Blood-brain barrier leakage is more widespread in patients …

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.

MeSH Terms

Aged Aging/metabolism Blood-Brain Barrier/diagnostic imaging,physiopathology Capillary Permeability/physiology Cardiovascular Diseases/physiopathology Cerebral Small Vessel Diseases/diagnostic imaging,physiopathology Contrast Media Female Gray Matter/diagnostic imaging,physiopathology Humans Image Interpretation, Computer-Assisted Linear Models Magnetic Resonance Imaging Male Multivariate Analysis Plasma Volume/physiology Severity of Illness Index Sex Characteristics White Matter/diagnostic imaging,physiopathology

Chemicals

Contrast Media

Authors & Affiliations

9 authors, click to expand affiliations / ORCID

Zhang C Eleana

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. [email protected].

Wong Sau May

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.

van de Haar Harm J

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.

Staals Julie

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.

Jansen Jacobus F A

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.

Jeukens Cécile R L P N

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.

Hofman Paul A M

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.

van Oostenbrugge Robert J

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.

Backes Walter H

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.

Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease.

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