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

NeuroExplorer：超高性能人脑 PET 成像仪，用于神经化学的高分辨率体内成像

• 批准号: 10261504
• 负责人: Richard E. Carson
• 金额: $ 207.4万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-12 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10261504
• 关键词: 20 year old; Adolescent; Algorithms; Americas; Area; Blood; Brain; Brain imaging; Brain scan; Carotid Arteries; Cell Nucleus; Child; Clinical; Collaborations; Data; Detection; Development; Disease; Dopamine; Dose; Effectiveness; Enzymes; Evaluation; Functional disorder; Future; Geometry; Goals; Healthcare; Hippocampus (Brain); Human; Image; Inferior; Length; Machine Learning; Manufacturer Name; Measures; Metabolism; Methods; Midbrain structure; Modeling; Motion; Nerve Degeneration; Neurotransmitters; Noise; Opioid; Performance; Pharmacology; Physics; Physiology; Positron-Emission Tomography; Proteins; Protocols documentation; Radioactive; Research; Resolution; Rest; Sampling; Sensory Receptors; Shapes; Structure; Substantia nigra structure; Synapses; System; Technology; Testing; Thalamic structure; Time; Tracer; X-Ray Computed Tomography; algorithm development; attenuation; base; body system; brain health; data quality; density; design; detector; experience; experimental study; frontier; human subject; imager; imaging system; improved; in vivo imaging; kinetic model; locus ceruleus structure; neurochemistry; neurotransmitter release; next generation; novel; operation; pre-clinical; radiotracer; raphe nuclei; receptor; reconstruction; solid state; statistics; ultra high resolution; uptake

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.

脑部正电子发射断层扫描 (PET) 的研究应用已存在 40 多年。 定量 PET 系统与新型放射性示踪剂的结合产生了许多成像参数。 数字分析以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 与目前可用的大脑专用 PET 系统相比，在休息和激活期间具有重要的优势。 PET 系统的灵敏度和分辨率 然而，最先进的脑 PET 系统还没有达到这一水平。 因此，迫切需要建立下一代 HRRT。 该提案汇集了一支经验丰富的协作团队。 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) 共同开发下一代产品。 NeuroEXPLORER (NX) PET 系统具有以下具体目标 1：设计和构建。 NeuroEXPLORER：我们将在两年内完成设计并构建NX系统。设计包括高。 高性能 LYSO-SiPM 模块，配备小型探测器、4 毫米交互深度、250 ps 飞行时间 分辨率和约 50 厘米的轴向长度，与 CT 配对进行衰减校正。 有效灵敏度比 HRRT 高 10 倍，人脑实际分辨率为 1.5-2 毫米。 该系统将包括内置的实时最先进的运动跟踪摄像头，并将使用新颖的技术进行测试 模型实验来评估全方位的操作，以验证小范围的显着改进 具体目标 2：全定量脑 PET 的算法开发。 我们将利用 EXPLORER 的经验为该系统开发新颖的算法。 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 使用颈动脉形状和提供超高分辨率人脑图像的校正算法。 几何学，我们将开发精确测量血液活动的方法，以便与人体动脉数据进行比较 目标是无需动脉采样即可进行动力学建模，我们将开发降噪方法。 机器学习可减少研究健康大脑的剂量并消除对 CT 扫描的需要 具体目标 3：人类范式演示，我们将通过人类受试者进行评估。 具体的成像范例来证明 NX 系统的有效性：1）演示 灵敏度显着提高（与 HRRT 直接比较）及其对检测的影响 药理作用，2) 利用高灵敏度可靠地测量小细胞核的摄取；3) 开放 成像神经递质动力学的新领域，包括多巴胺和阿片类药物的释放最终目标。 是一个功能齐全且具有特征的系统，可极大地扩展大脑 PET 方案的范围， 应用程序。