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

用于临床前实验室辐射研究的超高 (FLASH) 剂量率 X 射线柜系统

• 批准号: 10274920
• 负责人: Mohammad Rezaee
• 金额: $ 57.64万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10274920
• 关键词: Animals; Anodes; Biological; Charge; Collimator; Communities; Complex; Development; Dimensions; Dose; Dose-Rate; Electron Beam; Electrons; Explosion; Filtration; Fluoroscopy; Laboratories; Laboratory Research; Laboratory Study; Legal patent; Mechanics; Monte Carlo Method; Normal tissue morphology; Output; Pennsylvania; Performance; Positioning Attribute; Probability; Property; Protons; Radiation; Radiation Dose Unit; Radiation Physics; Radiation therapy; Research; Research Activity; Research Personnel; Robotics; Roentgen Rays; Source; System; Systems Development; Technology; Thick; Time; Toxic effect; Translational Research; Translations; Tube; Universities; Validation; base; cancer therapy; clinical translation; conventional therapy; design; design and construction; dosimetry; in vivo Model; industry partner; instrumentation; irradiation; novel; particle; pre-clinical; pre-clinical research; programs; systems research; tumor; voltage; x-ray irradiation

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.

项目总结/摘要 快速放射治疗，以超高剂量率（40 - 200）提供高辐射剂量（10 - 30戈伊） 戈伊/s），最近已经显示与常规的放射治疗相比， 照射，同时将肿瘤控制概率维持在类似水平。从那以后， 关于FLASH放射疗法的变革潜力。然而，FLASH的生物学机制 辐照（闪光效应）还没有得到很好理解。FLASH照射的临床应用 需要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，FLASH的研究采用复杂的加速器 技术有限的可访问性。我们提出研制一种新型的自屏蔽X射线辐照柜 系统，作为一种使能技术，大大提高了辐射的临床前研究能力， 研究社区。该系统采用两个市售的高容量150 kV透视 X射线源采用旋转阳极技术，平行相对布置。对于小于 2厘米厚，该系统可以提供闪光和传统的剂量率辐射，以支持 广泛的实验室辐射研究。我们提交我们的建议作为一个学术-工业 合作伙伴（AIP）设计和建造第一个用于临床前的FLASH千伏X射线柜系统 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、机器人技术和临床前辐射研究，Xstrahl， 制造并商业化用于临床前研究的FLASH机柜系统， 宾夕法尼亚大学（UPenn），以支持新系统的现场验证。JHU专利申请是 目前正在审查中。本课题4年研究工作的具体目标是：（1）设计一种新型的自屏蔽 临床前辐射研究系统的基础上，深入表征的剂量学特性， 闪光和常规辐射的X射线束，以及 系统支持小型和大型辐射场。(2)开发基于蒙特-卡罗的剂量计算 系统，以提供有关辐照的输送剂量、剂量率和LET分布的信息。 目标，与FLASH研究有关。(3)在JHU和UPenn对系统进行现场验证 剂量测定性能，并证明系统的闪光和常规照射能力， 体内模型。AIP成功开发该系统将使 FLASH功能为实验室研究人员，并大大提高机械和翻译 FLASH辐照的研究