The effects of basal vascular tone on hypercapnic and hypocapnic cerebrovascular reactivity: implications for clinical autoregulation studies

Introduction. Cerebrovascular reactivity (CVR) response to arterial gas tensions can offer insight into the compliance of blood vessels [1] and may be useful for experimentally simulating conditions of hemodynamic compromise in patients with carotid artery disease. Specifically, these patients may exhibit abnormalities in several vascular characteristics in response to reduced cerebral perfusion pressure, including autoregulatory vasodilation to compensate for reduced cerebral blood flow (CBF) in affected perfusion territories [2]. However, it is unclear how such baseline changes in cerebral blood volume (CBV) and/or CBF influence the BOLD reactivity measure. Here, we use BOLD fMRI and CO2 inhalation in healthy volunteers to understand how an increase in basal vasodilation influences the BOLD CVR to both a vasoconstrictive deep breathing task and vasodilatory respiratory challenge. The hypothesis to be investigated was that increased basal CO2 (and hence CBF and CBV) may attenuate the dilation CVR response, similar to the reduction in the HRF amplitude observed by [3] during neuronal stimulation and 5% CO2 inhalation, while not having an affect on the constriction CVR response. This divergence would indicate that the two CVR measurement techniques reflect different vascular changes. Methods. Data acquisition. Healthy volunteers (n=6) were scanned at 3.0T (Siemens) using body coil RF transmit and 12-channel head coil RF receive. Whole-brain BOLD fMRI data were collected with gradient-echo EPI (TR/TE/α=1500ms/38ms/73°, 3.5x3.5x4.0 mm). A structural image was also obtained for co-registration and mask generation (MPRAGE: TR/TI/TE=1778/900/4.4 ms, 1.7x1.7x2.0 mm). Two different baseline vascular conditions were created using inhalation of either 0% or 4% CO2 in humidified air. A two-source gas delivery system was designed to allow for instant switching of the gas supplied to a nonrebreathing reservoir bag and face mask covering the mouth and nose of the subject. During each of the baseline conditions, subjects were instructed with visual cues to perform hypercapnia-inducing (vasodilatory) respiratory challenges (three blocks of 15 second breath-holds) or hypocapnia-inducing (vasoconstrictive) respiratory challenges (three blocks of Cued Deep Breathing [4]). During the first inhalation of the CDB challenge, the gas supply was switched to normal air for 2 breaths to facilitate a hyperventilation-related decrease in CO2 levels. Three repetitions of each breathing challenge were administered, in a randomized order, interleaved with 90 seconds of normal breathing. A schematic of the protocol is shown in Fig. 1. Respiration was monitored using a bellows system, and a nasal cannula was inserted underneath the mask to continuously sample the O2 and CO2 content of expired air (BIOPAC MP150). Analysis. BOLD data were corrected for motion, slice timing, and drift artifacts, before being spline-interpolated to a temporal resolution of 0.25 seconds. The starting time for each breathing challenge was identified using the bellows trace. For both BOLD datasets, mean CDBand BH-response curves were calculated for every voxel by averaging the voxel timecourse within a 75-second window following the start times of the appropriate challenges. This mean response curve was smoothed (Gaussian kernel 9s) and the maximum or minimum signal change was measured for the BH or CDB data, respectively. The baseline value was calculated as the average BOLD signal in the 20 seconds preceding the challenges. The four resulting maps of %BOLD signal change were