title: Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease.
abstract: As blood-brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)-MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage.
  
  
  
  We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter.
  
  
  
  Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions.
  
  
  
  We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.
authors.affiliation: From the Departments of Neurology (C.E.Z., J.S., R.J.v.O.) and Radiology & Nuclear Medicine (S.M.W., H.J.v.d.H., J.F.A.J., C.R.L.P.N.J., P.A.M.H., W.H.B.), Maastricht University Medical Centre; Cardiovascular Research Institute Maastricht (CARIM) (C.E.Z., R.J.v.O.); and School for Mental Health and Neuroscience (MHeNS) (C.E.Z., S.M.W., H.J.v.d.H., J.S., J.F.A.J., P.A.M.H., R.J.v.O., W.H.B.), Maastricht, the Netherlands. eleana.zhang@mumc.nl.
authors.forename: C Eleana
authors.initials: CE
authors.lastname: Zhang
authors.affiliation: From the Departments of Neurology (C.E.Z., J.S., R.J.v.O.) and Radiology & Nuclear Medicine (S.M.W., H.J.v.d.H., J.F.A.J., C.R.L.P.N.J., P.A.M.H., W.H.B.), Maastricht University Medical Centre; Cardiovascular Research Institute Maastricht (CARIM) (C.E.Z., R.J.v.O.); and School for Mental Health and Neuroscience (MHeNS) (C.E.Z., S.M.W., H.J.v.d.H., J.S., J.F.A.J., P.A.M.H., R.J.v.O., W.H.B.), Maastricht, the Netherlands.
authors.forename: Sau May
authors.initials: SM
authors.lastname: Wong
authors.affiliation: From the Departments of Neurology (C.E.Z., J.S., R.J.v.O.) and Radiology & Nuclear Medicine (S.M.W., H.J.v.d.H., J.F.A.J., C.R.L.P.N.J., P.A.M.H., W.H.B.), Maastricht University Medical Centre; Cardiovascular Research Institute Maastricht (CARIM) (C.E.Z., R.J.v.O.); and School for Mental Health and Neuroscience (MHeNS) (C.E.Z., S.M.W., H.J.v.d.H., J.S., J.F.A.J., P.A.M.H., R.J.v.O., W.H.B.), Maastricht, the Netherlands.
authors.forename: Harm J
authors.initials: HJ
authors.lastname: van de Haar
authors.affiliation: From the Departments of Neurology (C.E.Z., J.S., R.J.v.O.) and Radiology & Nuclear Medicine (S.M.W., H.J.v.d.H., J.F.A.J., C.R.L.P.N.J., P.A.M.H., W.H.B.), Maastricht University Medical Centre; Cardiovascular Research Institute Maastricht (CARIM) (C.E.Z., R.J.v.O.); and School for Mental Health and Neuroscience (MHeNS) (C.E.Z., S.M.W., H.J.v.d.H., J.S., J.F.A.J., P.A.M.H., R.J.v.O., W.H.B.), Maastricht, the Netherlands.
authors.forename: Julie
authors.initials: J
authors.lastname: Staals
authors.affiliation: From the Departments of Neurology (C.E.Z., J.S., R.J.v.O.) and Radiology & Nuclear Medicine (S.M.W., H.J.v.d.H., J.F.A.J., C.R.L.P.N.J., P.A.M.H., W.H.B.), Maastricht University Medical Centre; Cardiovascular Research Institute Maastricht (CARIM) (C.E.Z., R.J.v.O.); and School for Mental Health and Neuroscience (MHeNS) (C.E.Z., S.M.W., H.J.v.d.H., J.S., J.F.A.J., P.A.M.H., R.J.v.O., W.H.B.), Maastricht, the Netherlands.
authors.forename: Jacobus F A
authors.initials: JF
authors.lastname: Jansen
authors.affiliation: From the Departments of Neurology (C.E.Z., J.S., R.J.v.O.) and Radiology & Nuclear Medicine (S.M.W., H.J.v.d.H., J.F.A.J., C.R.L.P.N.J., P.A.M.H., W.H.B.), Maastricht University Medical Centre; Cardiovascular Research Institute Maastricht (CARIM) (C.E.Z., R.J.v.O.); and School for Mental Health and Neuroscience (MHeNS) (C.E.Z., S.M.W., H.J.v.d.H., J.S., J.F.A.J., P.A.M.H., R.J.v.O., W.H.B.), Maastricht, the Netherlands.
authors.forename: Cécile R L P N
authors.initials: CR
authors.lastname: Jeukens
authors.affiliation: From the Departments of Neurology (C.E.Z., J.S., R.J.v.O.) and Radiology & Nuclear Medicine (S.M.W., H.J.v.d.H., J.F.A.J., C.R.L.P.N.J., P.A.M.H., W.H.B.), Maastricht University Medical Centre; Cardiovascular Research Institute Maastricht (CARIM) (C.E.Z., R.J.v.O.); and School for Mental Health and Neuroscience (MHeNS) (C.E.Z., S.M.W., H.J.v.d.H., J.S., J.F.A.J., P.A.M.H., R.J.v.O., W.H.B.), Maastricht, the Netherlands.
authors.forename: Paul A M
authors.initials: PA
authors.lastname: Hofman
authors.affiliation: From the Departments of Neurology (C.E.Z., J.S., R.J.v.O.) and Radiology & Nuclear Medicine (S.M.W., H.J.v.d.H., J.F.A.J., C.R.L.P.N.J., P.A.M.H., W.H.B.), Maastricht University Medical Centre; Cardiovascular Research Institute Maastricht (CARIM) (C.E.Z., R.J.v.O.); and School for Mental Health and Neuroscience (MHeNS) (C.E.Z., S.M.W., H.J.v.d.H., J.S., J.F.A.J., P.A.M.H., R.J.v.O., W.H.B.), Maastricht, the Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van Oostenbrugge
authors.affiliation: From the Departments of Neurology (C.E.Z., J.S., R.J.v.O.) and Radiology & Nuclear Medicine (S.M.W., H.J.v.d.H., J.F.A.J., C.R.L.P.N.J., P.A.M.H., W.H.B.), Maastricht University Medical Centre; Cardiovascular Research Institute Maastricht (CARIM) (C.E.Z., R.J.v.O.); and School for Mental Health and Neuroscience (MHeNS) (C.E.Z., S.M.W., H.J.v.d.H., J.S., J.F.A.J., P.A.M.H., R.J.v.O., W.H.B.), Maastricht, the Netherlands.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Backes
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000503:physiopathology; D059345:Cerebral Small Vessel Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D003287:Contrast Media; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D010953:Plasma Volume / Q000502:physiology; D012720:Severity of Illness Index; D012727:Sex Characteristics; D066127:White Matter / Q000000981:diagnostic imaging / Q000503:physiopathology
chemical_list: D003287:Contrast Media