Estimation of cerebrovascular reactivity amplitude and lag using breath-holding fMRI and the global BOLD signal: Application in diabetes and hypertension

In this work, we demonstrate a data-driven approach for estimating cerebrovascular reactivity (CVR) amplitude and lag from breathhold (BH) fMRI data alone. Our approach employs a frequency-domain approach that is independent of external recordings. CVR amplitude is estimated from the BOLD frequency spectrum and CVR lag is estimated from the Fourier phase using the global-mean BOLD signal as reference. Unlike referencing to external recordings, these lags are specific to the brain. We demonstrated our method in detecting regional CVR amplitude and lag differences across healthy (CTL), hypertensive (HT) and hypertension-plus-type-2-diabetes (HT + DM) groups of similar ages and sex ratios, with a total N of 49. We found CVR amplitude to be significantly higher in CTL compared to HT + DM, with minimal difference between CTL and HT. Also, voxelwise CVR lag estimated in the Fourier domain is a more sensitive marker of vascular dysfunction than CVR amplitude. CVR lag in HT is significantly shorter than in CTL, with minimal difference between CTL and HT + DM. Our results support the importance of joint CVR amplitude and lag assessments in clinical applications.