A quantitative postmortem MRI design sensitive to white matter hyperintensity differences and their relationship with...

Area of Science:

• Neuropathology
• Neuroimaging
• Aging Brain

Background:

• White matter hyperintensities (WMH) are common in the elderly and associated with cognitive slowing and motor dysfunction.
• The precise histopathologic underpinnings of WMH in normal aging brains remain incompletely understood.

Purpose of the Study:

• To investigate the neuropathologic basis of white matter lesions (WMLs) corresponding to WMH.
• To correlate postmortem fluid-attenuated inversion recovery (FLAIR) intensity with specific neuropathologic markers in normal aging brains.

Main Methods:

• Examined periventricular, subcortical, and normal-appearing white matter (NAWM) samples from 4 clinically and pathologically normal elderly individuals.
• Assessed FLAIR intensity, vacuolation, myelin basic protein (MBP) loss, axonal loss, astrocytic burden, microglial density, and oligodendrocyte loss.

Main Results:

• Periventricular WMLs showed higher FLAIR intensity, vacuolation, and MBP loss compared to subcortical WMLs and NAWM.
• Subcortical WMLs and NAWM had less axonal loss, astrocytic burden, microglial density, and oligodendrocyte loss than periventricular WMLs.
• Vacuolation, myelin density, and small vessel density correlated with white matter rarefaction.

Conclusions:

• Age-related myelin basic protein loss and decreased small vessel density may drive vacuolation in white matter.
• Vacuolation leads to interstitial fluid accumulation, contributing to elevated FLAIR intensity observed in WMH.
• Understanding these histopathologic changes is crucial for interpreting WMH in aging brains.