Abstract：
Objective. To fabricate and validate a novel focused collimator designed to spare normal tissue in a murine hemithoracic irradiation model using 250 MeV protons delivered at ultra-high dose rates (UHDRs) for preclinical FLASH radiation therapy (FLASH-RT) studies.Approach. A brass collimator was developed to shape 250 MeV UHDR protons from our Varian ProBeam. Six 13 mm apertures, of equivalent size to kV x-ray fields historically used to perform hemithorax irradiations, were precisely machined to match beam divergence, allowing concurrent hemithoracic irradiation of six mice while sparing the contralateral lung and abdominal organs. The collimated field profiles were characterized by film dosimetry, and a radiation survey of neutron activation was performed to ensure the safety of staff positioning animals.Main results. The brass collimator produced 1.2 mm penumbrae radiation fields comparable to kV x-rays used in preclinical studies. The penumbrae in the six apertures are similar, with full-width half-maxima of 13.3 mm and 13.5 mm for the central and peripheral apertures, respectively. The collimator delivered a similar dose at an average rate of 52 Gy s-1for all apertures. While neutron activation produces a high (0.2 mSv h-1) initial ambient equivalent dose rate, a parallel work-flow in which imaging and setup are performed without the collimator ensures safety to staff.Significance. Scanned protons have the greatest potential for future translation of FLASH-RT in clinical treatments due to their ability to treat deep-seated tumors with high conformality. However, the Gaussian distribution of dose in proton spots produces wider lateral penumbrae compared to other modalities. This presents a challenge in small animal pre-clinical studies, where millimeter-scale penumbrae are required to precisely target the intended volume. Offering high-throughput irradiation of mice with sharp penumbrae, our novel collimator-based platform serves as an important benchmark for enabling large-scale, cost-effective radiobiological studies of the FLASH effect in murine models.
摘要：
目的：制造和验证一种新型聚焦准直器，该准直器设计用于在小鼠半胸部照射模型中使用250MeV质子以超高剂量率（UHDRs）输送，用于临床前FLASH-RT研究。＆＃xD;方法：开发了黄铜准直器，可从我们的VarianProBeam中塑造250MeVUHDR质子。六个13毫米孔径，相当于历史上用于执行半胸部照射的kVX射线场的大小，精确加工以匹配光束发散，允许同时对六只小鼠进行半胸部照射，同时保留对侧肺和腹部器官。通过薄膜剂量测定对准直场轮廓进行了表征，并进行了中子活化的辐射调查，以确保工作人员定位动物的安全。＆＃xD;主要结果：黄铜准直器产生的1.2毫米penumbrae辐射场与临床前研究中使用的kVX射线相当。六个孔的半边是相似的，中心和外围孔的全宽半最大值(FWHM)为13.3mm和13.5mm，分别。对于所有孔,准直器以52Gy/s的平均速率递送相似的剂量。虽然中子活化产生高（0.2mSv/h）的初始环境等效剂量率，在没有准直器的情况下执行成像和设置的并行工作流程确保了工作人员的安全。＆＃xD;意义：扫描质子由于能够以高保形性治疗深层肿瘤，因此在临床治疗中具有未来FLASH-RT翻译的最大潜力。然而,与其他方式相比，质子点中剂量的高斯分布产生更宽的侧向轮廓。这在小动物临床前研究中提出了挑战，其中需要毫米级的penumbrae来精确地瞄准预期的体积。用锋利的手指为小鼠提供高通量照射，我们新颖的基于准直器的平台是实现大规模，小鼠模型中FLASH效应的具有成本效益的放射生物学研究。
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