mild Hypoxia in the Rats-EPR Oximetry with Multi-Probe Implantable Resonators Tumor pO 2 as a Surrogate Marker to Identify Therapeutic Window during Metronomic Chemotherapy of 9L Gliomas Repeated Tumor Oximetry to Identify Therapeutic Window During Metronomic Cyclophosphamide Treatment of 9L Gliomas The Evaluation of New and Isotopically Labeled Isoindoline Nitroxides and an Azaphenalene Nitroxide for EPR Oximetry Modulation of Tumor Hypoxia by Topical Formulations with Vasodilators for Enhancing Therapy Synergistic Combination of Hyperoxygenation and Radiotherapy by Repeated Assessments of Tumor pO 2 with EPR Oximetry Mechanical Stability Affects Angiogenesis During Early Fracture Healing Dynamic Changes in Oxygenation of Intracranial Tumor and Contralateral Brain During Tumor Growth and Carbogen Breathing: A Multi-Site EPR Oximetry with Implantable Resonators Repeated Assessment of Orthotopic Glioma pO 2 by Multi-site EPR Oximetry: A Technique with the Potential to Guide Therapeutic Optimization by Repeated Measurements of Oxygen Electron Paramagnetic Resonance Dosimetry for a Large-Scale Radiation Incident The Role of Oxygen During Fracture Healing Assessment of the Changes in 9L and C6 Glioma pO 2 by EPR Oximetry as a Prognostic Indicator of Differential Response to Radiotherapy Standard Error of Inverse Prediction for Dose-Response Relationship: Approximate and Exact Statistical Inference Comparative Evaluation of Dosimetric Methods for Triage in Large-scale Radiation Events A Decision Support Tool for Evaluating the Logistical Considerations of Biodosimetry Methods Electron Paramagnetic Resonance Dosimetry for a Large-Scale Radiation Incident Overview of Methods for Establishing Dose to Individuals for Managing Unplanned, Clinically Significant Exposures to Ionizing Radiation A Decision Support Tool for Evaluating the Effectiveness and Logistical Considerations of Biodosimetry Methods-Comparing Guidelines and New Technologies for the Response to a Nuclear Event A Method to Advance and Evaluate New Emergency Response Technologies -A Case Study Implementation using EPR Dosimetry L-band Surface-Coil Resonator with Voltage-Control Impedance-Matching for EPR Tooth Dosimetry Mitochondria-targeted Antioxidant Promotes Recovery of Skeletal Muscle Mitochondrial Function after Burn Trauma Assessed by in Vivo 31P Nuclear Magnetic Resonance and Electron Paramagnetic Resonance Spectroscopy Repeated Monitoring of Tumor Oxygen While Breathing Carbogen to Determine the Therapeutic Potential of Hyperoxic Therapy Hyperoxia and Transforming Growth Factor β1 Signaling in the Post-ischemic Mouse Heart Comparison of the Needs for Biodosimetry for Large-scale Radiation Events for Military versus Civilian Populations Real-time, in Vivo Determination of Dynamic Changes in Lung and Heart Tissue Oxygen Levels using EPR Oximetry Adv Overview of the Principles and Practice of Biodosimetry Advances in Probes and Methods for Clinical EPR Oximetry. Adv. Exp Development and Validation of an Ex Vivo Electron Paramagnetic Resonance Fingernail Biodosimetric Method Determination of the Average Native Background and the Light-induced EPR signals and their Variation in the Design and Evaluation of a 1.1-GHz Surface Coil Resonator for Electron Paramagnetic Resonance-Based Tooth Dosimetry Bench-to-Bedside Oximetry for Real-time Monitoring of Tumor pO 2 : A Critical Parameter which Influences Radiotherapeutic Outcome Advances in a Framework to Compare Bio-Dosimetry Methods for Triage in Large-Scale Radiation Events In Vivo EPR Tooth Dosimetry for Triage after a Radiation Event Involving Large Populations Real-time Monitoring of Ischemic and Contralateral Brain pO 2 during Stroke by Variable Length Multisite Resonators Skeletal Muscle and Glioma Oxygenation by Carbogen Inhalation in Rats: A Longitudinal Study by EPR Oximetry Using Single-Probe Implantable Oxygen Sensors Recurrent Low-dose Chemotherapy to Inhibit and Oxygenate Head and Neck Tumors Monitoring oxygen levels in orthotopic human glioma xenograft following carbogen inhalation and chemotherapy by implantable resonatorbased oximetry Effect of Hyperoxygenation on Tissue pO 2 and its Effect on Radiotherapeutic Efficacy of Orthotopic F98 Gliomas Deep-Tissue Oxygen Monitoring in the Brain of Rabbits for Stroke Research A Microwave Resonator for Limiting Depth Sensitivity for Electron Paramagnetic Resonance Spectroscopy of Surfaces SU-C-BRD-05: Non-Invasive in Vivo Biodosimetry in Radiotherapy Patients Using Electron Paramagnetic Resonance Imaging Tooth Enamel using Zero Echo Time (ZTE) Magnetic Resonance Imaging Calculation of Dose Conversion Factors for Doses in the Fingernails to Organ Doses at External Gamma Irradiation in Air Phase 1 Clinical Trial of OxyChip, an Implantable Absolute pO 2 Sensor for Tumor Oximetry Coaxial Dielectric Probe Technique for Distinguishing Direct and Repeated Measurement of Heart and Brain Oxygenation Using In Vivo EPR Oximetry In Vivo High-Resolution Magic Angle Spinning Magnetic and Electron Paramagnetic Resonance Spectroscopic Analysis of Mitochondria-Targeted Peptide in Drosophila Melanogaster with Trauma-Induced Thoracic Injury Are We Ready for a Radiological Terrorist Attack Yet? Report From the Centers for Medical Countermeasures Against Radiation Network Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure EPR Oximetry for Investigation of Hyperbaric O 2 Pre-Treatment for Tumor Radiosensitization Comparing the Effectiveness of Methods to Measure Oxygen in Tissues for Prognosis and Treatment of Cancer Direct and Repeated Clinical Measurements of pO 2 for Enhancing Cancer Therapy and Other Applications Skeletal Muscle Oxygenation Measured by EPR Oximetry Using a Highly Sensitive Polymer-Encapsulated Paramagnetic Sensor Evaluating the Special Needs of the Military for Radiation Biodosimetry for Tactical Warfare against Deployed Troops: Comparing Military to Civilian Needs for Biodosimetry Methods Evolution and Optimization of Tooth Models for Testing In Vivo EPR Tooth Dosimetry Surface Dielectric Resonators For X-Band EPR Spectroscopy Possible Nature of the Radiation-Induced Signal in Nails: High-Field EPR, Confirming Chemical Synthesis, and Quantum Chemical Calculations In-Vivo Radiation Dosimetry Using Portable L Band EPR: On-Site Measurement of Volunteers in Fukushima Prefecture Dielectric-Backed Aperture Resonators For X-Band In Vivo EPR Nail Dosimetry EPR Center Tooth Dosimetry Project Team. Advances In In Vivo EPR Tooth Biodosimetry: Meeting the Targets for Initial Triage Following a Large-Scale Radiation Event Flexible, Wireless, Inductively Coupled Surface Coil Resonator for EPR Tooth Dosimetry ROC Analysis for Evaluation of Radiation Biodosimetry Technologies Using Stable Free Radicals to Obtain Unique And Clinically Useful Data In Vivo in Human Subjects Introduction to the Special Issue from EPR Biodose Using India ink as a Sensor for Oximetry: Evidence of its Safety as a Medical Device Development of the Implantable Resonator System for Clinical EPR oximetry Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism Temporal Variation in the Response of Tumors to Hyperoxia with Breathing Carbogen and Oxygen Overview of the Principles and Practice of Biodosimetry Proceedings of the Food and Drug Administration's Public Workshop on New Red Blood Cell Product Regulatory Science In Vivo Electron Paramagnetic Resonance Tooth Dosimetry: Dependence of Radiation-Induced Signal Amplitude on the Enamel Thickness and Surface Area of Ex Vivo Human Teeth Guidance for Academics to Transfer 'Bench-ready' Medical Technology into Usual Clinical Practice. Case Study: Sensors and Spectrometer used in EPR Oximetry Developments in Biodosimetry Methods for Triage, with a Focus on X-band Electron Paramagnetic Resonance In Vivo Fingernail Dosimetry Development of the Novel Mouth Model as an Alternative Tool for the Improvement of In Vivo EPR Dosimetry System Clinical and Statistical Considerations When Assessing Oxygen Levels in Tumors: Illustrative Results from Clinical EPR Oximetry Studies Oxygen Level in a Tissue Scientific and Logistical Considerations When Screening for Radiation Risks by Using Biodosimetry Based on Biological Effects of Radiation Rather Than Dose: The Need for Prior Measurements of Homogeneity and Distribution of Dose Electron Paramagnetic Resonance (EPR) Oximetry as a Novel Approach to Monitor the Effectiveness and Quality of Red Blood Cell Transfusions Measurements of Normal Tissue Oxygenation Via Electron Paramagnetic Resonance (EPR) Oximetry During and After Breast Radiation Therapy: Baseline Evaluations and Response to Hyperoxygenation Measurement of Tissue Oxygen Homeostasis and pO 2 as a Novel Approach to Optimizing Red Blood Cell Quality Assessment What is the Meaning of an Oxygen Measurement? Analysis of Methods Purporting to Measure Oxygen in Targeted Tissues The Clinical Utility of Imaging Methods Used to Measure Hypoxia in Cervical Cancer High Resolution pO 2 Imaging Improves Quantification of the Hypoxic Fraction in Tumors during Radiotherapy How Best to Interpret Measures of Levels of Oxygen in Tissues to Make Them Effective Clinical Tools for Care of Patients with Cancer and Other Oxygen-Dependent Pathologies Dielectric-Backed Aperture Resonators for X-band Depth-Limited in Vivo EPR Nail Dosimetry OxyChip Implantation and Subsequent Electron Paramagnetic Resonance Oximetry in Human Tumors Is Safe and Feasible: First Experience in NIH Workshop 2018: Towards Minimally-invasive or Non-invasive Approaches to Assess Tissue Oxygenation Pre-and Post-Transfusion L-Band Electron Paramagnetic Resonance Tooth Dosimetry Applied to Affected Cattle Teeth in Fukushima RF/Microwave Resonators for Preclinical and Clinical EPR Applications: Current Status and Challenges the Scientific Council of IABERD. Complementary Lessons Learned from the Testing Strategies Used for Radiation Emergencies and COVID-19: A White Paper from the International Association of Biological and Electron Paramagnetic Resonance (EPR) Radiation Dosimetry (IABERD) What if a Major Radiation Incident Happened during a Pandemic? Considerations of the Impact on Biodosimetry Radiation Medical Countermeasures and Use of EPR Biodosimetry to Facilitate Effectiveness of Applied Clinical Procedures Review of Tissue Oxygenation Sensing During Radiotherapy Based Upon Cherenkov-Excited Luminescence Imaging Factors Determining Barrier Properties to Oxygen Transport Across Model and Cell Plasma Membranes Based on EPR Spin-Label Oximetry Flexible Segmented Surface Coil Resonator for In Vivo EPR Measurements in Human Subjects Quantification of Oxygen Depletion During FLASH Irradiation in vitro and in Vivo Dependence of Radiation-induced Signals on Geometry of Tooth Enamel using a 1.15 GHZ Electron Paramagnetic Resonance Spectrometer: Improvement of Dosimetric Accuracy Expanding EPR Oximetry into Transfusion Medicine Effects of Ultraviolet Rays on L-Band In Vivo EPR Dosimetry Using Tooth Enamel In Vivo CW-EPR Spectrometer Systems for Dosimetry and Oximetry in Preclinical and Clinical Applications Evaluation of a Refined Implantable Resonator for Deep-Tissue EPR Oximetry in the Oxygenation Status of Malignant Tumors vs. Normal Tissues: Critical Evaluation and Updated Data Source Based on Direct Measurements with pO 2 Microsensors Interaction of Melanin with Metal Ions Modulates Their Cytotoxic Potential History of EPR Studies from the H.M. Swartz Laboratories: Part 2-EPR Biodosimetry History of EPR Studies from the H.M. Swartz Laboratories: Part 3-EPR Oximetry Appl. Magn. Reson History of EPR Studies from the H.M. Swartz Laboratories: Part 1-Free Radicals and Paramagnetic Metals in Biological Systems and Associated EPR Instrumental Developments First-in-human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance with the OxyChip A Radiation Biological Analysis of the Oxygen Effect as a Possible Mechanism in FLASH Author contributions Ann Flood served as the overall lead guest editor for this festschrift. Steve Swarts served as the lead guest editor for all articles on which Ann or Hal Harold Swartz were coauthors; Steve was the topic guest editor for dosimetry-related articles. Murali Krishna was the topic guest editor for free radicals and EPR instrumental developments, and Bernard Gallez served as topic guest editor for oximetry-related articles.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.