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

Laura E. Jonkman, Roel Klaver, Lazar Fleysher, Matilde Inglese, Jeroen J.G. Geurts

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish
Pages (from-to)1804-1811
Number of pages8
JournalMultiple Sclerosis Journal
Issue number14
StatePublished - Dec 2016


  • 7T MRI
  • DTI
  • FA
  • MD
  • cortical lesions
  • histopathology
  • multiple sclerosis


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