An ultra-high (FLASH) dose rate x-ray cabinet system for pre-clinical laboratory radiation research

项目摘要/摘要 闪光放射治疗，在超高剂量率(40-200)下提供高辐射剂量(10-30Gy. 伽玛刀/S)，最近被证明与传统的 照射，同时将肿瘤控制概率维持在相似的水平。从那以后，巨大的兴奋随之而来。 关于闪光放射治疗的变革潜力。然而，闪光的生物学机制 辐射(闪光效应)还不是很清楚。闪光照射的临床翻译 必须进行全面的实验室研究，以阐明生物效应以及相关的 技术和物理要求。目前，闪光研究使用了复杂的加速器 可获得性有限的技术。我们计划研制一种新型的自屏蔽式x射线照射柜。 系统作为一种使能技术，极大地增强了放射治疗的临床前研究能力 研究社区。该系统采用了两种商用的大容量150千伏透视仪 采用平行相对布置的旋转阳极技术的X射线源。对于少于以下的介质 该系统厚度为2厘米，可以提供闪光和传统剂量率辐射，以支持 广泛的实验室辐射研究。我们把我们的提案作为学术-工业提交 合作(AIP)设计和建造第一个闪光千伏X射线柜系统，用于临床前 实验室研究。AIP由约翰·霍普金斯大学(JHU)组成，拥有辐射方面的专业知识 物理学、剂量学、蒙特卡罗模拟、机器人学和临床前放射研究 用于临床前研究的闪光柜系统的制造和商业化，加州大学 宾夕法尼亚州(UPenn)支持该新系统的现场验证。JHU的专利申请是 目前正在审查中。我们为期4年的研究工作的具体目标是：(1)设计一种新的自我屏蔽 基于深入表征辐射剂量学特性的临床前放射研究系统 闪光和常规辐射的x射线束，以及 系统支持小辐射场和大辐射场。(2)提出了基于蒙特卡罗方法的剂量计算方法。 提供关于受照剂量、剂量率和LET分布的信息的系统 目标，与闪光研究有关。(3)在JHU和UPenn进行系统的现场验证 剂量学性能，并展示了系统对闪光和常规辐照的能力 体内模型。AIP对该系统的成功开发将使AIP具有变革性 为实验室研究人员提供闪存功能，并显著增强机械性和转换性 闪光辐照的研究。

PROJECT SUMMARY/ABSTRACT Flash radiotherapy, the delivery of high radiation dose (10 – 30 Gy) at ultra-high dose rates (40 – 200 Gy/s), has recently been shown to reduce significantly normal tissue toxicity compared to conventional irradiation, while maintaining tumor control probability at similar level. Great excitement has since ensued about the transformative potential of FLASH radiotherapy. However, the biological mechanisms of FLASH irradiation (FLASH effect) are not well understood. The clinical translation of FLASH irradiation necessitates comprehensive laboratory studies to elucidate the biological effects as well as pertinent technological and physical requirements. At present, FLASH research employs complex accelerator technologies of limited accessibilities. We propose to develop a novel self-shielded x-ray irradiation cabinet system, as an enabling technology to greatly enhance the preclinical research capabilities of the radiation research community. The system employs two commercially available high capacity 150 kV fluoroscopy x-ray sources with rotating anode technology in a parallel-opposed arrangement. For a medium less than 2 cm in thickness, the system can deliver both FLASH and conventional dose-rate radiations to support a broad range of laboratory radiation research. We submit our proposal as an academic-industrial partnership (AIP) to design and construct the first FLASH kilo-voltage x-ray cabinet system for preclinical laboratory research. The AIP consists of Johns Hopkins University (JHU) with the expertise in radiation physics, dosimetry, Monte Carlo simulation, robotics, and preclinical radiation research, Xstrahl to manufacture and commercialize the FLASH cabinet system for preclinical research, and University of Pennsylvania (UPenn) to support in-field validation of the novel system. A JHU patent application is currently under review. Our specific aim for the 4-year research efforts are: (1) Design a new self-shielded pre-clinical radiation research system based on in-depth characterization of the dosimetric properties of the x-ray beam for both FLASH and conventional radiations, and the mechanical requirements of the system to support small and large radiation fields. (2) Develop a Monte-Carlo based dose calculation system to provide information on the delivered dose, dose rate, and LET distributions in the irradiated target, pertinent to FLASH research. (3) Conduct in-field validation, at JHU and UPenn, of the system dosimetric performance, and demonstrate the system capability for FLASH and conventional irradiation of in-vivo models. The successful development of the system by the AIP will make available transformative FLASH capabilities for the laboratory researchers, and significantly enhance mechanistic and translational research on FLASH irradiation.