Recent diffusion modeling studies aim to distinguish age-related degenerative processes specific to white matter fibers, such as axonal myelination and dispersion, from age-related elevated isotropic diffusivity, resulting from, e.g., enlargement of the extracellular space. Here we analytically investigate the relationship between two single-shell approaches for distinguishing these effects, respectively based on a one- and two-compartment model. We derive a nonlinear relationship between the models that renders a sensitivity advantage to the two-compartment model, and find that a linear elevation of an isotropic compartment with age explains the well-documented phenomenon of accelerated MD elevations (faster radially than axially) in aging.
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