Institute of Radiation Physics

Purpose The purpose of this work was to establish an empirical model of the ion recombination in the Advanced Markus ionization chamber for measurements in high dose rate/dose‐per‐pulse electron beams. In addition, we compared the observed ion recombination to calculations using the standard Boag two‐voltage‐analysis method, the more general theoretical Boag models, and the semiempirical general equation presented by Burns and McEwen. Methods Two independent methods were used to investigate the ion recombination: (a) Varying the grid tension of the linear accelerator (linac) gun (controls the linac output) and measuring the relative effect the grid tension has on the chamber response at different source‐to‐surface distances (SSD). (b) Performing simultaneous dose measurements and comparing the dose–response, in beams with varying dose rate/dose‐per‐pulse, with the chamber together with dose rate/dose‐per‐pulse independent Gafchromic™ EBT3 film. Three individual Advanced Markus chambers were used for the measurements with both methods. All measurements were performed in electron beams with varying mean dose rate, dose rate within pulse, and dose‐per‐pulse (10 −2 ≤ mean dose rate ≤ 10 3 Gy/s, 10 2 ≤ mean dose rate within pulse ≤ 10 7 Gy/s, 10 −4 ≤ dose‐per‐pulse ≤ 10 1 Gy), which was achieved by independently varying the linac gun grid tension, and the SSD. Results The results demonstrate how the ion collection efficiency of the chamber decreased as the dose‐per‐pulse increased, and that the ion recombination was dependent on the dose‐per‐pulse rather than the dose rate, a behavior predicted by Boag theory. The general theoretical Boag models agreed well with the data over the entire investigated dose‐per‐pulse range, but only for a low polarizing chamber voltage (50 V). However, the two‐voltage‐analysis method and the Burns & McEwen equation only agreed with the data at low dose‐per‐pulse values (≤ 10 −2 and ≤ 10 −1 Gy, respectively). An empirical model of the ion recombination in the chamber was found by fitting a logistic function to the data. Conclusions The ion collection efficiency of the Advanced Markus ionization chamber decreases for measurements in electron beams with increasingly higher dose‐per‐pulse. However, this chamber is still functional for dose measurements in beams with dose‐per‐pulse values up toward and above 10 Gy, if the ion recombination is taken into account. Our results show that existing models give a less‐than‐accurate description of the observed ion recombination. This motivates the use of the presented empirical model for measurements with the Advanced Markus chamber in high dose‐per‐pulse electron beams, as it enables accurate absorbed dose measurements (uncertainty estimation: 2.8–4.0%, k = 1). The model depends on the dose‐per‐pulse in the beam, and it is also influenced by the polarizing chamber voltage, with increasing ion recombination with a lowering of the voltage.

The clinical translation of FLASH radiotherapy (RT) requires challenges related to dosimetry and beam monitoring of ultra-high dose rate (UHDR) beams to be addressed. Detectors currently in use suffer from saturation effects under UHDR regimes, requiring the introduction of correction factors. There is significant interest from the scientific community to identify the most reliable solutions and suitable experimental approaches for UHDR dosimetry. This interest is manifested through the increasing number of national and international projects recently proposed concerning UHDR dosimetry. Attaining the desired solutions and approaches requires further optimization of already established technologies as well as the investigation of novel radiation detection and dosimetry methods. New knowledge will also emerge to fill the gap in terms of validated protocols, assessing new dosimetric procedures and standardized methods. In this paper, we discuss the main challenges coming from the peculiar beam parameters characterizing UHDR beams for FLASH RT. These challenges vary considerably depending on the accelerator type and technique used to produce the relevant UHDR radiation environment. We also introduce some general considerations on how the different time structure in the production of the radiation beams, as well as the dose and dose-rate per pulse, can affect the detector response. Finally, we discuss the requirements that must characterize any proposed dosimeters for use in UDHR radiation environments. A detailed status of the current technology is provided, with the aim of discussing the detector features and their performance characteristics and/or limitations in UHDR regimes. We report on further developments for established detectors and novel approaches currently under investigation with a view to predict future directions in terms of dosimetry approaches, practical procedures, and protocols. Due to several on-going detector and dosimetry developments associated with UHDR radiation environment for FLASH RT it is not possible to provide a simple list of recommendations for the most suitable detectors for FLASH RT dosimetry. However, this article does provide the reader with a detailed description of the most up-to-date dosimetric approaches, and describes the behavior of the detectors operated under UHDR irradiation conditions and offers expert discussion on the current challenges which we believe are important and still need to be addressed in the clinical translation of FLASH RT.

PURPOSE: The Oriatron eRT6 is an experimental high dose-per-pulse linear accelerator (linac) which was designed to deliver an electron beam with variable dose-rates, ranging from a few Gy/min up to hundreds of Gy/s. It was built to study the radiobiological effects of high dose-per-pulse/dose-rate electron beam irradiation, in the context of preclinical and cognitive studies. In this work, we report on the commissioning and beam monitoring of the Oriatron eRT6 prototype linac. MATERIALS AND METHODS: The beam was characterized in different steps. The output stability was studied by performing repeated measurements over a period of 20 months. The relative output variations caused by changing beam parameters, such as the temporal electron pulse width, the pulse repetition frequency and the pulse amplitude were also analyzed. Finally, depth dose curves and field sizes were measured for two different beam settings, resulting in one beam with a conventional radiotherapy dose-rate and one with a much higher dose-rate. Measurements were performed with Gafchromic EBT3 films and with a PTW Advanced Markus ionization chamber. In addition, we developed a beam current monitoring system based on the signals from an induction torus positioned at the beam exit of the waveguide and from a graphite beam collimator. RESULTS: The stability of the output over repeated measurements was found to be good, with a standard deviation smaller than 1%. However, non-negligible day-to-day variations of the beam output were observed. Those output variations showed different trends depending on the dose-rate. The analysis of the relative output variation as a function of various beam parameters showed that in a given configuration, the dose-rate could be reliably varied over three orders of magnitude. Interdependence effects on the output variation between the parameters were also observed. The beam energy and field size were found to be slightly dose-rate-dependent and suitable mainly for small animal irradiation. The beam monitoring system was able to measure in a reproducible way the total charge of electrons that exit the machine, as long as the electron pulse amplitude remains above a given threshold. Furthermore, we were able to relate the charge measured with the monitoring system to the absorbed dose in a solid water phantom. CONCLUSION: The Oriatron eRT6 was successfully commissioned for preclinical use and is currently in full operation, with studies being performed on the radiobiological effects of high dose-per-pulse irradiation.

Purpose The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose‐per‐pulse linear accelerator (linac), capable of delivering electron beams with a mean dose‐rate ( Ḋ m ) ranging from 0.07 to 3000 Gy/s and a dose‐rate in pulse ( Ḋ p ) of up to 8 × 10 6 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose‐rate dependence of their response. Material and methods Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Ḋ m dependence was studied at the clinical linac by changing the pulse repetition frequency ( f ) of the beam in order to vary Ḋ m between 0.55 and 4.40 Gy/min, while Ḋ p dependence was probed at the prototype machine for Ḋ p ranging from 7 × 10 3 to 8 × 10 6 Gy/s. Ḋ p dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo‐luminescent dosimeters (TLD) that have been reported as being dose‐rate independent up to such high dose‐rates. Results We report that uncertainty below 4% ( k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Ḋ m dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Ḋ p range attainable at the prototype linac confirming the absence of any dose‐rate dependence within the investigated range (7 × 10 3 to 8 × 10 6 Gy/s). This aspect was further corroborated by the linear relationship between the dose‐per‐pulse ( D p ) measured by films and the charge per pulse ( C p ) measured at the prototype linac exit. Conclusion Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% ( k = 2) and are dose‐rate and energy independent.

BACKGROUND: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. AIMS: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. MATERIALS AND METHODS: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. RESULTS: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. DISCUSSION: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. CONCLUSION: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.

The knowledge of the relationship that links radiation dose and image quality is a prerequisite to any optimization of medical diagnostic radiology. Image quality depends, on the one hand, on the physical parameters such as contrast, resolution, and noise, and on the other hand, on characteristics of the observer that assesses the image. While the role of contrast and resolution is precisely defined and recognized, the influence of image noise is not yet fully understood. Its measurement is often based on imaging uniform test objects, even though real images contain anatomical backgrounds whose statistical nature is much different from test objects used to assess system noise. The goal of this study was to demonstrate the importance of variations in background anatomy by quantifying its effect on a series of detection tasks. Several types of mammographic backgrounds and signals were examined by psychophysical experiments in a two-alternative forced-choice detection task. According to hypotheses concerning the strategy used by the human observers, their signal to noise ratio was determined. This variable was also computed for a mathematical model based on the statistical decision theory. By comparing theoretical model and experimental results, the way that anatomical structure is perceived has been analyzed. Experiments showed that the observer's behavior was highly dependent upon both system noise and the anatomical background. The anatomy partly acts as a signal recognizable as such and partly as a pure noise that disturbs the detection process. This dual nature of the anatomy is quantified. It is shown that its effect varies according to its amplitude and the profile of the object being detected. The importance of the noisy part of the anatomy is, in some situations, much greater than the system noise. Hence, reducing the system noise by increasing the dose will not improve task performance. This observation indicates that the tradeoff between dose and image quality might be optimized by accepting a higher system noise. This could lead to a better resolution, more contrast, or less dose.

Major advances in high precision treatment delivery and imaging have greatly improved the tolerance of radiotherapy (RT); however, the selective sparing of normal tissue and the reduction of neurocognitive side effects from radiation-induced toxicities remain significant problems for pediatric patients with brain tumors. While the overall survival of pediatric patients afflicted with medulloblastoma (MB), the most common type primary brain cancer in children, remains high (≥80%), lifelong neurotoxic side-effects are commonplace and adversely impact patients’ quality of life. To circumvent these clinical complications, we have investigated the capability of ultra-high dose rate FLASH-radiotherapy (FLASH-RT) to protect the radiosensitive juvenile mouse brain from normal tissue toxicities. Compared to conventional dose rate (CONV) irradiation, FLASH-RT was found to ameliorate radiation-induced cognitive dysfunction in multiple independent behavioral paradigms, preserve developing and mature neurons, minimize microgliosis and limit the reduction of the plasmatic level of growth hormone. The protective “FLASH effect” was pronounced, especially since a similar whole brain dose of 8 Gy delivered with CONV-RT caused marked reductions in multiple indices of behavioral performance (objects in updated location, novel object recognition, fear extinction, light-dark box, social interaction), reductions in the number of immature (doublecortin+) and mature (NeuN+) neurons and increased neuroinflammation, adverse effects that were not found with FLASH-RT. Our data point to a potentially innovative treatment modality that is able to spare, if not prevent, many of the side effects associated with long-term treatment that disrupt the long-term cognitive and emotional well-being of medulloblastoma survivors.

This article expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) about radiation protection for endoscopic procedures, in particular endoscopic retrograde cholangiopancreatography (ERCP). Particular cases, including pregnant women and pediatric patients, are also discussed. This Guideline was developed by a group of endoscopists and medical physicists to ensure that all aspects of radiation protection are adequately dealt with. A two-page executive summary of evidence statements and recommendations is provided. The target readership for this Guideline mostly includes endoscopists, anesthesiologists, and endoscopy assistants who may be exposed to X-rays during endoscopic procedures.

Y-microsphere selective internal radiation therapy (SIRT) is a valuable treatment in unresectable hepatocellular carcinoma (HCC). Partition-model predictive dosimetry relies on differential tumor-to-nontumor perfusion evaluated on pretreatment 99m Tcmacroaggregated albumin (MAA) SPECT/CT. The aim of this study was to evaluate agreement between the predictive dosimetry of 99m Tc-MAA SPECT/CT and posttreatment dosimetry based on 90 Y time-of-flight (TOF) PET/CT. Methods: We compared the 99m Tc-MAA SPECT/CT results for 27 treatment sessions (25 HCC patients, 41 tumors) with 90 Y SIRT (7 glass spheres, 20 resin spheres) and the posttreatment 90 Y TOF PET/CT results. Three-dimensional voxelized dose maps were computed from the 99m Tc-MAA SPECT/CT and 90 Y TOF PET/CT data. Mean absorbed dose (D mean ) was evaluated to compute the predicted-to-actual dose ratio (DR mean 5 D MAA mean =D 90Y mean ) in tumor volumes (TVs) and nontumor volumes (NTVs) for glass and resin spheres. The Lin concordance (r c ) was used to measure accuracy (C b ) and precision (r). Results: Administered activity ranged from 0.8 to 1.9 GBq for glass spheres and from 0.6 to 3.4 GBq for resin spheres, and the respective TVs ranged from 2 to 125 mL and from 6 to 1,828 mL. The mean dose D 90Y mean was 240 Gy for glass and 122 Gy for resin in TVs and 72 Gy for glass and 47 Gy for resin in NTVs. DR TV mean was 1.46 0.58 (0.65-2.53) for glass and 1.16 0.41 (0.54-2.54) for resin, and the respective values for DR NTV mean were 0.88 0.15 (0.56-1.00) and 0.86 0.2 (0.58-1.35). DR variability was substantially lower in NTVs than in TVs. The Lin concordance between D MAA mean and D 90Y mean (resin) was significantly better for tumors larger than 150 mL than for tumors 150 mL or smaller (r c 5 0.93 and C b 5 0.95 vs. r c 5 0.57 and C b 5 0.93; P , 0.05). Conclusion: In 90 Y radioembolization of HCC, predictive dosimetry based on 99m Tc-MAA SPECT/CT provided good estimates of absorbed doses calculated from posttreatment 90 Y TOF PET/CT for tumor and nontumor tissues. The low variability of DR NTV demonstrates that pretreatment dosimetry is particularly suitable for minimizing radiation-induced hepatotoxicity.

PURPOSE: To present the acceptance and the commissioning, to define the reference dose, and to prepare the reference data for a quality assessment (QA) program of an ultra-high dose rate (UHDR) electron device in order to validate it for preclinical animal FLASH radiotherapy (FLASH RT) experiments and for FLASH RT clinical human protocols. METHODS: device was evaluated with electron beams of 9 MeV in conventional (CONV) mode and of 6 and 9 MeV in UHDR mode (nominal energy). The acceptance was performed according to the acceptance protocol of the company. The commissioning consisted of determining the short- and long-term stability of the device, the measurement of percent depth dose curves (PDDs) and profiles at two different positions (with two different dose per pulse regimen) and for different collimator sizes, and the evaluation of the variability of these parameters when changing the pulse width and pulse repetition frequency. Measurements were performed using a redundant and validated dosimetric strategy with alanine and radiochromic films, as well as Advanced Markus ionization chamber for some measurements. RESULTS: The acceptance tests were all within the tolerances of the company's acceptance protocol. The linearity with pulse width was within 1.5% in all cases. The pulse repetition frequency did not affect the delivered dose more than 2% in all cases but 90 Hz, for which the larger difference was 3.8%. The reference dosimetry showed a good agreement within the alanine and films with variations of 2.2% or less. The short-term (resp. long-term) stability was less than 1.0% (resp. 1.8%) and was the same in both CONV and UHDR modes. PDDs, profiles, and reference dosimetry were measured at two positions, providing data for two specific dose rates (about 9 Gy/pulse and 3 Gy/pulse). Maximal beam size was 4 and 6 cm at 90% isodose in the two positions tested. There was no difference between CONV and UHDR mode in the beam characteristics tested. CONCLUSIONS: The device is commissioned for FLASH RT preclinical biological experiments as well as FLASH RT clinical human protocols.

In recent years, technological advances have allowed manufacturers to implement dual-energy computed tomography (DECT) on clinical scanners. With its unique ability to differentiate basis materials by their atomic number, DECT has opened new perspectives in imaging. DECT has been used successfully in musculoskeletal imaging with applications ranging from detection, characterization, and quantification of crystal and iron deposits; to simulation of noncalcium (improving the visualization of bone marrow lesions) or noniodine images. Furthermore, the data acquired with DECT can be postprocessed to generate monoenergetic images of varying kiloelectron volts, providing new methods for image contrast optimization as well as metal artifact reduction. The first part of this article reviews the basic principles and technical aspects of DECT including radiation dose considerations. The second part focuses on applications of DECT to musculoskeletal imaging including gout and other crystal-induced arthropathies, virtual noncalcium images for the study of bone marrow lesions, the study of collagenous structures, applications in computed tomography arthrography, as well as the detection of hemosiderin and metal particles.

To perform planned subtotal resection followed by gamma knife surgery (GKRS) in a series of patients with large vestibular schwannoma (VS), aiming at an optimal functional outcome for facial and cochlear nerves. Patient characteristics, surgical and dosimetric features, and outcome were collected prospectively at the time of treatment and during the follow-up. A consecutive series of 32 patients was treated between July 2010 and June 2016. Mean follow-up after surgery was 29 months (median 24, range 4–78). Mean presurgical tumor volume was 12.5 cm3 (range 1.47–34.9). Postoperative status showed normal facial nerve function (House–Brackmann I) in all patients. In a subgroup of 17 patients with serviceable hearing before surgery and in which cochlear nerve preservation was attempted at surgery, 16 (94.1%) retained serviceable hearing. Among them, 13 had normal hearing (Gardner–Robertson class 1) before surgery, and 10 (76.9%) retained normal hearing after surgery. Mean duration between surgery and GKRS was 6.3 months (range 3.8–13.9). Mean tumor volume at GKRS was 3.5 cm3 (range 0.5–12.8), corresponding to mean residual volume of 29.4% (range 6–46.7) of the preoperative volume. Mean marginal dose was 12 Gy (range 11–12). Mean follow-up after GKRS was 24 months (range 3–60). Following GKRS, there were no new neurological deficits, with facial and hearing functions remaining identical to those after surgery in all patients. Three patients presented with continuous growth after GKRS, were considered failures, and benefited from the same combined approach a second time. Our data suggest that large VS management, with planned subtotal resection followed by GKRS, might yield an excellent clinical outcome, allowing the normal facial nerve and a high level of cochlear nerve functions to be retained. Our functional results with this approach in large VS are comparable with those obtained with GKRS alone in small- and medium-sized VS. Longer term follow-up is necessary to fully evaluate this approach, especially regarding tumor control.

fixation changes are best explained as a response to changes in regional excess phosphorus supply due to sea level-driven variations in shallow sediment denitrification associated with the cyclic drowning and emergence of the continental shelves. This hypothesis is consistent with a glacial ocean that hosted globally lower rates of fixed N input and loss and a longer residence time for oceanic fixed N-a "sluggish" ocean N budget during ice ages. In addition, this work provides a clear sign of sea level-driven glacial/interglacial oscillations in biogeochemical fluxes at and near the ocean margins, with implications for coastal organisms and ecosystems.

UNLABELLED: Dose kernel convolution (DK) methods have been proposed to speed up absorbed dose calculations in molecular radionuclide therapy. Our aim was to evaluate the impact of tissue density heterogeneities (TDH) on dosimetry when using a DK method and to propose a simple density-correction method. METHODS: This study has been conducted on 3 clinical cases: case 1, non-Hodgkin lymphoma treated with (131)I-tositumomab; case 2, a neuroendocrine tumor treatment simulated with (177)Lu-peptides; and case 3, hepatocellular carcinoma treated with (90)Y-microspheres. Absorbed dose calculations were performed using a direct Monte Carlo approach accounting for TDH (3D-RD), and a DK approach (VoxelDose, or VD). For each individual voxel, the VD absorbed dose, D(VD), calculated assuming uniform density, was corrected for density, giving D(VDd). The average 3D-RD absorbed dose values, D(3DRD), were compared with D(VD) and D(VDd), using the relative difference Δ(VD/3DRD). At the voxel level, density-binned Δ(VD/3DRD) and Δ(VDd/3DRD) were plotted against ρ and fitted with a linear regression. RESULTS: The D(VD) calculations showed a good agreement with D(3DRD). Δ(VD/3DRD) was less than 3.5%, except for the tumor of case 1 (5.9%) and the renal cortex of case 2 (5.6%). At the voxel level, the Δ(VD/3DRD) range was 0%-14% for cases 1 and 2, and -3% to 7% for case 3. All 3 cases showed a linear relationship between voxel bin-averaged Δ(VD/3DRD) and density, ρ: case 1 (Δ = -0.56ρ + 0.62, R(2) = 0.93), case 2 (Δ = -0.91ρ + 0.96, R(2) = 0.99), and case 3 (Δ = -0.69ρ + 0.72, R(2) = 0.91). The density correction improved the agreement of the DK method with the Monte Carlo approach (Δ(VDd/3DRD) < 1.1%), but with a lesser extent for the tumor of case 1 (3.1%). At the voxel level, the Δ(VDd/3DRD) range decreased for the 3 clinical cases (case 1, -1% to 4%; case 2, -0.5% to 1.5%, and -1.5% to 2%). No more linear regression existed for cases 2 and 3, contrary to case 1 (Δ = 0.41ρ - 0.38, R(2) = 0.88) although the slope in case 1 was less pronounced. CONCLUSION: This study shows a small influence of TDH in the abdominal region for 3 representative clinical cases. A simple density-correction method was proposed and improved the comparison in the absorbed dose calculations when using our voxel S value implementation.

The main objective of WP1 of the ORAMED (Optimization of RAdiation protection for MEDical staff) project is to obtain a set of standardised data on extremity and eye lens doses for staff in interventional radiology (IR) and cardiology (IC) and to optimise staff protection. A coordinated measurement program in different hospitals in Europe will help towards this direction. This study aims at analysing the first results of the measurement campaign performed in IR and IC procedures in 34 European hospitals. The highest doses were found for pacemakers, renal angioplasties and embolisations. Left finger and wrist seem to receive the highest extremity doses, while the highest eye lens doses are measured during embolisations. Finally, it was concluded that it is difficult to find a general correlation between kerma area product and extremity or eye lens doses.

Assessment of image quality for digital x-ray mammography systems used in European screening programs relies mainly on contrast-detail CDMAM phantom scoring and requires the acquisition and analysis of many images in order to reduce variability in threshold detectability. Part II of this study proposes an alternative method based on the detectability index (d') calculated for a non-prewhitened model observer with an eye filter (NPWE). The detectability index was calculated from the normalized noise power spectrum and image contrast, both measured from an image of a 5 cm poly(methyl methacrylate) phantom containing a 0.2 mm thick aluminium square, and the pre-sampling modulation transfer function. This was performed as a function of air kerma at the detector for 11 different digital mammography systems. These calculated d' values were compared against threshold gold thickness (T) results measured with the CDMAM test object and against derived theoretical relationships. A simple relationship was found between T and d', as a function of detector air kerma; a linear relationship was found between d' and contrast-to-noise ratio. The values of threshold thickness used to specify acceptable performance in the European Guidelines for 0.10 and 0.25 mm diameter discs were equivalent to threshold calculated detectability indices of 1.05 and 6.30, respectively. The NPWE method is a validated alternative to CDMAM scoring for use in the image quality specification, quality control and optimization of digital x-ray systems for screening mammography.

PURPOSE: The Leksell Gamma Knife (LGK) Icon has been recently introduced to provide Gamma Knife technology with frameless stereotactic treatments which use an additional cone-beam CT (CBCT) imaging system and a motion tracking system (IFMM, Intra-Fraction Motion Management). The system was commissioned for the treatment unit itself as well as the imaging system. METHODS: The LGK Icon was calibrated using an A1SL ionization chamber. EBT3 radiochromic films were employed to independently check the machine calibration, to measure the relative output factors (ROFs) and to collect dose distributions. Coincidence between CBCT isocenter and radiological focus was evaluated by means of EBT3 films. CBCT image quality was investigated in terms of spatial resolution, contrast-to-noise ratio (CNR), and uniformity for the two presets available (low dose and high dose). Computed Tomography Dose Index (CTDI) was also measured for both presets. RESULTS: The absolute dose rate of the LGK Icon was 3.86 ± 0.09 Gy/min. This result was confirmed by EBT3 readings. ROF were found to be 0.887 ± 0.035 and 0.797 ± 0.032 for the 8 mm and 4 mm collimators, respectively, which are within 2% of the Monte Carlo-derived ROF values. Excellent agreement was found between calculated and measured dose distribution with the gamma pass rate >95% of points for the nine dose distributions analyzed with 3%/1 mm criteria. CBCT isocenter was found to be within 0.2 mm with respect to radiological focus. Image quality parameters were found to be well within the manufacturer's specifications with the high-dose preset being superior in terms of CNR and uniformity. CTDI values were 2.41 mGy and 6.32 mGy, i.e. -3.6% and 0.3% different from the nominal values for the low-dose and high-dose presets, respectively. CONCLUSIONS: The LGK Icon was successfully commissioned for clinical use. The use of the EBT3 to characterize the treatment unit was demonstrated to be feasible. The CBCT imaging system operates well within the manufacturer's specifications and provides good geometrical accuracy.

PURPOSE: To use novel voxel-based 3D printed textured phantoms in order to compare low-contrast detectability between two reconstruction algorithms, FBP (filtered-backprojection) and SAFIRE (sinogram affirmed iterative reconstruction) and determine what impact background texture (i.e., anatomical noise) has on estimating the dose reduction potential of SAFIRE. METHODS: Liver volumes were segmented from 23 abdominal CT cases. The volumes were characterized in terms of texture features from gray-level co-occurrence and run-length matrices. Using a 3D clustered lumpy background (CLB) model, a fitting technique based on a genetic optimization algorithm was used to find CLB textures that were reflective of the liver textures, accounting for CT system factors of spatial blurring and noise. With the modeled background texture as a guide, four cylindrical phantoms (Textures A-C and uniform, 165 mm in diameter, and 30 mm height) were designed, each containing 20 low-contrast spherical signals (6 mm diameter at nominal contrast levels of ∼3.2, 5.2, 7.2, 10, and 14 HU with four repeats per signal). The phantoms were voxelized and input into a commercial multimaterial 3D printer (Object Connex 350), with custom software for voxel-based printing (using principles of digital dithering). Images of the textured phantoms and a corresponding uniform phantom were acquired at six radiation dose levels (SOMATOM Flash, Siemens Healthcare) and observer model detection performance (detectability index of a multislice channelized Hotelling observer) was estimated for each condition (5 contrasts × 6 doses × 2 reconstructions × 4 backgrounds = 240 total conditions). A multivariate generalized regression analysis was performed (linear terms, no interactions, random error term, log link function) to assess whether dose, reconstruction algorithm, signal contrast, and background type have statistically significant effects on detectability. Also, fitted curves of detectability (averaged across contrast levels) as a function of dose were constructed for each reconstruction algorithm and background texture. FBP and SAFIRE were compared for each background type to determine the improvement in detectability at a given dose, and the reduced dose at which SAFIRE had equivalent performance compared to FBP at 100% dose. RESULTS: ). Overall, SAFIRE had higher d' compared to FBP (P = 0.02). The estimated dose reduction potential of SAFIRE was found to be 8%, 10%, 27%, and 8% for Texture-A, Texture-B, Texture-C and uniform phantoms. CONCLUSIONS: In all background types, detectability was higher with SAFIRE compared to FBP. However, the relative improvement observed from SAFIRE was highly dependent on the complexity of the background texture. Iterative algorithms such as SAFIRE should be assessed in the most realistic context possible.

Persistent vasculature abnormalities contribute to an altered CNS microenvironment that further compromises the integrity of the blood-brain barrier and exposes the brain to a host of neurotoxic conditions. Standard radiation therapy at conventional (CONV) dose rate elicits short-term damage to the blood-brain barrier by disrupting supportive cells, vasculature volume and tight junction proteins. While current clinical applications of cranial radiotherapy use dose fractionation to reduce normal tissue damage, these treatments still cause significant complications. While dose escalation enhances treatment of radiation-resistant tumors, methods to subvert normal tissue damage are clearly needed. In this regard, we have recently developed a new modality of irradiation based on the use of ultra-high-dose-rate FLASH that does not induce the classical pathogenic patterns caused by CONV irradiation. In previous work, we optimized the physical parameters required to minimize normal brain toxicity (i.e., FLASH, instantaneous intra-pulse dose rate, 6.9 · 106 Gy/s, at a mean dose rate of 2,500 Gy/s), which we then used in the current study to determine the effect of FLASH on the integrity of the vasculature and the blood-brain barrier. Both early (24 h, one week) and late (one month) timepoints postirradiation were investigated using C57Bl/6J female mice exposed to whole-brain irradiation delivered in single doses of 25 Gy and 10 Gy, respectively, using CONV (0.09 Gy/s) or FLASH (>106 Gy/s). While the majority of changes found one day postirradiation were minimal, FLASH was found to reduce levels of apoptosis in the neurogenic regions of the brain at this time. At one week and one month postirradiation, CONV was found to induce vascular dilation, a well described sign of vascular alteration, while FLASH minimized these effects. These results were positively correlated with and temporally coincident to changes in the immunostaining of the vasodilator eNOS colocalized to the vasculature, suggestive of possible dysregulation in blood flow at these latter times. Overall expression of the tight junction proteins, occludin and claudin-5, which was significantly reduced after CONV irradiation, remained unchanged in the FLASH-irradiated brains at one and four weeks postirradiation. Our data further confirm that, compared to isodoses of CONV irradiation known to elicit detrimental effects, FLASH does not damage the normal vasculature. These data now provide the first evidence that FLASH preserves microvasculature integrity in the brain, which may prove beneficial to cognition while allowing for better tumor control in the clinic.

BACKGROUND: Ultrahigh dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising antitumor efficacy compared to conventional dose-rate radiotherapy (CONV-RT). To investigate the translational potential of FLASH-RT to a human pediatric medulloblastoma brain tumor, we used a radiosensitive juvenile mouse model to assess adverse long-term neurological outcomes. METHODS: Cohorts of 3-week-old male and female C57Bl/6 mice exposed to hypofractionated (2 × 10 Gy, FLASH-RT or CONV-RT) whole brain irradiation and unirradiated controls underwent behavioral testing to ascertain cognitive status four months posttreatment. Animals were sacrificed 6 months post-irradiation and tissues were analyzed for neurological and cerebrovascular decrements. RESULTS: The neurological impact of FLASH-RT was analyzed over a 6-month follow-up. FLASH-RT ameliorated neurocognitive decrements induced by CONV-RT and preserved synaptic plasticity and integrity at the electrophysiological (long-term potentiation), molecular (synaptophysin), and structural (Bassoon/Homer-1 bouton) levels in multiple brain regions. The benefits of FLASH-RT were also linked to reduced neuroinflammation (activated microglia) and the preservation of the cerebrovascular structure, by maintaining aquaporin-4 levels and minimizing microglia colocalized to vessels. CONCLUSIONS: Hypofractionated FLASH-RT affords significant and long-term normal tissue protection in the radiosensitive juvenile mouse brain when compared to CONV-RT. The capability of FLASH-RT to preserve critical cognitive outcomes and electrophysiological properties over 6-months is noteworthy and highlights its potential for resolving long-standing complications faced by pediatric brain tumor survivors. While care must be exercised before clinical translation is realized, present findings document the marked benefits of FLASH-RT that extend from synapse to cognition and the microvasculature.