Cerebrovascular reactivity is the change in cerebral blood flow in response to a vasodilatory or vasoconstrictive stimulus. Measuring variations of cerebrovascular reactivity between different regions of the brain has the potential to not only advance understanding of how the cerebral vasculature controls the distribution of blood flow but also to detect cerebrovascular pathophysiology. While there are standardized and repeatable methods for estimating the changes in cerebral blood flow in response to a vasoactive stimulus, the same cannot be said for the stimulus itself. Indeed, the wide variety of vasoactive challenges currently employed in these studies impedes comparisons between them. This review therefore critically examines the vasoactive stimuli in current use for their ability to provide a standard repeatable challenge and for the practicality of their implementation. Such challenges include induced reductions in systemic blood pressure, and the administration of vasoactive substances such as acetazolamide and carbon dioxide. We conclude that many of the stimuli in current use do not provide a standard stimulus comparable between individuals and in the same individual over time. We suggest that carbon dioxide is the most suitable vasoactive stimulus. We describe recently developed computer-controlled MRI compatible gas delivery systems which are capable of administering reliable and repeatable vasoactive CO 2 stimuli. Abbreviations ACZ, acetazolamide; ASL, arterial spin labeling; BOLD, blood oxygen level-dependent; CBF, cerebral blood flow; CVR, cerebrovascular reactivity; DEF, dynamic end-tidal forcing; MRI, magnetic resonance imaging; SGD, sequential gas delivery (circuit); TCD, trans-cranial Doppler.Jorn Fierstra is currently enrolled in a neurosurgical training program at the University Medical Center Zürich, Switzerland. His PhD degree from Utrecht University, was based on research done in the Department of Neurosurgery, Neuroradiology and Anesthesiology of the University Health Network, Toronto, Canada, and he recently received an MD degree from Utrecht University, the Netherlands. His research interests include clinical investigations of cerebral vasculature pathophysiology and fMRI related research. Olivia Sobczyk is currently a PhD student in the Institute of Medical Science at the University of Toronto and the University Health Network, Toronto, Canada. She obtained her MSc in Biomedical Physics from Ryerson University, Toronto, Canada. Her research interests include mathematical modeling and investigation in cerebral hemodynamic processes, specifically cerebral vascular reactivity, and clinical investigation in the application of functioning imaging tools to investigate neurological disorders.
