AdaptiSPECT-C: A Next-Generation, Adaptive Brain-Imaging SPECT System for Drug Discovery and Clinical Imaging

AdaptiSPECT-C：用于药物发现和临床成像的下一代自适应脑成像 SPECT 系统

• 批准号: 9755231
• 负责人: LARS R FURENLID
• 金额: $ 91.1万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755231
• 关键词: Anatomy; Arizona; Biological Markers; Biomedical Research; Brain; Brain Diseases; Brain imaging; Calibration; Characteristics; Clinic; Clinical; Clinical Data; Code; Collimator; Computer software; Contracts; Data; Dementia; Detection; Development; Diagnostic; Differential Diagnosis; Dimensions; Discipline of Nuclear Medicine; Disease; Distributional Activity; Documentation; Drug Industry; Drug Kinetics; FDA approved; Face; Gamma Rays; Generations; Geometry; Head; Human; Image; Image Analysis; Imaging Device; Inflammation; Institution; Kinetics; Label; Lead; Lesion; Magnetic Resonance Imaging; Maps; Massachusetts; Mechanics; Modeling; Monitor; Motion; Names; Patient Care; Patients; Performance; Pharmacologic Substance; Phase; Photons; Positron-Emission Tomography; Protocols documentation; Radiation Dose Unit; Radioisotopes; Radionuclide Imaging; Radiopharmaceuticals; Research Contracts; Resolution; Rotation; Safety; Sampling; Self-Correction; Sensory Receptors; Slice; Specificity; Structure; Surface; System; Systems Analysis; Testing; Therapy Evaluation; Tracer; Universities; Variant; attenuation; base; biomarker development; clinical application; clinical imaging; commercialization; cost; design; detector; diagnosis evaluation; drug discovery; flexibility; human imaging; human subject; imaging agent; imaging system; improved; individual patient; innovation; molecular imaging; next generation; novel therapeutics; performance tests; pre-clinical; prototype; quantitative imaging; reconstruction; response; single photon emission computed tomography; tool

Advances in molecular imaging are yielding a new generation of single-photon-emission-computed- tomography (SPECT) brain-imaging agents that will lead the way in understanding the human brain by enabling the development of biomarkers with unprecedented specificity for mapping neuroreceptors and proteinopathies associated with disease and dementia. SPECT is an ideal tracer-imaging tool for investigating the underlying mechanisms in brain disorders, their differential diagnoses, and monitoring their treatment because of its lower cost and radiation dose relative to PET, longer half-lives of the radionuclides imaged, and ability to simultaneously image multiple imaging agents labeled with different radionuclides. However, most clinical brain SPECT is still being performed by 2-headed systems with collimators designed for planar scintigraphy. To meet the potential for better patient care offered by these new imaging agents, and vastly improve the utility of existing agents, a revolution in SPECT brain-imaging system design is required. In Phase 1 of this Biomedical Research Partnership (BRP) application we propose to meet this requirement by creating a multi-detector-module multi-pinhole (MPH) SPECT brain-imaging system ideally suited for quantitative dynamic and high-spatial-resolution static SPECT imaging. Based on its heritage and intent for clinical imaging, we have named this proposed system AdaptiSPECT-C. Dynamic imaging will be enabled by obtaining sufficient angular sampling without the need for rotation. The system will automatically adapt its imaging characteristics (aperture size and number of pinholes open for imaging) in response to the imaging tasks and individual patients. It will thereby optimize lesion detection and quantification, as well as provide optimal data for pharmacokinetic analysis within structures throughout the brain. Automatic alignment to existent CT diagnostic studies of the patient for use in providing anatomical correlation, formation of attenuation maps, and templates for PVE correction will be enabled through usage of depth- sensing cameras, which will also be used for correction for head motion. Comparison of AdaptiSPECT-C to clinical systems will be conducted through inviCRO, one of the nation's top contract research organizations (CROs) serving the pharmaceutical industry. These studies will provide the documentation of system performance necessary to enable “Big-Pharma” companies to use the system to gather the clinical data necessary for FDA approval of new pharmaceuticals. Our Specific Aims are: 1. Construct an adaptable brain-SPECT system and test performance versus design specifications; 2. Develop reconstruction software for optimal image quality and activity quantification; 3.Integrate depth-sensing camera imaging to correct patient motion and align existent CT slices; and 4. Incorporate analysis software, and validate system through prototype human imaging.

分子成像的进步正在产生新一代的单光子发射计算- 断层扫描（SPECT）脑成像剂，将引领了解人类大脑的方式， 使得能够开发出具有前所未有的特异性的生物标志物，用于映射神经受体， 与疾病和痴呆相关的蛋白质病。SPECT是一种理想的示踪成像工具， 研究脑部疾病的潜在机制、其鉴别诊断并监测其 治疗，因为它的成本和辐射剂量较低，相对于PET，放射性核素的半衰期较长 成像，以及同时成像用不同放射性核素标记的多种成像剂的能力。 然而，大多数临床脑SPECT仍然是由双头系统与准直器设计， 用于平面层析成像。为了满足这些新显像剂提供的更好的患者护理的潜力， 并极大地提高了现有试剂的效用，SPECT脑成像系统设计的一场革命是 必需的. 在生物医学研究合作伙伴关系（BRP）申请的第1阶段，我们建议满足以下要求： 通过创建多探测器模块多针孔（MPH）SPECT脑成像系统， 适用于定量动态和高空间分辨率静态SPECT成像。根据其遗产和 出于临床成像的目的，我们将该系统命名为AdaptiSPECT-C。动态成像将是 通过获得足够的角度采样而不需要旋转来实现。系统会自动 调整其成像特性（孔径大小和为成像而打开的针孔数量）， 成像任务和个体患者。因此，它将优化病变检测和量化，以及 为整个大脑结构内的药代动力学分析提供最佳数据。自动 - 与患者的现有CT诊断研究对准，以用于提供解剖学相关性， 衰减图的形成和PVE校正模板将通过使用深度- 传感相机，其也将用于头部运动的校正。AdaptiSPECT-C与 临床系统将通过美国最大的合同研究组织之一InvicRO进行 （CRO）服务于制药行业。这些研究将提供系统的文档 使“大型制药”公司能够使用该系统收集临床数据所需的性能 FDA批准新药所必需的。 我们的具体目标是：1。构建一个适应性强的脑SPECT系统， 设计规范; 2.开发重建软件以获得最佳图像质量和活动 3.整合深度感应相机成像，以校正患者运动并对齐现有CT 切片;和4.结合分析软件，并通过原型人体成像验证系统。