NeuroExplorer: Ultra-high Performance Human Brain PET Imager for Highly-resolved In Vivo Imaging of Neurochemistry

脑正电子发射断层扫描（PET）的研究应用已经有40多年的历史。 定量PET系统与新型放射性示踪剂的结合导致了许多成像帕拉， 深入了解正常的大脑生理学，包括神经递质动力学和受体药理学 在静止和激活期间。脑专用PET系统提供了比目前可用的重要优势 PET系统的灵敏度和分辨率。然而，最先进的脑PET技术还没有 超过20年的HRRT。因此，迫切需要建立下一代 用于人体研究的脑PET系统。该提案汇集了一个经验丰富的协作团队 来自耶鲁大学、加州大学戴维斯分校和美国联合影像医疗保健公司（UIHA）。开发下一代 NeuroEXPLORER（NX）PET系统具有以下目的。具体目标1：设计和构建 NeuroEXPLORER：我们将在2年内完成NX系统的设计和构建。设计包括高 高性能LYSO-SiPM模块，配有小型探测器，相互作用深度为4 mm，飞行时间为250 ps 分辨率，轴长约50 cm，与CT配对进行衰减校正。这个设计将产生一个 有效灵敏度是HRRT的10倍，人脑中的实际分辨率为1.5-2 mm。 该系统将包括内置的实时最先进的运动跟踪摄像头，并将使用新的 幻影实验，以评估全范围的运作，以验证显着改善小， 区域精度和准确度。具体目标2：全定量脑PET的算法开发。我们 将为这个系统开发新的算法。使用EXPLORER体验。落实 重建算法，以产生在空间和时间上具有均匀超高分辨率的动态图像， 扩展耶鲁大学的HRRT运动校正经验，我们将开发基于摄像头的运动检测和 校正算法，以提供超高分辨率的人脑图像。利用颈动脉的形状， 几何学，我们将开发方法，以准确地测量血液活动进行比较，以人体动脉数据 其目的是允许动力学建模而无需动脉采样。我们将开发降噪方法， 机器学习，以减少研究健康大脑的剂量，并消除对CT扫描的需要， 衰减校正具体目标3：人类范例示范。对于人类受试者，我们将评估 证明NX系统有效性的特定成像范例：1）证明 显著的灵敏度增加（与HRRT直接比较）及其对 药理作用，2）利用高灵敏度可靠地测量小细胞核中的摄取;和3）开放 新的前沿成像神经递质动力学，包括多巴胺和阿片类药物的释放。最终目标 是一个功能齐全、特征鲜明的系统，极大地扩展了脑部PET协议的范围， 应用.

Research applications of brain Positron Emission Tomography (PET) have been in place for over 40 years. The combination of quantitative PET systems with novel radiotracers has led to a numerous imaging para- digms to understand normal brain physiology including neurotransmitter dynamics and receptor pharmacology at rest and during activation. Brain-dedicated PET systems offer important advantages over currently available PET systems in terms of sensitivity and resolution. However, the state-of-the-art for brain PET has not progressed beyond the 20-year-old HRRT. Therefore, there is a compelling need to build the next generation of brain PET systems for human studies. This proposal brings together a highly experienced collaborative team from Yale, UC Davis, and United Imaging Healthcare America (UIHA). to develop the next generation NeuroEXPLORER (NX) PET system with the following Aims. Specific Aim 1: Design and Build the NeuroEXPLORER: In 2 years, we will complete the design and build the NX system. The design includes high performance LYSO-SiPM blocks with small detectors, 4-mm depth-of-interaction, 250 ps time-of-flight resolution, and axial length of ~50 cm, paired with CT for attenuation correction. This design will produce a factor of 10 greater effective sensitivity than the HRRT and practical resolution of 1.5-2 mm in the human brain. The system will include built-in real-time state-of-art motion tracking cameras and will be tested using novel phantom experiments to assess the full-range of operation to validate the dramatic improvement in small- region precision and accuracy. Specific Aim 2: Algorithm Development for Fully-Quantitative Brain PET. We will develop the novel algorithms for this system. Using EXPLORER experience. we will implement reconstruction algorithms to produce dynamic images with uniform ultra-high resolution in space and time, Extending Yale’s HRRT motion correction experience, we will develop camera-based motion detection and correction algorithms to deliver ultra-high resolution human brain images. Using the carotid artery shape and geometry, we will develop methods to accurately measure blood activity to be compared to human arterial data with the goal to permit kinetic modeling without arterial sampling. We will develop noise reduction methods with machine learning to reduce dose for studying health brains and to eliminate the need for the CT scan for attenuation correction. Specific Aim 3: Human Paradigm Demonstration. With human subjects, we will evaluate specific imaging paradigms to demonstrate the effectiveness of the NX system: 1) demonstration of the dramatic sensitivity increase (with a direct comparison to the HRRT) and its impact on detection of pharmacologic effects, 2) leveraging high sensitivity to reliably measure uptake in small nuclei; and 3) opening new frontiers of imaging neurotransmitter dynamics, including dopamine and opioid release. The ultimate goal is a fully functioning and characterized system that dramatically expands the scope of brain PET protocols and applications.