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室动物辐照的方法之间的显著技术差异使人们对当前临床前放射研究的适用性产生了疑问。为了弥补这一差距，我们采用了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模仿人类治疗机器。它配备了机载X射线锥束CT（CBCT），以引导焦点照射，并能够将焦点辐射传递到目标，精度为0.2 mm。经过两年多的使用，该系统已经实现了以前不可行的小鼠辐射研究。然而，CBCT成像对于定位用于照射的小软组织目标是不好的，这也变得很明显。对于越来越重要的一类在正常组织环境中生长的小的、预先可触及的、原位的或自发的肿瘤模型，该障碍尤其重要。我们确定，一个最强大的解决方案是将分子光学（生物发光和荧光）成像板上的SARRP，以补充X射线CT的指导。基于一种新颖的旋转单摄像机设计，结合CT的“先验”，我们在三年的研究期内的具体目标是：（1）设计和构建一个集成的X射线/生物发光断层成像（BLT）系统（BL作为我们最初的重点），它可以作为一个独立的研究设备，也可以在SARRP上引导焦点照射;（2）在三个学术伙伴机构评估机载X射线/BL断层扫描的准确性和最小边缘扩展，以便定位和确保覆盖软组织目标。我们提交我们的建议，以回应PAR-10-169的学术-工业合作伙伴关系，在体内成像研究。一个多学科的团队形成了辐射科学，机器人，光学成像和制造方面的专业知识。我们的主要工业合作伙伴是Gulmay Medical Ltd.，该公司与霍普金斯在当前SARRP产品的商业化方面存在合作关系。除了霍普金斯的系统外，Gulmay还将建造两个商业级原型。为了满足PAR-10-169计划的创新要求，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。除了Gulmay，Caliper Life Sciences还作为行业顾问参与，以捕捉商业化机会进行传播。

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.