Quantitative bioluminescence tomography for pre-clinical radiotherapy

用于临床前放射治疗的定量生物发光断层扫描

• 批准号: 10302251
• 负责人: Ken Kang-Hsin Wang
• 金额: $ 29.1万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10302251
• 关键词: 3-Dimensional; Address; Adoption; Algorithms; Animals; Bioluminescence; Biomedical Engineering; Calibration; Data; Dose; Environment; Evaluation; Functional Imaging; Funding; Glioblastoma; Heterogeneity; Human; Image; Knowledge; Light; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Methods; Modeling; Monitor; Normal tissue morphology; Optics; PET/CT scan; Pathologic; Performance; Positioning Attribute; Property; Radiation; Radiation therapy; Radiotherapy Research; Research; Research Personnel; Shapes; Signal Transduction; Stains; Surface; Survival Rate; System; Testing; Therapeutic Studies; Time; Tissues; Treatment outcome; Tumor Volume; Uncertainty; United States National Institutes of Health; Variant; anatomic imaging; base; bioluminescence imaging; charge coupled device camera; clinical practice; cone-beam computed tomography; contrast imaging; design; design and construction; image guided; imaging capabilities; imaging modality; improved; in vivo; in vivo imaging; innovation; irradiation; novel; pre-clinical; quantitative imaging; reconstruction; response; soft tissue; spectrograph; success; tomography; treatment comparison; treatment planning; treatment response; tumor; tumor growth

PROJECT SUMMARY/ABSTRACT Several groups, including ours, have initiated efforts to develop small-animal irradiators that mimic radiation therapy (RT) for human treatment. The major image modality used to guide irradiation is cone-beam CT (CBCT), and our CBCT-small animal radiation research platform (SARRP) was commercialized in 2010. Our system, and others, were transformative for pre-clinical RT research, and 115 machines are now in use world-wide by some 600 investigators. While CBCT provides excellent guidance capability, it is less adept at localizing soft tissue targets growing in a low image contrast environment. In contrast, bioluminescence imaging (BLI), provides strong image contrast and thus is an attractive solution for soft tissue targeting. However, commonly used 2D BLI on an animal surface is inadequate to guide irradiation, because optical transport from an internal bioluminescent tumor is highly susceptible to the effects of irregular torso and tissue optical properties. Recognition of these limitations led us to integrate 3D bioluminescence tomography (BLT) with SARRP. Our first BLT was designed to localize the center of mass (CoM) of an optical target for irradiation. This advance was received with much intrigue, however there was little practical adoption of the BLT system by SARRP users. It was clear that the investigators required two key unmet needs to be addressed, to significantly enhance their conduct of research: 1) knowledge of target shape is a fundamental need for RT. Without such information to guide radiation, large portions of normal tissue can be irradiated unnecessarily, leading to undesired experimental uncertainties. It is imperative that we advance BLT guidance beyond CoM, to a new and precise level of 3D target shape delineation; and 2) clinical practice recognizes the importance of complementary use of functional and anatomical image for RT. BLI measures cellular viability, thus it is an ideal imaging modality for longitudinally monitoring treatment outcome. However, the quantitative information that surface BLI provides for assessment is currently limited or even inaccurate. With the novel reconstruction algorithm and calibration methods proposed in this application, we will establish a new quantitative BLT (QBLT) to address this need. We hypothesize that the QBLT/CBCT-guided small animal radiation system will provide investigators new capabilities to localize soft tissue target, define its shape for conformal irradiation, and non-invasively quantify treatment outcome. Our aims are: Aim 1: design and construct a standalone QBLT system readily adapted to commercial radiation platform; Aim 2: optimize input data, and develop calibration method and reconstruction algorithm for target shape delineation and quantitative imaging; Aim 3: validate the QBLT-guided RT in vivo and assess its suitability for treatment assessment. The success of this proposal will significantly enhance small animal radiotherapy research with the capabilities of functional targeting and assessment beyond anatomical imaging.

项目概要/摘要 包括我们在内的几个团体已开始努力开发模拟辐射的小动物辐照器 用于人类治疗的疗法（RT）。用于引导照射的主要图像模式是锥束 CT (CBCT)， 我们的CBCT-小动物辐射研究平台（SARRP）于2010年商业化。我们的系统，以及 其他机器对临床前 RT 研究具有革命性意义，目前 115 台机器已在全球范围内被一些人使用 600名调查员。虽然 CBCT 提供出色的引导能力，但它不太擅长定位软组织 在低图像对比度环境中生长的目标。相比之下，生物发光成像 (BLI) 提供了强大的 图像对比度，因此是软组织靶向的有吸引力的解决方案。然而，常用的 2D BLI 动物表面不足以引导照射，因为来自内部生物发光的光传输 肿瘤非常容易受到不规则躯干和组织光学特性的影响。对这些的认可 由于局限性，我们将 3D 生物发光断层扫描 (BLT) 与 SARRP 集成。我们的第一个 BLT 被设计出来 定位照射光学目标的质心 (CoM)。这笔预付款收到了很多 然而，SARRP 用户很少实际采用 BLT 系统。很明显， 研究人员要求解决两个关键的未满足需求，以显着加强他们的研究行为： 1) 了解目标形状是 RT 的基本需求。如果没有此类信息来指导辐射，大 正常组织的某些部分可能会受到不必要的照射，从而导致不必要的实验不确定性。这是 我们必须将 BLT 引导推进到 CoM 之外，达到 3D 目标形状的新的精确水平 描绘； 2) 临床实践认识到功能和功能互补使用的重要性 RT 的解剖图像。 BLI 可测量细胞活力，因此它是纵向成像的理想成像方式 监测治疗结果。然而，表面 BLI 提供的用于评估的定量信息 目前的情况是有限的，甚至是不准确的。提出了新颖的重建算法和校准方法 在这个应用中，我们将建立一个新的定量BLT（QBLT）来解决这个需求。我们假设 QBLT/CBCT 引导的小动物辐射系统将为研究人员提供定位软体的新功能 组织目标，定义其适形照射的形状，并以非侵入方式量化治疗结果。我们的目标 目标1：设计并构建一个易于适应商业辐射平台的独立QBLT系统； 目标2：优化输入数据，开发目标形状的标定方法和重建算法 描绘和定量成像；目标 3：在体内验证 QBLT 引导的 RT 并评估其适用性 治疗评估。该提案的成功将显着增强小动物放射治疗 具有解剖成像之外的功能定位和评估能力的研究。