Next generation small animal radiation research platform

项目摘要 小动物辐射研究（SARR）对人类的发展至关重要。 放射治疗（RT），作为一个关键的对应执行全面的临床前研究的大型 在低成本的受控实验条件下，SARR依赖于专用平台 以与临床相似的方式对动物进行辐射剂量。当代SARR辐照器， 在过去的十年里，这些技术未能跟上人类RT的技术进步。 与现代RT治疗形成对比，现代RT治疗采用新的解剖和功能成像，逆向治疗计划， 并且常规地采用强度调制递送技术来精确地形成极其适形的 剂量分布的肿瘤，在目前的SARR系统的治疗形式类似于一个过时的形式， 这种技术上的差异大大削弱了SARR研究与人类RT的相关性， RT研究的探索，阻碍了SARR研究的快速开展。为了解决这个问题 问题，响应PAR-15-075，该项目将开发和翻译下一代SARR平台 通过学术-工业合作伙伴关系，加入UT西南的医学物理学家和放射生物学家 医疗中心（UTSW）与Faxitron Bioptics LLC（Faxitron）的工程专家。所开发的系统 由于其新颖的成像方法，将大大上级目前最先进的SARR平台 (dual能量锥形束CT和PET）、强度调制放射疗法以及高计算和治疗 交付效率。这些新的特征有望通过以下方式提高SARR研究与人类RT的相关性： 提供临床质量的治疗，通过提供技术自由度来支持现代RT的探索， 实现新的成像和治疗方法，并通过增强 计算速度和工作流程。我们将执行具有以下特定目标（SA）的研究：SA 1：优化 硬件设计和构建硬件系统，包括机械、成像和治疗子系统。 SA 2：完善软件设计并开发成像和治疗计划系统， 硬件平台SA 3：执行全面的系统测试，制定翻译计划，并演示 通过图像引导调强肺立体定向的动物研究， 使用大鼠进行全身放射治疗。该项目的创新包括新的技术能力， 下一代SARR平台，以及连贯的翻译活动，以提供新的能力，用户.项目的可行性是通过广泛的初步研究来确保的，研究团队将医疗 物理学家和放射生物学家（UTSW）具有强大的临床和研究专业知识和工程师（Faxitron）， 丰富的商业产品开发经验。通过填补SARR和人类之间的关键空白， RT，开发的系统将成为临床前研究的重要组成部分，用于探索 与人类RT高度相关的新型放射治疗策略。

PROJECT SUMMARY Small Animal Radiation Research (SARR) is of paramount importance for the advancement of human radiotherapy (RT) by serving as a critical counterpart to perform comprehensive preclinical studies on a large number of subjects under controlled experimental conditions at low costs. SARR relies on dedicated platforms to administer radiation dose to animals in a similar way as in the clinic. Current-generation SARR irradiators, developed in the past decade, have failed to keep pace with technology advancements in human RT. In stark contrast to modern RT treatments where novel anatomical and functional imaging, inverse treatment planning, and intensity modulated delivery techniques are routinely employed to precisely form an extremely conformal dose distribution to the tumor, the therapeutic form in current SARR systems resembles an obsolete form of human RT. This technology disparity has substantially impaired SARR study relevance to human RT, impeded explorations in RT research, and hindered rapid conduction of SARR studies. Towards addressing this problem, in response to PAR-15-075, this project will develop and translate a next-generation SARR platform through an academic-industrial partnership, joining medical physicists and radiobiologists at UT Southwestern Medical Center (UTSW) with engineering experts at Faxitron Bioptics LLC (Faxitron). The developed system will be substantially superior to the current state-of-the-art SARR platform due to its novel imaging methods (dual energy cone beam CT and PET), intensity modulated radiotherapy, and high computation and treatment delivery efficiency. These novel features are expected to improve SARR research relevance to human RT by delivering treatments of clinical quality, to support exploration in modern RT by offering technical freedom to realize novel imaging and therapy approaches, and to increase research efficiency by enhancing computational speed and workflow. We will perform studies with the following specific aims (SAs): SA1: Refine hardware design and construct the hardware system including mechanical, imaging, and therapy subsystems. SA2: Refine software design and develop an imaging and treatment planning system accompanied with the hardware platform. SA3: Perform comprehensive system tests, develop a translation plan, and demonstrate achieved advantages of the system via an animal study on image-guided intensity-modulated lung stereotactic body radiotherapy using rats. The innovation of this project includes novel technological capabilities enabled by the next-generation SARR platform, as well as coherent translation activities to deliver new capabilities to endusers. Project feasibility is ensured by extensive preliminary studies, and the research team integrating medical physicists and radiobiologists (UTSW) with strong clinical and research expertise and engineers (Faxitron) with extensive commercial product development experience. By filling the critical void between SARR and human RT, the developed system will become an essential component in preclinical research for the exploration of novel radiotherapeutic strategies with high relevance to human RT.