Improved laminar specificity and sensitivity by combining SE and GE BOLD signals.

The most widely used gradient-echo (GE) blood oxygenation level-dependent (BOLD) contrast has high sensitivity, but low specificity due to draining vein contributions, while spin-echo (SE) BOLD approach at ultra-high magnetic fields is highly specific to neural active sites but has lower sensitivity. To obtain high specificity and sensitivity, we propose to utilize a vessel-size-sensitive filter to the GE-BOLD signal, which suppresses macrovascular contributions and to combine selectively retained microvascular GE-BOLD signals with the SE-BOLD signals. To investigate our proposed idea, fMRI with 0.8 mm isotropic resolution was performed on the primary motor and sensory cortices in humans at 7 T by implementing spin- and gradient-echo (SAGE) echo planar imaging (EPI) acquisition. Microvascular-passed sigmoidal filters were designed based upon the vessel-size-sensitive ΔR2*/ΔR2 value for retaining GE-BOLD signals originating from venous vessels with ≤ 45 µm and ≤ 65 µm diameter. Unlike GE-BOLD fMRI, the laminar profile of SAGE-BOLD fMRI with the vessel-size-sensitive filter peaked at ∼ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity over GE-BOLD fMRI. Also, the functional sensitivity of SAGE BOLD at middle layers (0.75-1.5 mm) was improved by ∼ 80% to ∼100% when compared with SE BOLD. In summary, we showed that combined GE- and SE-BOLD fMRI with the vessel-size-sensitive filter indeed yielded improved laminar specificity and sensitivity and is therefore an excellent tool for high spatial resolution ultra-high filed (UHF)-fMRI studies for resolving mesoscopic functional units.

Improvement of sensitivity and specificity for laminar BOLD fMRI with double spin-echo EPI in humans at 7 T.

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.

Reproducibility and Reliability of Quantitative and Weighted T1 and T2∗ Mapping for Myelin-Based Cortical Parcellation at 7 Tesla.

Different magnetic resonance (MR) parameters, such as R1 (=1/T1) or T2∗, have been used to visualize non-invasively the myelin distribution across the cortical sheet. Myelin contrast is consistently enhanced in the primary sensory and some higher order cortical areas (such as MT or the cingulate cortex), which renders it suitable for subject-specific anatomical cortical parcellation. However, no systematic comparison has been performed between the previously proposed MR parameters, i.e., the longitudinal and transversal relaxation values (or their ratios), for myelin mapping at 7 Tesla. In addition, usually these MR parameters are acquired in a non-quantitative manner ("weighted" parameters). Here, we evaluated the differences in 'parcellability,' contrast-to-noise ratio (CNR) and inter- and intra-subject variability and reproducibility, respectively, between high-resolution cortical surface maps based on these weighted MR parameters and their quantitative counterparts in ten healthy subjects. All parameters were obtained in a similar acquisition time and possible transmit- or receive-biases were removed during post-processing. It was found that CNR per unit time and parcellability were lower for the transversal compared to the longitudinal relaxation parameters. Further, quantitative R1 was characterized by the lowest inter- and intra-subject coefficient of variation (5.53 and 1.63%, respectively), making R1 a better parameter to map the myelin distribution compared to the other parameters. Moreover, quantitative MRI approaches offer the advantage of absolute rather than relative characterization of the underlying biochemical composition of the tissue, allowing more reliable comparison within subjects and between healthy subjects and patients. Finally, we explored two parcellation methods (thresholding the MR parameter values vs. surface gradients of these values) to determine areal borders based on the cortical surface pattern. It is shown that both methods are partially observer-dependent, needing manual interaction (i.e., choice of threshold or connecting high gradient values) to provide unambiguous borders.