From Wiley via Jisc Publications RouterHistory: received 2020-10-06, rev-recd 2021-03-05, accepted 2021-03-08, pub-electronic 2021-03-29, pub-print 2021-09Article version: VoRPublication status: PublishedFunder: GE Healthcare; Id: http://dx.doi.org/10.13039/100006775Funder: Engineering and Physical Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000266; Grant(s): EP/M005909/1Purpose: We sought to determine the degree to which oxygen extraction fraction (OEF) estimated using quantitative susceptibility mapping (QSM) depends on two critical acquisition parameters that have a significant impact on acquisition time: voxel size and final echo time. Methods: Four healthy volunteers were imaged using a range of isotropic voxel sizes and final echo times. The 0.7 mm data were downsampled at different stages of QSM processing by a factor of 2 (to 1.4 mm), 3 (2.1 mm), or 4 (2.8 mm) to determine the impact of voxel size on each analysis step. OEF was estimated from 11 veins of varying diameter. Inter‐ and intra‐session repeatability were estimated for the optimal protocol by repeat scanning in 10 participants. Results: Final echo time was found to have no significant effect on OEF. The effect of voxel size was significant, with larger voxel sizes underestimating OEF, depending on the proximity of the vein to the superficial surface of the brain and on vein diameter. The last analysis step of estimating vein OEF values from susceptibility images had the largest dependency on voxel size. Inter‐session coefficients of variation on OEF estimates of between 5.2% and 8.7% are reported, depending on the vein. Conclusion: QSM acquisition times can be minimized by reducing the final echo time but an isotropic voxel size no larger than 1 mm is needed to accurately estimate OEF in most medium/large veins in the brain. Such acquisitions can be achieved in under 4 min