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 ¼ 0.002) and hypoxia (P ¼ 0.002) individually altered CMRO 2 (by À7.6 AE 1.7% and 16.7 AE 4.1%, respectively), inhalation of hypercapnic-hypoxia gas (5% CO 2 /13% O 2 ) did not change brain metabolism (CMRO 2 change: 1.5 AE 3.9%, P ¼ 0.92). Moreover, cerebral blood flow response to the hypercapnichypoxia challenge (in terms of % change per mmHg CO 2 change) was even greater than that to hypercapnia alone (P ¼ 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.

Hypercapnia is essential to reduce the cerebral oxidative metabolism during extreme apnea in humans

“…11 In addition, in our previous study 6 it was impossible to discern the metabolic impact of hypercapnia independent to the impact of severe hypoxia. As recently reported, 12 the attending hypoxia may well offset some of the reduction in CMRO 2 attributed to hypercapnia.…”

“…Hypoxia may increase the CMRO 2 4,5,12 and in turn counter some of the metabolic depression from hypercapnia during apnea. Using MRI, Peng et al, 12 recently quantified the opposing facet of hypoxia and hypercapnia on the CMRO 2 in humans. Here, Peng et al reported that hypercapnia (5% CO 2 inhalation) reduced the CMRO 2 by $8%, hypoxia (13% O 2 , balanced with N 2 ) increased the CMRO 2 by $17%, but the combination of the two (5% CO 2 and 13% O 2 , balanced with N 2 ) had no effect on the CMRO 2 .…”

Cross‐vendor harmonization of T2‐relaxation‐under‐spin‐tagging (TRUST) MRI for the assessment of cerebral venous oxygenation

“…The coefficient denotes the dependence of venous oxygenation on EtCO 2 . Previous studies have reported that value of is between 1 and 2%/mmHg . In this study, because we measured Y v and EtCO 2 twice on each scanner, we were able to calculate the value of from the ratio between Y v and EtCO 2 differences, which was found to be 1.6%/mmHg.…”

Functional magnetic resonance imaging in chronic ischaemic stroke

“…B 371: 20150353 the assumed blood flow and volume coupling between iso-metabolic stimulation and the functional stimulus/task under investigation. The identification of clinically translatable iso-metabolic perturbers remains an active area of research [70], as does the relationship between flow and volume changes under various ( patho)physiological conditions. Further insight into the metabolic changes in the peri-infarct tissue may be attained by combining BOLD fMRI with complementary MRI approaches such as amide proton transfer imaging to assess tissue pH.…”