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

描述(申请人提供)：在放射治疗中，用于人类治疗的方法和用于实验室动物照射的方法之间的显著技术差异使人怀疑当前临床前放射研究的适用性。为了弥补这一差距，我们先前采用了生物工程研究伙伴关系(BRP)机制，并构建了先进的小动物辐射研究平台(SARRP)。SARRP模仿了一台人类治疗机。它配备了星载X射线锥束CT(CBCT)来引导焦点照射，并能够以0.2 mm的精度向目标发射焦点辐射。在两年多的使用中，该系统已经实现了以前不可行的小鼠辐射研究。然而，同样明显的是，CBCT成像在定位用于照射的小软组织目标方面也很差。对于在正常组织环境中生长的越来越重要的一类小的、可触及的、原位的或自发的肿瘤模型来说，这一障碍尤其重要。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。基于结合了CT“Preors”的新型旋转式单相机设计，我们在3年的研究期间的具体目标是：(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为初始焦点)，该系统可以作为独立的研究设备，也可以安装在SARRP上来引导焦点照射；(2)在三个学术合作机构验证车载X光/BL断层扫描可以用于定位和确保覆盖软组织靶标的准确性和最小边际扩展。我们提交我们的建议是为了响应PAR-10-169关于活体成像研究的学术-产业合作伙伴关系的建议。形成了一个多学科的团队，拥有辐射科学、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古尔梅医疗有限公司，该公司与霍普金斯大学建立了现有的合作伙伴关系，将目前的SARRP产品商业化。除了霍普金斯的系统，古尔梅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。除了古尔梅，卡利珀生命科学公司还以行业顾问的身份参与，捕捉商业化机会进行传播。 与公众健康相关：我们建议开发一种集成的X射线/光学断层成像系统，该系统不仅可以作为独立的研究仪器，还可以安装在小动物辐射研究平台上，以指导对小鼠软组织目标的焦点照射。仅用x射线CT很难定位这些靶点。新的能力允许准确研究日益重要的原位肿瘤模型的辐射反应，甚至在它们可触及之前。项目说明第1页，共1页

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. PUBLIC HEALTH RELEVANCE: We propose to develop an integrated x-ray/optical tomographic imaging system that can function as a standalone research instrument, but also on board a small animal radiation research platform to guide focal irradiation of soft tissue targets in mice. These targets are difficult to localize with x-ray CT alone. The new capabilities allow the accurate study of radiation response of the increasingly important orthotopic tumor models, even before they are palpable. Project Narrative 1 of 1