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

Area of Science:

• Neuroimaging
• Biophysics
• Histology

Background:

• Diffusion MRI (dMRI) offers noninvasive in vivo microscopy of brain microstructure.
• The Standard Model (SM) interprets dMRI signals using parameters like axon dispersion and water fractions.
• Histological validation is crucial for accurate interpretation of SM parameters.

Purpose of the Study:

• To perform a comprehensive histological validation of Standard Model (SM) parameters in diffusion MRI (dMRI).
• To evaluate the sensitivity and specificity of SM metrics against histological data.
• To facilitate clinical adoption of dMRI-derived SM parameters as biomarkers.

Main Methods:

• Characterized white matter microstructure in sham and injured rat brains using volume electron microscopy and ex vivo dMRI.
• Assessed SM parameter sensitivity by correlation with histological counterparts.
• Evaluated specificity by lack of correlation with non-corresponding histological features.

Main Results:

• The Standard Model with Imaging (SMI) demonstrated the highest sensitivity and specificity compared to other SM estimators.
• Derived the functional form of the fiber orientation distribution based on exponentially decreasing rotational invariants.
• Established a comprehensive comparison between dMRI-derived SM parameters and histological findings.

Conclusions:

• Histological validation supports the use of dMRI-derived SM parameters.
• SMI is identified as a sensitive and specific metric for white matter microstructure assessment.
• This work may promote the clinical use of dMRI-SM parameters for neurological disorder biomarkers.