Design and validation of a synchrotron proton beam line for FLASH radiotherapy preclinical research experiments
Design and validation of a synchrotron proton beam line for FLASH radiotherapy preclinical research experiments
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DOI：
10.1002/mp.15370
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发表时间：
2021-12-10
期刊：
影响因子：
3.8
通讯作者：
Mohan, Radhe
中科院分区：
文献类型：
--
作者：
Titt, Uwe;Yang, Ming;Mohan, Radhe
目的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，产生并验证适合于体内小动物和体外超高剂量率(Flash)放射治疗实验的尺寸的质子束的剂量学准确性。进行这项研究是为了进一步研究闪光条件下扩展的布拉格峰(SOBP)的相关性。方法对小野固定水平束线的泄漏特性进行了改进，使其能在短至2ms的时间内发射加速质子，并控制发射剂量。在闪光剂量率下，将高斯型的横向光束轮廓转换为方形均匀的光束轮廓，同时避开低剂量区，这是在闪光照射期间保护正常组织的关键要求。利用蒙特卡罗技术设计了新的束流整形装置，在最大化剂量率的同时，在SOBP中产生高达约6厘米(3)的均匀剂量。这些装置包括一个散射箔、一个圆锥形平坦滤光器以最大限度地提高进入感兴趣区域的质子流量、能量滤光器、距离补偿器和准直器。组件的形状、大小和位置都不同，以提供所需的字段大小和SOBP。结果所设计和制作的器件在圆柱体中分别产生了直径为10 mm、15 mm和20 mm的圆形野以及10 mm、15 mm和20 mm的SOBP调制宽度，中心的均匀物理剂量率高达375GY/S，入口处的最低剂量率约为255GY/S。中心侧向剂量分布平坦度可调整到SOBP中心+/-1.5%以内。使用模拟对系统不确定性进行评估，如未对准和定位不确定性的影响，结果被用来提供适当的调整，以确保体外和体内临床前实验的高精度闪光光束传输。结论利用同步辐射产生的足够大的质子束进行闪光放射生物学实验是可行的。我们希望使用我们开发的系统来获取体外和体内小动物闪光放射生物学数据，作为剂量、剂量率、氧含量和线性能量转移的函数，以帮助我们了解闪光现象的潜在机制。
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 cm(3) 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.