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

基本信息

批准号：
10606547
负责人：
Junwei Du
金额：
--
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10606547
关键词：
Animals Area Background Radiation Biochemical Biological Assay Biological Models Biological Monitoring Biological Process Bismuth Cardiac Cardiovascular system Cells Circulation Clinical Research Code Coupled Dedications Development Diameter 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 Receptor Gene Resolution Signal Transduction Source System Therapeutic Thick Work analog cardiovascular imaging clinical diagnostics cost data acquisition design detector glucose metabolism heart imaging image translation imaging modality improved in vivo meter molecular imaging nanomolar novel pre-clinical pre-clinical research preclinical imaging preclinical study radiotracer receptor therapeutic gene tool transgene expression

项目摘要

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.

概括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对体内各种生物过程进行成像。 PET 的关键参数是其空间分辨率和灵敏度决定了在亚下对受试者的小区域中的放射性示踪剂进行成像和量化的能力纳摩尔浓度。但小动物PET的应用受到了限制空间分辨率和更重要的是灵敏度的结合阻碍了 PET 的使用应用范围包括低水平受体和转基因表达的成像、治疗细胞循环和快速动态成像以捕获心脏动态。该提案的主要目标是开发一种非常高灵敏度的小动物全身 PET 扫描仪专用于小鼠/大鼠疾病模型成像的超低剂量和快速动态应用。拟议的 PET 扫描仪将有 72 个交互深度 (DOI) 探测器模块，排列成 6 个环，环直径为 160毫米，轴向长度242毫米。所提出的 PET 扫描仪的几何形状旨在覆盖小鼠/大鼠的整个身体，并在整个身体上获得高灵敏度和高分辨率。将使用基于连接到锗酸铋 (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 是因为它具有高阻止本领、高光电比、低成本，最重要的是它的背景辐射可忽略不计（可显着减少背景事件，有利于超低剂量成像）。虽然镥基闪烁体具有许多吸引人的特性，但主要的限制是存在固有背景辐射，这是超低剂量成像的一个重要障碍。专用数据采集电子设备将为拟议的扫描仪设计。具体来说，一种新颖的类似物使用肖特基二极管来阻挡信号可忽略不计的 SiPM 噪声的信号复用读出方法将用于简化读出电子设备并提高空间分辨率和时间分辨率，以及共享光电探测器读出方法将用于识别所有晶体。该提案的结果将是 PET 扫描仪在 FOV 中心的灵敏度 >50%，并且轴向 FOV 中心 100 mm 范围内灵敏度 > 40%。预计分辨率约为 1 mm FOV 中心且整个 FOV 上的误差优于 1.5 毫米。灵敏度比之前高 4 倍以上目前可用的小动物 PET 扫描仪。它可能会促进小动物全身 PET 的使用用于监测导致源活动极低的生物过程并扩大应用范围临床前应用中这种强大的非侵入性平移成像方式。正电子发射断层扫描仪该提案中开发的产品也与 MRI 兼容，并将支持最终集成到 MRI 扫描仪中用于混合 PET/MRI 成像。