A novel perspective to calibrate temporal delays in cerebrovascular reactivity using hypercapnic and hyperoxic respiratory challenges

• Published in: NeuroImage (Orlando, Fla.) Vol. 187; pp. 154 - 165
• Main Authors: Champagne, Allen A., Bhogal, Alex A., Coverdale, Nicole S., Mark, Clarisse I., Cook, Douglas J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.02.2019; Elsevier Limited
• Subjects: Blood; Blood flow; BOLD signal; Brain research; Carbon dioxide; Cerebral blood flow; Cerebrovascular reactivity; Cortex; Functional magnetic resonance imaging; Hemoglobin; Hypercapnia; Hyperoxia; Inhalation; Medical research; Morphology; NMR; Nuclear magnetic resonance; Physiology; Plasma; Principal components analysis; RIPTiDe; Smooth muscle; Spin labeling; Substantia alba; Substantia grisea; Temporal delays; Vasoactive agents; RIPTiDe; Cerebrovascular reactivity; Hypercapnia; Temporal delays; Cerebral blood flow; Hyperoxia; BOLD signal
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2017.11.044

Redistribution of blood flow across different brain regions, arising from the vasoactive nature of hypercapnia, can introduce errors when examining cerebrovascular reactivity (CVR) response delays. In this study, we propose a novel analysis method to characterize hemodynamic delays in the blood oxygen level dependent (BOLD) response to hypercapnia, and hyperoxia, as a way to provide insight into transient differences in vascular reactivity between cortical regions, and across tissue depths. A pseudo-continuous arterial spin labeling sequence was used to acquire BOLD and cerebral blood flow simultaneously in 19 healthy adults (12 F; 20 ± 2 years) during boxcar CO2 and O2 gas inhalation paradigms. Despite showing distinct differences in hypercapnia-induced response delay times (P < 0.05; Bonferroni corrected), grey matter regions showed homogenous hemodynamic latencies (P > 0.05) once calibrated for bolus arrival time derived using non-vasoactive hyperoxic gas challenges. Longer hypercapnic temporal delays were observed as the depth of the white matter tissue increased, although no significant differences in response lag were found during hyperoxia across tissue depth, or between grey and white matter. Furthermore, calibration of hypercapnic delays using hyperoxia revealed that deeper white matter layers may be more prone to dynamic redistribution of blood flow, which introduces response lag times ranging between 1 and 3 s in healthy subjects. These findings suggest that the combination of hypercapnic and hyperoxic gas-inhalation MRI can be used to distinguish between differences in CVR that arise as a result of delayed stimulus arrival time (due to the local architecture of the cerebrovasculature), or preferential blood flow distribution. Calibrated response delays to hypercapnia provide important insights into cerebrovascular physiology, and may be used to correct response delays associated with vascular impairment. •Hypercapnic stimulus can introduce errors in vascular reactivity measurements.•Non-vasoactive hyperoxia can serve as an endogenous tracer for baseline CBV.•Combining hypercapnic and hyperoxic delays can highlight blood flow redistribution.•Calibrated delays provide insights about differences in CVR across tissue depth.