Dosimetry formalism and calibration procedure for electronic brachytherapy sources in terms of absorbed dose to water.

The LNE-LNHB has developed a methodology to standardize electronic brachytherapy sources in terms of absorbed dose to water. It is based on the measurement of the air-kerma rate at a given distance from the source and the Monte Carlo calculation of a conversion factor. This factor converts the air-kerma in measurement conditions into absorbed dose to water at a 1 cm reference depth in a water phantom. As a first application, the method was used to calibrate a Zeiss INTRABEAM system equipped with its 4 cm diameter spherical applicator. The absorbed-dose rate value obtained in the current study was found significantly higher than that provided by the manufacturer in line with the observations already reported by a few other teams.

Using LiF:Mg,Cu,P TLDs to estimate the absorbed dose to water in liquid water around an 192Ir brachytherapy source.

PURPOSE: The absorbed dose to water is the fundamental reference quantity for brachytherapy treatment planning systems and thermoluminescence dosimeters (TLDs) have been recognized as the most validated detectors for measurement of such a dosimetric descriptor. The detector response in a wide energy spectrum as that of an (192)Ir brachytherapy source as well as the specific measurement medium which surrounds the TLD need to be accounted for when estimating the absorbed dose. This paper develops a methodology based on highly sensitive LiF:Mg,Cu,P TLDs to directly estimate the absorbed dose to water in liquid water around a high dose rate (192)Ir brachytherapy source. METHODS: Different experimental designs in liquid water and air were constructed to study the response of LiF:Mg,Cu,P TLDs when irradiated in several standard photon beams of the LNE-LNHB (French national metrology laboratory for ionizing radiation). Measurement strategies and Monte Carlo techniques were developed to calibrate the LiF:Mg,Cu,P detectors in the energy interval characteristic of that found when TLDs are immersed in water around an (192)Ir source. Finally, an experimental system was designed to irradiate TLDs at different angles between 1 and 11 cm away from an (192)Ir source in liquid water. Monte Carlo simulations were performed to correct measured results to provide estimates of the absorbed dose to water in water around the (192)Ir source. RESULTS: The dose response dependence of LiF:Mg,Cu,P TLDs with the linear energy transfer of secondary electrons followed the same variations as those of published results. The calibration strategy which used TLDs in air exposed to a standard N-250 ISO x-ray beam and TLDs in water irradiated with a standard (137)Cs beam provided an estimated mean uncertainty of 2.8% (k = 1) in the TLD calibration coefficient for irradiations by the (192)Ir source in water. The 3D TLD measurements performed in liquid water were obtained with a maximum uncertainty of 11% (k = 1) found at 1 cm from the source. Radial dose values in water were compared against published results of the American Association of Physicists in Medicine and the European Society for Radiotherapy and Oncology and no significant differences (maximum value of 3.1%) were found within uncertainties except for one position at 9 cm (5.8%). At this location the background contribution relative to the TLD signal is relatively small and an unexpected experimental fluctuation in the background estimate may have caused such a large discrepancy. CONCLUSIONS: This paper shows that reliable measurements with TLDs in complex energy spectra require a study of the detector dose response with the radiation quality and specific calibration methodologies which model accurately the experimental conditions where the detectors will be used. The authors have developed and studied a method with highly sensitive TLDs and contributed to its validation by comparison with results from the literature. This methodology can be used to provide direct estimates of the absorbed dose rate in water for irradiations with HDR (192)Ir brachytherapy sources.

Six-month outcome of elderly people hospitalized via the emergency department: the SAFES cohort.

BACKGROUND: The objective of the study was to identify factors predictive of 6-month institutionalization or mortality in frail elderly patients after acute hospitalization. METHODS: A prospective cohort of elderly subjects 75 years and older was set up in nine French teaching hospitals. Data obtained from a comprehensive geriatric assessment were used in a Cox model to predict 6-month institutionalization or mortality. Institutionalization was defined as incident admission either to a nursing home or other long-term care facility during the follow-up period. RESULTS: Crude institutionalization and death rates after 6 months of follow-up were 18% and 24%, respectively. Independent predictors of institutionalization were: living alone (HR=1.83; 95% CI=1.27-2.62) or a higher number of children (HR=0.86; 95% CI=0.78-0.96), balance problems (HR=1.72; 95% CI=1.19-2.47), malnutrition or risk thereof (HR=1.93; 95% CI=1.24-3.01), and dementia syndrome (HR=1.88; 95% CI=1.32-2.67). Factors found to be independently related to 6-month mortality were exclusively medical factors: malnutrition or risk thereof (HR=1.92; 95% CI=1.17-3.16), delirium (HR=1.80; 95% CI=1.24-2.62), and a high level of comorbidity (HR=1.62; 95% CI=1.09-2.40). Institutionalization (HR=1.92; 95% CI=1.37-2.71) and unplanned readmission (HR=4.47; 95% CI=3.16-2.71) within the follow-up period were also found as independent predictors. CONCLUSION: The main factors predictive of 6-month outcome identified in this study are modifiable by global and multidisciplinary interventions. Their early identification and management would make it possible to modify frail elderly subjects' prognosis favorably.

Rapid cognitive decline, one-year institutional admission and one-year mortality: analysis of the ability to predict and inter-tool agreement of four validated clinical frailty indexes in the SAFEs cohort.

OBJECTIVES: To evaluate the predictive ability of four clinical frailty indexes as regards one-year rapid cognitive decline (RCD - defined as the loss of at least 3 points on the MMSE score), and one-year institutional admission (IA) and mortality respectively; and to measure their agreement for identifying groups at risk of these severe outcomes. DESIGN: One-year follow-up and multicentre study of old patients participating in the SAFEs cohort study. SETTING: Nine university hospitals in France. PARTICIPANTS: 1,306 patients aged 75 or older (mean age 85±6 years; 65% female) hospitalized in medical divisions through an Emergency department. MEASUREMENTS: Four frailty indexes (Winograd; Rockwood; Donini; and Schoevaerdts) reflecting the multidimensionality of the frailty concept, using an ordinal scoring system able to discriminate different grades of frailty, and constructed based on the accumulation of identified deficits after comprehensive geriatric assessment conducted during the first week of hospital stay, were used to categorize participants into three different grades of frailty: G1 - not frail; G2 - moderately frail; and G3 - severely frail. Comparisons between groups were performed using Fisher's exact test. Agreement between indexes was evaluated using Cohen's Kappa coefficient. RESULTS: All patients were classified as frail by at least one of the four indexes. The Winograd and Rockwood indexes mainly classified subjects as G2 (85% and 96%), and the Donini and Schoevaerdts indexes mainly as G3 (71% and 67%). Among the SAFEs cohort population, 250, 1047 and 1,306 subjects were eligible for analyses of predictability for RCD, 1-year IA and 1-year mortality respectively. At 1 year, 84 subjects (34%) experienced RCD, 377 (36%) were admitted into an institutional setting, and 445 (34%) had died. With the Rockwood index, all subjects who experienced RCD were classified in G2; and in G2 and G3 when the Donini and Schoevaerdts indexes were used. No significant difference was found between frailty grade and RCD, whereas frailty grade was significantly associated with an increased risk of IA and death, whatever the frailty index considered. Agreement between the different indexes of frailty was poor with Kappa coefficients ranging from -0.02 to 0.15. CONCLUSION: These findings confirm the poor clinimetric properties of these current indexes to measure frailty, underlining the fact that further work is needed to develop a better and more widely-accepted definition of frailty and therefore a better understanding of its pathophysiology.

Predictors of institution admission in the year following acute hospitalisation of elderly people.

OBJECTIVES: The aim of the study was to identify factors related to institutionalisation within one-year follow up of subjects aged 75 or over, hospitalised via the emergency department (ED). DESIGN: Prospective multicentre cohort. SETTING: Nine French university teaching hospitals. PARTICIPANTS: One thousand and forty seven (1 047) non institutionalised subjects aged 75 or over, hospitalised via ED. A sub-group analysis was performed on the 894 subjects with a caregiver. MEASUREMENTS: Patients were assessed using Comprehensive Geriatric Assessment (CGA) tools. Cox survival analysis was performed to identify predictors of institutionalisation at one year. RESULTS: Within one year after hospital admission, 210 (20.1%) subjects were institutionalised. For the overall study population, age >85 years (HR 1.6; 95%CI 1.1-2.1; p=0.005), inability to use the toilet (HR 1.6; 95%CI 1.1-2.4; p=0.007), balance disorders (HR 1.6; 95%CI 1.1-2.1; p=0.005) and presence of dementia syndrome (HR 1.9; 95%CI 1.4-2.6; p<0.001) proved to be independent predictors of institutionalisation; while a greater number of children was inversely linked to institutionalisation (HR 0.8; 95%CI 0.7-0.9; p<0.001). Bathing was of borderline significance (p=.09). For subjects with a caregiver, initial caregiver burden was significantly linked to institutionalisation within one year, in addition to the predictors observed in the overall study population. CONCLUSIONS: CGA performed at the beginning of hospitalisation in acute medical wards is useful to predict institutionalisation. Most of the predictors identified can lead to targeted therapeutic options with a view to preventing or delaying institution admission.

Digital instrumentation and management of dead time: first results on a NaI well-type detector setup.

The LNE-LNHB is engaged in a development program on digital instrumentation, the first step being the instrumentation of a NaI well-type detector set-up. The prototype acquisition card and its technical specifications are presented together with the first comparison with the classical NIM-based acquisition chain, for counting rates up to 100 kcps. The digital instrumentation is shown to be counting-loss free in this range. This validates the main option adopted in this project, namely the implementation of an extending dead time with live-time measurement already successfully used in the MTR2 NIM module developed at LNE-LNHB.

DUPLICATE: Digital instrumentation and management of dead time: First results on a NaI well-type detector setup.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, doi:10.1016/j.apradiso.2010.01.040. The duplicate article has therefore been withdrawn.

International exercise on 124Sb activity measurements.

An international exercise, registered as EUROMET project no. 907, was launched to measure both the activity of a solution of (124)Sb and the photon emission intensities of its decay. The same solution was sent by LNE-LNHB to eight participating laboratories. In order to identify possible biases, the participants were asked to use all possible activity measurement methods available in their laboratory and then to determine their reference value for comparison. Thus, measurement results from 4pibeta-gamma coincidence/anti-coincidence counting, CIEMAT/NIST liquid-scintillation counting, 4pigamma counting with well-type ionization chambers and well-type crystal detectors were given. The results are compared and show a maximum discrepancy of about 1.6%: possible explanations are proposed.

International exercise on 124Sb photon emission intensities determination.

An international exercise, registered as EUROMET project no. 907, was launched to measure both the activity of a solution of (124)Sb and the photon emission intensities of its decay. The same solution was sent by LNE-LNHB to eight participating laboratories, six of which sent results for photon emission intensities both in absolute and in relative terms. From these results and including previous published values, a consistent decay scheme was worked out, proving that problems in activity measurements have not been due to decay scheme data.

SESAME: a software tool for the numerical dosimetric reconstruction of radiological accidents involving external sources and its application to the accident in Chile in December 2005.

Estimating the dose distribution in a victim's body is a relevant indicator in assessing biological damage from exposure in the event of a radiological accident caused by an external source. This dose distribution can be assessed by physical dosimetric reconstruction methods. Physical dosimetric reconstruction can be achieved using experimental or numerical techniques. This article presents the laboratory-developed SESAME--Simulation of External Source Accident with MEdical images--tool specific to dosimetric reconstruction of radiological accidents through numerical simulations which combine voxel geometry and the radiation-material interaction MCNP(X) Monte Carlo computer code. The experimental validation of the tool using a photon field and its application to a radiological accident in Chile in December 2005 are also described.

Derivation and validation of a mortality-risk index from a cohort of frail elderly patients hospitalised in medical wards via emergencies: the SAFES study.

To identify predictive factors for 2-year mortality in frail elderly patients after acute hospitalisation, and from these to derive and validate a Mortality Risk Index (MRI). A prospective cohort of elderly patients was set up in nine teaching hospitals. This cohort was randomly split up into a derivation cohort (DC) of 870 subjects and a validation cohort (VC) of 436 subjects. Data obtained from a Comprehensive Geriatric Assessment were used in a Cox model to predict 2-year mortality and to identify risk groups for mortality. A ROC analysis was performed to explore the validity of the MRI. Five factors were identified and weighted using hazard ratios to construct the MRI: age 85 or over (1 point), dependence for the ADL (1 point), delirium (2 points), malnutrition risk (2 points), and co-morbidity level (2 points for medium level, 3 points for high level). Three risk groups were identified according to the MRI. Mortality rates increased significantly across risk groups in both cohorts. In the DC, mortality rates were: 20.8% in the low-risk group, 49.6% in the medium-risk group, and 62.1% in the high-risk group. In the VC, mortality rates were respectively 21.7, 48.5, and 65.4%. The area under the ROC curve for overall score was statistically the same in the DC (0.72) as in the VC (0.71). The proposed MRI appears as a simple and easy-to-use tool developed from relevant geriatric variables. Its accuracy is good and the validation procedure gives a good stability of results.

Predicting early mortality among elderly patients hospitalised in medical wards via emergency department: the SAFES cohort study.

OBJECTIVES: The aim of the study was, by early identification of deleterious prognostic factors that are open to remediation, to be in a position to assign elderly patients to different mortality risk groups to improve management. DESIGN: Prospective multicentre cohort. SETTING: Nine French teaching hospitals. PARTICIPANTS: One thousand three hundred and six (1 306) patients aged 75 and over, hospitalised after having passed through Emergency Department (ED). MEASUREMENTS: Patients were assessed using Comprehensive Geriatric Assessment (CGA) tools. A Cox survival analysis was performed to identify prognostic variables for six-week mortality. Receiver Operating Characteristics analysis was used to study the discriminant power of the model. A mortality risk score is proposed to define three risk groups for six-week mortality. RESULTS: Crude mortality rate after a six week follow-up was 10.6% (n=135). Prognostic factors identified were: malnutrition risk (HR=2.1; 95% CI: 1.1-3.8; p=.02), delirium (HR=1.7; 95% CI: 1.2-2.5; p=.006), and dependency: moderate dependency (HR=4.9; 95% CI: 1.5-16.5; p=.01) or severe dependency (HR=10.3; 95% CI: 3.2-33.1; p < .001). The discriminant power of the model was good: the c-statistic representing the area under the curve was 0.71 (95% IC: 0.67 - 0.75; p < .001). The six-week mortality rate increased significantly (p < .001) across the three risk groups: 1.1% (n=269; 95% CI=0.5-1.7) in the lowest risk group, 11.1% (n=854; 95% CI=9.4-12.9) in the intermediate risk group, and 22.4% (n=125; 95% CI=20.1-24.7) in the highest risk group. CONCLUSIONS: A simple score has been calculated (using only three variables from the CGA) and a practical schedule proposed to characterise patients according to the degree of mortality risk. Each of these three variables (malnutrition risk, delirium, and dependency) identified as independent prognostic factors can lead to a targeted therapeutic option to prevent early mortality.

An intercomparison of Monte Carlo codes used in gamma-ray spectrometry.

In an intercomparison exercise, the Monte Carlo codes most commonly used in gamma-ray spectrometry today were compared with each other in order to gauge the differences between them in terms of typical applications. No reference was made to experimental data; instead, the aim was to confront the codes with each other, as they were applied to the calculation of full-energy-peak and total efficiencies. Surprising differences between the results of different codes were revealed.

Modelling the effect of non-uniform radon progeny activities on transformation frequencies in human bronchial airways.

The effects of radiological and morphological source heterogeneities in straight and Y-shaped bronchial airways on hit frequencies and microdosimetric quantities in epithelial cells have been investigated previously. The goal of the present study is to relate these physical quantities to transformation frequencies in sensitive target cells and to radon-induced lung cancer risk. Based on an effect-specific track length model, computed linear energy transfer (LET) spectra were converted to corresponding transformation frequencies for different activity distributions and source-target configurations. Average transformation probabilities were considerably enhanced for radon progeny accumulations and target cells at the carinal ridge, relative to uniform activity distributions and target cells located along the curved and straight airway portions at the same exposure level. Although uncorrelated transformation probabilities produce a linear dose-effect relationship, correlated transformations first increase depending on the LET, but then decrease significantly when exceeding a defined number of hits or cumulative exposure level.

Comparison of calculated spectra for the interaction of photons in a liquid scintillator. Example of 54Mn 835 keV emission.

The CIEMAT/NIST and TDCR methods in liquid scintillation counting, initially developed for the activity standardization of pure-beta radionuclides, have been extended to the standardization of electron capture and beta-gamma radionuclides. Both methods require the calculation of the energy spectrum absorbed by the liquid scintillator. For radionuclides emitting X-rays or gamma-rays, when the energy is greater than a few tens of keV the Compton interaction is important and the absorption is not total. In this case, the spectrum absorbed by the scintillator must be calculated using analytical or stochastic models. An illustration of this problem is the standardization of 54Mn, which is a radionuclide decaying by electron capture. The gamma transition, very weakly converted, leads to the emission of an 835 keV photon. The calculation of the detection efficiency of this radionuclide requires the calculation of the energy spectrum transferred to the scintillator after the absorption of the gamma ray and the associated probability of absorption. The validity of the method is thus dependent on the correct calculation of the energy transferred to the scintillator. In order to compare the calculation results obtained using various calculation tools, and to provide the metrology community with some information on the choice of these tools, the LS working group of the ICRM organised a comparison of the calculated absorbed spectra for the 835 keV photon of 54Mn. The result is the spectrum of the energy absorbed by the scintillator per emission of an 835 keV gamma ray. This exercise was proposed for a standard 20 ml LS glass vial and for LS cocktail volumes of 10 and 15 ml. The calculation was done for two different cocktails: toluene and a widely used commercial cocktail, Ultima Gold. The paper describes the results obtained by nine participants using a total of 12 calculation codes.

Validation of a personalized dosimetric evaluation tool (Oedipe) for targeted radiotherapy based on the Monte Carlo MCNPX code.

Dosimetric studies are necessary for all patients treated with targeted radiotherapy. In order to attain the precision required, we have developed Oedipe, a dosimetric tool based on the MCNPX Monte Carlo code. The anatomy of each patient is considered in the form of a voxel-based geometry created using computed tomography (CT) images or magnetic resonance imaging (MRI). Oedipe enables dosimetry studies to be carried out at the voxel scale. Validation of the results obtained by comparison with existing methods is complex because there are multiple sources of variation: calculation methods (different Monte Carlo codes, point kernel), patient representations (model or specific) and geometry definitions (mathematical or voxel-based). In this paper, we validate Oedipe by taking each of these parameters into account independently. Monte Carlo methodology requires long calculation times, particularly in the case of voxel-based geometries, and this is one of the limits of personalized dosimetric methods. However, our results show that the use of voxel-based geometry as opposed to a mathematically defined geometry decreases the calculation time two-fold, due to an optimization of the MCNPX2.5e code. It is therefore possible to envisage the use of Oedipe for personalized dosimetry in the clinical context of targeted radiotherapy.

Current developments at IRSN on computational tools dedicated to assessing doses for both internal and external exposure.

The paper presents the OEDIPE (French acronym that stands for tool for personalised internal dose assessment) and SESAME (for simulation of external source accident with medical images) computational tools, dedicated to internal and external dose assessment, respectively, and currently being developed at the Institute for Radiological Protection and Nuclear Safety. The originality of OEDIPE and SESAME, by using voxel phantoms in association with Monte Carlo codes, lies in their ability to construct personalised voxel phantoms from medical images and automatically generate the Monte Carlo input file and visualise the expected results. OEDIPE simulates in vivo measurements to improve their calibration, and calculates the dose distribution taking both internal contamination and internal radiotherapy cases into account. SESAME enables radiological overexposure doses to be reconstructed, as also victim, source and accident environment modelling. The paper presents the principles on which these tools function and an overview of specificities and results linked to their fields of application.

Microdosimetry of radon progeny alpha particles in bronchial airway bifurcations.

A Monte Carlo code, initially developed for the calculation of microdosimetric spectra for alpha particles in cylindrical airways, has been extended to allow the computation of microdosimetric parameters for multiple source-target configurations in bronchial airway bifurcations. The objective of the present study was to investigate the effects of uniform and non-uniform radon progeny surface activity distributions in symmetric and asymmetric bronchial airway bifurcations on absorbed dose, hit frequency, lineal energy, single hit specific energy and LET spectra. In order to assess the effects of multiple hits, dose-dependent specific energy spectra were calculated by solving the compound Poisson process by iterative convolution. While the simulations showed significant differences of cellular dose quantities at different cell locations for uniformly distributed surface activities, even higher variations, as high as several orders of magnitude, were observed for non-uniform surface activity distributions, depending on the location of the cell and the local activity distribution.

Microdosimetry of inhomogeneous radon progeny distributions in bronchial airways.

A Monte Carlo code, initially developed for the calculation of microdosimetric spectra for alpha particles in cylindrical airways, has been extended to allow the computation (i) of additional microdosimetric parameters and (ii) for realistic exposure conditions in human bronchial airways with respect to surface activity distribution and airway geometry. The objective of the present study was to investigate the effects of non-uniform distributions of radon progeny activities in bronchial airways on cellular energy deposition parameters. Significant variations of hit frequencies, doses and microscopic energy deposition patterns were observed for epithelial cell nuclei, depending strongly on the assumed activity distributions. Thus, epithelial cells located at different positions in a given bronchial airway may experience a wide range of biological responses. The results obtained suggest that the hit frequency may be the primary physical parameter for alpha particles, supplemented by microdosimetric single event spectra, to be related to biological effects for chronic low level exposures.

Dosimetric comparison of Monte Carlo codes (EGS4, MCNP, MCNPX) considering external and internal exposures of the Zubal phantom to electron and photon sources.

This paper aims at comparing dosimetric assessments performed with three Monte Carlo codes: EGS4, MCNP4c2 and MCNPX2.5e, using a realistic voxel phantom, namely the Zubal phantom, in two configurations of exposure. The first one deals with an external irradiation corresponding to the example of a radiological accident. The results are obtained using the EGS4 and the MCNP4c2 codes and expressed in terms of the mean absorbed dose (in Gy per source particle) for brain, lungs, liver and spleen. The second one deals with an internal exposure corresponding to the treatment of a medullary thyroid cancer by 131I-labelled radiopharmaceutical. The results are obtained by EGS4 and MCNPX2.5e and compared in terms of S-values (expressed in mGy per kBq and per hour) for liver, kidney, whole body and thyroid. The results of these two studies are presented and differences between the codes are analysed and discussed.