Cortical depth profiles of auditory and visual 7 T functional MRI responses in human superior temporal areas.

Invasive neurophysiological studies in nonhuman primates have shown different laminar activation profiles to auditory vs. visual stimuli in auditory cortices and adjacent polymodal areas. Means to examine the underlying feedforward vs. feedback type influences noninvasively have been limited in humans. Here, using 1-mm isotropic resolution 3D echo-planar imaging at 7 T, we studied the intracortical depth profiles of functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signals to brief auditory (noise bursts) and visual (checkerboard) stimuli. BOLD percent-signal-changes were estimated at 11 equally spaced intracortical depths, within regions-of-interest encompassing auditory (Heschl's gyrus, Heschl's sulcus, planum temporale, and posterior superior temporal gyrus) and polymodal (middle and posterior superior temporal sulcus) areas. Effects of differing BOLD signal strengths for auditory and visual stimuli were controlled via normalization and statistical modeling. The BOLD depth profile shapes, modeled with quadratic regression, were significantly different for auditory vs. visual stimuli in auditory cortices, but not in polymodal areas. The different depth profiles could reflect sensory-specific feedforward versus cross-sensory feedback influences, previously shown in laminar recordings in nonhuman primates. The results suggest that intracortical BOLD profiles can help distinguish between feedforward and feedback type influences in the human brain. Further experimental studies are still needed to clarify how underlying signal strength influences BOLD depth profiles under different stimulus conditions.

Slice-direction geometric distortion evaluation and correction with reversed slice-select gradient acquisitions.

Accurate spatial alignment of MRI data acquired across multiple contrasts in the same subject is often crucial for data analysis and interpretation, but can be challenging in the presence of geometric distortions that differ between acquisitions. It is well known that single-shot echo-planar imaging (EPI) acquisitions suffer from distortion in the phase-encoding direction due to B0 field inhomogeneities arising from tissue magnetic susceptibility differences and other sources, however there can be distortion in other encoding directions as well in the presence of strong field inhomogeneities. High-resolution ultrahigh-field MRI typically uses low bandwidth in the slice-encoding direction to acquire thin slices and, when combined with the pronounced B0 inhomogeneities, is prone to an additional geometric distortion in the slice direction as well. Here we demonstrate the presence of this slice distortion in high-resolution 7T EPI acquired with a novel pulse sequence allowing for the reversal of the slice-encoding gradient polarity that enables the acquisition of pairs of images with equal magnitudes of distortion in the slice direction but with opposing polarities. We also show that the slice-direction distortion can be corrected using gradient reversal-based method applying the same software used for conventional corrections of phase-encoding direction distortion.

Accelerated spin-echo functional MRI using multisection excitation by simultaneous spin-echo interleaving (MESSI) with complex-encoded generalized slice dithered enhanced resolution (cgSlider) simultaneous multislice echo-planar imaging.

PURPOSE: Spin-echo functional MRI (SE-fMRI) has the potential to improve spatial specificity when compared with gradient-echo fMRI. However, high spatiotemporal resolution SE-fMRI with large slice-coverage is challenging as SE-fMRI requires a long echo time to generate blood oxygenation level-dependent (BOLD) contrast, leading to long repetition times. The aim of this work is to develop an acquisition method that enhances the slice-coverage of SE-fMRI at high spatiotemporal resolution. THEORY AND METHODS: An acquisition scheme was developed entitled multisection excitation by simultaneous spin-echo interleaving (MESSI) with complex-encoded generalized slice dithered enhanced resolution (cgSlider). MESSI uses the dead-time during the long echo time by interleaving the excitation and readout of 2 slices to enable 2× slice-acceleration, while cgSlider uses the stable temporal background phase in SE-fMRI to encode/decode 2 adjacent slices simultaneously with a "phase-constrained" reconstruction method. The proposed cgSlider-MESSI was also combined with simultaneous multislice (SMS) to achieve further slice-acceleration. This combined approach was used to achieve 1.5-mm isotropic whole-brain SE-fMRI with a temporal resolution of 1.5 s and was evaluated using sensory stimulation and breath-hold tasks at 3T. RESULTS: Compared with conventional SE-SMS, cgSlider-MESSI-SMS provides 4-fold increase in slice-coverage for the same repetition time, with comparable temporal signal-to-noise ratio. Corresponding fMRI activation from cgSlider-MESSI-SMS for both fMRI tasks were consistent with those from conventional SE-SMS. Overall, cgSlider-MESSI-SMS achieved a 32× encoding-acceleration by combining Rinplane × MB × cgSlider × MESSI = 4 × 2 × 2 × 2. CONCLUSION: High-quality, high-resolution whole-brain SE-fMRI was acquired at a short repetition time using cgSlider-MESSI-SMS. This method should be beneficial for high spatiotemporal resolution SE-fMRI studies requiring whole-brain coverage.

Intracortical smoothing of small-voxel fMRI data can provide increased detection power without spatial resolution losses compared to conventional large-voxel fMRI data.

Continued improvement in MRI acquisition technology has made functional MRI (fMRI) with small isotropic voxel sizes down to 1 mm and below more commonly available. Although many conventional fMRI studies seek to investigate regional patterns of cortical activation for which conventional voxel sizes of 3 mm and larger provide sufficient spatial resolution, smaller voxels can help avoid contamination from adjacent white matter (WM) and cerebrospinal fluid (CSF), and thereby increase the specificity of fMRI to signal changes within the gray matter. Unfortunately, temporal signal-to-noise ratio (tSNR), a metric of fMRI sensitivity, is reduced in high-resolution acquisitions, which offsets the benefits of small voxels. Here we introduce a framework that combines small, isotropic fMRI voxels acquired at 7 T field strength with a novel anatomically-informed, surface mesh-navigated spatial smoothing that can provide both higher detection power and higher resolution than conventional voxel sizes. Our smoothing approach uses a family of intracortical surface meshes and allows for kernels of various shapes and sizes, including curved 3D kernels that adapt to and track the cortical folding pattern. Our goal is to restrict smoothing to the cortical gray matter ribbon and avoid noise contamination from CSF and signal dilution from WM via partial volume effects. We found that the intracortical kernel that maximizes tSNR does not maximize percent signal change (ΔS/S), and therefore the kernel configuration that optimizes detection power cannot be determined from tSNR considerations alone. However, several kernel configurations provided a favorable balance between boosting tSNR and ΔS/S, and allowed a 1.1-mm isotropic fMRI acquisition to have higher performance after smoothing (in terms of both detection power and spatial resolution) compared to an unsmoothed 3.0-mm isotropic fMRI acquisition. Overall, the results of this study support the strategy of acquiring voxels smaller than the cortical thickness, even for studies not requiring high spatial resolution, and smoothing them down within the cortical ribbon with a kernel of an appropriate shape to achieve the best performance-thus decoupling the choice of fMRI voxel size from the spatial resolution requirements of the particular study. The improvement of this new intracortical smoothing approach over conventional surface-based smoothing is expected to be modest for conventional resolutions, however the improvement is expected to increase with higher resolutions. This framework can also be applied to anatomically-informed intracortical smoothing of higher-resolution data (e.g. along columns and layers) in studies with prior information about the spatial structure of activation.

Reduction of across-run variability of temporal SNR in accelerated EPI time-series data through FLEET-based robust autocalibration.

Temporal signal-to-noise ratio (tSNR) is a key metric for assessing the ability to detect brain activation in fMRI data. A recent study has shown substantial variation of tSNR between multiple runs of accelerated EPI acquisitions reconstructed with the GRAPPA method using protocols commonly used for fMRI experiments. Across-run changes in the location of high-tSNR regions could lead to misinterpretation of the observed brain activation patterns, reduced sensitivity of the fMRI studies, and biased results. We compared conventional EPI autocalibration (ACS) methods with the recently-introduced FLEET ACS method, measuring their tSNR variability, as well as spatial overlap and displacement of high-tSNR clusters across runs in datasets acquired from human subjects at 7T and 3T. FLEET ACS reconstructed data had higher tSNR levels, as previously reported, as well as better temporal consistency and larger overlap of the high-tSNR clusters across runs compared with reconstructions using conventional multi-shot (ms) EPI ACS data. tSNR variability across two different runs of the same protocol using ms-EPI ACS data was about two times larger than for the protocol using FLEET ACS for acceleration factors (R) 2 and 3, and one and half times larger for R=4. The level of across-run tSNR consistency for data reconstructed with FLEET ACS was similar to within-run tSNR consistency. The displacement of high-tSNR clusters across two runs (inter-cluster distance) decreased from ∼8mm in the time-series reconstructed using conventional ms-EPI ACS data to ∼4mm for images reconstructed using FLEET ACS. However, the performance gap between conventional ms-EPI ACS and FLEET ACS narrowed with increasing parallel imaging acceleration factor. Overall, the FLEET ACS method provides a simple solution to the problem of varying tSNR across runs, and therefore helps ensure that an assumption of fMRI analysis-that tSNR is largely consistent across runs-is met for accelerated acquisitions.

3D in utero quantification of T2* relaxation times in human fetal brain tissues for age optimized structural and functional MRI.

PURPOSE: Maximization of the blood oxygen level-dependent (BOLD) functional MRI (fMRI) contrast requires the echo time of the MR sequence to match the T2* value of the tissue of interest, which is expected to be higher in the fetal brain compared with the brain of a child or an adult. METHODS: T2* values of the cortical plate/cortical gray matter tissue in utero in healthy fetuses from mid-gestation onward (20-36 gestational weeks) were measured using 3D T2* maps calculated from 2D dual-echo T2*-weighted data corrected for between-slice motion and reconstructed in 1.0 mm3 isotropic resolution from a sequence of multiple time points, together with 1.0 mm3 isotropic resolution T2-weighted structural data. RESULTS: Mean T2* relaxation times of the cortical tissue were about twice as high as those reported previously in adults. In a supporting experiment applying single seed analysis, default mode and auditory networks appeared better localized and less noisy while using an echo time of 100 ms versus 43 ms. The results of the previous study reporting a trend for T2* values to decrease with fetal age were reproduced and extended to include cortical tissues and subjects in earlier gestation (20-26 gestational weeks). CONCLUSION: The first measurement of T2* values in fetal cortical tissues suggested the appropriate echo time range for fetal BOLD fMRI protocol optimization to be 130-190 ms. Magn Reson Med 78:909-916, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Detecting default mode networks in utero by integrated 4D fMRI reconstruction and analysis.

Recently, there has been considerable interest, especially for in utero imaging, in the detection of functional connectivity in subjects whose motion cannot be controlled while in the MRI scanner. These cases require two advances over current studies: (1) multiecho acquisitions and (2) post processing and reconstruction that can deal with significant between slice motion during multislice protocols to allow for the ability to detect temporal correlations introduced by spatial scattering of slices into account. This article focuses on the estimation of a spatially and temporally regular time series from motion scattered slices of multiecho fMRI datasets using a full four-dimensional (4D) iterative image reconstruction framework. The framework which includes quantitative MRI methods for artifact correction is evaluated using adult studies with and without motion to both refine parameter settings and evaluate the analysis pipeline. ICA analysis is then applied to the 4D image reconstruction of both adult and in utero fetal studies where resting state activity is perturbed by motion. Results indicate quantitative improvements in reconstruction quality when compared to the conventional 3D reconstruction approach (using simulated adult data) and demonstrate the ability to detect the default mode network in moving adults and fetuses with single-subject and group analysis. Hum Brain Mapp 37:4158-4178, 2016. © 2016 Wiley Periodicals, Inc.

Increase in the iron content of the substantia nigra and red nucleus in multiple sclerosis and clinically isolated syndrome: a 7 Tesla MRI study.

PURPOSE: To study iron deposition in the substantia nigra (SN) and red nuclei (RN), in patients with clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS) and healthy controls (HC). MATERIALS AND METHODS: Iron deposition was assessed using susceptibility maps and T2*-w images acquired at high resolution MRI at 7 Tesla (T). Mean intensities were calculated within circular regions of interest in the SN (d/v, dorsal/ventral) and RN on high resolution T2*-w, quantitative susceptibility maps and their product for: RRMS, CIS and HC (N = 14, 21, 27, respectively). RESULTS: Magnetic susceptibility was significantly greater in SNd and RN in RRMS compared with HC (P = 0.04 [0.001, 0.48] and P = 0.01 [0.005, 0.05]), with intermediate values for the CIS group. 1/T2*-w did not show significant inter-group differences (for SNv, SNd, RN, respectively: P = 0.5 [-0.352, 0976], P = 0.35 [-0.208, 0.778], P = 0.16 [-0.114, 0.885] for RRMS versus HC) and the T2*-susceptibility product maps showed the difference only for RN (P = 0.01, [0.009, 0.062]). Changes were independent of EDSS and disease duration. CONCLUSION: MR changes consistent with iron accumulation occurring in the SN and RN of CIS patients can be identified using susceptibility mapping; this may provide an additional method of monitoring early MS development.

Visualization of nigrosome 1 and its loss in PD: pathoanatomical correlation and in vivo 7 T MRI.

OBJECTIVE: This study assessed whether high-resolution 7 T MRI allowed direct in vivo visualization of nigrosomes, substructures of the substantia nigra pars compacta (SNpc) undergoing the greatest and earliest dopaminergic cell loss in Parkinson disease (PD), and whether any disease-specific changes could be detected in patients with PD. METHODS: Postmortem (PM) midbrains, 2 from healthy controls (HCs) and 1 from a patient with PD, were scanned with high-resolution T2*-weighted MRI scans, sectioned, and stained for iron and neuromelanin (Perl), TH, and calbindin. To confirm the identification of nigrosomes in vivo on 7 T T2*-weighted scans, we assessed colocalization with neuromelanin-sensitive T1-weighted scans. We then assessed the ability to depict PD pathology on in vivo T2*-weighted scans by comparing data from 10 patients with PD and 8 age- and sex-matched HCs. RESULTS: A hyperintense, ovoid area within the dorsolateral border of the otherwise hypointense SNpc was identified in the HC brains on in vivo and PM T2*-weighted MRI. Location, size, shape, and staining characteristics conform to nigrosome 1. Blinded assessment by 2 neuroradiologists showed consistent bilateral absence of this nigrosome feature in all 10 patients with PD, and bilateral presence in 7/8 HC. CONCLUSIONS: In vivo and PM MRI with histologic correlation demonstrates that high-resolution 7 T MRI can directly visualize nigrosome 1. The absence of nigrosome 1 in the SNpc on MRI scans might prove useful in developing a neuroimaging diagnostic test for PD.