30 Jun 21. Featured Paper

Imaging NeuroVascular, Endothelial & STructural Integrity in prepAration to TrEat Small Vessel Diseases. The INVESTIGATE-SVDs study Protocol. Part of the SVDs@Target Project.

Link to paper on Cerebral Circulation - Cognition & Behaviour

Authors

Gordon W. Blair, Michael S. Stringer, Michael J. Thrippleton, Francesca M. Chappell, Kirsten Shuler, Iona Hamilton, Daniela Jaime Garcia, Fergus N. Doubal, Anna Kopczak, Marco Duering, Michael Ingrisch, Danielle Kerkhofs, Julie Staals, Hilde van den Brink, Tine Arts, Walter H Backes, Robert van Oostenbrugge, Geert Jan Biessels, Martin Dichgans, Joanna M. Wardlaw

Abstract

Background: Sporadic cerebral small vessel disease (SVD) & cerebral autosomal dominant arteriopathy with subcortical infarcts & leukoencephalopathy (CADASIL) share clinical & neuroimaging features & possibly vascular dysfunction(s).

However few studies have included both conditions, assessed more than one vascular dysfunction simultaneously, or included more than one centre.

The INVESTIGATE-SVDs study will assess several cerebrovascular dysfunctions with MRI in participants with sporadic SVD or CADASIL at three European centres.

Methods: We will recruit participants with sporadic SVDs (ischaemic stroke or vascular cognitive impairment) & CADASIL in Edinburgh, Maastricht & Munich.

We will perform detailed clinical & neuropsychological phenotyping of the participants, & neuroimaging including structural MRI, cerebrovascular reactivity MRI (CVR: using carbon dioxide challenge), phase contrast MRI (arterial, venous & CSF flow & pulsatility), dynamic contrast-enhanced MRI (blood brain barrier (BBB) leakage) & multishell diffusion imaging.

Participants will measure their blood pressure (BP) & its variability over seven days using a telemetric device.

Discussion: INVESTIGATE-SVDs will assess the relationships of BBB integrity, CVR, pulsatility & CSF flow in sporadic SVD & CADASIL using a multisite, multimodal MRI protocol.

We aim to establish associations between these measures of vascular function, risk factors particularly BP & its variability, & brain parenchymal lesions in these two SVD phenotypes.

Additionally we will test feasibility of complex multisite MRI, provide reliable intermediary outcome measures & sample size estimates for future trials.

Keywords

• Blood-brain barrier permeability
• CADASIL
• Cerebral small vessel disease
• Cerebrovascular reactivity
• MRI