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Cerebrovascular reactivity measurement in cerebral small vessel disease: rationale and reproducibility of a protocol for MRI acquisition and image processing
Michael J. Thrippleton,a Yulu Shi,a Gordon Blair,a Iona Hamilton,a Gordon Waiter,b Christian Schwarzbauer,c Cyril Pernet,a Peter JD Andrews,d Ian Marshall,a Fergus Doubal,a Joanna M. Wardlawa,*
aNeuroimaging Sciences, University of Edinburgh, UK
bAberdeen Biomedical Imaging Centre, University of Aberdeen, UK
cFaculty of Applied Sciences & Mechatronics, Munich University of Applied Sciences, Germany
dCentre for Clinical Brain Sciences, University of Edinburgh, UK.
Michael J. Thrippleton: Centre for Clinical Brain Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK; telephone 0131 537 2943; email: m.j.thrippleton@ed.ac.uk
Yulu Shi: Centre for Clinical Brain Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK, yulu.shi@ed.ac.uk
Gordon Blair: Centre for Clinical Brain Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK, gordon.blair@ed.ac.uk
Iona Hamilton: Centre for Clinical Brain Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK, igerrish@exseed.ed.ac.uk
Gordon Waiter: Aberdeen Biomedical Imaging Centre, Division of Applied Medicine, University of Aberdeen Research MRI Centre, Lilian Sutton Building, Aberdeen AB25 2ZD, UK, g.waiter@abdn.ac.uk
Christian Schwarzbauer: Faculty of Applied Sciences & Mechatronics, Munich University of Applied Sciences, Lothstraße 34, 80335 München, Germany, christian.schwarzbauer@hm.edu
Cyril Pernet: Centre for Clinical Brain Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK, cyril.pernet@ed.ac.uk
Peter Andrews: Centre for Clinical Brain Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK, p.andrews@ed.ac.uk
Ian Marshall: Centre for Clinical Brain Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK, ian.marshall@ed.ac.uk
Fergus Doubal: Centre for Clinical Brain Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK, fergus.doubal@ed.ac.uk
*Corresponding author: Professor Joanna M. Wardlaw, Centre for Clinical Brain Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK; telephone: +44 (0)131 537 2943; fax: +44 (0)131 537 2661; e-mail: joanna.wardlaw@ed.ac.uk.
Keywords: cerebrovascular reactivity, cerebral small vessel disease, MRI, stroke
Words: 4053
Tables: 2
Figures: 4
Supplementary Figures: 5
Abstract (word limit: 250)
Background Impaired autoregulation may contribute to the pathogenesis of cerebral small vessel disease (SVD). Reliable protocols for measuring microvascular reactivity are required to test this hypothesis and for providing secondary endpoints in clinical trials.
Aims To develop and assess a protocol for acquisition and processing of cerebrovascular reactivity (CVR) by MRI, in subcortical tissue of patients with SVD and minor stroke.
Methods We recruited 15 healthy volunteers, testing paradigms using 1- and 3-minute 6% CO2 challenges with repeat scanning, and 15 patients with history of minor stroke. We developed a protocol to measure CVR and delay times, assessing tolerability and reproducibility in grey and white matter (GM, WM) areas.
Results The 3-minute paradigm yielded more reproducible data than the 1-minute paradigm (CV respectively: 7.9–15.4% and 11.7–70.2% for CVR in GM), and was less reproducible in WM (16.1–24.4% and 27.5–141.0%). Tolerability was similar for the two paradigms, but mean CVR and CVR delay were significantly higher for the 3-minute paradigm in most regions. Patient tolerability was high with no evidence of greater failure rate (1/15 patients vs. 2/15 volunteers withdrew at the first visit). GM CVR was lower in patients than in volunteers (0.110—0.234 vs. 0.172—0.313 %/mmHg; p ................
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