Cerebrovascular reactivity measurement in cerebral small vessel disease: Rationale and reproducibility of a protocol for MRI acquisition and image processing

Michael J. Thrippleton, Yulu Shi, Gordon Blair, Iona Hamilton, Gordon Waiter, Christian Schwarzbauer, Cyril Pernet, Peter J.D. Andrews, Ian Marshall, Fergus Doubal, Joanna M. Wardlaw*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


Background: Impaired autoregulation may contribute to the pathogenesis of cerebral small vessel disease. 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 by MRI, in subcortical tissue of patients with small vessel disease and minor stroke. Methods: We recruited 15 healthy volunteers, testing paradigms using 1- and 3-min 6% CO2 challenges with repeat scanning, and 15 patients with history of minor stroke. We developed a protocol to measure cerebrovascular reactivity and delay times, assessing tolerability and reproducibility in grey and white matter areas. Results: The 3-min paradigm yielded more reproducible data than the 1-min paradigm (CV respectively: 7.9–15.4% and 11.7–70.2% for cerebrovascular reactivity in grey matter), and was less reproducible in white matter (16.1–24.4% and 27.5–141.0%). Tolerability was similar for the two paradigms, but mean cerebrovascular reactivity and cerebrovascular reactivity delay were significantly higher for the 3-min 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). Grey matter cerebrovascular reactivity was lower in patients than in volunteers (0.110–0.234 vs. 0.172–0.313%/mmHg; p < 0.05 in 6/8 regions), as was the white matter cerebrovascular reactivity delay (16.2–43.9 vs. 31.1–47.9 s; p < 0.05 in 4/8 regions). Conclusions: An effective and well-tolerated protocol for measurement of cerebrovascular reactivity was developed for use in ongoing and future trials to investigate small vessel disease pathophysiology and to measure treatment effects.

Original languageEnglish
Pages (from-to)195-206
Number of pages12
JournalInternational Journal of Stroke
Issue number2
Early online date21 Sept 2017
Publication statusPublished - 2018

Bibliographical note

We thank K. Shuler and the radiography staff for providing expert research support.

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded primarily by the Chief Scientist Office of Scotland (grant ETM/326) and the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund. Support was also received from: NHS Lothian Research and Development Office (MJT), the China Scholarships Council/University of Edinburgh (YS), the Scottish Imaging Network: A Platform for Scientific Excellence (“SINAPSE,” funded by the Scottish Funding Council and the Chief Scientist Office of Scotland; GB, radiography staff), the Alzheimer’s Society (grant ref AS-PG-14-033; GB), the European Union Horizon 2020, “SVDs@target” (grant No 666881; GB), Fondation Leducq (grant 16 CVD 05). The Stroke Association Garfield Weston Foundation Senior Lectureship (FD), NHS Research fellowship (FD) and the Medical Research Council (FD).


  • cerebral small vessel disease
  • Cerebrovascular reactivity
  • magnetic resonance imaging
  • stroke


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