Fuzzy ripple artifact in high resolution fMRI: identification, cause, and mitigation.

Purpose: High resolution fMRI is a rapidly growing research field focused on capturing functional signal changes across cortical layers. However, the data acquisition is limited by low spatial frequency EPI artifacts; termed here as Fuzzy Ripples. These artifacts limit the practical applicability of acquisition protocols with higher spatial resolution, faster acquisition speed, and they challenge imaging in lower brain areas. Methods: We characterize Fuzzy Ripple artifacts across commonly used sequences and distinguish them from conventional EPI Nyquist ghosts, off-resonance effects, and GRAPPA artifacts. To investigate their origin, we employ dual polarity readouts. Results: Our findings indicate that Fuzzy Ripples are primarily caused by readout-specific imperfections in k-space trajectories, which can be exacerbated by inductive coupling between third-order shims and readout gradients. We also find that these artifacts can be mitigated through complex-valued averaging of dual polarity EPI or by disconnecting the third-order shim coils. Conclusion: The proposed mitigation strategies allow overcoming current limitations in layer-fMRI protocols: (1)Achieving resolutions beyond 0.8mm is feasible, and even at 3T, we achieved 0.53mm voxel functional connectivity mapping.(2)Sub-millimeter sampling acceleration can be increased to allow sub-second TRs and laminar whole brain protocols with up to GRAPPA 8.(3)Sub-millimeter fMRI is achievable in lower brain areas, including the cerebellum.