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: 10471435
• 负责人: Richard E. Carson
• 金额: $ 206.75万
• 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/10471435
• 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.

脑正电子发射断层扫描(PET)的研究应用已有40多年的历史。 定量PET系统与新型放射性示踪剂的结合已经导致了大量的成像辅助。 了解包括神经递质动力学和受体药理学在内的正常脑生理学 在休息和激活过程中。大脑专用PET系统比目前可用的系统具有重要的优势 PET系统在灵敏度和分辨率方面的优势。然而，脑部PET的最新技术并没有 超过了已有20年历史的HRRT。因此，迫切需要建立下一代 用于人体研究的脑PET系统。这项提议汇集了一支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联合成像医疗美国公司(UIHA)。发展下一代 NeuroEXPLORER(NX)PET系统具有以下目标。具体目标1：设计和建造 NeuroEXPLORER：在两年内，我们将完成NX系统的设计和建造。该设计包括高 高性能Lyso-SiPM块，带有小探测器、4 mm交互深度、250 ps飞行时间 分辨率和轴向长度约50厘米，与CT配对进行衰减校正。这种设计将产生一种 有效灵敏度比HRRT高10倍，人脑实际分辨率为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，并将使用新颖的 评估全范围操作的幻影实验，以验证在小范围- 区域精确度和准确度。具体目标2：全定量脑正电子发射计算机断层扫描算法开发。我们 将为这个系统开发新的算法。使用资源管理器的经验。我们将实施 重建算法，以产生在空间和时间上具有统一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 提供超高分辨率人脑图像的校正算法。使用颈动脉的形状和 几何学，我们将开发准确测量血液活动的方法，并将其与人类动脉数据进行比较 其目标是允许在没有动脉采样的情况下进行动力学建模。我们将开发降噪方法，包括 机器学习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：人类范式示范。对于人类受试者，我们将评估 演示NX系统有效性的特定成像范例：1)演示 敏感度显著提高(与HRRT直接比较)及其对检测 药理效应；2)利用高灵敏度可靠地测量小核团的摄取；以及3)开放 成像神经递质动力学的新前沿，包括多巴胺和阿片类药物释放。终极目标 是一个全功能和特色化的系统，极大地扩展了Brain PET协议和 申请。