Impact of repeated blast exposure on active-duty United States Special Operations Forces.

United States (US) Special Operations Forces (SOF) are frequently exposed to explosive blasts in training and combat, but the effects of repeated blast exposure (RBE) on SOF brain health are incompletely understood. Furthermore, there is no diagnostic test to detect brain injury from RBE. As a result, SOF personnel may experience cognitive, physical, and psychological symptoms for which the cause is never identified, and they may return to training or combat during a period of brain vulnerability. In 30 active-duty US SOF, we assessed the relationship between cumulative blast exposure and cognitive performance, psychological health, physical symptoms, blood proteomics, and neuroimaging measures (Connectome structural and diffusion MRI, 7 Tesla functional MRI, [11C]PBR28 translocator protein [TSPO] positron emission tomography [PET]-MRI, and [18F]MK6240 tau PET-MRI), adjusting for age, combat exposure, and blunt head trauma. Higher blast exposure was associated with increased cortical thickness in the left rostral anterior cingulate cortex (rACC), a finding that remained significant after multiple comparison correction. In uncorrected analyses, higher blast exposure was associated with worse health-related quality of life, decreased functional connectivity in the executive control network, decreased TSPO signal in the right rACC, and increased cortical thickness in the right rACC, right insula, and right medial orbitofrontal cortex-nodes of the executive control, salience, and default mode networks. These observations suggest that the rACC may be susceptible to blast overpressure and that a multimodal, network-based diagnostic approach has the potential to detect brain injury associated with RBE in active-duty SOF.

Eddy current-induced artifact correction in high b-value ex vivo human brain diffusion MRI with dynamic field monitoring.

PURPOSE: To investigate whether spatiotemporal magnetic field monitoring can correct pronounced eddy current-induced artifacts incurred by strong diffusion-sensitizing gradients up to 300 mT/m used in high b-value diffusion-weighted (DW) EPI. METHODS: A dynamic field camera equipped with 16 1 H NMR field probes was first used to characterize field perturbations caused by residual eddy currents from diffusion gradients waveforms in a 3D multi-shot EPI sequence on a 3T Connectom scanner for different gradient strengths (up to 300 mT/m), diffusion directions, and shots. The efficacy of dynamic field monitoring-based image reconstruction was demonstrated on high-gradient strength, submillimeter resolution whole-brain ex vivo diffusion MRI. A 3D multi-shot image reconstruction framework was developed that incorporated the nonlinear phase evolution measured with the dynamic field camera. RESULTS: Phase perturbations in the readout induced by residual eddy currents from strong diffusion gradients are highly nonlinear in space and time, vary among diffusion directions, and interfere significantly with the image encoding gradients, changing the k-space trajectory. During the readout, phase modulations between odd and even EPI echoes become non-static and diffusion encoding direction-dependent. Superior reduction of ghosting and geometric distortion was achieved with dynamic field monitoring compared to ghosting reduction approaches such as navigator- and structured low-rank-based methods or MUSE followed by image-based distortion correction with the FSL tool "eddy." CONCLUSION: Strong eddy current artifacts characteristic of high-gradient strength DW-EPI can be well corrected with dynamic field monitoring-based image reconstruction.

The effects of axonal beading and undulation on axonal diameter estimation from diffusion MRI: Insights from simulations in human axons segmented from three-dimensional electron microscopy.

The increasing availability of high-performance gradient systems in human MRI scanners has generated great interest in diffusion microstructural imaging applications such as axonal diameter mapping. Practically, sensitivity to axon diameter in diffusion MRI is attained at strong diffusion weightings b , where the deviation from the expected 1 / b scaling in white matter yields a finite transverse diffusivity, which is then translated into an axon diameter estimate. While axons are usually modeled as perfectly straight, impermeable cylinders, local variations in diameter (caliber variation or beading) and direction (undulation) are known to influence axonal diameter estimates and have been observed in microscopy data of human axons. In this study, we performed Monte Carlo simulations of diffusion in axons reconstructed from three-dimensional electron microscopy of a human temporal lobe specimen using simulated sequence parameters matched to the maximal gradient strength of the next-generation Connectome 2.0 human MRI scanner ( ≲ 500 mT/m). We show that axon diameter estimation is accurate for nonbeaded, nonundulating fibers; however, in fibers with caliber variations and undulations, the axon diameter is heavily underestimated due to caliber variations, and this effect overshadows the known overestimation of the axon diameter due to undulations. This unexpected underestimation may originate from variations in the coarse-grained axial diffusivity due to caliber variations. Given that increased axonal beading and undulations have been observed in pathological tissues, such as traumatic brain injury and ischemia, the interpretation of axon diameter alterations in pathology may be significantly confounded.

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.

Motion guidance lines for robust data consistency-based retrospective motion correction in 2D and 3D MRI.

PURPOSE: To develop a robust retrospective motion-correction technique based on repeating k-space guidance lines for improving motion correction in Cartesian 2D and 3D brain MRI. METHODS: The motion guidance lines are inserted into the standard sequence orderings for 2D turbo spin echo and 3D MPRAGE to inform a data consistency-based motion estimation and reconstruction, which can be guided by a low-resolution scout. The extremely limited number of required guidance lines are repeated during each echo train and discarded in the final image reconstruction. Thus, integration within a standard k-space acquisition ordering ensures the expected image quality/contrast and motion sensitivity of that sequence. RESULTS: Through simulation and in vivo 2D multislice and 3D motion experiments, we demonstrate that respectively 2 or 4 optimized motion guidance lines per shot enables accurate motion estimation and correction. Clinically acceptable reconstruction times are achieved through fully separable on-the-fly motion optimizations (˜1 s/shot) using standard scanner GPU hardware. CONCLUSION: The addition of guidance lines to scout accelerated motion estimation facilitates robust retrospective motion correction that can be effectively introduced without perturbing standard clinical protocols and workflows.

High-fidelity, high-spatial-resolution diffusion magnetic resonance imaging of ex vivo whole human brain at ultra-high gradient strength with structured low-rank echo-planar imaging ghost correction.

Diffusion magnetic resonance imaging (dMRI) of whole ex vivo human brain specimens enables three-dimensional (3D) mapping of structural connectivity at the mesoscopic scale, providing detailed evaluation of fiber architecture and tissue microstructure at a spatial resolution that is difficult to access in vivo. To account for the short T2 and low diffusivity of fixed tissue, ex vivo dMRI is often acquired using strong diffusion-sensitizing gradients and multishot/segmented 3D echo-planar imaging (EPI) sequences to achieve high spatial resolution. However, the combination of strong diffusion-sensitizing gradients and multishot/segmented EPI readout can result in pronounced ghosting artifacts incurred by nonlinear spatiotemporal variations in the magnetic field produced by eddy currents. Such ghosting artifacts cannot be corrected with conventional correction solutions and pose a significant roadblock to leveraging human MRI scanners with ultrahigh gradients for ex vivo whole-brain dMRI. Here, we show that ghosting-correction approaches that correct for either polarity-related ghosting or shot-to-shot variations in a separate manner are suboptimal for 3D multishot diffusion-weighted EPI experiments in fixed human brain specimens using strong diffusion-sensitizing gradients on the 3-T Connectom MRI scanner, resulting in orientationally biased dMRI estimates. We apply a recently developed advanced k-space reconstruction method based on structured low-rank matrix (SLM) modeling that handles both polarity-related ghosting and shot-to-shot variation simultaneously, to mitigate artifacts in high-angular resolution multishot dMRI data acquired in several fixed human brain specimens at 0.7-0.8-mm isotropic spatial resolution using b-values up to 10,000 s/mm2 and gradient strengths up to 280 mT/m. We demonstrate the improved mapping of diffusion tensor imaging and fiber orientation distribution functions in key neuroanatomical areas distributed across the whole brain using SLM-based EPI ghost correction compared with alternative techniques.

Validation of a highly accelerated post-contrast wave-controlled aliasing in parallel imaging (CAIPI) 3D-T1 MPRAGE compared to standard 3D-T1 MPRAGE for detection of intracranial enhancing lesions on 3-T MRI.

OBJECTIVES: High-resolution post-contrast T1-weighted imaging is a workhorse sequence in the evaluation of neurological disorders. The T1-MPRAGE sequence has been widely adopted for the visualization of enhancing pathology in the brain. However, this three-dimensional (3D) acquisition is lengthy and prone to motion artifact, which often compromises diagnostic quality. The goal of this study was to compare a highly accelerated wave-controlled aliasing in parallel imaging (CAIPI) post-contrast 3D T1-MPRAGE sequence (Wave-T1-MPRAGE) with the standard 3D T1-MPRAGE sequence for visualizing enhancing lesions in brain imaging at 3 T. METHODS: This study included 80 patients undergoing contrast-enhanced brain MRI. The participants were scanned with a standard post-contrast T1-MPRAGE sequence (acceleration factor [R] = 2 using GRAPPA parallel imaging technique, acquisition time [TA] = 5 min 18 s) and a prototype post-contrast Wave-T1-MPRAGE sequence (R = 4, TA = 2 min 32 s). Two neuroradiologists performed a head-to-head evaluation of both sequences and rated the visualization of enhancement, sharpness, noise, motion artifacts, and overall diagnostic quality. A 15% noninferiority margin was used to test whether post-contrast Wave-T1-MPRAGE was noninferior to standard T1-MPRAGE. Inter-rater and intra-rater agreement were calculated. Quantitative assessment of CNR/SNR was performed. RESULTS: Wave-T1-MPRAGE was noninferior to standard T1-MPRAGE for delineating enhancing lesions with unanimous agreement in all cases between raters. Wave-T1-MPRAGE was noninferior in the perception of noise (p < 0.001), motion artifact (p < 0.001), and overall diagnostic quality (p < 0.001). CONCLUSION: High-accelerated post-contrast Wave-T1-MPRAGE enabled a two-fold reduction in acquisition time compared to the standard sequence with comparable performance for visualization of enhancing pathology and equivalent perception of noise, motion artifacts and overall diagnostic quality without loss of clinically important information. KEY POINTS: • Post-contrast wave-controlled aliasing in parallel imaging (CAIPI) T1-MPRAGE accelerated the acquisition of three-dimensional (3D) high-resolution post-contrast images by more than two-fold. • Post-contrast Wave-T1-MPRAGE was noninferior to standard T1-MPRAGE with unanimous agreement between reviewers (100% in 80 cases) for the visualization of intracranial enhancing lesions. • Wave-T1-MPRAGE was equivalent to the standard sequence in the perception of noise in 94% (75 of 80) of cases and was preferred in 16% (13 of 80) of cases for decreased motion artifact.

Advanced brain MRI may help understand the link between migraine and multiple sclerosis.

BACKGROUND: There is a clinical association between migraine and multiple sclerosis. MAIN BODY: Migraine and MS patients share similar demographics, with the highest incidence among young, female and otherwise healthy patients. The same hormonal constellations/changes trigger disease exacerbation in both entities. Migraine prevalence is increased in MS patients, which is further enhanced by disease-modifying treatment. Clinical data show that onset of migraine typically starts years before the clinical diagnosis of MS, suggesting that there is either a unidirectional relationship with migraine predisposing to MS, and/or a "shared factor" underlying both conditions. Brain imaging studies show white matter lesions in both MS and migraine patients. Neuroinflammatory mechanisms likely play a key role, at least as a shared downstream pathway. In this review article, we provide an overview of the literature about 1) the clinical association between migraine and MS as well as 2) brain MRI studies that help us better understand the mechanistic relationship between both diseases with implications on their underlying pathophysiology. CONCLUSION: Studies suggest a migraine history predisposes patients to develop MS. Advanced brain MR imaging may shed light on shared and distinct features, while helping us better understand mechanisms underlying both disease entities.

SDnDTI: Self-supervised deep learning-based denoising for diffusion tensor MRI.

Diffusion tensor magnetic resonance imaging (DTI) is a widely adopted neuroimaging method for the in vivo mapping of brain tissue microstructure and white matter tracts. Nonetheless, the noise in the diffusion-weighted images (DWIs) decreases the accuracy and precision of DTI derived microstructural parameters and leads to prolonged acquisition time for achieving improved signal-to-noise ratio (SNR). Deep learning-based image denoising using convolutional neural networks (CNNs) has superior performance but often requires additional high-SNR data for supervising the training of CNNs, which reduces the feasibility of supervised learning-based denoising in practice. In this work, we develop a self-supervised deep learning-based method entitled "SDnDTI" for denoising DTI data, which does not require additional high-SNR data for training. Specifically, SDnDTI divides multi-directional DTI data into many subsets of six DWI volumes and transforms DWIs from each subset to along the same diffusion-encoding directions through the diffusion tensor model, generating multiple repetitions of DWIs with identical image contrasts but different noise observations. SDnDTI removes noise by first denoising each repetition of DWIs using a deep 3-dimensional CNN with the average of all repetitions with higher SNR as the training target, following the same approach as normal supervised learning based denoising methods, and then averaging CNN-denoised images for achieving higher SNR. The denoising efficacy of SDnDTI is demonstrated in terms of the similarity of output images and resultant DTI metrics compared to the ground truth generated using substantially more DWI volumes on two datasets with different spatial resolutions, b-values and numbers of input DWI volumes provided by the Human Connectome Project (HCP) and the Lifespan HCP in Aging. The SDnDTI results preserve image sharpness and textural details and substantially improve upon those from the raw data. The results of SDnDTI are comparable to those from supervised learning-based denoising and outperform those from state-of-the-art conventional denoising algorithms including BM4D, AONLM and MPPCA. By leveraging domain knowledge of diffusion MRI physics, SDnDTI makes it easier to use CNN-based denoising methods in practice and has the potential to benefit a wider range of research and clinical applications that require accelerated DTI acquisition and high-quality DTI data for mapping of tissue microstructure, fiber tracts and structural connectivity in the living human brain.

Estimating axial diffusivity in the NODDI model.

To estimate microstructure-related parameters from diffusion MRI data, biophysical models make strong, simplifying assumptions about the underlying tissue. The extent to which many of these assumptions are valid remains an open research question. This study was inspired by the disparity between the estimated intra-axonal axial diffusivity from literature and that typically assumed by the Neurite Orientation Dispersion and Density Imaging (NODDI) model (d∥=1.7µm2/ms). We first demonstrate how changing the assumed axial diffusivity results in considerably different NODDI parameter estimates. Second, we illustrate the ability to estimate axial diffusivity as a free parameter of the model using high b-value data and an adapted NODDI framework. Using both simulated and in vivo data we investigate the impact of fitting to either real-valued or magnitude data, with Gaussian and Rician noise characteristics respectively, and what happens if we get the noise assumptions wrong in this high b-value and thus low SNR regime. Our results from real-valued human data estimate intra-axonal axial diffusivities of ∼2-2.5µm2/ms, in line with current literature. Crucially, our results demonstrate the importance of accounting for both a rectified noise floor and/or a signal offset to avoid biased parameter estimates when dealing with low SNR data.

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.

Scout accelerated motion estimation and reduction (SAMER).

PURPOSE: To demonstrate a navigator/tracking-free retrospective motion estimation technique that facilitates clinically acceptable reconstruction time. METHODS: Scout accelerated motion estimation and reduction (SAMER) uses a single 3-5 s, low-resolution scout scan and a novel sequence reordering to independently determine motion states by minimizing the data-consistency error in a SENSE plus motion forward model. This eliminates time-consuming alternating optimization as no updates to the imaging volume are required during the motion estimation. The SAMER approach was assessed quantitatively through extensive simulation and was evaluated in vivo across multiple motion scenarios and clinical imaging contrasts. Finally, SAMER was synergistically combined with advanced encoding (Wave-CAIPI) to facilitate rapid motion-free imaging. RESULTS: The highly accelerated scout provided sufficient information to achieve accurate motion trajectory estimation (accuracy ~0.2 mm or degrees). The novel sequence reordering improved the stability of the motion parameter estimation and image reconstruction while preserving the clinical imaging contrast. Clinically acceptable computation times for the motion estimation (~4 s/shot) are demonstrated through a fully separable (non-alternating) motion search across the shots. Substantial artifact reduction was demonstrated in vivo as well as corresponding improvement in the quantitative error metric. Finally, the extension of SAMER to Wave-encoding enabled rapid high-quality imaging at up to R = 9-fold acceleration. CONCLUSION: SAMER significantly improved the computational scalability for retrospective motion estimation and correction.

Optimization of magnetization transfer contrast for EPI FLAIR brain imaging.

PURPOSE: To evaluate the impact of magnetization transfer (MT) on brain tissue contrast in turbo-spin-echo (TSE) and EPI fluid-attenuated inversion recovery (FLAIR) images, and to optimize an MT-prepared EPI FLAIR pulse sequence to match the tissue contrast of a clinical reference TSE FLAIR protocol. METHODS: Five healthy volunteers underwent 3T brain MRI, including single slice TSE FLAIR, multi-slice TSE FLAIR, EPI FLAIR without MT-preparation, and MT-prepared EPI FLAIR with variations of the MT-preparation parameters, including number of preparation pulses, pulse amplitude, and resonance offset. Automated co-registration and gray matter (GM) versus white matter (WM) segmentation was performed using a T1-MPRAGE acquisition, and the GM versus WM signal intensity ratio (contrast ratio) was calculated for each FLAIR acquisition. RESULTS: Without MT preparation, EPI FLAIR showed poor tissue contrast (contrast ratio = 0.98), as did single slice TSE FLAIR. Multi-slice TSE FLAIR provided high tissue contrast (contrast ratio = 1.14). MT-prepared EPI FLAIR closely approximated the contrast of the multi-slice TSE FLAIR images for two combinations of the MT-preparation parameters (contrast ratio = 1.14). Optimized MT-prepared EPI FLAIR provided a 50% reduction in scan time compared to the reference TSE FLAIR acquisition. CONCLUSION: Optimized MT-prepared EPI FLAIR provides comparable brain tissue contrast to the multi-slice TSE FLAIR images used in clinical practice.

An artificial intelligence-accelerated 2-minute multi-shot echo planar imaging protocol for comprehensive high-quality clinical brain imaging.

PURPOSE: We introduce and validate an artificial intelligence (AI)-accelerated multi-shot echo-planar imaging (msEPI)-based method that provides T1w, T2w, T2∗ , T2-FLAIR, and DWI images with high SNR, high tissue contrast, low specific absorption rates (SAR), and minimal distortion in 2 minutes. METHODS: The rapid imaging technique combines a novel machine learning (ML) scheme to limit g-factor noise amplification and improve SNR, a magnetization transfer preparation module to provide clinically desirable contrast, and high per-shot EPI undersampling factors to reduce distortion. The ML training and image reconstruction incorporates a tunable parameter for controlling the level of denoising/smoothness. The performance of the reconstruction method is evaluated across various acceleration factors, contrasts, and SNR conditions. The 2-minute protocol is directly compared to a 10-minute clinical reference protocol through deployment in a clinical setting, where five representative cases with pathology are examined. RESULTS: Optimization of custom msEPI sequences and protocols was performed to balance acquisition efficiency and image quality compared to the five-fold longer clinical reference. Training data from 16 healthy subjects across multiple contrasts and orientations were used to produce ML networks at various acceleration levels. The flexibility of the ML reconstruction was demonstrated across SNR levels, and an optimized regularization was determined through radiological review. Network generalization toward novel pathology, unobserved during training, was illustrated in five clinical case studies with clinical reference images provided for comparison. CONCLUSION: The rapid 2-minute msEPI-based protocol with tunable ML reconstruction allows for advantageous trade-offs between acquisition speed, SNR, and tissue contrast when compared to the five-fold slower standard clinical reference exam.

White Matter Lesions in Migraine.

Migraine, the third most common disease worldwide, is a well-known independent risk factor for subclinical focal deep white matter lesions (WMLs), even in young and otherwise healthy individuals with no cardiovascular risk factors. These WMLs are more commonly seen in migraine patients with transient neurologic symptoms preceding their headaches, the so-called aura, and those with a high attack frequency. The pathophysiology of migraine-related deep white matter hyperintensities remains poorly understood despite their prevalence. Characteristic differences in their distribution compared with those of common periventricular WMLs in the elderly suggest a different underlying mechanism. Both ischemic and inflammatory mechanisms have been proposed, as there is increased cerebral vulnerability to ischemia in migraineurs, whereas there is also evidence of blood-brain barrier disruption with associated release of proinflammatory substances during migraine attacks. An enhanced susceptibility to spreading depolarization, the electrophysiological event underlying migraine, may be the mechanism that causes repetitive episodes of cerebral hypoperfusion and neuroinflammation during migraine attacks. WMLs can negatively affect both physical and cognitive function, underscoring the public health importance of migraine, and suggesting that migraine is an important contributor to neurologic deficits in the general population.

Clinical validation of Wave-CAIPI susceptibility-weighted imaging for routine brain MRI at 1.5 T.

OBJECTIVES: Wave-CAIPI (Controlled Aliasing in Parallel Imaging) enables dramatic reduction in acquisition time of 3D MRI sequences such as 3D susceptibility-weighted imaging (SWI) but has not been clinically evaluated at 1.5 T. We sought to compare highly accelerated Wave-CAIPI SWI (Wave-SWI) with two alternative standard sequences, conventional three-dimensional SWI and two-dimensional T2*-weighted Gradient-Echo (T2*w-GRE), in patients undergoing routine brain MRI at 1.5 T. METHODS: In this study, 172 patients undergoing 1.5 T brain MRI were scanned with a more commonly used susceptibility sequence (standard SWI or T2*w-GRE) and a highly accelerated Wave-SWI sequence. Two radiologists blinded to the acquisition technique scored each sequence for visualization of pathology, motion and signal dropout artifacts, image noise, visualization of normal anatomy (vessels and basal ganglia mineralization), and overall diagnostic quality. Superiority testing was performed to compare Wave-SWI to T2*w-GRE, and non-inferiority testing with 15% margin was performed to compare Wave-SWI to standard SWI. RESULTS: Wave-SWI performed superior in terms of visualization of pathology, signal dropout artifacts, visualization of normal anatomy, and overall image quality when compared to T2*w-GRE (all p < 0.001). Wave-SWI was non-inferior to standard SWI for visualization of normal anatomy and pathology, signal dropout artifacts, and overall image quality (all p < 0.001). Wave-SWI was superior to standard SWI for motion artifact (p < 0.001), while both conventional susceptibility sequences were superior to Wave-SWI for image noise (p < 0.001). CONCLUSIONS: Wave-SWI can be performed in a 1.5 T clinical setting with robust performance and preservation of diagnostic quality. KEY POINTS: • Wave-SWI accelerated the acquisition of 3D high-resolution susceptibility images in 70% of the acquisition time of the conventional T2*GRE. • Wave-SWI performed superior to T2*w-GRE for visualization of pathology, signal dropout artifacts, and overall diagnostic image quality. • Wave-SWI was noninferior to standard SWI for visualization of normal anatomy and pathology, signal dropout artifacts, and overall diagnostic image quality.

Improving in vivo human cerebral cortical surface reconstruction using data-driven super-resolution.

Accurate and automated reconstruction of the in vivo human cerebral cortical surface from anatomical magnetic resonance (MR) images facilitates the quantitative analysis of cortical structure. Anatomical MR images with sub-millimeter isotropic spatial resolution improve the accuracy of cortical surface and thickness estimation compared to the standard 1-millimeter isotropic resolution. Nonetheless, sub-millimeter resolution acquisitions require averaging multiple repetitions to achieve sufficient signal-to-noise ratio and are therefore long and potentially vulnerable to subject motion. We address this challenge by synthesizing sub-millimeter resolution images from standard 1-millimeter isotropic resolution images using a data-driven supervised machine learning-based super-resolution approach achieved via a deep convolutional neural network. We systematically characterize our approach using a large-scale simulated dataset and demonstrate its efficacy in empirical data. The super-resolution data provide improved cortical surfaces similar to those obtained from native sub-millimeter resolution data. The whole-brain mean absolute discrepancy in cortical surface positioning and thickness estimation is below 100 µm at the single-subject level and below 50 µm at the group level for the simulated data, and below 200 µm at the single-subject level and below 100 µm at the group level for the empirical data, making the accuracy of cortical surfaces derived from super-resolution sufficient for most applications.

Improved cortical surface reconstruction using sub-millimeter resolution MPRAGE by image denoising.

Automatic cerebral cortical surface reconstruction is a useful tool for cortical anatomy quantification, analysis and visualization. Recently, the Human Connectome Project and several studies have shown the advantages of using T1-weighted magnetic resonance (MR) images with sub-millimeter isotropic spatial resolution instead of the standard 1-mm isotropic resolution for improved accuracy of cortical surface positioning and thickness estimation. Nonetheless, sub-millimeter resolution images are noisy by nature and require averaging multiple repetitions to increase the signal-to-noise ratio for precisely delineating the cortical boundary. The prolonged acquisition time and potential motion artifacts pose significant barriers to the wide adoption of cortical surface reconstruction at sub-millimeter resolution for a broad range of neuroscientific and clinical applications. We address this challenge by evaluating the cortical surface reconstruction resulting from denoised single-repetition sub-millimeter T1-weighted images. We systematically characterized the effects of image denoising on empirical data acquired at 0.6 mm isotropic resolution using three classical denoising methods, including denoising convolutional neural network (DnCNN), block-matching and 4-dimensional filtering (BM4D) and adaptive optimized non-local means (AONLM). The denoised single-repetition images were found to be highly similar to 6-repetition averaged images, with a low whole-brain averaged mean absolute difference of ~0.016, high whole-brain averaged peak signal-to-noise ratio of ~33.5 dB and structural similarity index of ~0.92, and minimal gray matter-white matter contrast loss (2% to 9%). The whole-brain mean absolute discrepancies in gray matter-white matter surface placement, gray matter-cerebrospinal fluid surface placement and cortical thickness estimation were lower than 165 µm, 155 µm and 145 µm-sufficiently accurate for most applications. These discrepancies were approximately one third to half of those from 1-mm isotropic resolution data. The denoising performance was equivalent to averaging ~2.5 repetitions of the data in terms of image similarity, and 1.6-2.2 repetitions in terms of the cortical surface placement accuracy. The scan-rescan variability of the cortical surface positioning and thickness estimation was lower than 170 µm. Our unique dataset and systematic characterization support the use of denoising methods for improved cortical surface reconstruction at sub-millimeter resolution.

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.

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.