Asymmetric spin echo multi-echo echo planar imaging (ASEME-EPI) sequence for pre-clinical high-field fMRI

Abstract

In functional magnetic resonance imaging (fMRI) of the blood oxygen level-dependent (BOLD) contrast, gradient-recalled echo (GRE) acquisitions offer high sensitivity but suffer from susceptibility-induced signal loss and lack specificity to microvasculature. In contrast, spin echo (SE) acquisitions provide improved specificity at the cost of reduced sensitivity. This study introduces Asymmetric Spin Echo Multi-Echo Echo Planar Imaging (ASEME-EPI), a technique designed to combine the benefits of both GRE and SE for high-field preclinical fMRI. ASEME-EPI employs a spin echo readout followed by two asymmetric spin echo (ASE) GRE readouts, providing an initial T2-weighted SE image and subsequent T2*-weighted ASE images. A feasibility study for the technique was implemented on a 9.4 T pre-clinical MRI system and tested using a visual stimulation in northern tree shrews. Comparing ASEME-EPI with conventional GRE echo planar imaging (GRE-EPI) and SE echo planar imaging (SE-EPI) acquisitions, results showed that ASEME-EPI achieved BOLD contrast-to-noise ratio (CNR) comparable to GRE-EPI while offering improved specificity in activation maps. ASEME-EPI activation was more confined to the primary visual cortex (V1), unlike GRE-EPI which showed activation extending beyond anatomical boundaries. Additionally, ASEME-EPI demonstrated the ability to recover signal in areas of severe field inhomogeneity where GRE-EPI suffered from signal loss. The performance of ASEME-EPI is attributed to its multi-echo nature, allowing for SNR-optimized combination of echoes, effectively denoising the data. The inclusion of the initial SE also contributes to signal recovery in areas prone to susceptibility artifacts. This feasibility study demonstrates the potential of ASEME-EPI for high-field pre-clinical fMRI, offering a promising compromise between GRE sensitivity and SE specificity while addressing challenges of T2* decay at high field strengths.

Fig 1.. Signal evolution illustration for the ASEME-EPI acquisition.

Three echoes are drawn preceded by a 90° and 180° RF preparation. The first echo is a SE with the seceding echoes being ASEs; the ASEs are GRE readouts. T2* and T2 relaxation curves are included. The center of the spin echo occurs at $t_{\text{e}ff}=0$ which serves as the shifted time origin for analysis. The initial SE signal at $t_{\text{e}ff}=0$ is $S_{0,eff}$ with the resultant signal intensities measured for the ASEs having undergone T2* attenuation relative to $S_{0,eff}$. The initial SE signal $S_{0,eff}$ can be related back to $S_0$ through T2 decay.

Fig 2.. Normalized BOLD mean (a) CNR, (b) βcontrast, and (c) standard deviation of the residuals to the fit model.

Voxels with t-statistics corresponding to $\alpha \ge {\alpha }_{empirical}$ were plotted; ${\alpha }_{empirical}$ values can be found in S1 Table. The shapes designate different subjects and the gray bars mark the inter-subject means. Normalized mean BOLD CNR is normalized ${\beta }_{contrast}$ divided by the normalized standard deviation of the residuals to the fit model, or (b) divided by (c). No significant differences were found between GRE and the other acquisitions after performing a Wilcoxon signed-rank test ($H_0:{\mu }_D=0$, $H_a:{\mu }_D<0$) on the normalized mean CNRs.

Fig 3.. Activation maps in the same slice and the same subject (▲; Fig 2) across the seven acquisitions.

T-statistic thresholds were adjusted per acquisition to achieve a FWE of 0.01, and details of the thresholds for each series are provided in S2 Table. Activation maps are shown over EPI images of the respective schemes.