Biodosimetry versus physical dosimetry for emergency dose assessment following large-scale radiological exposures

Existing data on intercomparisons involving biodosimetry or physical dosimetry methods are analyzed and the results interpreted regarding their efficacy in triage in emergency dosimetry following mass casualty radiological events. The biodosimetry technique examined is dicentric chromosome aberrations (DCA). The physical dosimetry techniques include electron paramagnetic resonance (EPR) of biological material (teeth) and physical material (smartphone screen glass), and optically stimulated luminescence (OSL) of electronic components (surface mount resistors) from mobile phones. Issues relating to calibration and interpretation of the data are discussed. An important conclusion of the analysis is that more research is critically needed to interpret the efficacy of the various methods. Included in this needed research are intercomparisons of the various methods in controlled experiments and the need to harmonize protocols.     

An initial limited biodosimetry inter-comparison exercise: FOI and DRDC Ottawa

While biodosimetry is a valuable tool in radiation dose assessment, the dicentric assay, which is the most validated method to date, requires some degree of technical competence. Recently published ISO guidelines indicate the need for documenting competence and establishment of quality control programs. Inter-laboratory comparisons are required to document the ability to perform reproducible and accurate assessments. FOI and DRDC Ottawa have conducted an initial limited biodosimetry exercise inter-comparison for quality assurance purposes. The exercise involved blinded exchange of three previously prepared slides from each laboratory from samples that had been evaluated for each lab's dose–response curve. Approximately 100 cells from each slide were evaluated and aberration frequencies reported and compared to the expected frequencies. The limited number of cells evaluated for each sample could not permit statistically distinguishing a 20% difference in all the samples. However, the results indicated reasonable agreement in analyses for all samples for triage purposes. Comparison of aberration frequencies, rather than dose estimates, further illustrates consistent scoring criteria between the two laboratories. The exercise conducted by FOI and DRDC Ottawa provided an efficient means of documenting expertise. Such cooperation further establishes the international biodosimetry network and ensures our readiness for emergency response.     

Method for efficient establishment of technical biodosimetry competence

The current gold standard in biodosimetry, the dicentric assay, requires documented technical competence. Expertise is developed over time by evaluation of thousands of metaphases. Competence is documented through establishment of a dose–response curve, required by any service laboratory performing biodosimetry. Consistent and reliable evaluations must be established for new observers that might contribute to analyses for biological dose assessments. Discrepancies in evaluations jeopardize the reliability of assessments.The Swedish Defence Research Agency (FOI) together with the Norwegian Radiation Protection Authority (NRPA) conducted an inter-calibration exercise for the purpose of establishing comparable scoring criteria for evaluation of aberrations in metaphases. The exercise revealed specific aberrations that were difficult to identify and were consistent sources of uncertainty. Subsequently, a report detailing the FOI's scoring criteria was developed with visual examples and a strategy for establishing technical competence in metaphase scoring in an efficient manner evolved. Key components of the strategy are the review of guidance for biodosimetry, performance of inter-calibration exercises with previously established data sets, review of incongruous evaluations with a well-established observer, follow-up exercises depending on the initial outcome, and inter-comparisons to document agreement.Methods suggested here could be applied in training of new personnel. Documentation of methods in other laboratories could facilitate more consistent scoring criteria among the biodosimetry community, a problem observed in previous international inter-comparisons. Improved consistency among biodosimetry laboratories could facilitate reliably sharing the work load among different members of the biodosimetry community in the event of a mass casualty accident.     

The Chromosome Network for biodosimetry in Japan

The Chromosome Network in Japan was established just after the critical Tokai-mura accident in 2001 with the purposes of (1) integrating work to be ready for a large-scale radiation accident, (2) establishing standard methods for cytogenetic dose estimation, (3) creating a standard dose response curve in Japan, (4) preparing a training program for cytogenetic dose estimation and (5) training successors for biodosimetry work. In order to perform the cytogenetic dose estimation according to the same criteria, an inter-laboratory comparison is being experimentally carried out among the laboratories in the Chromosome Network.     

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.     

Optically stimulated luminescence (OSL) of dental enamel for retrospective assessment of radiation exposure

This paper briefly reviews the optically stimulated luminescence (OSL) properties of dental enamel and discusses the potential and challenges of OSL for filling the technology gap in biodosimetry required for medical triage following a radiological/nuclear accident or terrorist event. The OSL technique uses light to stimulate a radiation-induced luminescence signal from materials previously exposed to ionizing radiation. This luminescence originates from radiation-induced defects in insulating crystals and is proportional to the absorbed dose of ionizing radiation. In our research conducted to date, we focused on fundamental investigations of the OSL properties of dental enamel using extracted teeth and tabletop OSL readers. The objective was to obtain information to support the development of the necessary instrumentation for retrospective dosimetry using dental enamel in laboratory, or for in situ and non-invasive accident dosimetry using dental enamel in emergency triage. An OSL signal from human dental enamel was detected using blue, green, or IR stimulation. Blue/green stimulation associated with UV emission detection seems to be the most appropriate combination in the sense that there is no signal from un-irradiated samples and the shape of the OSL decay is clear. Improvements in the minimum detection level were achieved by incorporating an ellipsoidal mirror in the OSL system to maximize light collection. Other possibilities to improve the sensitivity and research steps necessary to establish the feasibility of the technique for retrospective assessment of radiation exposure are also discussed.     

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.     

Retrospective and emergency dosimetry in response to radiological incidents and nuclear mass-casualty events: A review

This paper reviews recent research on the application of the physical dosimetry techniques of electron paramagnetic resonance (EPR) and luminescence (optically stimulated luminescence, OSL, and thermoluminescence, TL) to determine radiation dose following catastrophic, large-scale radiological events. Such data are used in dose reconstruction to obtain estimates of dose due to the exposure to external sources of radiation, primarily gamma radiation, by individual members of the public and by populations. The EPR and luminescence techniques have been applied to a wide range of radiological studies, including nuclear bomb detonation (e.g., Hiroshima and Nagasaki), nuclear power plant accidents (e.g., Chernobyl), radioactive pollution (e.g., Mayak plutonium facility), and in the future could include terrorist events involving the dispersal of radioactive materials. In this review we examine the application of these techniques in ‘emergency’ and ‘retrospective’ modes of operation that are conducted on two distinct timescales. For emergency dosimetry immediate action to evaluate dose to individuals following radiation exposure is required to assess deterministic biological effects and to enable rapid medical triage. Retrospective dosimetry, on the other hand, contributes to the reconstruction of doses to populations and individuals following external exposure, and contributes to the long-term study of stochastic processes and the consequential epidemiological effects. Although internal exposure, via ingestion of radionuclides for example, can be a potentially significant contributor to dose, this review is confined to those dose components arising from exposure to external radiation, which in most studies is gamma radiation.The nascent emergency dosimetry measurement techniques aim to perform direct dose evaluations for individuals who, as members of the public, are most unlikely to be carrying a dosimeter issued for radiation monitoring purposes in the event of a radiation incident. Hence attention has focused on biological or physical materials they may have in their possession that could be used as surrogate dosimeters. For EPR measurements, in particular, this includes material within the body (such as bone or tooth biopsy) requiring invasive procedures, but also materials collected non-invasively (such as clippings taken from finger- or toenails) and artefacts within their personal belongings (such as electronic devices of which smart phones are the most common). For luminescence measurements, attention has also focused on components within electronic devices, including smartphones, and a wide range of other personal belongings such as paper and other polymer-based materials (including currency, clothing, bank cards, etc.). The paper reviews progress made using both EPR and luminescence techniques, along with their current limitations.For the longer-established approach of retrospective dosimetry, luminescence has been the most extensively applied method and, by employing minerals found in construction materials, it consequently is employed in dosimetry using structures within the environment. Recent developments in its application to large-scale radiation releases are discussed, including the atomic bomb detonations at Hiroshima and Nagasaki, fallout from the Chernobyl reactor and atmospheric nuclear bomb tests within the Semipalatinsk Nuclear Test Site and fluvially transported pollution within the Techa River basin due to releases from the Mayak facility. The developments made in applying OSL and TL techniques are discussed in the context of these applications. EPR measurements with teeth have also provided benchmark values to test the dosimetry models used for Chernobyl liquidators (clean-up workers), residents of Semipalatinsk Nuclear Tests Sites and inhabitants of the Techa River basin.For both emergency and retrospective dosimetry applications, computational techniques employing radiation transport simulations based on Monte Carlo code form an essential component in the application of dose determinations by EPR and OSL to dose reconstruction problems. We include in the review examples where the translation from the physical quantity of cumulative dose determined in the sampled medium to a dose quantity that can be applied in the reconstruction of dose to individuals and/or populations; these take into account the source terms, release patterns and the movements of people in the affected areas. One role for retrospective luminescence dosimetry has been to provide benchmark dose determinations for testing the models employed in dose reconstruction for exposed populations, notably at Hiroshima and Nagasaki. The discussion is framed within the context of the well-known radiation incidents mentioned above.     

Electron paramagnetic resonance radiation dosimetry in fingernails

There is now an increased need for accident dosimetry due to the increased risk of significant exposure to ionizing radiation from terrorism or accidents. In such scenarios, dose measurements should be made in individuals rapidly and with sufficient accuracy to enable effective triage. Electron paramagnetic resonance (EPR) is a physical method of high potential for meeting this need, providing direct measurements of the radiation-induced radicals, which are unambiguous signatures of exposure to ionizing radiation. For individual retrospective dosimetry, EPR in tooth enamel is a proven and effective technique when isolated teeth can be obtained. There are some promising developments that may make these measurements feasible without the need to remove the teeth, but their field applicability remains to be demonstrated. However, currently it is difficult under emergency conditions to obtain tooth enamel in sufficient amounts for accurate dose measurements. Since fingernails are much easier to sample, they can be used in potentially exposed populations to determine if they were exposed to life-threatening radiation doses. Unfortunately, only a few studies have been carried out on EPR radiation-induced signals in fingernails, and, while there are some promising aspects, the reported results were generally inconclusive. In this present paper, we report the results of a systematic investigation of the potential use of fingernails as retrospective radiation dosimeters.     

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.     

BiodosEPR-2006 Meeting: Acute dosimetry consensus committee recommendations on biodosimetry applications in events involving uses of radiation by terrorists and radiation accidents

In the aftermath of a radiological terrorism incident or mass-casualty radiation accident, first responders and receivers require prior guidance and pre-positioned resources for assessment, triage and medical management of affected individuals [NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA]. Several recent articles [Dainiak, N., Waselenko, J.K., Armitage, J.O., MacVittie, T.J., Farese, A.M., 2003. The hematologist and radiation casualties. Hematology (Am. Soc. Hematol. Educ. Program) 473–496; Waselenko, J.K., MacVittie, T.J., Blakely, W.F., Pesik, N., Wiley, A.L., Dickerson, W.E., Tsu, H., Confer, D.L., Coleman, C.N., Seed, T., Lowry, P., Armitage, J.O., Dainiak, N., Strategic National Stockpile Radiation Working Group, 2004. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann. Intern. Med. 140(12), 1037–1051; Blakely, W.F., Salter, C.A., Prasanna, P.G., 2005. Early-response biological dosimetry—recommended countermeasure enhancements for mass-casualty radiological incidents and terrorism. Health Phys. 89(5), 494–504; Goans, R.E., Waselenko, J.K., 2005. Medical management of radiation casualties. Health Phys. 89(5), 505–512; Swartz, H.M., Iwasaki, A., Walczak, T., Demidenko, E., Salikhov, I., Lesniewski, P., Starewicz, P., Schauer, D., Romanyukha, A., 2005. Measurements of clinically significant doses of ionizing radiation using non-invasive in vivo EPR spectroscopy of teeth in situ. Appl. Radiat. Isot. 62, 293–299; Weisdorf, D., Chao, N., Waselenko, J.K., Dainiak, N., Armitage, J.O., McNiece, I., Confer, D., 2006. Acute radiation injury: contingency planning for triage, supportive care, and transplantation. Biol. Blood Marrow Transplant. 12(6), 672–682], national [National Council of Radiation Protection and Measurements (NCRP), 1994. Management of persons accidentally contaminated with radionuclides. NCRP Report No. 65, Bethesda, Maryland, USA; NCRP, 2001. Management of terrorist events involving radioactive material. NCRP Report No. 138, Bethesda, Maryland, USA; NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA] and international [IAEA, 2005. Generic procedures for medical response during a nuclear or radiological emergency. EPR-Medical 2005, IAEA, Vienna, Austria] agencies have reviewed strategies for acute-phase biodosimetry. Consensus biodosimetric guidelines include: (a) clinical signs and symptoms, including peripheral blood counts, time to onset of nausea and vomiting and presence of impaired cognition and neurological deficits, (b) radioactivity assessment, (c) personal and area dosimetry, (d) cytogenetics, (e) in vivo electron paramagnetic resonance (EPR) and (f) other dosimetry approaches (i.e. blood protein assays, etc.). Emerging biodosimetric technologies may further refine triage and dose assessment strategies. However, guidance is needed regarding which biodosimetry techniques are most useful for different radiological scenarios and consensus protocols must be developed.The Local Organizing Committee for the Second International Conference on Biodosimetry and Seventh International Symposium on EPR Dosimetry and Applications (BiodosEPR-2006 Meeting) convened an Acute Dosimetry Consensus Committee composed of national and international experts to: (a) review the current literature for biodosimetry applications for acute-phase applications in radiological emergencies, (b) describe the strengths and weaknesses of each technique, (c) provide recommendations for the use of biodosimetry assays for selected defined radiation scenarios, and (d) develop protocols to apply these recommended biological dosimetry techniques with currently available supplies and equipment for first responders.The Acute Dosimetry Consensus Committee developed recommendations for use of a prioritized multiple-assay biodosimetric-based strategy, concluding that no single assay is sufficiently robust to address all of the potential radiation scenarios including management of mass casualties and diagnosis for early medical treatment. These recommendations may be used by first responders/first receivers that span time-windows of (i.e. 0–5 days) after the radiological incident for three radiological scenarios including: (a) radiation exposure device (RED), (b) radiological dispersal device (RDD), and (c) an improvised (or otherwise acquired) nuclear device (IND). Consensus protocols for various bioassays (i.e. signs and symptoms recording, bioassay sampling for radioactivity analysis, nail-clipping sampling for EPR analysis and blood collection for hematology, cytogenetics, and blood chemistry analyses) are presented as Appendix materials. As stated in NCRP Commentary No. 19 [NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA], multi-parameter triage (i.e. time to vomiting, lymphocyte kinetics, and other biodosimetry indicators) offers the current best strategy for early assessment of absorbed dose.     

Canadian biodosimetry capacity for response to radiation emergencies

In December 2001, Canada's response to the international political climate was launched by the creation of the Chemical, Biological, Radiological/Nuclear Research & Technology Initiative (CRTI). The National Biological Dosimetry Response Plan (NBDRP), established through partnering the expertise of three federal departments and one university, was created in response to this initiative. The NBDRP objectives were to develop a network of laboratories with expertise to perform biological dosimetry by cytogenetics and to investigate new technologies that may be applicable in the development of the new biodosimetry program. Since the creation of the NBDRP, Canada has made significant progress in enhancing expertise and resources to be better prepared for radiological/nuclear events. Through participation in exercises, the existing capacities were tested and recommendations for improvements were made. This paper describes the results from two exercises. The first exercise was designed to test the culturing, analysis, and reporting procedures within a single laboratory, and the second exercise was intended to test the capacity of the NBDRP. Future exercises will further challenge the network resulting in an improved national response capability.     

Protocol for emergency EPR dosimetry in fingernails

There is an increased need for after-the-fact dosimetry because of the high risk of radiation exposures due to terrorism or accidents. In case of such an event, a method is needed to make measurements of dose in a large number of individuals rapidly and with sufficient accuracy to facilitate effective medical triage. Dosimetry based on EPR measurements of fingernails potentially could be an effective tool for this purpose. This paper presents the first operational protocols for EPR fingernail dosimetry, including guidelines for collection and storage of samples, parameters for EPR measurements, and the method of dose assessment. In a blinded test of this protocol application was carried out on nails freshly sampled and irradiated to 4 and 20 Gy; this protocol gave dose estimates with an error of less than 30%.     

Uncertainty and routine use of Aerial l-alanine – Electron spin resonance dosimetry system

Aerial l-alanine pellet dosimeter is characterized by MiniScope MS300 electron spin resonance spectrometer measurements using Aer'EDE Version 2.0.4. software for dose calculation. The measurement traceability is achieved by Aerial dosimetry laboratory where dosimeters for calibration curve were irradiated by electron beam accelerator. Dose determinations in Aerial are traceable to National Physical Laboratory (NPL). The software used for construction of calibration curve gives also the standard deviation of the residuals of measurements for calibration that is used for dose uncertainty calculation. In aim to determine whether this value can actually be taken as absorbed dose uncertainty during usage of this dosimetry system, alanine dosimeters were irradiated with doses between 5 and 32 kGy by ⁶⁰Co laboratory source for internal calibration. The dose rate at the places for irradiation was (20 ± 0.5) mGy s⁻¹ determined by Fricke dosimeter. Measurement of each irradiated dosimeter was repeated ten times in ten days. The results of measurements were analyzed to identify the sources of uncertainty, as well as their quantification in evaluation of total measurement uncertainty. In addition to statistical effects, the very low dose rate that was used for the irradiation of alanine dosimeters affects the measurements of absorbed dose, particularly for higher absorbed doses where the measured dose can be up to 3% lower than the real.     

BiodosEPR-2006 consensus committee report on biodosimetric methods to evaluate radiation doses at long times after exposure

The requirements for biodosimetric techniques used at long times after exposure, i.e., 6 months to more than 50 years, are unique compared to the requirements for methods used for immediate dose estimation. In addition to the fundamental requirement that the assay measures a physical or biologic change that is proportional to the energy absorbed, the signal must be highly stable over time to enable reasonably precise determinations of the absorbed dose decades later. The primary uses of these biodosimetric methods have been to support long-term health risk (epidemiologic) studies or to support compensation (damage) claims. For these reasons, the methods must be capable of estimating individual doses, rather than group mean doses. Even when individual dose estimates can be obtained, inter-individual variability remains as one of the most difficult problems in using biodosimetry measurements to rigorously quantify individual exposures. Other important criteria for biodosimetry methods include obtaining samples with minimal invasiveness, low detection limits, and high precision. Cost and other practical limitations generally prohibit biodosimetry measurements on a large enough sample to replace analytical dose reconstruction in epidemiologic investigations. However, these measurements can be extremely valuable as a means to corroborate analytical or model-based dose estimates, to help reduce uncertainty in individual doses estimated by other methods and techniques, and to assess bias in dose reconstruction models. There has been extensive use of three biodosimetric techniques in irradiated populations: EPR (using tooth enamel), FISH (using blood lymphocytes), and GPA (also using blood); these methods have been supplemented with luminescent methods applied to building materials and artifacts. A large number of investigations have used biodosimetric methods many years after external and, to a lesser extent, internal exposure to reconstruct doses received from accidents, from occupational exposures, from environmental releases of radioactive materials, and from medical exposures. In most applications, the intent has been to either identify highly exposed persons or confirmed suspected exposures. Improvements in methodology, however, have led many investigators to attempt quantification of whole-body doses received, or in a few instances, to estimate organ doses. There will be a continued need for new and improved biodosimetric techniques not only to assist in future epidemiologic investigations but to help evaluate the long-term consequences following nuclear accidents or events of radiologic terrorism.     

Investigation of cosmic rays and their secondaries at aircraft altitudes

A very extensive study of the radiation field at aircraft altitudes has been carried out over the last few years. These investigations formed part of a European wide collaboration involving several laboratories with extensive experience in cosmic ray research and/or dosimetry. Among the main topics investigated were the charge spectra, LET spectra, anisotropy and dose values. The measurements were performed on subsonic and supersonic flights covering a wide range of altitudes and latitudes. Several active and passive instruments were employed in these studies and some results obtained with nuclear track detectors are described here. Comparisons are made with the results of other experiments and theoretical estimates using computer codes.     

High dose measurements using thermoluminescence of CaSO4:Dy

Thermoluminescence dosimetry has been very successful in monitoring the personnel level doses due to high sensitivity and reusability. However, these dosimeters saturate at high doses involved in radiation processing. Present investigations show that the range of high dose measurements can be increased by an order of magnitude by increasing the concentration of dysprosium in CaSO₄:Dy. A further increase in high dose measurements is possible by considering the ratio of two high temperature peaks. As the ratio of two peaks is an intrinsic property of the material, it is expected that the initial calibration of these dosimeters may not be required. This may be advantageous at very high doses where calibration of the dosimeters is quite problematic. Use of thermoluminescence peaks higher than 300°C also make this technique appropriate for high dose measurements at high temperatures.