In Vivo 3T Magnetic Resonance Spectroscopy Measurements of Excitation and Inhibition in Humans

核磁共振(核磁共振)波谱测量活体中的大脑代谢物(神经化学)，提供对基本大脑生理学的基本见解。这项研究计划将特别关注表明大脑兴奋、抑制和功能的代谢物。这些代谢物中的许多在1H谱上是模糊的，很难区分。NSERC Discovery Grant将开发改进、高效和具体测量这些代谢物的方法，并整合各种措施，以了解用于功能成像的血氧水平依赖(BOLD)信号的基础。检测被更丰富的代谢物遮挡的代谢物的一种方法是在采集时操纵光谱，这一过程被称为“编辑”。编辑减少光谱以揭示特定的代谢物(例如，GABA，主要的抑制性神经递质；NAAG，谷氨酸的调节剂；谷胱甘肽，氧化应激的标志)。这些采集持续时间较长，通常只测量一种代谢物，因此，为了比较代谢物，需要多次采集。在第一个目标中，将开发利用编辑来检测多个代谢物的方法，包括联合编辑和双重编辑策略。一些代谢物虽然丰富，但具有非常相似的光谱，区分这些光谱是具有挑战性的。其中一个例子是谷氨酸和谷氨酰胺。谷氨酸主要定位于神经元，是主要的兴奋性神经递质，在细胞代谢中起着重要作用。谷氨酰胺主要存在于胶质细胞中，是谷氨酸的前体，是合成GABA的碳链。区分和准确地定量谷氨酸和谷氨酰胺是高度相关的。第二个目标是开发谷氨酸和谷氨酰胺测量以及适当的组织校正策略，以消除测量对体素中白质和灰质比例的依赖。BOLD成像正迅速成为认知神经科学研究中最常用的工具之一。关于大胆激活依赖于潜在的GABA水平，文献中有不同之处。这可能是由于对影响BOLD信号的代谢物建模不完整所致。最终，对可能影响BOLD信号的多种代谢物的综合研究将被整合起来，以提高我们对BOLD信号和大脑激活的潜在影响的理解。这项NSERC发现拨款将开发出了解大脑新陈代谢、功能和激活的重要技术。

Nuclear Magnetic Resonance (NMR) spectroscopy measures brain metabolites (neurochemistry) in vivo, providing fundamental insight into basic brain physiology. This research program will specifically focus on metabolites that indicate brain excitation, inhibition and function. Many of these metabolites are obscured and difficult to differentiate in the 1H spectrum. This NSERC Discovery Grant will develop methods for improved, efficient and specific measurement of these metabolites and integrate measures to understand the basis of the blood oxygen level dependent (BOLD) signal used for functional imaging.One method to detect metabolites that are obscured by more abundant metabolites is to manipulate the spectrum at acquisition, a process known as “editing”. Editing reduces the spectrum to reveal a particular metabolite (e.g., GABA, the primary inhibitory neurotransmitter; NAAG, a modulator of glutamate; glutathione, a marker of oxidative stress). These acquisitions are long in duration and typically only measure one metabolite, therefore, to compare metabolites, multiple acquisitions are required. In the first aim, methods to detect multiple metabolites with editing will be developed, including co-editing and dual-editing strategies.Some metabolites, while abundant, have very similar spectra and differentiating these spectra is challenging. One example of this is glutamate and glutamine. Glutamate, primarily located in neurons, is the primary excitatory neurotransmitter and has a fundamental role in cell metabolism. Glutamine, primarily in glia, is a precursor for glutamate and serves as the carbon backbone in GABA synthesis. Differentiating and accurately quantifying glutamate and glutamine is highly relevant. The second aim will develop glutamate and glutamine measurements and appropriate tissue correction strategies to remove measurement dependency on the proportions of white matter and grey matter in the voxel.BOLD imaging is rapidly becoming one of the most-used tools in cognitive neuroscience research. There are discrepancies in the literature as to the dependency of BOLD activation on underlying GABA levels. This may be due to incomplete modeling of the metabolites that impact the BOLD signal. In the final aim, a comprehensive study of multiple metabolites that may impact the BOLD signal will be integrated to improve our understanding of the underlying influences of the BOLD signal and brain activation.This NSERC Discovery Grant will develop important techniques to understand brain metabolism, function and activation.