Purpose T2‐relaxation‐under‐spin‐tagging (TRUST) is an MR technique for the non‐invasive assessment of whole‐brain cerebral oxygen extraction fraction (OEF), through measurement of the venous blood T2 relaxation time in the sagittal sinus. A key limitation of TRUST, however, is the lack of spatial specificity of the measurement. We sought to develop a modified TRUST sequence, selective localized TRUST (SL‐TRUST), having sensitivity to venous blood T2 within a targeted brain region, and therefore achieving spatially localized measurements of cerebral tissue OEF, while still retaining acquisition in the sagittal sinus. Methods A method for selective localization of TRUST sequence was developed, and the reproducibility of the technique was evaluated in healthy participants. Regional measurements were achieved for a single hemisphere and for a 3D‐localized 70 × 70 × 80 mm3 tissue region using SL‐TRUST and compared to a global TRUST measure. An additional measure of venous blood T1 in the sagittal sinus was used to estimate subject‐specific hematocrit. Six subjects were scanned over 4 sessions, including intra‐session repeat measurements. Results The average T2 in the sagittal sinus was found to be 60.8 ± 8.9, 62.7 ± 7.9, 64.6 ± 8.4, and 66.3 ± 10.3 ms (mean ± SD) for conventional TRUST, global SL‐TRUST, hemispheric SL‐TRUST, and 3D‐localized SL‐TRUST, respectively. Intra‐, inter‐session, and inter‐subject coefficients of variation for OEF using SL‐TRUST were found to be comparable and in some cases superior to those obtained using TRUST. Conclusion OEF comparison of 2 contralateral regions was achievable in under 5 min suggesting SL‐TRUST offers potential for quantifying regional OEF differences in both healthy and clinical populations.

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