γ-H2AX foci as in vivo effect biomarker in children emphasize the importance to minimize x-ray doses in paediatric CT imaging.

OBJECTIVES: Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting. METHODS: From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring γ-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models. RESULTS: Despite the low CT doses, a median increase of 0.13 γ-H2AX foci/cell was observed. Plotting the induced γ-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose-response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13 ‰ respectively. CONCLUSION: CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols. .

Web-based scoring of the dicentric assay, a collaborative biodosimetric scoring strategy for population triage in large scale radiation accidents.

In the case of a large scale radiation accident high throughput methods of biological dosimetry for population triage are needed to identify individuals requiring clinical treatment. The dicentric assay performed in web-based scoring mode may be a very suitable technique. Within the MULTIBIODOSE EU FP7 project a network is being established of 8 laboratories with expertise in dose estimations based on the dicentric assay. Here, the manual dicentric assay was tested in a web-based scoring mode. More than 23,000 high resolution images of metaphase spreads (only first mitosis) were captured by four laboratories and established as image galleries on the internet (cloud). The galleries included images of a complete dose effect curve (0-5.0 Gy) and three types of irradiation scenarios simulating acute whole body, partial body and protracted exposure. The blood samples had been irradiated in vitro with gamma rays at the University of Ghent, Belgium. Two laboratories provided image galleries from Fluorescence plus Giemsa stained slides (3 h colcemid) and the image galleries from the other two laboratories contained images from Giemsa stained preparations (24 h colcemid). Each of the 8 participating laboratories analysed 3 dose points of the dose effect curve (scoring 100 cells for each point) and 3 unknown dose points (50 cells) for each of the 3 simulated irradiation scenarios. At first all analyses were performed in a QuickScan Mode without scoring individual chromosomes, followed by conventional scoring (only complete cells, 46 centromeres). The calibration curves obtained using these two scoring methods were very similar, with no significant difference in the linear-quadratic curve coefficients. Analysis of variance showed a significant effect of dose on the yield of dicentrics, but no significant effect of the laboratories, different methods of slide preparation or different incubation times used for colcemid. The results obtained to date within the MULTIBIODOSE project by a network of 8 collaborating laboratories throughout Europe are very promising. The dicentric assay in the web based scoring mode as a high throughput scoring strategy is a useful application for biodosimetry in the case of a large scale radiation accident.

Automatic scoring of dicentric chromosomes as a tool in large scale radiation accidents.

Mass casualty scenarios of radiation exposure require high throughput biological dosimetry techniques for population triage in order to rapidly identify individuals who require clinical treatment. The manual dicentric assay is a highly suitable technique, but it is also very time consuming and requires well trained scorers. In the framework of the MULTIBIODOSE EU FP7 project, semi-automated dicentric scoring has been established in six European biodosimetry laboratories. Whole blood was irradiated with a Co-60 gamma source resulting in 8 different doses between 0 and 4.5Gy and then shipped to the six participating laboratories. To investigate two different scoring strategies, cell cultures were set up with short term (2-3h) or long term (24h) colcemid treatment. Three classifiers for automatic dicentric detection were applied, two of which were developed specifically for these two different culture techniques. The automation procedure included metaphase finding, capture of cells at high resolution and detection of dicentric candidates. The automatically detected dicentric candidates were then evaluated by a trained human scorer, which led to the term 'semi-automated' being applied to the analysis. The six participating laboratories established at least one semi-automated calibration curve each, using the appropriate classifier for their colcemid treatment time. There was no significant difference between the calibration curves established, regardless of the classifier used. The ratio of false positive to true positive dicentric candidates was dose dependent. The total staff effort required for analysing 150 metaphases using the semi-automated approach was 2 min as opposed to 60 min for manual scoring of 50 metaphases. Semi-automated dicentric scoring is a useful tool in a large scale radiation accident as it enables high throughput screening of samples for fast triage of potentially exposed individuals. Furthermore, the results from the participating laboratories were comparable which supports networking between laboratories for this assay.

Characterization of the c.190T>C missense mutation in BRCA1 codon 64 (Cys64Arg).

In the Milan area (Northern Italy), we identified a family characterized by a high prevalence of ovarian and breast cancer cases (5 out of 6 subjects, over 3 generations), and a predominant prevalence of ovarian lesions (4 out of 5 patients). Analysis of BRCA1 and BRCA2 genes allowed the identification of the missense c.190T>C mutation in codon 64 (Cys64Arg) of BRCA1. The aims of the present investigation were to characterize the functional implications of the c.190T>C mutation at the molecular level, and to search whether additional polymorphisms might be linked to the peculiar phenotypic features observed in the Italian pedigree. Molecular modelling studies suggested that substitution of the cysteine 64 with an arginine likely disrupts the architecture of the BRCA1 RING finger domain, responsible for the interaction with BARD1, essential for the tumor-suppressor activity of the BRCA1-BARD1 complex. By splicing site information analysis, exonic splicing enhancer site characterization, and analysis of transcript fragment length and sequence, we showed that the c.190T>C mutation was able to modulate the splicing of exon 5 in a fashion opposite to the c.190T>G transversion, responsible for the functionally-related Cys64Gly amino acid substitution. Genotyping of BRCA1 and BRCA2 in the Italian family revealed the presence of two significant polymorphisms: the cancer-associated c.2612C>T SNP in BRCA1, and the c.-26G>A SNP in the BRCA2 gene, acting as an ovarian cancer risk modifier in carriers of deleterious BRCA1 mutations. Analysis of these SNPs in a genotypically-unrelated Polish family, characterized by prevalent breast neoplasms in carriers of the c.190T>C mutation, revealed a genetic profile consistent with the hypothetic role of both polymorphisms.

The influence of small field sizes, penumbra, spot size and measurement depth on perturbation factors for microionization chambers.

The purpose of this study was the investigation of perturbation factors for microionization chambers in small field dosimetry and the influence of penumbra for different spot sizes. To this purpose, correlated sampling was implemented in the EGSnrc Monte Carlo (MC) user code cavity: CScavity. CScavity was first benchmarked against results in the literature for an NE2571 chamber. An efficiency increase of 17 was attained for the calculation of a realistic chamber perturbation factor in a water phantom. Calculations have been performed for microionization chambers of type PinPoint 31006 and PinPoint 31016 in full BEAMnrc linac simulations. Investigating the physical backgrounds of the differences for these small field settings, perturbation factors have been split up into (1) central electrode perturbation, (2) wall perturbation, (3) air-to-water perturbation (chamber volume air-to-water) and (4) water volume perturbation (water chamber volume to 1 mm(3) voxel). The influence of different spot sizes, position in penumbra, measuring depth and detector geometry on these perturbation factors has been investigated, in a 0.8 x 0.8 cm(2) field setting. p(cel) for the PP31006 steel electrode shows a variation of up to 1% in the lateral position, but only 0.4% for the PP31016 with an Al electrode. The air-to-water perturbation in the optimal scanning direction for both profiles and depth is most influenced by the radiation field, and only to a small extent the chamber geometry. The PP31016 geometry (shorter, larger radius) requires less total perturbation within the central axis of the field, but results in slightly larger variations off axis in the optimal scanning direction. Smaller spot sizes (0.6 mm FWHM) and sharper penumbras, compared to larger spot sizes (2 mm FWHM), result in larger perturbation starting in the penumbra. The longer geometries of the PP31006/14/15 exhibit in the non-optimal scanning direction large variations in total perturbation (p(tot) 1.201(4) (0.6 mm spot, 3 mm off axis, type A MC uncertainty) to 0.803(4) (5 mm off axis)) mainly due to volume perturbation. Therefore in IMRT settings, when the detector is not always in the optimal scanning direction, the PP31016 geometry requires less extreme perturbation (max p(tot) 1.130(3)) and shows less variation. However, these results suggest that small variations in positioning, spot size or MLC result in large differences in perturbation factors. Therefore even these 0.016 cm(3) ionization chambers are limited in their use for a field setting of 0.8 x 0.8 cm(2), as used in this investigation.

Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?

The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G(2) assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G(2) scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (

On the calibration process of film dosimetry: OLS inverse regression versus WLS inverse prediction.

The purpose of this study was both putting forward a statistically correct model for film calibration and the optimization of this process. A reliable calibration is needed in order to perform accurate reference dosimetry with radiographic (Gafchromic) film. Sometimes, an ordinary least squares simple linear (in the parameters) regression is applied to the dose-optical-density (OD) curve with the dose as a function of OD (inverse regression) or sometimes OD as a function of dose (inverse prediction). The application of a simple linear regression fit is an invalid method because heteroscedasticity of the data is not taken into account. This could lead to erroneous results originating from the calibration process itself and thus to a lower accuracy. In this work, we compare the ordinary least squares (OLS) inverse regression method with the correct weighted least squares (WLS) inverse prediction method to create calibration curves. We found that the OLS inverse regression method could lead to a prediction bias of up to 7.3 cGy at 300 cGy and total prediction errors of 3% or more for Gafchromic EBT film. Application of the WLS inverse prediction method resulted in a maximum prediction bias of 1.4 cGy and total prediction errors below 2% in a 0-400 cGy range. We developed a Monte-Carlo-based process to optimize calibrations, depending on the needs of the experiment. This type of thorough analysis can lead to a higher accuracy for film dosimetry.

Interventional cardiovascular procedures in Belgium: effective dose and conversion factors.

Effective dose (E), representing the risk of late radiation-induced effects, can be estimated by the use of conversion factors (CF), converting direct measurable quantities such as dose-area-product into E. Eight Belgian hospitals participated in the study with a total number of 318 procedures. E-values, calculated with PCXMC, were compared for the different hospitals for diagnostic and therapeutic procedures separately. E-values varied significantly depending on the hospital where the procedure was performed (P < 0.001), on filtration insertion (P < 0.001), on whether a centre is a training centre or not, the dose conscious action of the cardiologists and the complexity of the procedure (P < 0.001). Hospital-specific CF were calculated. An average CF of 0.185 mSv Gycm(-2) was obtained with a satisfactory correlation (r = 0.966, P < 0.001). The differences in CF between hospitals were due to, a large extent, the availability of additional filtration in cinegraphy mode (P < 0.001) and not to the differences in irradiation geometries in the clinical protocol of the interventional procedures.

A large-scale multicentre study in Belgium of dose area product values and effective doses in interventional cardiology using contemporary X-ray equipment.

In this paper, a large-scale multicentre patient dose study performed in eight Belgian interventional cardiology departments is presented. Effective dose (E) was calculated based on a detailed dose-area product (DAP)-registration during each procedure and by using conversion coefficients generated by the Monte Carlo-based computer program PCXMC. Conversion coefficients were found to be 0.177 mSv Gycm(-2) for systems that do not use any additional copper filtration in cineradiography and 0.207 mSv Gycm(-2) for systems that use additional copper filtration in cineradiography. Mean E values of 9.6 and 15.3 mSv for diagnostic and therapeutic procedures, respectively, were obtained. DAP distributions were investigated in order to derive dose reference levels: 71 and 106 Gycm2 for diagnostic and therapeutic procedures, respectively, are proposed. Significant differences were observed in DAP distributions taking into account whether additional copper filtration was used in the cineradiography mode. Apart from the skin, the organs most at risk are lungs and heart. The probability of fatal cancer for the studied population amounted to 1.1x10(-4) and 2.1x10(-4) for diagnostic and therapeutic procedures, respectively, for the age distribution of the patients considered in this multicentre study.

Monte Carlo modeling of the ModuLeaf miniature MLC for small field dosimetry and quality assurance of the clinical treatment planning system.

The purpose of this investigation was the verification of both the measured data and quality of the implementation of the add-on ModuLeaf miniature multileaf collimator (ML mMLC) into the clinical treatment planning system for conformal stereotactic radiosurgery treatment. To this end the treatment head with ML mMLC was modeled in the BEAMnrc Monte Carlo (MC) code. The 6 MV photon beams used in the setup were first benchmarked with a set of measurements. A total ML mMLC transmission of 1.13% of the 10 x 10 cm2 open field dose was measured and reproduced with the BEAMnrc/DOSXYZnrc code. Correspondence between calculated and measured output factors (OFs) was within 2%. Correspondence between MC and measured profiles was within 2% dose and 2 mm distance, only for the smallest 0.5 x 0.5 cm2 field the results were within 3% dose. In the next step, the MC model was compared with Gafchromic film measurements and Pinnacle(3) 7.4 f (convolution superposition algorithm) calculated dose distributions, using a gamma evaluation comparison, for a multi-beam patient setup delivered to a Lucytrade mark phantom. The gamma evaluation of the MC versus Gafchromic film resulted in 3.4% of points not fulfilling gamma

Denoising of Monte Carlo dose calculations: smoothing capabilities versus introduction of systematic bias.

In order to evaluate the performance of denoising algorithms applied to Monte Carlo calculated dose distributions, conventional evaluation methods (rms difference, 1% and 2% difference) can be used. However, it is illustrated that these evaluation methods sometimes underestimate the introduction of bias, since possible bias effects are averaged out over the complete dose distribution. In the present work, a new evaluation method is introduced based on a sliding window superimposed on a difference dose distribution (reference dose-noisy/denoised dose). To illustrate its importance, a new denoising technique (ANRT) is presented based upon a combination of the principles of bilateral filtering and Savitzky-Golay filters. This technique is very conservative in order to limit the introduction of bias in high dose gradient regions. ANRT is compared with IRON for three challenging cases, namely an electron and photon beam impinging on heterogeneous phantoms and two IMRT treatment plans of head-and-neck cancer patients to determine the clinical relevance of the obtained results. For the electron beam case, IRON outperforms ANRT concerning the smoothing capabilities, while no differences in systematic bias are observed. However, for the photon beam case, although ANRT and IRON perform equally well on the conventional evaluation tests (rms difference, 1% and 2% difference), IRON clearly introduces much more bias in the penumbral regions while ANRT seems to introduce no bias at all. When applied to the IMRT patient cases, both denoising methods perform equally well regarding smoothing and bias introduction. This is probably caused by the summation of a large set of different beam segments, decreasing dose gradients compared to a single beam. A reduction in calculation time without introducing large systematic bias can shorten a Monte Carlo treatment planning process considerably and is therefore very useful for the initial trial and error phase of the treatment planning process.

Radiation Sensitivity of Human CD34(+) Cells Versus Peripheral Blood T Lymphocytes of Newborns and Adults: DNA Repair and Mutagenic Effects.

As hematopoietic stem and progenitor cells (HSPCs) self-renew throughout life, accumulation of genomic alterations can potentially give rise to radiation carcinogenesis. In this study we examined DNA double-strand break (DSB) induction and repair as well as mutagenic effects of ionizing radiation in CD34(+) cells and T lymphocytes from the umbilical cord of newborns. The age dependence of DNA damage repair end points was investigated by comparing newborn T lymphocytes with adult peripheral blood T lymphocytes. As umbilical cord blood (UCB) contains T lymphocytes that are practically all phenotypically immature, we examined the radiation response of separated naive (CD45RA(+)) and memory (CD45RO(+)) T lymphocytes. The number of DNA DSBs was assessed by microscopic scoring of γ-H2AX/53BP1 foci 0.5 h after low-dose radiation exposure, while DNA repair was studied by scoring the number of residual γ-H2AX/53BP1 foci 24 h after exposure. Mutagenic effects were studied by the cytokinesis block micronucleus (CBMN) assay. No significant differences in the number of DNA DSBs induced by low-dose (100-200 mGy) radiation were observed among the three different cell types. However, residual γ-H2AX/53BP1 foci levels 24 h postirradiation were significantly lower in CD34(+) cells compared to newborn T lymphocytes, while newborn T lymphocytes showed significantly higher foci yields than adult T lymphocytes. No significant differences in the level of radiation-induced micronuclei at 2 Gy were observed between CD34(+) cells and newborn T lymphocytes. However, newborn T lymphocytes showed a significantly higher number of micronuclei compared to adult T lymphocytes. These results confirm that CD34(+) cell quiescence promotes mutagenesis after exposure. Furthermore, we can conclude that newborn peripheral T lymphocytes are significantly more radiosensitive than adult peripheral T lymphocytes. Using the results from the comparative study of radiation-induced DNA damage repair end points in naive (CD45RA(+)) and memory (CD45RO(+)) T lymphocytes, we could demonstrate that the observed differences between newborn and adult T lymphocytes can be explained by the immunophenotypic change of T lymphocytes with age, which is presumably linked with the remodeling of the closed chromatin structure of naive T lymphocytes.

Microsatellite polymorphisms in DNA repair genes XRCC1, XRCC3 and XRCC5 in patients with gynecological tumors: association with late clinical radiosensitivity and cancer incidence.

This study investigates the association of microsatellite polymorphisms in XRCC1, XRCC3 and XRCC5 with the development of late radiation-induced radiotherapy reactions and examines the correlation between these microsatellites and cancer incidence. Sixty-two women with cervical or endometrial cancer treated with radiotherapy were included in the study. According to the CTCAEv3.0 scale, 22 patients showed late adverse radiotherapy reactions (grade 2 or more). PCR on lymphocyte DNA followed by automated fragment analysis was performed to examine the number of tandem repeat units at each locus. No significant association was found between the repeat length at any of the microsatellites in XRCC1, XRCC3 or XRCC5 and the incidence of late radiotherapy complications. Since higher odds ratios (ORs) were found for the rare XRCC1 [AC]11 and [AC]21 repeats (OR = 2.65, P = 0.325 and OR = 8.67, P = 0.093, respectively), the possible involvement of these small and large repeats in clinical radiosensitivity cannot be completely ruled out. When specific numbers of repeats were examined, no significant correlation was found between the microsatellite repeat length in XRCC1 and XRCC5 and cancer incidence. A weak correlation between XRCC3 [AC]16 homozygotes and cancer incidence was found (OR = 2.56, P = 0.055). A large-scale multicenter study of cancer patients with a high number of radiosensitive individuals is needed to clarify the value of rare polymorphic microsatellite repeats in XRCC1 and XRCC3 as a biomarker of clinical radiosensitivity or increased cancer risk.

Experimental verification of lung dose with radiochromic film: comparison with Monte Carlo simulations and commercially available treatment planning systems.

The purpose of this study was to assess the absorbed dose in and around lung tissue by performing radiochromic film measurements, Monte Carlo simulations and calculations with superposition convolution algorithms. We considered a layered polystyrene phantom of 12 x 12 x 12 cm3 containing a central cavity of 6 x 6 x 6 cm3 filled with Gammex RMI lung-equivalent material. Two field configurations were investigated, a small 1 x 10 cm2 field and a larger 10 x 10 cm2 field. First, we performed Monte Carlo simulations to investigate the influence of radiochromic film itself on the measured dose distribution when the film intersects a lung-equivalent region and is oriented parallel to the central beam axis. To that end, the film and the lung-equivalent materials were modelled in detail, taking into account their specific composition. Next, measurements were performed with the film oriented both parallel and perpendicular to the central beam axis to verify the results of our Monte Carlo simulations. Finally, we digitized the phantom in two commercially available treatment planning systems, Helax-TMS version 6.1A and Pinnacle version 6.2b, and calculated the absorbed dose in the phantom with their incorporated superposition convolution algorithms to compare with the Monte Carlo simulations. Comparing Monte Carlo simulations with measurements reveals that radiochromic film is a reliable dosimeter in and around lung-equivalent regions when the film is positioned perpendicular to the central beam axis. Radiochromic film is also able to predict the absorbed dose accurately when the film is positioned parallel to the central beam axis through the lung-equivalent region. However, attention must be paid when the film is not positioned along the central beam axis, in which case the film gradually attenuates the beam and decreases the dose measured behind the cavity. This underdosage disappears by offsetting the film a few centimetres. We find deviations of about 3.6% between Monte Carlo and the superposition convolution algorithm of Pinnacle behind the lung region, for both field configurations. Pinnacle is quite accurate in the lung region. Deviations up to 5.6% for the small field are found in the lung region between Monte Carlo and the superposition convolution algorithm of Helax-TMS. Behind the lung region, Helax-TMS is in better agreement with Monte Carlo. Radiochromic film measurements or Monte Carlo simulations are reliable methods to establish the dose in and around lung tissue.

Investigation of geometrical and scoring grid resolution for Monte Carlo dose calculations for IMRT.

Monte Carlo based treatment planning of two different patient groups treated with step-and-shoot IMRT (head-and-neck and lung treatments) with different CT resolutions and scoring methods is performed to determine the effect of geometrical and scoring voxel sizes on DVHs and calculation times. Dose scoring is performed in two different ways: directly into geometrical voxels (or in a number of grouped geometrical voxels) or into scoring voxels defined by a separate scoring grid superimposed on the geometrical grid. For the head-and-neck cancer patients, more than 2% difference is noted in the right optical nerve when using voxel dimensions of 4 x 4 x 4 mm3 compared to the reference calculation with 1 x 1 x 2 mm3 voxel dimensions. For the lung cancer patients, 2% difference is noted in the spinal cord when using voxel dimensions of 4 x 4 x 10 mm3 compared to the 1 x 1 x 5 mm3 calculation. An independent scoring grid introduces several advantages. In cases where a relatively high geometrical resolution is required and where the scoring resolution is less important, the number of scoring voxels can be limited while maintaining a high geometrical resolution. This can be achieved either by grouping several geometrical voxels together into scoring voxels or by superimposing a separate scoring grid of spherical voxels with a user-defined radius on the geometrical grid. For the studied lung cancer cases, both methods produce accurate results and introduce a speed increase by a factor of 10-36. In cases where a low geometrical resolution is allowed, but where a high scoring resolution is required, superimposing a separate scoring grid on the geometrical grid allows a reduction in geometrical voxels while maintaining a high scoring resolution. For the studied head-and-neck cancer cases, calculations performed with a geometrical resolution of 2 x 2 x 2 mm3 and a separate scoring grid containing spherical scoring voxels with a radius of 2 mm produce accurate results and introduce a speed increase by a factor of 13. The scoring grid provides an additional degree of freedom for limiting calculation time and memory requirements by selecting optimized scoring and geometrical voxel dimensions in an independent way.

The importance of accurate linear accelerator head modelling for IMRT Monte Carlo calculations.

Two Monte Carlo dose engines for radiotherapy treatment planning, namely a beta release of Peregrine and MCDE (Monte Carlo dose engine), were compared with Helax-TMS (collapsed cone superposition convolution) for a head and neck patient for the Elekta SLi plus linear accelerator. Deviations between the beta release of Peregrine and MCDE up to 10% were obtained in the dose volume histogram of the optical chiasm. It was illustrated that the differences are not caused by the particle transport in the patient, but by the modelling of the Elekta SLi plus accelerator head and more specifically the multileaf collimator (MLC). In MCDE two MLC modules (MLCQ and MLCE) were introduced to study the influence of the tongue-and-groove geometry, leaf bank tilt and leakage on the actual dose volume histograms. Differences in integral dose in the optical chiasm up to 3% between the two modules have been obtained. For single small offset beams though the FWHM of lateral profiles obtained with MLCE can differ by more than 1.5 mm from profiles obtained with MLCQ. Therefore, and because the recent version of MLCE is as fast as MLCQ, we advise to use MLCE for modelling the Elekta MLC. Nevertheless there still remains a large difference (up to 10%) between Peregrine and MCDE. By studying small offset beams we have shown that the profiles obtained with Peregrine are shifted, too wide and too flat compared with MCDE and phantom measurements. The overestimated integral doses for small beam segments explain the deviations observed in the dose volume histograms. The Helax-TMS results are in better agreement with MCDE, although deviations exceeding 5% have been observed in the optical chiasm. Monte Carlo dose deviations of more than 10% as found with Peregrine are unacceptable as an influence on the clinical outcome is possible and as the purpose of Monte Carlo treatment planning is to obtain an accuracy of 2%. We would like to emphasize that only the Elekta MLC has been tested in this work, so it is certainly possible that alpha releases of Peregrine provide more accurate results for other accelerators.

Decoupling initial electron beam parameters for Monte Carlo photon beam modelling by removing beam-modifying filters from the beam path.

A new method is presented to decouple the parameters of the incident e(-) beam hitting the target of the linear accelerator, which consists essentially in optimizing the agreement between measurements and calculations when the difference filter, which is an additional filter inserted in the linac head to obtain uniform lateral dose-profile curves for the high energy photon beam, and flattening filter are removed from the beam path. This leads to lateral dose-profile curves, which depend only on the mean energy of the incident electron beam, since the effect of the radial intensity distribution of the incident e- beam is negligible when both filters are absent. The location of the primary collimator and the thickness and density of the target are not considered as adjustable parameters, since a satisfactory working Monte Carlo model is obtained for the low energy photon beam (6 MV) of the linac using the same target and primary collimator. This method was applied to conclude that the mean energy of the incident e- beam for the high energy photon beam (18 MV) of our Elekta SLi Plus linac is equal to 14.9 MeV. After optimizing the mean energy, the modelling of the filters, in accordance with the information provided by the manufacturer, can be verified by positioning only one filter in the linac head while the other is removed. It is also demonstrated that the parameter setting for Bremsstrahlung angular sampling in BEAMnrc ('Simple' using the leading term of the Koch and Motz equation or 'KM' using the full equation) leads to different dose-profile curves for the same incident electron energy for the studied 18 MV beam. It is therefore important to perform the calculations in 'KM' mode. Note that both filters are not physically removed from the linac head. All filters remain present in the linac head and are only rotated out of the beam. This makes the described method applicable for practical usage since no recommissioning process is required.

Osteopontin and bone metabolism: a histology and scintigraphy study in rats.

Osteopontin (OPN) is one of the major non-collagen proteins in extracellular bone matrix. To elucidate the function of OPN in bone metabolism, a cellular defect was created in parietal bone and tibia of 12 rats. In Group 1, the left defects were filled with OPN-coated hydroxyapatite (OPN-H). In Group 2, the right defects were filled with non-coated hydroxyapatite (N-H). In both groups, the contra lateral defects were used as control defects. In Group 3, OPN-H was inserted in the left defects and N-H in the right defects. Bone metabolism was measured by (45)Ca and technetium-99m methylene diphosphonate scintigraphy for 4 weeks. Scintigraphy did not show any significant differences in bone metabolism between the defects filled with OPN-H and N-H. A higher bone metabolism was measured between the parietal defects filled with OPN-H or N-H in comparison with the parietal control defects. This difference, however, was not significant and was less for tibia defects. Histological observation (7th week) shows less inflammatory cells at the tibia defects filled with OPN-H compared to the tibia defects filled with N-H. This study did not show any acceleration or inhibition of bone metabolism in parietal or tibia bone in rats, but there is some evidence that OPN might influence inflammatory cells in bone matrix.

Analysis of image quality in digital chest imaging.

An evaluation of the image quality of an amorphous silicon flat-panel detector system and a computed radiology system compared with a screen-film system was performed by means of contrast-detail phantom images. Hard and soft copy images were evaluated. Although patient dose at clinical settings was strongly decreased with the amorphous silicon system, the low-contrast visibility with this system was still significantly better than with the screen-film system. For the computed radiology system, low-contrast visibility was comparable to the screen-film system. Best results were obtained by soft copy reading at full resolution with adaptation of contrast and brightness. Changing tube voltage (102-133 kV), or additional filtration, did not significantly affect image quality. However, low-contrast visibility improved significantly with increasing exposure. It was clearly demonstrated that, in chest imaging, the amorphous silicon system has superior imaging characteristics compared to the screen-film and the computed radiology system.

Cytogenetic biodosimetry of an accidental exposure of a radiological worker using multiple assays.

A technician involved in the maintenance of X-ray equipment visited the occupational medicine service with complaints of skin lesions, apparently caused by an accidental exposure three months earlier. To estimate the dose received by the technician in the accident, biodosimetry was performed 6 and 18 months post-exposure with the dicentric and micronucleus assays. Part of the latest blood sample was also used for retrospective dosimetry by fluorescence in situ hybridisation (FISH) analysis for translocations. The data obtained 6 and 18 months post-exposure indicate that both dicentrics and micronuclei disappear with a half-time of 1 y. After correction for delayed blood sampling, dose values of 0.75 Gy (95% confidence limits 0.56-1.05 Gy) from dicentrics and 0.96 Gy (95% confidence limits 0.79-1.18 Gy) from micronuclei were obtained. FISH analysis of translocations resulted in a dose estimate of 0.79 Gy (95% confidence limits 0.61-0.99 Gy). The satisfactory agreement between the three cytogenetic endpoints supports the use of the micronucleus assay for triage purposes in the case of large scale radiological accidents and provides further evidence for the valid use of FISH for translocations as a reliable retrospective biological dosimeter.