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.

项目摘要/摘要 包括我们在内的几个小组已经开始努力开发模仿辐射的小动物辐射器 治疗治疗（RT）。用于指导照射的主要图像方式是锥形束CT（CBCT）， 我们的CBCT-SMALL动物辐射研究平台（SARRP）在2010年进行了商业化。我们的系统和 其他的，对临床前RT研究进行了变革，现在有115台机器正在全球使用 600名调查员。虽然CBCT提供了出色的指导能力，但它在定位软组织方面不太熟练 在低图像对比度环境中生长的目标。相反，生物发光成像（BLI）可提供强大 图像对比是软组织靶向的有吸引力的解决方案。但是，通常使用的2d Bli 动物表面不足以指导辐射，因为来自内部生物发光的光学传输 肿瘤高度易受不规则躯干和组织光学特性的影响。认识这些 局限性导致我们将3D生物发光断层扫描（BLT）与SARRP整合在一起。我们的第一个BLT是设计的 定位光学目标的质量（COM）中心。这次进步得到了很多 然而，SARRP用户几乎没有实用的BLT系统采用。显然， 调查人员需要解决两个关键的未满足，以显着增强其研究的行为： 1）目标形状的知识是RT的基本需求。没有这样的信息来指导辐射，很大 正常组织的一部分可以不必要地辐射，导致不希望的实验不确定性。这是 必须将BLT指导超越COM，升至3D目标形状的新水平 描述； 2）临床实践认识到功能互补使用和 RT的解剖图像。 BLI测量细胞活力，因此它是纵向的理想成像方式 监测治疗结果。但是，表面BLI为评估提供的定量信息 目前有限甚至不准确。提出了新的重建算法和校准方法 在此应用程序中，我们将建立一个新的定量BLT（QBLT）来满足此需求。我们假设这一点 QBLT/CBCT指导的小动物辐射系统将为调查人员提供新的功能来定位软 组织靶标，定义其形状以用于保质照射，并非侵入性地量化治疗结果。我们的目标 为：目标1：设计和构建一个独立的QBLT系统，很容易适应商业辐射平台； AIM 2：优化输入数据，并为目标形状开发校准方法和重建算法 描述和定量成像；目标3：在体内验证QBLT引导的RT，并评估其适用性 治疗评估。该提议的成功将显着增强小动物放射疗法 具有功能性靶向和评估能力以外的解剖成像的能力进行研究。