Noninvasive Quantification of Brain Glucose Metabolism Using a Portable Positron Emission Tomography Camera.

使用便携式正电子发射断层扫描相机对脑葡萄糖代谢进行无创定量。

• 批准号: 9891057
• 负责人: Francesca Zanderigo
• 金额: $ 46.72万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891057
• 关键词: Affect; Area; Athletic; Benchmarking; Binding; Biological; Biological Markers; Biological Sciences; Blood; Blood specimen; Bolus Infusion; Brain; Brain Diseases; Brain Injuries; Brain imaging; Brain region; Catheterization; Clinical; Communities; Computer software; Conflict (Psychology); Cues; Data; Data Analyses; Development; Devices; Diagnosis; Disease Progression; Dose; Drug Monitoring; Environment; Future; Gender; Generations; Glucose; Gold; Human; Image; Injections; Kinetics; Label; Libraries; Mental disorders; Metabolic; Metabolism; Methods; Military Personnel; Modeling; Molecular; Neurology; Neurotransmitters; Oncology; Outcome; Outcome Measure; Positron-Emission Tomography; Prevention; Procedures; Psychiatry; Pythons; Radioactive; Randomized; Research; Resolution; Rest; Risk; Scanning; Signal Transduction; Site; Specialized Center; Standardization; System; Technology; Testing; Time; Tissues; Tracer; Validation; Work; aging brain; analysis pipeline; analytical method; arm; base; brain tissue; clinical application; clinical biomarkers; clinical practice; fluorodeoxyglucose; glucose metabolism; healthy volunteer; improved; interest; kinetic model; metabolic rate; nervous system disorder; neurochemistry; neurosurgery; novel; novel strategies; novel therapeutics; portability; response; tool; uptake

Abstract. Positron Emission Tomography (PET) is a unique tool for investigating the living brain and is used in many research fields and clinical practice to quantify molecular components of neurotransmitter systems as well as the incorporation or metabolism of specific compounds through the injection of tracer doses of radioactively labeled molecules that bind to a brain target. Current PET scanners, however, require the subject to lie still during scanning, and can only be used in centers large enough to support such a device. Newer portable PET cameras, such as CerePETTM (Brain Biosciences, Inc.), are paving the way for a wide array of novel applications, including quantifying metabolic and neurochemical responses to environmental cues relevant to psychiatric/neurological diseases and performing PET close to sites where brain injury occurs. The device’s enhanced sensitivity over current scanners can also result in reduced required injected dose of tracer, greatly facilitating longitudinal assessments of disease progression. Portable scanners can radically transform PET applications, and developing analytic methods for data collected using these devices is critical to facilitate a broader valid use of quantitative PET. A significant limitation in the use of portable PET devices, and PET imaging in general, is the need for arterial blood sampling from the subject’s arm during scan, for current gold- standard quantification of tracer uptake and binding to the target in relation to tracer blood levels. Arterial blood sampling carries risks and is uncomfortable for the subject being imaged. Our group has been developing new methods to estimate outcome measures from PET data, including using simultaneous modeling across multiple brain regions to quantify tracers with reversible kinetics in absence of blood data or a reference region. We seek here to develop a new method to quantify the net influx rate of PET tracers with irreversible kinetics using only PET images. We will gather PET and arterial blood data in 20 healthy volunteers, who will be imaged at rest in two separate scans in two different PET cameras, A) a current PET camera (Siemens BiographTM mCT) and B) the portable CerePETTM, after a bolus infusion of [18F]fluorodeoxyglucose (18F-FDG), a tracer with irreversible kinetics that is the most widely used to quantify glucose metabolism. We propose to: 1) Develop a new tissue-based, blood-free method to quantify the net influx rate of PET irreversible tracers, and optimize it for application with short scan times, common in clinical settings; 2) Validate the method in comparison to arterial blood-based quantification using the newly collected 18F-FDG data; 3) Develop and disseminate a library of software routines for implementation of the validated method for use with current and portable PET scanners, to allow its incorporation into pipelines for analysis of brain imaging data. This method can significantly help widen the application of fully quantitative PET imaging with 18F-FDG and other tracers with irreversible kinetics, and enhance PET contribution to understanding the molecular underpinnings of brain disorders, and identifying clinically useful biomarkers.

抽象的。正电子发射断层扫描（PET）是研究活体大脑的独特工具，用于 许多研究领域和临床实践将神经递质系统的分子成分定量为 以及通过注射示踪剂剂量的特定化合物的合并或代谢 与大脑靶标结合的放射性标记分子。但是，当前的宠物扫描仪需要该主题 在扫描过程中静止不动，只能用于足够大的中心以支撑此设备。较新 便携式宠物摄像机，例如Cerepettm（Brain Biosciences，Inc。） 新颖的应用，包括量化对环境线索的代谢和神经化学反应 与精神病/神经系统疾病有关，并在发生脑损伤的部位附近进行宠物。这 设备对当前扫描仪的灵敏度增强也可能导致减少所需的注射剂量示踪剂， 极大地支持疾病进展的纵向评估。便携式扫描仪可以从根本上转换 宠物应用程序，并为使用这些设备收集的数据开发分析方法至关重要 定量宠物的更广泛的有效使用。使用便携式宠物设备和宠物的使用限制很大 一般而言，成像是在扫描过程中需要从受试者的手臂中进行动脉血液采样，目前的金 - 与示踪剂血液水平有关的示踪剂吸收并与靶标结合的标准定量。动脉血 采样会带来风险，并且对被成像的受试者感到不舒服。我们的小组一直在发展新的 从PET数据中估算结果度量的方法，包括使用跨越的简单建模 在没有血液数据或参考区域的情况下，多个大脑区域可量化具有可逆动力学的示踪剂。 我们在这里寻求开发一种新方法，以量化不可逆的宠物示踪剂的净影响率 动力学仅使用宠物图像。我们将在20位健康志愿者中收集宠物和动脉血数据，他们将 在两个不同的宠物摄像机中进行两次单独的扫描中的休息成像，a）当前的宠物相机（西门子 大满贯的小肠MCT）和B）在注入[18F]氟脱氧葡萄糖（18F-FDG）之后，便携 具有不可逆动力学的示踪剂，是用于量化葡萄糖代谢的最广泛使用的示踪剂。我们建议： 1）开发一种新的基于组织的，无血液的方法来量化PET不可逆示踪剂的净影响率， 并在临床环境中常见的短扫描时间进行优化以适用于扫描时间； 2）验证该方法 使用新收集的18F-FDG数据与基于动脉血液的定量进行比较； 3）发展和 传播软件例程库，以实现经过验证的方法，以与当前和 便携式宠物扫描仪，使其允许将其合并到管道中以分析脑成像数据。此方法 可以大大帮助扩大使用18F-FDG和其他示踪剂的完全定量PET成像的应用 具有不可逆转的动力学，并增强了PET对理解大脑分子基础的贡献 疾病，并识别临床上有用的生物标志物。