Edinburgh Imaging

27 Jun 17. Papers - imaging cerebral SVD

We announce two recently published papers, which explore imaging of cerebral small vessel disease.

Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study.

Joanna M. Wardlaw, Stephen J. Makin, Maria C. Valdés Hernández, Paul A. Armitage, Anna K. Heye, Francesca M. Chappell, Susana Muñoz-Maniega, Eleni Sakka, Kirsten Shuler, Martin S. Dennis, Michael J. Thrippleton.

Introduction - Small vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD-induced brain damage.

Methods - We assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling) ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency.

Results - In 201 patients, median age 67 (range 34–97), BBB leakage, and interstitial fluid were higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter increased with proximity to WMH (P < .0001), with WMH severity (P = .033), age (P = .03), and hypertension (P < .0001). BBB leakage in WMH predicted declining cognition at 1 year.

Discussion - BBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia.

Published in Alzheimer's & Dementia, June 2017. doi:10.1016/j.jalz.2016.09.006


Advanced Neuroimaging of Cerebral Small Vessel Disease.

Gordon W. Blair, Maria Valdez Hernandez, Michael J. Thrippleton, Fergus N. Doubal, Joanna M. Wardlaw.

Cerebral small vessel disease (SVD) is characterised by damage to deep grey and white matter structures of the brain and is responsible for a diverse range of clinical problems that include stroke and dementia. In this review, we describe advances in neuroimaging published since January 2015, mainly with magnetic resonance imaging (MRI), that, in general, are improving quantification, observation and investigation of SVD focussing on three areas: quantifying the total SVD burden, imaging brain microstructural integrity and imaging vascular malfunction. Methods to capture ‘whole brain SVD burden’ across the spectrum of SVD imaging changes will be useful for patient stratification in clinical trials, an approach that we are already testing. More sophisticated imaging measures of SVD microstructural damage are allowing the disease to be studied at earlier stages, will help identify specific factors that are important in development of overt SVD imaging features and in understanding why specific clinical consequences may occur. Imaging vascular function will help establish the precise blood vessel and blood flow alterations at early disease stages and, together with microstructural integrity measures, may provide important surrogate endpoints in clinical trials testing new interventions. Better knowledge of SVD pathophysiology will help identify new treatment targets, improve patient stratification and may in future increase efficiency of clinical trials through smaller sample sizes or shorter follow-up periods. However, most of these methods are not yet sufficiently mature to use with confidence in clinical trials, although rapid advances in the field suggest that reliable quantification of SVD lesion burden, tissue microstructural integrity and vascular dysfunction are imminent.

Published in Current Treatment Options in Cardiovascular Medicine, July 2017. doi:10.1007/s11936-017-0555-1