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Cerebrovascular reactivity (CVR)-weighted blood-oxygenation-level-dependent magnetic resonance imaging (BOLD-MRI) experiments are frequently used in conjunction with hyperoxia. Owing to complex interactions between hyperoxia and hypercapnia, quantitative effects of these gas mixtures on BOLD responses, blood and tissue R 2  ∗ , and blood oxygenation are incompletely understood. Here we performed BOLD imaging (3T; TE/TR = 35/2,000 ms; spatial resolution = 3×3×3.5 mm 3 ) in healthy volunteers ( n = 12; age = 29±4.1 years) breathing (i) room air (RA), (ii) normocapnic-hyperoxia (95% O 2 /5% N 2 , HO), (iii) hypercapnic-normoxia (5% CO 2 /21% O 2 /74% N 2 , HC-NO), and (iv) hypercapnic-hyperoxia (5% CO 2 /95% O 2 , HC-HO). For HC-HO, experiments were performed with separate RA and HO baselines to control for changes in O 2 . T 2 -relaxation-under-spin-tagging MRI was used to calculate basal venous oxygenation. Signal changes were quantified and established hemodynamic models were applied to quantify vasoactive blood oxygenation, blood–water R∗ 2 , and tissue-water R∗ 2 . In the cortex, fractional BOLD changes (stimulus/baseline) were HO/RA = 0.011 ± 0.007; HC-NO/RA = 0.014±0.004; HC-HO/HO = 0.020±0.008; and HC-HO/RA = 0.035 ±0.010; for the measured basal venous oxygenation level of 0.632, this led to venous blood oxygenation levels of 0.660 (HO), 0.665 (HC-NO), and 0.712 (HC-HO). Interleaving a HC-HO stimulus with HO baseline provided a smaller but significantly elevated BOLD response compared with a HC-NO stimulus. Results provide an outline for how blood oxygenation differs for several gas stimuli and provides quantitative information on how hypercapnic BOLD CVR and R∗ 2  are altered during hyperoxia.

The Cumulative Influence of Hyperoxia and Hypercapnia on Blood Oxygenation and R2*

The Cumulative Influence of Hyperoxia and Hypercapnia on Blood Oxygenation and R₂^*