An integrated x-ray/optical tomography system for preclinical radiation research

描述（由申请人提供）：在放射治疗中，用于人类治疗的方法与用于实验动物照射的方法之间的显着技术差距使当前临床前放射研究的适用性受到质疑。为了弥补这一差距，我们利用生物工程研究伙伴关系（BRP）机制，构建了一个先进的小动物辐射研究平台（SARRP）。SARRP模仿人类治疗机。它配备了机载x射线锥束CT （CBCT）来引导焦点辐射，并能够以0.2mm的精度向目标提供焦点辐射。在使用了两年多的时间里，该系统使以前不可行的小鼠辐射研究成为可能。然而，CBCT成像对于定位照射的小软组织目标也很明显。对于在正常组织环境中生长的越来越重要的小的、可触及前的、原位的或自发的肿瘤模型来说，这一障碍尤为重要。我们认为最有效的解决方案是在SARRP上结合分子光学（生物发光和荧光）成像，以补充x射线CT引导。基于一种新颖的旋转单相机设计，结合CT“先验”，我们的3年研究期的具体目标是：(1)设计和构建一个集成的x射线/生物发光断层扫描（BLT）系统（以BL为我们的初始重点），可以作为一个独立的研究设备，也可以作为机载SARRP来指导焦点照射；(2)在三个学术合作机构验证机载x射线/BL断层扫描用于定位和确保软组织目标覆盖的准确性和最小边际扩展。我们提交了我们的提案，以响应PAR-10-169在体内成像研究的学术-工业伙伴关系。拥有辐射科学、机器人技术、光学成像和制造等专业知识的多学科团队。我们的主要工业合作伙伴是Gulmay医疗有限公司，该公司与霍普金斯大学在目前的SARRP产品商业化方面有合作关系。除了霍普金斯大学的系统外，Gulmay还将建造两个商业级原型。为了满足PAR-10-169项目的创新需求，宾夕法尼亚大学和弗吉尼亚大学作为次要合作伙伴参与，并代表最终用户对这两个系统进行现场验证。除Gulmay外，Caliper生命科学公司还作为工业顾问参与，以捕捉商业化传播机会。

DESCRIPTION (provided by applicant): In radiation therapy, the significant technological disparity between methods used for human treatment and those for laboratory animal irradiation brings into question the suitability of current preclinical radiation research. In an effort to bridge the gap, we have previously employed the Bioengineering Research Partnership (BRP) mechanism and constructed an advanced small animal radiation research platform (SARRP). The SARRP mimics a human treatment machine. It is equipped with on-board x-ray cone-beam CT (CBCT) to guide focal irradiation and is capable of delivering focal radiation to a target with accuracy of 0.2mm. In use for over 2 years, the system has enabled previously infeasible radiation studies with mice. However, it has also become evident that CBCT imaging is poor for localizing small soft tissue targets for irradiation. The hurdle is particularly significant for the increasingly important class of small, pre-palpable, orthotopic, or spontaneous, tumor models growing in a normal tissue environment. We identify that a most powerful solution is to incorporate molecular-optical (bioluminescence and fluorescence) imaging on board the SARRP to complement x-ray CT guidance. Based on a novel rotating single camera design which incorporates CT "priors", our specific aims for the 3-year research period are to: (1) Design and construct an integrated x-ray /bioluminescence tomography (BLT) system (with BL as our initial focus) that can function as a standalone research apparatus and also on-board the SARRP to guide focal irradiation; (2) Validate at three academic partner institutions the accuracy and minimum margin expansion with which on-board x-ray/BL tomography can be used to localize and ensure coverage of a soft tissue target. We submit our proposal in response to PAR-10-169 for academic-industrial partnership for in vivo imaging research. A multi-disciplinary team is formed with expertise in radiation sciences, robotics, optical imaging and manufacturing. Our major industrial partner is Gulmay Medical Ltd. which has an existing partnership with Hopkins in commercializing the current SARRP product. In addition to Hopkins' system, two commercial grade prototypes will be constructed by Gulmay. In fulfillment of the innovation requirements of the PAR-10-169 program, the University of Pennsylvania and University of Virginia participate as minor partners and represent the end-users to conduct in-field validation of these two systems. In addition to Gulmay, Caliper Life Sciences also participates as industrial consultant to capture commercialization opportunities for dissemination.