Ultra-high spatial resolution BOLD fMRI in humans using combined segmented-accelerated VFA-FLEET with a recursive RF pulse design

Purpose To alleviate the spatial encoding limitations of single-shot echo-planar imaging (EPI) by developing multi-shot segmented EPI for ultra-high-resolution functional MRI (fMRI) with reduced ghosting artifacts from subject motion and respiration. Theory and Methods Segmented EPI can reduce readout duration and reduce acceleration factors, however, the time elapsed between segment acquisitions (on the order of seconds) can result in intermittent ghosting, limiting its use for fMRI. Here, "FLEET" segment ordering, where segments are looped over before slices, was combined with a variable flip angle progression (VFA-FLEET) to improve inter-segment fidelity and maximize signal for fMRI. Scaling a sinc pulse's flip angle for each segment (VFA-FLEET-Sinc) produced inconsistent slice profiles and ghosting, therefore, a recursive Shinnar-Le Roux (SLR) radiofrequency (RF) pulse design was developed (VFA-FLEET-SLR) to generate unique pulses for every segment that together produce consistent slice profiles and signals. Results The temporal stability of VFA-FLEET-SLR was compared against conventional-segmented EPI and VFA-FLEET-Sinc at 3T and 7T. VFA-FLEET-SLR showed reductions in both intermittent and stable ghosting compared to conventional-segmented and VFA-FLEET-Sinc, resulting in improved image quality with a minor trade-off in temporal SNR. Combining VFA-FLEET-SLR with acceleration, we achieved a 0.6-mm isotropic acquisition at 7T, without zoomed imaging or partial Fourier, demonstrating reliable detection of blood oxygenation level-dependent (BOLD) responses to a visual stimulus. To counteract the increased repetition time from segmentation, simultaneous multi-slice VFA-FLEET-SLR was demonstrated using RF-encoded controlled aliasing. Conclusions VFA-FLEET with a recursive RF pulse design supports acquisitions with low levels of artifact and spatial blur, enabling fMRI at previously inaccessible spatial resolutions with a "full-brain" field of view.