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

Abstract

Cerebrovascular reactivity (CVR), i.e., the ability of cerebral vasculature to dilate or constrict in response to vasoactive stimuli, is a biomarker of vascular health. Exogenous administration of inhaled carbon dioxide, i.e., hypercapnia (HC), remains the "gold-standard" intervention to assess CVR. More tolerable paradigms that enable CVR quantification when HC is difficult/contraindicated have been proposed. However, because these paradigms feature mechanistic differences in action, an assessment of agreement of these more tolerable paradigms to HC is needed. We aim to determine the agreement of CVR assessed during HC, breath-hold (BH), and resting state (RS) paradigms. Healthy adults were subject to HC, BH, and RS paradigms. End tidal carbon dioxide (EtCO2) and cerebral blood flow (CBF, assessed with diffuse correlation spectroscopy) were monitored continuously. CVR (%/mmHg) was quantified via linear regression of CBF versus EtCO2 or via a general linear model (GLM) that was used to minimize the influence of systemic and extracerebral signal contributions. Strong agreement ( ; ) among CVR paradigms was demonstrated when utilizing a GLM to regress out systemic/extracerebral signal contributions. Linear regression alone showed poor agreement across paradigms ( ; ). More tolerable experimental paradigms coupled with regression of systemic/extracerebral signal contributions may offer a viable alternative to HC for assessing CVR.