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Modeling diffusion of intracellular metabolites in the mouse brain up to very high diffusion-weighting: Diffusion in long fibers (almost) accounts for non-monoexponential attenuation.

PURPOSE: To investigate how intracellular metabolites diffusion measured in vivo up to very high q/b in the mouse brain can be explained in terms of simple geometries.

METHODS: 10 mice were scanned using our new STE-LASER sequence, at 11.7 Tesla (T), up to qmax  = 1 μm-1 at diffusion time td  = 63.2 ms, corresponding to bmax  = 60 ms/µm². We model cell fibers as randomly oriented cylinders, with radius a and intracellular diffusivity Dintracyl, and fit experimental data as a function of q to estimate Dintracyl and a.

RESULTS: Randomly oriented cylinders account well for measured attenuation, giving fiber radii and Dintracyl in the expected ranges (0.5-1.5 µm and 0.30-0.45 µm2 /ms, respectively). The only exception is N-acetyl-aspartate (NAA) (extracted a∼0), which we show to be compatible with a small fraction of the NAA pool being confined in highly restricted compartments (with short T2 ).

CONCLUSION: The non-monoexponential signal attenuation of intracellular metabolites in the mouse brain can be described by diffusion in long and thin cylinders, yielding realistic Dintra and fiber diameters. However, this simple model may require small "corrections" for NAA, in the form of a small fraction of the NAA signal originating from a highly restricted compartment. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

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