Department of Radiation Physics, M.D. Anderson Cancer Center, University of Texas, Houston, Texas.
Particle Therapy Division, HITACHI America Ltd., Houston, Texas.
Med Phys. 2022 Jan;49(1):497-509. doi: 10.1002/mp.15370. Epub 2021 Dec 10.
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.
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 cm 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.
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.
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.
本工作的主要目的是利用基于同步加速器的治疗输送系统，生成和验证适用于体内小动物和体外超高剂量率（FLASH）放射治疗实验的质子束的剂量学准确性。这项研究旨在为研究在 FLASH 条件下扩展布拉格峰（SOBP）的相关性奠定基础。
修改小场固定水平束线的溢出特性，以便在 2 毫秒内加速质子，并控制所传递的剂量。在 FLASH 剂量率下，将高斯型横向束轮廓转换为方形均匀轮廓，同时避免低剂量区域，这是在 FLASH 照射期间保护正常组织的关键要求。使用蒙特卡罗技术设计了新颖的束成形装置，以在 SOBP 中产生高达约 6 厘米的均匀剂量，同时使质子进入感兴趣区域的通量最大化。这些装置包括散射箔、锥形平坦化滤波器，以最大化质子进入感兴趣区域的通量、能量滤波器、射程补偿器和准直器。通过改变组件的形状、大小和位置来提供所需的射野大小和 SOBP。
设计和制造的设备用于在圆柱形体积中产生 10、15 和 20 毫米直径的圆形射野尺寸和 10、15 和 20 毫米的 SOBP 调制宽度，在 SOBP 中心的均匀物理剂量率高达 375Gy/s，在入口处的最小剂量率约为 255Gy/s。SOBP 中心处的侧向剂量分布的平坦度可以在 SOBP 中心处调整到±1.5%以内。通过模拟评估了系统不确定性，例如对准误差和定位不确定性的影响，并使用这些结果进行适当调整，以确保体外和体内临床前实验的高精度 FLASH 束输送。
利用足够尺寸的同步加速器产生的质子束进行 FLASH 放射生物学实验是可行的。我们期望使用我们开发的系统来获取体外和体内小动物 FLASH 放射生物学数据，作为剂量、剂量率、氧含量和线性能量传递的函数，以帮助我们理解 FLASH 现象的潜在机制。
