Ultra-fast imaging for the safe delivery of electron FLASH radiation therapy

摘要 放射治疗是一种辅助治疗，与大多数手术和化疗一起使用， 每四个人中就有一个在他们的一生中被传递。虽然图像引导和适形规划 尽管减少了对健康组织的剂量，但仍然存在组织损伤的实质性风险，这设定了 剂量沉积到肿瘤。最近，健康组织损伤的最小化被证明发生 当超高剂量率（UHDR）用于照射时，称为闪光效应。UHDR定义为 一组复杂的高平均剂量率（>40戈伊/s）、瞬时剂量率（>106戈伊/s）、总剂量值 （> 8 Gy）和时间脉冲结构。FLASH承诺将正常组织毒性降低20-50%， 临床研究中心合作伙伴达特茅斯-希区柯克，已经是第一个证明每周例行交付的FLASH对 临床使用的直线加速器。这种修饰显示出巨大的翻译潜力，以提供电子闪光 （eFLASH）在任何放射治疗中心使用现有的系统。然而，尽管该领域的大多数研究都集中在 在阐明闪光的放射生物学机制方面，减轻闪光风险的工作主要是 未触及，但将是更广泛的临床实施的关键。检测监测的新技术 由于FLASH操作的毫秒级时间尺度， 传统的方法不适合。在这个项目中，我们利用了我们的相机平台BeamSite®， 第一个放射治疗视频系统，现在FDA批准并在临床上使用，开发BeamSite-ULTRA， 专门用于闪存成像。在我们的第一阶段赠款中，我们成功地展示了在 在体模中捕获单束脉冲能量所需的高帧速率和传输速度 组织.在第二阶段，我们将把BeamSite-ULTRA作为一种坚固、可制造、可通过FDA认证的 商业系统。我们将量化空间和时间脉冲结构，演示光束和 系统的门控潜力，并建立质子和电子FLASH临床功能 设置.这项工作包括一个广泛的行业和学术医学同事团队，使用eFLASH 达特茅斯-希区柯克医学中心的资源和堪萨斯大学的质子治疗设施 医学中心

Abstract Radiation therapy is a supplementary curative treatment used adjuvant with most surgery and chemotherapy, being delivered to nearly 1 out of every 4 people in their lifetime. While image guidance and conformal planning reduced the dose to healthy tissue, there is still a substantial risk of tissue damage that sets the upper limit of dose deposited to the tumor. Recently the minimization of healthy tissue damage was demonstrated to occur when ultra-high dose rates (UHDR) were used for irradiation, known as the FLASH effect. UHDR are defined as a complex set of high average dose rates (>40 Gy/s), instantaneous dose rates (>106 Gy/s), total dose values (>8Gy) and temporal pulse structures. FLASH promises a reduction in normal tissue toxicity by 20-50% and our clinical site partner Dartmouth-Hitchcock, has been the first to demonstrate routine weekly delivery of FLASH on a clinically used linac. This modification shows enormous translational potential to deliver electron FLASH (eFLASH) in any radiotherapy center using existing systems. However, while most research in the field is focused on elucidating the radiobiological mechanisms of FLASH, work towards mitigating the risks of FLASH is largely untouched, yet will be pivotal for wider clinical implementation. New techniques for detection monitoring of radiation need to be developed due to the millisecond timescales at which FLASH operates which make traditional methods unsuitable. In this project, we have leveraged our camera platform, BeamSite®, the world’s first video system for radiotherapy, now FDA cleared and in use clinically, to developed BeamSite-ULTRA, specifically for imaging FLASH. In our Phase I grant, we successfully demonstrated the ability to image at the high frame rates and transfer speeds necessary to capture a single beam pulse energy in phantoms and on tissue. In this Phase II, we will advance BeamSite-ULTRA as a robust, manufacturable, and FDA clearable commercial system. We will quantify both spatial and temporal pulse structures, demonstrate beam-on and gating-off potential of the system, and establish the capabilities in both proton and electron FLASH clinical settings. The work includes an extensive team of industry and academic medicine colleagues, using the eFLASH resources at Dartmouth-Hitchcock Medical Center and the proton treatment facilities at the University of Kansas Medical Center.