Characterization of regional heterogeneity in cerebrovascular reactivity dynamics using novel hypocapnia task and...

We offer a new method for characterizing the magnitude and dynamics of the vascular response to changes in arterial gas tensions using non-invasive blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) and paradigms appropriate for clinical settings. A novel respiratory task, "Cued Deep Breathing" (CDB), consisting of two consecutive cycles of cued breaths, has been developed to cause transient hypocapnia, and consequently a strong, short-lived BOLD signal decrease. Data from CDB hypocapnia paradigms and traditional breath-holding hypercapnia paradigms were analyzed on a voxel-wise basis to map regional heterogeneity in magnitude and timing parameters. The tasks caused comparable absolute BOLD percent signal changes (approximately 0.5-3.0% in gray matter) and both datasets suggested consistent regional heterogeneity in the response timing: parts of the basal ganglia, particularly the putamen, and bilateral areas of medial cortex reached their maximum signal change several seconds earlier than remaining cortical gray matter voxels. This phenomenon and a slightly delayed response in posterior cortical regions were present in group-maps of ten healthy subjects. An auxiliary experiment in different subjects measured end-tidal CO2 changes associated with the new CDB task and quantitatively compared the resulting reactivity maps with those acquired using a traditional hypercapnia challenge of 4% CO2 gas inspiration. The CDB task caused average end-tidal CO2 decreases between 6.0+/-1.1 and 10.5+/-2.6 mm Hg, with levels returning to baseline after approximately three breaths, giving evidence that the task indeed causes transient mild hypocapnia. Similarity between resulting reactivity maps suggest CDB offers an alternative method for mapping cerebrovascular reactivity.