In vivo EPR tooth dosimetry for triage after a radiation event involving large populations.

The management of radiation injuries following a catastrophic event where large numbers of people may have been exposed to life-threatening doses of ionizing radiation will rely critically on the availability and use of suitable biodosimetry methods. In vivo electron paramagnetic resonance (EPR) tooth dosimetry has a number of valuable and unique characteristics and capabilities that may help enable effective triage. We have produced a prototype of a deployable EPR tooth dosimeter and tested it in several in vitro and in vivo studies to characterize the performance and utility at the state of the art. This report focuses on recent advances in the technology, which strengthen the evidence that in vivo EPR tooth dosimetry can provide practical, accurate, and rapid measurements in the context of its intended use to help triage victims in the event of an improvised nuclear device. These advances provide evidence that the signal is stable, accurate to within 0.5 Gy, and can be successfully carried out in vivo. The stability over time of the radiation-induced EPR signal from whole teeth was measured to confirm its long-term stability and better characterize signal behavior in the hours following irradiation. Dosimetry measurements were taken for five pairs of natural human upper central incisors mounted within a simple anatomic mouth model that demonstrates the ability to achieve 0.5 Gy standard error of inverse dose prediction. An assessment of the use of intact upper incisors for dose estimation and screening was performed with volunteer subjects who have not been exposed to significant levels of ionizing radiation and patients who have undergone total body irradiation as part of bone marrow transplant procedures. Based on these and previous evaluations of the performance and use of the in vivo tooth dosimetry system, it is concluded that this system could be a very valuable resource to aid in the management of a massive radiological event.

A Deployable In Vivo EPR Tooth Dosimeter for Triage After a Radiation Event Involving Large Populations.

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.

Development of a novel mouth model as an alternative tool to test the effectiveness of an in vivo EPR dosimetry system.

In a large-scale radiation event, thousands may be exposed to unknown amounts of radiation, some of which may be life-threatening without immediate attention. In such situations, a method to quickly and reliably estimate dose would help medical responders triage victims to receive life-saving care. We developed such a method using electron paramagnetic resonance (EPR) to make in vivo measurements of the maxillary incisors. This report provides evidence that the use of in vitro studies can provide data that are fully representative of the measurements made in vivo. This is necessary because, in order to systematically test and improve the reliability and accuracy of the dose estimates made with our EPR dosimetry system, it is important to conduct controlled studies in vitro using irradiated human teeth. Therefore, it is imperative to validate whether our in vitro models adequately simulate the measurements made in vivo, which are intended to help guide decisions on triage after a radiation event. Using a healthy volunteer with a dentition gap that allows using a partial denture, human teeth were serially irradiated in vitro and then, using a partial denture, placed in the volunteer's mouth for measurements. We compared dose estimates made using in vivo measurements made in the volunteer's mouth to measurements made on the same teeth in our complex mouth model that simulates electromagnetic and anatomic properties of the mouth. Our results demonstrate that this mouth model can be used in in vitro studies to develop the system because these measurements appropriately model in vivo conditions.

Experimental Procedures for Sensitive and Reproducible In Situ EPR Tooth Dosimetry.

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.

In Vivo EPR For Dosimetry.

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.

Evolution and Optimization of Tooth Models for Testing In Vivo EPR Tooth Dosimetry.

Testing and verification are an integral part of any cycle to design, manufacture and improve a novel device intended for use in humans. In the case of testing Dartmouth's electron paramagnetic resonance (EPR) in vivo tooth dosimetry device, in vitro studies are needed throughout its development to test its performance, i.e. to verify its current capability for assessing dose in individuals potentially exposed to ionizing radiation. Since the EPR device uses the enamel of human teeth to assess dose, models that include human teeth have been an integral mechanism to carry out in vitro studies during development and testing its ability to meet performance standards for its ultimate intended in vivo use. As the instrument improves over time, new demands for in vitro studies change as well. This paper describes the tooth models used to perform in vitro studies and their evolution to meet the changing demands for testing in vivo EPR tooth dosimetry.

Tooth Retrospective Dosimetry Using Electron Paramagnetic Resonance: Influence of Irradiated Dental Composites.

In the aftermath of a major radiological accident, the medical management of overexposed individuals will rely on the determination of the dose of ionizing radiations absorbed by the victims. Because people in the general population do not possess conventional dosimeters, after the fact dose reconstruction methods are needed. Free radicals are induced by radiations in the tooth enamel of victims, in direct proportion to dose, and can be quantified using Electron Paramagnetic Resonance (EPR) spectrometry, a technique that was demonstrated to be very appropriate for mass triage. The presence of dimethacrylate based restorations on teeth can interfere with the dosimetric signal from the enamel, as free radicals could also be induced in the various composites used. The aim of the present study was to screen irradiated composites for a possible radiation-induced EPR signal, to characterize it, and evaluate a possible interference with the dosimetric signal of the enamel. We investigated the most common commercial composites, and experimental compositions, for a possible class effect. The effect of the dose was studied between 10 Gy and 100 Gy using high sensitivity X-band spectrometer. The influence of this radiation-induced signal from the composite on the dosimetric signal of the enamel was also investigated using a clinical L-Band EPR spectrometer, specifically developed in the EPR center at Dartmouth College. In X-band, a radiation-induced signal was observed for high doses (25-100 Gy); it was rapidly decaying, and not detected after only 24 h post irradiation. At 10 Gy, the signal was in most cases not measurable in the commercial composites tested, with the exception of 3 composites showing a significant intensity. In L-band study, only one irradiated commercial composite influenced significantly the dosimetric signal of the tooth, with an overestimation about 30%. In conclusion, the presence of the radiation-induced signal from dental composites should not significantly influence the dosimetry for early dose assessment.

Electron paramagnetic resonance dosimetry for a large-scale radiation incident.

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.

Physically-based biodosimetry using in vivo EPR of teeth in patients undergoing total body irradiation.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Development of in vivo tooth EPR for individual radiation dose estimation and screening.

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.