Evaluation of 2D multiband EPI imaging for high-resolution, whole-brain, task-based fMRI studies at 3T: Sensitivity and slice leakage artifacts

Abstract

Functional magnetic resonance imaging (fMRI) studies that require high-resolution whole-brain coverage have long scan times that are primarily driven by the large number of thin slices acquired. Two-dimensional multiband echo-planar imaging (EPI) sequences accelerate the data acquisition along the slice direction and therefore represent an attractive approach to such studies by improving the temporal resolution without sacrificing spatial resolution. In this work, a 2D multiband EPI sequence was optimized for 1.5mm isotropic whole-brain acquisitions at 3T with 10 healthy volunteers imaged while performing simultaneous visual and motor tasks. The performance of the sequence was evaluated in terms of BOLD sensitivity and false-positive activation at multiband (MB) factors of 1, 2, 4, and 6, combined with in-plane GRAPPA acceleration of 2× (GRAPPA 2), and the two reconstruction approaches of Slice-GRAPPA and Split Slice-GRAPPA. Sensitivity results demonstrate significant gains in temporal signal-to-noise ratio (tSNR) and t-score statistics for MB 2, 4, and 6 compared to MB 1. The MB factor for optimal sensitivity varied depending on anatomical location and reconstruction method. When using Slice-GRAPPA reconstruction, evidence of false-positive activation due to signal leakage between simultaneously excited slices was seen in one instance, 35 instances, and 70 instances over the ten volunteers for the respective accelerations of MB 2×GRAPPA 2, MB 4×GRAPPA 2, and MB 6×GRAPPA 2. The use of Split Slice-GRAPPA reconstruction suppressed the prevalence of false positives significantly, to 1 instance, 5 instances, and 5 instances for the same respective acceleration factors. Imaging protocols using an acceleration factor of MB 2×GRAPPA 2 can be confidently used for high-resolution whole-brain imaging to improve BOLD sensitivity with very low probability for false-positive activation due to slice leakage. Imaging protocols using higher acceleration factors (MB 3 or MB 4×GRAPPA 2) can likely provide even greater gains in sensitivity but should be carefully optimized to minimize the possibility of false activations.

Keywords: High resolution; Multiband excitation; Simultaneous multislice; Whole brain; fMRI.

Fig. 1

(A) Example magnitude images from Volunteer 5 for the four multiband factors and two reconstruction types. Images are displayed after the post-processing steps of realignment and smoothing. (B) Corresponding tSNR_S maps from the same volunteer.

Fig. 2

Comparison of temporal SNR values across MB factors and reconstruction types. Traditional tSNR values (Eq. (1)) are shown in panels A–C; scaled tSNR values, tSNR_S, taking into account the effective degrees of freedom (Eq. (2)) are shown in panels D–F. Voxel-wise tSNR and tSNR_S values were averaged over the anatomical ROIs for each volunteer, and the mean and standard deviation over volunteers of these average values is presented. One-tailed t-tests were used to determine significant differences. Significant differences between the MB factors are shown in blue text and significant differences between reconstruction types are shown in green text, with *a significance level of p < 0.05 and **a significance level of p < 0.01.

Fig. 3

Example t-score maps in five transverse planes from Volunteer 1 for the four multiband factors and two reconstruction types. The t-scores show activation from left visual hemifield and left hand finger-tapping stimuli. The t-scores are overlaid on the post-processed MB EPI images with a threshold of p < 0.001, uncorrected.

Fig. 4

Sensitivity analysis: number of activated voxels. The bar plots show the number of activated voxels within an anatomical region of interest that passed the significance threshold corresponding to p < 0.001, uncorrected (mean and standard deviation over all volunteers). Significant differences between the MB factors are shown in blue text, with *a significance level of p < 0.05 and **a significance level of p < 0.01. There were no significant differences between the reconstruction types.

Fig. 5

Sensitivity analysis: mean of highest 1% of t-score values. The bar plots show the mean value of the highest 1% of t-score values within an anatomical region of interest (mean and standard deviation over all volunteers). Significant differences between the MB factors are shown in blue text and significant differences between reconstruction types are shown in green text, with *a significance level of p < 0.05 and **a significance level of p < 0.01.

Fig. 6

Example of false-positive activation due to signal leakage between simultaneously excited slices. The top image shows the suspected false-positive activation from an MB 6 scan of Volunteer 2 with Slice-GRAPPA (SG) reconstruction, originating from the voxel at the blue cross and aliasing into voxels at the yellow arrows. The horizontal dashed yellow lines indicate the six slices that were simultaneously excited and acquired with the blue cross slice. The yellow crosses indicate the alias locations due to the combined CAIPI shift of FOV/3 and in-plane GRAPPA 2. The bottom row of images shows the MB 1, MB 2, and MB 4 results from the same volunteer. No activation is seen within a 3 × 3 × 3 voxel ROI around the suspected false-positive locations from the MB 6 scan (yellow boxes). These three regions of activation from the MB 6 scan were therefore deemed to be false-positive activations.

Fig. 7

Examples of false-positive activation for MB 6 and MB 4 scans. The same notation is used as in Fig. 6, where the blue crosses indicates the seed voxel, the dashed yellow lines give the simultaneously excited slices, the yellow crosses give the alias locations, and the yellow arrows indicate confirmed instances of false-positive activation.

Fig. 8

Comparison of false-positive activations in Slice-GRAPPA and Split Slice-GRAPPA reconstructions. For the examples shown here, all of the false positives seen using Slice-GRAPPA reconstruction are suppressed when using Split Slice-GRAPPA reconstruction.

Fig. 9

Activation maps and corresponding signal leakage maps for Slice-GRAPPA and Split Slice-GRAPPA reconstructions. Data are from Volunteer 1, MB 6, the same as shown in the first column of Fig. 8. The activation maps show the “seed” voxel with a blue arrow, alias locations at the intersection of the yellow dashed lines, and confirmed false positives with yellow arrows. Leakage maps show the signal originating in the “seed” slice and leakage from this slice into the simultaneously excited slices.

Fig. 10

Summary of false-positive activations seen over all volunteers. For each MB factor and reconstruction type, the bar plots show the total number of confirmed instances of false-positive activation found over all ten volunteers.