The substrate of increased cortical FA in MS: A 7T post-mortem MRI and histopathology study

Mult Scler. 2016 Dec;22(14):1804-1811. doi: 10.1177/1352458516635290. Epub 2016 Mar 4.

Abstract

Background: Using diffusion tensor imaging (DTI), it was previously found that demyelinated gray matter (GM) lesions have increased fractional anisotropy (FA) when compared to normal-appearing gray matter (NAGM) in multiple sclerosis (MS). The biological substrate underlying this FA change is so far unclear; both neurodegenerative changes and microglial activation have been proposed as causal contributors.

Objective: To test the proposed hypothesis that microglia activation is responsible for increased FA in cortical GM lesions.

Methods: We investigated post-mortem cortical DTI changes in hemispheric, coronally cut sections and investigated the underlying histopathology using immunohistochemistry.

Results: Overall, there were few activated microglia/macrophages, and no difference between GM lesions and NAGM was observed. However, cell density was increased in GM lesions compared to NAGM (309.67 ± standard deviation (SD) 124.44 vs 249.95 ± SD 56.75, p = 0.002).

Conclusion: FA increase was not due to lesional and non-lesional differences in microglia activation and/or proliferation. We found an increase in general cellular density without a notable difference in cellular size, that is, tissue compaction, as a possible alternative explanation.

Keywords: 7T MRI; DTI; FA; MD; cortical lesions; histopathology; multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anisotropy
  • Diffusion Tensor Imaging / methods*
  • Female
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology*