Edinburgh Imaging

30 Apr 19. Featured Paper

Quantifying blood-brain barrier leakage in small vessel disease: Review and consensus recommendations.

Link to paper on ELSEVIER journal



Michael J.Thrippleton, Walter H.Backes, Steven Sourbron, Michael Ingrisch, Matthias J.P.van Osch, Martin Dichgans, Franz Fazekas, Stefan Ropele, Richard Frayne, Robert J.van Oostenbrugge, Eric E. Smith, Joanna M.Wardlaw



Cerebral small vessel disease (cSVD) comprises pathological processes of the small vessels in the brain that may manifest clinically as stroke, cognitive impairment, dementia, or gait disturbance.

It is generally accepted that endothelial dysfunction, including blood-brain barrier (BBB) failure, is pivotal in the pathophysiology.

Recent years have seen increasing use of imaging, primarily dynamic contrast-enhanced magnetic resonance imaging, to assess BBB leakage, but there is considerable variability in the approaches and findings reported in the literature.

Although dynamic contrast-enhanced magnetic resonance imaging (MRI) is well established, challenges emerge in Cerebral small vessel disease (cSVD) because of the subtle nature of BBB impairment.

The purpose of this work, authored by members of the HARNESS Initiative, is to provide an in-depth review and position statement on magnetic resonance imaging measurement of subtle BBB leakage in clinical research studies, with aspects requiring further research identified.

We further aim to provide information and consensus recommendations for new investigators wishing to study BBB failure in cSVD and dementia.



As a group with substantial collective technical and clinical experience in the Cerebral small vessel disease (cSVD) and MRI fields, our intention in writing this review is to provide researchers with comprehensive information, advice, and consensus-based recommendations for performing such measurements in research studies, to describe the limitations so that authors and readers may better assess the quality and implications of studies, and to identify areas where further research and development will benefit future clinical applications.

For clarity, we note that our recommendations are not intended as a medical guideline and that DCE-MRI quantification of subtle BBB leakage is not yet suitable for use as a clinical decision-making tool. 

We hope that these recommendations will encourage a greater degree of harmonization in future studies where possible, in order that data from multiple centers can be more easily compared and pooled. We have focused on DCE-MRI as the method that is, at present, most advanced and most widely used, and which we believe provides a quantitative, though relative, measure of BBB integrity. Nevertheless, the technique is relatively immature in the context of measuring subtle BBB leakage, and we note that our recommendations do not represent the final word on the subject but rather a pragmatic “baseline” approach that may inform the design of future studies, lead to greater harmonization and interstudy comparability, and provide a starting point for future initiatives to further standardize, develop, and validate the method. 

The alternative techniques for assessing BBB integrity described in this article may also undergo further development and merit greater prominence in future reviews.