X-ray/optical tomographic guidance and assessment for pre-clinical radiation Research

项目概要/摘要 在过去的10年里，我们的团队进行了多学科的努力，以弥合技术差距， 用于人类治疗和临床前研究的放射方法。我们聘请了生物工程研究所 建立先进的小动物辐射研究平台（SARRP）的伙伴关系机制。的 SARRP配备锥形束CT（CBCT）以引导局灶性照射，并由Xstrahl商业化 2010年该系统对于临床前辐射研究具有变革性意义，目前已有66台机器投入使用 全球有超过300名研究人员进行研究。认识到CBCT成像不足以定位肿瘤模型 在低图像对比度的环境中生长，我们在船上开发了生物发光断层扫描（BLT）， SARRP补充CBCT指南。这一努力得到了先前学术界和工业界的支持。 伙伴关系（AIP）机制。BLT实用程序是"第一个"定位光学系统质心（CoM）的工具。 用于照射的靶。虽然这种合作关系的成功导致了BLT系统的商业化 在2016年Xstrahl的测试中，用户对BLT平台的采用率很低。很明显，调查人员高度重视 我希望能够在SARRP上定义靶体积的3D形状，以充分补充现代 人性化的治疗我们必须将BLT制导提升到一个新的3D目标水平 超出CoM的形状描绘，并允许定量评估目标对辐射的反应。车载 PET成像已被引入，以使生物学引导的RT在人类。小动物辐射研究 生物和功能靶向和评估能力也将大大增强， 解剖学荧光断层扫描（FT）将允许深入的生物和机械询问的关键 关于肿瘤及其微环境对RT的反应的信息。它补充了生物发光 成像研究肿瘤和正常组织的反应，当使用工程生物发光模型， available.当考虑到组合分子时，FT的研究潜力尤其显著 放射治疗策略，如免疫治疗。荧光成像也有一个额外的 因此，本发明的优点在于适合于临床转化为PET成像的替代物。集成CBCT/BLT/FT 补充SARRP的能力将为临床前辐射研究提供一个强大的平台。 Xstrahl和约翰霍普金斯团队将继续合作，开发和商业化这些新的 能力的我们的目标是（1）。设计和建造一个新的先进的BLT/FT系统，以引导辐照- 登上SARRP和离线成像研究，（2）。制定靶体积的定量BLT/FT 确定和治疗评估（3）。评估和验证光学系统性能， 体模和体内模型。新的先进分子光学成像技术的成功推广 这些能力大大加强了SARRP用户进行辐射研究的能力。

PROJECT SUMMARY/ABSTRACT Over the past 10 years, our group has made multi-disciplinary efforts to bridge the technological gap between radiation methods for human treatment and pre-clinical research. We employed the Bioengineering Research Partnership mechanism to construct an advanced small animal radiation research platform (SARRP). The SARRP is equipped with cone-beam CT (CBCT) to guide focal irradiation and was commercialized by Xstrahl in 2010. The system was transformative for pre-clinical radiation research as 66 machines are now in use world-wide by > 300 investigators. Recognizing that CBCT imaging is inadequate for localizing tumor models growing in a low image contrast environment, we developed bioluminescence tomography (BLT) on board the SARRP to complement CBCT guidance. The effort was supported by the previous academic-industrial partnership (AIP) mechanism. The BLT utility is the “first” to localize the center of mass (CoM) of an optical target for irradiation. Although the success of this partnership led to the commercialization of the BLT system by Xstrahl in 2016, the adoption of the BLT platform by users is lackluster. It is clear that investigators highly desire the ability to define the 3D shape of the target volume on the SARRP to fully complement modern human treatment. It becomes imperative that we need to advance BLT guidance to a new level of 3D target shape delineation beyond CoM and to allow quantitative assessment of target response to radiation. On-board PET imaging has been introduced to enable biology-guided RT in humans. Small animal radiation research would also be greatly enhanced with capabilities of biologic and functional targeting and assessment beyond anatomy. Fluorescence tomography (FT) would allow in-depth biological and mechanistic interrogation of key information about the tumor and its microenvironment response to RT. It complements bioluminescence imaging to study tumor and normal tissue response, when the use of engineered bioluminescent models is not available. The research potentials of FT are particularly significant when considering combinational molecular therapeutic strategies with radiation, such as immunotherapy. Fluorescence imaging also has an added advantage to be amenable to clinical translation as a surrogate for PET imaging. Integrated CBCT/BLT/FT capabilities that complements the SARRP would provide a powerful platform for pre-clinical radiation research. Xstrahl and the Johns Hopkins team will continue the partnership to develop and commercialize these new capabilities. Our aims are (1). Design and construct a new advanced BLT/FT system to guide irradiation on- board the SARRP and for off-line imaging studies, (2). Develop quantitative BLT/FT for target volume determination and treatment assessment, (3). Assess and validate the optical system performance with phantom and in vivo model. The successful dissemination of new advanced molecular optical imaging capabilities significantly enhances the conduct of radiation research for the SARRP users.