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.

摘要：正电子发射断层扫描 (PET) 是研究活体大脑的独特工具，可用于研究活体大脑。 许多研究领域和临床实践来量化神经递质系统的分子成分 以及通过注射示踪剂剂量来掺入或代谢特定化合物 然而，目前的 PET 扫描仪需要受试者进行放射性标记的分子结合。 在扫描过程中保持静止，并且只能在足够大的中心使用以支持此类较新的设备。 便携式 PET 相机，例如 CerePETTM（Brain Biosciences, Inc.），正在为广泛的应用铺平道路。 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/神经系统疾病相关，并在脑损伤发生部位附近进行 PET。 与当前扫描仪相比，设备的增强灵敏度还可以减少所需的示踪剂注射剂量， 极大地促进疾病进展的纵向评估 便携式扫描仪可以从根本上改变。 PET 应用以及开发使用这些设备收集的数据的分析方法对于促进 定量 PET 的更广泛有效使用 便携式 PET 设备和 PET 使用的重大限制。 一般来说，成像需要在扫描过程中从受试者的手臂上采集动脉血样本，以获取当前的金 示踪剂摄取和与示踪剂血液水平相关的目标结合的标准定量。 采样存在风险，并且会让被成像的对象感到不舒服，我们的团队一直在开发新的。 从 PET 数据估计结果测量的方法，包括使用跨 在缺乏血液数据或参考区域的情况下，多个大脑区域可以利用可逆动力学来量化示踪剂。 我们在此寻求开发一种新方法来量化不可逆 PET 示踪剂的净流入率 我们将仅使用 PET 图像来收集 20 名健康志愿者的 PET 和动脉血数据。 在两个不同的 PET 相机中进行两次单独的扫描，在静止状态下成像，A) 当前的 PET 相机（西门子 BiographTM mCT) 和 B) 便携式 CerePETTM，在推注[18F]氟脱氧葡萄糖 (18F-FDG) 后， 具有不可逆动力学的示踪剂，最广泛用于量化葡萄糖代谢我们建议： 1) 开发一种新的基于组织的无血方法来量化 PET 不可逆示踪剂的净流入率， 并针对临床环境中常见的短扫描时间应用进行优化 2) 验证该方法； 使用新收集的 18F-FDG 数据与基于动脉血的定量进行比较 3) 开发和 传播软件例程库，用于实施经过验证的方法，以与当前和 便携式 PET 扫描仪，以允许将其纳入脑成像数据分析的流程中。 可以显着帮助扩大 18F-FDG 和其他示踪剂的定量全 PET 成像的应用 具有不可逆动力学，增强 PET 对理解大脑分子基础的贡献 疾病，并确定临床上有用的生物标志物。