Measuring Cerebrovascular Reactivity: Sixteen Avoidable Pitfalls

Olivia Sobczyk; Jorn Fierstra; Lakshmikumar Venkatraghavan; Julien Poublanc; James Duffin; Joseph A Fisher; David J Mikulis

doi:10.3389/fphys.2021.665049

Measuring Cerebrovascular Reactivity: Sixteen Avoidable Pitfalls

Front Physiol. 2021 Jul 7:12:665049. doi: 10.3389/fphys.2021.665049. eCollection 2021.

Authors

Olivia Sobczyk^{1

2}, Jorn Fierstra³, Lakshmikumar Venkatraghavan¹, Julien Poublanc², James Duffin^{1

4}, Joseph A Fisher^{1

4

5}, David J Mikulis^{2

5}

Affiliations

¹ Department of Anaesthesia and Pain Management, University Health Network, University of Toronto, Toronto, ON, Canada.
² Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory, University Health Network, Toronto, ON, Canada.
³ Department of Neurosurgery, University Hospital Zurich, Zürich, Switzerland.
⁴ Department of Physiology, University of Toronto, Toronto, ON, Canada.
⁵ Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Abstract

An increase in arterial PCO₂ is the most common stressor used to increase cerebral blood flow for assessing cerebral vascular reactivity (CVR). That CO₂ is readily obtained, inexpensive, easy to administer, and safe to inhale belies the difficulties in extracting scientifically and clinically relevant information from the resulting flow responses. Over the past two decades, we have studied more than 2,000 individuals, most with cervical and cerebral vascular pathology using CO₂ as the vasoactive agent and blood oxygen-level-dependent magnetic resonance imaging signal as the flow surrogate. The ability to deliver different forms of precise hypercapnic stimuli enabled systematic exploration of the blood flow-related signal changes. We learned the effect on CVR of particular aspects of the stimulus such as the arterial partial pressure of oxygen, the baseline PCO₂, and the magnitude, rate, and pattern of its change. Similarly, we learned to interpret aspects of the flow response such as its magnitude, and the speed and direction of change. Finally, we were able to test whether the response falls into a normal range. Here, we present a review of our accumulated insight as 16 "lessons learned." We hope many of these insights are sufficiently general to apply to a range of types of CO₂-based vasoactive stimuli and perfusion metrics used for CVR.

Keywords: carbon dioxide; cerebral blood flow; cerebrovascular reactivity; cerebrovascular reactivity to carbon dioxide; vascular responses.