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Purpose: Multichannel Transcranial Magnetic Stimulation (mTMS) [1] is a novel non-invasive brain stimulation technique allowing multiple sites to be stimulated simultaneously or sequentially under electronic control without movement of the coils. To enable simultaneous mTMS and MR imaging, we have designed and constructed a whole-head 28-channel receive-only RF coil at 3T. Methods: A helmet-shaped structure was designed considering a specific layout for a mTMS system with holes for positioning the TMS units next to the scalp. Diameter of the TMS units defined the diameter of RF loops. The placement of the preamplifiers was designed to minimize possible interactions and to allow straightforward positioning of the mTMS units around the RF coil. Interactions between TMS-MRI were analyzed for the whole-head system extending the results presented in previous publications [2]. Both SNR- and g-factors maps were obtained to compare the imaging performance of the coil with commercial head coils. Results: Sensitivity losses for the RF elements containing TMS units show a well-defined spatial pattern. Simulations indicate that the losses are predominantly caused by eddy currents on the coil wire windings. The average SNR performance of the TMSMR 28-channel coil is about 66% and 86% of the SNR of the 32/20-channel head coil respectively. The g-factor values of the TMSMR 28-channel coil are similar to the 32-channel coil and significantly better than the 20-channel coil. Conclusion: We present the TMSMR 28-channel coil, a head RF coil array to be integrated with a multichannel 3-axisTMS coil system, a novel tool that will enable causal mapping of human brain function.

Measurement(s) brain measurement Technology Type(s) diffusion magnetic resonance imaging Factor Type(s) diffusion time • gradient strength • direction Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.16910290

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.

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.

Abstract Breast-conserving surgery (BCS) is a commonly utilized treatment for early stage breast cancers but has relatively high reexcision rates due to post-surgical identification of positive margins. A fast, specific, sensitive, easy-to-use tool for assessing margins intraoperatively could reduce the need for additional surgeries, and while many techniques have been explored, the clinical need is still unmet. We assess the potential of Magnetic Particle Imaging (MPI) for intraoperative margin assessment in BCS, using a passively or actively tumor-targeted iron oxide agent and two hardware devices: a hand-held Magnetic Particle detector for identifying residual tumor in the breast, and a small-bore MPI scanner for quickly imaging the tumor distribution in the excised specimen. Here, we present both hardware systems and demonstrate proof-of-concept detection and imaging of clinically relevant phantoms.

Measurement(s) brain measurement Technology Type(s) magnetic resonance imaging Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14058443

Multi-parametric quantitative MRI has shown great potential to improve the sensitivity and specificity of clinical diagnosis and to enhance our understanding of complex brain processes, but suffers from long scan time especially at high spatial resolution. To address this longstanding challenge, we introduce a novel approach, termed 3D Echo Planar Time-resolved Imaging (3D-EPTI), which significantly increases the acceleration capacity of MRI sampling, and provides high acquisition efficiency for multi-parametric MRI. This is achieved by exploiting the spatiotemporal correlation of MRI data at multiple timescales through new encoding strategies within and between efficient continuous readouts. Specifically, an optimized spatiotemporal CAIPI encoding within the readouts combined with a radial-block sampling strategy across the readouts enables an acceleration rate of 800 fold in the k-t space. A subspace reconstruction was employed to resolve thousands of high-quality multi-contrast images. We have demonstrated the ability of 3D-EPTI to provide robust and repeatable whole-brain simultaneous T1, T2, T2*, PD and B1+ mapping at high isotropic resolution within minutes (e.g., 1-mm isotropic resolution in 3 minutes), and to enable submillimeter multi-parametric imaging to study detailed brain structures.

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.

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.

In vivo diffusion-weighted magnetic resonance imaging is limited in signal-to-noise-ratio (SNR) and acquisition time, which constrains spatial resolution to the macroscale regime. Ex vivo imaging, which allows for arbitrarily long scan times, is critical for exploring human brain structure in the mesoscale regime without loss of SNR. Standard head array coils designed for patients are sub-optimal for imaging ex vivo whole brain specimens. The goal of this work was to design and construct a 48-channel ex vivo whole brain array coil for high-resolution and high b-value diffusion-weighted imaging on a 3T Connectome scanner. The coil was validated with bench measurements and characterized by imaging metrics on an agar brain phantom and an ex vivo human brain sample. The two-segment coil former was constructed for a close fit to a whole human brain, with small receive elements distributed over the entire brain. Imaging tests including SNR and G-factor maps were compared to a 64-channel head coil designed for in vivo use. There was a 2.9-fold increase in SNR in the peripheral cortex and a 1.3-fold gain in the center when compared to the 64-channel head coil. The 48-channel ex vivo whole brain coil also decreases noise amplification in highly parallel imaging, allowing acceleration factors of approximately one unit higher for a given noise amplification level. The acquired diffusion-weighted images in a whole ex vivo brain specimen demonstrate the applicability and advantage of the developed coil for high-resolution and high b-value diffusion-weighted ex vivo brain MRI studies.

Abstract Objective To evaluate alterations in apparent axon diameter and axon density obtained by high‐gradient diffusion MRI in the corpus callosum of MS patients and the relationship of these advanced diffusion MRI metrics to neurologic disability and cognitive impairment in MS. Methods Thirty people with MS (23 relapsing‐remitting MS [RRMS], 7 progressive MS [PMS]) and 23 healthy controls were scanned on a human 3‐tesla (3T) MRI scanner equipped with 300 mT/m maximum gradient strength using a comprehensive multishell diffusion MRI protocol. Data were fitted to a three‐compartment geometric model of white matter to estimate apparent axon diameter and axon density in the midline corpus callosum. Neurologic disability and cognitive function were measured using the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Minimal Assessment of Cognitive Function in MS battery. Results Apparent axon diameter was significantly larger and axon density reduced in the normal‐appearing corpus callosum (NACC) of MS patients compared to healthy controls, with similar trends seen in PMS compared to RRMS. Larger apparent axon diameter in the NACC of MS patients correlated with greater disability as measured by the EDSS (r = 0.555, P = 0.007) and poorer performance on the Symbol Digits Modalities Test (r = ‐0.593, P = 0.008) and Brief Visuospatial Memory Test–Revised (r = −0.632, P

The paper describes a new magnetic resonance imaging (MRI) phased-array receive-only (Rx) coil for studying decompression sickness and disorders of hyperbaricity, including nitrogen narcosis. Functional magnetic resonance imaging (fMRI) is noninvasive, is considered safe, and may allow studying the brain under hyperbaric conditions. All of the risks associated with simultaneous MRI and HBO2 therapy are described in detail, along with all of the mitigation strategies and regulatory testing. One of the most significant risks for this type of study is a fire in the hyperbaric chamber caused by the sparking of the MRI coils as a result of high-voltage RF arcs. RF pulses at 128 MHz elicit signals from human tissues, and RF sparking occurs commonly and is considered safe in normobaric conditions. We describe how we built a coil for HBO2-MRI studies by modifying an eight-channel phased-array MRI coil with all of the mitigation strategies discussed. The coil was fabricated and tested with a unique testing platform that simulated the worst-case RF field of a three-Tesla MRI in a Hyperlite hyperbaric chamber at 3 atm pressure. The coil was also tested in normobaric conditions for image quality in a 3 T scanner in volunteers and SNR measurement in phantoms. Further studies are necessary to characterize the coil safety in HBO2/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.

We provide a comprehensive diffusion MRI dataset acquired with a novel biomimetic phantom mimicking human white matter. The fiber substrates in the diffusion phantom were constructed from hollow textile axons (“taxons”) with an inner diameter of 11.8±1.2 µm and outer diameter of 33.5±2.3 µm. Data were acquired on the 3 T CONNECTOM MRI scanner with multiple diffusion times and multiple q-values per diffusion time, which is a dedicated acquisition for validation of microstructural imaging methods, such as compartment size and volume fraction mapping. Minimal preprocessing was performed to correct for susceptibility and eddy current distortions. Data were deposited in the XNAT Central database (project ID: dMRI_Phant_MGH).

Abstract Rapid switching of applied magnetic fields in the kilohertz frequency range in the human body induces electric fields powerful enough to cause Peripheral Nerve Stimulation (PNS). PNS has become one of the main constraints on the use of high gradient fields for fast imaging with the latest MRI gradient technology. In recent MRI gradients, the applied fields are powerful enough that PNS limits their application in fast imaging sequences like echo-planar imaging. Application of Magnetic Particle Imaging (MPI) to humans is similarly PNS constrained. Despite its role as a major constraint, PNS considerations are only indirectly incorporated in the coil design process, mainly through using the size of the linear region as a proxy for PNS thresholds or by conducting human experiments after constructing coil prototypes. We present for the first time, a framework to simulate PNS thresholds for realistic coil geometries to directly address PNS in the design process. Our PNS model consists of an accurate body model for electromagnetic field simulations, an atlas of peripheral nerves, and a neurodynamic model to predict the nerve responses to imposed electric fields. With this model, we were able to reproduce measured PNS thresholds of two leg/arm solenoid coils with good agreement.

Adult visual cortex is organized into regions that respond to categories such as faces and scenes, but it is unclear if this depends on experience. Here, authors measured brain activity in 4–6 month old infants looking at faces and scenes and find that their visual cortex is organized similarly to adults.

Despite extensive neuroimaging research of primary sensory cortices involved in auditory and visual functions, subcortical structures within these domains, such as the inferior and superior colliculi, the medial and lateral geniculate nuclei and the superior olivary complex, are currently understudied with magnetic resonance imaging (MRI) in living humans. This is because a precise localization of these nuclei is hampered by the limited contrast and sensitivity of conventional neuroimaging methods for deep brain nuclei. In this work, we used 7 Tesla multi-modal (T2-weighted and diffusion fractional anisotropy) 1.1 mm isotropic resolution MRI to achieve high sensitivity and contrast for single-subject brainstem and thalamic nuclei delineation. After precise coregistration to stereotactic space, we generated an in vivo human probabilistic atlas of auditory (medial geniculate nucleus, inferior colliculus, and superior olivary complex) and visual (lateral geniculate nucleus and superior colliculus) subcortical nuclei. We foresee the use of this atlas as a tool to precisely identify the location and shape of auditory/visual deep nuclei in research as well as clinical human studies.

Task-free connectivity analyses have emerged as a powerful tool in functional neuroimaging. Because the cross-correlations that underlie connectivity measures are sensitive to distortion of time-series, here we used a novel dynamic phantom to provide a ground truth for dynamic fidelity between blood oxygen level dependent (BOLD)-like inputs and fMRI outputs. We found that the de facto quality-metric for task-free fMRI, temporal signal to noise ratio (tSNR), correlated inversely with dynamic fidelity; thus, studies optimized for tSNR actually produced time-series that showed the greatest distortion of signal dynamics. Instead, the phantom showed that dynamic fidelity is reasonably approximated by a measure that, unlike tSNR, dissociates signal dynamics from scanner artifact. We then tested this measure, signal fluctuation sensitivity (SFS), against human resting-state data. As predicted by the phantom, SFS—and not tSNR—is associated with enhanced sensitivity to both local and long-range connectivity within the brain’s default mode network.