  Biophysical modeling of diffusion MRI (dMRI) offers the exciting potential of
bridging the gap between the macroscopic MRI resolution and microscopic
cellular features, effectively turning the MRI scanner into a noninvasive in
vivo microscope. In brain white matter, the Standard Model (SM) interprets the
dMRI signal in terms of axon dispersion, intra- and extra-axonal water
fractions and diffusivities. However, for SM to be fully applicable and
correctly interpreted, it needs to be carefully evaluated using histology.
Here, we perform a comprehensive histological validation of the SM parameters,
by characterizing WM microstructure in sham and injured rat brains using volume
(3d) electron microscopy (EM) and ex vivo dMRI. Sensitivity is evaluated by how
close each SM metric is to its histological counterpart, and specificity by how
independent it is from other, non-corresponding histological features. This
comparison reveals that SM is sensitive and specific to microscopic properties,
clearing the way for the clinical adoption of in vivo dMRI derived SM
parameters as biomarkers for neurological disorders.
