Bayesian optimization to design a novel x-ray shaping device.

PURPOSE: In radiation therapy, x-ray dose must be precisely sculpted to the tumor, while simultaneously avoiding surrounding organs at risk. This requires modulation of x-ray intensity in space and/or time. Typically, this is achieved using a multi leaf collimator (MLC)-a complex mechatronic device comprising over one hundred individually powered tungsten 'leaves' that move in or out of the radiation field as required. Here, an all-electronic x-ray collimation concept with no moving parts is presented, termed "SPHINX": Scanning Pencil-beam High-speed Intensity-modulated X-ray source. SPHINX utilizes a spatially distributed bremsstrahlung target and collimator array in conjunction with magnetic scanning of a high energy electron beam to generate a plurality of small x-ray "beamlets." METHODS: A simulation framework was developed in Topas Monte Carlo incorporating a phase space electron source, transport through user defined magnetic fields, bremsstrahlung x-ray production, transport through a SPHINX collimator, and dose in water. This framework was completely parametric, meaning a simulation could be built and run for any supplied geometric parameters. This functionality was coupled with Bayesian optimization to find the best parameter set based on an objective function which included terms to maximize dose rate for a user defined beamlet width while constraining inter-channel cross talk and electron contamination. Designs for beamlet widths of 5, 7, and 10 mm2 were generated. Each optimization was run for 300 iterations and took approximately 40 h on a 24-core computer. For the optimized 7-mm model, a simulation of all beamlets in water was carried out including a linear scanning magnet calibration simulation. Finally, a back-of-envelope dose rate formalism was developed and used to estimate dose rate under various conditions. RESULTS: The optimized 5-, 7-, and 10-mm models had beamlet widths of 5.1 , 7.2 , and 10.1 mm2 and dose rates of 3574, 6351, and 10 015 Gy/C, respectively. The reduction in dose rate for smaller beamlet widths is a result of both increased collimation and source occlusion. For the simulation of all beamlets in water, the scanning magnet calibration reduced the offset between the collimator channels and beam centroids from 2.9 ±1.9 mm to 0.01 ±0.03 mm. A slight reduction in dose rate of approximately 2% per degree of scanning angle was observed. Based on a back-of-envelope dose rate formalism, SPHINX in conjunction with next-generation linear accelerators has the potential to achieve substantially higher dose rates than conventional MLC-based delivery, with delivery of an intensity modulated 100 × 100 mm2 field achievable in 0.9 to 10.6 s depending on the beamlet widths used. CONCLUSIONS: Bayesian optimization was coupled with Monte Carlo modeling to generate SPHINX geometries for various beamlet widths. A complete Monte Carlo simulation for one of these designs was developed, including electron beam transport of all beamlets through scanning magnets, x-ray production and collimation, and dose in water. These results demonstrate that SPHINX is a promising candidate for sculpting radiation dose with no moving parts, and has the potential to vastly improve both the speed and robustness of radiotherapy delivery. A multi-beam SPHINX system may be a candidate for delivering magavoltage FLASH RT in humans.

Thermal limits on MV x-ray production by bremsstrahlung targets in the context of novel linear accelerators.

PURPOSE: To study the impact of target geometrical and linac operational parameters, such as target material and thickness, electron beam size, repetition rate, and mean current on the ability of the radiotherapy treatment head to deliver high-dose-rate x-ray irradiation in the context of novel linear accelerators capable of higher repetition rates/duty cycle than conventional clinical linacs. METHODS: The depth dose in a water phantom without a flattening filter and heat deposition in an x-ray target by 10 MeV pulsed electron beams were calculated using the Monte-Carlo code MCNPX, and the transient temperature behavior of the target was simulated by ANSYS. Several parameters that affect both the dose distribution and temperature behavior were investigated. The target was tungsten with a thickness ranging from 0 to 3 mm and a copper heat remover layer. An electron beam with full width at half maximum (FWHM) between 0 and3 mm and mean current of 0.05-2 mA was used as the primary beam at repetition rates of 100, 200, 400, and 800 Hz. RESULTS: For a 10 MeV electron beam with FWHM of 1 mm, pulse length of 5 µs, by using a thin tungsten target with thickness of 0.2 mm instead of 1 mm, and by employing a high repetition rate of 800 Hz instead of 100 Hz, the maximum dose rate delivered can increase two times from 0.57 to 1.16 Gy/s. In this simple model, the limiting factor on dose rate is the copper heat remover's softening temperature, which was considered to be 500°C in our study. CONCLUSIONS: A high dose rate can be obtained by employing thin targets together with high repetition rate electron beams enabled by novel linac designs, whereas the benefit of thin targets is marginal at conventional repetition rates. Next generation linacs used to increase dose rate need different target designs compared to conventional linacs.

Experimental Platform for Ultra-high Dose Rate FLASH Irradiation of Small Animals Using a Clinical Linear Accelerator.

PURPOSE: A key factor limiting the effectiveness of radiation therapy is normal tissue toxicity, and recent preclinical data have shown that ultra-high dose rate irradiation (>50 Gy/s, "FLASH") potentially mitigates this effect. However, research in this field has been strongly limited by the availability of FLASH irradiators suitable for small animal experiments. We present a simple methodologic approach for FLASH electron small animal irradiation with a clinically available linear accelerator (LINAC). METHODS AND MATERIALS: We investigated the FLASH irradiation potential of a Varian Clinac 21EX in both clinical mode and after tuning of the LINAC. We performed detailed FLUKA Monte Carlo and experimental dosimetric characterization at multiple experimental locations within the LINAC head. RESULTS: Average dose rates of ≤74 Gy/s were achieved in clinical mode, and the dose rate after tuning exceeded 900 Gy/s. We obtained 220 Gy/s at 1-cm depth for a >4-cm field size with 90% homogeneity throughout a 2-cm-thick volume. CONCLUSIONS: We present an approach for using a clinical LINAC for FLASH irradiation. We obtained dose rates exceeding 200 Gy/s after simple tuning of the LINAC, with excellent dosimetric properties for small animal experiments. This will allow for increased availability of FLASH irradiation to the general research community.