Design and validation of a synchrotron proton beam line for FLASH radiotherapy preclinical research experiments.

PURPOSE: The main purpose of this work was to generate and validate the dosimetric accuracy of proton beams of dimensions that are appropriate for in vivo small animal and in vitro ultrahigh dose rate (FLASH) radiotherapy experiments using a synchrotron-based treatment delivery system. This study was performed to enable future investigations of the relevance of a spread-out Bragg peak (SOBP) under FLASH conditions. METHODS: The spill characteristics of the small field fixed horizontal beam line were modified to deliver accelerated protons in times as short as 2 ms and to control the dose delivered. A Gaussian-like transverse beam profile was transformed into a square uniform one at FLASH dose rates, while avoiding low-dose regions, a crucial requirement to protect normal tissue during FLASH irradiation. Novel beam-shaping devices were designed using Monte Carlo techniques to produce up to about 6 cm3 of uniform dose in SOBPs while maximizing the dose rate. These included a scattering foil, a conical flattening filter to maximize the flux of protons into the region of interest, energy filters, range compensators, and collimators. The shapes, sizes, and positions of the components were varied to provide the required field sizes and SOBPs. RESULTS: The designed and fabricated devices were used to produce 10-, 15-, and 20-mm diameter, circular field sizes and 10-, 15-, and 20-mm SOBP modulation widths at uniform physical dose rates of up to 375 Gy/s at the center of the SOBP and a minimum dose rate of about 255 Gy/s at the entrance, respectively, in cylindrical volumes. The flatness of lateral dose profiles at the center could be adjusted to within ±1.5% at the center of the SOBP. Assessment of systematic uncertainties, such as impact of misalignments and positioning uncertainties, was performed using simulations, and the results were used to provide appropriate adjustments to ensure high-accuracy FLASH beam delivery for both in vitro and in vivo preclinical experiments. CONCLUSIONS: It is feasible to use synchrotron-generated proton beams of sufficient dimensions for FLASH radiobiology experiments. We expect to use the system we developed to acquire in vitro and in vivo small animal FLASH radiobiology data as a function of dose, dose rate, oxygen content, and linear energy transfer to help us understand the underlying mechanisms of the FLASH phenomenon.

Multi-step material decomposition for spectral computed tomography.

Spectral images from photon counting detectors are being explored for material decomposition applications such as for obtaining quantitative maps of tissue types and contrast agents. While these detectors allow acquisition of multi-energy data in a single exposure, separating the total photon counts into multiple energy bins can lead to issues of count starvation and increased quantum noise in resultant maps. Furthermore, the complex decomposition problem is often solved in a single inversion step making it difficult to separate materials with close properties. We propose a multi-step decomposition method which allows solving the problem in multiple steps using the same spectral data collected in a single exposure. During each step, quantitative accuracy of a single material is under focus and one can flexibly optimize the bins chosen in that step. The result thus obtained becomes part of the input data for the next step in the multi-step process. This makes the problem less ill-conditioned and allows better quantitation of more challenging materials within the object. In comparison to a conventional single-step method, we show excellent quantitative accuracy for decomposing up to six materials involving a mix of soft tissue types and contrast agents in micro-CT sized digital phantoms.