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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
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Multiple sclerosis normal-appearing white matter: pathology-imaging correlations.

Natalia M Moll1, Anna M Rietsch, Smitha Thomas

  • 1Neuroinflammation Research Center and Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Annals of Neurology
|December 14, 2011
PubMed
Summary
This summary is machine-generated.

Subtle MRI changes in normal-appearing white matter (NAWM) in multiple sclerosis (MS) are linked to axonal swelling near lesions and microglial activation farther away. These findings reveal distinct pathologic bases for white matter abnormalities in MS.

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Area of Science:

  • Neuroimaging
  • Neuropathology
  • Multiple Sclerosis Research

Background:

  • Subtle abnormalities in magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) are observed in normal-appearing white matter (NAWM) in multiple sclerosis (MS).
  • The underlying pathological basis for these imaging changes in NAWM remains incompletely understood.

Purpose of the Study:

  • To determine the pathological substrates of subtle MTR and DTI abnormalities in NAWM in MS brains.
  • To investigate the relationship between imaging parameters and specific neuropathological markers in different white matter regions.

Main Methods:

  • Utilized a rapid postmortem protocol with in situ magnetic resonance imaging (MRI) on MS brain tissues.
  • Analyzed four types of MRI-defined regions of interest: T2T1MTR lesions, NAWM close to lesions (sa-WM Close), NAWM far from lesions (sa-WM Far), and normal NAWM.
  • Performed immunohistochemical analysis for myelin, axonal markers, microglia/macrophages, astrocytes, plasma proteins, and blood vessels.

Main Results:

  • Regions close to white matter lesions (sa-WM Close) showed significantly more axonal swellings.
  • Activated microglia and macrophages were increased in lesions, sa-WM Far, and sa-WM Close regions compared to normal NAWM.
  • MTR and DTI measures correlated with myelin density, axonal area, and counts; however, in nonlesional white matter, these measures correlated with microglial activation, not axonal or myelin integrity.

Conclusions:

  • The pathological basis for MRI abnormalities in NAWM differs based on proximity to focal white matter lesions.
  • Axonal pathology and microglial activation are key contributors to subtle MRI changes near MS lesions.
  • Distant NAWM abnormalities may be driven by microglial activation related to cortical lesion proximity.