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.

大脑正电子发射断层扫描（PET）的研究应用已经存在了40多年。 定量宠物系统与新型放射性示例的组合导致了许多成像 挖掘以了解正常的脑生理学，包括神经递质动力学和受体药理学 休息和激活期间。脑专用宠物系统比当前可用的重要优势 宠物系统在灵敏度和解决方案方面。但是，脑宠物的最先进还没有 超越了20岁的HRRT。因此，迫切需要建立下一代 人类研究的脑宠物系统。该建议汇集了一个经验丰富的合作团队 来自耶鲁大学，加州大学戴维斯分校和联合成像医疗保健美国（UIHA）。发展下一代 具有以下目的的Neuroxplorer（NX）PET系统。特定目标1：设计和构建 Neuroxplorer：在2年内，我们将完成设计并构建NX系统。设计包括高 带有小探测器的性能溶液-SIPM块，4毫米的交流，250 PS飞行时间 分辨率，轴向长度约为50 cm，与CT配对进行衰减校正。该设计将产生一个 与HRRT相比，有效敏感性高10，在人脑中实际分辨率为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机，并将使用小说进行测试 幻影实验，以评估全部操作，以验证小型的急剧改善 区域的精度和准确性。特定目的2：全量化脑宠物的算法开发。我们 将开发该系统的新算法。使用资源管理器的经验。我们将实施 重建算法以在时空和时间上产生具有均匀超高分辨率的动态图像， 延长耶鲁大学的HRRT运动校正经验，我们将开发基于相机的运动检测和 校正算法以提供超高分辨率的人脑图像。使用颈动脉形状和 几何形状，我们将开发方法以准确测量血液活性与人动脉数据进行比较 目的是允许动力学建模而无需进行伪影采样。我们将使用 机器学习以减少研究健康大脑的剂量，并消除对CT扫描的需求 衰减校正。特定目标3：人类范式示范。对于人类主题，我们将评估 特定的成像范例以证明NX系统的有效性：1）证明 显着敏感性提高（与HRRT直接比较）及其对检测的影响 药理学效应，2）利用高灵敏度可靠地测量小核中的吸收； 3）开放 成像神经递质动力学的新边界，包括多巴胺和阿片类药物释放。最终目标 是一个功能齐全和特征的系统，可显着扩大大脑宠物协议的范围和 申请。