Monte Carlo calculated absorbed-dose energy dependence of EBT3 and EBT4 films for 5-200 MeV electrons and 100 keV-15 MeV photons.

PURPOSE: To use Monte Carlo simulations to study the absorbed-dose energy dependence of GAFChromic EBT3 and EBT4 films for 5-200 MeV electron beams and 100 keV-15 MeV photon beams considering two film compositions: a previous EBT3 composition (Bekerat et al.) and the final composition of EBT3/current composition of EBT4 (Palmer et al.). METHODS: A water phantom was simulated with films at 5-50 mm depth in 5 mm intervals. The water phantom was irradiated with flat, monoenergetic 5-200 MeV electron beams and 100 and 150 keV kilovoltage and 1-15 MeV megavoltage photon beams and the dose to the active layer of the films was scored. Simulations were rerun with the films defined as water to compare the absorbed-dose response of film to water, f - 1 ( Q ) = D f i l m D w a t e r $f^{-1}(Q)=\frac{D_{film}}{D_{water}}$ . RESULTS: For electrons, the Bekerat et al. composition had variations in f - 1 ( Q ) $f^{-1}(Q)$ of up to ( 1.9 ± 0.1 ) % $(1.9\,\pm \,0.1)\%$ from 5 to 200 MeV. Similarly, the Palmer et al. composition had differences in f - 1 ( Q ) $f^{-1}(Q)$ up to ( 2.5 ± 0.2 ) % $(2.5 \pm 0.2)\%$ from 5 to 200 MeV. For photons, f - 1 ( Q ) $f^{-1}(Q)$ varied up to ( 2.4 ± 0.3 ) % $(2.4 \pm 0.3)\%$ and ( 4.5 ± 0.7 ) % $(4.5 \pm 0.7)\%$ from 100 keV to 15 MeV for the Bekerat et al. and Palmer et al. compositions, respectively. The depth of films did not appear to significantly affect f - 1 ( Q ) $f^{-1}(Q)$ for photons at any energy and for electrons at energies > $>$  50 MeV. However, for 5 and 10 MeV electrons, decreases of up to ( 10.2 ± 1.1 ) % $(10.2 \pm 1.1)\%$ in f - 1 ( Q ) $f^{-1}(Q)$ were seen due to stacked films and increased beam attenuation in films compared to water. CONCLUSIONS: The up to ( 2.5 ± 0.2 ) % $(2.5 \pm 0.2)\%$ and ( 4.5 ± 0.7 ) % $(4.5 \pm 0.7)\%$ variations in f - 1 ( Q ) $f^{-1}(Q)$ for electrons and photons, respectively, across the energies considered in this study indicate the importance of calibrating films with the energy intended for measurement. Additionally, this work emphasizes potential issues with stacking films to measure depth dose curves, particularly for electron beams with energies ≤ $\le$ 10 MeV.

Characterization of a new low-dose and low-energy Gafchromic film LD-V1.

PURPOSE: To characterize the dose-response, energy dependence, postexposure changes, orientation dependence, and spatial capabilities of LD-V1, a new low-dose Gafchromic film for low-energy x-ray dosimetry. METHODS: A single sheet of LD-V1 Gafchromic film was cut into 15 × 20 mm2 rectangles with a notch to track orientation. Eight different doses between 5 and 320 mGy were delivered by an MXR-160/22 x-ray tube using x-ray beams of 90, 100, and 120 kVp filtered with 3 mm of Al and 2 mm of Ti. The 120 kVp films were scanned at 1, 1.5, 2, 3, 12, 24, 48, 72, and 168 h postexposure in portrait orientation and additionally scanned in landscape orientation at 24 h. The 90 and 100 kVp films were scanned at 24 h postexposure in portrait orientation. Lastly, a 20 × 200 mm2 strip of film was irradiated using a thin-slit imaging collimator and scanned 24 h postexposure to test the film performance in an x-ray imaging application. RESULTS: Of the three color channels, the red channel was found to produce a dose-response curve with a large range of net optical density (netOD) values across the considered dose range. A prominent energy dependence was discovered, resulting in dose discrepancies on the scale of 17 mGy between 90 and 120 kVp for a dose of 80 mGy. The measured postexposure changes suggest that the calibration irradiation-to-scan time should be longer than 12 h with a ± 4 h scanning time window for dose errors of <0.5%. An average dose difference of 3.4% was found between the two scanning orientations. Lastly, noise of 4% was measured in the thin slit collimator film for a dose of 30 mGy. CONCLUSIONS: We have characterized the LD-V1 film for low-energy, low-dose x-ray dosimetry. Energy, scan-time, and orientation dependencies should be considered when using this film.

Monte Carlo simulations of EBT3 film dose deposition for percentage depth dose (PDD) curve evaluation.

PURPOSE: To use Monte Carlo (MC) calculations to evaluate the effects of Gafchromic EBT3 film orientation on percentage depth dose (PDD) curves. METHODS: Dose deposition in films placed in a water phantom, and oriented either parallel or perpendicular with respect to beam axis, were simulated with MC and compared to PDDs scored in a homogenous water phantom. The effects of introducing 0.01-1.00 mm air gaps on each side of the film as well as a small 1°-3° tilt for film placed in parallel orientation were studied. PDDs scored based on two published EBT3 film compositions were compared. Three photon beam energies of 120 kVp, 220 kVp, and 6 MV and three field sizes between 1 × 1 and 5 × 5 cm2 were considered. Experimental PDDs for a 6-MV 3 × 3 cm2 beam were acquired. RESULTS: PDD curves for films in perpendicular orientation more closely agreed to water PDDs than films placed in parallel orientation. The maximum difference between film and water PDD for films in parallel orientation was -12.9% for the 220 kVp beam. For the perpendicular film orientation, the maximum difference decreased to 5.7% for the 120 kVp beam. The inclusion of an air gap had the largest effect on the 6-MV 1 × 1 cm2 beam, for which the dose in the buildup region was underestimated by 21.2% compared to the simulation with no air gap. A 2° film tilt decreased the difference between the parallel film and homogeneous water phantom PDDs from -5.0% to -0.5% for the 6 MV 3 × 3 cm2 beam. The "newer" EBT3 film composition resulted in larger PDD discrepancies than the previous composition. Experimental film data qualitatively agreed with MC simulations. CONCLUSIONS: PDD measurements with films should either be performed with film in perpendicular orientation to the beam axis or in parallel orientation with a ~ 2º tilt and no air gaps.

[18F]-SuPAR: A Radiofluorinated Probe for Noninvasive Imaging of DNA Damage-Dependent Poly(ADP-ribose) Polymerase Activity.

Poly(ADP ribose) polymerase (PARP) enzymes generate poly(ADP ribose) post-translational modifications on target proteins for an array of functions centering on DNA and cell stress. PARP isoforms 1 and 2 are critically charged with the surveillance of DNA integrity and are the first line guardians of the genome against DNA breaks. Here we present a novel probe ([18F]-SuPAR) for noninvasive imaging of PARP-1/2 activity using positron emission tomography (PET). [18F]-SuPAR is a radiofluorinated nicotinamide adenine dinucleotide (NAD) analog that can be recognized by PARP-1/2 and incorporated into the long branched polymers of poly(ADP ribose) (PAR). The measurement of PARP-1/2 activity was supported by a reduction of radiotracer uptake in vivo following PARP-1/2 inhibition with talazoparib treatment, a potent PARP inhibitor recently approved by FDA for treatment of breast cancer, as well as ex vivo colocalization of radiotracer analog and poly(ADP ribose). With [18F]-SuPAR, we were able to map the dose- and time-dependent activation of PARP-1/2 following radiation therapy in breast and cervical cancer xenograft mouse models. Tumor response to therapy was determined by [18F]-SuPAR PET within 8 h of administration of a single dose of radiation equivalent to one round of stereotactic ablative radiotherapy.

Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas.

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs), have great potential as an unlimited donor source for cell-based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein, we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present evidence that EBRT is effective in arresting growth of hESC-derived teratomas in vivo at day 28 post-implantation by using a microCT irradiator capable of targeted treatment in small animals. Within several days of irradiation, teratomas derived from injection of undifferentiated hESCs and hiPSCs demonstrated complete growth arrest lasting several months. In addition, EBRT reduced reseeding potential of teratoma cells during serial transplantation experiments, requiring irradiated teratomas to be seeded at 1 × 103 higher doses to form new teratomas. We demonstrate that irradiation induces teratoma cell apoptosis, senescence, and growth arrest, similar to established radiobiology mechanisms. Taken together, these results provide proof of concept for the use of EBRT in the treatment of existing teratomas and highlight a strategy to increase the safety of stem cell-based therapies. Stem Cells 2017;35:1994-2000.

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.

Simultaneous iodine and barium imaging with photon-counting CT.

Objective.The objective of this study is to explore the capabilities of photon-counting computed tomography (PCCT) in simultaneously imaging and differentiating materials with close atomic numbers, specifically barium (Z= 56) and iodine (Z= 53), which is challenging for conventional computed tomography (CT).Approach.Experiments were conducted using a bench-top PCCT system equipped with a cadmium zinc telluride detector. Various phantom setups and contrast agent concentrations (1%-5%) were employed, along with a biological sample. Energy thresholds were tuned to the K-edge absorption energies of barium (37.4 keV) and iodine (33.2 keV) to capture multi-energy CT images. K-edge decomposition was performed using K-edge subtraction and principal component analysis (PCA) techniques to differentiate and quantify the contrast agents.Main results.The PCCT system successfully differentiated and accurately quantified barium and iodine in both phantom combinations and a biological sample, achieving high correlations (R2≈1) between true and reconstructed concentrations. PCA outperformed K-edge subtraction, particularly in the presence of calcium, by providing superior differentiation between barium and iodine.Significance.This study demonstrates the potential of PCCT for reliable, detailed imaging in both clinical and research settings, particularly for contrast agents with similar atomic numbers. The results suggest that PCCT could offer significant improvements in imaging quality over conventional CT, especially in applications requiring precise material differentiation.

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.

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.

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.

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.

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.

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.

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).

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/.

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.

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.

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.

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.