Volume electron microscopy in injured rat brain validates white matter microstructure metrics from diffusion MRI

TL;DR

This study validates the biophysical Standard Model of diffusion MRI in rat brain white matter using volume electron microscopy, confirming its potential for noninvasive microscopic brain imaging and biomarker development.

Contribution

It provides a comprehensive histological validation of the Standard Model parameters, demonstrating their sensitivity and specificity to microscopic microstructure features.

Findings

SM parameters closely match histological microstructure features

SM shows high sensitivity to axon dispersion and water fractions

SM parameters are specific and independent from unrelated tissue features

Abstract

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.