Intracellular metabolites in the primate brain are primarily localized in long fibers rather than in cell bodies, as shown by diffusion-weighted magnetic resonance spectroscopy

Due to their pure intracellular compartmentation, the translational diffusion of brain metabolites in vivo depends on the intracellular environment, including viscosity, molecular crowding and subcellular structures. However, as the diffusion time is increased, metabolites have enough time to significantly encounter cell boundaries, so that cell size and geometry are expected to strongly determine metabolite diffusion path. In the present work, diffusion-weighted nuclear magnetic resonance spectroscopy was used to investigate brain metabolite diffusion in vivo, at long and ultra-long diffusion times (from ~ 80 ms to more than 1 s), in a voxel with equal proportions of white and grey matter in macaque monkeys. No dramatic dependence of the ADC on the diffusion time was observed, suggesting that metabolites' apparent diffusion is largely unrestricted over these time-scales. In an attempt to explain this stability and relate it to plausible cell geometries, data were analyzed with two simple geometrical models describing diffusion either in fibers such as axons, dendrites and astrocytic processes, or in closed cell bodies. Results support the idea that DW-MRS is sensitive to cell shape, and that a vast fraction of brain metabolites is diffusing in long fibers rather than being confined in cell bodies.