Physically-based biodosimetry using in vivo EPR of teeth in patients undergoing total body irradiation

Purpose:?The ability to estimate individual exposures to radiation following a large attack or incident has been identified as a necessity for rational and effective emergency medical response. In vivo electron paramagnetic resonance (EPR) spectroscopy of tooth enamel has been developed to meet this need.

Materials and methods:?A novel transportable EPR spectrometer, developed to facilitate tooth dosimetry in an emergency response setting, was used to measure upper incisors in a model system, in unirradiated subjects, and in patients who had received total body doses of 2 Gy.

Results:?A linear dose response was observed in the model system. A statistically significant increase in the intensity of the radiation-induced EPR signal was observed in irradiated versus unirradiated subjects, with an estimated standard error of dose prediction of 0.9?±?0.3 Gy.

Conclusions:?These results demonstrate the current ability of in vivo EPR tooth dosimetry to distinguish between subjects who have not been irradiated and those who have received exposures that place them at risk for acute radiation syndrome. Procedural and technical developments to further increase the precision of dose estimation and ensure reliable operation in the emergency setting are underway. With these developments EPR tooth dosimetry is likely to be a valuable resource for triage following potential radiation exposure of a large population.     

Specific issues in small animal dosimetry and irradiator calibration

Abstract

Purpose: In response to the increased risk of radiological terrorist attack, a network of Centers for Medical Countermeasures against Radiation (CMCR) has been established in the United States, focusing on evaluating animal model responses to uniform, relatively homogenous whole- or partial-body radiation exposures at relatively high dose rates. The success of such studies is dependent not only on robust animal models but on accurate and reproducible dosimetry within and across CMCR. To address this issue, the Education and Training Core of the Duke University School of Medicine CMCR organised a one-day workshop on small animal dosimetry. Topics included accuracy in animal dosimetry accuracy, characteristics and differences of cesium-137 and X-ray irradiators, methods for dose measurement, and design of experimental irradiation geometries for uniform dose distributions. This paper summarises the information presented and discussed.

Conclusions: Without ensuring accurate and reproducible dosimetry the development and assessment of the efficacy of putative countermeasures will not prove successful. Radiation physics support is needed, but is often the weakest link in the small animal dosimetry chain. We recommend: (i) A user training program for new irradiator users, (ii) subsequent training updates, and (iii) the establishment of a national small animal dosimetry center for all CMCR members.     

Investigation of the influence of calibration practices on cytogenetic laboratory performance for dose estimation

Abstract

Purpose: In the frame of the QA program of RENEB, an inter-laboratory comparison (ILC) of calibration sources used in biological dosimetry was achieved to investigate the influence of calibration practices and protocols on the results of the dose estimation performance as a first step to harmonization and standardization of dosimetry and irradiation practices in the European biological dosimetry network.

Materials and methods: Delivered doses by irradiation facilities used by RENEB partners were determined with EPR/alanine dosimetry system. Dosimeters were irradiated in the same conditions as blood samples. A short survey was also performed to collect the information needed for the data analysis and evaluate the diversity of practices.

Results: For most of partners the deviation of delivered dose from the targeted dose remains below 10%. Deviations larger than 10% were observed for five facilities out of 21. Origins of the largest discrepancies were identified. Correction actions were evaluated as satisfactory. The re-evaluation of some ILC results for the fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC) assays has been performed leading to an improvement of the overall performances.

Conclusions: This work has shown the importance of dosimetry in radiobiology studies and the needs of harmonization, standardization in irradiation and dosimetry practices and educational training for biologists using ionizing radiation.     

Numerical signal treatment for optimized alanine/ESR dosimetry in the therapy-level dose range

Electron spin resonance (ESR) spectra of alanine detectors irradiated to absorbed doses below 5 Gy are affected by a varying non-linear background which mainly influences the lower limit of detection in alanine/ESR dosimetry. A mathematical method based on fast Fourier transform is described capable of filtering simultaneously background and noise in the frequency domain of ESR spectra. It provides clearer alanine/ESR signals down to 50 mGy. Even in non-irradiated but long-term stored alanine detectors an ESR signal could be observed similar to irradiated alanine (pre-signal). A linear ESR signal vs absorbed dose relationship was found above 200 mGy, after correction for background and pre-signal. The number of repeated ESR read-out cycles and hence the time required for a precise and reliable low-dose evaluation have significantly been reduced. The method has been worked out for the therapy-level dosimetry range and tested on a Bruker ESP 300 and for comparison Bruker EMS 104 ESR spectrometer.     

Canadian Cytogenetic Emergency Network (CEN) for biological dosimetry following radiological/nuclear accidents

Purpose: To test the ability of the cytogenetic emergency network (CEN) of laboratories, currently under development across Canada, to provide rapid biological dosimetry using the dicentric assay for triage assessment, that could be implemented in the event of a large-scale radiation/nuclear emergency.

Materials and methods: A workshop was held in May 2004 in Toronto, Canada, to introduce the concept of CEN and recruit clinical cytogenetic laboratories at hospitals across the country. Slides were prepared for dicentric assay analysis following in vitro irradiation of blood to a range of gamma-ray doses. A minimum of 50 metaphases per slide were analyzed by 41 people at 22 different laboratories to estimate the exposure level.

Results: Dose estimates were calculated based on a dose response curve generated at Health Canada. There were a total of 104 dose estimates and 96 (92.3%) of them fell within the expected range using triage scoring criteria. Half of the laboratories analyzed 50 metaphases in ≤ 1 hour and the time to score them was proportional to dose. The capacity and scoring expertise of the various participating laboratories were found to be generally acceptable.

Conclusions: The dose estimates generated through triage scoring by this network were acceptable for emergency biological dosimetry. When this network is fully operational, it will be the first of its kind in Canada able to respond to radiological/nuclear emergencies by providing triage quality biological dosimetry for a large number of samples. This network represents an alternate expansion of existing international emergency biological dosimetry cytogenetic networks.     

Uncertainties in alanine dosimetry in the therapeutic dose range

A method for evaluating the overall uncertainty of alanine EPR transfer dosimetry in the therapeutic dose range is described. The method uses experimental data on EPR signal reproducibility from replicate dosimeters irradiated to low doses (1–5 Gy), estimates of Type B uncertainties, and Monte Carlo simulations of heteroscedastic orthogonal linear regression. A Bruker ECS106 spectrometer and Bruker alanine dosimeters have been used for this evaluation. The results demonstrate that alanine dosimetry can be used for transfer dosimetry in that range with the overall uncertainty 1.5–4% (1σ) depending on the dose, the number of replicate dosimeters, and the duration of the calibration session (the session should not exceed one working day).     

Limitations of conventional internal dosimetry at the cellular level

A theoretic examination of the validity at the cellular level of assumptions used in classic internal dosimetry has been undertaken. An alternate dosimetric model accounting for the consequences of selective uptake of a radiolabeled compound by specific cells in a multicellular cluster of hexagonal geometry has been developed. At the cellular level, derived dose estimates for electrons have been compared to dose estimates obtained employing the assumptions of conventional internal dosimetry. The study has been performed for all electron energies and then applied specifically to electrons emitted by 99mTc, 201Tl, 111In, and 123I. The dosimetric consequences of altering (a) the intracellular-to-extracellular radionuclide concentration, (b) the labeled cell density, and (c) the cell size have been examined for the labeled and nonlabeled cells in a cell cluster, and the conditions in which conventional dosimetry underestimates or overestimates the dose to individual cells have been indicated. It is shown that when selective intracellular uptake of a radiolabeled compound occurs in specific cells within a cell cluster, conventional dosimetry underestimates the radiation dose delivered to the labeled cells by twofold to more than 25-fold if the emitted electrons have ranges of a few micrometers or less, i.e., energies smaller than approximately 10 keV. Under the same conditions, conventional dosimetry overestimates slightly (20% to 50%) the electron radiation dose to the nonlabeled cells of the cell cluster. It is shown that inclusion of photons in the calculation of the total dose to individual cells does not alter significantly the conclusions of the present investigation.     

A review of dosimetry used in epidemiological studies considered to evaluate the linear no-threshold (LNT) dose-response model for radiation protection

Abstract

Background: Accurate dosimetry is key to deriving the dose response from radiation exposure in an epidemiological study. It becomes increasingly important to estimate dose as accurately as possible when evaluating low dose and low dose rate as the calculation of excess relative risk per Gray (ERR/Gy) is very sensitive to the number of excess cancers observed, and this can lead to significant errors if the dosimetry is of poor quality. By including an analysis of the dosimetry, we gain a far better appreciation of the robustness of the work from the standpoint of its value in supporting the shape of the dose response curve at low doses and low dose rates. This article summarizes a review of dosimetry supporting epidemiological studies currently being considered for a re-evaluation of the linear no-threshold assumption as a basis for radiation protection. The dosimetry for each study was evaluated based on important attributes from a dosimetry perspective. Our dosimetry review consisted of dosimetry supporting epidemiological studies published in the literature during the past 15 years. Based on our review, it is clear there is wide variation in the quality of the dosimetry underlying each study. Every study has strengths and weaknesses. The article describes the results of our review, explaining which studies clearly stand out for their strengths as well as common weaknesses among all investigations.

Purpose: To summarize a review of dosimetry used in epidemiological studies being considered by the National Council on Radiation Protection and Measurements (NCRP) in an evaluation of the linear no-threshold dose-response model that underpins the current framework of radiation protection.

Materials and methods: The authors evaluated each study using criteria considered important from a dosimetry perspective. The dosimetry analysis was divided into the following categories: (1) general study characteristics, (2) dose assignment, (3) uncertainty, (4) dose confounders (5) dose validation, and (6) strengths and weaknesses of the dosimetry. Our review focused on approximately 20 studies published in the literature primarily during the past 15 years.

Results: Based on the review, it is clear there is wide variation in the quality of the dosimetry underlying each study. Every study has strengths and weaknesses. This paper describes the results of our review, identifies common weaknesses among all investigations, and recognizes studies that clearly stand out for their overall strengths.

Conclusions: The paper concludes by offering recommendations to investigators on possible ways in which dosimetry could be improved in future epidemiological studies.     

Endocavitary in vivo Dosimetry for IMRT Treatments of Gynecologic Tumors

The accuracy and reproducibility of endometrial carcinoma treatment with intensity-modulated radiotherapy (IMRT) was assessed by means of in vivo dosimetry. Six patients who had previously undergone radical hysterectomy for endometrial carcinoma were treated with IMRT using a vaginal applicator with radio-opaque fiducial markers. An ion-chamber inserted into the applicator supplied an endocavitary in vivo dosimetry for quality assurance purposes. The ratio R = D/D_TPS between the in vivo measured dose D and the predicted dose by the treatment planning system D_TPS was determined for every fraction of the treatment. Results showed that 90% and 100% of the ratios resulted equal to 1 within 5% and 10%, respectively. The mean value of the ratios distribution for the 6 patients was R = 0.995 and the SD = 0.034. The ratio R* between the measured and predicted total doses for each patient was near to 1, within 2%. The dosimetric results suggest that the use of a vaginal applicator in an image-guided approach could make the interfractions target position stable and reproducible, allowing a safe use of the IMRT technique in the treatment of postoperative vaginal vault. In vivo dosimetry may supply useful information about the discrimination of random vs. systematic errors. The workload is minimum and this in vivo dosimetry can be applied also in the clinical routine.     

基于电子射野影像系统与加速器日志文件重建模体内剂量的初步比较

目的 研究基于电子射野影像系统（EPID）与加速器日志文件（dynalogs file）重建模体内剂量的差异性。方法 收集12例盆腔患者的容积旋转调强（VMAT）计划,将计划信息复制到“Cheese”模体上重新计算剂量,而后在瓦里安加速器（RapidArc）上执行,“Cheese”模体置于等中心处获取射野影像（EPI）,将EPI传入EPIgray软件中重建剂量。同时利用Mobius软件调用加速器日志文件,实现对模体计划剂量的重建。以A1SL型号的电离室和配套的剂量仪测量整个计划执行结束后射野等中心（电离室中心）处剂量值,在计划系统（TPS）中读取电离室敏感体积体内的平均剂量值（设置电离室中心与等中心重合）。结果 电离室测量值与TPS中读取的等中心处剂量值相比,两者偏差为1.31%。两种方式重建的射野等中心的剂量分别与电离室测量数值相比,差异均无统计学意义（P>0.05）。结论 两种重建体内剂量的方法均能为VMAT在体剂量验证提供参考。     

ESR dosimetry of a deceased radiation worker

A case of overexposure of an industrial radiographer using ¹⁹²Ir sources and having a filmbadge dosimeter record of 104 mSv has been examined with ESR dosimetry of postmortem tooth and bone specimens. ESR measurements of the tooth enamel showed an intense signal of CO₂⁻ and gave the equivalent dose (ED) of 14 Gy by the additive dose method using γ-rays from a source of ⁶⁰Co. The doses for a finger bone and humerus were 14.7 and 7.0 Gy, respectively. It was concluded that he had been exposed to radiation repeatedly over 10 yr and that ESR dosimetry can give a life-long cumulative dose for personnel using radiation.     

Dosimetry of the microSelectron-HDR Ir-192 source using PRESAGE™ and optical CT

Optical CT, using a solid polyurethane (PRESAGE™) radiochromic dosimeter, has been used to evaluate dose distributions produced by the microSelectron-HDR Ir-192 source. The anisotropy functions obtained through optical CT are in good agreement with Monte Carlo and previously published results especially at polar angle above 20°. The results indicated an evident potential for using solid polymer dosimetry as an accurate method for 3-D dosimetry, although refinements to the existing methods are necessary before the technique can be used clinically.     

Feasibility study of radiophotoluminescent glass rod dosimeter postal dose intercomparison for high energy photon beam

A radiophotoluminescent glass rod dosimeter (GRD) system has recently become commercially available. In this study we evaluated whether the GRD would be suitable for external dosimetric audit program in radiotherapy. For this purpose, we introduced a methodology of the absorbed dose determination with the GRD by establishing calibration coefficient and various correction factors (non-linearity dose response, fading, energy dependence and angular dependence). A feasibility test of the GRD postal dose intercomparison was also performed for eight high photon beams by considering four radiotherapy centers in Korea. In the accuracy evaluation of the GRD dosimetry established in this study, we obtained within 1.5% agreements with the ionization chamber dosimetry for the ⁶⁰Co beam. It was also observed that, in the feasibility study, all the relative deviations were smaller than 3%. Based on these results, we believe that the new GRD system has considerable potential to be used for a postal dose audit program.     

The harmonization process to set up and maintain an operational biological and physical retrospective dosimetry network: QA QM applied to the RENEB network

Abstract

Purpose: The European Network of Biological and Physical Retrospective Dosimetry ‘RENEB’ has contributed to European radiation emergency preparedness. To give homogeneous dose estimation results, RENEB partners must harmonize their processes.

Materials and methods: A first inter-comparison focused on biological and physical dosimetry was used to detect the outliers in terms of dose estimation. Subsequently, trainings were organized to improve both tools dose estimation. A second inter-comparison was performed to validate training efficiency. Simultaneously, based on ISO standards, a QA&QM manual on all dosimetry assays was produced which states a common basis and harmonized procedures for each assay. The evaluation of the agreement of RENEB partners to follow the QA&QM manual was performed through a questionnaire. The integration of new members into the network was carried out in the same way, whatever the assays.

Results: The training courses on biological and physical dosimetry were judged to be successful because most of the RENEB members’ dose estimates improved in the second inter-comparison. The QA&QM manual describes the consensus for the minimum requirements and the performance criteria for both dosimetry assays. The questionnaire revealed that the whole network capacity currently can manage between 15 and 3800 samples once.

Conclusion: The methodology used to harmonize all dosimetry practice within the network RENEB was highly successful. The network is operational to manage a mass casualty radiation accident for immediate dose assessment.     

Radiation dose by spiral CT and conventional tomography of the sternoclavicular joints and the manubrium sterni

 Objective, design and patients. Conventional frontal tomography of the sternum has to some extent been replaced by spiral computed tomography (CT). The objective of this study was to analyse this change of procedure in terms of dosimetry by measurement of the radiation dose to individual organs using an anthropomorphic Rando Alderson phantom. Results. The total effective radiation dose in examination of the sternoclavicular joints and the manubrium sterni was found to be lower using spiral CT than conventional tomography, the values being 0.6 and 0.8 mSv, respectively. Conclusion. As spiral CT is diagnostically comparable and in some respects superior to tomography, its use is recommended for studies of the sternum.     

牙釉质EPR剂量测定方法的主要影响因素分析

EPR(电子顺磁共振)剂量测定方法是回顾性测定个人辐射剂量的主要方法,它能够准确估算出很久以前发生的辐射照射事件的吸收剂量值,其理论基础是在牙釉质中,辐射所致自由基水平随着辐射剂量的增加而增加。目前,将EPR方法用于低剂量测定还存在一些困难,为了降低测量阈值,减小误差,优化方法,需要进一步研究该方法的影响因素。本文重点分析了影响牙釉质EPR剂量方法测量阈值和测量结果不确定度的主要因素,并对解决这些问题的修正方法进行了讨论。     

Dosimetric properties of various colored commercial glasses.

Brazilian commercial glasses of various colors (bronze, brown and green) have been studied to evaluate their potential as radiation-sensitive materials in gamma high-dose dosimetry. Characteristics of their optical absorption responses (reproducibility, room temperature stability, and calibration curves) have been obtained using a spectrophotometer and a simple densitometer specially designed for glass samples. The glass spectra feature a decay at room temperature that has to be taken into consideration. The results show that the colored glasses can be used in dosimetry; the upper limit of the dose range depends on the glass type.     

手表红宝石事故剂量计在电离辐射事故剂量测量中的应用

研制了两种用于手表红宝石事故剂理计测量的特殊热释光剂量读出装置；对国内、外１０种不同种类、型号的手表红宝石热释光剂理特性进行了实验研究，结果表明：在热释发光曲线、灵敏度、重复使用性、衰退性、光敏性、能量响应、剂量响应等性能满足事故个人剂量测量的要求，手表红宝石是目前人体佩戴物中方便易得的实用个人事故剂量计；在几起辐射事故中得到了成功的应用，其中列举了一起有代表性的＾６０Ｃｏ源事故受照者的剂量测量和     

Monoclonal antibodies and neuroblastoma

Several antineuroblastoma monoclonal antibodies (MoAbs) have been described and two have been used in radioimmunoimaging and radioimmunotherapy in patients. MoAb 3F8 is a murine IgG3 antibody specific for the ganglioside GD2. Radioiodine-labeled 3F8 has been shown to specifically target human neuroblastoma in patients, and radioimmunoimaging with this agent has provided consistently high uptakes with tumor-to-background ratios of greater than or equal to 10:1. Radioimmunotherapy has been attempted with both MoAb 3F8 and MoAb UJ13A, and although encouraging results have been obtained, dosimetry data and tissue dose response information for these agents is lacking, which impedes the development of such therapy. 124I, a positron emitter, can be used with 3F8 in positron emission tomography (PET) scanning to provide dosimetry information for radioimmunotherapy. The tumor radiation dose response from radiolabeled MoAb also can be followed with PET images with fluorodeoxyglucose (FDG) scanning of neuroblastoma tumors. Results to date indicate that radioimmunoimaging has clinical use in the diagnosis of neuroblastoma and the potential for radioimmunotherapy for this cancer remains high.     

Using NanoDot dosimetry to study the RS 2000 X-ray Biological Irradiator

Abstract

Purpose: To use NanoDot dosimeters to study the RS 2000 X-ray Biological Irradiator dosimetry characteristics and perform in vivo dosimetry for cell or small animal experiments.

Methods and materials: We first calibrated the Landauer NanoDot^? Reader by irradiating some NanoDot dosimeters with a set of known doses at specific positions defined by the irradiator. A group of five NanoDot dosimeters were placed at five specific positions where the dose rates were known and provided by the irradiator. Each group was irradiated for a set of times respectively. By correlating the readings of dosimeters with the given irradiated doses, we established the dose-reading relationship for the irradiator under the specific running condition. The established calibration curve was validated by exposing arbitrary known doses to a set of dosimeters, using the Landauer NanoDot^? Reader to measure the doses, and then making the comparison between the two doses. To study the dose gradient of the X-ray inside the irradiated target (dose variation/cm), we placed dosimeters under different thicknesses of water-equivalent bolus and irradiated them, then measured the doses to determine the dose gradient.

Results: Using the method described above, we were able to calibrate the Landauer InLight NanoDot^? Reader and use NanoDot dosimeters to measure the actual doses delivered to the targets for the cell/small animal experiments that use the RS 2000 X-ray Biological Irradiator.

Conclusions: NanoDots are ideal dosimeters to use for in vivo dosimetry for cell/small animal irradiation experiments. The dose decrease inside the animal tissue is about 20% per cm.