title: Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI.
abstract: OBJECTIVE
  To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics.
  
  
  METHODS
  Dynamic contrast-enhanced MRI was used to measure BBB permeability in 27 patients with MS and compared to 24 matched healthy controls.
  
  
  RESULTS
  Permeability measured as K(trans) was significantly higher in periventricular normal appearing white matter (NAWM) and thalamic gray matter in MS patients when compared to healthy controls, with periventricular NAWM showing the most pronounced difference. Recent relapse coincided with significantly higher permeability in periventricular NAWM, thalamic gray matter, and MS lesions. Immunomodulatory treatment and recent relapse were significant predictors of permeability in MS lesions and periventricular NAWM. Our results suggest that after an MS relapse permeability gradually decreases, possibly an effect of immunomodulatory treatment.
  
  
  CONCLUSIONS
  Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS.
authors.affiliation: Functional Imaging Unit, Dept. of Diagnostics, Glostrup Hospital, University of Copenhagen, Denmark ; Dept. of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
authors.forename: S P
authors.initials: SP
authors.lastname: Cramer
authors.affiliation: Functional Imaging Unit, Dept. of Diagnostics, Glostrup Hospital, University of Copenhagen, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Simonsen
authors.affiliation: Dept. of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
authors.forename: J L
authors.initials: JL
authors.lastname: Frederiksen
authors.affiliation: Functional Imaging Unit, Dept. of Diagnostics, Glostrup Hospital, University of Copenhagen, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Rostrup
authors.affiliation: Functional Imaging Unit, Dept. of Diagnostics, Glostrup Hospital, University of Copenhagen, Denmark ; Dept. of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: H B W
authors.initials: HB
authors.lastname: Larsson
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology; D003287:Contrast Media; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D055420:Perfusion Imaging; D012720:Severity of Illness Index; D066127:White Matter / Q000473:pathology
chemical_list: D003287:Contrast Media
keywords: Blood–brain barrier; DCE MRI; Disease modifying therapy; MRI; Multiple sclerosis; Perfusion MRI