title: The substrate of increased cortical FA in MS: A 7T post-mortem MRI and histopathology study.
abstract: 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.
  
  
  
  To test the proposed hypothesis that microglia activation is responsible for increased FA in cortical GM lesions.
  
  
  
  We investigated post-mortem cortical DTI changes in hemispheric, coronally cut sections and investigated the underlying histopathology using immunohistochemistry.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands le.jonkman@vumc.nl.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Jonkman
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Klaver
authors.affiliation: Department of Radiology, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Lazar
authors.initials: L
authors.lastname: Fleysher
authors.affiliation: Departments of Radiology, Neurology, and Neuroscience, Mount Sinai School of Medicine, New York, NY, USA/Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Inglese
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jeroen Jg
authors.initials: JJ
authors.lastname: Geurts
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology*
keywords: 7T MRI; DTI; FA; MD; cortical lesions; histopathology; multiple sclerosis