Measuring cerebrovascular reactivity: what stimulus to use?

Abstract

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.

Assessing Cerebrovascular Reactivity Abnormality by Comparison to a Reference Atlas

“…With respect to CVR z-maps, the consistency of the stimulus, PaCO 2 , which is independent of the ventilatory response, 17 is a crucial enabling element. For example, the PaCO 2 stimuli resulting from breath-holding and inspiring a fixed PCO 2 are patient dependent and thus highly variable, 15 and therefore unsuitable. With a consistent PCO 2 stimulus, CVR z-scores should enable the comparison of CVR scores between centers.…”

“…The implementation of prospective end-tidal gas control has been described in detail elsewhere. 15 In brief, subjects were fitted with a face mask, and connected to a sequential gas delivery breathing circuit. 16 The patterns of PETCO 2 and PETO 2 were programmed into the automated gas blender (RespirAct TM , Thornhill Research, Toronto, Canada) running the prospective gas targeting algorithm of Slessarev et al 17 A standardized step CO 2 stimulus was implemented, consisting of the following sequence: a baseline PETCO 2 of 40 mm Hg for 60 seconds, step to a hypercapnia of 50 mm Hg for 45 seconds, baseline for 90 seconds, hypercapnia for 120 seconds, and return to baseline for 60 seconds, all during isoxic normoxia targeted at 100 mm Hg.…”

Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence

“…6 Improvements of BOLD CVR methodologies have been proposed [13,15] and may increase sensitivity and quantification of (regional) CVR measurements in subjects with high-grade cerebral glioma.…”

“…[5] Cerebrovascular reactivity (CVR) is a functional parameter that can be assessed with MRI by obtaining Blood Oxygen-Level Dependent (BOLD) volumes. CVR is determined as the BOLD signal response due to deoxyhemoglobin washout related to carbon dioxide (CO 2 ) changes as the vasoactive stimulus, [6]and can be measured on high spatial resolution covering the entire brain. Using this concept, Hsu et al [7] have demonstrated that BOLD MRI generates CVR patterns to better distinguish normal brain tissue from glioma tissue.…”

Iterative analysis of cerebrovascular reactivity dynamic response by temporal decomposition

“…(2007). Specific details and novelties of this technique as compared to other vasoactive stimuli have been described more specifically in a previous publication (Fierstra et al., 2013). The preprogrammed sequence consisted of an initial 100 s baseline P et CO 2 at 40 mmHg, after which a P et CO 2 step was increased to 10 mmHg above baseline for 80 s and a return to baseline for 100 s, before free breathing was restored.…”