Abstract

Mapping mesoscopic cortical functional units such as columns or laminae is increasingly pursued by ultra-high field (UHF) functional magnetic resonance imaging (fMRI). The most popular approach for high-resolution fMRI is currently gradient-echo (GE) blood oxygenation level-dependent (BOLD) fMRI. However, its spatial accuracy is reduced due to its sensitivity to draining vessels, including pial veins, whereas spin-echo (SE) BOLD signal is expected to have higher spatial accuracy, albeit with lower sensitivity than the GE-BOLD signal. Here, we introduce a new double spin-echo (dSE) echo-planar imaging (EPI) method to improve the sensitivity of SE-BOLD contrast by averaging two spin-echoes using three radiofrequency pulses. Human fMRI experiments were performed with slices perpendicular to the central sulcus between motor and sensory cortices at 7 T during fist-clenching with touching. First, we evaluated the feasibility of single-shot dSE-EPI for BOLD fMRI with 1.5 mm isotropic resolution and found that dSE-BOLD fMRI has higher signal-to-noise ratio (SNR), temporal SNR (tSNR), and higher functional sensitivity than conventional SE-BOLD fMRI. Second, to investigate the laminar specificity of dSE-BOLD fMRI, we implemented a multi-shot approach to achieve 0.8-mm isotropic resolution with sliding-window reconstruction. Unlike GE-BOLD fMRI, the cortical profile of dSE-BOLD fMRI peaked at ~ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity in humans over GE-BOLD fMRI. The proposed multi-shot dSE-EPI method is viable for high spatial resolution UHF-fMRI studies in the pursuit of resolving mesoscopic functional units.

Highlights

  • High spatio-temporal resolution functional magnetic resonance imaging permits the investigation of detailed functional units, such as the cortical columns or laminae

  • We demonstrated the feasibility of double spin-echo (dSE)-echo-planar imaging (EPI) by comparing sensitivity indexes such as signal-to-noise ratio (SNR), temporal SNR, and contrast-to-noise ratio (CNR) between dSE-EPI and conventional SE-EPI, obtained from resting-state functional magnetic resonance imaging (fMRI)

  • Monte Carlo (MC) simulation was performed using parameters closely matched with Experiment #1 to obtain insight into the signal sources of dSEBOLD measurements

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Summary

Introduction

High spatio-temporal resolution functional magnetic resonance imaging (fMRI) permits the investigation of detailed functional units, such as the cortical columns or laminae. It is generally accepted that gradient-echo (GE)-BOLD signal is highest at the surface of the cortex due to the high density of draining veins (Kim and Ugurbil, 2003; Zhao et al, 2004), which are distal to neural activation. For this reason, the GE-BOLD signal without draining vein removal may not be accurate spatially to sub-millimeter functional structures at high magnetic fields (Havlicek and Uludağ, 2020; Markuerkiaga et al, 2016; Marquardt et al, 2020). Spin-echo (SE)-BOLD signal is expected to be confined in the gray matter (Harel et al, 2006; Lee et al, 1999; Yacoub et al, 2003; Zhao et al, 2006, 2004) because

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