Related Experiment Video
Updated: May 16, 2026
Assessing Cortical Cerebral Microinfarcts on High Resolution MR Images
Published on: November 20, 2015
A quantitative postmortem MRI design sensitive to white matter hyperintensity differences and their relationship with
Melissa E Murray1, Prashanthi Vemuri, Greg M Preboske
1Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA. murray.melissa@mayo.edu
Abstract:
White matter hyperintensities (WMHs) associate with both cognitive slowing and motor dysfunction in the neurologically normal elderly. A full understanding of the pathology underlying this clinicoradiologic finding is currently lacking in autopsy-confirmed normal brains. To determine the histopathologic basis of WMH seen on magnetic resonance imaging, we studied the relationship between postmortem fluid-attenuated inversion recovery (FLAIR) intensity and neuropathologic markers of WM lesions (WMLs) that correspond to WMH in cognitively normal aging brains. Samples of periventricular (n = 24), subcortical (n = 26), and normal-appearing WM (NAWM, n = 31) from 4clinically and pathologically confirmed normal cases were examined. The FLAIR intensity, vacuolation, and myelin basic protein immunoreactivity loss were significantly higher in periventricular WML versus subcortical WML; both were higher than in NAWM. The subcortical WML and NAWM had significantly less axonal loss, astrocytic burden, microglial density, and oligodendrocyte loss than those of the periventricular WML. Thus, vacuolation, myelin density, and small vessel density contribute to the rarefaction of WM, whereas axonal density, oligodendrocyte density, astroglial burden, and microglial density did not. These data suggest that the age-related loss of myelin basic protein and the decrease in small vessel density may contribute to vacuolation of WM. Vacuolation enables interstitial fluid to accumulate, which contributes to the prolonged T2 relaxation and elevated FLAIR intensity in the WM.
Insights
White matter hyperintensities (WMH) in older adults are linked to cognitive and motor issues. Histopathology reveals that myelin loss and reduced small vessel density contribute to WMH, impacting brain function.
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.
