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

Significance: 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.

Aim: We aim to determine the agreement of CVR assessed during HC, breath-hold (BH), and resting state (RS) paradigms.

Approach: 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.

Results: Strong agreement ( $\mathrm{CCC}\ge 0.69$ ; $R\ge 0.76$ ) among CVR paradigms was demonstrated when utilizing a GLM to regress out systemic/extracerebral signal contributions. Linear regression alone showed poor agreement across paradigms ( $\mathrm{CCC}\le 0.35$ ; $R\le 0.45$ ).

Conclusions: More tolerable experimental paradigms coupled with regression of systemic/extracerebral signal contributions may offer a viable alternative to HC for assessing CVR.