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

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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.