Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation.

Purpose: Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs. spread-out-Bragg-peak [SOBP]) on acute radiation-induced gastrointestinal toxicity (RIGIT) in mice. We also compared RIGIT between synchrotron-based protons and linac-based electrons with matched mean dose rates. Methods and Materials: We administered abdominal irradiation (12-14 Gy single fraction) to female C57BL/6J mice with an 87 MeV synchrotron-based proton beamline (2 cm diameter field size as a lateral beam). Dose rates were 0.2 Gy/s (S-T pCONV), 0.3 Gy/s (SOBP pCONV), 150 Gy/s (S-T pFLASH), and 230 Gy/s (SOBP pFLASH). RIGIT was assessed by the jejunal regenerating crypt assay and survival. We also compared responses to proton [pFLASH and pCONV] with responses to electron CONV (eCONV, 0.4 Gy/s) and electron FLASH (eFLASH, 188-205 Gy/s). Results: The number of regenerating jejunal crypts at each matched dose was lowest for pFLASH (similar between S-T and SOBP), greater and similar between pCONV (S-T and SOBP) and eCONV, and greatest for eFLASH. Correspondingly, mice that received pFLASH SOBP had the lowest survival rates (50% at 50 days), followed by pFLASH S-T (80%), and pCONV SOBP (90%), but 100% of mice receiving pCONV S-T survived (log-rank P = 0.047 for the four groups). Conclusions: Our findings are consistent with an increase in RIGIT after synchrotron-based pFLASH versus pCONV. This negative proton-specific FLASH effect versus linac-based electron irradiation underscores the importance of understanding the physical and biological factors that will allow safe and effective clinical translation.

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.

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.

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.

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.

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.

Physics and biology of ultrahigh dose-rate (FLASH) radiotherapy: a topical review.

Ultrahigh dose-rate radiotherapy (RT), or 'FLASH' therapy, has gained significant momentum following various in vivo studies published since 2014 which have demonstrated a reduction in normal tissue toxicity and similar tumor control for FLASH-RT when compared with conventional dose-rate RT. Subsequent studies have sought to investigate the potential for FLASH normal tissue protection and the literature has been since been inundated with publications on FLASH therapies. Today, FLASH-RT is considered by some as having the potential to 'revolutionize radiotherapy'. FLASH-RT is considered by some as having the potential to 'revolutionize radiotherapy'. The goal of this review article is to present the current state of this intriguing RT technique and to review existing publications on FLASH-RT in terms of its physical and biological aspects. In the physics section, the current landscape of ultrahigh dose-rate radiation delivery and dosimetry is presented. Specifically, electron, photon and proton radiation sources capable of delivering ultrahigh dose-rates along with their beam delivery parameters are thoroughly discussed. Additionally, the benefits and drawbacks of radiation detectors suitable for dosimetry in FLASH-RT are presented. The biology section comprises a summary of pioneering in vitro ultrahigh dose-rate studies performed in the 1960s and early 1970s and continues with a summary of the recent literature investigating normal and tumor tissue responses in electron, photon and proton beams. The section is concluded with possible mechanistic explanations of the FLASH normal-tissue protection effect (FLASH effect). Finally, challenges associated with clinical translation of FLASH-RT and its future prospects are critically discussed; specifically, proposed treatment machines and publications on treatment planning for FLASH-RT are reviewed.

On the capabilities of conventional x-ray tubes to deliver ultra-high (FLASH) dose rates.

PURPOSE: By means of Monte Carlo (MC) simulations and indirect measurements, we have evaluated the maximum dose rates achievable with conventional x-ray tubes and related them to FLASH therapy dose rates of >40 Gy/s. METHODS: Monte Carlo models of two 160 kV x-ray tubes, the 3-kW MXR-160/22 and the 6-kW MXR-165, were built in the EGSnrc/BEAMnrc code. The dose rate in a water phantom placed against the x-ray tube surface, located at 3.7 and 3.5 cm from the focal spot for the MXR-160/22 and MXR-165 x-ray tube, respectively, was calculated with DOSXYZnrc. Dose delivered with the 120-kV beam in a plastic water phantom for the MXR-160/22 was measured and calculated. Gafchromic EBT3 films were placed at 15 and 18 mm depths in the plastic water phantom that was irradiated with a low tube current of 0.2 mA for 30 s. RESULTS: The maximum 160-kV phantom surface dose rate was determined to be FLASH capable, calculated as (114.3 ± 0.6) Gy/s and (160.0 ± 0.8) Gy/s for the MXR-160/22 and MXR-165 x-ray tubes, respectively. The dose rate in a 1-cm diameter region was found to be (110.6 ± 2.8) Gy/s and (151.9 ± 2.6) Gy/s and remained FLASH capable to depths of 1.4 and 2.0 mm for the MXR-160/22 and MXR-165 x-ray tube, respectively. The 120-kV dose profiles measured with EBT3 films agreed with MC simulations to within 3.6% for regions outside of heel effect and at both measurement depths; this presented a good validation data set for the simulations of phantom surface dose rate using the 160-kV beam. CONCLUSIONS: We have indirectly determined that, with a careful experimental design, conventional x-ray tubes can be made suitable for use in FLASH radiotherapy and dosimetry experiments.

Preclinical dose verification using a 3D printed mouse phantom for radiobiology experiments.

PURPOSE: Dose verification in preclinical radiotherapy is often challenged by a lack of standardization in the techniques and technologies commonly employed along with the inherent difficulty of dosimetry associated with small-field kilovoltage sources. As a consequence, the accuracy of dosimetry in radiobiological research has been called into question. Fortunately, the development and characterization of realistic small-animal phantoms has emerged as an effective and accessible means of improving dosimetric accuracy and precision in this context. The application of three-dimensional (3D) printing, in particular, has enabled substantial improvements in the conformity of representative phantoms with respect to the small animals they are modeled after. In this study, our goal was to evaluate a fully 3D printed mouse phantom for use in preclinical treatment verification of sophisticated therapies for various anatomical targets of therapeutic interest. METHODS: An anatomically realistic mouse phantom was 3D printed based on segmented microCT data of a tumor-bearing mouse. The phantom was modified to accommodate both laser-cut EBT3 radiochromic film within the mouse thorax and a plastic scintillator dosimeter (PSD), which may be placed within the brain, abdomen, or 1-cm flank subcutaneous tumor. Various treatments were delivered on an image-guided small-animal irradiator in order to determine the doses to isocenter using a PSD and validate lateral- and depth-dose distributions using film dosimeters. On-board cone-beam CT imaging was used to localize isocenter to the film plane or PSD active element prior to irradiation. The PSD irradiations comprised a 3 × 3 mm2 brain arc, 5 × 5 mm2 parallel-opposed pair (POP), and 5-beam 10 × 10 mm2 abdominal coplanar arrangement while two-dimensional (2D) film dose distributions were acquired using a 3 × 3 mm2 arc and both 5 × 5 and 10 × 10 mm2 3-beam coplanar plans. A validated Monte Carlo (MC) model of the source was used as to verify the accuracy of the film and PSD dose measurements. computer-aided design (CAD) geometries for the mouse phantom and dosimeters were imported directly into the MC code to allow for highly accurate reproduction of the physical experiment conditions. Experimental and MC-derived film data were co-registered and film dose profiles were compared for points above 90% of the dose maximum. Point dose measurements obtained with the PSD were similarly compared for each of the candidate (brain, abdomen, and tumor) treatment sites. RESULTS: For each treatment configuration and anatomical target, the MC-calculated and measured doses met the proposed 5% agreement goal for dose accuracy in radiobiology experiments. The 2D film and MC dose distributions were successfully registered and mean doses for lateral profiles were found to agree to within 2.3% in all cases. Isocentric point-dose measurements taken with the PSD were similarly consistent, with a maximum percentage deviation of 3.2%. CONCLUSIONS: Our study confirms the utility of 3D printed phantom design in providing accurate dose estimates for a variety of preclinical treatment paradigms. As a tool for pretreatment dose verification, the phantom may be of particular interest to researchers for its ability to facilitate precise dosimetry while fostering a reduction in cost for radiobiology experiments.

Technical Note: Manufacturing of a realistic mouse phantom for dosimetry of radiobiology experiments.

PURPOSE: The goal of this work was to design a realistic mouse phantom as a useful tool for accurate dosimetry in radiobiology experiments. METHODS: A subcutaneous tumor-bearing mouse was scanned in a microCT scanner, its organs manually segmented and contoured. The resulting geometries were converted into a stereolithographic file format (STL) and sent to a multimaterial 3D printer. The phantom was split into two parts to allow for lung excavation and 3D-printed with an acrylic-like material and consisted of the main body (mass density ρ=1.18 g/cm3 ) and bone (ρ=1.20 g/cm3 ). The excavated lungs were filled with polystyrene (ρ=0.32 g/cm3 ). Three cavities were excavated to allow the placement of a 1-mm diameter plastic scintillator dosimeter (PSD) in the brain, the center of the body and a subcutaneous tumor. Additionally, a laser-cut Gafchromic film can be placed in between the two phantom parts for 2D dosimetric evaluation. The expected differences in dose deposition between mouse tissues and the mouse phantom for a 220-kVp beam delivered by the small animal radiation research platform (SARRP) were calculated by Monte Carlo (MC). RESULTS: MicroCT scans of the phantom showed excellent material uniformity and confirmed the material densities given by the manufacturer. MC dose calculations revealed that the dose measured by tissue-equivalent dosimeters inserted into the phantom in the brain, abdomen, and subcutaneous tumor would be underestimated by 3-5%, which is deemed to be an acceptable error assuming the proposed 5% accuracy of radiobiological experiments. CONCLUSIONS: The low-cost mouse phantom can be easily manufactured and, after a careful dosimetric characterization, may serve as a useful tool for dose verification in a range of radiobiology experiments.

Monte Carlo optimization of a microbeam collimator design for use on the small animal radiation research platform (SARRP).

Microbeam radiation therapy (MRT) is a pre-clinical, spatially-fractionated treatment modality noted for its ability to achieve a large differential response between normal and tumoral tissues. In the present study, TOPAS Monte Carlo (MC) simulations were used to optimize the design of a compact, affordable multi-slit collimator (MSC) suitable for use with the small animal radiation research platform (SARRP). MRT dose distributions in a (1 × 1 × 3)cm3 water phantom were simulated for a tungsten MSC using different focal spot sizes (0.4, 3 mm), beam energies (40, 80, 220 kVp), slit widths (100, 125, 150, 175, 200 µm), collimator thicknesses (1.5, 2.5, 3 cm) and collimator-to-surface distances (CSD of 1 and 3 cm). Key MRT figures of merit, namely the peak-to-valley dose ratio (PVDR), full-width at half-maximum and peak dose rate were determined. Use of the small focal spot maximized the PVDR (~40 at surface) and reduced the system's sensitivity to changes in CSD, but decreased the collimated beam output to 55.2 cGy min-1. The large focal spot was ill-suited for large CSD irradiations, but increased the beam output by a factor of 2.8, to 153.0 cGy min-1, and decreased the sensitivity to changes in slit width. A modular MSC, using divergent plastic spacer materials in place of excavated slits, was also investigated. Polypropylene and polyethylene terephthalate material spacers were considered and while neither reduced the PVDR compared to air slits, the dose rate was reduced by 37% and 47%, respectively. Lastly, a steel parallel-slit MSC was used in a preliminary test of MRT delivery using the SARRP. Discrepancies between the results of film dosimetry and the corresponding MC simulations highlight the need to fabricate a more well-defined collimator for use in future validation and radiobiological work. The simulated results of this study are being used to inform the design of such a collimator, which will additionally boast a high degree of modularity at reasonable cost.