Maximizing sensitivity for ultra-low dose PET imaging

摘要 小动物正电子发射断层扫描(PET)已成为临床前研究的有力工具 以成像体内广泛的生物过程。PET的关键参数是它的空间分辨率和 敏感度决定了在受试者的小范围内对放射性示踪剂进行成像和量化的能力 纳摩尔浓度。然而，小动物PET的应用受到了限制。 由于空间分辨率和更重要的是灵敏度的结合，这阻碍了PET在 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，以捕捉心脏动力学。 本课题的主要目标是研制一种灵敏度极高的全身小动物PET扫描仪 专门用于为小鼠/大鼠疾病模型成像的超低剂量和快速动态应用。建议数 PET扫描仪将有72个相互作用深度(DOI)探测器模块，排列成6个环，环直径 160毫米，轴长242毫米。建议的PET扫描仪的几何形状设计为覆盖 在小鼠/大鼠的全身，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的双端读出检测器 提取DOI信息，以保持整个视场(FOV)高而均匀的空间分辨率。 之所以选择BGO，是因为它的阻挡能力强，光电比高，成本低，最重要的是它 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)。虽然基于钚的闪烁体有许多吸引人的特性，但一个主要的限制是 本底辐射，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。具体地说，一种新的模拟 一种利用肖特基二极管阻断信号可忽略的SiPM噪声的信号多路复用读出方法 用于简化读出电子设备并提高空间分辨率和定时分辨率，以及一种 将使用共享光电探测器读出方法来识别所有的晶体。 这项提议的结果将是PET扫描仪将在视野的中心具有50%的灵敏度和 轴向视野中心100 mm范围内的灵敏度为40%。预计分辨率为~1毫米。 FOV的中心位置，整个FOV的宽度小于1.5 mm。灵敏度超过4倍。 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 用于监测导致极低来源活度的生物过程，并扩大应用范围 用于临床前应用的这种强大的、非侵入性和平移性的成像设备。PET扫描仪 在此方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。

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.