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This paper describes an integrated approach for neuroimaging data acquisition, analysis and sharing. Building on methodological advances from the Human Connectome Project (HCP) and elsewhere, the HCP-style paradigm applies to new and existing data sets that meet core requirements and may accelerate progress in understanding the brain in health and disease. Noninvasive human neuroimaging has yielded many discoveries about the brain. Numerous methodological advances have also occurred, though inertia has slowed their adoption. This paper presents an integrated approach to data acquisition, analysis and sharing that builds upon recent advances, particularly from the Human Connectome Project (HCP). The 'HCP-style' paradigm has seven core tenets: (i) collect multimodal imaging data from many subjects; (ii) acquire data at high spatial and temporal resolution; (iii) preprocess data to minimize distortions, blurring and temporal artifacts; (iv) represent data using the natural geometry of cortical and subcortical structures; (v) accurately align corresponding brain areas across subjects and studies; (vi) analyze data using neurobiologically accurate brain parcellations; and (vii) share published data via user-friendly databases. We illustrate the HCP-style paradigm using existing HCP data sets and provide guidance for future research. Widespread adoption of this paradigm should accelerate progress in understanding the brain in health and disease.

We evaluate residual aliasing among simultaneously excited and acquired slices in slice accelerated multiband (MB) echo planar imaging (EPI). No in-plane accelerations were used in order to maximize and evaluate achievable slice acceleration factors at 3T. We propose a novel leakage (L-) factor to quantify the effects of signal leakage between simultaneously acquired slices. With a standard 32-channel receiver coil at 3T, we demonstrate that slice acceleration factors of up to eight (MB=8) with blipped controlled aliasing in parallel imaging (CAIPI), in the absence of in-plane accelerations, can be used routinely with acceptable image quality and integrity for whole brain imaging. Spectral analyses of single-shot fMRI time series demonstrate that temporal fluctuations due to both neuronal and physiological sources were distinguishable and comparable up to slice-acceleration factors of nine (MB=9). The increased temporal efficiency could be employed to achieve, within a given acquisition period, higher spatial resolution, increased fMRI statistical power, multiple TEs, faster sampling of temporal events in a resting state fMRI time series, increased sampling of q-space in diffusion imaging, or more quiet time during a scan. [Display omitted] •High slice accelerations using multiband (MB) GRE-EPI with blipped CAIPI.•Acceptable MB factors up to 8 with a 32-channel receiver coil at 3T.•Neuronal and physiological sources are distinguishable at high MB factors.•Leakage (L-) factor evaluates residual aliasing among simultaneously acquired slices.•High temporal efficiency with MB-EPI benefits various applications.

Functional magnetic resonance imaging (fMRI) studies that require high-resolution whole-brain coverage have long scan times that are primarily driven by the large number of thin slices acquired. Two-dimensional multiband echo-planar imaging (EPI) sequences accelerate the data acquisition along the slice direction and therefore represent an attractive approach to such studies by improving the temporal resolution without sacrificing spatial resolution. In this work, a 2D multiband EPI sequence was optimized for 1.5mm isotropic whole-brain acquisitions at 3T with 10 healthy volunteers imaged while performing simultaneous visual and motor tasks. The performance of the sequence was evaluated in terms of BOLD sensitivity and false-positive activation at multiband (MB) factors of 1, 2, 4, and 6, combined with in-plane GRAPPA acceleration of 2× (GRAPPA 2), and the two reconstruction approaches of Slice-GRAPPA and Split Slice-GRAPPA. Sensitivity results demonstrate significant gains in temporal signal-to-noise ratio (tSNR) and t-score statistics for MB 2, 4, and 6 compared to MB 1. The MB factor for optimal sensitivity varied depending on anatomical location and reconstruction method. When using Slice-GRAPPA reconstruction, evidence of false-positive activation due to signal leakage between simultaneously excited slices was seen in one instance, 35 instances, and 70 instances over the ten volunteers for the respective accelerations of MB 2×GRAPPA 2, MB 4×GRAPPA 2, and MB 6×GRAPPA 2. The use of Split Slice-GRAPPA reconstruction suppressed the prevalence of false positives significantly, to 1 instance, 5 instances, and 5 instances for the same respective acceleration factors. Imaging protocols using an acceleration factor of MB 2×GRAPPA 2 can be confidently used for high-resolution whole-brain imaging to improve BOLD sensitivity with very low probability for false-positive activation due to slice leakage. Imaging protocols using higher acceleration factors (MB 3 or MB 4×GRAPPA 2) can likely provide even greater gains in sensitivity but should be carefully optimized to minimize the possibility of false activations. •MB factors 1, 2, 4, and 6 and two reconstructions were evaluated for fMRI performance.•MB accelerations 2, 4, and 6 improved BOLD sensitivity metrics over MB 1.•False-positive activation due to signal leakage was seen at high accelerations.•Use of Split Slice-GRAPPA reconstruction significantly reduces false positives.

Whole-brain functional magnetic resonance imaging (fMRI), in conjunction with multiband acceleration, has played an important role in mapping the functional connectivity throughout the entire brain with both high temporal and spatial resolution. Ultrahigh magnetic field strengths (7T and above) allow functional imaging with even higher functional contrast-to-noise ratios for improved spatial resolution and specificity compared to traditional field strengths (1.5T and 3T). High-resolution 7T fMRI, however, has primarily been constrained to smaller brain regions given the amount of time it takes to acquire the number of slices necessary for high resolution whole brain imaging. Here we evaluate a range of whole-brain high-resolution resting state fMRI protocols (0.9, 1.25, 1.5, 1.6 and 2mm isotropic voxels) at 7T, obtained with both in-plane and slice acceleration parallel imaging techniques to maintain the temporal resolution and brain coverage typically acquired at 3T. Using the processing pipeline developed by the Human Connectome Project, we demonstrate that high resolution images acquired at 7T provide increased functional contrast to noise ratios with significantly less partial volume effects and more distinct spatial features, potentially allowing for robust individual subject parcellations and descriptions of fine-scaled patterns, such as visuotopic organization.

Resting-state functional magnetic resonance imaging has become a powerful tool for the study of functional networks in the brain. Even \"at rest,\" the brain's different functional networks spontaneously fluctuate in their activity level; each network's spatial extent can therefore be mapped by finding temporal correlations between its different subregions. Current correlation-based approaches measure the average functional connectivity between regions, but this average is less meaningful for regions that are part of multiple networks; one ideally wants a network model that explicitly allows overlap, for example, allowing a region's activity pattern to reflect one network's activity some of the time, and another network's activity at other times. However, even those approaches that do allow overlap have often maximized mutual spatial independence, which may be suboptimal if distinct networks have significant overlap. In this work, we identify functionally distinct networks by virtue of their temporal independence, taking advantage of the additional temporal richness available via improvements in functional magnetic resonance imaging sampling rate. We identify multiple \"temporal functional modes,\" including several that subdivide the default-mode network (and the regions anticorrelated with it) into several functionally distinct, spatially overlapping, networks, each with its own pattern of correlations and anticorrelations. These functionally distinct modes of spontaneous brain activity are, in general, quite different from resting-state networks previously reported, and may have greater biological interpretability.

The Human Connectome Project (HCP) relies primarily on three complementary magnetic resonance (MR) methods. These are: 1) resting state functional MR imaging (rfMRI) which uses correlations in the temporal fluctuations in an fMRI time series to deduce ‘functional connectivity’; 2) diffusion imaging (dMRI), which provides the input for tractography algorithms used for the reconstruction of the complex axonal fiber architecture; and 3) task based fMRI (tfMRI), which is employed to identify functional parcellation in the human brain in order to assist analyses of data obtained with the first two methods. We describe technical improvements and optimization of these methods as well as instrumental choices that impact speed of acquisition of fMRI and dMRI images at 3T, leading to whole brain coverage with 2mm isotropic resolution in 0.7s for fMRI, and 1.25mm isotropic resolution dMRI data for tractography analysis with three-fold reduction in total dMRI data acquisition time. Ongoing technical developments and optimization for acquisition of similar data at 7T magnetic field are also presented, targeting higher spatial resolution, enhanced specificity of functional imaging signals, mitigation of the inhomogeneous radio frequency (RF) fields, and reduced power deposition. Results demonstrate that overall, these approaches represent a significant advance in MR imaging of the human brain to investigate brain function and structure. •We describe technical advances accomplished in the Human Connectome Project (HCP).•Highly accelerated imaging significantly improves fMRI and diffusion weighted MRI.•Instrumentation improvements in the HCP lead to superior diffusion-weighted MRI.•We describe of HCP efforts at both 3 and 7T, comparing their relative merits.•We describe recent developments with RF pulses for improved slice accelerated MRI.

T1-weighted divided by T2-weighted (T1w/T2w) myelin maps were initially developed for neuroanatomical analyses such as identifying cortical areas, but they are increasingly used in statistical comparisons across individuals and groups with other variables of interest. Existing T1w/T2w myelin maps contain radiofrequency transmit field (B1+) biases, which may be correlated with these variables of interest, leading to potentially spurious results. Here we propose two empirical methods for correcting these transmit field biases using either explicit measures of the transmit field or alternatively a ‘pseudo-transmit’ approach that is highly correlated with the transmit field at 3T. We find that the resulting corrected T1w/T2w myelin maps are both better neuroanatomical measures (e.g., for use in cross-species comparisons), and more appropriate for statistical comparisons of relative T1w/T2w differences across individuals and groups (e.g., sex, age, or body-mass-index) within a consistently acquired study at 3T. We recommend that investigators who use the T1w/T2w approach for mapping cortical myelin use these B1+ transmit field corrected myelin maps going forward.

Resting state functional connectivity refers to the temporal correlations between spontaneous hemodynamic signals obtained using functional magnetic resonance imaging. This technique has demonstrated that the structure and dynamics of identifiable networks are altered in psychiatric and neurological disease states. Thus, resting state network organizations can be used as a diagnostic, or prognostic recovery indicator. However, much about the physiological basis of this technique is unknown. Thus, providing a translational bridge to an optimal animal model, the macaque, in which invasive circuit manipulations are possible, is of utmost importance. Current approaches to resting state measurements in macaques face unique challenges associated with signal-to-noise, the need for contrast agents limiting translatability, and within-subject designs. These limitations can, in principle, be overcome through ultra-high magnetic fields. However, imaging at magnetic fields above 7T has yet to be adapted for fMRI in macaques. Here, we demonstrate that the combination of high channel count transmitter and receiver arrays, optimized pulse sequences, and careful anesthesia regimens, allows for detailed single-subject resting state analysis at high resolutions using a 10.5 Tesla scanner. In this study, we uncover thirty spatially detailed resting state components that are highly robust across individual macaques and closely resemble the quality and findings of connectomes from large human datasets. This detailed map of the rsfMRI ‘macaque connectome’ will be the basis for future neurobiological circuit manipulation work, providing valuable biological insights into human connectomics.

•We achieved 3D-FID-MRSI via concentric ring trajectory readouts at 10.5 t with nominal 2.75 mm isotropic resolution within 25 min.•Mapping of up to 13 brain metabolites plus macromolecules including overlapping and low concentrated neurochemicals such as aspartate, GABA, glucose, glutamine and NAAG.•Dedicated parallel transmit and receive coil setup, with up to 80 coils, ensured high SNR and homogenous field distributions. Ultra-high-field magnetic resonance (MR) systems (7 T and 9.4 T) offer the ability to probe human brain metabolism with enhanced precision. Here, we present the preliminary findings from 3D MR spectroscopic imaging (MRSI) of the human brain conducted with the world's first 10.5 T whole-body MR system. Employing a custom-built 16-channel transmit and 80-channel receive MR coil at 10.5 T, we conducted MRSI acquisitions in six healthy volunteers to map metabolic compounds in the human cerebrum in vivo. Three MRSI protocols with different matrix sizes and scan times (4.4 × 4.4 × 4.4 mm³: 10 min, 3.4 × 3.4 × 3.4 mm³: 15 min, and 2.75×2.75×2.75 mm³: 25 min) were tested. Concentric ring trajectories were utilized for time-efficient encoding of a spherical 3D k-space with ∼4 kHz spectral bandwidth. B0/B1 shimming was performed based on respective field mapping sequences and anatomical T1-weighted MRI were obtained. By combining the benefits of an ultra-high-field system with the advantages of free-induction-decay (FID-)MRSI, we present the first metabolic maps acquired at 10.5 T in the healthy human brain at both high (voxel size of 4.4³ mm³) and ultra-high (voxel size of 2.75³ mm³) isotropic spatial resolutions. Maps of 13 metabolic compounds (aspartate, choline compounds and creatine + phosphocreatine, γ-aminobutyric acid (GABA), glucose, glutamine, glutamate, glutathione, myo-inositol, scyllo-inositol, N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), taurine) and macromolecules were obtained individually. The spectral quality was outstanding in the parietal and occipital lobes, but lower in other brain regions such as the temporal and frontal lobes. The average total NAA (tNAA = NAA + NAAG) signal-to-noise ratio over the whole volume of interest was 12.1± 8.9 and the full width at half maximum of tNAA was 24.7± 9.6 Hz for the 2.75 × 2.75 × 2.75 mm³ resolution. The need for an increased spectral bandwidth in combination with spatio-spectral encoding imposed significant challenges on the gradient system, but the FID approach proved very robust to field inhomogeneities of ∆B0 = 45 ± 38 Hz (frequency offset ± spatial STD) and B1+ = 65 ± 11° within the MRSI volume of interest. These preliminary findings highlight the potential of 10.5 T MRSI as a powerful imaging tool for probing cerebral metabolism. By providing unprecedented spatial and spectral resolution, this technology could offer a unique view into the metabolic intricacies of the human brain, but further technical developments will be necessary to optimize data quality and fully leverage the capabilities of 10.5 T MRSI. [Display omitted]

We evaluate residual aliasing among simultaneously excited and acquired slices in slice accelerated multiband (MB) echo planar imaging (EPI). No in-plane accelerations were used in order to maximize and evaluate achievable slice acceleration factors at 3 T. We propose a novel leakage (L-) factor to quantify the effects of signal leakage between simultaneously acquired slices. With a standard 32-channel receiver coil at 3 T, we demonstrate that slice acceleration factors of up to eight (MB=8) with blipped controlled aliasing in parallel imaging (CAIPI), in the absence of in-plane accelerations, can be used routinely with acceptable image quality and integrity for whole brain imaging. Spectral analyses of single-shot fMRI time series demonstrate that temporal fluctuations due to both neuronal and physiological sources were distinguishable and comparable up to slice-acceleration factors of nine (MB=9). The increased temporal efficiency could be employed to achieve, within a given acquisition period, higher spatial resolution, increased fMRI statistical power, multiple TEs, faster sampling of temporal events in a resting state fMRI time series, increased sampling of q-space in diffusion imaging, or more quiet time during a scan.