BackgroundOxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂) may serve as biomarkers in several diseases. OEF and CMRO₂ can be estimated from venous blood oxygenation (Y_v) levels, which in turn can be calculated from venous blood T2 values (T2_b). T2_b can be measured using different MRI sequences, including T2‐relaxation‐under‐spin‐tagging (TRUST) and T2‐prepared‐blood‐relaxation‐imaging‐with‐inversion‐recovery (T2‐TRIR). The latter measures both T2_b and T1 (T1_b) but was found previously to overestimate T2_b compared to TRUST. It remained unclear, however, if this bias is constant across higher and lower oxygen saturations.PurposeTo compare TRUST and T2‐TRIR across a range of O₂ saturations using hypoxic and hypercapnic gas challenges.Study TypeProspective.PopulationTwelve healthy volunteers (four female, age 36 ± 10 years).Field Strength/SequenceA 3T; turbo‐field echo‐planar‐imaging (TFEPI), echo‐planar‐imaging (EPI), and fast‐field‐echo (FFE).AssessmentTRUST‐ and T2‐TRIR‐derived T2_b, Y_v, OEF, and CMRO₂ were compared across different respiratory challenges. T1_b from T2‐TRIR was used to estimate Hct (Hct_TRIR) and compared with venipuncture (Hct_VP).Statistical TestsShapiro–Wilk, one‐sample and paired‐sample t‐test, repeated measures ANOVA, Friedman test, Bland–Altman, and correlation analysis. Bonferroni multiple‐comparison correction was performed. Significance level was 0.05.ResultsA significant bias was observed between TRUST‐ and T2‐TRIR‐derived T2_b, Y_v, and OEF values (−13 ± 11 msec, −5.3% ± 3.5% and 5.9 ± 4.1%, respectively). For Y_v and OEF, this bias was constant across the range of measured values. T1_b was significantly lower during severe hypoxia and hypercapnia compared to baseline (1712 ± 86 msec and 1634 ± 79 msec compared to 1757 ± 90 msec). While no significant bias was found between Hct_VP and Hct_TRIR (0.02% ± 0.06%, P = 0.20), the correlation between these Hct values was significant but weak (r = 0.19).Data ConclusionGiven the constant bias, TRUST‐ and T2‐TRIR‐derived venous T2_b values can be used interchangeably to estimate Y_v, OEF, and CMRO₂ across a broad range of oxygen saturations. Hct from T2‐TRIR‐derived T1‐values only weakly correlated with Hct from venipuncture.Evidence Level2Technical EfficacyStage 2.