Simultaneous pure T2 and varying T2'-weighted BOLD fMRI using Echo Planar Time-resolved Imaging for mapping cortical-depth dependent responses

Abstract

Spin-echo (SE) BOLD fMRI has high microvascular specificity, and thus provides a more reliable means to localize neural activity compared to conventional gradient-echo BOLD fMRI. However, the most common SE BOLD acquisition method, SE-EPI, is known to suffer from T₂' contrast contamination with undesirable draining vein bias. To address this, in this study, we extended a recently developed distortion/blurring-free multi-shot EPI technique, Echo-Planar Time-resolved Imaging (EPTI), to cortical-depth dependent SE-fMRI at 7T to test whether it could provide purer SE BOLD contrast with minimal T₂' contamination for improved neuronal specificity. From the same acquisition, the time-resolved feature of EPTI also provides a series of asymmetric SE (ASE) images with varying T₂' weightings, and enables extraction of data equivalent to conventional SE EPI with different echo train lengths (ETLs). This allows us to systematically examine how T₂'-contribution affects different SE acquisition strategies using a single dataset. A low-rank spatiotemporal subspace reconstruction was implemented for the SE-EPTI acquisition, which incorporates corrections for both shot-to-shot phase variations and dynamic B₀ drifts. SE-EPTI was used in a visual task fMRI experiment to demonstrate that i) the pure SE image provided by EPTI results in the highest microvascular specificity; ii) the ASE EPTI series, with a graded introduction of T₂' weightings at time points farther away from the pure SE, show a gradual sensitivity increase along with increasing draining vein bias; iii) the longer ETL seen in conventional SE EPI acquisitions will induce more draining vein bias. Consistent results were observed across multiple subjects, demonstrating the robustness of the proposed technique for SE-BOLD fMRI with high specificity.

Keywords: Laminar fMRI; Microvascular specificity; Multi-echo; Spin-echo; T(2) BOLD; Ultra-high field.

Fig. 1.

Sequence diagram (a) and spatiotemporal CAIPI encoding of EPTI (b). Multi-contrast distortion-free images are generated at a small TE increment of an echo-spacing. (c) The recovered k-t data after reconstruction can provide SE image with pure T₂ weighting (gray), asymmetric SE (ASE) images with both T₂ and T₂′ weighting (orange), and extracted SE-EPI with different ETLs (green) to investigate the effect of T₂′ contamination.

Fig. 2.

(a) EPTI reconstruction framework with dynamic B₀ correction and shot-to-shot phase variation correction. (b) Illustration of the estimation method for shot-to-shot B₀ variation using multi-channel 1D navigators. (c) Subspace reconstruction to resolve multi-contrast images by solving a small number of coefficient maps of the subspace bases.

Fig. 3.

Evaluation of the shot-to-shot B₀ variation estimation and correction method. (a) Simulated shot-to-shot B₀ variation maps of the 3-shot acquisition (spatially 2^nd order). (b) Estimated B₀ variation maps using multi-channel 1D navigators. (c) Reconstructed pure SE images (TE = 64 ms) and their corresponding error maps (× 5) without variations, with variations but without correction, and after correction. (d) Reconstructed images and error maps for the ASE at TE = 82.5 ms. The RMSEs were listed at the bottom of each error map.

Fig. 4.

Examples of multi-echo EPTI images (left) acquired in the fMRI experiment covering the visual cortex (right). The images are shown for each dynamic after averaging all the runs. Three orthogonal views are presented for 5 selected echoes out of the total 45 echoes.

Fig. 5.

(a) Distortion comparison between the TSE reference, conventional EPI, EPTI and EPTI-extracted EPI. The image contours extracted from the TSE image are applied to all images (red lines). Conventional EPI shows obvious distortions at multiple areas (yellow arrows), while EPTI and EPTI-extracted EPI have almost identical image contours with the TSE image. (b) Evaluation of dynamic distortion changes. The zoomed-in 1D PE profiles (extracted from the locations indicated by the yellow dotted lines on the left) across different dynamics and runs are shown on the right to compare the level of dynamic distortion in conventional EPI, EPTI and EPTI-extracted EPI.

Fig. 6.

(a) Normalized z-score activation maps of different EPTI echo images. The white arrow shows an example region where the activation in the CSF is reduced relative to that in the gray matter in echoes with less T₂′ contributions. Normalization was performed based on the sum of the positive z-scores of each echo to normalize the sensitivity differences and to better visualize activation pattern. (b) Cortical depth dependent profiles of z-score and percent signal change of all the echoes (color-coded by echo indices shown on the top) across V1. The profiles from different echoes are normalized to have the same value at 0.5 cortical depth of the SE (echo 23) to better compare the slope difference.

Fig. 7.

Comparison of activation in unnormalized z-score between ASE images (echo 7 and 39), pure SE image (echo 23), and extracted SE ms-EPI (6-shot and 4-shot) all obtained from EPTI. The three SE images (second, fourth and fifth columns) show overall lower sensitivity but better spatial specificity than ASE echoes (first and third columns). The extracted SE ms-EPI, however, still suffers from substantial contamination and shows large amount of activation remaining in the CSF similar to the ASE echoes, while the pure SE has the peak of the activation more in the gray matter regions rather than centered in the CSF (highlighted by the white arrows).

Fig. 8.

Cortical-depth profiles of the unnormalized (left two columns) and normalized (right two columns) z-score and percent signal change in three subjects (N = 3). Five EPTI data are compared in each plot, including selected ASE images (echo 7 and 39), pure SE image (echo 23), extracted SE ms-EPI with ETL = 26 ms (6 shots) and 39 ms (4 shots). In all three subjects, the pure SE image shows the lowest slope with decreased activation at the CSF-GM interface, indicating a reduced level of bias from large veins.

Fig. 9.

(a) Comparison between activation maps of the conventional GE-EPI, SE-EPI, and EPTI images. The EPTI ASE images (echo 7 and 39) with T₂′ weighting show similar activation localization as the conventional GE ss-EPI, and the EPTI pure SE image (echo 23) provides less bias in CSF than the conventional SE ss-EPI and the extracted SE ms-EPI. (b) Comparison of the cortical-depth profiles between the acquired GE ss-EPI, SE ss-EPI, selected EPTI echo images and the EPTI-extracted SE ms-EPIs with different ETLs.