EURADOS project on the impact of the proposed ICRU operational dose quantities.

Following the publication of the joint The International Commissions on Radiation Units and Measurements (ICRU) and on Radiological Protection (ICRP) report on new operational quantities for radiation protection, the European Dosimetry Group (EURADOS) have carried out an initial evaluation. The EURADOS report analyses the impact that the new quantities will have on: radiation protection practice; calibration and reference fields; European and national regulation; international standards and, especially, dosemeter and instrument design. The task group included experienced scientists drawn from across the various EURADOS working groups.

Absorbed dose in the operator's brain in interventional radiology practices: evaluation through KAP value conversion factors.

In order to address the recent concerns over a possible increasing in brain tumour mortality among interventional radiologists and cardiologist, this work evaluated the exposure conditions of the operator's brain during interventional procedures using Monte Carlo simulations with anthropomorphic phantoms. The absorbed doses in several predefined segments of the operator's brain were estimated in a typical interventional radiology irradiation scenario. The doses were normalized to the KAP values simulated for ten X-ray beam qualities and four projections (PA, RAO 25°, LAO 25° and CRA 25°). For the interventional radiology scenario, because of the position of the operator, no difference was found in the exposure between the left and right regions of the brain for the first operator. However, for the second operator standing at a farer distance from the tube, the exposure of the left part of the brain is up to two times higher than that of the right part. The results are in agreement with dose measurements reported in the literature. The conversion factors, obtained as the absorbed dose per KAP, can be used to obtain a first estimate of the exposure of the brain of the operators during interventional procedures.

SESAME: A TOOL FOR NUMERICAL DOSIMETRIC RECONSTRUCTION OF PATIENTS OVEREXPOSURES IN INTERVENTIONAL RADIOLOGY.

Radiation overexposure accidents are rare but can have severe health consequences. Evaluating the dose received by the patient is a crucial step in the medical management. For that purpose, for more than 15 years, IRSN has been developing an in-house tool named SESAME for the numerical reconstruction of radiological accidents due to external sources. Recently, two new functionalities were implemented in SESAME to allow accurate reconstructions of interventional radiology (IR) overexposures. The experimental validation of SESAME for the reconstruction of overexposures in IR is presented. First, an anthropomorphic dummy equipped with dosemeters was irradiated following conditions similar to a fluoroscopically guided interventional procedure. Then the procedure was simulated using SESAME. Finally measured doses were compared to calculated doses. Even with a limited amount of data available, SESAME can provide valuable dose information for the medical team in charge of the patient, such as skin dose mapping and dose distribution in depth.

Effect of the radiation protective apron on the response of active and passive personal dosemeters used in interventional radiology and cardiology.

In fluoroscopy guided interventional procedures, workers use protective garments and often two personal dosemeters, the readings of which are used for the estimation of the effective dose; whereas the dosemeter above the protection can be used for the estimation of the equivalent dose of the lens of the eye. When a protective apron is worn the scattered field that reaches the dosemeter is different from the case where no protection is used; this study analyses the changes in the response of seven passive and eight active personal dosemeters (APDs) when they are placed above a lead or lead equivalent garment for S-Cs and x-ray diagnostic qualities. Monte Carlo simulations are used to support the experimental results. It is found that for passive dosemeters, the influence on the dosemeter's response to the lead or lead equivalent was within the range 15%-38% for the x-ray qualities. This effect is smaller, of the order of 10%, when lead-free garments are used, and much smaller, within 1%-10%, for most of the APDs used in the study. From these results it is concluded that when comparing passive and active dosemeter measurements worn above the protection, a difference of 20%-40% is expected. The effect is small when deriving the effective dose from double dosimetry algorithms, but it can be of major importance when eye lens monitoring is based on the use of the dosemeter worn above the protection.

SIMULATION OF EARLY RADIATION-INDUCED DNA DAMAGE ON DIFFERENT TYPES OF CELL NUCLEI.

This work presents a comparison of simulated early radiation-induced DNA damage represented by yields of double-strand breaks (DSB) in three different human cell nuclei geometries representing fibroblasts, lymphocytes and endothelial cells for protons and alpha particles of different energies and for different irradiation configurations. Each cell nucleus model includes a multi-scale description of the DNA target from the molecular level to the whole human genome representation (6 Gbp) in the G0/G1 phase of the cell cycle and was generated with the DnaFabric software. The three nuclei differ in shape, volume, and therefore DNA density. A calculation chain based on Geant4-DNA that takes into account the physical, physico-chemical and chemical stages was used to simulate the irradiation of the different cell nuclei. Results show an increase of DSB/primary/µm with an increase of DNA density and an increase of DSB/Gy/Gbp with an increase of the cell nucleus volume which indicates that the cell nucleus shape and size have an impact on early DNA damage, which may play a role in latter effects.

Simulation of early DNA damage after the irradiation of a fibroblast cell nucleus using Geant4-DNA.

In order to improve the understanding of the mechanisms involved in the generation of early DNA damage, a new calculation chain based on the Geant4-DNA toolkit was developed. This work presents for the first time the simulation of the physical, physicochemical and chemical stages of early radiation damage at the scale of an entire human genome (fibroblast, male) and using Geant4-DNA models. The DnaFabric software was extended to generate and export this nucleus model to a text file with a specific format that can be read by Geant4 user applications. This calculation chain was used to simulate the irradiation of the nucleus by primary protons of different energies (0,5; 0,7; 0,8; 1; 1,5; 2; 3; 4; 5; 10; 20 MeV) and the results, in terms of DNA double strand breaks, agree with experimental data found in the literature (pulsed field electrophoresis technique). These results show that the simulation is consistent and that its parameters are well balanced. Among the different parameters that can be adjusted, our results demonstrate that the criterion used to select direct strand break appears to have a very significant role on the final number of simulated double strand breaks.

Study of commercial detector responses in non-equilibrium small photon fields of a 1000MU/min CyberKnife system.

PURPOSE: The purpose of this study was to analyze the detector responses in non-equilibrium small photon fields. METHODS: Five detectors (PTW 31014 ionization chamber, PTW 60016, PTW 60017 and Sun Nuclear EDGE diodes and PTW 60003 diamond detector) and one passive dosimeter (Harshaw micro-LiF) as well as a 1000MU/min CyberKnife were modeled with the PENELOPE Monte Carlo code. Field factors, [Formula: see text] were calculated and perturbations due to volume averaging effect, active material effect and coating effect were quantified for the five detectors and passive dosimeter. RESULTS: The PTW 31014 ionization chamber under-response is mainly due to the fluence perturbation caused by the presence of air as detecting material. Regarding diodes, the high density materials used in their active volume and in their coating is responsible for their over-response. Regarding the PTW 60003 diamond, its under-response for the 5mm field size is due to a large volume averaging effect whereas for largest field sizes a nearly perfect compensation between the volume averaging effect and the material effect due to the diamond density occurs. Despite its small size, a volume averaging effect was observed for the micro-LiF for the 5mm field size. CONCLUSION: Perturbations due to volume averaging effect, active material effect and coating effect were investigated and quantified for five active detectors. Since these perturbations can cause opposite effects, wrong conclusions may be drawn regarding the radiological water-equivalence of detectors. Thus, we recommend performing such a study for each novel detector available on the market.

EURADOS INTERCOMPARISONS IN EXTERNAL RADIATION DOSIMETRY: SIMILARITIES AND DIFFERENCES AMONG EXERCISES FOR WHOLE-BODY PHOTON, WHOLE-BODY NEUTRON, EXTREMITY, EYE-LENS AND PASSIVE AREA DOSEMETERS.

The European Radiation Dosimetry Group (EURADOS) has been organising dosimetry intercomparisons for many years in response to an identified requirement from individual monitoring services (IMS) for independent performance tests for dosimetry systems. The participation in intercomparisons gives IMS the opportunity to show compliance with their own quality management system, compare results with other participants and develop plans for improving their dosimetry systems. In response to growing demand, EURADOS has increased the number of intercomparisons for external radiation dosimetry. Most of these fit into the programme of self-financing intercomparisons for dosemeters routinely used by IMS. This programme is being coordinated by EURADOS working group 2 (WG2). Up to now, this programme has included four intercomparisons for whole-body dosemeters in photon fields, one for extremity dosemeters in photon and beta fields, and one for whole-body dosemeters in neutron fields. Other EURADOS working groups have organised additional intercomparisons including events in 2014 for eye-lens dosemeters and passive area dosemeters for environmental monitoring. In this paper, the organisation and achievements of these intercomparisons are compared in detail focusing on the similarities and differences in their execution.

Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF) per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This comparison allowed us to calculate a volume of 1.6 µm3 for which the spread of the specific energy distribution could explain the entire variability of RIF counts per cell in an exposed cell population. The definition of this volume may allow to use a microdosimetric quantity to predict heterogeneity in DNA damage. Moreover, this value is consistent with the order of magnitude of the volume occupied by the hydrated sugar-phosphate backbone of the DNA molecule, which is the part of the DNA molecule responsible for strand breaks.

EPR retrospective dosimetry with fingernails: report on first application cases.

For localized irradiation to hands, in case of sources accidentally handled, it is very difficult to estimate the dose distribution by calculation. Doses may reach several tens of grays, and the dose distribution is usually very heterogeneous. Until recently, doses in such situations could be estimated only by analysis of bone biopsies using Electron Paramagnetic Resonance (EPR) spectroscopy. This technique was used previously on surgical wastes or after amputation of a finger. In this case, the dose information was available in one or a few locations on the hand only, due to the limited number of biopsy fragments usually collected. The idea to measure free radicals (FRs) induced by radiation in nails to estimate a dose is not new, but up to now, no application cases were reported. As a matter of fact, the EPR analysis of nails is complex due to the presence of intrinsic signals and parasitic signals induced by the mechanical stress (when nails are collected), which overlaps the radio-induced components. In addition, the radio-induced FRs identified up to now are unstable and very sensitive to humidity. In these conditions, it was difficult to foresee any application for dosimetry with fingernails. Recently, stable radio-induced FRs in nails has been identified and an associated protocol for dose assessment developed. This protocol has been applied by the Institut de Radioprotection et de Sûreté Nucléaire on fingernail samples from victims of three different radiological accidents that occurred between 2008 and 2012 in different places.

Characterization of MOSFET detectors for in vivo dosimetry in interventional radiology and for dose reconstruction in case of overexposure.

As MOSFET (Metal Oxide Semiconductor Field Effect Transistor) detectors allow dose measurements in real time, the interest in these dosimeters is growing. The aim of this study was to investigate the dosimetric properties of commercially available TN-502RD-H MOSFET silicon detectors (Best Medical Canada, Ottawa, Canada) in order to use them for in vivo dosimetry in interventional radiology and for dose reconstruction in case of overexposure. Reproducibility of the measurements, dose rate dependence, and dose response of the MOSFET detectors have been studied with a Co source. Influence of the dose rate, frequency, and pulse duration on MOSFET responses has also been studied in pulsed x-ray fields. Finally, in order to validate the integrated dose given by MOSFET detectors, MOSFETs and TLDs (LiF:Mg,Cu,P) were fixed on an Alderson-Rando phantom in the conditions of an interventional neuroradiology procedure, and their responses have been compared. The results of this study show the suitability of MOSFET detectors for in vivo dosimetry in interventional radiology and for dose reconstruction in case of accident, provided a well-corrected energy dependence, a pulse duration equal to or higher than 10 ms, and an optimized contact between the detector and the skin of the patient are achieved.

Personal monitor glass badge: theoretical dosemeter response calculated with the Monte Carlo transport code MCNPX.

This paper describes the results of the simulation of a radiophotoluminescent (RPL) dosemeter with the Monte Carlo transport code MCNPX. The aim of this study is to calculate the response with MCNPX of the RPL dosemeter in terms of equivalent doses H(p) (0.07) and H(p)(10) using X-ray photon radiation qualities N series, together with S-Cs and S-Co nuclide radiation qualities, specified in ISO 4037-1. After comparison with reference values versus experimental results, the deviation of the theoretical responses of the RPL dosemeter proved to be lower than 5 % for reference values and lower than 10 % for experimental results. This good correlation validates the model over the energy range studied.

Simulation of DNA damage clustering after proton irradiation using an adapted DBSCAN algorithm.

In this work the "Density Based Spatial Clustering of Applications with Noise" (DBSCAN) algorithm was adapted to early stage DNA damage clustering calculations. The resulting algorithm takes into account the distribution of energy deposit induced by ionising particles and a damage probability function that depends on the total energy deposit amount. Proton track simulations were carried out in small micrometric volumes representing small DNA containments. The algorithm was used to determine the damage concentration clusters and thus to deduce the DSB/SSB ratios created by protons between 500keV and 50MeV. The obtained results are compared to other calculations and to available experimental data of fibroblast and plasmid cells irradiations, both extracted from literature.

New emerging concepts in the medical management of local radiation injury.

Treatment of severe radiation burns remains a difficult medical challenge. The response of the skin to ionizing radiation results in a range of clinical manifestations. The most severe manifestations are highly invalidating. Although several therapeutic strategies (excision, skin grafting, skin or muscle flaps) have been used with some success, none have proven entirely satisfying. The concept that stem cell injections could be used for reducing normal tissue injury has been discussed for a number of years. Mesenchymal stem cells therapy may be a promising therapeutic approach for improving radiation-induced skin and muscle damages. Pre-clinical and clinical benefit of mesenchymal stem cell injection for ulcerated skin and muscle restoration after high dose radiation exposure has been successfully demonstrated. Three first patients suffering from severe radiological syndrome were successfully treated in France based on autologous human grade mesenchymal stem cell injection combined to plastic surgery or skin graft. Stem cell therapy has to be improved to the point that hospitals can put safe, efficient, and reliable clinical protocols into practice.

Intercomparison of active personal dosemeters in interventional radiology.

The use of active personal dosemeters (APD) in interventional radiology was evaluated by Working Group 9 (Radiation protection dosimetry of medical staff) of the CONRAD project, which is a Coordination Action supported by the European Commission within its sixth Framework Programme. Interventional radiology procedures can be very complex and they can lead to relatively high doses to personnel who stand close to the primary radiation field and are mostly exposed to radiation scattered by the patient. For the adequate dosimetry of the scattered photons, APDs must be able to respond to low-energy [10-100 keV] and pulsed radiation with relatively high instantaneous dose rates. An intercomparison of five APD models deemed suitable for application in interventional radiology was organised in March 2007. The intercomparison used pulsed and continuous radiation beams, at CEA-LIST (Saclay, France) and IRSN (Fontenay-aux-Roses, France), respectively. A specific configuration, close to the clinical practice, was considered. The reference dose, in terms of Hp(10), was derived from air kerma measurements and from the measured and calculated energy distributions of the scattered radiation field. Additional Monte Carlo calculations were performed to investigate the energy spectra for different experimental conditions of the intercomparison. The results of this intercomparison are presented in this work and indicate which APDs are able to provide a correct response when used in the specific low-energy spectra and dose rates of pulsed X-rays encountered in interventional radiology.

EX vivo ESR measurements associated with Monte Carlo calculations for accident dosimetry: application to the 2001 Georgian accident.

Electron spin resonance (ESR) spectroscopy and the Monte Carlo (MC) technique were jointly applied to the physical dose reconstruction of the accident that occurred on 2 December 2001 in Georgia. Three people were exposed to two very-high-activity (2.6 x 10(15) Bq) 90Sr sources. Following this exposure, the two most seriously affected victims exhibited severe radiological injuries localised in the back as well as a haematopoietic syndrome. The information concerning the circumstances of the accident in terms of sequences of irradiation and the exposure time was not clearly established. The physical dose reconstruction of the accident was performed for one victim, treated in France, using both MC simulations and ESR measurements made on one vertebra and two rib samples removed from the victim for medical reasons. The complementary nature of the two tools made it possible to estimate the dose distribution within the body with reasonable accuracy and helped to develop the treatment strategy.

Application of autologous hematopoietic cell therapy to a nonhuman primate model of heterogeneous high-dose irradiation.

We developed a model of heterogeneous irradiation in a nonhuman primate to test the feasibility of autologous hematopoietic cell therapy for the treatment of radiation accident victims. Animals were irradiated either with 8 Gy to the body with the right arm shielded to obtain 3.4 Gy irradiation or with 10 Gy total body and 4.4 Gy to the arm. Bone marrow mononuclear cells were harvested either before irradiation or after irradiation from an underexposed area of the arm and were expanded in previously defined culture conditions. We showed that hematopoietic cells harvested after irradiation were able to expand and to engraft when reinjected 7 days after irradiation. Recovery was observed in all 8-Gy-irradiated animals, and evidence for a partial recovery was observed in 10-Gy-irradiated animals. However, in 10-Gy-irradiated animals, digestive disease was observed from day 16 and resulted in the death of two animals. Immunohistological examinations showed damage to the intestine, lungs, liver and kidneys and suggested radiation damage to endothelial cells. Overall, our results provide evidence that such an in vivo model of heterogeneous irradiation may be representative of accidental radiation exposures and may help to define the efficacy of therapeutic interventions such as autologous cell therapy in radiation accident victims.

MIRD Pamphlet No 19: absorbed fractions and radionuclide S values for six age-dependent multiregion models of the kidney.

UNLABELLED: As one of the major organs of the excretory pathway, the kidneys represent a frequent source of radiopharmaceutical uptake in both diagnostic and therapeutic nuclear medicine. The unique organization of the functional tissues of the organ ensures transient changes in suborgan localization of renal activity. Current single-region dosimetric models of the kidneys, however, force the assumption of a uniform distribution of radioactivity across the entire organ. The average absorbed dose to the kidneys predicted by such models can misrepresent local regional doses to specific substructures. METHODS: To facilitate suborgan dosimetry for the kidneys, 6 new age-dependent multiregion kidney models are presented. The outer dimensions of the models conform to those used currently in single-region kidney models, whereas interior structures are defined for the renal cortex, the medullary pyramids with papillae (2 vertical and 3 horizontal), and the renal pelvis. Absorbed fractions of energy were calculated for both photon and electron sources (10 keV to 4 MeV) located in each source region within the 6 age-dependent models. The absorbed fractions were then used to assemble S values for radionuclides of potential interest in suborgan kidney dosimetry. RESULTS: For the adult, the absorbed dose to the renal cortex for (90)Y-labeled compounds retained within that subregion is approximately 1.3 times that predicted by the single-region kidney model, whereas the medullary dose is only 26% of that same single-region value. For compounds that are rapidly filtered in the kidneys, the renal cortex dose is approximately one-half of that predicted under the single-region model, whereas the tissues of the medullary pyramids receive an absorbed dose 1.5-1.8 times larger. CONCLUSION: The multiregion model described here permits estimates of regional kidney dose not previously supported by current single-region models. Full utilization of the new model, however, requires serial imaging of the kidneys with regions of interest assigned to the renal cortex and medulla.