Hemodynamic and metabolic changes during hypercapnia with normoxia and hyperoxia using pCASL and TRUST MRI in healthy adults

Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic stimuli are also employed in calibrated BOLD functional MRI for quantifying neuronally-evoked changes in cerebral oxygen metabolism (CMRO ₂). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO ₂ or O ₂ does not affect CMRO ₂. We evaluated the null hypothesis that two common hypercapnic stimuli, ‘CO ₂ in air’ and carbogen, are iso-metabolic. TRUST and ASL MRI were used to measure the cerebral venous oxygenation and cerebral blood flow (CBF), from which the oxygen extraction fraction (OEF) and CMRO ₂ were calculated for room-air, ‘CO ₂ in air’ and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for ‘CO ₂ in air’ and carbogen, respectively). CMRO ₂ decreased for ‘CO ₂ in air’ (−13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO ₂ during carbogen did not significantly change. Our findings indicate that ‘CO ₂ in air’ is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO ₂ reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli.