title: Increased perfusion in normal appearing white matter in high inflammatory multiple sclerosis patients.
abstract: OBJECTIVE
  Although cerebral perfusion alterations have long been acknowledged in multiple sclerosis (MS), the relationship between measurable perfusion changes and the status of highly active MS has not been examined. We hypothesized that alteration of perfusion can be detected in normal appearing white matter and is increased in high inflammatory patients.
  
  
  METHODS
  Thirty-three patients with relapsing-remitting MS underwent four monthly 3T MRI scans including dynamic susceptibility contrast perfusion-weighted MRI. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured in normal appearing white matter. Patients were stratified in a high- and low-inflammatory group according to the number of new contrast enhancing lesions.
  
  
  RESULTS
  Thirteen patients were classified as high-inflammatory. Compared to low-inflammatory patients, the high-inflammatory group demonstrated significantly higher CBV (p = 0.001) and CBF (p = 0.014) values. A mixed model analysis to assess independent variables associated with CBV and CBF revealed that white matter lesion load and atrophy measurements had no significant influence on CBF and CBV.
  
  
  CONCLUSIONS
  This work provides evidence that high inflammatory lesion load is associated with increased CBV and CBF, underlining the role of global modified microcirculation prior to leakage of the blood-brain barrier in the pathophysiology of MS. Perfusion changes might therefore be sensitive to active inflammation apart from lesion development without local blood-brain barrier breakdown, and could be utilized to further assess the metabolic aspect of current inflammation.
authors.affiliation: Department of Diagnostic and Interventional Neuroradiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Maxim
authors.initials: M
authors.lastname: Bester
authors.affiliation: Department of Diagnostic and Interventional Neuroradiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Department of Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
authors.forename: Nils Daniel
authors.initials: ND
authors.lastname: Forkert
authors.affiliation: Department of Neurology, Institute for Neuroimmunology and Clinical MS Research, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jan Patrick
authors.initials: JP
authors.lastname: Stellmann
authors.forename: Klarissa
authors.initials: K
authors.lastname: Stürner
authors.affiliation: Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Lilian
authors.initials: L
authors.lastname: Aly
authors.affiliation: Department of Medical Biometry and Epidemiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Drabik
authors.affiliation: Department of Neurology, Institute for Neuroimmunology and Clinical MS Research, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Kim Lea
authors.initials: KL
authors.lastname: Young
authors.affiliation: Department of Neurology, Institute for Neuroimmunology and Clinical MS Research, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Heesen
authors.affiliation: Department of Diagnostic and Interventional Neuroradiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Fiehler
authors.affiliation: Department of Diagnostic and Interventional Neuroradiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Siemonsen
mesh_terms: D000328:Adult; D002560:Cerebrovascular Circulation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000503:physiopathology; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000503:physiopathology*; D011446:Prospective Studies; D066127:White Matter / Q000098:blood supply* / Q000503:physiopathology; D055815:Young Adult