Agreement in cerebrovascular reactivity assessed with diffuse correlation spectroscopy across experimental paradigms improves with short separation regression

Abstract

12 Significance: Cerebrovascular reactivity (CVR), i.e., the ability of cerebral vasculature to dilate or constrict 13 in response to vasoactive stimuli, is a biomarker of vascular health. Exogenous administration of inhaled 14 carbon dioxide, i.e., hypercapnia, remains the "gold-standard" intervention to assess CVR. More tolerable 15 paradigms have been proposed that enable CVR quantification when hypercapnia is 16 difficult/contraindicated. However, because these paradigms feature mechanistic differences in action, 17 assessment of agreement of these more tolerable paradigms to hypercapnia is needed. 18 Aim: To determine the agreement of CVR assessed during hypercapnia, breath-hold, and resting state. 19 Approach: Healthy adults were subject to hypercapnia, breath-hold, and resting state paradigms. End 20 tidal carbon dioxide (EtCO2) and cerebral blood flow (CBF, assessed with Diffuse Correlation 21 Spectroscopy) were monitored continuously. CVR (%/mmHg) was quantified via linear regression of CBF 22 vs EtCO2 or via a general linear model that was used to minimize the influence of systemic and 23 extracerebral signal contributions. 24 Results: Strong agreement among CVR paradigms was demonstrated when utilizing a general linear model 25 to regress out systemic/extracerebral signal contributions. Linear regression alone showed poor 26 agreement across paradigms. 27 Conclusions: More tolerable experimental paradigms coupled with regression of systemic/extracerebral 28 signal contributions may offer a viable alternative to hypercapnia for assessing CVR. 29 30