While most brain metabolites detected by in vivo MRS are intracellular, some of them, in particular energy metabolism substrates such as glucose, lactate and acetate, are also known to be significantly present in the extracellular space. Although of high metabolic significance and of practical importance for metabolic flux quantification in labeling studies, the accurate determination of the extracellular fraction remains challenging. Here we propose to use diffusion-weighted MRS combined with modeling of tissue microstructure to estimate acetate’s extracellular fraction in the rat brain, which we find to be ~45%.
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