[Show abstract][Hide abstract] ABSTRACT: This paper describes an optimized design of a surface coil resonator for in vivo electron paramagnetic resonance (EPR)-based tooth dosimetry. Using the optimized resonator, dose estimates with the standard error of the mean of approximately 0.5 Gy were achieved with irradiated human teeth. The product of the quality factor and the filling factor of the resonator was computed as an index of relative signal intensity in EPR tooth dosimetry by the use of 3-D electromagnetic wave simulator and radio frequency circuit design environment (ANSYS HFSS and Designer). To verify the simulated results of the signal intensity in our numerical model of the resonator and a tooth sample, we experimentally measured the radiation-induced signals from an irradiated tooth with an optimally designed resonator. In addition to the optimization of the resonator design, we demonstrated the improvement of the stability of EPR spectra by decontamination of the surface coil resonator using an HCl solution, confirming that contamination of small magnetic particles on the silver wire of the surface coil had degraded the stability of the EPR spectral baseline.
No preview · Article · Jun 2014 · IEEE transactions on bio-medical engineering
[Show abstract][Hide abstract] ABSTRACT: With possibilities for radiation terrorism and intensified concerns about nuclear accidents since the recent Fukushima Daiichi event, the potential exposure of large numbers of individuals to radiation that could lead to acute clinical effects has become a major concern. For the medical community to cope with such an event and avoid overwhelming the medical care system, it is essential to identify not only individuals who have received clinically significant exposures and need medical intervention but also those who do not need treatment. The ability of electron paramagnetic resonance to measure radiation-induced paramagnetic species, which persist in certain tissues (e.g., teeth, fingernails, toenails, bone, and hair), has led to this technique becoming a prominent method for screening significantly exposed individuals. Although the technical requirements needed to develop this method for effective application in a radiation event are daunting, remarkable progress has been made. In collaboration with General Electric and through funding committed by the Biomedical Advanced Research and Development Authority, electron paramagnetic resonance tooth dosimetry of the upper incisors is being developed to become a Food and Drug Administration-approved and manufacturable device designed to carry out triage for a threshold dose of 2 Gy. Significant progress has also been made in the development of electron paramagnetic resonance nail dosimetry based on measurements of nails in situ under point-of-care conditions, and in the near future this may become a second field-ready technique. Based on recent progress in measurements of nail clippings, it is anticipated that this technique may be implementable at remotely located laboratories to provide additional information when the measurements of dose on-site need to be supplemented. The authors conclude that electron paramagnetic resonance dosimetry is likely to be a useful part of triage for a large-scale radiation incident.
[Show abstract][Hide abstract] ABSTRACT: In order to meet the potential need for emergency large-scale retrospective radiation biodosimetry following an accident or attack, we have developed instrumentation and methodology for in vivo electron paramagnetic resonance spectroscopy to quantify concentrations of radiation-induced radicals within intact teeth. This technique has several very desirable characteristics for triage, including independence from confounding biologic factors, a non-invasive measurement procedure, the capability to make measurements at any time after the event, suitability for use by non-expert operators at the site of an event, and the ability to provide immediate estimates of individual doses. Throughout development there has been a particular focus on the need for a deployable system, including instrumental requirements for transport and field use, the need for high throughput, and use by minimally trained operators.Numerous measurements have been performed using this system in clinical and other non-laboratory settings, including in vivo measurements with unexposed populations as well as patients undergoing radiation therapies. The collection and analyses of sets of three serially-acquired spectra with independent placements of the resonator, in a data collection process lasting approximately five minutes, provides dose estimates with standard errors of prediction of approximately 1 Gy. As an example, measurements were performed on incisor teeth of subjects who had either received no irradiation or 2 Gy total body irradiation for prior bone marrow transplantation; this exercise provided a direct and challenging test of our capability to identify subjects who would be in need of acute medical care.
[Show abstract][Hide abstract] ABSTRACT: The ability to estimate individual exposures to radiation following a large attack or incident has been identified as a necessity for rational and effective emergency medical response. In vivo electron paramagnetic resonance (EPR) spectroscopy of tooth enamel has been developed to meet this need.
A novel transportable EPR spectrometer, developed to facilitate tooth dosimetry in an emergency response setting, was used to measure upper incisors in a model system, in unirradiated subjects, and in patients who had received total body doses of 2 Gy.
A linear dose response was observed in the model system. A statistically significant increase in the intensity of the radiation-induced EPR signal was observed in irradiated versus unirradiated subjects, with an estimated standard error of dose prediction of 0.9 ± 0.3 Gy.
These results demonstrate the current ability of in vivo EPR tooth dosimetry to distinguish between subjects who have not been irradiated and those who have received exposures that place them at risk for acute radiation syndrome. Procedural and technical developments to further increase the precision of dose estimation and ensure reliable operation in the emergency setting are underway. With these developments EPR tooth dosimetry is likely to be a valuable resource for triage following potential radiation exposure of a large population.
No preview · Article · Jun 2011 · International Journal of Radiation Biology
[Show abstract][Hide abstract] ABSTRACT: The development of in vivo EPR has made it feasible to perform tooth dosimetry measurements in situ, greatly expanding the potential for using this approach for immediate screening after radiation exposures. The ability of in vivo tooth dosimetry to provide estimates of absorbed dose has been established through a series of experiments using unirradiated volunteers with specifically irradiated molar teeth placed in situ within gaps in their dentition and in natural canine teeth of patients who have completed courses of radiation therapy for head and neck cancers. Multiple measurements in patients who have received radiation therapy demonstrate the expected heterogeneous dose distributions. Dose-response curves have been generated using both populations and, using the current methodology and instrument, the standard error of prediction based on single 4.5-min measurements is approximately 1.5 Gy for inserted molar teeth and between 2.0 and 2.5 Gy in the more irregularly shaped canine teeth. Averaging of independent measurements can reduce this error significantly to values near 1 Gy. Developments to reduce these errors are underway, focusing on geometric optimization of the resonators, detector positioning techniques, and optimal data averaging approaches. In summary, it seems plausible that the EPR dosimetry techniques will have an important role in retrospective dosimetry for exposures involving large numbers of individuals.
[Show abstract][Hide abstract] ABSTRACT: There is growing awareness of the need for methodologies that can be used retrospectively to provide the biodosimetry needed to carry out screening and triage immediately after an event in which large numbers of people have potentially received clinically significant doses of ionizing radiation. The general approach to developing such methodologies has been a technology centric one, often ignoring the system integrations considerations that are key to their effective use. In this study an integrative approach for the evaluation and development of a physical biodosimetry technology was applied based on in vivo electron paramagnetic resonance (EPR) dosimetry. The EPR measurements are based on physical changes in tissues whose magnitudes are not affected by the factors that can confound biologically-based assessments. In this study the use of a pilot simulation exercise to evaluate an experimental EPR system and gather stakeholders' feedback early on in the development process is described. The exercise involved: ten non-irradiated participants, representatives from a local fire department; Department of Homeland Security certified exercise evaluators, EPR experts, physicians; and a human factors engineer. Stakeholders were in agreement that the EPR technology in its current state of development could be deployed for the screening of mass casualties. Furthermore, stakeholders' recommendations will be prioritized and incorporated in future developments of the EPR technique. While the results of this exercise were aimed specifically at providing feedback for the development of EPR dosimetry for screening mass casualties, the methods and lessons learned are likely to be applicable to other biodosimetric methods.
[Show abstract][Hide abstract] ABSTRACT: Finite element analysis is used to evaluate and design L-band surface loop resonators for in vivo electron paramagnetic resonance (EPR) tooth dosimetry. This approach appears to be practical and useful for the systematic examination and evaluation of resonator configurations to enhance the precision of dose estimates. The effects of loop positioning in the mouth are examined, and it is shown that the sensitivity to loop position along a row of molars is decreased as the loop is moved away from the teeth.
[Show abstract][Hide abstract] ABSTRACT: EPR oximetry using implantable resonators allows measurements at much deeper sites than are possible with surface resonators (> 80 vs. 10 mm) and achieves greater sensitivity at any depth. We report here the development of an improved technique that enables us to obtain the information from multiple sites and at a variety of depths. The measurements from the various sites are resolved using a simple magnetic field gradient. In the rat brain multi-probe implanted resonators measured pO(2) at several sites simultaneously for over 6 months under normoxic, hypoxic, and hyperoxic conditions. This technique also facilitates measurements in moving parts of the animal such as the heart, because the orientation of the paramagnetic material relative to the sensing loop is not altered by the motion. The measured response is fast, enabling measurements in real time of physiological and pathological changes such as experimental cardiac ischemia in the mouse heart. The technique also is quite useful for following changes in tumor pO(2), including applications with simultaneous measurements in tumors and adjacent normal tissues.
Full-text · Article · Jan 2010 · Advances in Experimental Medicine and Biology
[Show abstract][Hide abstract] ABSTRACT: As a result of terrorism, accident, or war, populations potentially can be exposed to doses of ionizing radiation that could cause direct clinical effects within days or weeks. There is a critical need to determine the magnitude of the exposure to individuals so that those with significant risk have appropriate procedures initiated immediately, while those without a significant probability of acute effects can be reassured and removed from the need for further consideration in the medical/emergency system. In many of the plausible scenarios there is an urgent need to make the determination very soon after the event and while the subject is still present. In vivo EPR measurements of radiation-induced changes in the enamel of teeth is a method, perhaps the only such method, which can differentiate among doses sufficiently for classifying individuals into categories for treatment with sufficient accuracy to facilitate decisions on medical treatment. In its current state, the in vivo EPR dosimeter can provide estimates of absorbed dose with an error approximately +/- 50 cGy over the range of interest for acute biological effects of radiation, assuming repeated measurements of the tooth in the mouth of the subject. The time required for acquisition, the lower limit, and the precision are expected to improve, with improvements in the resonator and the algorithm for acquiring and calculating the dose. The magnet system that is currently used, while potentially deployable, is somewhat large and heavy, requiring that it be mounted on a small truck or trailer. Several smaller magnets, including an intraoral magnet are under development, which would extend the ease of use of this technique.
Full-text · Article · Aug 2007 · Radiation Measurements
[Show abstract][Hide abstract] ABSTRACT: In vivo electron paramagnetic resonance (EPR) tooth dosimetry provides a means for non-invasive retrospective assessment of personal radiation exposure. While there is a clear need for such capabilities following radiation accidents, the most pressing need for the development of this technology is the heightened likelihood of terrorist events or nuclear conflicts. This technique will enable such measurements to be made at the site of an incident, while the subject is present, to assist emergency personnel as they perform triage for the affected population. At Dartmouth Medical School this development is currently being tested with normal volunteers with irradiated teeth placed in their mouths and with patients who have undergone radiation therapy. Here we describe progress in practical procedures to provide accurate and reproducible in vivo dose estimates.
Full-text · Article · Aug 2007 · Radiation Measurements
[Show abstract][Hide abstract] ABSTRACT: As a result of terrorism, accident or war, populations potentially can be exposed to doses of ionising radiation that could cause direct clinical effects within days or weeks. There is a critical need to determine the magnitude of the exposure to individuals so that those with significant risk can have appropriate procedures initiated immediately, while those without a significant probability of acute effects can be reassured and removed from the need for further consideration in the medical/emergency system. It is extremely unlikely that adequate dosemeters will be worn by the potential victims, and it also will be unlikely that prompt and accurate dose reconstruction at the level of individuals will be possible. Therefore, there is a critical need for a method to measure the dose from radiation-induced effects that occur within the individual. In vivo EPR measurements of radiation-induced changes in the enamel of teeth is a method, perhaps the only such method, which can differentiate among doses sufficiently to classify individuals into categories for treatment with sufficient accuracy to facilitate decisions on medical treatment. In its current state, the in vivo EPR dosemeter can provide estimates of absorbed dose of +/- 0.5 Gy in the range from 1 to >10 Gy. The lower limit and the precision are expected to improve, with improvements in the resonator and the algorithm for acquiring and calculating the dose. In its current state of development, the method is already sufficient for decision-making action for individuals with regard to acute effects from exposure to ionising radiation for most applications related to terrorism, accidents or nuclear warfare.
No preview · Article · Feb 2006 · Radiation Protection Dosimetry
[Show abstract][Hide abstract] ABSTRACT: Electron paramagnetic resonance (EPR) oximetry is a powerful technology that allows the monitoring of oxygenation in tissues. The measurement of tissue oxygenation can be achieved using lithium phthalocyanine (LiPc) crystals as oxygen reporters. In order to have biocompatibility for the sensing system and to assure long-term stability in the responsiveness of the system, we developed films of Teflon AF 2400 with embedded LiPc crystals. These systems can be used as retrievable inserts or parts of an implantable resonator or catheter. Atomic force microscopy studies revealed that the surface of the films was regular and planar. The response to oxygen of the sensor (EPR linewidth as a function of pO(2)) remained unchanged after implantation in mice, and was not affected by sterilization or irradiation. The use of resonators, holding LiPc embedded in Teflon AF 2400, implanted in the gastrocnemius muscle of rabbits allowed the monitoring of oxygen during several weeks. Several assays also demonstrated the biocompatibility of the system: (1) no hemolytic effect was noted; (2) no toxicity was found using the systemic injection test of extracts; (3) histological analysis in rabbit muscle in which the films were implanted for 1 week or 3 months was similar to standard polyethylene biocompatible devices. These advanced oxygen sensors are promising tools for future pre-clinical and clinical developments of EPR oximetry. These developments can be applied for other applications of biosensors where there is a need for oxygen permeable membranes.
Full-text · Article · Feb 2006 · Biosensors & Bioelectronics
[Show abstract][Hide abstract] ABSTRACT: This article describes an EPR spectrometer specifically designed and constructed for EPR spectroscopy in humans. The spectrometer is based on a permanent magnet, suitable for measurements at 1200 MHz. The magnet has a full 50 cm gap between the poles, which facilitates accurate and comfortable placement of the subject for the EPR measurement at any location on the human body. The bridge includes features to facilitate clinical operations, including an indicator for phasing of the reference arm and a 2 level RF amplifier. Resonators with holders for each type and site of measurement have been developed that comfortably position the resonator and the patient and prevent artifacts due to motion. The initial applications for which the spectrometer has been designed are for oximetry using loops on the surface, oximetry using implanted resonators for measuring deep sites, and measurements in the teeth for determination of exposures to clinically significant doses of ionizing radiation.
No preview · Article · Nov 2005 · Magnetic Resonance in Medicine
[Show abstract][Hide abstract] ABSTRACT: There are plausible circumstances in which populations potentially have been exposed to doses of ionizing radiation that could cause direct clinical effects within days or weeks, but there is no clear knowledge as to the magnitude of the exposure to individuals. In vivo EPR is a method, perhaps the only such method that can differentiate among doses sufficiently to classify individuals into categories for treatment with sufficient accuracy to facilitate decisions on medical treatment. Individuals with significant risk then can have appropriate procedures initiated immediately, while those without a significant probability of acute effects could be reassured and removed from the need for further medical treatment. In its current state, the in vivo EPR dosimeter can provide estimates of absorbed dose of +/-25 cGy in the range of 100-->1000 cGy. This is expected to improve, with improvements in the resonator, the algorithm for calculating dose, and the uniformity of the magnetic field. In its current state of development, it probably is sufficient for most applications related to terrorism or nuclear warfare, for decision-making for action for individuals in regard to acute effects from exposure to ionizing radiation.
No preview · Article · Mar 2005 · Applied Radiation and Isotopes
[Show abstract][Hide abstract] ABSTRACT: The development and use of in vivo techniques for strictly experimental applications in animals has been very successful, and these results now have made possible some very attractive potential clinical applications. The area with the most obvious immediate, effective and widespread clinical use is oximetry, where EPR almost uniquely can make repeated and accurate measurements of pO2 in tissues. Such measurements can provide clinicians with information that can impact directly on diagnosis and therapy, especially for oncology, peripheral vascular disease and wound healing. The other area of immediate and timely importance is the unique ability of in vivo EPR to measure clinically significant exposures to ionizing radiation 'after-the-fact', such as may occur due to accidents, terrorism or nuclear war. There are a number of other capabilities of in vivo EPR that also potentially could become extensively used in human subjects. In pharmacology the unique capabilities of in vivo EPR to detect and characterize free radicals could be applied to measure free radical intermediates from drugs and oxidative process. A closely related area of potential widespread applications is the use of EPR to measure nitric oxide. These often unique capabilities, combined with the sensitivity of EPR spectra to the immediate environment (e.g. pH, molecular motion, charge) have already resulted in some very productive applications in animals and these are likely to expand substantially in the near future. They should provide a continually developing base for extending clinical uses of in vivo EPR. The challenges for achieving full implementation include adapting the spectrometer for safe and comfortable measurements in human subjects, achieving sufficient sensitivity for measurements at the sites of the pathophysiological processes that are being measured, and establishing a consensus on the clinical value of the measurements.
Full-text · Article · Aug 2004 · NMR in Biomedicine