Introduction

Neurons with similar properties cluster together into sub-millimeter columnar and laminar structures, moreover neural activity occurs at millisecond resolution. Advances in fMRI approaches increase either spatial or temporal resolution but never both. Instead, line-scanning fMRI in rodents¹ can achieve very high resolution across cortical depth (50 μm) and time (50 ms), by sacrificing volume coverage and resolution along the cortical surface. This high spatiotemporal resolution can also allow us to isolate microvessel responses and to characterize the distribution of blood flow and laminar fMRI profiles across cortical depth. Here, we present the first human line-scanning implementation and results. First, we will focus on the evaluation of the quality of the saturation pulses, followed by the description of optimal coil combination for the reconstruction and finally we will demonstrate the sensitivity of line-scanning fMRI in a comparison with standard 2D GE-EPI BOLD fMRI using a visual task.

Methods

We scanned five healthy volunteers at 7T MRI (Philips) with a 32 channel receive head coil (Nova Medical). Line-scanning data acquisition used a modified 2D gradient-echo sequence: line resolution=250μm, TR/TE=200/13-22ms, 520 timepoints, flip angle=16°, array size=720, line thickness=2.5mm, in-plane line width=4mm, fat suppression using SPIR. Two saturation pulses (5 ms pulse duration) suppressed the signal outside the line of interest. We computed the outer volume suppression quality as the ratio signal along the line and outside the line. The phase-encoding in the direction perpendicular to the line was turned off². The line was positioned along the right-left axis, crossing the visual cortex (Figure 1). We acquired functional data using a block design in 6 runs. Visual stimuli were 20 Hz flickering checkerboard, presented for 10 s on/off. Reconstruction was performed offline (MatLab, Gyrotools). We combined multi-channel coil data in four different ways: 1) sum-of-squares (SoS), 2) tSNR-weighted SoS, 3) coil sensitivity weighted SoS (csm), 4) tSNR and coil sensitivity weighted SoS (tSNR+csm). Resulting tSNR was used to select the best coil combination. Functional data were analyzed using a GLM approach and t-statistic values were computed to detect active voxels. We also compared line-scanning data to a standard 2D GE-EPI BOLD acquisition with: 1x1 mm² in-plane spatial resolution, TR/TE=200/22 ms, 600 dynamics, flip angle=30°, FOV=176x176 mm², SENSE factor 3, partial Fourier=0.8. Here, we averaged the 2D BOLD timeseries data in the region of interest coinciding with the line before computing t-statistics, resulting in an activation profile along the line. Following manual coregistration and averaging of line-scanning data every 4 voxels (in order to match the different spatial resolutions of the two acquisitions), we also calculated the correlation between the t-statistic values of line-scanning and 2D GE-EPI BOLD.

Results

The achieved undesired signal suppression outside the relevant cortical area was (97±0.4)% (Figure 1).
Figure 2 shows the tSNR for the four different coil combinations. The weighted combination of both tSNR and csm outperformed the other variants in terms of final tSNR. This coil combination was selected for subsequent line-scanning reconstructions. Line-scanning data averaged over 6 runs is shown in Figure 3a, for a representative subject. The average line signal intensity profile through the occipital lobe is shown in Figure 3b.
Figure 4a shows the t-statistic values overlaid on the anatomical scan. Note the good spatial correspondence between the positive BOLD t-statistic values and the grey matter ribbon, indicated with white arrows. Figure 4b shows the time course of an example active voxel along with the GLM.
Finally, in Figure 5 the comparison between the line-scanning (left column) and standard 2D GE-EPI BOLD (right column) shows a high similarity in BOLD sensitivity expressed by the t-statistic line profile. Good correlation (R=0.75±0.17) was found between the t-statistic values for the two acquisitions.

Discussion & Conclusion

We report first line-scanning fMRI results in humans with very high spatiotemporal resolution and show similar BOLD sensitivity to standard 2D GE-EPI BOLD. Adequate outer volume suppression can be achieved with saturation pulses. A coil combination including coil sensitivity maps and tSNR/channel for the reconstruction furnishes a promising temporal stability, since the resulting tSNR values are comparable to sub-milllimeter 3D imaging and sufficient for BOLD signal detection³, relatively to voxel size. Note that for the current line-scanning data processing no temporal filtering was applied. Future experiments will examine physiological noise contributions and its removal. Moreover, further development will investigate improvements in signal suppression outside the line of interest (2D spatial excitation, spin-echo beam excitation using orthogonal 90-180° pulses) and increased SNR using surface coil arrays⁴.
Overall, the line-scanning fMRI technique seems very promising due to its potential in detecting evoked BOLD responses with sub-millimeter and sub-second resolution. Potential applications for line-scanning are microvessel function measurements in clinical research on cerebrovascular diseases but also fMRI at the mesoscopic scale such as cortical lamina⁵.

Acknowledgements

This study was supported by the Royal Netherlands Academy of Arts and Sciences Research Fund 2018 (KNAW BDO/3489) and the Visiting Professors Programme 2017 (KNAW WF/RB/3781) granted to the Spinoza Centre for Neuroimaging.