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

人体兴奋和抑制的体内 3T 磁共振波谱测量

• 批准号: RGPIN-2017-03875
• 负责人: Harris, Ashley
• 金额: $ 2.19万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=653091
• 关键词: Vivo; 3T; Magnetic; Resonance; Spectroscopy

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.

核磁共振（NMR）光谱测量脑代谢物（神经化学）在体内，提供基本的洞察基本脑生理学。该研究项目将特别关注指示大脑兴奋、抑制和功能的代谢物。许多代谢物在1H光谱中是模糊的，难以区分。这项NSERC发现基金将开发改进、高效和特异性测量这些代谢物的方法，并整合测量方法，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掩盖的代谢物的一种方法是在获取时操纵光谱，这一过程被称为“编辑”。编辑减少了光谱以显示特定的代谢物（例如，GABA，主要抑制性神经递质；NAAG，谷氨酸调节剂；谷胱甘肽，氧化应激标志物）。这些收购持续时间很长，通常只测量一种代谢物，因此，为了比较代谢物，需要进行多次收购。在第一个目标中，将开发通过编辑检测多种代谢物的方法，包括共同编辑和双重编辑策略。******一些代谢产物，虽然丰富，有非常相似的光谱和区分这些光谱是具有挑战性的。其中一个例子就是谷氨酸和谷氨酰胺。谷氨酸主要存在于神经元中，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神经胶质细胞中，是谷氨酸的前体，在GABA合成中作为碳骨架。区分和准确定量谷氨酸和谷氨酰胺是高度相关的。第二个目标将开发谷氨酸和谷氨酰胺测量和适当的组织校正策略，以消除对体素中白质和灰质比例的测量依赖。******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BOLD激活对潜在GABA水平的依赖性，文献中存在差异。这可能是由于影响BOLD信号的代谢物建模不完整。在最终目的中，我们将对可能影响BOLD信号的多种代谢物进行综合研究，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发现基金将开发重要的技术来了解大脑的代谢、功能和激活。