Subject head motion is a major challenge in DWI, leading to image blurring, signal losses, and biases in the estimated diffusion parameters. Here, we investigate a combined application of prospective motion correction and spatial-angular locally low-rank constrained reconstruction to obtain robust, multi-shot, high-resolution diffusion-weighted MRI under substantial motion.Methods: Single-shot EPI with retrospective motion correction can mitigate motion artifacts and resolve any mismatching of gradient encoding orientations; however, it is limited by low spatial resolution and image distortions. Multi-shot acquisition strategies could achieve higher resolution and image fidelity but increase the vulnerability to motion artifacts and phase variations related to cardiac pulsations from shot to shot. We use prospective motion correction with optical markerless motion tracking to remove artifacts and reduce image blurring due to bulk motion, combined with locally low-rank regularization to correct for remaining artifacts due to shot-to-shot phase variations. Results:The approach was evaluated on healthy adult volunteers at 3 Tesla under different motion patterns. In multi-shot DWI, image blurring due to motion with 20 mm translations and 30 • rotations was successfully removed by prospective motion correction, and aliasing artifacts caused by shot-to-shot phase variations were addressed by locally low-rank regularization. The ability of prospective motion correction to preserve the orientational information in DTI without requiring a reorientation of the b-matrix is highlighted. Conclusion:The described technique is proved to hold valuable potential for mapping brain diffusivity and connectivity at high resolution for studies in subjects/cohorts where motion is common, including neonates, pediatrics, and patients with neurological disorders.

Conventional echo‐planar imaging (EPI) uses a radiofrequency pulse for excitation and a prolonged echo train to sample k space, while off‐resonance and T2* decay effects caused by magnetic susceptibility variation accumulate within each echo, leading to geometric distortion. Multishot EPI methods, which divide k space into segments, can shorten the effective echo spacing and reduce the distortion on EPI images. But multiple shots cost longer scan time and render susceptibility to motion. In this study, we propose a new “multishot” EPI method termed pseudo multishot EPI (pmsEPI), in which phase‐encoding lines are segmented as in multishot EPI but are collected within a single shot. With the magnetization divided into different pathways via interleaved excitation instead of refocusing in a single long echo train, the total phase error accumulation is reduced in each segmented acquisition, thereby improving distortion of the resultant EPI image. The performance of the pmsEPI method is demonstrated by phantom and in vivo brain experiments on a 3‐T scanner. The experimental results show that the distortion displacements of pmsEPI acquisition compared with conventional EPI decrease by 50% with two pseudo shots and 66% with three pseudo shots, validating the ability of the method to obtain images with reduced distortion in a single shot, although magnetization splitting may induce more than 40% SNR loss and minor artifacts. Specifically, the ability of pmsEPI in diffusion‐weighted imaging with different trajectory options is highlighted, and the flexibility is demonstrated in a single‐shot blip up and down acquisition.

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