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

Abstract

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 (CMRO2). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO2 or O2 does not affect CMRO2. We evaluated the null hypothesis that two common hypercapnic stimuli, ‘CO2 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 CMRO2 were calculated for room-air, ‘CO2 in air’ and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for ‘CO2 in air’ and carbogen, respectively). CMRO2 decreased for ‘CO2 in air’ (−13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO2 during carbogen did not significantly change. Our findings indicate that ‘CO2 in air’ is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO2 reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli.

Lag-Optimized Blood Oxygenation Level Dependent Cerebrovascular Reactivity Estimates Derived From Breathing Task Data Have a Stronger Relationship With Baseline Cerebral Blood Flow

“…Under the assumption that our vasoactive breathing task stimuli are isometabolic, the BOLD-CVR response should reflect the CBF-CVR response ( Zhou et al, 2015 ). However, there are many physiological factors that can contribute to a BOLD signal change other than a CBF change ( Kim and Ogawa, 2012 ), and the assumption of an isometabolic state under hypercapnia may not always be valid ( Driver et al, 2017 ; Yablonskiy, 2011 ; Deckers et al, 2021 ; Xu et al, 2011 ). Furthermore, BOLD-CVR and CBF-CVR may have differing dependencies on the baseline condition ( Stefanovic et al, 2006 ; Halani et al, 2015 ) and on the type of vascular stimulus ( Halani et al, 2015 ).…”

Lag-optimized BOLD cerebrovascular reactivity derived from breathing task data has a stronger relationship with baseline cerebral blood flow

“…Under the assumption that our vasoactive breathing task stimuli are isometabolic, the BOLD-CVR response should reflect the CBF-CVR response (Zhou et al, 2015). However, there are many physiological factors that can contribute to a BOLD signal change other than a CBF change (Kim and Ogawa, 2012), and the assumption of an isometabolic state under hypercapnia may not always be valid (Deckers et al, 2021; Driver et al, 2017; Xu et al, 2011; Yablonskiy, 2011). Furthermore, BOLD-CVR and CBF-CVR may have differing dependencies on the baseline condition (Halani et al, 2015; Stefanovic et al, 2006) and on the type of vascular stimulus (Halani et al, 2015).…”

Cerebral oxygen extraction fractionMRI: Techniques and applications

“…A number of studies have investigated the change in OEF and CMRO 2 under various physiological challenges, including hypercapnia, 47,58,94,[115][116][117]274 hypocapnia (e.g., induced by hyperventilation), 112,115,[275][276][277] hyperoxia, 48,118,278,279 hypoxia, 48,116,278,[280][281][282] caffeine ingestion, 17,46,101,119,283,284 acetazolamide injection, 101,255,285 and acute glucose ingestion. 286…”

“…Increased 47,58,94,115,116,274 Decreased 47,58,94,115,116,274 Mixed literature reporting decreased 47,116,117,274 or unchanged 94,115 Hypocapnia Decreased 112,115,[275][276][277] Increased 112,115,[275][276][277] Unchanged 112,115,[275][276][277] Hyperoxia Decreased 48,315 or unchanged 118,278,279 Unchanged 48,118,278,279 Mixed literature reporting decreased, 48 or unchanged 118,278,279 Hypoxia Increased 48,116,278,…”