The association between BOLD-based cerebrovascular reactivity (CVR) and end-tidal CO₂ in healthy subjects

Cerebrovascular reactivity (CVR) mapping using CO₂-inhalation can provide important insight into vascular health. At present, blood-oxygenation-level-dependent (BOLD) MRI acquisition is the most commonly used CVR method due to its high sensitivity, high spatial resolution, and relatively straightforward processing. However, large variations in CVR across subjects and across different sessions of the same subject are often observed, which can cloud the ability of this promising measure in detecting diseases or monitoring treatment responses. The present work aims to identify the physiological components underlying the observed variability in CVR data. When studying the association between CVR value and the subject's CO₂ levels in a total of N = 253 healthy participants, we found that CVR was lower in individuals with a higher basal end-tidal CO₂, EtCO₂ (slope = -0.0036 ± 0.0008%/mmHg², p < 0.001), or with a greater EtCO₂ change (ΔEtCO₂) with hypercapnic condition (slope = -0.0072 ± 0.0018%/mmHg², p < 0.001). In a within-subject setting, when studying the CVR difference between two repeated scans (with repositioning) in relation to the corresponding differences in basal EtCO₂ and ΔEtCO₂ (n = 11), it was found that CVR values were lower if the basal EtCO₂ or ΔEtCO₂ during that particular scan session was greater. The present work suggests that basal physiological state and the level of hypercapnic stimulus intensity should be considered in application studies of CVR in order to reduce inter-subject and intra-subject variations in the data. Potential approaches to use these findings to reduce noise and augment sensitivity are proposed.