Simulation study of a novel small animal FLASH irradiator (SAFI) with integrated inverse-geometry CT based on circularly distributed kV X-ray sources.

Ultra-high dose rate (UHDR) radiotherapy (RT) or FLASH-RT can potentially reduce normal tissue toxicity. A small animal irradiator that can deliver FLASH-RT treatments similar to clinical RT treatments is needed for pre-clinical studies of FLASH-RT. We designed and simulated a novel small animal FLASH irradiator (SAFI) based on distributed x-ray source technology. The SAFI system comprises a distributed x-ray source with 51 focal spots equally distributed on a 20 cm diameter ring, which are used for both FLASH-RT and onboard micro-CT imaging. Monte Carlo simulation was performed to estimate the dosimetric characteristics of the SAFI treatment beams. The maximum dose rate, which is limited by the power density of the tungsten target, was estimated based on finite-element analysis (FEA). The maximum DC electron beam current density is 2.6 mA/mm2, limited by the tungsten target's linear focal spot power density. At 160 kVp, 51 focal spots, each with a dimension of [Formula: see text] mm2 and 10° anode angle, can produce up to 120 Gy/s maximum DC irradiation at the center of a cylindrical water phantom. We further demonstrate forward and inverse FLASH-RT planning, as well as inverse-geometry micro-CT with circular source array imaging via numerical simulations.

Synchronized high-speed scintillation imaging of proton beams, generated by a gantry-mounted synchrocyclotron, on a pulse-by-pulse basis.

BACKGROUND: With the emergence of more complex and novel proton delivery techniques, there is a need for quality assurance tools with high spatiotemporal resolution to conveniently measure the spatial and temporal properties of the beam. In this context, scintillation-based dosimeters, if synchronized with the radiation beam and corrected for ionization quenching, are appealing. PURPOSE: To develop a synchronized high-speed scintillation imaging system for characterization and verification of the proton therapy beams on a pulse-by-pulse basis. MATERIALS AND METHODS: A 30 cm × 30 cm × 5 cm block of BC-408 plastic scintillator placed in a light-tight housing was irradiated by proton beams generated by a Mevion S250 proton therapy synchrocyclotron. A high-speed camera system, placed perpendicular to the beam direction and facing the scintillator, was synchronized to the accelerator's pulses to capture images. Opening and closing of the camera's shutter was controlled by setting a proper time delay and exposure time, respectively. The scintillation signal was recorded as a set of two-dimensional (2D) images. Empirical correction factors were applied to the images to correct for the nonuniformity of the pixel sensitivity and quenching of the scintillator. Proton range and modulation were obtained from the corrected images. RESULTS: The camera system was able to capture all data on a pulse-by-pulse basis at a rate of ∼504 frames per second. The applied empirical correction method for ionization quenching was effective and the corrected composite image provided a 2D map of dose distribution. The measured range (depth of distal 90%) through scintillation imaging agreed within 1.2 mm with that obtained from ionization chamber measurement. CONCLUSION: A high-speed camera system capable of capturing scintillation signals from individual proton pulses was developed. The scintillation imaging system is promising for rapid proton beam characterization and verification.

A reconstruction approach for proton computed tomography by modeling the integral depth dose of the scanning proton pencil beam.

PURPOSE: To present a proton computed tomography (pCT) reconstruction approach that models the integral depth dose (IDD) of the clinical scanning proton beam into beamlets. Using a multilayer ionization chamber (MLIC) as the imager, the proposed pCT system and the reconstruction approach can minimize extra ambient neutron dose and simplify the beamline design by eliminating an additional collimator to confine the proton beam. METHODS: Monte Carlo simulation was applied to digitally simulate the IDDs of the exiting proton beams detected by the MLIC. A forward model was developed to model each IDD into a weighted sum of percentage depth doses of the constituent beamlets separated laterally by 1 mm. The water equivalent path lengths (WEPLs) of the beamlets were determined by iteratively minimizing the squared L2-norm between the forward projected and simulated IDDs. The final WEPL values were reconstructed to pCT images, that is, proton stopping power ratio (SPR) maps, through simultaneous algebraic reconstruction technique with total variation regularization. The reconstruction process was tested with a digital cylindrical water-based phantom and an ICRP adult reference computational phantom. The mean of SPR within regions of interest (ROIs) and the WEPL along a 4 mm-wide beam ( WEP L 4 mm ${\rm{WEP}}{{\rm{L}}_{4{\rm{mm}}}}$ ) were compared with the reference values. The spatial resolution was analyzed at the edge of a cortical insert of the cylindrical phantom. RESULTS: The percentage deviations from reference SPR were within ±1% in all selected ROIs. The mean absolute error of the reconstructed SPR was 0.33%, 0.19%, and 0.27% for the cylindrical phantom, the adult phantom at the head and lung region, respectively. The corresponding percentage deviations from reference WEP L 4 mm ${\rm{WEP}}{{\rm{L}}_{4{\rm{mm}}}}$ were 0.48 ± 0.64%, 0.28 ± 0.48%, and 0.22 ± 0.49%. The full width at half maximum of the line spread function (LSF) derived from the radial edge spread function (ESF) of a cortical insert was 0.13 cm. The frequency at 10% of the modulation transfer function (MTF) was 6.38 cm-1 . The mean signal-to-noise ratio (SNR) of all the inserts was 2.45. The mean imaging dose was 0.29 and 0.25 cGy at the head and lung region of the adult phantom, respectively. CONCLUSION: A new pCT reconstruction approach was developed by modeling the IDDs of the uncollimated scanning proton beams in the pencil beam geometry. SPR accuracy within ±1%, spatial resolution of better than 2 mm at 10% MTF, and imaging dose at the magnitude of mGy were achieved. Potential side effects caused by neutron dose were eliminated by removing the extra beam collimator.

Spread-out Bragg peak proton FLASH irradiation using a clinical synchrocyclotron: Proof of concept and ion chamber characterization.

PURPOSE: The purpose of this work is to (a) demonstrate the feasibility of delivering a spread-out Bragg peak (SOBP) proton beam in ultra-high dose rate (FLASH) using a proton therapy synchrocyclotron as a major step toward realizing an experimental platform for preclinical studies, and (b) evaluate the response of four models of ionization chambers in such a radiation field. METHODS: A clinical Mevion HYPERSCAN® synchrocyclotron was adjusted for ultra-high dose rate proton delivery. Protons with nominal energy of 230 MeV were delivered in pulses with temporal width ranging from 12.5 µs to 24 µs spanning from conventional to FLASH dose rates. A boron carbide absorber and a range modulator block were placed in the beam path for range modulation and creating an SOBP dose profile. The radiation field was defined by a brass aperture with 11 mm diameter. Two Faraday cups were used to determine the number of protons per pulse at various dose rates. The dosimetric response of two cylindrical (IBA CC04 and CC13) and two plane-parallel (IBA PPC05 and PTW Advanced Markus® ) ionization chambers were evaluated. The dose rate was measured using the plane-parallel ionization chambers. The integral depth dose (IDD) was measured with a PTW Bragg Peak® ionization chamber. The lateral beam profile was measured with EBT-XD radiochromic film. Monte Carlo simulation was performed in TOPAS as the secondary check for the measurements and as a tool for further optimization of the range modulators' design. RESULTS: Faraday cups measurement showed that the maximum protons per pulse is 39.9 pC at 24 µs pulse width. A good agreement between the measured and simulated IDD and lateral beam profiles was observed. The cylindrical ionization chambers showed very high ion recombination and deemed not suitable for absolute dosimetry at ultra-high dose rates. The average dose rate measured using the PPC05 ionization chamber was 163 Gy/s at the pristine Bragg peak and 126 Gy/s at 1 cm depth for the SOBP beam. The SOBP beam range and modulation were measured 24.4 mm and 19 mm, respectively. The pristine Bragg peak beam had 25.6 mm range. Simulation results showed that the IDD and profile flatness can be improved by the cavity diameter of the range modulator and the number of scanned spots, respectively. CONCLUSIONS: Feasibility of delivering protons in an SOBP pattern with >100 Gy/s average dose rate using a clinical synchrocyclotron was demonstrated. The dose heterogeneity can be improved through optimization of the range modulator and number of delivered spots. Plane-parallel chambers with smaller gap between electrodes are more suitable for FLASH dosimetry compared to the other ion chambers used in this work.

A Monte Carlo based analytic model of the in-room neutron ambient dose equivalent for a Mevion gantry-mounted passively scattered proton system.

The goal of this study was to develop a Monte Carlo (MC)-based analytical model that can predict the in-room ambient dose equivalent from a Mevion gantry-mounted passively scattered proton system. The Mevion S250 and treatment vault were simulated using the MCNPX MC code. The results of the in-room neutron dose measurements, using an FHT 762 WENDI-II detector, were employed to benchmark the MC-derived values. After tuning the MCNPX MC code, for the same beam delivery parameters, the code was used to calculate the neutron spectra and ambient dose equivalent in the vault and at varying angles from the isocenter. Then, based on the calculations, an analytical model was reconstructed and data were fitted to derive the model parameters at 95% confidence intervals (CI). The MCNPX codes were tuned to within about 19% of the measured values for most of the measurements in the vault. For the maze, up to 0.08 mSv Gy-1 discrepancies were found between the experimental measurements and MCNPX calculated results. The analytical model showed up to 18% discrepancy for distances between 100 and 600 cm from the isocenter compared to the MC calculations. The model may underestimate the neutron ambient dose equivalent up to 21% for distances less than 100 cm from the isocenter. The proposed analytical model can be used to estimate the contribution of the secondary neutron dose from the Mevion S250 for the design of local shielding inside the proton therapy treatment vault.

A Monte Carlo-based analytic model of neutron dose equivalent for a mevion gantry-mounted passively scattered proton system for craniospinal irradiation.

PURPOSE: To calculate in- and out-of-field neutron spectra and dose equivalent, using Monte Carlo (MC) simulation, for a Mevion gantry-mounted passively scattered proton system in craniospinal irradiation. An analytical model based on the MC calculations that estimates in- and out-of-field neutron dose equivalent from proton Craniospinal irradiation (CSI) was also developed. METHODS: The MCNPX MC code was used to simulate a Mevion S250 proton therapy system. The simulated proton depth doses and profiles for pristine and spread-out Bragg peaks were benchmarked against the measured data. Previous measurements using extended-range Bonner spheres were used to verify the calculated neutron spectra and dose equivalent. Using the benchmarked results as a reference condition, a correction-based analytical model was reconstructed by fitting the data to derive model parameters at 95% confidence interval. Sensitivity analysis of brass aperture opening, thickness of the Lucite (PMMA) range compensator, and modulation width was performed to obtain correction parameters for nonreference conditions. RESULTS: For the neutron dose equivalent per therapeutic proton dose, the MCNPX calculated dose equivalent matched the measured values to within 8%. The benchmarked neutron dose equivalent at the isocenter was 41.2 and 20.8 mSv/Gy, for cranial and spinal fields, respectively. For in- and out-of-field neutron dose calculations, the correction-based analytical model showed up to 17% discrepancy compared to the MC calculations. The correction factors may provide a conservative estimation of neutron dose, especially for depth ≤ 5 cm and regions underneath the brass aperture. CONCLUSION: The proposed analytical model can be used to estimate the contribution of the neutron dose to the overall CSI treatment dose. Moreover, the model can be employed to estimate the neutron dose to the implantable cardiac electronic devices.

Feasibility of proton FLASH irradiation using a synchrocyclotron for preclinical studies.

PURPOSE: It has been recently shown that radiotherapy at ultrahigh dose rates (>40 Gy/s, FLASH) has a potential advantage in sparing healthy organs compared to that at conventional dose rates. The purpose of this work is to show the feasibility of proton FLASH irradiation using a gantry-mounted synchrocyclotron as a first step toward implementing an experimental setup for preclinical studies. METHODS: A clinical Mevion HYPERSCAN® synchrocyclotron was modified to deliver ultrahigh dose rates. Pulse widths of protons with 230 MeV energy were manipulated from 1 to 20 µs to deliver in conventional and ultrahigh dose rate. A boron carbide absorber was placed in the beam for range modulation. A Faraday cup was used to determine the number of protons per pulse at various dose rates. Dose rate was determined by the dose measured with a plane-parallel ionization chamber with respect to the actual delivery time. The integral depth dose (IDD) was measured with a Bragg ionization chamber. Monte Carlo simulation was performed in TOPAS as the secondary check for the measurements. RESULTS: Maximum protons charge per pulse, measured with the Faraday cup, was 54.6 pC at 20 µs pulse width. The measured IDD agreed well with the Monte Carlo simulation. The average dose rate measured using the ionization chamber showed 101 Gy/s at the entrance and 216 Gy/s at the Bragg peak with a full width at half maximum field size of 1.2 cm. CONCLUSIONS: It is feasible to deliver protons at 100 and 200 Gy/s average dose rate at the plateau and the Bragg peak, respectively, in a small ~1 cm2 field using a gantry-mounted synchrocyclotron.

The visible signal responsible for proton therapy dosimetry using bare optical fibers is not Cerenkov radiation.

PURPOSE: Proton beam dosimetry using bare plastic optical fibers has emerged as a simple approach to proton beam dosimetry. The source of the signal in this method has been attributed to Cerenkov radiation. The aim of this work was a phenomenological study of the nature of the visible light responsible for the signal in bare fiber optic dosimetry of proton therapy beams. METHODS: Plastic fiber optic probes embedded in solid water phantoms were irradiated with proton beams of energies 100, 180, and 225 MeV produced by a proton therapy cyclotron. Luminescence spectroscopy was performed by a CCD-coupled spectrometer. The spectra were acquired at various depths in phantom to measure the percentage depth dose (PDD) for each beam energy. For comparison, the PDD curves were acquired using a standard multilayer ion chamber device. In order to further analyze the contribution of the Cerenkov radiation in the spectra, Monte Carlo simulation was performed using fluka Monte Carlo code to stochastically simulate radiation transport, ionizing radiation dose deposition, and optical emission of Cerenkov radiation. RESULTS: The measured depth doses using the bare fiber are in agreement with measurements performed by the multilayer ion chamber device, indicating the feasibility of using bare fiber probes for proton beam dosimetry. The spectroscopic study of proton-irradiated fibers showed a continuous spectrum with a shape different from that of Cerenkov radiation. The Monte Carlo simulations confirmed that the amount of the generated Cerenkov light does not follow the radiation absorbed dose in a medium. CONCLUSIONS: The source of the optical signal responsible for the proton dose measurement using bare optical fibers is not Cerenkov radiation. It is fluorescence of the plastic material of the fiber.

Spectroscopic separation of Cerenkov radiation in high-resolution radiation fiber dosimeters.

We have investigated Cerenkov radiation generated in phosphor-based optical fiber dosimeters irradiated with clinical electron beams. We fabricated two high-spatial resolution fiber-optic probes, with 200 and 400 µm core diameters, composed of terbium-based phosphor tips. A generalizable spectroscopic method was used to separate Cerenkov radiation from the transmitted signal by the fiber based on the assumption that the recorded signal is a linear superposition of two basis spectra: characteristic luminescence of the phosphor medium and Cerenkov radiation. We performed Monte Carlo simulations of the Cerenkov radiation generated in the fiber and found a strong dependence of the recorded Cerenkov radiation on the numerical aperture of the fiber at shallow phantom depths; however, beyond the depth of maximum dose that dependency is minimal. The simulation results agree with the experimental results for Cerenkov radiation generated in fibers. The spectroscopic technique used in this work can be used for development of high-spatial resolution fiber micro dosimeters and for optical characterization of various scintillating materials, such as phosphor nanoparticles, in ionizing radiation fields of high energy.