Role of articulatory motor networks in perceptual categorization of speech signals: a 7T fMRI study.

Speech and language processing involve complex interactions between cortical areas necessary for articulatory movements and auditory perception and a range of areas through which these are connected and interact. Despite their fundamental importance, the precise mechanisms underlying these processes are not fully elucidated. We measured BOLD signals from normal hearing participants using high-field 7 Tesla fMRI with 1-mm isotropic voxel resolution. The subjects performed 2 speech perception tasks (discrimination and classification) and a speech production task during the scan. By employing univariate and multivariate pattern analyses, we identified the neural signatures associated with speech production and perception. The left precentral, premotor, and inferior frontal cortex regions showed significant activations that correlated with phoneme category variability during perceptual discrimination tasks. In addition, the perceived sound categories could be decoded from signals in a region of interest defined based on activation related to production task. The results support the hypothesis that articulatory motor networks in the left hemisphere, typically associated with speech production, may also play a critical role in the perceptual categorization of syllables. The study provides valuable insights into the intricate neural mechanisms that underlie speech processing.

Linear multi-scale modeling of diffusion MRI data: A framework for characterization of oriented structures across length scales.

Diffusion-weighted magnetic resonance imaging (DW-MRI) has evolved to provide increasingly sophisticated investigations of the human brain's structural connectome in vivo. Restriction spectrum imaging (RSI) is a method that reconstructs the orientation distribution of diffusion within tissues over a range of length scales. In its original formulation, RSI represented the signal as consisting of a spectrum of Gaussian diffusion response functions. Recent technological advances have enabled the use of ultra-high b-values on human MRI scanners, providing higher sensitivity to intracellular water diffusion in the living human brain. To capture the complex diffusion time dependence of the signal within restricted water compartments, we expand upon the RSI approach to represent restricted water compartments with non-Gaussian response functions, in an extended analysis framework called linear multi-scale modeling (LMM). The LMM approach is designed to resolve length scale and orientation-specific information with greater specificity to tissue microstructure in the restricted and hindered compartments, while retaining the advantages of the RSI approach in its implementation as a linear inverse problem. Using multi-shell, multi-diffusion time DW-MRI data acquired with a state-of-the-art 3 T MRI scanner equipped with 300 mT/m gradients, we demonstrate the ability of the LMM approach to distinguish different anatomical structures in the human brain and the potential to advance mapping of the human connectome through joint estimation of the fiber orientation distributions and compartment size characteristics.

Mapping the human connectome using diffusion MRI at 300 mT/m gradient strength: Methodological advances and scientific impact.

Tremendous efforts have been made in the last decade to advance cutting-edge MRI technology in pursuit of mapping structural connectivity in the living human brain with unprecedented sensitivity and speed. The first Connectom 3T MRI scanner equipped with a 300 mT/m whole-body gradient system was installed at the Massachusetts General Hospital in 2011 and was specifically constructed as part of the Human Connectome Project. Since that time, numerous technological advances have been made to enable the broader use of the Connectom high gradient system for diffusion tractography and tissue microstructure studies and leverage its unique advantages and sensitivity to resolving macroscopic and microscopic structural information in neural tissue for clinical and neuroscientific studies. The goal of this review article is to summarize the technical developments that have emerged in the last decade to support and promote large-scale and scientific studies of the human brain using the Connectom scanner. We provide a brief historical perspective on the development of Connectom gradient technology and the efforts that led to the installation of three other Connectom 3T MRI scanners worldwide - one in the United Kingdom in Cardiff, Wales, another in continental Europe in Leipzig, Germany, and the latest in Asia in Shanghai, China. We summarize the key developments in gradient hardware and image acquisition technology that have formed the backbone of Connectom-related research efforts, including the rich array of high-sensitivity receiver coils, pulse sequences, image artifact correction strategies and data preprocessing methods needed to optimize the quality of high-gradient strength diffusion MRI data for subsequent analyses. Finally, we review the scientific impact of the Connectom MRI scanner, including advances in diffusion tractography, tissue microstructural imaging, ex vivo validation, and clinical investigations that have been enabled by Connectom technology. We conclude with brief insights into the unique value of strong gradients for diffusion MRI and where the field is headed in the coming years.

Rehabilitating the addicted brain with transcranial magnetic stimulation.

Substance use disorders (SUDs) are one of the leading causes of morbidity and mortality worldwide. In spite of considerable advances in understanding the neural underpinnings of SUDs, therapeutic options remain limited. Recent studies have highlighted the potential of transcranial magnetic stimulation (TMS) as an innovative, safe and cost-effective treatment for some SUDs. Repetitive TMS (rTMS) influences neural activity in the short and long term by mechanisms involving neuroplasticity both locally, under the stimulating coil, and at the network level, throughout the brain. The long-term neurophysiological changes induced by rTMS have the potential to affect behaviours relating to drug craving, intake and relapse. Here, we review TMS mechanisms and evidence that rTMS is opening new avenues in addiction treatments.

A 3-axis coil design for multichannel TMS arrays.

PURPOSE: Multichannel Transcranial Magnetic Stimulation (mTMS) arrays enable multiple sites to be stimulated simultaneously or sequentially under electronic control without moving the system's stimulation coils. Here, we build and characterize the performance of a novel modular 3-axis TMS coil that can be utilized as a unit element in large-scale multichannel TMS arrays. METHODS: We determined the basic physical characteristics of the 3-axis TMS coil x-, y- and z-elements using a custom 2-channel programmable stimulator prototype. We mapped the temporal rate-of-change of the induced magnetic field (dB/dt) on a 2D plane parallel to the coil surface (including an extended line for full spatial coverage) and compared those values with predictions from magnetic field simulations. Temperature measurements were carried out to assess the incorporated air-cooling method. We measured the mutual and self-inductances of the x/y/z-elements to assess coupling between them. Additionally, we measured and calculated the coupling between z-elements in the array configuration. Finally, we performed electric field simulations to evaluate the stimulation intensity and focality of the coil and compared the results to conventional TMS coils as well as demonstrated suitability of the 3-axis coil for a multichannel array configuration. RESULTS: The experimentally obtained dB/dt values validated the computational model of the 3-axis coil and therefore confirmed that both the coil and stimulator system are operating as intended. The air-cooling system was effective for brief high-frequency pulse trains and extended single- and paired-pulse TMS protocols. The electromagnetic simulations suggested that an array of the 3-axis coils would have comparable stimulation intensity to conventional TMS coils, therefore enabling clearly suprathreshold stimulation of the human brain. The recorded coil coupling between the x/y/z-elements was < 1% and the maximal coupling between z-elements in the array configuration was 1.8% and 3.4% for the measured and calculated values, respectively. CONCLUSION: We presented a 3-axis coil intended for multichannel TMS arrays. The electromagnetic measurements and simulations verified that the coil fabrication met the desired specifications and that the inductive coupling between the elements was negligible. The air-cooled 3-axis TMS coil appears suitable to be used as an element in multichannel TMS arrays.

Scan-rescan repeatability of axonal imaging metrics using high-gradient diffusion MRI and statistical implications for study design.

Axon diameter mapping using diffusion MRI in the living human brain has attracted growing interests with the increasing availability of high gradient strength MRI systems. A systematic assessment of the consistency of axon diameter estimates within and between individuals is needed to gain a comprehensive understanding of how such methods extend to quantifying differences in axon diameter index between groups and facilitate the design of neurobiological studies using such measures. We examined the scan-rescan repeatability of axon diameter index estimation based on the spherical mean technique (SMT) approach using diffusion MRI data acquired with gradient strengths up to 300 mT/m on a 3T Connectom system in 7 healthy volunteers. We performed statistical power analyses using data acquired with the same protocol in a larger cohort consisting of 15 healthy adults to investigate the implications for study design. Results revealed a high degree of repeatability in voxel-wise restricted volume fraction estimates and tract-wise estimates of axon diameter index derived from high-gradient diffusion MRI data. On the region of interest (ROI) level, across white matter tracts in the whole brain, the Pearson's correlation coefficient of the axon diameter index estimated between scan and rescan experiments was r = 0.72 with an absolute deviation of 0.18 µm. For an anticipated 10% effect size in studies of axon diameter index, most white matter regions required a sample size of less than 15 people to observe a measurable difference between groups using an ROI-based approach. To facilitate the use of high-gradient strength diffusion MRI data for neuroscientific studies of axonal microstructure, the comprehensive multi-gradient strength, multi-diffusion time data used in this work will be made publicly available, in support of open science and increasing the accessibility of such data to the greater scientific community.

Rapid computation of TMS-induced E-fields using a dipole-based magnetic stimulation profile approach.

BACKGROUND: TMS neuronavigation with on-line display of the induced electric field (E-field) has the potential to improve quantitative targeting and dosing of stimulation, but present commercially available solutions are limited by simplified approximations. OBJECTIVE: Developing a near real-time method for accurate approximation of TMS induced E-fields with subject-specific high-resolution surface-based head models that can be utilized for TMS navigation. METHODS: Magnetic dipoles are placed on a closed surface enclosing an MRI-based head model of the subject to define a set of basis functions for the incident and total E-fields that define the subject's Magnetic Stimulation Profile (MSP). The near real-time speed is achieved by recognizing that the total E-field of the coil only depends on the incident E-field and the conductivity boundary geometry. The total E-field for any coil position can be obtained by matching the incident field of the stationary dipole basis set with the incident E-field of the moving coil and applying the same basis coefficients to the total E-field basis functions. RESULTS: Comparison of the MSP-based approximation with an established TMS solver shows great agreement in the E-field amplitude (relative maximum error around 5%) and the spatial distribution patterns (correlation >98%). Computation of the E-field took ~100 ms on a cortical surface mesh with 120k facets. CONCLUSION: The numerical accuracy and speed of the MSP approximation method make it well suited for a wide range of computational tasks including interactive planning, targeting, dosing, and visualization of the intracranial E-fields for near real-time guidance of coil positioning.

Connectome 2.0: Developing the next-generation ultra-high gradient strength human MRI scanner for bridging studies of the micro-, meso- and macro-connectome.

The first phase of the Human Connectome Project pioneered advances in MRI technology for mapping the macroscopic structural connections of the living human brain through the engineering of a whole-body human MRI scanner equipped with maximum gradient strength of 300 mT/m, the highest ever achieved for human imaging. While this instrument has made important contributions to the understanding of macroscale connectional topology, it has also demonstrated the potential of dedicated high-gradient performance scanners to provide unparalleled in vivo assessment of neural tissue microstructure. Building on the initial groundwork laid by the original Connectome scanner, we have now embarked on an international, multi-site effort to build the next-generation human 3T Connectome scanner (Connectome 2.0) optimized for the study of neural tissue microstructure and connectional anatomy across multiple length scales. In order to maximize the resolution of this in vivo microscope for studies of the living human brain, we will push the diffusion resolution limit to unprecedented levels by (1) nearly doubling the current maximum gradient strength from 300 mT/m to 500 mT/m and tripling the maximum slew rate from 200 T/m/s to 600 T/m/s through the design of a one-of-a-kind head gradient coil optimized to minimize peripheral nerve stimulation; (2) developing high-sensitivity multi-channel radiofrequency receive coils for in vivo and ex vivo human brain imaging; (3) incorporating dynamic field monitoring to minimize image distortions and artifacts; (4) developing new pulse sequences to integrate the strongest diffusion encoding and highest spatial resolution ever achieved in the living human brain; and (5) calibrating the measurements obtained from this next-generation instrument through systematic validation of diffusion microstructural metrics in high-fidelity phantoms and ex vivo brain tissue at progressively finer scales with accompanying diffusion simulations in histology-based micro-geometries. We envision creating the ultimate diffusion MRI instrument capable of capturing the complex multi-scale organization of the living human brain - from the microscopic scale needed to probe cellular geometry, heterogeneity and plasticity, to the mesoscopic scale for quantifying the distinctions in cortical structure and connectivity that define cyto- and myeloarchitectonic boundaries, to improvements in estimates of macroscopic connectivity.

Axon diameter index estimation independent of fiber orientation distribution using high-gradient diffusion MRI.

Axon diameter mapping using high-gradient diffusion MRI has generated great interest as a noninvasive tool for studying trends in axonal size in the human brain. One of the main barriers to mapping axon diameter across the whole brain is accounting for complex white matter fiber configurations (e.g., crossings and fanning), which are prevalent throughout the brain. Here, we present a framework for generalizing axon diameter index estimation to the whole brain independent of the underlying fiber orientation distribution using the spherical mean technique (SMT). This approach is shown to significantly benefit from the use of real-valued diffusion data with Gaussian noise, which reduces the systematic bias in the estimated parameters resulting from the elevation of the noise floor when using magnitude data with Rician noise. We demonstrate the feasibility of obtaining whole-brain orientationally invariant estimates of axon diameter index and relative volume fractions in six healthy human volunteers using real-valued diffusion data acquired on a dedicated high-gradient 3-Tesla human MRI scanner with 300 mT/m maximum gradient strength. The trends in axon diameter index are consistent with known variations in axon diameter from histology and demonstrate the potential of this generalized framework for revealing coherent patterns in axonal structure throughout the living human brain. The use of real-valued diffusion data provides a viable solution for eliminating the Rician noise floor and should be considered for all spherical mean approaches to microstructural parameter estimation.

Evaluation of RF interactions between a 3T birdcage transmit coil and transcranial magnetic stimulation coils using a realistically shaped head phantom.

PURPOSE: Multichannel transcranial magnetic stimulation (TMS)1 is an emerging technology that allows multiple sites to be stimulated simultaneously or sequentially under electronic control without movement of the coils. A multichannel TMS/MRI head coil array for 3 Tesla is currently under development to mitigate challenges of concurrent TMS/fMRI as well as enable potential new applications. The influence of the multichannel TMS system on the MR image quality and safety must be carefully investigated. METHODS: A standard birdcage volume coil for 3 Tesla systems was simulated using a commercial numerical electromagnetic solver. Two setups, consisting of 1) a MR-compatible TMS coil, and 2) a 3-axis TMS coil array, were simulated to quantify changes in the transmit field B1+ and the SAR. A realistically shaped homogeneous head model was used in the computations. RESULTS: The stimulation coils produced enhancements and attenuations on the transmit field with effects greater than 5% up to 2.4 cm and 3.3 cm under the scalp for the MR-compatible TMS coil and 3-axis TMS coil array, respectively. The 10 g-SAR distribution did not change significantly in either of the cases; however, the nominal SAR maximum locus was shifted between existing hot spots. CONCLUSION: The simulated B1+ variations found near the TMS coils indicate the possibility of inducing sequence-dependent image artefacts predominatly limited to the vicinity of the coil(s). However, we conclude that neither the MR-compatible commercial TMS coil nor the 3-axis TMS coil array siginificantly elevate SAR in the head or neck beyond accepted safety limits.

Age-related alterations in axonal microstructure in the corpus callosum measured by high-gradient diffusion MRI.

Cerebral white matter exhibits age-related degenerative changes during the course of normal aging, including decreases in axon density and alterations in axonal structure. Noninvasive approaches to measure these microstructural alterations throughout the lifespan would be invaluable for understanding the substrate and regional variability of age-related white matter degeneration. Recent advances in diffusion magnetic resonance imaging (MRI) have leveraged high gradient strengths to increase sensitivity toward axonal size and density in the living human brain. Here, we examined the relationship between age and indices of axon diameter and packing density using high-gradient strength diffusion MRI in 36 healthy adults (aged 22-72) in well-defined central white matter tracts in the brain. A recently validated method for inferring the effective axonal compartment size and packing density from diffusion MRI measurements acquired with 300 mT/m maximum gradient strength was applied to the in vivo human brain to obtain indices of axon diameter and density in the corpus callosum, its sub-regions, and adjacent anterior and posterior fibers in the forceps minor and forceps major. The relationships between the axonal metrics, corpus callosum area and regional gray matter volume were also explored. Results revealed a significant increase in axon diameter index with advancing age in the whole corpus callosum. Similar analyses in sub-regions of the corpus callosum showed that age-related alterations in axon diameter index and axon density were most pronounced in the genu of the corpus callosum and relatively absent in the splenium, in keeping with findings from previous histological studies. The significance of these correlations was mirrored in the forceps minor and forceps major, consistent with previously reported decreases in FA in the forceps minor but not in the forceps major with age. Alterations in the axonal imaging metrics paralleled decreases in corpus callosum area and regional gray matter volume with age. Among older adults, results from cognitive testing suggested an association between larger effective compartment size in the corpus callosum, particularly within the genu of the corpus callosum, and lower scores on the Montreal Cognitive Assessment, largely driven by deficits in short-term memory. The current study suggests that high-gradient diffusion MRI may be sensitive to the axonal substrate of age-related white matter degeneration reflected in traditional DTI metrics and provides further evidence for regionally selective alterations in white matter microstructure with advancing age.

Electrically Small Dipole Antenna Probe for Quasistatic Electric Field Measurements in Transcranial Magnetic Stimulation.

The present paper designs, constructs, and tests an electrically small dipole antenna probe for the measurement of electric field distributions with the ultimate purpose to directly measure electric fields induced by a transcranial magnetic stimulation (TMS) coil. Its unique features include applicability to measurements in both air and conducting medium, high spatial resolution, large frequency band from 100 Hz to 300 KHz, efficient feedline isolation via a printed Dyson balun, and accurate mitigation of noise. Prior work in this area is thoroughly reviewed. The proposed probe design is realized in hardware; implementation details and design tradeoffs are described. Test data are presented for the measurement of a constant wave capacitor electric field, demonstrating the probe's ability to properly measure electric fields caused by a charge distribution. Test data are also presented for the measurement of a constant wave solenoidal electric field, demonstrating the probe's ability to measure electric fields caused by Faraday's law of induction. Those are the primary fields for the transcranial magnetic stimulation. Further steps necessary for the application of this probe as an instrument for TMS coil design are discussed.

Validation of diffusion MRI estimates of compartment size and volume fraction in a biomimetic brain phantom using a human MRI scanner with 300 mT/m maximum gradient strength.

Diffusion microstructural imaging techniques have attracted great interest in the last decade due to their ability to quantify axon diameter and volume fraction in healthy and diseased human white matter. The estimates of compartment size and volume fraction continue to be debated, in part due to the lack of a gold standard for validation and quality control. In this work, we validate diffusion MRI estimates of compartment size and volume fraction using a novel textile axon ("taxon") phantom constructed from hollow polypropylene yarns with distinct intra- and extra-taxonal compartments to mimic white matter in the brain. We acquired a comprehensive set of diffusion MRI measurements in the phantom using multiple gradient directions, diffusion times and gradient strengths on a human MRI scanner equipped with maximum gradient strength (Gmax) of 300 mT/m. We obtained estimates of compartment size and restricted volume fraction through a straightforward extension of the AxCaliber/ActiveAx frameworks that enables estimation of mean compartment size in fiber bundles of arbitrary orientation. The voxel-wise taxon diameter estimates of 12.2 ±â€¯0.9 µm were close to the manufactured inner diameter of 11.8 ±â€¯1.2 µm with Gmax = 300 mT/m. The estimated restricted volume fraction demonstrated an expected decrease along the length of the fiber bundles in accordance with the known construction of the phantom. When Gmax was restricted to 80 mT/m, the taxon diameter was overestimated, and the estimates for taxon diameter and packing density showed greater uncertainty compared to data with Gmax = 300 mT/m. In conclusion, the compartment size and volume fraction estimates resulting from diffusion measurements on a human scanner were validated against ground truth in a phantom mimicking human white matter, providing confidence that this method can yield accurate estimates of parameters in simplified but realistic microstructural environments. Our work also demonstrates the importance of a biologically analogous phantom that can be applied to validate a variety of diffusion microstructural imaging methods in human scanners and be used for standardization of diffusion MRI protocols for neuroimaging research.

High-resolution in vivo diffusion imaging of the human brain with generalized slice dithered enhanced resolution: Simultaneous multislice (gSlider-SMS).

PURPOSE: To develop an efficient acquisition for high-resolution diffusion imaging and allow in vivo whole-brain acquisitions at 600- to 700-µm isotropic resolution. METHODS: We combine blipped-controlled aliasing in parallel imaging simultaneous multislice (SMS) with a novel slab radiofrequency (RF) encoding gSlider (generalized slice-dithered enhanced resolution) to form a signal-to-noise ratio-efficient volumetric simultaneous multislab acquisition. Here, multiple thin slabs are acquired simultaneously with controlled aliasing, and unaliased with parallel imaging. To achieve high resolution in the slice direction, the slab is volumetrically encoded using RF encoding with a scheme similar to Hadamard encoding. However, with gSlider, the RF-encoding bases are specifically designed to be highly independent and provide high image signal-to-noise ratio in each slab acquisition to enable self-navigation of the diffusion's phase corruption. Finally, the method is combined with zoomed imaging (while retaining whole-brain coverage) to facilitate low-distortion single-shot in-plane encoding with echo-planar imaging at high resolution. RESULTS: A 10-slices-per-shot gSlider-SMS acquisition was used to acquire whole-brain data at 660 and 760 µm isotropic resolution with b-values of 1500 and 1800 s/mm2 , respectively. Data were acquired on the Connectome 3 Tesla scanner with 64-channel head coil. High-quality data with excellent contrast were achieved at these resolutions, which enable the visualization of fine-scale structures. CONCLUSIONS: The gSlider-SMS approach provides a new, efficient way to acquire high-resolution diffusion data. Magn Reson Med 79:141-151, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

HIgh b-value and high Resolution Integrated Diffusion (HIBRID) imaging.

The parameter selection for diffusion MRI experiments is dominated by the "k-q tradeoff" whereby the Signal to Noise Ratio (SNR) of the images is traded for either high spatial resolution (determined by the maximum k-value collected) or high diffusion sensitivity (effected by b-value or the q vector) but usually not both. Furthermore, different brain regions (such as gray matter and white matter) likely require different tradeoffs between these parameters due to the size of the structures to be visualized or the length-scale of the microstructure being probed. In this case, it might be advantageous to combine information from two scans - a scan with high q but low k (high angular resolution in diffusion but low spatial resolution in the image domain) to provide maximal information about white matter fiber crossing, and one low q but high k (low angular resolution but high spatial resolution) for probing the cortex. In this study, we propose a method, termed HIgh b-value and high Resolution Integrated Diffusion (HIBRID) imaging, for acquiring and combining the information from these two complementary types of scan with the goal of studying diffusion in the cortex without compromising white matter fiber information. The white-gray boundary and pial surface obtained from anatomical scans are incorporated as prior information to guide the fusion. We study the complementary advantages of the fused datasets, and assess the quality of the HIBRID data compared to either alone.

Direct neural current imaging in an intact cerebellum with magnetic resonance imaging.

The ability to detect neuronal currents with high spatiotemporal resolution using magnetic resonance imaging (MRI) is important for studying human brain function in both health and disease. While significant progress has been made, we still lack evidence showing that it is possible to measure an MR signal time-locked to neuronal currents with a temporal waveform matching concurrently recorded local field potentials (LFPs). Also lacking is evidence that such MR data can be used to image current distribution in active tissue. Since these two results are lacking even in vitro, we obtained these data in an intact isolated whole cerebellum of turtle during slow neuronal activity mediated by metabotropic glutamate receptors using a gradient-echo EPI sequence (TR=100ms) at 4.7T. Our results show that it is possible (1) to reliably detect an MR phase shift time course matching that of the concurrently measured LFP evoked by stimulation of a cerebellar peduncle, (2) to detect the signal in single voxels of 0.1mm(3), (3) to determine the spatial phase map matching the magnetic field distribution predicted by the LFP map, (4) to estimate the distribution of neuronal current in the active tissue from a group-average phase map, and (5) to provide a quantitatively accurate theoretical account of the measured phase shifts. The peak values of the detected MR phase shifts were 0.27-0.37°, corresponding to local magnetic field changes of 0.67-0.93nT (for TE=26ms). Our work provides an empirical basis for future extensions to in vivo imaging of neuronal currents.

MGH-USC Human Connectome Project datasets with ultra-high b-value diffusion MRI.

The MGH-USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300 mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH-USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU-Minn Connectome Database (ConnectomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH-Harvard-USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH-USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography.

Characterization of Axonal Disease in Patients with Multiple Sclerosis Using High-Gradient-Diffusion MR Imaging.

Purpose To evaluate the ability of high-gradient-diffusion magnetic resonance (MR) imaging by using gradient strengths of up to 300 mT/m to depict axonal disease in lesions and normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) and to compare high-gradient-diffusion MR findings in these patients with those in healthy control subjects. Materials and Methods In this HIPAA-compliant institutional review board-approved prospective study in which all subjects provided written informed consent, six patients with relapsing-remitting MS and six healthy control subjects underwent diffusion-weighted imaging with a range of diffusion weightings performed with a 3-T human MR imager by using gradient strengths of up to 300 mT/m. A model of intra-axonal, extra-axonal, and free water diffusion was fitted to obtain estimates of axon diameter and density. Differences in axon diameter and density between lesions and NAWM in patients with MS were assessed by using the nonparametric Wilcoxon matched-pairs signed rank test, and differences between NAWM in subjects with MS and white matter in healthy control subjects were assessed by using the Mann-Whitney U test. Results MS lesions showed increased mean axon diameter (10.3 vs 7.9 µm in the genu, 10.4 vs 9.3 µm in the body, and 10.6 vs 8.2 µm in the splenium; P < .05) and decreased axon density ([0.48 vs 1.1] × 10(10)/m(2) in the genu, [0.40 vs 0.70] × 10(10)/m(2) in the body, and [0.35 vs 1.1] × 10(10)/m(2) in the splenium; P < .05) compared with adjacent NAWM. No significant difference in mean axon diameter or axon density was detected between NAWM in subjects with MS and white matter in healthy control subjects. Conclusion High-gradient-diffusion MR imaging using gradient strengths of up to 300 mT/m can be used to characterize axonal disease in patients with MS, with results that agree with known trends from neuropathologic data showing increased axon diameter and decreased axon density in MS lesions when compared with NAWM. (©) RSNA, 2016 Online supplemental material is available for this article.

Q-space truncation and sampling in diffusion spectrum imaging.

PURPOSE: To characterize the q-space truncation and sampling on the spin-displacement probability density function (PDF) in diffusion spectrum imaging (DSI). METHODS: DSI data were acquired using the MGH-USC connectome scanner (Gmax = 300 mT/m) with bmax = 30,000 s/mm2 , 17 × 17 × 17, 15 × 15 × 15 and 11 × 11 × 11 grids in ex vivo human brains and bmax = 10,000 s/mm2 , 11 × 11 × 11 grid in vivo. An additional in vivo scan using bmax =7,000 s/mm2 , 11 × 11 × 11 grid was performed with a derated gradient strength of 40 mT/m. PDFs and orientation distribution functions (ODFs) were reconstructed with different q-space filtering and PDF integration lengths, and from down-sampled data by factors of two and three. RESULTS: Both ex vivo and in vivo data showed Gibbs ringing in PDFs, which becomes the main source of artifact in the subsequently reconstructed ODFs. For down-sampled data, PDFs interfere with the first replicas or their ringing, leading to obscured orientations in ODFs. CONCLUSION: The minimum required q-space sampling density corresponds to a field-of-view approximately equal to twice the mean displacement distance (MDD) of the tissue. The 11 × 11 × 11 grid is suitable for both ex vivo and in vivo DSI experiments. To minimize the effects of Gibbs ringing, ODFs should be reconstructed from unfiltered q-space data with the integration length over the PDF constrained to around the MDD. Magn Reson Med 76:1750-1763, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

The impact of gradient strength on in vivo diffusion MRI estimates of axon diameter.

Diffusion magnetic resonance imaging (MRI) methods for axon diameter mapping benefit from higher maximum gradient strengths than are currently available on commercial human scanners. Using a dedicated high-gradient 3T human MRI scanner with a maximum gradient strength of 300 mT/m, we systematically studied the effect of gradient strength on in vivo axon diameter and density estimates in the human corpus callosum. Pulsed gradient spin echo experiments were performed in a single scan session lasting approximately 2h on each of three human subjects. The data were then divided into subsets with maximum gradient strengths of 77, 145, 212, and 293 mT/m and diffusion times encompassing short (16 and 25 ms) and long (60 and 94 ms) diffusion time regimes. A three-compartment model of intra-axonal diffusion, extra-axonal diffusion, and free diffusion in cerebrospinal fluid was fitted to the data using a Markov chain Monte Carlo approach. For the acquisition parameters, model, and fitting routine used in our study, it was found that higher maximum gradient strengths decreased the mean axon diameter estimates by two to three fold and decreased the uncertainty in axon diameter estimates by more than half across the corpus callosum. The exclusive use of longer diffusion times resulted in axon diameter estimates that were up to two times larger than those obtained with shorter diffusion times. Axon diameter and density maps appeared less noisy and showed improved contrast between different regions of the corpus callosum with higher maximum gradient strength. Known differences in axon diameter and density between the genu, body, and splenium of the corpus callosum were preserved and became more reproducible at higher maximum gradient strengths. Our results suggest that an optimal q-space sampling scheme for estimating in vivo axon diameters should incorporate the highest possible gradient strength. The improvement in axon diameter and density estimates that we demonstrate from increasing maximum gradient strength will inform protocol development and encourage the adoption of higher maximum gradient strengths for use in commercial human scanners.