Maximizing sensitivity for ultra-low dose PET imaging

最大限度提高超低剂量 PET 成像的灵敏度

• 批准号: 10393010
• 负责人: Junwei Du
• 金额: $ 60.93万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393010
• 关键词: Animals; Area; Background Radiation; Biochemical; Biological Assay; Biological Models; Biological Monitoring; Biological Process; Bismuth; Blood Circulation; Caliber; Cardiac; Cardiovascular system; Cells; Clinical Research; Code; Coupled; Crystallization; Development; Disease model; Dose; Electronics; Event; Funding; Geometry; Goals; Heart; Hybrids; Image; Imaging Techniques; Individual; Length; Low Dose Radiation; Lutetium; Magnetic Resonance Imaging; Measurement; Methods; Modeling; Mus; Noise; Outcome; Performance; Polishes; Positioning Attribute; Positron-Emission Tomography; Property; Radioisotopes; Rattus; Resolution; Signal Transduction; Source; System; Therapeutic; Thick; Work; analog; base; cardiovascular imaging; cellular imaging; clinical diagnostics; cost; data acquisition; design; detector; glucose metabolism; heart imaging; imaging modality; improved; in vivo; molecular imaging; nanomolar; novel; pre-clinical; pre-clinical research; preclinical imaging; preclinical study; radiotracer; receptor; receptor expression; tool; transgene expression

Summary Small-animal positron emission tomography (PET) has been widely used as a powerful tool for preclinical studies to image a wide range of biological processes in vivo. The key parameters in PET are its spatial resolution and sensitivity that determine the ability to image and quantify radiotracers in a small region of the subject at sub- nanomolar concentrations. However, the applications of small-animal PET have been limited in its application by a combination of spatial resolution and more importantly, the sensitivity, which hampers the use of PET for a range of applications including imaging of low-levels of receptor and transgene expression, imaging of therapeutic cell circulation and fast dynamic imaging to capture cardiac dynamics. The main goal of this proposal is to develop a very high sensitivity total-body small-animal PET scanner dedicated for ultra-low dose and fast dynamic applications for imaging mouse/rat disease models. The proposed PET scanner will have 72 depth-of-interaction (DOI) detector modules arranged in 6 rings, with a ring diameter of 160 mm and an axial length of 242 mm. The geometry of the proposed PET scanner is designed to cover the whole body of the mouse/rat and to obtain high sensitivity and high resolution across the entire body. Dual-ended readout detectors based on SiPMs coupled to both ends of bismuth germanate (BGO) will be used to extract DOI information to maintain high and uniform spatial resolution across the whole field of view (FOV). BGO is chosen due to its high stopping power, high photoelectric ratio, low cost and the most importantly its negligible background radiation (which can significantly reduce the background events to benefit ultra-low dose imaging). While lutetium-based scintillators have many attractive properties, a major limitation is the presence of intrinsic background radiation, which is a significant barrier for ultra-low dose imaging. Dedicated data acquisition electronics will be designed for the proposed scanner. Specifically, a novel analog signal multiplexing readout method using Schottky diodes to block the noise of SiPMs with negligible signals will be used to simplify the readout electronics and to improve the spatial resolution and the timing resolution, and a shared-photodetector readout method will be used to identify all the crystals. The outcome of this proposal will be a PET scanner will have a sensitivity >50% at the center of the FOV and a sensitivity > 40% within the central 100 mm of the axial FOV. The resolution is predicted to be ~ 1 mm at the center of the FOV and better than 1.5 mm across the entire FOV. The sensitivity is more than 4x better than currently available small-animal PET scanners. It can potentially promote the use of total-body small-animal PET for monitoring biological processes that result in very low source activities and expand the range of applications for this powerful, non-invasive and translational imaging modality in preclinical applications. The PET scanner developed in this proposal is also MRI-compatible and will support eventual integration inside an MRI scanner for hybrid PET/MRI imaging.

总结 小动物正电子发射断层扫描（PET）已被广泛用作临床前研究的有力工具 来成像体内的各种生物过程。PET中的关键参数是其空间分辨率， 灵敏度，其确定在低于100 μ m的受试者的小区域中成像和量化放射性示踪剂的能力。 纳摩尔浓度。然而，小动物PET的应用一直受到限制 通过空间分辨率和更重要的是灵敏度的组合，这阻碍了PET用于 应用范围包括低水平受体和转基因表达的成像， 治疗性细胞循环和快速动态成像以捕获心脏动力学。 本计画的主要目标是发展一种高灵敏度的全身小动物正子断层扫描仪 专用于超低剂量和快速动态应用，用于成像小鼠/大鼠疾病模型。拟议 PET扫描仪将有72个相互作用深度（DOI）探测器模块，排列在6个环中，环直径 所提出的PET扫描仪的几何形状被设计成覆盖 在小鼠/大鼠的整个身体上，并在整个身体上获得高灵敏度和高分辨率。 将使用基于耦合到锗酸铋（BGO）两端的SiPM的双端读出探测器 提取DOI信息以在整个视场（FOV）上保持高且均匀的空间分辨率。 选择BGO是因为其高阻止能力、高光电比、低成本，最重要的是其 可忽略的背景辐射（可显著减少背景事件，以利于超低剂量 成像）。虽然基于镥的澄清剂具有许多有吸引力的性质，但主要的限制是存在 固有背景辐射，这是超低剂量成像的重要障碍。 将为拟议的扫描仪设计专用的数据采集电子设备。具体来说，一种新的类似物 使用肖特基二极管的信号复用读出方法以可忽略的信号阻挡SiPM的噪声， 用于简化读出电子器件并提高空间分辨率和定时分辨率， 将使用共享光电探测器读出方法来识别所有晶体。 该提案的结果将是PET扫描仪在FOV中心的灵敏度>50%， 在轴向FOV的中心100 mm内灵敏度> 40%。预计分辨率为~ 1 mm， 在整个FOV范围内，最好小于1.5 mm。灵敏度超过4倍优于 目前可用的小动物PET扫描仪。它可以潜在地促进全身小动物PET的使用 用于监测导致非常低的源活动的生物过程，并扩大应用范围 这种强大的、非侵入性和平移成像模式在临床前应用中的优势。PET扫描仪 在本提案中开发的一种磁共振成像系统也与MRI兼容，并将支持最终集成到MRI扫描仪中 PET/MRI混合成像。