Roberto J. Nicolalde

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.

Proposed triage categories for large-scale radiation incidents using high-accuracy biodosimetry methods.

A catastrophic event such as a nuclear device detonation in a major U.S. city would cause a mass casualty with millions affected. Such a disaster would require screening to accurately and effectively identify patients likely to develop acute radiation syndrome (ARS). A primary function of such screening is to sort the unaffected, or worried-well, from those patients who will truly become symptomatic. This paper reviews the current capability of high-accuracy biodosimetry methods as screening tools for populations and reviews the current triage and medical guidelines for diagnosing and managing ARS. This paper proposes that current triage categories, which broadly categorize patients by likelihood of survival based on current symptoms, be replaced with new triage categories that use high-accuracy biodosimetry methods. Using accurate whole-body exposure dose assessment to predict ARS symptoms and subsyndromes, clinical decision-makers can designate the appropriate care setting, initiate treatment and therapies, and best allocate limited clinical resources, facilitating mass-casualty care following a nuclear disaster.

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.

ELECTRON PARAMAGNETIC RESONANCE DOSIMETRY FOR A LARGE-SCALE RADIATION INCIDENT

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.

The view from the trenches: part 1-emergency medical response plans and the need for EPR screening.

Few natural disasters or intentional acts of war or terrorism have the potential for such severe impact upon a population and infrastructure as the intentional detonation of a nuclear device within a major U.S. city. In stark contrast to other disasters or even a “dirty bomb,” hundreds of thousands will be affected and potentially exposed to a clinically significant dose of ionizing radiation. This will result in immediate deaths and injuries and subsequently the development of Acute Radiation Syndrome (ARS). Additionally, millions more who are unlikely to develop ARS will seek medical evaluation and treatment, overwhelming the capacity of an already compromised medical system. In this paper, the authors propose that in vivo electron paramagnetic resonance (EPR) dosimetry be utilized to screen large numbers of potentially exposed victims, and that this screening process be incorporated into the medical-surge framework that is currently being implemented across the nation for other catastrophic public health emergencies. The National Incident Management System (NIMS), the National Response Framework (NRF), the Target Capabilities List (TCL), Homeland Security Presidential Directives (HSPD), as well as additional guidance from multiple federal agencies provide a solid framework for this response. The effective screening of potentially-exposed victims directly following a nuclear attack could decrease the number of patients seeking immediate medical care by greater than 90%.

ADVANCES IN A FRAMEWORK TO COMPARE BIO-DOSIMETRY METHODS FOR TRIAGE IN LARGE-SCALE RADIATION EVENTS

Planning and preparation for a large-scale nuclear event would be advanced by assessing the applicability of potentially available bio-dosimetry methods. Using an updated comparative framework the performance of six bio-dosimetry methods was compared for five different population sizes (100-1,000,000) and two rates for initiating processing of the marker (15 or 15,000 people per hour) with four additional time windows. These updated factors are extrinsic to the bio-dosimetry methods themselves but have direct effects on each methods ability to begin processing individuals and the size of the population that can be accommodated. The results indicate that increased population size, along with severely compromised infrastructure, increases the time needed to triage, which decreases the usefulness of many time intensive dosimetry methods. This framework and model for evaluating bio-dosimetry provides important information for policy-makers and response planners to facilitate evaluation of each method and should advance coordination of these methods into effective triage plans.

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 Dartmouths 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.

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

This paper introduces an early prototype of a decision support tool (DST) for evaluating the effectiveness and logistical considerations of biodosimetry methods. Biodosimetry methods allow the estimation of an individuals radiation exposure and facilitate the process of screening the population into treatment categories following a potential large-scale nuclear or radiological event. The DST was implemented using STELLA® software with preliminary comparisons among six biodosimetry methods, including the current federal guidelines. Preliminary results under the models assumptions show a great variability among methods on their efficiency for screening large numbers of potential victims. In the future, a revised version of the DST would be a useful tool for the emergency response community to evaluate the effectiveness of various strategies for preattack stockpiling and capacity building, and postattack distribution and dispensing of biodosimetry technologies.

A method to advance and evaluate new emergency response technologies: A case study implementation using EPR dosimetry

The goal of this study was to develop and test a new methodology, the Disaster Technology Assessment Cycle (DTAC), for the effective development and assessment of new clinical emergency response technologies that can improve the speed and ease with which they can be transferred from laboratory-based prototypes used in controlled settings to being implemented in a public health disaster context. To evaluate the DTAC, we used a case study approach, focusing on a prototype of a medical device, an Electron Paramagnetic Resonance (EPR) dosimeter, that can be used to screen the population for significant radiation exposures after a catastrophic nuclear event. The DTAC is based on the participatory-based design paradigm. The DTAC was effective at evaluating and guiding the development of the EPR technology in aspects related to the context in which it will ultimately be used, and facilitated its translation from a laboratory-based prototype to a field deployable system.

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 volunteers mouth for measurements. We compared dose estimates made using in vivo measurements made in the volunteers 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.