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

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， 许多研究领域和临床实践来量化神经递质系统的分子组分， 以及通过注射示踪剂剂量的 放射性标记的分子结合到大脑目标上。然而，目前的PET扫描仪需要受试者 在扫描过程中静止不动，只能在足够大的中心使用，以支持这样的设备。较新 便携式PET照相机，例如CerePET ™（BrainBiosciences，Inc.），正在为一系列 新的应用，包括量化代谢和神经化学反应的环境线索， 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。的 设备相对于当前扫描仪的增强的灵敏度还可以导致减少所需的示踪剂注射剂量， 极大地促进了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，并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的更广泛的有效使用。便携式PET设备的使用中的一个显著限制，并且PET 一般来说，成像是在扫描期间需要从受试者的手臂进行动脉血液采样，对于当前的金- 与示踪剂血液水平相关的示踪剂摄取和与靶的结合的标准定量。动脉血 采样具有风险并且对于被成像的对象来说是不舒服的。我们的团队一直在开发新的 从PET数据估计结局指标的方法，包括使用跨 多个大脑区域，以在没有血液数据或参考区域的情况下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的方法来量化PET示踪剂的净流入率， 仅使用PET图像的动力学。我们将收集20名健康志愿者的PET和动脉血数据， 在两个不同的PET相机中的两个单独的扫描中在静止时成像，A）当前的PET相机（Siemens BiographTM mCT）和B）便携式CerePET TM，在推注[18 F]氟脱氧葡萄糖（18 F-FDG）后， 一种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液方法，以量化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）将该方法应用于 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 传播用于实施经验证方法的软件例程库， 便携式PET扫描仪，以允许将其并入用于分析脑成像数据的管道中。该方法 可显著拓宽18F-FDG和其他示踪剂的全定量PET成像的应用 具有不可逆动力学，并增强PET对理解大脑分子基础的贡献 疾病和鉴定临床上有用的生物标志物。

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.