title: Imaging the tip of the iceberg: visualization of cortical lesions in multiple sclerosis.
abstract: BACKGROUND
  Cortical lesions (CLs) occur frequently in multiple sclerosis (MS), but only few CLs are observed on conventional magnetic resonance imaging (MRI). Why some CLs are visible and others are not is currently unknown. Here, we investigated whether CLs that are visible on conventional MRI differ from MRI-invisible CLs in terms of underlying histopathology and quantitative MRI (qMRI) measures.
  
  
  METHODS
  A total of 16 brain slices from 10 patients with chronic MS were analysed histopathologically and with conventional and qMRI. A region-of-interest approach was used to compare MRI-visible CLs with MRI-invisible CLs.
  
  
  RESULTS
  Although under-powering cannot be completely excluded in this study, MRI-visible CLs did not seem to differ from MRI-invisible CLs in terms of histopathology or qMRI measures. They were, however, significantly larger than their invisible counterparts (mean 13.3 ± 1.7 mm(2) versus 6.9 ± 1.3 mm(2); p = 0.001). Furthermore, the number of MRI-visible lesions correlated with the overall number of CLs in the brain slice (r = 0.96, p < 0.01) and with the overall percentage of demyelination (r = 0.78, p < 0.01) per hemispheric brain slice.
  
  
  CONCLUSIONS
  MRI visibility of CLs is determined by lesion size, and not by any distinctive underlying pathology. Visible CLs are associated with a higher total cortical lesion load, which suggests that when CLs in patients with MS become detectable on MRI, they merely represent 'the tip of the pathological iceberg'.
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. alex.seewann@gmail.com
authors.forename: Alexandra
authors.initials: A
authors.lastname: Seewann
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: Kooi
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Knol
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001921:Brain / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*