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 method's 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.

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.

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.

A Framework for Comparative Evaluation of Dosimetric Methods to Triage a Large Population Following a Radiological Event.

BACKGROUND: To prepare for a possible major radiation disaster involving large numbers of potentially exposed people, it is important to be able to rapidly and accurately triage people for treatment or not, factoring in the likely conditions and available resources. To date, planners have had to create guidelines for triage based on methods for estimating dose that are clinically available and which use evidence extrapolated from unrelated conditions. Current guidelines consequently focus on measuring clinical symptoms (e.g., time-to-vomiting), which may not be subject to the same verification of standard methods and validation processes required for governmental approval processes of new and modified procedures. Biodosimeters under development have not yet been formally approved for this use. Neither set of methods has been tested in settings involving large-scale populations at risk for exposure. OBJECTIVE: To propose a framework for comparative evaluation of methods for such triage and to evaluate biodosimetric methods that are currently recommended and new methods as they are developed. METHODS: We adapt the NIH model of scientific evaluations and sciences needed for effective translational research to apply to biodosimetry for triaging very large populations following a radiation event. We detail criteria for translating basic science about dosimetry into effective multi-stage triage of large populations and illustrate it by analyzing 3 current guidelines and 3 advanced methods for biodosimetry. CONCLUSIONS: This framework for evaluating dosimetry in large populations is a useful technique to compare the strengths and weaknesses of different dosimetry methods. It can help policy-makers and planners not only to compare the methods' strengths and weaknesses for their intended use but also to develop an integrated approach to maximize their effectiveness. It also reveals weaknesses in methods that would benefit from further research and evaluation.

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.

A critical assessment of biodosimetry methods for large-scale incidents.

Recognition is growing regarding the possibility that terrorism or large-scale accidents could result in potential radiation exposure of hundreds of thousands of people and that the present guidelines for evaluation after such an event are seriously deficient. Therefore, there is a great and urgent need for after-the-fact biodosimetric methods to estimate radiation dose. To accomplish this goal, the dose estimates must be at the individual level, timely, accurate, and plausibly obtained in large-scale disasters. This paper evaluates current biodosimetry methods, focusing on their strengths and weaknesses in estimating human radiation exposure in large-scale disasters at three stages. First, the authors evaluate biodosimetry's ability to determine which individuals did not receive a significant exposure so they can be removed from the acute response system. Second, biodosimetry's capacity to classify those initially assessed as needing further evaluation into treatment-level categories is assessed. Third, we review biodosimetry's ability to guide treatment, both short- and long-term, is reviewed. The authors compare biodosimetric methods that are based on physical vs. biological parameters and evaluate the features of current dosimeters (capacity, speed and ease of getting information, and accuracy) to determine which are most useful in meeting patients' needs at each of the different stages. Results indicate that the biodosimetry methods differ in their applicability to the three different stages, and that combining physical and biological techniques may sometimes be most effective. In conclusion, biodosimetry techniques have different properties, and knowledge of their properties for meeting the different needs for different stages will result in their most effective use in a nuclear disaster mass-casualty event.

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%.

The view from the trenches: part 2-technical considerations for EPR screening.

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.

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.

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.