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

临床前辐射研究的 X 射线/光学断层扫描指导和评估

• 批准号: 10684628
• 负责人: Ken Kang-Hsin Wang
• 金额: $ 35.28万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684628
• 关键词: 3-Dimensional; Address; Adopted; Adoption; Algorithms; Anatomy; Animals; Biological; Biological Response Modifier Therapy; Biology; Bioluminescence; Biomedical Engineering; Complement; Data; Data Analyses; Docking; Engineering; Environment; Epidermal Growth Factor Receptor; Equation; Excision; Fluorescence; Fluorescent Probes; Functional Imaging; Glioblastoma; Heterogeneity; Human; Hypoxia; Immunotherapy; Industrialization; Knowledge; Lasers; Light; Measures; Methods; Modeling; Modernization; Molecular; Normal tissue morphology; Optical Tomography; Optics; Performance; Positioning Attribute; Positron-Emission Tomography; Property; Radiation; Radiation therapy; Research; Research Personnel; Roentgen Rays; Rotation; Sensitivity and Specificity; Shapes; Signal Transduction; Source; Specific qualifier value; System; Technology; Testing; Therapeutic; Time; Tissues; Tumor Tissue; Uncertainty; X-Ray Computed Tomography; anti-tumor immune response; bioluminescence imaging; cancer imaging; clinical translation; commercialization; cone-beam computed tomography; contrast imaging; design and construction; fluorescence imaging; fluorophore; imaging capabilities; imaging study; imaging system; improved; in vivo; in vivo Model; in vivo evaluation; industry partner; irradiation; metabolic rate; multidisciplinary; novel; optical imaging; pre-clinical; pre-clinical assessment; pre-clinical research; radiation response; reconstruction; response; serial imaging; soft tissue; spectrograph; success; therapy design; tomography; treatment research; tumor; 3-Dimensional; Address; Adopted; Adoption; Algorithms; Anatomy; Animals; Biological; Biological Response Modifier Therapy; Biology; Bioluminescence; Biomedical Engineering; Complement; Data; Data Analyses; Docking; Engineering; Environment; Epidermal Growth Factor Receptor; Equation; Excision; Fluorescence; Fluorescent Probes; Functional Imaging; Glioblastoma; Heterogeneity; Human; Hypoxia; Immunotherapy; Industrialization; Knowledge; Lasers; Light; Measures; Methods; Modeling; Modernization; Molecular; Normal tissue morphology; Optical Tomography; Optics; Performance; Positioning Attribute; Positron-Emission Tomography; Property; Radiation; Radiation therapy; Research; Research Personnel; Roentgen Rays; Rotation; Sensitivity and Specificity; Shapes; Signal Transduction; Source; Specific qualifier value; System; Technology; Testing; Therapeutic; Time; Tissues; Tumor Tissue; Uncertainty; X-Ray Computed Tomography; anti-tumor immune response; bioluminescence imaging; cancer imaging; clinical translation; commercialization; cone-beam computed tomography; contrast imaging; design and construction; fluorescence imaging; fluorophore; imaging capabilities; imaging study; imaging system; improved; in vivo; in vivo Model; in vivo evaluation; industry partner; irradiation; metabolic rate; multidisciplinary; novel; optical imaging; pre-clinical; pre-clinical assessment; pre-clinical research; radiation response; reconstruction; response; serial imaging; soft tissue; spectrograph; success; therapy design; tomography; treatment research; tumor

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.

项目摘要/摘要 在过去的10年中，我们的小组已经做出了多学科的努力，以弥合 人类治疗和临床前研究的辐射方法。我们采用了生物工程研究 构建先进的小型动物辐射研究平台（SARRP）的合伙机制。这 SARRP配备了锥形束CT（CBCT）来指导局灶性照射，并通过Xstrahl商业化 在2010年。该系统对临床前辐射研究进行了变革，因为现在正在使用66台机器 在世界范围内> 300名调查人员。认识到CBCT成像不足以定位肿瘤模型 在低图像对比度环境中，我们在船上开发了生物发光层析成像（BLT） SARRP完成CBCT指导。这项工作得到了以前的学术工业的支持 合作伙伴关系（AIP）机制。 BLT实用程序是定位光学质量中心（com）的“第一个” 辐照的目标。尽管这种伙伴关系的成功导致了BLT系统的商业化 Xstrahl在2016年，用户采用BLT平台并不乏力。显然调查人员很高 希望能够定义SARRP上目标体积的3D形状以完全补充现代 人类待遇。我们必须必须将BLT指导推向新的3D目标水平 形成com以外的描述，并允许对目标响应辐射的响应进行定量评估。车载 引入了PET成像以使人类的生物学引导RT能够。小动物辐射研究 通过生物学和功能靶向和评估功能，也将大大提高 解剖学。荧光断层扫描（FT）将允许对密钥进行深入的生物学和机械询问 有关肿瘤及其对RT的微环境反应的信息。它完成了生物发光 成像研究肿瘤和正常组织反应，当使用工程生物发光模型不是 可用的。考虑复合分子时，FT的研究潜力特别重要 带有放射线的治疗策略，例如免疫疗法。荧光成像还添加了 优势可以作为临床翻译作为宠物成像的替代物。集成的CBCT/BLT/FT 完成SARRP的功能将为临床前辐射研究提供强大的平台。 Xstrahl和Johns Hopkins团队将继续建立和商业化这些新的合作伙伴关系 功能。我们的目标是（1）。设计和构建一个新的高级BLT/FT系统，以指导辐射 登上SARRP并进行离线成像研究，（2）。为目标体积开发定量BLT/ft 确定和治疗评估，（3）。评估和验证光学系统性能 幻影和体内模型。新的高级分子光学成像的成功传播 功能大大增强了SARRP用户的辐射研究的进行。