A high-resolution large-area detector for quality assurance in radiotherapy.

Hadron therapy is an advanced radiation modality for treating cancer, which currently uses protons and carbon ions. Hadrons allow for a highly conformal dose distribution to the tumour, minimising the detrimental side-effects due to radiation received by healthy tissues. Treatment with hadrons requires sub-millimetre spatial resolution and high dosimetric accuracy. This paper discusses the design, fabrication and performance tests of a detector based on Gas Electron Multipliers (GEM) coupled to a matrix of thin-film transistors (TFT), with an active area of 60 × 80 mm2 and 200 ppi resolution. The experimental results show that this novel detector is able to detect low-energy (40 kVp X-rays), high-energy (6 MeV) photons used in conventional radiation therapy and protons and carbon ions of clinical energies used in hadron therapy. The GEM-TFT is a compact, fully scalable, radiation-hard detector that measures secondary electrons produced by the GEMs with sub-millimetre spatial resolution and a linear response for proton currents from 18 pA to 0.7 nA. Correcting known detector defects may aid in future studies on dose uniformity, LET dependence, and different gas mixture evaluation, improving the accuracy of QA in radiotherapy.

Rethinking the Role of Biodosimetry to Assess Risks for Acute Radiation Syndrome in Very Large Radiation Events: Reconsidering Legacy Concepts.

The development of effective uses of biodosimetry in large-scale events has been hampered by residual, i.e., "legacy" thinking based on strategies that scale up from biodosimetry in small accidents. Consequently, there remain vestiges of unrealistic assumptions about the likely magnitude of victims in "large" radiation events and incomplete analyses of the logistics for making biodosimetry measurements/assessments in the field for primary triage. Elements remain from an unrealistic focus on developing methods to use biodosimetry in the initial stage of triage for a million or more victims. Based on recent events and concomitant increased awareness of the potential for large-scale events as well as increased sophistication in planning and experience in the development of biodosimetry, a more realistic assessment of the most effective roles of biodosimetry in large-scale events is urgently needed. We argue this leads to a conclusion that the most effective utilization of biodosimetry in very large events would occur in a second stage of triage, after initially winnowing the population by identifying those most in need of acute medical attention, based on calculations of geographic sites where significant exposures could have occurred. Understanding the potential roles and limitations of biodosimetry in large-scale events involving significant radiation exposure should lead to development of the most effective and useful biodosimetric techniques for each stage of triage for acute radiation syndrome injuries, i.e., based on more realistic assumptions about the underlying event and the logistics for carrying out biodosimetry for large populations.

[Dosimetric analysis of different optimization algorithms for three-dimensional brachytherapy for gynecologic tumors].

OBJECTIVE: To investigate the dosimetric difference between manual and inverse optimization in 3-dimensional (3D) brachytherapy for gynecologic tumors. METHODS: This retrospective study was conducted among a total of 110 patients with gynecologic tumors undergoing intracavitary combined with interstitial brachytherapy or interstitial brachytherapy. Based on the original images, the brachytherapy plans were optimized for each patient using Gro, IPSA1, IPSA2 (with increased volumetric dose limits on the basis of IPSA1) and HIPO algorithms. The dose-volume histogram (DVH) parameters of the clinical target volume (CTV) including V200, V150, V100, D90, D98 and CI, and the dosimetric parameters D2cc, D1cc, and D0.1cc for the bladder, rectum, and sigmoid colon were compared among the 4 plans. RESULTS: Among the 4 plans, Gro optimization took the longest time, followed by HIPO, IPSA2 and IPSA1 optimization. The mean D90, D98, and V100 of HIPO plans were significantly higher than those of Gro and IPSA plans, and D90 and V100 of IPSA1, IPSA2 and HIPO plans were higher than those of Gro plans (P < 0.05), but the CI of the 4 plans were similar (P > 0.05). For the organs at risk (OARs), the HIPO plan had the lowest D2cc of the bladder and rectum; the bladder absorbed dose of Gro plans were significantly greater than those of IPSA1 and HIPO (P < 0.05). The D2cc and D1cc of the rectum in IPSA1, IPSA2 and HIPO plans were better than Gro (P < 0.05). The D2cc and D1cc of the sigmoid colon did not differ significantly among the 4 plans. CONCLUSION: Among the 4 algorithms, the HIPO algorithm can better improve dose coverage of the target and lower the radiation dose of the OARs, and is thus recommended for the initial plan optimization. Clinically, the combination of manual optimization can achieve more individualized dose distribution of the plan.

CNN application for automated determination of the patient's size to obtain the size-specific dose estimated in CT.

Introduction. The currently available dosimetry techniques in computed tomography can be inaccurate which overestimate the absorbed dose. Therefore, we aimed to provide an automated and fast methodology to more accurately calculate the SSDE usingDwobtained by using CNN from thorax and abdominal CT study images.Methods. The SSDE was determined from the 200 records files. For that purpose, patients' size was measured in two ways: (a) by developing an algorithm following the AAPM Report No. 204 methodology; and (b) using a CNN according to AAPM Report No. 220.Results. The patient's size measured by the in-house software in the region of thorax and abdomen was 27.63 ± 3.23 cm and 28.66 ± 3.37 cm, while CNN was 18.90 ± 2.6 cm and 21.77 ± 2.45 cm. The SSDE in thorax according to 204 and 220 reports were 17.26 ± 2.81 mGy and 23.70 ± 2.96 mGy for women and 17.08 ± 2.09 mGy and 23.47 ± 2.34 mGy for men. In abdomen was 18.54 ± 2.25 mGy and 23.40 ± 1.88 mGy in women and 18.37 ± 2.31 mGy and 23.84 ± 2.36 mGy in men.Conclusions. Implementing CNN-based automated methodologies can contribute to fast and accurate dose calculations, thereby improving patient-specific radiation safety in clinical practice.

Thermoluminescent dosimeters (TLD-100) for absorbed dose measurements in alpha-emitting radionuclides.

Early works that used thermoluminescent dosimeters (TLDs) to measure absorbed dose from alpha particles reported relatively high variation (10%) between TLDs, which is undesirable for modern dosimetry applications. This work outlines a method to increase precision for absorbed dose measured using TLDs with alpha-emitting radionuclides by applying an alpha-specific chip factor (CF) that individually characterizes the TLD sensitivity to alpha particles. Variation between TLDs was reduced from 21.8% to 6.7% for the standard TLD chips and 7.9% to 3.3% for the thin TLD chips. It has been demonstrated by this work that TLD-100 can be calibrated to precisely measure the absorbed dose to water from alpha-emitting radionuclides.

[Research on Position Verification of Multi-Leaf Collimator (MLC) and Dose Verification Based on Electronic Portal Imaging Device].

Objective: A quality control (QC) system based on the electronic portal imaging device (EPID) system was used to realize the Multi-Leaf Collimator (MLC) position verification and dose verification functions on Primus and VenusX accelerators. Methods: The MLC positions were calculated by the maximum gradient method of gray values to evaluate the deviation. The dose of images acquired by EPID were reconstructed using the algorithm combining dose calibration and dose calculation. The dose data obtained by EPID and two-dimensional matrix (MapCheck/PTW) were compared with the dose calculated by Pinnacle/TiGRT TPS for γ passing rate analysis. Results: The position error of VenusX MLC was less than 1 mm. The position error of Primus MLC was significantly reduced after being recalibrated under the instructions of EPID. For the dose reconstructed by EPID, the average γ passing rates of Primus were 98.86% and 91.39% under the criteria of 3%/3 mm, 10% threshold and 2%/2 mm, 10% threshold, respectively. The average γ passing rates of VenusX were 98.49% and 91.11%, respectively. Conclusion: The EPID-based accelerator quality control system can improve the efficiency of accelerator quality control and reduce the workload of physicists.

An artificial neural network based approach for predicting the proton beam spot dosimetric characteristics of a pencil beam scanning technique.

Utilising Machine Learning (ML) models to predict dosimetric parameters in pencil beam scanning proton therapy presents a promising and practical approach. The study developed Artificial Neural Network (ANN) models to predict proton beam spot size and relative positional errors using 9000 proton spot data. The irradiation log files as input variables and corresponding scintillation detector measurements as the label values. The ANN models were developed to predict six variables: spot size in thex-axis,y-axis, major axis, minor axis, and relative positional errors in thex-axis andy-axis. All ANN models used a Multi-layer perception (MLP) network using one input layer, three hidden layers, and one output layer. Model performance was validated using various statistical tools. The log file recorded spot size and relative positional errors, which were compared with scintillator-measured data. The Root Mean Squared Error (RMSE) values for the x-spot and y-spot sizes were 0.356 mm and 0.362 mm, respectively. Additionally, the maximum variation for the x-spot relative positional error was 0.910 mm, while for the y-spot, it was 1.610 mm. The ANN models exhibit lower prediction errors. Specifically, the RMSE values for spot size prediction in the x, y, major, and minor axes are 0.053 mm, 0.049 mm, 0.053 mm, and 0.052 mm, respectively. Additionally, the relative spot positional error prediction model for the x and y axes yielded maximum errors of 0.160 mm and 0.170 mm, respectively. The normality of models was validated using the residual histogram and Q-Q plot. The data over fit, and bias were tested using K (k = 5) fold cross-validation, and the maximum RMSE value of the K fold cross-validation among all the six ML models was less than 0.150 mm (R-Square 0.960). All the models showed excellent prediction accuracy. Accurately predicting beam spot size and positional errors enhances efficiency in routine dosimetric checks.

Breakthrough electroneutron multi-response miniature dosimetry/spectrometry in medical accelerator.

Breakthrough multi-response miniature dosimetry/spectrometry of electroneutrons (EN) was made on surface and in-depths of whole-body polyethylene phantom under 10 cm × 10 cm electron beam of 20 MV Varian Clinac 2100C electron medical accelerator commonly applied for prostate treatment. While dosimetry/spectrometry of photoneutrons (PN) has been well characterized for decades, those of ENs lagged behind due to very low EN reaction cross section and lack of sensitive neutron dosimeters/spectrometers meeting neutron dosimetry requirements. Recently, Sohrabi "miniature neutron dosimeter/spectrometer" and "Stripe polycarbonate dosimeter" have broken this barrier and determined seven EN ambient dose equivalent (ENDE) (µSv.Gy-1) responses from electron beam and from albedo ENs including beam thermal (21 ± 2.63), albedo thermal (43 ± 3.70), total thermal (64 ± 6.33), total epithermal (32 ± 3.90), total fast (112.00), total thermal + epithermal (l96 ± 10), and total thermal + epithermal + fast (208 ± 10.23) ENs. Having seven ENDE responses of this study and seven PNDE responses of previous study with the same accelerator obtained at identical conditions by the same principle author provided the opportunity to compare the two sets of responses. The PNDE (µSv.Gy-1) responses have comparatively higher values and 22.60 times at isocenter which provide for the first time breakthrough ENDE responses not yet reported in any studies before worldwide.

Dosimetric Systems in Pre-Treatment QA for Stereotactic Treatments: Correlation Agreements and Target Volume Dependency.

AIM: This study comprehensively investigated pre-treatment quality assurance (QA) for 100 cancer patients undergoing stereotactic treatments (SRS/SRT) using various detectors. METHODS: The study conducted QA for SRS/SRT treatments planned with a 6MV SRS beam at a dose rate of 1,000 MU/min, utilizing Eclipse v13.6 Treatment Planning System (TPS). Point dose measurements employed 0.01cm3 and 0.13cm3 cylindrical ionization chambers, while planar dose verification utilized Gafchromic EBT-XD Film and Portal Imager (aS1000). Plans were categorized by target volume, and a thorough analysis compared point dose agreements, planar dose gamma pass rates, and their correlations with chamber volume mean dose, detector type, and point dose agreement. Additionally, the consistency between different ionization chambers was assessed. RESULTS: Point dose agreement generally improved with increasing target volume, except for volumes over 10cm3 with 0.01cm3 chambers, showing a contrary trend. Significant differences (p<0.05) were observed between TPS and measured doses for both chambers. Gamma pass rate improved with increasing target volume in EBT XD and aS1000 analyses, except for the >10cm3 group in EBT XD. EBT XD demonstrated better agreement with TPS for target volumes up to 10cm3 compared to aS1000, with a statistically significant difference (p<0.05) between the detectors. Strong correlations were found between chamber point dose and chamber volume mean dose agreement, as well as between the two gamma criteria analyses of the same detector type in the planar dose correlation analysis. However, weak correlations were discovered for other analyses. CONCLUSION: This study found weak correlation between different detector types in pre-treatment QA for point dose and planar dose evaluation. However, within a specific detector type, strong correlation was observed for different point dose evaluation methods and gamma criteria. This highlights the importance of cautious interpretation of QA results, particularly for SRS QA, due to the lack of correlation between detector types.

Experimental comparison of cylindrical and plane parallel ionization chambers for reference dosimetry in continuous and pulsed scanned proton beams.

Objective. In this experimental work we compared the determination of absorbed dose to water using four ionization chambers (ICs), a PTW-34045 Advanced Markus, a PTW-34001 Roos, an IBA-PPC05 and a PTW-30012 Farmer, irradiated under the same conditions in one continuous- and in two pulsed-scanned proton beams.Approach. The ICs were positioned at 2 cm depth in a water phantom in four square-field single-energy scanned-proton beams with nominal energies between 80 and 220 MeV and in the middle of 10 × 10 × 10 cm3dose cubes centered at 10 cm or 12.5 cm depth in water. The water-equivalent thickness (WET) of the entrance window and the effective point of measurement was considered when positioning the plane parallel (PP) ICs and the cylindrical ICs, respectively. To reduce uncertainties, all ICs were calibrated at the same primary standards laboratory. We used the beam quality (kQ) correction factors for the ICs under investigation from IAEA TRS-398, the newly calculated Monte Carlo (MC) values and the anticipated IAEA TRS-398 updated recommendations.Main results. Dose differences among the four ICs ranged between 1.5% and 3.7% using both the TRS-398 and the newly recommendedkQvalues. The spread among the chambers is reduced with the newlykQvalues. The largest differences were observed between the rest of the ICs and the IBA-PPC05 IC, obtaining lower dose with the IBA-PPC05.Significance. We provide experimental data comparing different types of chambers in different proton beam qualities. The observed dose differences between the ICs appear to be related to inconsistencies in the determination of thekQvalues. For PP ICs, MC studies account for the physical thickness of the entrance window rather than the WET. The additional energy loss that the wall material invokes is not negligible for the IBA-PPC05 and might partially explain the lowkQvalues determined for this IC. To resolve this inconsistency and to benchmark MC values,kQvalues measured using calorimetry are needed.

Dosimetric impact of contour editing on CT and MRI deep-learning autosegmentation for brain OARs.

PURPOSE: To establish the clinical applicability of deep-learning organ-at-risk autocontouring models (DL-AC) for brain radiotherapy. The dosimetric impact of contour editing, prior to model training, on performance was evaluated for both CT and MRI-based models. The correlation between geometric and dosimetric measures was also investigated to establish whether dosimetric assessment is required for clinical validation. METHOD: CT and MRI-based deep learning autosegmentation models were trained using edited and unedited clinical contours. Autosegmentations were dosimetrically compared to gold standard contours for a test cohort. D1%, D5%, D50%, and maximum dose were used as clinically relevant dosimetric measures. The statistical significance of dosimetric differences between the gold standard and autocontours was established using paired Student's t-tests. Clinically significant cases were identified via dosimetric headroom to the OAR tolerance. Pearson's Correlations were used to investigate the relationship between geometric measures and absolute percentage dose changes for each autosegmentation model. RESULTS: Except for the right orbit, when delineated using MRI models, the dosimetric statistical analysis revealed no superior model in terms of the dosimetric accuracy between the CT DL-AC models or between the MRI DL-AC for any investigated brain OARs. The number of patients where the clinical significance threshold was exceeded was higher for the optic chiasm D1% than other OARs, for all autosegmentation models. A weak correlation was consistently observed between the outcomes of dosimetric and geometric evaluations. CONCLUSIONS: Editing contours before training the DL-AC model had no significant impact on dosimetry. The geometric test metrics were inadequate to estimate the impact of contour inaccuracies on dose. Accordingly, dosimetric analysis is needed to evaluate the clinical applicability of DL-AC models in the brain.

Assessing the sensitivity and suitability of a range of detectors for SIMT PSQA.

PURPOSE: Single-isocenter multi-target intracranial stereotactic radiotherapy (SIMT) is an effective treatment for brain metastases with complex treatment plans and delivery optimization necessitating rigorous quality assurance. This work aims to assess five methods for quality assurance of SIMT treatment plans in terms of their suitability and sensitivity to delivery errors. METHODS: Sun Nuclear ArcCHECK and SRS MapCHECK, GafChromic EBT Radiochromic Film, machine log files, and Varian Portal Dosimetry were all used to measure 15 variations of a single SIMT plan. Variations of the original plan were created with Python. They comprised various degrees of systematic MLC offsets per leaf up to 2 mm, random per-leaf variations with differing minimum and maximum magnitudes, simulated collimator, and dose miscalibrations (MU scaling). The erroneous plans were re-imported into Eclipse and plan-quality degradation was assessed by comparing each plan variation to the original clinical plan in terms of the percentage of clinical goals passing relative to the original plan. Each erroneous plan could be then ranked by the plan-quality degradation percentage following recalculation in the TPS so that the effects of each variation could be correlated with γ pass rates and detector suitability. RESULTS & CONCLUSIONS: It was found that 2%/1 mm is a good starting point for the ArcCHECK, Portal Dosimetry, and the SRS MapCHECK methods, respectively, and provides clinically relevant error detection sensitivity. Looser dose criteria of 5%/1 mm or 5%/1.5 mm are suitable for film dosimetry and log-file-based methods. The statistical methods explored can be expanded to other areas of patient-specific QA and detector assessment.

Iterative image reconstruction algorithm analysis for optical CT radiochromic gel dosimetry.

Background.Modern radiation therapy technologies aim to enhance radiation dose precision to the tumor and utilize hypofractionated treatment regimens. Verifying the dose distributions associated with these advanced radiation therapy treatments remains an active research area due to the complexity of delivery systems and the lack of suitable three-dimensional dosimetry tools. Gel dosimeters are a potential tool for measuring these complex dose distributions. A prototype tabletop solid-tank fan-beam optical CT scanner for readout of gel dosimeters was recently developed. This scanner does not have a straight raypath from source to detector, thus images cannot be reconstructed using filtered backprojection (FBP) and iterative techniques are required.Purpose.To compare a subset of the top performing algorithms in terms of image quality and quantitatively determine the optimal algorithm while accounting for refraction within the optical CT system. The following algorithms were compared: Landweber, superiorized Landweber with the fast gradient projection perturbation routine (S-LAND-FGP), the fast iterative shrinkage/thresholding algorithm with total variation penalty term (FISTA-TV), a monotone version of FISTA-TV (MFISTA-TV), superiorized conjugate gradient with the nonascending perturbation routine (S-CG-NA), superiorized conjugate gradient with the fast gradient projection perturbation routine (S-CG-FGP), superiorized conjugate gradient with with two iterations of CG performed on the current iterate and the nonascending perturbation routine (S-CG-2-NA).Methods.A ray tracing simulator was developed to track the path of light rays as they traverse the different mediums of the optical CT scanner. Two clinical phantoms and several synthetic phantoms were produced and used to evaluate the reconstruction techniques under known conditions. Reconstructed images were analyzed in terms of spatial resolution, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), signal non-uniformity (SNU), mean relative difference (MRD) and reconstruction time. We developed an image quality based method to find the optimal stopping iteration window for each algorithm. Imaging data from the prototype optical CT scanner was reconstructed and analysed to determine the optimal algorithm for this application.Results.The optimal algorithms found through the quantitative scoring metric were FISTA-TV and S-CG-2-NA. MFISTA-TV was found to behave almost identically to FISTA-TV however MFISTA-TV was unable to resolve some of the synthetic phantoms. S-CG-NA showed extreme fluctuations in the SNR and CNR values. S-CG-FGP had large fluctuations in the SNR and CNR values and the algorithm has less noise reduction than FISTA-TV and worse spatial resolution than S-CG-2-NA. S-LAND-FGP had many of the same characteristics as FISTA-TV; high noise reduction and stability from over iterating. However, S-LAND-FGP has worse SNR, CNR and SNU values as well as longer reconstruction time. S-CG-2-NA has superior spatial resolution to all algorithms while still maintaining good noise reduction and is uniquely stable from over iterating.Conclusions.Both optimal algorithms (FISTA-TV and S-CG-2-NA) are stable from over iterating and have excellent edge detection with ESF MTF 50% values of 1.266 mm-1and 0.992 mm-1. FISTA-TV had the greatest noise reduction with SNR, CNR and SNU values of 424, 434 and 0.91 × 10-4, respectively. However, low spatial resolution makes FISTA-TV only viable for large field dosimetry. S-CG-2-NA has better spatial resolution than FISTA-TV with PSF and LSF MTF 50% values of 1.581 mm-1and 0.738 mm-1, but less noise reduction. S-CG-2-NA still maintains good SNR, CNR, and SNU values of 168, 158 and 1.13 × 10-4, respectively. Thus, S-CG-2-NA is a well rounded reconstruction algorithm that would be the preferable choice for small field dosimetry.

Tissue equivalent conversion of silicon-based microdosemeters in hadron therapy.

Silicon has been developed as a microdosemeter, as it can provide sensitive volumes at submicrometric levels, does not need a gas supply, has a fast response, and has low power consumption. However, since the energy response in silicon is not the same as that in tissue, a spectral conversion from silicon to tissue is necessary to obtain the probability distribution of energy deposition in tissue. In this work, we present a method for microdosimetric spectra conversion from silicon to tissue based on the scaled Fourier transformation and the geometric scaling factor, which shows relatively good results in the spectral conversion from diamond to tissue. The results illustrate that the method can convert the energy deposition spectra from silicon to tissue with proper accuracy. Meanwhile, the inconsistency between the converted and actual spectra due to the inherent difference was also observed. Whereas, the reasons for the disagreement are different. For the plateau part of the Bragg curve, the discrepancy between the converted and actual spectra is due to the poor tissue equivalent of silicon. For the proximal part of the Bragg curve, the spectral difference is attributed to the different shapes of the energy deposition spectra obtained in silicon and water, which is the same as that in the diamond. In summary, this method can be employed in the tissue equivalent conversion of silicon microdosemeter, but the poor tissue equivalent of silicon limited the accuracy of this method. In addition, the correction for the deviation between the converted and calculated spectra due to the difference in spectral shapes is required to improve the practicality of this mod.

Challenges in commissioning the "TSET" technique: A new approach towards monitor unit calculation and beam profile measurements.

INTRODUCTION: Total skin electron beam therapy, commonly known as TSET, is a good choice of treatment for patients suffering from mycosis fungoides. The aim of this study was to introduce a new approach to the beam profile measurement using diodes and to calculate the monitor units required for the TSET treatment by the use of a simple setup of output measurement. Dosimetric measurements required for the treatment were taken to establish the Stanford technique in the department, and the measured data was compared with the published data. MATERIALS AND METHODS: High-energy Linear Accelerator Clinac-DHX, Varian medical system, Palo Alto, CA, was commissioned for TSET. The output of the machine was measured by the use of a Parallel-Plate Chamber (PPC40) as per the TRS 398 recommendation. Diode dosimeters (EDD2 and EDD5) were used for beam profile measurements due to easy setup and to reduce the measurement time. RESULTS: Homogeneous dose distribution within a field size of 80 cm x160 cm was observed with the variation of -5.0% on the horizontal axis and -5.4% on the vertical axis. The calculated monitor unit to deliver 200 cGy per fraction per field at the source to surface (SSD) of 416 cm was 489 MU. CONCLUSION: The technique described for the output measurements is simple and accurate. Results of the absorbed dose and MU measured were within good agreement compared to the published literature.

Dosimetric validation of SmART-RAD Monte Carlo modelling for x-ray cabinet radiobiology irradiators.

Objective. Accuracy and reproducibility in the measurement of radiation dose and associated reporting are critically important for the validity of basic and preclinical radiobiological studies performed with kilovolt x-ray radiation cabinets. This is essential to enable results of radiobiological studies to be repeated, as well as enable valid comparisons between laboratories. In addition, the commonly used single point dose value hides the 3D dose heterogeneity across the irradiated sample. This is particularly true for preclinical rodent models, and is generally difficult to measure directly. Radiation transport simulations integrated in an easy to use application could help researchers improve quality of dosimetry and reporting.Approach. This paper describes the use and dosimetric validation of a newly-developed Monte Carlo (MC) tool, SmART-RAD, to simulate the x-ray field in a range of standard commercial x-ray cabinet irradiators used for preclinical irradiations. Comparisons are made between simulated and experimentally determined dose distributions for a range of configurations to assess the potential use of this tool in determining dose distributions through samples, based on more readily available air-kerma calibration point measurements.Main results. Simulations gave very good dosimetric agreement with measured depth dose distributions in phantoms containing both water and bone equivalent materials. Good spatial and dosimetric agreement between simulated and measured dose distributions was obtained when using beam-shaping shielding.Significance. The MC simulations provided by SmART-RAD provide a useful tool to go from a limited number of dosimetry measurements to detailed 3D dose distributions through a non-homogeneous irradiated sample. This is particularly important when trying to determine the dose distribution in more complex geometries. The use of such a tool can improve reproducibility and dosimetry reporting in preclinical radiobiological research.

The Micronucleus Assay on Cryopreserved Whole Blood.

The in vitro cytokinesis-block micronucleus (CBMN) assay is a widely used technique in radiobiology research, biological dosimetry, genotoxicity studies, and in vitro radiosensitivity testing. This cytogenetic method is based on the detection of micronuclei in binucleated cells resulting from chromosomal fragments lagging during cell division. Fresh whole blood samples are the most preferred sample type for the CBMN assay. However, the disadvantages of working with fresh blood samples include immediate processing after blood collection and the limited number of repeated analyses that can be performed without extra blood sampling. As the need for fresh blood samples can be logistically challenging, CBMN assay on cryopreserved whole blood samples would be of great advantage, especially in large-scale patient studies. This paper describes a protocol to freeze whole blood samples and to perform the CBMN assay on these frozen blood samples. Blood samples from healthy volunteers have been frozen and thawed at different time points and then, subjected to a modified micronucleus assay protocol. The results demonstrate that this optimized procedure allows the performance of the CBMN assay on frozen blood samples. The described cryopreservation protocol may also be very useful for other cytogenetic assays and a variety of functional assays requiring proliferating lymphocytes.

Flexible Cotton Fabric-Based Ionizing Radiation Dosimeter for 2D Dose Distribution Measurements over a Wide Dose Range at High Dose Rates.

This work presents an ecological, flexible 2D radiochromic dosimeter for measuring ionizing radiation in the kilogray dose range. Cotton woven fabric made of cellulose was volume-modified with nitrotetrazolium blue chloride as a radiation-sensitive compound. Its features include a color change during exposure from yellowish to purple-brown and flexibility that allows it to adapt to various shapes. It was found that (i) the dose response is up to ~80 kGy, (ii) it is independent of the dose rate for 1.1-73.1 kGy/min, (iii) it can be measured in 2D using a flatbed scanner, (iv) the acquired images can be filtered using a mean filter, which improves its dose resolution, (v) the dose resolution is -0.07 to -0.4 kGy for ~0.6 to ~75.7 kGy for filtered images, and (vi) two linear dose subranges can be distinguished: ~0.6 to ~7.6 kGy and ~9.9 to ~62.0 kGy. The dosimeter combined with flatbed scanner reading and data processing using dedicated software packages constitutes a comprehensive system for measuring dose distributions for objects with complex shapes.

Long-term, non-invasive FTIR detection of low-dose ionizing radiation exposure.

Non-invasive methods of detecting radiation exposure show promise to improve upon current approaches to biological dosimetry in ease, speed, and accuracy. Here we developed a pipeline that employs Fourier transform infrared (FTIR) spectroscopy in the mid-infrared spectrum to identify a signature of low dose ionizing radiation exposure in mouse ear pinnae over time. Mice exposed to 0.1 to 2 Gy total body irradiation were repeatedly measured by FTIR at the stratum corneum of the ear pinnae. We found significant discriminative power for all doses and time-points out to 90 days after exposure. Classification accuracy was maximized when testing 14 days after exposure (specificity > 0.9 with a sensitivity threshold of 0.9) and dropped by roughly 30% sensitivity at 90 days. Infrared frequencies point towards biological changes in DNA conformation, lipid oxidation and accumulation and shifts in protein secondary structure. Since only hundreds of samples were used to learn the highly discriminative signature, developing human-relevant diagnostic capabilities is likely feasible and this non-invasive procedure points toward rapid, non-invasive, and reagent-free biodosimetry applications at population scales.