No abstract

Cerebrovascular reactivity (CVR) is an important metric of cerebrovascular health. While the BOLD fMRI method in conjunction with carbon-dioxide (CO 2 ) based vascular manipulation has been the most commonly used, the BOLD signal is not a direct measure of vascular changes, and the use of arterial-spin labeling (ASL) cerebral blood flow (CBF) imaging is increasingly advocated. Nonetheless, given the differing dependencies of BOLD and CBF on vascular baseline conditions and the diverse CO 2 manipulation types currently used in the literature, knowledge of potential biases introduced by each technique is critical for the interpretation of CVR measurements. In this work, we use simultaneous BOLD-CBF acquisitions during both vasodilatory (hypercapnic) and vasoconstrictive (hypocapnic) stimuli to measure CVR. We further imposed different levels of baseline vascular tension by inducing hypercapnic and hypocapnic baselines, separately from normocapnia by 4 mm Hg. We saw significant and diverse dependencies on vascular stimulus and baseline condition in both BOLD and CBF CVR measurements: (i) BOLD-based CVR is more sensitive to basal vascular tension than CBF-based CVR; (ii) the use of a combination of vasodilatory and vasoconstrictive stimuli maximizes the sensitivity of CBF-based CVR to vascular tension changes; (iii) the BOLD and CBF vascular response delays are both significantly lengthened at predilated baseline. As vascular tension can often be altered by potential pathology, our findings are important considerations when interpreting CVR measurements in health and disease.

The resting-state fMRI (rs-fMRI) signal is affected by a variety of low-frequency physiological phenomena, including variations in cardiac-rate (CRV), respiratory-volume (RVT), and end-tidal CO2 (PETCO2). While these effects have become better understood in recent years, the impact that their correction has on the quality of rs-fMRI measurements has yet to be clarified. The objective of this paper is to investigate the effect of correcting for CRV, RVT and PETCO2 on the rs-fMRI measurements. Nine healthy subjects underwent a test-retest rs-fMRI acquisition using repetition times (TRs) of 2 s (long-TR) and 0.323 s (short-TR), and the data were processed using eight different physiological correction strategies. Subsequently, regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and resting-state connectivity of the motor and default-mode networks are calculated for each strategy. Reproducibility is calculated using intra-class correlation and the Dice Coefficient, while the accuracy of functional-connectivity measures is assessed through network separability, sensitivity and specificity. We found that: (1) the reproducibility of the rs-fMRI measures improved significantly after correction for PETCO2; (2) separability of functional networks increased after PETCO2 correction but was not affected by RVT and CRV correction; (3) the effect of physiological correction does not depend on the data sampling-rate; (4) the effect of physiological processes and correction strategies is network-specific. Our findings highlight limitations in our understanding of rs-fMRI quality measures, and underscore the importance of using multiple quality measures to determine the optimal physiological correction strategy.