Searching for a truly “iso-metabolic” gas challenge in physiological MRI

Abstract

Hypercapnia challenge (e.g. inhalation of CO 2 ) has been used in calibrated fMRI as well as in the mapping of vascular reactivity in cerebrovascular diseases. An important assumption underlying these measurements is that CO 2 is a pure vascular challenge but does not alter neural activity. However, recent reports have suggested that CO 2 inhalation may suppress neural activity and brain metabolic rate. Therefore, the goal of this study is to propose and test a gas challenge that is truly “iso-metabolic,” by adding a hypoxic component to the hypercapnic challenge, since hypoxia has been shown to enhance cerebral metabolic rate of oxygen (CMRO 2 ). Measurement of global CMRO 2 under various gas challenge conditions revealed that, while hypercapnia (P = 0.002) and hypoxia (P = 0.002) individually altered CMRO 2 (by −7.6 ± 1.7% and 16.7 ± 4.1%, respectively), inhalation of hypercapnic-hypoxia gas (5% CO 2 /13% O 2 ) did not change brain metabolism (CMRO 2 change: 1.5 ± 3.9%, P = 0.92). Moreover, cerebral blood flow response to the hypercapnic-hypoxia challenge (in terms of % change per mmHg CO 2 change) was even greater than that to hypercapnia alone (P = 0.007). Findings in this study suggest that hypercapnic-hypoxia gas challenge may be a useful maneuver in physiological MRI as it preserves vasodilatory response yet does not alter brain metabolism.