Spin-Echo Resting-State Functional Connectivity in High-Susceptibility Regions: Accuracy, Reliability, and the Impact of Physiological Noise

Gradient-echo (GE) echo-planar imaging (EPI) is the method of choice in blood-oxygenation level-dependent (BOLD) functional MRI (fMRI) studies, as it demonstrates substantially higher BOLD sensitivity than its spin-echo (SE) counterpart. However, it is also well known that the GE-EPI signal is prone to signal dropouts and shifts due to susceptibility effects near air-tissue interfaces. SE-EPI, in contrast, is minimally affected by these artifacts. In this study, we quantify, for the first time, the sensitivity and specificity of SE and GE EPI for resting-state fMRI functional connectivity (fcMRI) mapping, using the 1000-brain fcMRI atlas (Yeo et al., 2011 ) as the pseudoground truth. Moreover, we assess the influence of physiological processes on resting-state BOLD measured using both regular and ultrafast GE and SE acquisitions. Our work demonstrates that SE-EPI and GE-EPI are associated with similar sensitivities, specificities, and intersubject reproducibility in fcMRI for most brain networks, generated using both seed-based analysis and independent component analysis. More importantly, SE-based fcMRI measurements demonstrated significantly higher sensitivity, specificity, and intersubject reproducibility in high-susceptibility regions, spanning the limbic and frontal networks in the 1000-brain atlas. In addition, SE-EPI is significantly less sensitive to prominent sources of physiological noise, including low-frequency respiratory volume and heart rate variations. Our work suggests that SE-EPI should be increasingly adopted in the study of networks spanning susceptibility-affected brain regions, including those that are important to memory, language, and emotion.