Retrospective Dose Estimation Research Articles

Radiological injuries under low energy x-rays in mice depending on dose and protocol: comparative characterization of lesion severity and impact of the in vivo bone response on retrospective dose estimations

Objective. To improve our knowledge about the biological effects of over exposures involving low-energy x-rays, we developed and characterized a preclinical mouse model allowing to mimic different lesion severity degrees induced by 80 kV x-ray depending on the dose and protocol (single or repeated exposure). Approach. Mice were locally exposed (paw) to 80 kV x-rays in a single (15, 30 or 45 Gy in K air) or repeated exposition (2 × 15 or 3 × 15 Gy in K air) to assess different degrees of lesion severity. Six post-irradiation euthanasia time points (0, 7, 14, 21, 42, and 84 days) were determined to follow up the evolution of lesions based on the lesion score, weighing and cutaneous blood perfusion. The bone dose was estimated at the different time points by electron paramagnetic resonance (EPR) spectroscopy. Main results. The monitoring of the lesion severity allows to classify the exposure protocols according to their severity. EPR spectroscopy measurements allow to determine the bone dose on the day of irradiation which is 7 times higher than the initial dose for single protocols. However, the initial signal measured at the end of the repeated exposure was 27% lower than the signal measured for a single dose. The study of the kinetics of EPR signal showed a decrease of the EPR signal which is dependent on the exposure protocol but not on dose highlighting the impact of bone physiology on the bone dose estimation. Significance: the preclinical model developed allows to assess the impact of the dose and protocol on the lesion severity induced by low-energy x-ray. For the first time, the dynamics of free radicals have been quantified in an in vivo model, highlighting that the doses actually administered can be underestimated if samples are taken weeks or even months after exposure.

Three-Color FISH Method: A Comparison of Retrospective Cytogenetic Dose Estimations in Different Patients Undergoing Acute Emergency Irradiation

This work presents the results of the use of three-color FISH-staining of chromosomes (DNA probes to 1, 4 and 12 pairs of chromosomes) for the cytogenetic study of peripheral blood lymphocyte cultures of four patients at different times after irradiation in various emergency situations. All victims had initial dose estimations: one by EPR signal in the tooth enamel (1.12 Gy) and three by the dicentric frequencies (1.9; 3.2 and 4.3 Gy). There was a strong significant linear correlation between the observed translocation frequencies and the initial dose estimations. Retrospective indication of the dose by translocation frequencies was carried out with the help of own dose-effect curve, the obtained on the basis of experiments with the irradiation of blood of healthy donors in vitro. At the same time, dose estimates in the long terms after irradiation in three of these patients with the greatest lesion were significantly lower than they were established earlier (1.26; 2.06 and 2.47 Gy). The coincidence of the initial and repeated results was observed only in one remaining patient.

Dose Variations Using an X-Ray Cabinet to Establish in vitro Dose-Response Curves for Biological Dosimetry Assays.

In biological dosimetry, dose-response curves are essential for reliable retrospective dose estimation of individual exposure in case of a radiation accident. Therefore, blood samples are irradiated in vitro and evaluated based on the applied assay. Accurate physical dosimetry of the irradiation performance is a critical part of the experimental procedure and is influenced by the experimental setup, especially when X-ray cabinets are used. The aim of this study was to investigate variations and pitfalls associated with the experimental setups used to establish calibration curves in biological dosimetry with X-ray cabinets. In this study, irradiation was performed with an X-ray source (195 kV, 10 mA, 0.5 mm Cu filter, dose rate 0.52 Gy/min, 1st and 2nd half-value layer = 1.01 and 1.76 mm Cu, respectively, average energy 86.9 keV). Blood collection tubes were irradiated with a dose of 1 Gy in vertical or horizontal orientation in the center of the beam area with or without usage of an additional fan heater. To evaluate the influence of the setups, physical dose measurements using thermoluminescence dosimeters, electron paramagnetic resonance dosimetry and ionization chamber as well as biological effects, quantified by dicentric chromosomes and micronuclei, were compared. This study revealed that the orientation of the sample tubes (vertical vs. horizontal) had a significant effect on the radiation dose with a variation of −41% up to +49% and contributed to a dose gradient of up to 870 mGy inside the vertical tubes due to the size of the sample tubes and the associated differences in the distance to the focal point of the tube. The number of dicentric chromosomes and micronuclei differed by ~30% between both orientations. An additional fan heater had no consistent impact. Therefore, dosimetric monitoring of experimental irradiation setups is mandatory prior to the establishment of calibration curves in biological dosimetry. Careful consideration of the experimental setup in collaboration with physicists is required to ensure traceability and reproducibility of irradiation conditions, to correlate the radiation dose and the number of aberrations correctly and to avoid systematical bias influencing the dose estimation in the frame of biological dosimetry.

ТРЁХЦВЕТНЫЙ FISH-МЕТОД: КРИВЫЕ ДОЗА-ЭФФЕКТ ДЛЯ ТРАНСЛОКАЦИЙ В КУЛЬТУРАХ ЛИМФОЦИТОВ ПЕРИФЕРИЧЕСКОЙ КРОВИ ПОСЛЕ ГАММА-ОБЛУЧЕНИЯ IN VITRO

Purpose: Plotting dose-effect curves for translocations identified using the tricolor FISH method based on the results of cytogenetic analysis of cultures of peripheral blood lymphocytes of healthy donors after in vitro gamma irradiation. 
 Material and methods: Venous blood was obtained from three donors (2 men and 1 woman aged from 28 to 41 years) and subjected to in vitro gamma irradiation from a 60Co source at doses of 0.10; 0.15; 0.25; 0.35; 0.50; 0.75; 1.00; 1.50; 2.00 and 3.00 Gy at 37 ° C (dose rate 0.5 Gy / min). For tricolor FISH staining, two different sets of DNA probes were used for chromosome pairs 1, 4, 12 and 2, 3, 8. Metaphases with a quasi-diploid number of chromosomes (40-46) and a complete set of all FISH-stained chromosomes, taking into account their total length, were selected for analysis. Differentiation of stable and unstable cells was also carried out. In the cytogenetic analysis, traditional terminology was used with the designation of translocations as reciprocal (complete, two-sided), non-reciprocal (terminal, incomplete, or unilateral), or interstitial.
 Results: The obtained numerical data were used to statistically compare the frequencies of FISH-recorded translocations when using different sets of DNA probes, when calculating of chromosome aberrations were in all (unstable and stable) and stable metaphase cells, when comparing of the frequencies of FISH-recorded translocations and dicentrics, and assessing of the contribution of the level of translocations between FISH-stained chromosome pairs in the total translocation frequency. The plotted dose-effect curves generally corresponded to the linear-quadratic form.
 Conclusion: Dose dependences obtained for translocations using two different selected tricolor sets of DNA probes did not differ statistically significantly. At the same time, cytogenetic analysis of only stable metaphase cells revealed a tendency to register lower levels of translocations than when analyzing all cells (unstable and stable ), at the highest doses of 2 and 3 Gy. The levels of dicentrics formed with the participation of FISH-stained chromosomes were significantly lower than the number of observed translocations. The quantitative contribution of translocations between FISH-stained pairs of chromosomes turned out to be very low, which clearly does not contribute to an increase in the sensitivity of the FISH method of retrospective dose estimation as compared to its one-color version. At the same time, the three-color FISH-staining makes it possible to identify such variants of chromosomal rearrangements that are not recorded using the one-color FISH method.

Potential Use of Environmental Biological Samples for Retrospective Electron Paramagnetic Resonance Dosimetry of Radiation Accidents

Retrospective dosimetry is one of the most important tools of accident dosimetry for environmental dose estimation when large-scale radiological incidents and nuclear mass-casualty events occur. Electron paramagnetic resonance (EPR) dosimetry is a physical method for the retrospective assessment of absorbed dose based on the measurement of stable radiation-induced radicals in materials. Different from the fast disappearance of radials in aqueous systems, the radials can persist indefinitely in some organized matrices. Therefore, environmental materials contained in creatures from sea or land can be potentially used as environmental dosimeters for a retrospective dose analysis. This study aims to assess the EPR signals of free radicals from environmental biological samples, potentially for the retrospective dose estimation. The evaluated samples involve ox bone, cyclina shell, clam shell, chitin from squid, and human tissue (enamel and fingernail). First, we dehydrate and grind these materials to the powder with different sizes. Subsequently, all materials were irradiated with different doses ranging from 5 Gy to 50 Gy using 6 MV linear accelerator, and EPR spectra of these materials were obtained from the calculation of peak-to-peak amplitudes. The dose-response curve of EPR signals versus irradiated dose for the six materials shows good linearity (R2~0.99). For the grain-size experiment, the ox bone and tooth with 0.5 mm, the chitin with 0.1 mm, and the others with 1 mm have the strongest signal. For the storage temperature experiment, the optimal temperature of storage is at −20 °C for tooth, fingernail, ox bone, and chitin, at 45 °C for clam shell and cyclina shell where the signal fading is minimal. In conclusion, the developed dose-response curves of the six materials may potentially help a fast, rough retrospective dose reconstruction under the environment when radiation accidents occur.

Trends in Estimated Thyroid, Salivary Gland, Brain, and Eye Lens Doses From Intraoral Dental Radiography Over Seven Decades (1940 TO 2009).

The purpose of this study is to support retrospective dose estimation for epidemiological studies by providing estimates of historical absorbed organ doses to the brain, lens of the eye, salivary glands, and thyroid from intraoral dental radiographic examinations performed from 1940 to 2009. We simulated organ doses to an adult over 10 y time periods from 1940 to 2009, based on commonly used sets of x-ray machine settings collected from the literature. Simulations to estimate organ dose were performed using personal computer x-ray Monte Carlo software. Overall, organ doses were less than 1 mGy for a single intraoral radiograph for all decades. From 1940 to 2009, doses to the brain, eye lens, salivary glands, and thyroid decreased by 86, 96, 95, and 89%, respectively. Of these four organs, the salivary glands received the highest doses, with values decreasing from about 0.23 mGy in the 1940s to 0.025 mGy in the 2000s for a single intraoral radiograph. Based on simulations using collected historical data on x-ray technical parameters, improvements in technology and optimization of the technical settings used to perform intraoral dental radiography have resulted in a decrease in absorbed dose to the brain, eye lens, salivary glands, and thyroid over the period from 1940 to 2009.

Experimental evaluation of a radiation dose management system-integrated 3D skin dose map by comparison with XR-RV3 Gafchromic® films

ObjectiveTo assess the interactive Skin Dose Map® tool (SDMTool) integrated to the radiation dose management system (RDMS) DoseWatch® with Gafchromic® films for implementation in routine practice. MethodsA retrospective dose estimation software SDMTool was used to calculate Peak Skin Dose (PSD) and display the patient skin dose distribution. PSD was calculated with a triangle mesh of 0.055 cm2 resolution on ICRP 110 male anthropomorphic phantom and with a square ROI of 1 cm2 on flat phantom. The tool uses Radiation Dose Structured Reports (RDSR) data to model exposure events and calculate the PSD per event. The PSD and the skin dose distribution estimated with SDMTool were evaluated in comparison with Gafchromic® films positioned under the PMMA phantom (20 cm) for 13 configurations. Measurements were performed on a Philips system. Statistical analysis were carried out to compare PSDFilm and PSDSDM. ResultsAverage differences between PSDFilm and PSDSDM were 6% ± 6% (range from −3% to 22%) for flat phantom and 5% ± 7% (range from −3% to 25%) for ICRP phantom. Concordance was good between the measured PSDFilm and the estimated PSDSDM with Lin’s coefficient estimation and 95% Confidence Interval of 0.979 [0.875; 0.984] for flat phantom and 0.977 [0.877; 0.985] for ICRP phantom. Dose map representations are concordant for 11 of the 13 tests on PMMA phantom. Disparities arose from the limitations of the RSDR format: table displacement during fluoroscopy events and the use of wedge filter. ConclusionThe results found in this experimental evaluation show that the SDMTool is a suitable alternative to Gafchromic® film to calculate PSD.

Construction of fluorescence in situ hybridization (FISH) translocation dose-response calibration curve with multiple donor data sets using R, based on ISO 20046:2019 recommendations

Purpose: Dose-response curve (DRC) generation is an important aspect in cytogenetic biodosimetry for accurate dose estimation for individuals suspected of prior irradiation. DRC construction with dicentric chromosomes after acute radiation is well-established following the publication of the IAEA EPR-Biodosimetry 2011 and ISO 19238:2014. However, the short half-life of dicentrics might not be suitable for retrospective dose estimation in radiation medical workers, radiation accident clean-up workers and the general public living in areas with higher than average amount of radiation. There is an urgent need for a chromosome translocation-based DRC, which is constructed based on translocation identification with fluorescence in situ hybridization (FISH). Despite several attempts to generate such a DRC in the past 40 years, no internationally standardized protocol has been developed until 2019, resulting in possible statistical uncertainties between DRCs previously generated.Materials and methods: Using the recently published ISO 20049:2019, a DRC from five healthy donors (four males: 23, 35, 44, 55 years old, one female: 33 years old) was generated with age-adjusted translocations scored per cell equivalent (age-adjusted Tr/CE), using a modified R-script previously published in EPR-Biodosimetry, for 60Co gamma-ray doses of 0, 0.01, 0.02, 0.05, 0.1, 0.2, 0.5 and 1 Gy. The translocation data set used, based on probes used for chromosomes number 1, 2, and 4, was previously published by Abe et al. in 2018.Results: The results output from R include the DRC coefficients (C, α, β), their p-values, the goodness-of-fit Pearson’s chi square value and its corresponding p-value, and the DRC with its 95% confidence interval (CI). The equation of the DRC obtained was 0.0005 (±0.0001) +0.0178 (±0.0037) D + 0.0901 (±0.0054) D2. DRC generated with averaged Tr/CE had a wider 95% CI than DRC generated with pooled Tr/CE, resulting in a 1.3–1.5 times increase in estimated dose range. No outliers between α coefficients from previously published modified DRCs and our DRC were detected with robust Z-score.Conclusions: ISO 20046:2019 should be referenced for future FISH translocation-based DRC generation to ensure statistical reliability of dose estimation. Important considerations for FISH translocation-based DRC up to 1 Gy include scoring more than 2000 CE per dose, the use of multiple donors, age-adjustment of observed translocations, the use of a minimum of 5 dose points including 0 Gy, scoring of total simple translocations in only stable cells and the decision of using pooled or averaged age-adjusted Tr/CE.

Conversion of computational human phantoms into DICOM-RT for normal tissue dose assessment in radiotherapy patients

Radiotherapy (RT) treatment planning systems (TPS) are designed for the fast calculation of dose to the tumor bed and nearby organs at risk using x-ray computed tomography (CT) images. However, CT images for a patient are typically available for only a small portion of the body, and in some cases, such as for retrospective epidemiological studies, no images may be available at all. When dose to organs that lie out-of-scan must be estimated, a convenient alternative for the unknown patient anatomy is to use a matching whole-body computational phantom as a surrogate. The purpose of the current work is to connect such computational phantoms to commercial RT TPS for retrospective organ dose estimation. A custom software with graphical user interface (GUI), called the DICOM-RT Generator, was developed in MATLAB to convert voxel computational phantoms into the digital imaging and communications in medicine radiotherapy (DICOM-RT) format, compatible with commercial TPS. DICOM CT image sets for the phantoms are created via a density-to-Hounsfield unit (HU) conversion curve. Accompanying structure sets containing the organ contours are automatically generated by tracing binary masks of user-specified organs on each phantom CT slice. The software was tested on a library of body size-dependent phantoms, the International Commission on Radiological Protection reference phantoms, and a canine voxel phantom, taking only a few minutes per conversion. The resulting DICOM-RT files were tested on several commercial TPS. As an example application, a library of converted phantoms was used to estimate organ doses for members of the National Wilms Tumor Study (NWTS) cohort. The converted phantom library, in DICOM format, and a standalone MATLAB-compiled executable of the DICOM-RT Generator are available for others to use for research purposes (http://ncidose.cancer.gov).

Photon energy readings in OSL dosimeter filters: an application to retrospective dose estimation for nuclear medicine workers

This work investigates the applicability of using data from personal monitoring dosimeters to assess photon energies to which medical workers were exposed. Such determinations would be important for retrospective assessments of organ doses to be used in occupational radiation epidemiology studies, particularly in the absence of work history or other information regarding the energy of the radiation source. Monthly personal dose equivalents and filter ratios under two different metallic filters contained in the Luxel+® dosimeter were collected from Landauer, Inc. from 19 nuclear medicine (NM) technologists employed by three medical institutions, the institution A only performing traditional NM imaging (primarily using 99mTc) and institutions B and C also performing positron emission tomography (PET, using 18F). Calibration data of the Luxel+® dosimeter for various xray spectra were used to establish ranges of filter ratios from 1.1 to 1.6 for 99mTc and below 1.1 for 18F. Median filter ratios were 1.33 (Interquartile range (IQR), 0.15) for institution A, 1.08 (IQR, 0.16) for institution B, and 1.08 (IQR, 0.14) for institution C. The distributions of these filter ratios were statistically-significantly different between the institution A only performing traditional NM imaging and institutions B and C also performing PET imaging. In this proof-of-concept study, filter ratios from personal monitoring dosimeters were used to assess differences in photon energies to which NM technologists were exposed. Dosimeters from technologists only performing traditional NM procedures mostly showed Al/Cu filter ratios above 1.2, those likely performing only PET in a particular month had filter ratios below 1.1, and those which showed filter ratios between 1.1 and 1.2 likely came from technologists rotating between traditional NM and PET imaging in the same month. These results suggest that it is possible to distinguish technologists who only worked with higher-energy procedures versus those who only worked with other types of NM procedures.

Local bone-marrow exposure: how to interpret the data on stable chromosome aberrations in circulating lymphocytes? (some comments on the use of FISH method for dose reconstruction for Techa riverside Residents).

The method of fluorescence in situ hybridization (FISH) applied to peripheral blood T lymphocytes is used for retrospective dose estimation, and the results obtained from the analysis of stable chromosomal aberrations are usually interpreted as a dose accumulated in the red bone marrow (RBM). However, after local internal exposure of the RBM, doses derived from FISH were found to be lower than those derived from direct measurements of radionuclides accumulated in the bodies of exposed persons. These results were obtained for people residing near the Techa River contaminated by 89,90Sr (beta-emitters) in 1949-1956 (Chelyabinsk Oblast, Russia). A new analysis has been performed of the combined results of FISH studies (n=178) undertaken during 1994-2012 for persons living on the Techa Riverside. Analysis confirms the lower slope of the translocation yield per Gy (8.0±0.7×10-3) for Techa residents in comparison with FISH data for donors with external exposures (11.6±1.6×10-3, Tawn et al., Radiat Res 184(3):296-303, 2015). It was suggested that some portion of T cells remained unexposed, because they represented the descendants of T cell progenitors, which had migrated to the thymus before the start of 89,90Sr intakes. To clarify this problem, the dynamics of T-cell Genera (TG), combining all descendants of specific T-cell progenitor reaching the thymus, was considered. Rates of TGs produced by RBM over different age periods of human life were estimated with the use of the mathematic model of T-cell homeostasis (Bains, Mathematical modeling of T-cell homeostasis. A thesis submitted for the degree of Doctor of Philosophy of the University College London. http://discovery.ucl.ac.uk/20159/1/20159.pdf , 2010). The rate of TG loss during the lifetime was assumed to be very small in comparison with production rate. The recirculation of mature T lymphocytes in contaminated RBM was taken into account. According to our model estimates, at the time of blood sampling, the fraction of exposed T lymphocytes (whose progenitors were irradiated) ranged from 20 to 80% depending on the donors' age at the start of exposure to 89,90Sr. Dose to T lymphocytes, estimated from FISH studies, should be about 0.6-0.9 of RBM dose for residents of the upper Techa region and about 0.4-0.8 in the middle Techa region. Our results could explain the lower value of translocation yield per Gy obtained for Techa residents. The approaches for further model improvement and validation are discussed in this paper.

LONG-TERM BIODOSIMETRY REDUX.

This paper revisits and reiterates the needs, purposes and requirements of biodosimetric assays for long-term dose and health risk assessments. While the most crucial need for biodosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure assessment. Hence, the needs for retrospective dose estimation are likely to be greater in the future. The value of biodosimetry can be considerably enhanced with the development of new or improved methods, particularly with suitability for application at long periods of time after exposure.

Convolution-based estimation of organ dose in tube current modulated CT

Estimating organ dose for clinical patients requires accurate modeling of the patient anatomy and the dose field of the CT exam. The modeling of patient anatomy can be achieved using a library of representative computational phantoms (Samei et al Pediatr. Radiol. 44 460–7). The modeling of the dose field can be challenging for CT exams performed with a tube current modulation (TCM) technique. The purpose of this work was to effectively model the dose field for TCM exams using a convolution-based method. A framework was further proposed for prospective and retrospective organ dose estimation in clinical practice.The study included 60 adult patients (age range: 18–70 years, weight range: 60–180 kg). Patient-specific computational phantoms were generated based on patient CT image datasets. A previously validated Monte Carlo simulation program was used to model a clinical CT scanner (SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany). A practical strategy was developed to achieve real-time organ dose estimation for a given clinical patient. CTDIvol-normalized organ dose coefficients () under constant tube current were estimated and modeled as a function of patient size. Each clinical patient in the library was optimally matched to another computational phantom to obtain a representation of organ location/distribution. The patient organ distribution was convolved with a dose distribution profile to generate values that quantified the regional dose field for each organ. The organ dose was estimated by multiplying with the organ dose coefficients (). To validate the accuracy of this dose estimation technique, the organ dose of the original clinical patient was estimated using Monte Carlo program with TCM profiles explicitly modeled. The discrepancy between the estimated organ dose and dose simulated using TCM Monte Carlo program was quantified. We further compared the convolution-based organ dose estimation method with two other strategies with different approaches of quantifying the irradiation field.The proposed convolution-based estimation method showed good accuracy with the organ dose simulated using the TCM Monte Carlo simulation. The average percentage error (normalized by CTDIvol) was generally within 10% across all organs and modulation profiles, except for organs located in the pelvic and shoulder regions.This study developed an improved method that accurately quantifies the irradiation field under TCM scans. The results suggested that organ dose could be estimated in real-time both prospectively (with the localizer information only) and retrospectively (with acquired CT data).

The two-dimensional Monte Carlo: a new methodologic paradigm for dose reconstruction for epidemiological studies.

Retrospective dose estimation, particularly dose reconstruction that supports epidemiological investigations of health risk, relies on various strategies that include models of physical processes and exposure conditions with detail ranging from simple to complex. Quantification of dose uncertainty is an essential component of assessments for health risk studies since, as is well understood, it is impossible to retrospectively determine the true dose for each person. To address uncertainty in dose estimation, numerical simulation tools have become commonplace and there is now an increased understanding about the needs and what is required for models used to estimate cohort doses (in the absence of direct measurement) to evaluate dose response. It now appears that for dose-response algorithms to derive the best, unbiased estimate of health risk, we need to understand the type, magnitude and interrelationships of the uncertainties of model assumptions, parameters and input data used in the associated dose estimation models. Heretofore, uncertainty analysis of dose estimates did not always properly distinguish between categories of errors, e.g., uncertainty that is specific to each subject (i.e., unshared error), and uncertainty of doses from a lack of understanding and knowledge about parameter values that are shared to varying degrees by numbers of subsets of the cohort. While mathematical propagation of errors by Monte Carlo simulation methods has been used for years to estimate the uncertainty of an individual subject's dose, it was almost always conducted without consideration of dependencies between subjects. In retrospect, these types of simple analyses are not suitable for studies with complex dose models, particularly when important input data are missing or otherwise not available. The dose estimation strategy presented here is a simulation method that corrects the previous deficiencies of analytical or simple Monte Carlo error propagation methods and is termed, due to its capability to maintain separation between shared and unshared errors, the two-dimensional Monte Carlo (2DMC) procedure. Simply put, the 2DMC method simulates alternative, possibly true, sets (or vectors) of doses for an entire cohort rather than a single set that emerges when each individual's dose is estimated independently from other subjects. Moreover, estimated doses within each simulated vector maintain proper inter-relationships such that the estimated doses for members of a cohort subgroup that share common lifestyle attributes and sources of uncertainty are properly correlated. The 2DMC procedure simulates inter-individual variability of possibly true doses within each dose vector and captures the influence of uncertainty in the values of dosimetric parameters across multiple realizations of possibly true vectors of cohort doses. The primary characteristic of the 2DMC approach, as well as its strength, are defined by the proper separation between uncertainties shared by members of the entire cohort or members of defined cohort subsets, and uncertainties that are individual-specific and therefore unshared.

Prediction of the location and size of the stomach using patient characteristics for retrospective radiation dose estimation following radiotherapy

Following cancer radiotherapy, reconstruction of doses to organs, other than the target organ, is of interest for retrospective health risk studies. Reliable estimation of doses to organs that may be partially within or fully outside the treatment field requires reliable knowledge of the location and size of the organs, e.g., the stomach, which is at risk from abdominal irradiation. The stomach location and size are known to be highly variable between individuals, but have been little studied. Moreover, for treatments conducted years ago, medical images of patients are usually not available in medical records to locate the stomach. In light of the poor information available to locate the stomach in historical dose reconstructions, the purpose of this work was to investigate the variability of stomach location and size among adult male patients and to develop prediction models for the stomach location and size using predictor variables generally available in medical records of radiotherapy patients treated in the past. To collect data on stomach size and position, we segmented the contours of the stomach and of the skeleton on contemporary computed tomography (CT) images for 30 male patients in supine position. The location and size of the stomach was found to depend on body mass index (BMI), ponderal index (PI), and age. For example, the anteroposterior dimension of the stomach was found to increase with increasing BMI (≈0.25 cm kg–1 m2) whereas its craniocaudal dimension decreased with increasing PI (≈−3.3 cm kg–1 m3) and its transverse dimension increased with increasing PI (≈2.5 cm kg–1 m3). Using the prediction models, we generated three-dimensional computational stomach models from a deformable hybrid phantom for three patients of different BMI. Based on a typical radiotherapy treatment, we simulated radiotherapy treatments on the predicted stomach models and on the CT images of the corresponding patients. Those dose calculations demonstrated good agreement between predicted and actual stomachs compared with doses derived from a reference model of the body that might be used in the absence of individual CT scan data.

Assessment of retrospective dose estimation, with fluorescence in situ hybridization (FISH), of six victims previously exposed to accidental ionizing radiation

The present study aims to evaluate the use of the fluorescence in situ hybridization (FISH) translocation assay for retrospective dose estimation of acute accidental exposure to radiation in the past. Reciprocal translocation analysis by FISH with three whole-chromosome probes was performed on normal peripheral blood samples. Samples were irradiated with 0–5Gy 60Co γ-rays in vitro, and dose–effect curves were established. FISH-based translocation analyses for six accident victims were then performed, and biological doses were estimated retrospectively by comparison with the dose–effect curves. Reconstructed doses by FISH were compared with estimated doses obtained by analysis of di-centrics performed soon after exposure, or with dose estimates from tooth-enamel electron paramagnetic resonance (EPR) data obtained at the same time as the FISH analysis. Follow-up FISH analyses for an adolescent victim were performed. Results showed that dose–effect curves established in the present study follow a linear-quadratic model, regardless of the background translocation frequency. Estimated doses according to two dose–effect curves for all six victims were similar. FISH dose estimations of three adult victims exposed to accidental radiation less than a decade prior to analysis (3, 6, or 7 years ago) were consistent with those estimated with tooth-enamel EPR measurements or analyses of di-centrics. Estimated doses of two other adult victims exposed to radiation over a decade prior to analysis (16 or 33 years ago) were underestimated and two to three times lower than the values obtained from analysis of di-centrics or tooth-enamel EPR. Follow-up analyses of the adolescent victim showed that doses estimated by FISH analysis decrease rapidly over time. Therefore, the accuracy of dose estimates by FISH is acceptable only when analysis is performed less than 7 years after exposure. Measurements carried out more than a decade after exposure through FISH analysis resulted in underestimation of the biological doses compared with values obtained through analysis of di-centrics and tooth-enamel EPR.

Cytogenetic analysis in 16-year follow-up study of a mother and fetus exposed in a radiation accident in Xinzhou, China

In November 1992, a radiation accident occurred in Xinzhou, due to the collection by a farmer of an unused 60Co source; 37 individuals were exposed to ionizing radiation. Three individuals died and the farmer's 19-weeks-pregnant wife suffered acute radiation symptoms. Conventional chromosome analysis, cytokinesis-block micronuclei (CBMN) assay and fluorescence in situ hybridization (FISH) painting with three pairs of whole chromosome probes were used to analyze chromosomal aberrations for the pregnant female and her baby during the 16 years following the accident. The yields of dicentrics and rings (dic+r) continually declined between 41 days and 16 years after the accident. The frequency of binucleated MN also decreased over time for both mother and daughter. Sixteen years after exposure, the yields of dic+r and binucleated MN decreased to normal levels, but the reciprocal translocation frequencies remained elevated, for both mother and daughter. FISH results showed a decreasing yield of translocations with time. Based on the changes in maternal translocation frequency, the daughter's dose at the time of exposure was estimated as 1.82 (1.35–2.54)Gy. This was consistent with the clinical manifestations of severe mental retardation and low IQ score. FISH-based translocation analysis can be used for follow-up studies on accidental exposure and, after correction, for retrospective dose estimation for individuals prenatally exposed to radiation.

Uncertainties dose evaluation induced by non-exhaustivity data

Introduction The individual dose estimation to organs at risk has known important evolution last years, with new tools whose permits to obtain histogram dose-volume. However, dose reconstruction based on retrospective epidemiology studies are often realized dozens of years after initial radiotherapy, based sometimes on non-exhaustive data, both on patient anatomy as the beams. The aim is to establish the link between the missing data rate and the uncertainties induced on out-of-field dose by the non-exhaustivity of the data. Methods and materials Statistics are used for evaluating the missing data rate in patient radiotherapy files from french, british, Italian and dutch cohorts. The around twenty variables contributing to the patient anatomy modelisation and dose calculation are evaluated. Statistics methods (multiples imputation) are used to complete the missing data. For uncertainties dose calculation, the formalism defined in TRS 384 is applied, variances are deducted from the statistical study. Results The primary results indicate that, according to the considered parameter, missing data rate is very inconstant and strongly linked to the year of treatment and the institution. The dose uncertainties induced is very linked to the considered parameter. Conclusion The results of the study should allow a better knowledge of the uncertainties in retrospective dose estimations used for long term studies of effects of radiotherapy.

Comparative Measurements of the External Radiation Exposure in a 137Cs Contaminated Village in Belarus Based on Optically Stimulated Luminescence in NaCl and Thermoluminescence in LiF

Laboratory studies have shown that ordinary household salt (NaCl) exhibits several promising properties for retrospective dosimetry; e.g., a linear dose response and a low detection limit, down to a few mGy or even less. In an attempt to test NaCl as a dosimeter outside the laboratory, the first results from the use of NaCl as a dosimeter under normal environmental conditions are reported here. For this purpose, special dosimeter kits with NaCl and lithium fluoride (LiF) chips were designed. The dosimeter kits were positioned at different locations in a Chernobyl Cs-contaminated village in Belarus during the summers of 2008, 2009, and 2010. The results from the two luminescent detectors were also compared with those of measurements carried out with a handheld 75 cm NaI(Tl) detector and with a 8 dm high pressure ionization chamber. The radiation level in the village was inhomogeneous, and depending on the type of house and countermeasures carried out, the ambient dose rate inside and around the houses varied between 0.05 μSv h and 0.50 μSv h. Based on the different measurements, the annual external effective dose to a hypothetical adult population in the village was estimated as 1-1.5 mSv y. Detector readings from the two luminescent materials correlated relatively strongly to that of the ambient survey NaI(Tl) detector. After three repeated surveys using similar dosimeter kits for prospective dosimetry, the potential use of ordinary household salt as a complement to other techniques for retrospective dose estimations is more evident, and shortcomings of the technique have been identified.

Standardisation and Validation of Cytogenetic Markers to Quantify Radiation Absorbed Dose

The amounts of radiation exposure received by radiation workers are monitored generally by physical dosimeters like thermoluminescence dosimeter (TLD) and film badge. However, in practice the over-exposure recorded by physical dosimeters need to be confirmed with biological dosimeters. In addition to confirming the dose recorded by physical dosimeters, biological dosimeters play an important role in estimating the doses received during accidental exposures. Exposure to high levels of radiation induces certain biochemical, biophysical, and immunological changes (biomarkers) in a cell. Measurement of these changes are generally precise but cannot be effectively used to assess the dose, as the level of these changes return to normalcy within hours to months after exposure. Thus, among various biological indicators, cytogenetic indicators are considered practical and reliable for dose estimation. The paper highlights the importance and establishment of biodosimetry facility using genetic markers such as the sensitive dicentric chromosomes, rapid micronucleus assay and stable translocations measured using fluorescence in situ hybridisation and GTG banding for retrospective dose estimation. Finally, the development of gH2AX assay, as a potential marker of triage dosimeter, is discussed. Defence Science Journal, 2011, 61(2), pp.125-132 , DOI:http://dx.doi.org/10.14429/dsj.61.832