X-ray-Sensitive Doped CaF2-Based MRI Contrast Agents for Local Radiation Dose Measurement.

Ionizing radiation has become widely used in medicine, with application in diagnostic techniques, such as computed tomography (CT) and radiation therapy (RT), where X-rays are used to diagnose and treat tumors. The X-rays used in CT and, in particular, in RT can have harmful side effects; hence, an accurate determination of the delivered radiation dose is of utmost importance to minimize any damage to healthy tissues. For this, medical specialists mostly rely on theoretical predictions of the delivered dose or external measurements of the dose. To extend the practical use of ionizing radiation-based medical techniques, such as magnetic resonance imaging (MRI)-guided RT, a more precise measurement of the internal radiation dose internally is required. In this work, a novel approach is presented to measure dose in liquids for potential future in vivo applications. The strategy relies on MRI contrast agents (CAs) that provide a dose-sensitive signal. The demonstrated materials are (citrate-capped) CaF2 nanoparticles (NPs) doped with Eu3+ or Fe2+/Fe3+ ions. Free electrons generated by ionizing radiation allow the reduction of Eu3+, which produces a very small contrast in MRI, to Eu2+, which induces a strong contrast. Oxidative species generated by high-energy X-rays can be measured indirectly using Fe2+ because it oxidizes to Fe3+, increasing the contrast in MRI. Notably, in the results, a strong increase in the proton relaxation rates is observed for the Eu3+-doped NPs at 40 kV. At 6 MV, a significant increase in proton relaxation rates is observed using CaF2 NPs doped with Fe2+/Fe3+ after irradiation. The presented concept shows great promise for use in the clinic to measure in vivo local ionizing radiation dose, as these CAs can be intravenously injected in a saline solution.

Material decomposition with a prototype photon-counting detector CT system: expanding a stoichiometric dual-energy CT method via energy bin optimization and K-edge imaging.

Objective.Computed tomography (CT) has advanced since its inception, with breakthroughs such as dual-energy CT (DECT), which extracts additional information by acquiring two sets of data at different energies. As high-flux photon-counting detectors (PCDs) become available, PCD-CT is also becoming a reality. PCD-CT can acquire multi-energy data sets in a single scan by spectrally binning the incident x-ray beam. With this, K-edge imaging becomes possible, allowing high atomic number (high-Z) contrast materials to be distinguished and quantified. In this study, we demonstrated that DECT methods can be converted to PCD-CT systems by extending the method of Bourqueet al(2014). We optimized the energy bins of the PCD for this purpose and expanded the capabilities by employing K-edge subtraction imaging to separate a high-atomic number contrast material.Approach.The method decomposes materials into their effective atomic number (Zeff) and electron density relative to water (ρe). The model was calibrated and evaluated using tissue-equivalent materials from the RMI Gammex electron density phantom with knownρevalues and elemental compositions. TheoreticalZeffvalues were found for the appropriate energy ranges using the elemental composition of the materials.Zeffvaried slightly with energy but was considered a systematic error. Anex vivobovine tissue sample was decomposed to evaluate the model further and was injected with gold chloride to demonstrate the separation of a K-edge contrast agent.Main results.The mean root mean squared percent errors on the extractedZeffandρefor PCD-CT were 0.76% and 0.72%, respectively and 1.77% and 1.98% for DECT. The tissue types in theex vivobovine tissue sample were also correctly identified after decomposition. Additionally, gold chloride was separated from theex vivotissue sample with K-edge imaging.Significance.PCD-CT offers the ability to employ DECT material decomposition methods, along with providing additional capabilities such as K-edge imaging.

Mini-GRID radiotherapy on the CLEAR very-high-energy electron beamline: collimator optimization, film dosimetry, and Monte Carlo simulations.

Objective.Spatially-fractionated radiotherapy (SFRT) delivered with a very-high-energy electron (VHEE) beam and a mini-GRID collimator was investigated to achieve synergistic normal tissue-sparing through spatial fractionation and the FLASH effect.Approach.A tungsten mini-GRID collimator for delivering VHEE SFRT was optimized using Monte Carlo (MC) simulations. Peak-to-valley dose ratios (PVDRs), depths of convergence (DoCs, PVDR ≤ 1.1), and peak and valley doses in a water phantom from a simulated 150 MeV VHEE source were evaluated. Collimator thickness, hole width, and septal width were varied to determine an optimal value for each parameter that maximized PVDR and DoC. The optimized collimator (20 mm thick rectangular prism with a 15 mm × 15 mm face with a 7 × 7 array of 0.5 mm holes separated by 1.1 mm septa) was 3D-printed and used for VHEE irradiations with the CERN linear electron accelerator for research beam. Open beam and mini-GRID irradiations were performed at 140, 175, and 200 MeV and dose was recorded with radiochromic films in a water tank. PVDR, central-axis (CAX) and valley dose rates and DoCs were evaluated.Main results.Films demonstrated peak and valley dose rates on the order of 100 s of MGy/s, which could promote FLASH-sparing effects. Across the three energies, PVDRs of 2-4 at 13 mm depth and DoCs between 39 and 47 mm were achieved. Open beam and mini-GRID MC simulations were run to replicate the film results at 200 MeV. For the mini-GRID irradiations, the film CAX dose was on average 15% higher, the film valley dose was 28% higher, and the film PVDR was 15% lower than calculated by MC.Significance.Ultimately, the PVDRs and DoCs were determined to be too low for a significant potential for SFRT tissue-sparing effects to be present, particularly at depth. Further beam delivery optimization and investigations of new means of spatial fractionation are warranted.

Dosimetric characterization of a novel UHDR megavoltage X-ray source for FLASH radiobiological experiments.

A first irradiation platform capable of delivering 10 MV X-ray beams at ultra-high dose rates (UHDR) has been developed and characterized for FLASH radiobiological research at TRIUMF. Delivery of both UHDR (FLASH mode) and low dose-rate conventional (CONV mode) irradiations was demonstrated using a common source and experimental setup. Dose rates were calculated using film dosimetry and a non-intercepting beam monitoring device; mean values for a 100 µA pulse (peak) current were nominally 82.6 and 4.40 × 10-2 Gy/s for UHDR and CONV modes, respectively. The field size for which > 40 Gy/s could be achieved exceeded 1 cm down to a depth of 4.1 cm, suitable for total lung irradiations in mouse models. The calculated delivery metrics were used to inform subsequent pre-clinical treatments. Four groups of 6 healthy male C57Bl/6J mice were treated using thoracic irradiations to target doses of either 15 or 30 Gy using both FLASH and CONV modes. Administration of UHDR X-ray irradiation to healthy mouse models was demonstrated for the first time at the clinically-relevant beam energy of 10 MV.

Non-coplanar lung SABR treatments delivered with a gantry-mounted x-ray tube.

Objective.To create two non-coplanar, stereotactic ablative radiotherapy (SABR) lung patient treatment plans compliant with the radiation therapy oncology group (RTOG) 0813 dosimetric criteria using a simple, isocentric, therapy with kilovoltage arcs (SITKA) system designed to provide low cost external radiotherapy treatments for low- and middle-income countries (LMICs).Approach.A treatment machine design has been proposed featuring a 320 kVp x-ray tube mounted on a gantry. A deep learning cone-beam CT (CBCT) to synthetic CT (sCT) method was employed to remove the additional cost of planning CTs. A novel inverse treatment planning approach using GPU backprojection was used to create a highly non-coplanar treatment plan with circular beam shapes generated by an iris collimator. Treatments were planned and simulated using the TOPAS Monte Carlo (MC) code for two lung patients. Dose distributions were compared to 6 MV volumetric modulated arc therapy (VMAT) planned in Eclipse on the same cases for a Truebeam linac as well as obeying the RTOG 0813 protocols for lung SABR treatments with a prescribed dose of 50 Gy.Main results.The low-cost SITKA treatments were compliant with all RTOG 0813 dosimetric criteria. SITKA treatments showed, on average, a 6.7 and 4.9 Gy reduction of the maximum dose in soft tissue organs at risk (OARs) as compared to VMAT, for the two patients respectively. This was accompanied by a small increase in the mean dose of 0.17 and 0.30 Gy in soft tissue OARs.Significance.The proposed SITKA system offers a maximally low-cost, effective alternative to conventional radiotherapy systems for lung cancer patients, particularly in low-income countries. The system's non-coplanar, isocentric approach, coupled with the deep learning CBCT to sCT and GPU backprojection-based inverse treatment planning, offers lower maximum doses in OARs and comparable conformity to VMAT plans at a fraction of the cost of conventional radiotherapy.

Characterization of a 0.8 mm3Medscint plastic scintillator detector system for small field dosimetry.

Objective. Plastic scintillator detectors (PSDs) have demonstrated ability to meet requirements of small field dosimetry. Medscint developed a 1 mm long, 1 mm diameter cylindrical PSD with effective volume of 0.8 mm3. Clinically relevant, small field dosimetric properties of this detector, combined with a novel scintillation dosimetry system-HYPERSCINT RP-200, and HYPERDOSE analysis software were evaluated in this study.Approach. This novel scintillator-based dosimetry system was characterized with 6 MV-WFF and 10 MV-FFF x-ray beams delivered by Varian TrueBeamTMlinear accelerator. The detector was characterized for leakage, short-term repeatability, dose response linearity, angular response, dose rate response, and field size dependence for radiation field sizes of 0.25 × 0.25 to 10 × 10 cm2. Measured detector specific output ratios were compared with microDiamond output factors to determine small field output correction factors,kQclin,Qmsrfclin,fmsr.Main results. The dosimetry system showed excellent short-term repeatability with standard deviation of only 0.04 ± 0.01%. It demonstrated good dose linearity with variations less than 1.0% for 14.4 cGy and above. The dosimetry system was found to be independent of dose rate and angle of irradiation, with deviations for both below 0.5%. Leakage was found to be comparable to background readings. For 6 MV-WFF energy beams, detector specific output ratios for field sizes down to 1 × 1 cm2agreed with output factors measured with PTW TN60019 microDiamond, thus,kQclin,Qmsrfclin,fmsrequates to unity for these field sizes. For 10 MV-FFF energy beams, detector specific output ratios for field sizes down to 2 × 2 cm2agreed with PTW TN60019 microDiamond output factors, thus,kQclin,Qmsrfclin,fmsrequates to unity for these field sizes.kQclin,Qmsrfclin,fmsrfor field sizes down to 0.5 × 0.5 cm2were determined to be within 6% of unity for both 6 MV-WFF and 10 MV-FFF energy beams.Significance. The HYPERSCINT RP-200 dosimetry system coupled with a 0.8 mm3PSD showed excellent dosimetric properties and was found to be clinically relevant for relative dosimetry down to field sizes of 0.5 × 0.5 cm2and potentially smaller.

A feasibility study of ultra-high dose rate mini-GRID therapy using very-high-energy electron beams for a simulated pediatric brain case.

Ultra-high dose rate (UHDR, >40 Gy/s), spatially-fractionated minibeam GRID (mini-GRID) therapy using very-high-energy electrons (VHEE) was investigated using Monte Carlo simulations. Multi-directional VHEE treatments with and without mini-GRID-fractionation were compared to a clinical 6 MV volumetric modulated arc therapy (VMAT) plan for a pediatric glioblastoma patient using dose-volume histograms, volume-averaged dose rates in critical patient structures, and planning target volume D98s. Peak-to-valley dose ratios (PVDRs) and dose rates in organs at risk (OARs) were evaluated due to their relevance for normal-tissue sparing in FLASH and spatially-fractionated techniques. Depths of convergence, defined where the PVDR is first ≤1.1, and depths at which dose rates fall below the UHDR threshold were also evaluated. In a water phantom, the VHEE mini-GRID treatments presented a surface (5 mm depth) PVDR of (51±2) and a depth of convergence of 42 mm at 150 MeV and a surface PVDR of (33±1) with a depth of convergence of 57 mm at 250 MeV. For a pediatric GBM case, VHEE treatments without mini-GRID-fractionation produced 25% and 22% lower volume-averaged doses to OARs compared to the 6 MV VMAT plan and 8/9 and 9/9 of the patient structures were exposed to volume-averaged dose rates >40 Gy/s for the 150 MeV and 250 MeV plans, respectively. The 150 MeV and 250 MeV mini-GRID treatments produced 17% and 38% higher volume-averaged doses to OARs and 3/9 patient structures had volume-averaged dose rates above 40 Gy/s. VHEE mini-GRID plans produced many comparable dose metrics to the clinical VMAT plan, encouraging further optimization.

Framework for Quality Assurance of Ultrahigh Dose Rate Clinical Trials Investigating FLASH Effects and Current Technology Gaps.

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology FLASH working group on quality assurance of potential UHDR clinical trials and reviews current technology gaps to overcome. An important but separate consideration is the appropriate design of trials to most effectively answer clinical and scientific questions about FLASH. This paper begins with an overview of UHDR RT delivery methods. UHDR beam delivery parameters are then covered, with a focus on electron and proton modalities. The definition and control of safe UHDR beam delivery and current and needed dosimetry technologies are reviewed and discussed. System and site credentialing for large, multi-institution trials are reviewed. Quality assurance is then discussed, and new requirements are presented for treatment system standard analysis, patient positioning, and treatment planning. The tables and figures in this paper are meant to serve as reference points as we move toward FLASH-RT clinical trial performance. Some major questions regarding FLASH-RT are discussed, and next steps in this field are proposed. FLASH-RT has potential but is associated with significant risks and complexities. We need to redefine optimization to focus not only on the dose but also on the dose rate in a manner that is robust and understandable and that can be prescribed, validated, and confirmed in real time. Robust patient safety systems and access to treatment data will be critical as FLASH-RT moves into the clinical trials.

Design and CT imaging of casper, an anthropomorphic breathing thorax phantom.

The goal of this work was to build an anthropomorphic thorax phantom capable of breathing motion with materials mimicking human tissues in x-ray imaging applications. The thorax phantom, named Casper, was composed of resin (body), foam (lungs), glow polyactic acid (bones) and natural polyactic acid (tumours placed in the lungs). X-ray attenuation properties of all materials prior to manufacturing were evaluated by means of photon-counting computed tomography (CT) imaging on a table-top system. Breathing motion was achieved by a scotch-yoke mechanism with diaphragm motion frequencies of 10-20 rpm and displacements of 1 to 2 cm. Casper was manufactured by means of 3D printing of moulds and ribs and assembled in a complex process. The final phantom was then scanned using a clinical CT scanner to evaluate material CT numbers and the extent of tumour motion. Casper CT numbers were close to human CT numbers for soft tissue (46 HU), ribs (125 HU), lungs (-840 HU) and tumours (-45 HU). For a 2 cm diaphragm displacement the largest tumour displacement was 0.7 cm. The five tumour volumes were accurately assessed in the static CT images with a mean absolute error of 4.3%. Tumour sizes were either underestimated for smaller tumours or overestimated for larger tumours in dynamic CT images due to motion blurring with a mean absolute difference from true volumes of 10.3%. More Casper information including a motion movie and manufacturing data can be downloaded from http://web.uvic.ca/~bazalova/Casper/.

Publicly available framework for simulating and experimentally validating clinical PET systems.

BACKGROUND: Monte Carlo (MC) simulations are a powerful tool to model medical imaging systems. However, before simulations can be considered the ground truth, they have to be validated with experiments. PURPOSE: To provide a pipeline that models a clinical positron emission tomography (PET)/CT system using MC simulations after extensively validating the results against experimental measurements. METHODS: A clinical four-ring PET imaging system was modeled using Geant4 application for tomographic emission (v. 9.0). To validate the simulations, PET images were acquired of a cylindrical phantom, point source, and image quality phantom with the modeled system and the simulations of the experimental procedures. For the purpose of validating the quantification capabilities and image quality provided by the simulation pipeline, the simulations were compared against the measurements in terms of their count rates and sensitivity as well as their image uniformity, resolution, recovery coefficients (RCs), coefficients of variation, contrast, and background variability. RESULTS: When compared to the measured data, the number of true detections in the MC simulations was within 5%. The scatter fraction was found to be 30.0% ± 2.2% and 28.8% ± 1.7% in the measured and simulated scans, respectively. Analyzing the measured and simulated sinograms, the sensitivities were found to be 8.2 and 7.8 cps/kBq, respectively. The fraction of random coincidences were 19% in the measured data and 25% in the simulation. When calculating the image uniformity within the axial slices, the measured image exhibited a uniformity of 0.015 ± 0.005, whereas the simulated image had a uniformity of 0.029 ± 0.011. In the axial direction, the uniformity was measured to be 0.024 ± 0.006 and 0.040 ± 0.015 for the measured and simulated data, respectively. Comparing the image resolution, an average percentage difference of 2.9% was found between the measurements and simulations. The RCs calculated in both the measured and simulated images were found to be within the EARL ranges, except for that of the simulation of the smallest sphere. The coefficients of variation for the measured and simulated images were found to be 12% and 13%, respectively. Lastly, the background variability was consistent between the measurements and simulations, whereas the average percentage difference in the sphere contrasts was found to be 8.8%. CONCLUSION: The clinical PET/CT system was modeled and validated to provide a simulation pipeline for the community. The pipeline and the validation procedures have been made available (https://github.com/teaghan/PET_MonteCarlo).

Metal artifact correction in photon-counting detector computed tomography: metal trace replacement using high-energy data.

BACKGROUND: Metal artifacts have been an outstanding issue in computed tomography (CT) since its first uses in the clinic and continue to interfere. Metal artifact reduction (MAR) methods continue to be proposed and photon-counting detectors (PCDs) have recently been the subject of research toward this purpose. PCDs offer the ability to distinguish the energy of incident x-rays and sort them in a set number of energy bins. High-energy data captured using PCDs have been shown to reduce metal artifacts in reconstructions due to reduced beam hardening. PURPOSE: High-energy reconstructions using PCD-CT have their drawbacks, such as reduced image contrast and increased noise. Here, we demonstrate a MAR algorithm, trace replacement MAR (TRMAR), in which the data corrupted by metal artifacts in full energy spectrum projections are corrected using the high-energy data captured during the same scan. The resulting reconstructions offer similar MAR to that seen in high-energy reconstructions, but with improved image quality. METHODS: Experimental data were collected using a bench-top PCD-CT system with a cadmium zinc telluride PCD. Simulations were performed to determine the optimal high-energy threshold and to test TRMAR in simulations using the XCAT phantom and a biological sample. For experiments a 100-mm diameter cylindrical phantom containing vials of water, two screws, various densities of Ca(ClO4 )2 , and a spatial resolution phantom was imaged with and without the screws. The screws were segmented in the initial reconstruction and forward projected to identify them in the sinogram space in order to perform TRMAR. The resulting reconstructions were compared to the control and to reconstructions corrected using normalized metal artifact reduction (NMAR). Additionally, a beef short rib was imaged with and without metal to provide a more realistic phantom. RESULTS: XCAT simulations showed a reduction in the streak artifact from -978 HU in uncorrected images to -10 HU with TRMAR. The magnitude of the metal artifact in uncorrected images of the 100-mm phantom was -442 HU, compared to the desired -81 HU with no metal. TRMAR reduced the magnitude of the artifact to -142 HU, with NMAR reducing the magnitude to -96 HU. Relative image noise was reduced from 176% in the high-energy image to 56% using TRMAR. Density quantification was better with NMAR, with the Ca(ClO4 )2 vial affected most by metal artifacts showing 0.8% error compared to 2.1% with TRMAR. Small features were preserved to a greater extent with TRMAR, with the limiting spatial frequency at 20% of the MTF fully maintained at 1.31 lp/mm, while with NMAR it was reduced to 1.22 lp/mm. Images of the beef short rib showed better delineation of the shape of the metal using TRMAR. CONCLUSIONS: NMAR offers slightly better performance compared to TRMAR in streak reduction and image quality metrics. However, TRMAR is less susceptible to metal segmentation errors and can closely approximate the reduction in the streak metal artifact seen in NMAR at 1/3 the computation time. With the recent introduction of PCD-CT into the clinic, TRMAR offers notable potential for fast, effective MAR.

Monte Carlo optimization of a GRID collimator for preclinical megavoltage ultra-high dose rate spatially-fractionated radiation therapy.

Objective. A 2-dimensional pre-clinical SFRT (GRID) collimator was designed for use on the ultra-high dose rate (UHDR) 10 MV ARIEL beamline at TRIUMF. TOPAS Monte Carlo simulations were used to determine optimal collimator geometry with respect to various dosimetric quantities.Approach. The GRID-averaged peak-to-valley dose ratio (PVDR) and mean dose rate of the peaks were investigated with the intent of maximizing both values in a given design. The effects of collimator thickness, focus position, septal width, and hole width on these metrics were found by testing a range of values for each parameter on a cylindrical GRID collimator. For each tested collimator geometry, photon beams with energies of 10, 5, and 1 MV were transported through the collimator and dose rates were calculated at various depths in a water phantom located 1.0 cm from the collimator exit.Main results. In our optimization, hole width proved to be the only collimator parameter which increased both PVDR and peak dose rates. From the optimization results, it was determined that our optimized design would be one which achieves the maximum dose rate for a PVDR≥5at 10 MV. Ultimately, this was achieved using a collimator with a thickness of 75 mm, 0.8 mm septal and hole widths, and a focus position matched to the beam divergence. This optimized collimator maintained the PVDR of 5 in the phantom between water depths of 0-10 cm at 10 MV and had a mean peak dose rate of3.06±0.02Gys-1at 0-1 cm depth.Significance. We have investigated the impact of various GRID-collimator design parameters on the dose rate and spatial fractionation of 10, 5, and 1 MV photon beams. The optimized collimator design for the 10 MV ultra-high dose rate photon beam could become a useful tool for radiobiology studies synergizing the effects of ultra-high dose rate (FLASH) delivery and spatial fractionation.

Lead-doped scintillator dosimeters for detection of ultrahigh dose-rate x-rays.

Objective.Lead-doped scintillator dosimeters may be well suited for the dosimetry of FLASH-capable x-ray radiotherapy beams. Our study explores the dose rate dependence and temporal resolution of scintillators that makes them promising in the accurate detection of ultrahigh dose-rate (UHDR) x-rays.Approach.We investigated the response of scintillators with four material compositions to UHDR x-rays produced by a conventional x-ray tube. Scintillator output was measured using the HYPERSCINT-RP100 dosimetry research platform. Measurements were acquired at high frame rates (400 fps) which allowed for accurate dose measurements of sub-second radiation exposures from 1 to 100 ms. Dose-rate dependence was assessed by scaling tube current of the x-ray tube. Scintillator measurements were validated against Monte Carlo simulations of the probe geometries and UHDR x-ray system. Calibration factors converting dose-to-medium to dose-to-water were obtained from simulation data of plastic and lead-doped scintillator materials.Main Results.The results of this work suggest that lead-doped scintillators were dose-rate independent for UHDR x-rays from 1.1 to 40.1 Gy s-1and capable of measuring conventional radiotherapy dose-rates (0.1 Gy s-1) at extended distance from the x-ray focal spot. Dose-to-water measured with a 5% lead-doped scintillator detector agreed with simulations within 0.6%.Significance.Lead-doped scintillators may be a valuable tool for the accurate real-time dosimetry of FLASH-capable UHDR x-ray beams.

Design optimization of an electron-to-photon conversion target for ultra-high dose rate x-ray (FLASH) experiments at TRIUMF.

OBJECTIVE: To develop a bremsstrahlung target and megavoltage (MV) x-ray irradiation platform for ultrahigh dose-rate (UHDR) irradiation of small-animals on the Advanced Rare Isotope Laboratory (ARIEL) electron linac (e-linac) at TRIUMF. APPROACH: An electron-to-photon converter design for UHDR radiotherapy (RT) was centered around optimization of a tantalum-aluminum (Ta-Al) explosion-bonded target. Energy deposition within a homogeneous water-phantom and the target itself were evaluated using EGSnrc and FLUKA MC codes, respectively, for various target thicknesses (0.5-1.5 mm), beam energies (Ee-= 8, 10 MeV) and electron (Gaussian) beam sizes (2σ= 2-10 mm). Depth dose-rates in a 3D-printed mouse phantom were also calculated to infer the compatibility of the 10 MV dose distributions for FLASH-RT in small-animal models. Coupled thermo-mechanical FEA simulations in ANSYS were subsequently used to inform the stress-strain conditions and fatigue life of the target assembly. MAIN RESULTS: Dose-rates of up to 128 Gy s-1at the phantom surface, or 85 Gy s-1at 1 cm depth, were obtained for a 1 × 1 cm2field size, 1 mm thick Ta target and 7.5 cm source-to-surface distance using the FLASH-mode beam (Ee-= 10 MeV, 2σ= 5 mm,P = 1 kW); furthermore, removal of the collimation assembly and using a shorter (3.5 cm) SSD afforded dose-rates >600 Gy s-1, albeit at the expense of field conformality. Target temperatures were maintained below the tantalum, aluminum and cooling-water thresholds of 2000 °C, 300 °C and 100 °C, respectively, while the aluminum strain behavior remained everywhere elastic and helped ensure   the converter survives its prescribed 5 yr operational lifetime. SIGNIFICANCE: Effective design iteration, target cooling and failure mitigation have culminated in a robust target compatible with intensive transient (FLASH) and steady-state (diagnostic) applications. The ARIEL UHDR photon source will facilitate FLASH-RT experiments concerned with sub-second, pulsed or continuous beam irradiations at dose rates in excess of 40 Gy s-1.

Investigation of image quality of MV and kV CBCT with low-Z beams and high DQE detector.

PURPOSE: To investigate cone beam computed tomography (CBCT) image quality using novel combinations of kilovoltage (kV) and megavoltage (MV) beams and detector materials. METHODS: MV and kV CBCT imaging was simulated using the Fastcat hybrid Monte Carlo application. CBCT imaging with various beam energies was investigated: 2.5 and 6 MV photon beams generated with carbon, aluminum, and tungsten targets and a 120 kVp x-ray tube beam based off of a Varian Truebeam on-board imager (OBI). Cadmium tungstate (CWO), gadolinium oxysulfide (GOS), and cesium iodide (CsI) detectors with identical pixel pitch of 0.784 mm were evaluated. Modulation transfer functions (MTF) for all detector/beam combinations were calculated. MV and kV CBCT images for each detector/beam combination of a contrast phantom containing inserts with rib and spongiosa bone, lung, and adipose tissues were simulated with an imaging dose of 7 mGy. Contrast to noise ratio (CNR) of all inserts were compared for all detector/beam combinations. CBCT images of an anthropomorphic head phantom with silver amalgam fillings were also generated. RESULTS: The CWO/120 kVp beam combination resulted in the highest MTF at low frequencies and the CsI detector showed the highest MTF for all other beams and at high frequencies. The CWO/120 kVp beam combination showed the highest CNR for all tissues. The unoptimized CWO/2.5 MV carbon target beam showed the highest CNR of the MV beam/detector combinations with CNR 4% and 17% worse than the optimized Truebeam CsI 120 kVp setup with a bowtie filter and antiscatter grid. Additionally, the CWO 2.5 MV setup showed qualitative reduction of metal artifacts surrounding silver amalgam fillings in an anthropomorphic head phantom. CONCLUSION: This finding makes a compelling case that further optimization of this CWO carbon target setup could produce CBCT images with similar CNR to current OBI CBCT for equivalent dose with added resilience to metal artifacts.

Dose calculations for preclinical radiobiology experiments conducted with single-field cabinet irradiators.

PURPOSE: To provide percentage depth dose (PDD) data along the central axis for dosimetry calculations in small-animal radiation biology experiments performed in cabinet irradiators. The PDDs are provided as a function of source-to-surface distance (SSD), field size, and animal size. METHODS: The X-ray tube designs for four biological cabinet irradiators, the RS2000, RT250, MultiRad350, and XRAD320, were simulated using the BEAMnrc Monte Carlo code to generate 160, 200, 250, and 320 kVp photon beams, respectively. The 320 kVp beam was simulated with two filtrations: a soft F1 aluminium filter and a hard F2 thoraeus filter made of aluminium, tin, and copper. Beams were collimated into circular fields with diameters of 0.5-10 cm at SSDs of 10-60 cm. Monte Carlo dose calculations in 1-5-cm diameter homogeneous (soft tissue) small-animal phantoms as well as in heterogeneous phantoms with 3-mm diameter cylindrical lung and bone inserts (rib and cortical bone) were performed using DOSXYZnrc. The calculated depth doses in three test-cases were estimated by applying SSD, field size, and animal size correction factors to a reference case (40-cm SSD, 1-cm field, and 5-cm animal size), and these results were compared with the specifically simulated (i.e., expected) doses to assess the accuracy of this method. Dosimetry for two test-case scenarios of 160 and 250 kVp beams (representative of end-user beam qualities) was also performed, whereby the simulated PDDs at two different depths were compared with the results based on the interpolation from reference data. RESULTS: The depth doses for three test-cases calculated at 200, 320 kVp F1, and 320 kVp F2 with half value layers (HVLs) ranging from ∼0.6 to 3.6 mm Cu, agreed well with the expected doses, yielding dose differences of 1.2%, 0.1%, and 1.0%, respectively. The two end-user test-cases for 160 and 250 kVp beams with respective HVLs of ∼0.8 and 1.8 mm Cu yielded dose differences of 1.4% and 3.2% between the simulated and the interpolated PDDs. The dose increase at the bone-tissue proximal interface ranged from 1.2 to 2.5 times the dose in soft tissue for rib and 1.3 to 3.7 times for cortical bone. The dose drop-off at 1-cm depth beyond the bone ranged from 1.3% to 6.0% for rib and 3.2% to 11.7% for cortical bone. No drastic dose perturbations occurred in the presence of lung, with lung-tissue interface dose of >99% of soft tissue dose and <3% dose increase at 1-cm depth beyond lung. CONCLUSIONS: The developed dose estimation method can be used to translate the measured dose at a point to dose at any depth in small-animal phantoms, making it feasible for preclinical calculation of dose distributions in animals irradiated with cabinet-style irradiators. The dosimetric impact of bone must be accurately quantified as dramatic dose perturbations at and beyond the bone interfaces can occur due to the relative importance of the photoelectric effect at kilovoltage energies. These results will help improve dosimetric accuracy in preclinical experiments.

FLASH radiotherapy with photon beams.

Ultra-high-dose rate "FLASH" radiotherapy (FLASH-RT) has been shown to drastically reduce normal tissue toxicities while being as efficacious as conventional dose rate radiotherapy to treat tumors. A large number of preclinical studies describing this so-called FLASH effect have led to the clinical translation of FLASH-RT using ultra-high-dose rate electron and proton beams. Although the vast majority of radiation therapy treatments are delivered using X-rays, few preclinical data using ultra-high-dose rate X-ray irradiation have been published. This review focuses on different methods that can be used to generate ultra-high-dose rate X-rays and their beam characteristics along with their effect on the biological tissues and the perspectives for the development of FLASH-RT with X-rays.

Single-Crystal Bismuth Thiophosphate, BiPS4, as a Nontoxic and Mechanically Robust X-ray Detector.

Bismuth thiophosphate, BiPS4, is a promising nontoxic, high-density ternary chalcogenide semiconductor. Polycrystalline BiPS4 was synthesized from the stoichiometric melt of Bi, P, and S. Phosphorus was purified via an in-situ sublimation method. Single crystals of BiPS4 were grown using a modified vertical Bridgman method with a thermal gradient of 18 °C/cm. The material exhibits an electrical resistivity of 2 × 109 Ω·cm. The Knoop hardness of the single crystals is 128 ± 0.8 kg mm-2. A blocking contact behavior was observed with asymmetric contacts of Ga/BiPS4/Ag. A clear photocurrent response was observed from a BiPS4 crystal under an electric field as low as 1.14 V mm-1. Using a tungsten X-ray source, an X-ray sensitivity of 52 µ Gy-1 cm-2 was measured under an electric field of 80 V mm-1. When a single-crystal BiPS4 radiation detector device was used in a pulse-height radiation detection system, a clear charge collection response was observed under a 241Am α-particle radiation source.

Experimental validation of Fastcat kV and MV cone beam CT (CBCT) simulator.

PURPOSE: To experimentally validate the Fastcat cone beam computed tomography (CBCT) simulator against kV and MV CBCT images acquired with a Varian Truebeam linac. METHODS: kV and MV CBCT images of a Catphan 504 phantom were acquired using a 100 kVp beam with the on-board imager (OBI) and a 6 MV treatment beam with the electronic portal imaging device (EPID), respectively. The kV Fastcat simulation was performed using detailed models of the x-ray source, bowtie filter, a high resolution voxelized virtual Catphan phantom, anti-scatter grid, and the CsI scintillating detector. Likewise, an MV Fastcat CBCT was simulated with detailed models for the beam energy spectrum, flattening filter, a high-resolution voxelized virtual Catphan phantom, and the gadolinium oxysulfide (GOS) scintillating detector. Experimental and simulated CBCT images of the phantom were compared with respect to HU values, contrast to noise ratio (CNR), and dose linearity. Detector modulation transfer function (MTF) for the two detectors were also experimentally validated. Fastcat's dose calculations were compared to Monte Carlo (MC) dose calculations performed with Topas. RESULTS: For the kV and MV simulations, respectively: Contrast agreed within 14 and 9 HUs and detector MTF agreed within 4.2% and 2.5%. Likewise, CNR had a root mean squared error (RMSE) of 2.6% and 1.4%. Dose agreed within 2.4% and 1.6% of MC values. The kV and MV CBCT images took 71 and 72 s to simulate in Fastcat with 887 and 493 projections, respectively. CONCLUSIONS: We present a multienergy experimental validation of a fast and accurate CBCT simulator against a commercial linac. The simulator is open source and all models found in this work can be downloaded from https://github.com/jerichooconnell/fastcat.git.

Characterization of an x-ray tube-based ultrahigh dose-rate system for in vitro irradiations.

PURPOSE: To present an x-ray tube system capable of in vitro ultrahigh dose-rate (UHDR) irradiation of small < 0.3 mm samples and to characterize it by means of a plastic scintillation detector (PSD). METHODS AND MATERIALS: A conventional x-ray tube was modified for the delivery of short UHDR irradiations. A beam shutter system with a sample holder was designed and installed in a close proximity of an x-ray tube window to enable <1 s irradiations at UHDR. The dosimetry was performed with a small 0.5-mm long 0.5-mm in diameter PSD irradiated with 80, 100, and 120 kVp beams and beam currents of 1-37.5 mA. The PSD signal was recorded at frame rates of 20 and 50 fps for shutter exposure between 100 and 1125 ms. Irradiation reproducibility was studied with the PSD. The x-ray tube irradiation setup was modeled with Monte Carlo (MC) and dose on a surface of a phantom was also measured with films. The effect of dose delivery uncertainty to 300-µm spheroids due to positioning and spheroid size was evaluated. RESULTS: MC simulations showed good agreement with PSD measurements acquired at both frame rates of 20 and 50 fps in terms of beam temporal profile. PSD-measured dose exhibited excellent linearity as a function of instantaneous dose rate from 3.1 to 118.0 Gy/s as well as shutter exposure time from 100 and 1125 ms for all investigated beam energies. PSD absorbed dose for the 80, 100, and 120 kVp beams agreed with MC simulations to within 5%. The total delivered doses ranged from 0.4 Gy for a 1-mA, 80 kVp beam, and 100 ms shutter exposure to 166.9 Gy for a 37.5-mA, 80 kVp beam, and a 1125 ms exposure. PSD irradiation reproducibility was < 0.5%. Simulated and measured dose fall off agreed and it was steep along the axis of the shutter slit (1%/0.1 mm) and with depth (2%/0.1 mm at 1-mm depth). Spheroid positioning uncertainty of 300 µm resulted in dose difference of < 3% for x and y shifts but up to 7% uncertainty for a z-shift parallel to the beam axis. A 16% difference in spheroid size resulted in <5% dose difference in spheroid absorbed dose. CONCLUSIONS: We have presented a cost-effective x-ray tube-based system with a beam shutter designed for in vitro UHDR delivery and reaching dose rates of up to 118.0 Gy/s. The described shutter system can be easily implemented at other institutions, which might enable new researchers to investigate the radiobiology of UHDR irradiations in vitro.