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Dose reconstruction for therapeutic and diagnostic radiation exposures: use in epidemiological studies.

This paper describes methods developed specifically for reconstructing individual organ- and tissue-absorbed dose of radiation from past exposures from medical treatments and procedures for use in epidemiological studies. These methods have evolved over the past three decades and have been applied to a variety of medical exposures including external-beam radiation therapy and brachytherapy for malignant and benign diseases as well as diagnostic examinations. The methods used for estimating absorbed dose to organs in and outside the defined treatment volume generally require archival data collection, abstraction and review, and phantom measurements to simulate past exposure conditions. Three techniques are used to estimate doses from radiation therapy: (1) calculation in three-dimensional mathematical computer models using an extensive database of out-of-beam doses measured in tissue-equivalent materials, (2) measurement in anthropomorphic phantoms constructed of tissue-equivalent material, and (3) calculation using a three-dimensional treatment-planning computer. For diagnostic exposures, doses are estimated from published data and software based on Monte Carlo techniques. We describe and compare these methods of dose estimation and discuss uncertainties in estimated organ doses and potential for future improvement. Seven epidemiological studies are discussed to illustrate the methods.

Body Burden↗

Dose reconstruction for residents living in 60Co-contaminated rebar buildings.

The first 60Co-contaminated rebar building was discovered in Taipei city in 1992. As of 18 July 1997, 144 buildings with 1,327 housing units were confirmed to contain 60Co-contaminated rebars. All these reinforced concrete buildings were constructed between 1982 and 1984. Thousands of residents have been exposed to ionizing radiation of various degrees. Preliminary assessments by the Atomic Energy Council showed that the accumulated maximal doses ranged from a few mSv to several Sv. The purpose of this work was to reconstruct more reliable individual doses for epidemiologic and medical uses. This reconstruction provided the best estimated doses as well as conceivable upper and lower bounds. The variation of residential day-life activities by individual members in a family was considered according to their sex, age, profession, etc. Intensive data on exposure rates were collected using thermoluminescent dosimeters positioned at 1 m height and 1 m x 1 m intersections with additional measurements at special locations such as bed, sofa, dining table, etc. Thermoluminescent dosimeter measurements were performed in all 24 residences studied in this work. This showed that the Atomic Energy Council maximal doses were 2-6 times higher than the present best estimated doses. Among all family members, elders and housewives received the highest doses; children received the lowest doses. The difference in doses among all family members belonging to different cohort categories is within a factor of two.

Adolescent↗

Collective radiation biodosimetry for dose reconstruction of acute accidental exposures: a review.

Quantification of the biologically relevant dose is required to establish cause and effect between radiation detriment or burden and important biological outcomes. Most epidemiologic studies of unanticipated radiation exposure fail to establish cause and effect because researchers have not been able to construct a valid quantification of dose for the exposed population. However, no one biodosimetric technique (biophysical or biological) meets all the requirements of an ideal dosimeter. This paper reviews how the collection of biodosimetric data for victims of radiation accidents can be used to create a dosimetric "gold standard." Particular emphasis is placed on the use of electron spin resonance, a standard for radiation accident dosimetry. As an example of this technique, a review will be presented of a previously reported study of an individual exposed to a 60Co sterilization source.

Dental Enamel↗

Dose reconstruction of x-ray irradiation of the larynx.

The authors have determined the dose distribution in the neck for parallel opposed and three field orthovoltage X-ray irradiation techniques of the larynx. LiF:Mg, Ti rods and pellets combined with film densitometry were used. Absorbed dose measured in the region of vocal chords is about 20% lower than that assessed by assuming full backscatter (perpendicular incidence) and by using standard isodose tables.

Film Dosimetry↗

Parameters affecting EPR dose reconstruction in teeth.

The aim of this paper is to analyze the lower limit of detection (LLD), linearity of dose response, variation of radiation sensitivity between different tooth enamel samples, and time/temperature stability of EPR biodosimetry in tooth enamel. The theoretical LLD is shown to be 0.46 mGy, which is far lower than the measured value of about 30 mGy. The main issues to lowering LLD are the differentiation of the radiation-induced component against the total EPR spectrum and the complex nature of the dose dependence of the EPR signal. The following questions are also discussed in detail: need for exfoliated or extracted teeth from persons of interest, accounting for background radiation contribution; conversion of tooth enamel absorbed dose to effective dose; accounting for internal exposure specifically from bone-seeking radionuclides. Conclusions on future development of EPR retrospective biodosimetry are made.

Algorithms↗

Individual dose reconstruction among residents living in the vicinity of the Semipalatinsk nuclear test site using EPR spectroscopy of tooth enamel.

Individual accumulated doses were determined by EPR spectroscopy of tooth enamel for 26 adult persons residing in territories adjacent to the Semipalatinsk Nuclear Test Site (SNTS). The absorbed dose values due to radiation from nuclear tests were obtained after subtracting the contribution of natural background radiation from the total accumulated dose. The determined dose values ranged up to 250 mGy, except for one person from Semipalatinsk city with a measured dose of 2.8 +/- 0.4 Gy. Increased dose values were determined for the individuals whose teeth were formed before 1962, the end of the atmospheric nuclear tests. These values were found to be significantly larger than those obtained for a group of younger residents of heavily exposed territories and the residents of territories not exposed to radioactive fallout. These increased dose values are consistent with those based on officially registered data for the Northeastern part of Kazakstan adjacent to SNTS, which was exposed to high levels of radioactive fallout from nuclear tests in period 1949-1962.

Adult↗

Viremia and immunogenicity in nonhuman primates of a tetravalent yellow fever-dengue chimeric vaccine: genetic reconstructions, dose adjustment, and antibody responses against wild-type dengue virus isolates.

Chimeric yellow fever (YF)-dengue (DEN) viruses (ChimeriVax-DEN) were reconstructed to correct amino acid substitutions within the envelope genes of original constructs described by Guirakhoo et al. (2001, J. Virol. 75, 7290-7304). Viruses were analyzed and compared to the previous constructs containing mutations in terms of their growth kinetics in Vero cells, neurovirulence in mice, and immunogenicity in monkeys as monovalent or tetravalent formulations. All chimeras grew to high titers [ approximately 7 to 8 log(10), plaque-forming units (PFU)/ml] in Vero cells and were less neurovirulent than YF 17D vaccine in mice. For monkey experiments, the dose of DEN2 chimera was lowered to 3 log(10) PFU in the tetravalent mixture in an effort to reduce its dominant immunogenicity. The magnitude of viremia in ChimeriVax-DEN immunized monkeys was similar to that of YF-VAX, but significantly lower than those induced by wild-type DEN viruses. All monkeys developed high levels of neutralizing antibodies against homologous (chimeras) or heterologous (wild-type DEN viruses isolated from different geographical regions) viruses after a single dose of monovalent or tetravalent vaccine. Administration of a second dose of tetravalent vaccine 2 months later increased titers to both homologous and heterologous viruses. A dose adjustment for dengue 2 chimera resulted in a more balanced response against dengue 1, 2, and 3 viruses, but a somewhat higher response against chimeric dengue 4 virus. This indicates that further formulations for dose adjustments need to be tested in monkeys to identify an optimal formulation for humans.

Amino Acid Substitution↗

Thyroid dose reconstruction for the population of Belarus after the Chernobyl accident.

An 131I environment transfer model--adapted for Belorussian conditions--was applied to estimate thyroid doses for different population groups. For this purpose the available data were analysed and the important radioecological parameters assessed i.e. (a) the elimination rate of 131I from grass due to weathering and growth dilution, (b) the initial interception of 131I by vegetation, (c) the transfer coefficient for 131I from grass to cow's milk, (d) the yield to pasture grass and (e) the milk consumption rate. Additionally, the influence of applied countermeasures has been taken into account, such as the interruption of locally produced milk consumption, and the appropriate correction factors have been estimated. As a result, the average age-dependent thyroid doses were assessed for the Belorussian population. The highest average doses in children (> 1 Gy) have been estimated for the Bragin, Khoiniki, Narovlia and Vetka raions of the Gomel oblast. The thyroid exposure tends to decrease from the southeastern (closest to the Chernobyl nuclear power plant areas) to the northwestern part of the republic. When comparing the assessed thyroid doses with estimates derived from direct 131I activity measurements in thyroids (for the locations with more than 15 direct measurements), the results agree fairly well. The model calculation may perhaps overestimate thyroid doses of the population residing in the settlements of the central and northern parts of Belarus, distant from the areas with direct measurements of 131I activities in soil, grass and milk. These thyroid dose estimates may serve as a basis for further epidemiological studies and risk analyses.

Adolescent↗

Dose reconstruction by EPR spectroscopy of tooth enamel: application to the population of Zaborie village exposed to high radioactive contamination after the Chernobyl accident.

Individual irradiation doses were determined by electron paramagnetic resonance spectroscopy of the tooth enamel of the inhabitants of Zaborie, the most contaminated inhabited settlement not evacuated after the Chernobyl accident. Dose determination was performed using a specially developed automatic spectrum processing procedure. Spectrum processing was carried out in different operating modes, and average results were taken in order to reduce the contribution of uncertainty in dose determination caused by spectrum processing. The absorbed doses determined in enamel were corrected to take into account the contribution of natural background radiation and to determine the individual excess dose due to radioactive contamination of the territory. Individual excess doses are compared to calculated individualized doses to teeth, estimated using the local radioactive contamination levels, dose rates, and information concerning individual behavior. The individual excess doses measured by electron paramagnetic resonance spectroscopy and the calculated individualized doses are fully independent. Mean square variation between results of two methods was found to be 34 mGy, which is consistent with error estimation for both methods. This result can validate both the methodology of signal processing presented here when using electron paramagnetic resonance dosimetry of tooth enamel for low doses and the methodology of individualized dose calculation.

Algorithms↗

The suitability of FISH chromosome painting and ESR-spectroscopy of tooth enamel assays for retrospective dose reconstruction.

A comparative analysis of two groups of highly irradiated victims was carried out in order to evaluate the suitability of two assays for retrospective dose assessment: late translocations and electron spin resonance (ESR) dosimetry. The first group comprised 24 subjects who exhibited acute radiation syndrome (ARS) due to overexposure as a result of nuclear submarine accidents during the period 1961-1985. Their grades of ARS and individual doses were ascertained by Navy physicians who carried out primary examinations and treatment of the exposed seamen. Cytogenetic analyses were made 16-40 y after their accidents. During medical treatment seven tooth samples were collected for ESR analysis from this group. The second group consisted of ten highly irradiated men from the Chernobyl accident. Comparison was made between estimates of their average whole-body penetrating radiation doses derived from several biological parameters. In three cases ESR measurements on tooth enamel from this group were also made. Retrospective dosimetry using FISH translocations was attempted 10-13 y later. Yields of late translocations were in good agreement with initially estimated doses and with doses obtained by ESR spectroscopy analysis of tooth enamel long after exposure. It was concluded that both persisting stable translocations and ESR spectroscopy signals are suitable with similar efficiencies for retrospective biodosimetry after acute whole-body exposure.

Adult↗

Cytogenetic damage in lymphocytes for the purpose of dose reconstruction: a review of three recent radiation accidents.

The analysis of chromosomal aberrations in peripheral blood of radiation accident victims is an established method of biological dosimetry. The dose estimate on the basis of an in vitro calibration curve is straightforward when the radiation exposure is homogeneous and the analysis not delayed. In recent years three radiation accidents occurred, where the irradiation or sampling conditions precluded a simple estimation of the dose. During the Georgian accident soldiers carried in their pockets small sources of 137Cs leading to partial and protracted body exposures. During the Tokai-mura accident, three employees involved in the process of 235U enrichment were exposed to very high doses of gamma rays and neutrons. During the Bialystok accident, five patients with breast cancer undergoing radiotherapy were exposed to a single dose of electrons which reached about 100 Gy. In the present paper the approaches chosen to estimate, by cytogenetic methods, the doses absorbed by the people involved in the accidents are described.

Breast Neoplasms↗

Development of an improved dose reconstruction system for the Techa River population affected by the operation of the Mayak Production Association.

The Techa River Dosimetry System (TRDS) has been developed to provide estimates of dose received by approximately 30,000 members of the Extended Techa River Cohort (ETRC). Members of the ETRC were exposed beginning in 1949 to significant levels of external and internal (mainly from (90)Sr) dose but at low to moderate dose rates. Members of this cohort are being studied in an effort to test the hypothesis that exposure at low to moderate dose rates has the same ability to produce stochastic health effects as exposure at high dose rates. The current version of the TRDS is known as TRDS-2000 and is the subject of this paper. The estimated doses from (90)Sr are supported strongly by approximately 30,000 measurements made with a tooth beta-particle counter, measurements of bones collected at autopsy, and approximately 38,000 measurements made with a special whole-body counter that detects the bremsstrahlung from (90)Y. The median doses to the red bone marrow and the bone surface are 0.21 and 0.37 Gy, respectively. The maximum doses to the red bone marrow and bone surface are 2.0 and 5.2 Gy, respectively. Distributions of dose to other organs are provided and are lower than the values given above. Directions for future work are discussed.

Body Burden↗

Translocation analysis by the FISH-painting method for retrospective dose reconstruction in individuals exposed to ionizing radiation 10 years after exposure.

Fluorescence in situ hybridization (FISH) is a powerful method largely used for detecting chromosomal rearrangements, translocations in particular, which are important biomarkers for dose assessment in case of human exposure to ionizing radiation. To test the possibility of using the translocation analysis by FISH-painting method in retrospective dose assessment, we carried out in vitro experiments in irradiated human lymphocytes, in parallel with the analysis of translocations in lymphocytes from 10 individuals, who were exposed to 137cesium in the Goiânia (Brazil) accident (samples collected 10 years after exposure). The in vitro dose-response curve for the genomic translocation frequencies (FGs) fits a linear quadratic model, according to the equation: Y=0.0243X(2)+0.0556X. The FG values were also calculated for the individuals exposed to 137cesium, ranging from 0.58 to 5.91 per 100 cells, and the doses were estimated and compared with the results obtained by dicentric analysis soon after the accident, taking the opportunity to test the validity of translocation analysis in retrospective biodosimetry. A tentative of retrospective dosimetry was performed, indicating that the method is feasible only for low level exposure (below 0.5Gy), while for higher doses there is a need to apply appropriate correction factors, which take into consideration mainly the persistence of chromosomal translocations along with time, and the influence of endogenous and exogenous factors determining the inter-individual variability in the cellular responses to radiation.

Adolescent↗

A comprehensive dose reconstruction methodology for former rocketdyne/atomics international radiation workers.

Incomplete radiation exposure histories, inadequate treatment of internally deposited radionuclides, and failure to account for neutron exposures can be important uncertainties in epidemiologic studies of radiation workers. Organ-specific doses from lifetime occupational exposures and radionuclide intakes were estimated for an epidemiologic study of 5,801 Rocketdyne/Atomics International (AI) radiation workers engaged in nuclear technologies between 1948 and 1999. The entire workforce of 46,970 Rocketdyne/AI employees was identified from 35,042 Kardex work histories cards, 26,136 electronic personnel listings, and 14,189 radiation folders containing individual exposure histories. To obtain prior and subsequent occupational exposure information, the roster of all workers was matched against nationwide dosimetry files from the Department of Energy, the Nuclear Regulatory Commission, the Landauer dosimetry company, the U.S. Army, and the U.S. Air Force. Dosimetry files of other worker studies were also accessed. Computation of organ doses from radionuclide intakes was complicated by the diversity of bioassay data collected over a 40-y period (urine and fecal samples, lung counts, whole-body counts, nasal smears, and wound and incident reports) and the variety of radionuclides with documented intake including isotopes of uranium, plutonium, americium, calcium, cesium, cerium, zirconium, thorium, polonium, promethium, iodine, zinc, strontium, and hydrogen (tritium). Over 30,000 individual bioassay measurements, recorded on 11 different bioassay forms, were abstracted. The bioassay data were evaluated using ICRP biokinetic models recommended in current or upcoming ICRP documents (modified for one inhaled material to reflect site-specific information) to estimate annual doses for 16 organs or tissues taking into account time of exposure, type of radionuclide, and excretion patterns. Detailed internal exposure scenarios were developed and annual internal doses were derived on a case-by-case basis for workers with committed equivalent doses indicated by screening criteria to be greater than 10 mSv to the organ with the highest internal dose. Overall, 5,801 workers were monitored for radiation at Rocketdyne/AI: 5,743 for external exposure and 2,232 for internal intakes of radionuclides; 41,169 workers were not monitored for radiation. The mean cumulative external dose based on Rocketdyne/AI records alone was 10.0 mSv, and the dose distribution was highly skewed with most workers experiencing low cumulative doses and only a few with high doses (maximum 500 mSv). Only 45 workers received greater than 200 mSv while employed at Rocketdyne/AI. However, nearly 32% (or 1,833) of the Rocketdyne/AI workers had been monitored for radiation at other nuclear facilities and incorporation of these doses increased the mean dose to 13.5 mSv (maximum 1,005 mSv) and the number of workers with >200 mSv to 69. For a small number of workers (n=292), lung doses from internal radionuclide intakes were relatively high (mean 106 mSv; maximum 3,560 mSv) and increased the overall population mean dose to 19.0 mSv and the number of workers with lung dose>200 mSv to 109. Nearly 10% of the radiation workers (584) were monitored for neutron exposures (mean 1.2 mSv) at Rocketdyne/AI, and another 2% were monitored for neutron exposures elsewhere. Interestingly, 1,477 workers not monitored for radiation at Rocketdyne/AI (3.6%) were found to have worn dosimeters at other nuclear facilities (mean external dose of 2.6 mSv, maximum 188 mSv). Without considering all sources of occupational exposure, an incorrect characterization of worker exposure would have occurred with the potential to bias epidemiologic results. For these pioneering workers in the nuclear industry, 26.5% of their total occupational dose (collective dose) was received at other facilities both prior to and after employment at Rocketdyne/AI. In addition, a small number of workers monitored for internal radionuclides contributed disproportionately to the number of workers with high lung doses. Although nearly 12% of radiation workers had been monitored for neutron exposures during their career, the cumulative dose levels were small in comparison with other external and internal exposure. Risk estimates based on nuclear worker data must be interpreted cautiously if internally deposited radionuclides and occupational doses received elsewhere are not considered.

Adult↗

Possibility of using porcelain samples of high-voltage line insulators for radiation dose reconstruction by EPR spectroscopy.

In electron paramagnetic resonance spectra of irradiated porcelain samples from high-voltage supply line insulators three overlapping single signals were observed. The dependencies of the amplitude of these signals on the microwave power, irradiation dose and the stability in darkness and in natural light were investigated. It was concluded that for dosimetric purposes it is reasonable to use the radiation-induced signal with g = 2.001, which could be ascribed to the E' centres of quartz. The microwave power dependence of the amplitude of this signal is saturated at 1 mW, the dose dependence is saturated at about 60 mGy. A minimal level of dose determination is about 1 Gy, and it is limited mainly by the accuracy of subtraction of the background signal existing in the unirradiated sample. The radiation-induced signal is stable in the darkness, but rapidly faded in natural light, therefore, for dosimetric purposes it is possible to use only insulators covered with dark glaze or ceramic samples from the very interior of the insulators.

Ceramics↗

New approach for dose reconstruction: application to one case of localized irradiation with radiological burns.

When localized accidental irradiation occurs, it is necessary to determine the extent to which tissues and vital organs have been damaged, mainly in the vicinity of the source. At present, biological markers cannot be used to estimate the heterogeneity of the dose distribution. An alternative is to map the absorbed dose in the different regions of the body. Using a Monte Carlo calculation code, it is possible to simulate the accident while taking into account the specific morphology of the irradiated individual and his environment, as well as the source characteristics. The calculated values are matched to the clinical signs of the lesion, particularly around the rim of the radiation-induced necrosis. This technique was applied successfully on two patients who presented very severe lesions due to acute localized irradiation after an accident that occurred at Lilo (Georgia) in 1996-1997; only the most demonstrative case is presented here.

Bone and Bones↗

The use of deciduous molars in EPR dose reconstruction.

In the present study naturally loose deciduous molars were investigated. The feasibility of separating enamel from small size molars was analysed. EPR spectrum parameters of whole molars and separated enamel only were evaluated before and after laboratory irradiation. The Electron paramagnetic resonance (EPR) signal amplitudes of CO (2) (-) and native signals were determined by spectrum deconvolution, as a function of radiation dose in the range 0.1-10 Gy. A detection threshold of absorbed dose from deciduous molars of 198 and 21 mGy is estimated for massive (that contained both enamel and dentine) and grainy samples (that contained enamel only), respectively. The elimination of the organic material from the massive deciduous samples reduced the mean bias dose for the native signal from 90+/-18 to 34+/-13 mGy. A decay of the background signal within 2 weeks after irradiation was found, while the dosimetric signal was stable before and after the irradiation process. The presented results suggest deciduous teeth to be suitable for retrospective dose assessment. To get reasonable dose estimates, however, any organic material must be eliminated, and the measurements should be performed 2 weeks after the chemical and mechanical preparation and the irradiation process are done.

Body Burden↗

Uncertainties in thyroid dose reconstruction after Chernobyl.

The most significant impact of the Chernobyl accident of 26 April 1986 is the increased incidence of thyroid cancer among Belarusians, Russians and Ukrainians who were exposed as children to radioiodines in fallout resulting from atmospheric releases. The US National Cancer Institute (NCI), in cooperation with the ministries of health of Belarus and Ukraine, is involved in epidemiological studies of thyroid diseases related to the accident. Individual thyroid doses, as well as uncertainties, have been estimated for the members of the cohort studies (approximately 13,000 Ukrainians and 12,000 Belarusians). The cohort subjects, who were selected from the large group of children whose thyroids were monitored for gamma radiation within a few weeks of the accident, provided personal information on their residence history and dietary habits during interviews. Thyroid dose estimates range from 1 mGy to more than 20 Gy. The uncertainties are found to be approximately log-normally distributed, with geometric standard deviations ranging from 1.6 to 5.0. The medians of the geometric standard deviations are 1.7 for the Ukrainian subjects and 2.1 for the Belarusian subjects. The major sources of uncertainty in the thyroid dose estimates are found to be those related to the thyroid mass of the subject and to the estimation of the thyroidal content of 131I at the time of thyroid monitoring.

Adolescent↗