title: Blood-brain barrier permeability of normal appearing white matter in relapsing-remitting multiple sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) affects the integrity of the blood-brain barrier (BBB). Contrast-enhanced T1 weighted magnetic resonance imaging (MRI) is widely used to characterize location and extent of BBB disruptions in focal MS lesions. We employed quantitative T1 measurements before and after the intravenous injection of a paramagnetic contrast agent to assess BBB permeability in the normal appearing white matter (NAWM) in patients with relapsing-remitting MS (RR-MS).
  
  
  RESULTS
  Fifty-nine patients (38 females) with RR-MS undergoing immunomodulatory treatment and nine healthy controls (4 females) underwent quantitative T1 measurements at 3 tesla before and after injection of a paramagnetic contrast agent (0.2 mmol/kg Gd-DTPA). Mean T1 values were calculated for NAWM in patients and total cerebral white matter in healthy subjects for the T1 measurements before and after injection of Gd-DTPA. The pre-injection baseline T1 of NAWM (945±55 [SD] ms) was prolonged in RR-MS relative to healthy controls (903±23 ms, p = 0.028). Gd-DTPA injection shortened T1 to a similar extent in both groups. Mean T1 of NAWM was 866±47 ms in the NAWM of RR-MS patients and 824±13 ms in the white matter of healthy controls. The regional variability of T1 values expressed as the coefficient of variation (CV) was comparable between the two groups at baseline, but not after injection of the contrast agent. After intravenous Gd-DTPA injection, T1 values in NAWM were more variable in RR-MS patients (CV = 0.198±0.046) compared to cerebral white matter of healthy controls (CV = 0.166±0.018, p = 0.046).
  
  
  CONCLUSIONS
  We found no evidence of a global BBB disruption within the NAWM of RR-MS patients undergoing immunomodulatory treatment. However, the increased variation of T1 values in NAWM after intravenous Gd-DTPA injection points to an increased regional inhomogeneity of BBB function in NAWM in relapsing-remitting MS.
authors: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark. hlund@drcmr.dk
authors: Henrik
authors: H
authors: Lund
authors: Martin
authors: M
authors: Krakauer
authors: Arnold
authors: A
authors: Skimminge
authors: Finn
authors: F
authors: Sellebjerg
authors: Ellen
authors: E
authors: Garde
authors: Hartwig R
authors: HR
authors: Siebner
authors: Olaf B
authors: OB
authors: Paulson
authors: Dan
authors: D
authors: Hesse
authors: Lars G
authors: LG
authors: Hanson
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D019786:Gadolinium DTPA / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D010539:Permeability
chemical_list: D019786:Gadolinium DTPA