A 0.5 mm resolution total-body small-animal PET

摘要 小动物正电子发射断层扫描(PET)的关键参数是空间分辨率和灵敏度 确定在亚纳摩尔的受试者的一小块区域内成像和量化放射性示踪剂的能力 浓度。然而，小动物PET的应用受到了限制。 空间分辨率和灵敏度的结合，这阻碍了PET在一系列应用中的使用 包括小鼠脑成像、主动脉微钙化和炎症成像、高分辨率全身成像 使用图像衍生输入函数进行动态成像和运动建模研究。 该方案的目标是1)开发一种0.5 mm分辨率的全身小动物PET专用扫描仪 用于高分辨率和快速动态应用的小鼠疾病模型成像，以及2)提供临床前 使用鼠标模型开发、验证和表征将输入人类的范例和方案的工具 研究，如全身和大脑研究。拟议的正电子发射计算机断层扫描仪将有128个交互深度 (DOI)探测器。设计的环径为110 mm，轴长为167 mm 以覆盖鼠标的整个身体，并在整个身体获得高分辨率和高灵敏度。 基于两端耦合的线性梯度硅光电倍增管(LG-SiPM)的双端读出探测器 间距大小为0.5 mm、长度为20 mm的40×40氧化正硅酸锶(LYSO)阵列将 用于提取DOI信息，以在整个身体范围内保持高而统一的空间分辨率 老鼠。选择Lyso是因为它的高光产额(高空间分辨率和能量分辨率)，高光圈 功率(用于高灵敏度)和快速衰减时间(高事件率能力)。 将为拟议的双端读出探测器设计专用的数据采集电子设备 通过升级我们经过充分研究的电子系统来扫描，并将使用信号多路复用读出方法 为了将每个检测器的40个信号减少到9个信号(8个用于位置信息，1个用于定时信息)，以 降低读出电子设备的成本、复杂性和热量。 这项提议的结果将是一种分辨率为0.5 mm、分辨率为0.5 mm的全身小动物PET扫描仪 视野中心的灵敏度为~24.5%。分辨率为~0.5 mm，灵敏度为 比鼠标体积的15%更好。空间/体分辨率超过2倍/8倍 目前可用的小动物PET扫描仪具有类似的灵敏度，并且灵敏度提高了20倍以上 比目前可用的分辨率相近的小动物PET扫描仪更高。建议的扫描仪可以促进 全身小动物PET用于监测生物过程，导致精细结构和 扩大这一强大的、活体、非侵入性和平移成像设备的应用范围 临床前应用。该提案中开发的PET扫描仪也是与MRI兼容的，并将支持 最终集成到MRI扫描仪中，用于混合PET/MRI成像。

Summary The key parameters of small-animal positron emission tomography (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 sensitivity, which hampers the use of PET for a range of applications including mouse brain imaging, aortic microcalcification and inflammation imaging, high-resolution total-body dynamic imaging and kinetic modeling studies with using image-derived input function. The goals of this proposal are 1) to develop a 0.5 mm resolution total-body small-animal PET scanner dedicated for high-resolution and fast dynamic applications for imaging mouse disease models, and 2) provide a pre-clinical tool using mouse models to develop, validate, characterize the paradigms and protocols that will feed into human studies, such as total-body and brain studies. The proposed PET scanner will have 128 depth-of-interaction (DOI) detectors. The ring diameter and the axial length are 110 mm and 167 mm, respectively, which is designed to cover the entire body of the mouse and to obtain high resolution and high sensitivity across the entire body. Dual-ended readout detectors based on linearly-graded silicon photomultipliers (LG-SiPMs) coupled to both ends of 40 x 40 lutetium yttrium oxyorthosilicate (LYSO) arrays with a pitch size of 0.5 mm and length of 20 mm will be used to extract DOI information to maintain high and uniform spatial resolution across the entire body of the mouse. LYSO is chosen due to its high light yield (for high spatial resolution and energy resolution), high stopping power (for high sensitivity), and fast decay time (high event rate ability). Dedicated data acquisition electronics for dual-ended readout detectors will be designed for the proposed scanner by upgrading our well-studied electronics system, and a signal multiplexing readout method will be used to reduce the 40 signals of each detector to 9 signals (8 for position information and 1 for timing information) to reduce the cost, complexity, and heat of the readout electronics. The outcome of this proposal will be a total-body small animal PET scanner with a resolution < 0.5 mm and a sensitivity ~24.5 % at the center of the field of view. The resolution will be ~0.5 mm and the sensitivity will be better than 15 % across the volume of the mouse. The spatial/volume resolution is more than 2x/8x better than currently available small-animal PET scanners with similar sensitivity, and the sensitivity is more than 20x better than currently available small-animal PET scanners with similar resolution. The proposed scanner can promote the use of total-body small-animal PET for monitoring biological processes that result in fine structures and expand the range of applications for this powerful, in vivo, 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.