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， 在他们的一生中，几乎每4个人中就有1个被递送到手中。而图像制导和保形规划 虽然减少了对健康组织的剂量，但仍有相当大的组织损伤风险，这设定了 沉积在肿瘤上的剂量。最近，健康组织的损害被证明是最小的。 当超高剂量率(UHDR)被用于照射时，被称为闪光效应。UHDR定义为 一组复杂的高平均剂量率(&gt；40Gy/S)、瞬时剂量率(&gt；106Gy/S)、总剂量值 (&gt；8Gy)和时间脉冲结构。闪光灯承诺将正常组织毒性降低20%-50%，我们的 临床网站合作伙伴达特茅斯-希区柯克是第一个展示Flash On每周例行交付的公司 一种临床使用的直线加速器。这一改进显示出巨大的平移潜力，可以提供电子闪光 (EFlash)在使用现有系统的任何放射治疗中心。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，减少闪光风险的工作主要是 尚未触及，但将是更广泛的临床实施的关键。用于检测和监测的新技术 由于闪光灯运行的毫秒级时间尺度，需要开发辐射 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®，这是世界上 第一个用于放射治疗的视频系统，现在FDA批准并用于临床，开发了BeamSite-Ultra， 专门用于成像闪光灯。在我们的第一阶段资助中，我们成功地展示了在 在模体中捕获单束脉冲能量所需的高帧速率和传输速度 组织。在此第二阶段，我们将推进BeamSite-Ultra作为一款坚固、可制造和FDA许可的产品 商业系统。我们将量化空间和时间脉冲结构，演示束流和 系统的关断电势，并建立了质子和电子闪光临床能力 设置。这项工作包括一个由行业和学术医学同事组成的广泛团队，使用eFlash 达特茅斯-希区柯克医学中心和堪萨斯大学质子治疗设施的资源 医疗中心。

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.