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Purpose  To develop a new water–fat separation and B 0  estimation algorithm to effectively suppress the multiple resonances of fat signal in EPI. This is especially relevant for DWI where fat is often a confounding factor.    Methods  Water–fat separation based on chemical‐shift encoding enables robust fat suppression in routine MRI. However, for EPI the different chemical‐shift displacements of the multiple fat resonances along the phase‐encoding direction can be problematic for conventional separation algorithms. This work proposes a suitable model approximation for EPI under B 0  and fat off‐resonance effects, providing a feasible multi‐peak water–fat separation algorithm. Simulations were performed to validate the algorithm. In vivo validation was performed in 6 volunteers, acquiring spin‐echo EPI images in the leg (B 0  homogeneous) and head‐neck (B 0  inhomogeneous) regions, using a TE‐shifted interleaved EPI sequence with/without diffusion sensitization. The results are numerically and statistically compared with voxel‐independent water–fat separation and fat saturation techniques to demonstrate the performance of the proposed algorithm.    Results  The reference separation algorithm without the proposed spatial shift correction caused water–fat ambiguities in simulations and in vivo experiments. Some spectrally selective fat saturation approaches also failed to suppress fat in regions with severe B 0  inhomogeneities. The proposed algorithm was able to achieve improved fat suppression for DWI data and ADC maps in the head–neck and leg regions.    Conclusion  The proposed algorithm shows improved suppression of the multi‐peak fat components in multi‐shot interleaved EPI applications compared to the conventional fat saturation approaches and separation algorithms.

Regularized joint water–fat separation with B 0 map estimation in image space for 2D‐navigated interleaved EPI based diffusion MRI