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: 10302256
• 负责人: Ken Kang-Hsin Wang
• 金额: $ 24.66万
• 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/10302256
• 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; Sensitivity and Specificity; Shapes; Signal Transduction; Source; System; 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 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，以弥合不同领域之间的技术差距 我们采用了生物工程研究的放射方法进行人体治疗和临床前研究。 建立先进小动物辐射研究平台（SARRP）的伙伴机制。 SARRP配备锥束CT（CBCT）引导局灶照射，并由Xstrahl商业化 2010 年。该系统对临床前辐射研究具有变革意义，目前有 66 台机器投入使用 全球超过 300 名研究人员认识到 CBCT 成像不足以定位肿瘤模型。 在低图像对比度环境中生长，我们在船上开发了生物发光断层扫描（BLT） SARRP 是对 CBCT 指导的补充，这项工作得到了之前学术界和工业界的支持。 BLT 实用程序是第一个定位光学质心 (CoM) 的机制。 尽管这种合作关系的成功导致了 BLT 系统的商业化。 Xstrahl 在 2016 年的调查显示，用户对 BLT 平台的采用情况平平，调查人员对此高度评价。 希望能够在 SARRP 上定义目标体积的 3D 形状，以充分补充现代 我们必须将 BLT 指导提升到 3D 目标的新水平。 超出 CoM 的形状描绘，并允许定量评估目标对辐射的响应。 PET 成像的引入使得生物学引导的人类放射治疗成为可能。 生物和功能靶向和评估能力也将大大增强 荧光断层扫描（FT）将允许对关键的生物学和机械学进行深入的询问。 有关肿瘤及其微环境对 RT 反应的信息它补充了生物发光。 当不能使用工程生物发光模型时，通过成像来研究肿瘤和正常组织的反应 当考虑组合分子时，FT 的研究潜力尤其重要。 放射治疗策略，例如荧光成像，也有附加作用。 优点是可以作为 PET 成像替代品进行临床转化。 补充 SARRP 的能力将为临床前辐射研究提供强大的平台。 Xstrahl 和约翰霍普金斯大学团队将继续合作开发这些新产品并将其商业化 我们的目标是 (1) 设计和构建新的先进 BLT/FT 系统来引导照射。 登上 SARRP 并进行离线成像研究，(2) 开发目标体积的定量 BLT/FT。 测定和治疗评估，(3) 评估和验证光学系统性能。 体模和体内模型的成功传播新的先进分子光学成像。 能力显着增强了 SARRP 用户的辐射研究工作。