Robust estimation of dynamic cerebrovascular reactivity using breath-holding fMRI: application in diabetes and hypertension

Abstract

AbstractBreath-holding (BH) tasks during functional magnetic resonance imaging (fMRI) acquisitions are gaining popularity for non-invasive mapping of carbon-dioxide (CO2) driven cerebrovascular reactivity (CVR), which is a valuable clinical marker of vascular function. However, compliance to BH tasks is often unclear, and the ability to record end-tidal CO2often limited, rendering the optimal analysis of BH fMRI data a challenge. In this work, we demonstrate an adaptive data-driven approach for estimating CVR from BH fMRI data that minimizes errors due to subject non-compliance and regional CVR time delay variability. Building on previous work, we propose a frequency-domain-based approach for CVR estimation without the need for end-tidal CO2(PETCO2) recordings. CVR amplitude is estimated in units of %ΔBOLD directly from the data-driven BH frequency. Serious deviations from the designed task paradigm were suppressed and thus did not bias the estimated CVR values. We demonstrate our method in detecting regional CVR amplitude and time-lag differences in a group of 56 individuals, consisting of healthy (CTL), hypertensive (HT) and diabetic-hypertensive (DM+HT) groups of similar ages and sex ratios. The CVR amplitude was lowest in HT+DM, and HT had a lower CVR amplitude than CTL regionally but the voxelwise comparison did not yield statistical significance. Notably, we demonstrate that the voxelwise CVR time delay estimated in Fourier domain is a more sensitive marker of vascular dysfunction than CVR amplitude. While HT+DM seems to confer longer CVR delays, HT seems to confer shorter delays than CTL. These are the first MRI-based observations of CVR time delay differences between diabetic-hypertensive patients and healthy controls. These results demonstrate the feasibility of extracting CVR amplitude and CVR time delay using BH challenges without PETCO2recordings, and the unique clinical value of CVR time-delay information.