Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease
Abstract
Objective
To investigate the link between blood-brain-barrier (BBB) permeability and cerebral blood flow (CBF) and the relation with white matter hyperintensities (WMH) in cerebral small vessel disease (cSVD).
Methods
Twenty-seven patients with cSVD received dynamic susceptibility contrast and dynamic contrast-enhanced MRI to determine CBF and BBB permeability (expressed as leakage rate and volume), respectively. Structural MRI were segmented into normal-appearing white matter (NAWM) and WMH, for which a perilesional zone was defined. In these regions, we investigated the BBB permeability, CBF, and their relation using Pearson correlation r.
Results
We found a decrease in CBF of 2.2 mL/min/100 g (p < 0.01) and an increase in leakage volume of 0.7% (p < 0.01) per mm closer to the WMH in the perilesional zones. Lower CBF values correlated with higher leakage measures in the NAWM and WMH (−0.53 < r < −0.40, p < 0.05). This relation was also observed in the perilesional zones, which became stronger in the proximity of WMH (p = 0.03).
Conclusion
BBB impairment and hypoperfusion appear in the WMH and NAWM, which increase in the proximity of the WMH, and are linked. Both BBB and CBF are regulated in the neurovascular unit (NVU) and the observed link might be due to the physiologic regulation mechanism of the NVU. This link may suggest an early overall deterioration of this unit.
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© 2019 American Academy of Neurology.
Publication History
Received: March 21, 2018
Accepted: November 28, 2018
Published online: March 13, 2019
Published in print: April 9, 2019
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Study Funding
This project has received funding from NWO (Netherlands Organization for Scientific Research, grant: 017.009.048), the European Union's Horizon 2020 research and innovation program (grant: 666881, SVDs@target), Hersenstichting (grant: 2013[1]-195), and Stichting de Weijerhorst Foundation.
Authors
Author Contributions
S.M. Wong: drafting/revising the manuscript, data acquisition, study concept or design, analysis or interpretation of data, accepts responsibility for conduct of research and final approval, acquisition of data, statistical analysis. J.F.A. Jansen: drafting/revising the manuscript, data acquisition, study concept or design, analysis or interpretation of data, accepts responsibility for conduct of research and final approval, obtaining funding. E. Zhang: data acquisition, accepts responsibility for conduct of research and final approval. E. Hoff: drafting/revising the manuscript, accepts responsibility for conduct of research and final approval, acquisition of data. J. Staals: drafting/revising the manuscript, accepts responsibility for conduct of research and final approval, study supervision. R. van Oostenbrugge: study concept or design, analysis or interpretation of data, accepts responsibility for conduct of research and final approval, study supervision, obtaining funding. W.H. Backes: drafting/revising the manuscript, data acquisition, study concept or design, analysis or interpretation of data, accepts responsibility for conduct of research and final approval, acquisition of data, statistical analysis, study supervision, obtaining funding.
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