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Purpose: Training auto-encoders on simulated signal evolution and inserting the decoder into the forward model improves reconstructions through more compact, Bloch-equation-based representations of signal in comparison to linear subspaces. Methods: Building on model-based nonlinear and linear subspace techniques that enable reconstruction of signal dynamics, we train auto-encoders on dictionaries of simulated signal evolution to learn more compact, non-linear, latent representations. The proposed Latent Signal Model framework inserts the decoder portion of the auto-encoder into the forward model and directly reconstructs the latent representation. Latent Signal Models essentially serve as a proxy for fast and feasible differentiation through the Bloch-equations used to simulate signal. This work performs experiments in the context of T2-shuffling, gradient echo EPTI, and MPRAGE-shuffling. We compare how efficiently auto-encoders represent signal evolution in comparison to linear subspaces. Simulation and in-vivo experiments then evaluate if reducing degrees of freedom by inserting the decoder into the forward model improves reconstructions in comparison to subspace constraints. Results: An auto-encoder with one real latent variable represents FSE, EPTI, and MPRAGE signal evolution as well as linear subspaces characterized by four basis vectors. In simulated/in-vivo T2-shuffling and in-vivo EPTI experiments, the proposed framework achieves consistent quantitative NRMSE and qualitative improvement over linear approaches. From qualitative evaluation, the proposed approach yields images with reduced blurring and noise amplification in MPRAGE shuffling experiments. Conclusion: Directly solving for non-linear latent representations of signal evolution improves time-resolved MRI reconstructions through reduced degrees of freedom.

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.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.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.Optimized MT-prepared EPI FLAIR provides comparable brain tissue contrast to the multi-slice TSE FLAIR images used in clinical practice.

Sparse Bayesian learning (SBL) is a powerful framework for tackling the sparse coding problem while also providing uncertainty quantification. The most popular inference algorithms for SBL exhibit prohibitively large computational costs for high-dimensional problems due to the need to maintain a large covariance matrix. To resolve this issue, we introduce a new method for accelerating SBL inference -- named covariance-free expectation maximization (CoFEM) -- that avoids explicit computation of the covariance matrix. CoFEM solves multiple linear systems to obtain unbiased estimates of the posterior statistics needed by SBL. This is accomplished by exploiting innovations from numerical linear algebra such as preconditioned conjugate gradient and a little-known diagonal estimation rule. For a large class of compressed sensing matrices, we provide theoretical justifications for why our method scales well in high-dimensional settings. Through simulations, we show that CoFEM can be up to thousands of times faster than existing baselines without sacrificing coding accuracy. Through applications to calcium imaging deconvolution and multi-contrast MRI reconstruction, we show that CoFEM enables SBL to tractably tackle high-dimensional sparse coding problems of practical interest., 13 pages

PURPOSE: To introduce wave-encoded acquisition and reconstruction techniques for highly accelerated EPI with reduced g-factor penalty and image artifacts.THEORY AND METHODS: Wave-EPI involves application of sinusoidal gradients during the EPI readout, which spreads the aliasing in all spatial directions, thereby taking better advantage of 3D coil sensitivity profiles. The amount of voxel spreading that can be achieved by the wave gradients during the short EPI readout period is constrained by the slew rate of the gradient coils and peripheral nerve stimulation monitor. We propose to use a "half-cycle" sinusoidal gradient to increase the amount of voxel spreading that can be achieved while respecting the slew and stimulation constraints. Extending wave-EPI to multi-shot acquisition minimizes geometric distortion and voxel blurring at high in-plane resolutions, while structured low-rank regularization mitigates shot-to-shot phase variations. To address gradient imperfections, we propose to use different point spread functions for the k-space lines with positive and negative polarities, which are calibrated with a FLEET-based reference scan.RESULTS: Wave-EPI enabled whole-brain single-shot gradient-echo (GE) and multi-shot spin-echo (SE) EPI acquisitions at high acceleration factors at 3T and was combined with g-Slider encoding to boost the SNR level in 1 mm isotropic diffusion imaging. Relative to blipped-CAIPI, wave-EPI reduced average and maximum g-factors by up to 1.21- and 1.37-fold at Rin × Rsms = 3 × 3, respectively.CONCLUSION: Wave-EPI allows highly accelerated single- and multi-shot EPI with reduced g-factor and artifacts and may facilitate clinical and neuroscientific applications of EPI by improving the spatial and temporal resolution in functional and diffusion imaging.

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.

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.

Diffusion MRI (dMRI) of whole, intact, fixed postmortem human brain at high spatial resolution serves as key bridging technology for 3D mapping of structural connectivity and tissue microstructure at the mesoscopic scale. Ex vivo dMRI offers superior spatial resolution compared to in vivo dMRI but comes with its own technical challenges due to the significantly reduced T2 relaxation times and decreased diffusivity incurred by tissue fixation. The altered physical properties of fixed tissue necessitate the use of alternative acquisition strategies to preserve SNR and achieve sufficient diffusion weighting. Multi-shot or segmented 3D echo planar imaging (EPI) sequences have been used to shorten echo times (TEs) with reduced distortions from field inhomogeneity and eddy currents on small-bore MR scanners and have been adopted for high b-value dMRI of ex vivo whole human brain specimens.The advent of stronger gradients on human MRI scanners has led to improved image quality and a wider range of diffusion-encoding parameters for dMRI but at the cost of more severe eddy currents that result in spatial and temporal variations in the background magnetic field, which cannot be corrected for using standard vendor-provided ghost correction solutions. In this work, we show that conventional ghost correction techniques based on navigators and linear phase correction may be insufficient for EPI sequences using strong diffusion-sensitizing gradients in ex vivo dMRI experiments, resulting in orientationally biased dMRI estimates. This previously unreported problem is a critical roadblock in any effort to leverage scanners with ultra-high gradients for high-precision mapping of human neuroanatomy at the mesoscopic scale. We propose an advanced reconstruction method based on structured low-rank matrix modeling that reduces the ghosting substantially. We show that this method leads to more accurate and reliable dMRI metrics, as exemplified by diffusion tensor imaging and high angular diffusion imaging analyses in distributed neuroanatomical areas of fixed whole human brain specimens. Our findings advocate for the use of advanced reconstruction techniques for recovering unbiased metrics from ex vivo dMRI acquisitions and represent a crucial step toward making full use of strong diffusion-encoding gradients for neuroscientific studies seeking to study brain structure at multiple spatial scales.

Purpose: Brain imaging exams typically take 10-20 min and involve multiple sequential acquisitions. A low-distortion whole-brain echo planar imaging (EPI)-based approach was developed to efficiently encode multiple contrasts in one acquisition, allowing for calculation of quantitative parameter maps and synthetic contrast-weighted images.Methods: inversion prepared spin- and gradient-echo EPI was developed with sliceorder shuffling across measurements for efficient acquisition with T-1, T-2, and T-2* weighting. A dictionary-matching approach was used to fit the images to quantitative parameter maps, which in turn were used to create synthetic weighted images with typical clinical contrasts. Dynamic slice-optimized multi-coil shimming with a B-0 shim array was used to reduce B-0 inhomogeneity and, therefore, image distortion by >50%. Multi-shot EPI was also implemented to minimize distortion and blurring while enabling high in-plane resolution. A low-rank reconstruction approach was used to mitigate errors from shot-to-shot phase variation.Results: The slice-optimized shimming approach was combined with in-plane parallel-imaging acceleration of 4x to enable single-shot EPI with more than eightfold distortion reduction. The proposed sequence efficiently obtained 40 contrasts across the whole-brain in just over 1 min at 1.2 x 1.2 x 3 mm resolution. The multishot variant of the sequence achieved higher in-plane resolution of 1 x 1 x 4 mm with good image quality in 4 min. Derived quantitative maps showed comparable values to conventional mapping methods.Conclusion: The approach allows fast whole-brain imaging with quantitative parameter maps and synthetic weighted contrasts. The slice-optimized multi-coil shimming and multi-shot reconstruction approaches result in minimal EPI distortion, giving the sequence the potential to be used in rapid screening applications.

Purpose: B1+ and T1 corrections and dynamic multi-coil shimming approaches were proposed to improve the fidelity of high isotropic resolution Generalized slice dithered enhanced resolution (gSlider) diffusion imaging. Methods: An extended reconstruction incorporating B1+ inhomogeneity and T1 recovery information was developed to mitigate slab-boundary artifacts in short-TR gSlider acquisitions. Slab-by-slab dynamic B0 shimming using a multi-coil integrated {\Delta}B0/Rx shim-array, and high in-plane acceleration (Rinplane=4) achieved with virtual-coil GRAPPA were also incorporated into a 1 mm isotropic resolution gSlider acquisition/reconstruction framework to achieve an 8-11 fold reduction in geometric distortion compared to single-shot EPI. Results: The slab-boundary artifacts were alleviated by the proposed B1+ and T1 corrections compared to the standard gSlider reconstruction pipeline for short-TR acquisitions. Dynamic shimming provided >50% reduction in geometric distortion compared to conventional global 2nd order shimming. 1 mm isotropic resolution diffusion data show that the typically problematic temporal and frontal lobes of the brain can be imaged with high geometric fidelity using dynamic shimming. Conclusions: The proposed B1+ and T1 corrections and local-field control substantially improved the fidelity of high isotropic resolution diffusion imaging, with reduced slab-boundary artifacts and geometric distortion compared to conventional gSlider acquisition and reconstruction. This enabled high-fidelity whole-brain 1 mm isotropic diffusion imaging with 64 diffusion-directions in 20 minutes using a 3T clinical scanner.

BACKGROUND Rapid volumetric imaging protocols could better utilize limited scanner resources. PURPOSE To develop and validate an optimized 6-minute high-resolution volumetric brain MRI examination using Wave-CAIPI encoding. STUDY TYPE Prospective. POPULATION/SUBJECTS Ten healthy subjects and 20 patients with a variety of intracranial pathologies. FIELD STRENGTH/SEQUENCE At 3 T, MPRAGE, T2 -weighted SPACE, SPACE FLAIR, and SWI were acquired at 9-fold acceleration using Wave-CAIPI and for comparison at 2-4-fold acceleration using conventional GRAPPA. ASSESSMENT Extensive simulations were performed to optimize the Wave-CAIPI protocol and minimize both g-factor noise amplification and potential T1 /T2 blurring artifacts. Moreover, refinements in the autocalibrated reconstruction of Wave-CAIPI were developed to ensure high-quality reconstructions in the presence of gradient imperfections. In a randomized and blinded fashion, three neuroradiologists assessed the diagnostic quality of the optimized 6-minute Wave-CAIPI exam and compared it to the roughly 3× slower GRAPPA accelerated protocol using both an individual and head-to-head analysis. STATISTICAL TEST A noninferiority test was used to test whether the diagnostic quality of Wave-CAIPI was noninferior to the GRAPPA acquisition, with a 15% noninferiority margin. RESULTS Among all sequences, Wave-CAIPI achieved negligible g-factor noise amplification (gavg ≤ 1.04) and burring artifacts from T1 /T2 relaxation. Improvements of our autocalibration approach for gradient imperfections enabled increased robustness to gradient mixing imperfections in tilted-field of view (FOV) prescriptions as well as variations in gradient and analog-to-digital converter (ADC) sampling rates. In the clinical evaluation, Wave-CAIPI achieved similar mean scores when compared with GRAPPA (MPRAGE: OW = 4.03, OG = 3.97; T2 w SPACE: OW = 4.00, OG = 4.00; SPACE FLAIR: OW = 3.97, OG = 3.97; SWI: OW = 3.93, OG = 3.83) and was statistically noninferior (N = 30, P

PurposeA major obstacle to the clinical implementation of quantitative MR is the lengthy acquisition time required to derive multi-contrast parametric maps. We sought to reduce the acquisition time for quantitative susceptibility mapping (QSM) and macromolecular tissue volume (MTV) by acquiring both contrasts simultaneously by leveraging their redundancies. The Joint Virtual Coil concept with generalized autocalibrating partially parallel acquisitions (JVC-GRAPPA) was applied to reduce acquisition time further.MethodsThree adult volunteers were imaged on a 3T scanner using a multi-echo 3D GRE sequence acquired at three head orientations. MTV, QSM, R2*, T1, and proton density maps were reconstructed. The same sequence (GRAPPA R=4) was performed in subject #1 with a single head orientation for comparison. Fully sampled data was acquired in subject #2, from which retrospective undersampling was performed (R=6 GRAPPA and R=9 JVC-GRAPPA). Prospective undersampling was performed in subject #3 (R=6 GRAPPA and R=9 JVC-GRAPPA) using gradient blips to shift k-space sampling in later echoes.ResultsSubject #1’s multi-orientation and single-orientation MTV maps were not significantly different based on RMSE. For subject #2, the retrospectively undersampled JVC-GRAPPA and GRAPPA generated similar results as fully sampled data. This approach was validated with the prospectively undersampled images in subject #3. Using QSM, R2*, and MTV, the contributions of myelin and iron content to susceptibility was estimated.ConclusionWe have developed a novel strategy to simultaneously acquire data for the reconstruction of five intrinsically co-registered 1-mm isotropic resolution multi-parametric maps, with a scan time of 6 minutes using JVC-GRAPPA.

Purpose To develop a scan-specific model that estimates and corrects k-space errors made when reconstructing accelerated MRI data. Methods Scan-specific artifact reduction in k-space (SPARK) trains a convolutional-neural-network to estimate and correct k-space errors made by an input reconstruction technique by back-propagating from the mean-squared-error loss between an auto-calibration signal (ACS) and the input technique's reconstructed ACS. First, SPARK is applied to generalized autocalibrating partially parallel acquisitions (GRAPPA) and demonstrates improved robustness over other scan-specific models, such as robust artificial-neural-networks for k-space interpolation (RAKI) and residual-RAKI. Subsequent experiments demonstrate that SPARK synergizes with residual-RAKI to improve reconstruction performance. SPARK also improves reconstruction quality when applied to advanced acquisition and reconstruction techniques like 2D virtual coil (VC-) GRAPPA, 2D LORAKS, 3D GRAPPA without an integrated ACS region, and 2D/3D wave-encoded imaging. Results SPARK yields SSIM improvement and 1.5 - 2× root mean squared error (RMSE) reduction when applied to GRAPPA and improves robustness to ACS size for various acceleration rates in comparison to other scan-specific techniques. When applied to advanced reconstruction techniques such as residual-RAKI, 2D VC-GRAPPA and LORAKS, SPARK achieves up to 20% RMSE improvement. SPARK with 3D GRAPPA also improves RMSE performance by ~2×, SSIM performance, and perceived image quality without a fully sampled ACS region. Finally, SPARK synergizes with non-Cartesian, 2D and 3D wave-encoding imaging by reducing RMSE between 20% and 25% and providing qualitative improvements. Conclusion SPARK synergizes with physics-based acquisition and reconstruction techniques to improve accelerated MRI by training scan-specific models to estimate and correct reconstruction errors in k-space.

Purpose We combine SNR-efficient acquisition and model-based reconstruction strategies with newly available hardware instrumentation to achieve distortion-free in vivo diffusion MRI of the brain at submillimeter-isotropic resolution with high fidelity and sensitivity on a clinical 3T scanner. Methods We propose blip-up/down acquisition (BUDA) for multishot EPI using interleaved blip-up/blip-down phase encoding and incorporate B0 forward-modeling into structured low-rank reconstruction to enable distortion-free and navigator-free diffusion MRI. We further combine BUDA-EPI with an SNR-efficient simultaneous multislab acquisition (generalized slice-dithered enhanced resolution ["gSlider"]), to achieve high-isotropic-resolution diffusion MRI. To validate gSlider BUDA-EPI, whole-brain diffusion data at 860-μm and 780-μm data sets were acquired. Finally, to improve the conditioning and minimize noise penalty in BUDA reconstruction at very high resolutions where B0 inhomogeneity can have a detrimental effect, the level of B0 inhomogeneity was reduced by incorporating slab-by-slab dynamic shimming with a 32-channel AC/DC coil into the acquisition. Whole-brain 600-μm diffusion data were then acquired with this combined approach of gSlider BUDA-EPI with dynamic shimming. Results The results of 860-μm and 780-μm datasets show high geometry fidelity with gSlider BUDA-EPI. With dynamic shimming, the BUDA reconstruction's noise penalty was further alleviated. This enables whole-brain 600-μm isotropic resolution diffusion imaging with high image quality. Conclusions The gSlider BUDA-EPI method enables high-quality, distortion-free diffusion imaging across the whole brain at submillimeter resolution, where the use of multicoil dynamic B0 shimming further improves reconstruction performance, which can be particularly useful at very high resolutions.

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-ch 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 of the developed coil for high-resolution and high b-value diffusion-weighted ex vivo brain MRI studies.

Purpose To create a realistic in silico head phantom for the second QSM reconstruction challenge and for future evaluations of processing algorithms for QSM. Methods We created a digital whole-head tissue property phantom by segmenting and postprocessing high-resolution (0.64 mm isotropic), multiparametric MRI data acquired at 7 T from a healthy volunteer. We simulated the steady-state magnetization at 7 T using a Bloch simulator and mimicked a Cartesian sampling scheme through Fourier-based processing. Computer code for generating the phantom and performing the MR simulation was designed to facilitate flexible modifications of the phantom in the future, such as the inclusion of pathologies as well as the simulation of a wide range of acquisition protocols. Specifically, the following parameters and effects were implemented: TR and TE, voxel size, background fields, and RF phase biases. Diffusion-weighted imaging phantom data are provided, allowing future investigations of tissue-microstructure effects in phase and QSM algorithms. Results The brain part of the phantom featured realistic morphology with spatial variations in relaxation and susceptibility values similar to the in vivo setting. We demonstrated some of the phantom's properties, including the possibility of generating phase data with nonlinear evolution over TE due to partial-volume effects or complex distributions of frequency shifts within the voxel. Conclusion The presented phantom and computer programs are publicly available and may serve as a ground truth in future assessments of the faithfulness of quantitative susceptibility reconstruction algorithms.

Purpose: Reducing scan times is important for wider adoption of high-resolution volumetric MRI in research and clinical practice. Emerging fast imaging and deep learning techniques provide promising strategies to accelerate volumetric MRI without compromising image quality. In this study, we aim to leverage an advanced fast imaging technique, wave-controlled aliasing in parallel imaging (Wave-CAIPI), and a novel denoising generative adversarial network (GAN) to achieve accelerated high-fidelity, high-signal-to-noise-ratio (SNR) volumetric MRI. Methods: 3D T2-weighted fluid-attenuated inversion recovery (FLAIR) image data were acquired on 33 multiple sclerosis (MS) patients using a prototype Wave-CAIPI sequence (acceleration factor R=3×2, 2.75 minutes) and a standard T2-SPACE FLAIR sequence (R=2, 7.25 minutes). A hybrid denoising GAN entitled "HDnGAN" composed of a 3D generator (i.e., a modified 3D U-Net entitled MU-Net) and a 2D discriminator was proposed to denoise Wave-CAIPI images with the standard FLAIR images as the target. HDnGAN was trained and validated on data from 25 MS patients by minimizing a combined content loss (i.e., mean squared error (MSE)) and adversarial loss with adjustable weight λ, and evaluated on data from 8 patients unseen during training. The quality of HDnGAN-denoised images was compared to those from other denoising methods including AONLM, BM4D, MU-Net, and 3D GAN in terms of their similarity to standard FLAIR images, quantified using MSE and VGG perceptual loss. The images from different methods were assessed by two neuroradiologists using a five-point score regarding sharpness, SNR, lesion conspicuity, and overall quality. Finally, the performance of these denoising methods was compared at higher noise levels using simulated data with added Rician noise. Results: HDnGAN effectively denoised noisy Wave-CAIPI images with sharpness and rich textural details, which could be adjusted by controlling λ. Quantitatively, HDnGAN (λ=10-3) achieved low MSE (7.43×10-4±0.94×10-4) and the lowest VGG perceptual loss (1.09×10-2±0.18×10-2). The reader study showed that HDnGAN (λ=10-3) significantly improved the SNR of Wave-CAIPI images (4.19±0.39 vs. 2.94±0.24, P-3) (3.31±0.46, P-3) (3.5±0.82, P=0.001) regarding lesion conspicuity. The overall quality score of HDnGAN (λ=10-3) (4.25±0.43) was significantly higher than those from Wave-CAIPI (3.69±0.46, P=0.003), BM4D (3.50±0.71, P=0.001), MU-Net (3.25±0.75, P-3) (3.50±0.50, P

Purpose: To improve image quality and accelerate the acquisition of 3D MRF. Methods: Building on the multi-axis spiral-projection MRF technique, a subspace reconstruction with locally low rank (LLR) constraint and a modified spiral-projection spatiotemporal encoding scheme termed tiny-golden-angle-shuffling (TGAS) were implemented for rapid whole-brain high-resolution quantitative mapping. The LLR regularization parameter and the number of subspace bases were tuned using retrospective in-vivo data and simulated examinations, respectively. B0 inhomogeneity correction using multi-frequency interpolation was incorporated into the subspace reconstruction to further improve the image quality by mitigating blurring caused by off-resonance effect. Results: The proposed MRF acquisition and reconstruction framework can produce provide high quality 1-mm isotropic whole-brain quantitative maps in a total acquisition time of 1 minute 55 seconds, with higher-quality results than ones obtained from the previous approach in 6 minutes. The comparison of quantitative results indicates that neither the subspace reconstruction nor the TGAS trajectory induce bias for T1 and T2 mapping. High quality whole-brain MRF data were also obtained at 0.66-mm isotropic resolution in 4 minutes using the proposed technique, where the increased resolution was shown to improve visualization of subtle brain structures. Conclusion: The proposed TGAS-SPI-MRF with optimized spiral-projection trajectory and subspace reconstruction can enable high-resolution quantitative mapping with faster acquisition speed., Comment: 40 pages, 11 figures, 2 tables

Myelin water imaging techniques based on multi-compartment relaxometry have been developed as an important tool to measure myelin concentration in vivo, but are limited by the long scan time of multi-contrast multi-echo acquisition. In this work, a fast imaging technique, termed variable flip angle Echo Planar Time-Resolved Imaging (vFA-EPTI), is developed to acquire multi-echo and multi-flip-angle gradient-echo data with significantly reduced acquisition time, providing rich information for multi-compartment analysis of gradient-echo myelin water imaging (GRE-MWI). The proposed vFA-EPTI method achieved 26 folds acceleration with good accuracy by utilizing an efficient continuous readout, optimized spatiotemporal encoding across echoes and flip angles, as well as a joint subspace reconstruction. An approach to estimate off-resonance field changes between different flip-angle acquisitions was also developed to ensure high-quality joint reconstruction across flip angles. The accuracy of myelin water fraction (MWF) estimate under high acceleration was first validated by a retrospective undersampling experiment using a lengthy fully-sampled data as reference. Prospective experiments were then performed where whole-brain MWF and multi-compartment quantitative maps were obtained in 5 min at 1.5 mm isotropic resolution and 24 min at 1 mm isotropic resolution at 3T. Additionally, ultra-high resolution data at 600 µm isotropic resolution were acquired at 7T, which show detailed structures within the cortex such as the line of Gennari, demonstrating the ability of the proposed method for submillimeter GRE-MWI that can be used to study cortical myeloarchitecture in vivo.

Purpose The aim of the second quantitative susceptibility mapping (QSM) reconstruction challenge (Oct 2019, Seoul, Korea) was to test the accuracy of QSM dipole inversion algorithms in simulated brain data. Methods A two-stage design was chosen for this challenge. The participants were provided with datasets of multi-echo gradient echo images synthesized from two realistic in silico head phantoms using an MR simulator. At the first stage, participants optimized QSM reconstructions without ground truth data available to mimic the clinical setting. At the second stage, ground truth data were provided for parameter optimization. Submissions were evaluated using eight numerical metrics and visual ratings. Results A total of 98 reconstructions were submitted for stage 1 and 47 submissions for stage 2. Iterative methods had the best quantitative metric scores, followed by deep learning and direct inversion methods. Priors derived from magnitude data improved the metric scores. Algorithms based on iterative approaches and total variation (and its derivatives) produced the best overall results. The reported results and analysis pipelines have been made public to allow researchers to compare new methods to the current state of the art. Conclusion The synthetic data provide a consistent framework to test the accuracy and robustness of QSM algorithms in the presence of noise, calcifications and minor voxel dephasing effects. Total Variation-based algorithms produced the best results among all metrics. Future QSM challenges should assess whether this good performance with synthetic datasets translates to more realistic scenarios, where background fields and dipole-incompatible phase contributions are included.

We propose Nonlinear Dipole Inversion (NDI) for high-quality Quantitative Susceptibility Mapping (QSM) without regularization tuning, while matching the image quality of state-of-the-art reconstruction techniques. In addition to avoiding over-smoothing that these techniques often suffer from, we also obviate the need for parameter selection. NDI is flexible enough to allow for reconstruction from an arbitrary number of head orientations and outperforms COSMOS even when using as few as 1-direction data. This is made possible by a nonlinear forward-model that uses the magnitude as an effective prior, for which we derived a simple gradient descent update rule. We synergistically combine this physics-model with a Variational Network (VN) to leverage the power of deep learning in the VaNDI algorithm. This technique adopts the simple gradient descent rule from NDI and learns the network parameters during training, hence requires no additional parameter tuning. Further, we evaluate NDI at 7 T using highly accelerated Wave-CAIPI acquisitions at 0.5 mm isotropic resolution and demonstrate high-quality QSM from as few as 2-direction data., National Institutes of Health (U.S.) (Grants R01EB020613, R01EB019437, P41EB015896, U01EB025162, S10RR023401, S10RR019307, S10RR019254, S10RR023043))

PurposeThe aim of the second quantitative susceptibility mapping (QSM) reconstruction challenge (Oct 2019, Seoul, Korea) was to test the accuracy of QSM dipole inversion algorithms in simulated brain data.MethodsA two-stage design was chosen for this challenge. The participants were provided with datasets of multi-echo gradient echo images synthesized from two realisticin silicohead phantoms using an MR simulator. At the first stage, participants optimized QSM reconstructions without ground-truths available to mimic the clinical setting. At the second stage, ground-truths were provided for parameter optimization.Submissions were evaluated using eight numerical metrics and visual ratings.ResultsA total of 98 reconstructions were submitted for stage 1 and 47 submissions for stage 2. Iterative methods had the best quantitative metric scores, followed by deep-learning and direct inversion methods. Priors derived from magnitude data improved the metric scores. Algorithms based on iterative approaches and Total Variation (and its derivatives) produced the best overall results. The reported results and analysis pipelines have been made public to allow researchers to compare new methods to the current state of the art.ConclusionThe synthetic data provides a consistent framework to test the accuracy and robustness of QSM algorithms in the presence of noise, calcifications and minor voxel dephasing effects. Total Variation-based algorithmsproduced the best results along all metrics. Future QSM challenges should asses if this good performance with synthetic datasets translates to more realistic scenarios, where background fields and dipole-incompatible phase contributions are included.

PurposeTo create a realistic in-silico head phantom for the second Quantitative Susceptibility Mapping (QSM) Reconstruction Challenge and for future evaluations of processing algorithms for QSM.MethodsWe created a digital whole-head tissue property phantom by segmenting and post-processing high-resolution (0.64mm isotropic), multi-parametric MRI data acquired at 7T from a healthy volunteer. We simulated the steady-state magnetization at 7T using a Bloch simulator and mimicked a Cartesian sampling scheme through Fourier-based processing. Computer code for generating the phantom and performing the MR simulation was designed to facilitate flexible modifications of the phantom in the future, such as the inclusion of pathologies, as well as the simulation of a wide range of acquisition protocols. Specifically, the following parameters and effects were implemented: repetition time and echo time, voxel size, background fields, and RF phase biases. Diffusion weighted imaging phantom data is provided allowing future investigations of tissue microstructure effects in phase and QSM algorithms.ResultsThe brain-part of the phantom featured realistic morphology with spatial variations in relaxation and susceptibility values similar to the in vivo setting. We demonstrated some of the phantom’s properties, including the possibility of generating phase data with non-linear evolution over echo time due to partial volume effects or complex distributions of frequency shifts within the voxel.ConclusionThe presented phantom and computer programs are publicly available and may serve as a ground truth in future assessments of the faithfulness of quantitative susceptibility reconstruction algorithms.

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-millimeter 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–white surface placement, gray–CSF surface placement and cortical thickness estimation were lower than 165 μm, 155 μm and 145 μm—sufficiently accurate for most applications. The denoising performance is 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 precision 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 sub-millimeter resolution.

Purpose Quantitative Susceptibility Mapping (QSM) is usually performed by minimizing a functional with data fidelity and regularization terms. A weighting parameter controls the balance between these terms. There is a need for techniques to find the proper balance that avoids artifact propagation and loss of details. Finding the point of maximum curvature in the L-curve is a popular choice, although it is slow, often unreliable when using variational penalties, and has a tendency to yield overregularized results. Methods We propose 2 alternative approaches to control the balance between the data fidelity and regularization terms: 1) searching for an inflection point in the log-log domain of the L-curve, and 2) comparing frequency components of QSM reconstructions. We compare these methods against the conventional L-curve and U-curve approaches. Results Our methods achieve predicted parameters that are better correlated with RMS error, high-frequency error norm, and structural similarity metric-based parameter optimizations than those obtained with traditional methods. The inflection point yields less overregularization and lower errors than traditional alternatives. The frequency analysis yields more visually appealing results, although with larger RMS error. Conclusion Our methods provide a robust parameter optimization framework for variational penalties in QSM reconstruction. The L-curve-based zero-curvature search produced almost optimal results for typical QSM acquisition settings. The frequency analysis method may use a 1.5 to 2.0 correction factor to apply it as a stand-alone method for a wider range of signal-to-noise-ratio settings. This approach may also benefit from fast search algorithms such as the binary search to speed up the process.

PURPOSE: Quantitative susceptibility mapping (QSM) is influenced by iron as well as myelin, which makes interpretation of pathologic changes challenging. Concurrent acquisition of MR sequences that are sensitive to axonal/myelin integrity, such as diffusion tensor imaging (DTI), may provide context for interpreting quantitative susceptibility (QS) signal. The purpose of our study was to investigate alterations in normal-appearing white matter (NAWM) in multiple sclerosis (MS) using QSM in conjunction with DTI. METHODS: Twenty relapsing–remitting MS patients and 20 age-matched healthy controls (HC) were recruited for this prospective study. QS, radial diffusivity (RD), fractional anisotropy (FA), and R2* maps within the whole brain as well as individual tracts were generated for comparison between NAWM and HC white matter (HCWM). RESULTS: MS lesions demonstrated significant differences in QS, FA, RD, and R2* compared to HCWM (p < 0.03). These metrics did not show a significant difference between whole-brain NAWM and HCWM. Among NAWM tracts, the cingulate gyri demonstrated significantly decreased QS compared to HCWM (p = 0.004). The forceps major showed significant differences in FA and RD without corresponding changes in QS (p < 0.01). CONCLUSION: We found discordant changes in QSM and DTI metrics within the cingulate gyri and forceps major. This may potentially reflect the influence of paramagnetic substrates such as iron, which could be decreased along these NAWM tracts. Our results point to the potential role of QSM as a unique biomarker, although additional validation studies are needed.

PURPOSE: To develop a method for fast distortion- and blurring- free imaging. THEORY: EPI with Point-Spread-Function (PSF) mapping can achieve distortion- and blurring-free imaging at a cost of long acquisition time. In this study, an acquisition/reconstruction technique, termed “tilted-CAIPI”, is proposed to achieve >20× acceleration for PSF-EPI. The proposed method systematically optimized the k-space sampling trajectory with B(0)-inhomogeneity-informed reconstruction, to exploit the inherent signal correlation in PSF-EPI and take full advantage of coil sensitivity. Susceptibility-induced phase accumulation is regarded as an additional encoding which is estimated by calibration data and integrated into reconstruction. Self-navigated phase correction was developed to correct shot-to-shot phase variation in diffusion imaging. METHODS: Tilted-CAIPI was implemented at 3T, with incorporation of partial Fourier and simultaneous multislice to achieve further accelerations. T(2)-weigthed, T(2)(*)-weighted and diffusion-weighted imaging experiments were conducted to evaluate the proposed method. RESULTS: The ability of tilted-CAIPI to provide highly accelerated imaging without distortion and blurring was demonstrated through in-vivo brain experiments, where only 8 shots per simultaneous slice group were required to provide high-quality, high-SNR imaging at 0.8–1mm resolution. CONCLUSION: Tilted-CAIPI achieved fast distortion- and blurring- free imaging with high SNR. Whole-brain T(2)-weighted, T(2)(*)-weighted and diffusion imaging can be obtained in just 15–60s.

Purpose Quantitative susceptibility mapping can be performed through the minimization of a function consisting of data fidelity and regularization terms. For data consistency, a Gaussian-phase noise distribution is often assumed, which breaks down when the signal-to-noise ratio is low. A previously proposed alternative is to use a nonlinear data fidelity term, which reduces streaking artifacts, mitigates noise amplification, and results in more accurate susceptibility estimates. We hereby present a novel algorithm that solves the nonlinear functional while achieving computation speeds comparable to those for a linear formulation. Methods We developed a nonlinear quantitative susceptibility mapping algorithm (fast nonlinear susceptibility inversion) based on the variable splitting and alternating direction method of multipliers, in which the problem is split into simpler subproblems with closed-form solutions and a decoupled nonlinear inversion hereby solved with a Newton-Raphson iterative procedure. Fast nonlinear susceptibility inversion performance was assessed using numerical phantom and in vivo experiments, and was compared against the nonlinear morphology-enabled dipole inversion method. Results Fast nonlinear susceptibility inversion achieves similar accuracy to nonlinear morphology-enabled dipole inversion but with significantly improved computational efficiency. Conclusion The proposed method enables accurate reconstructions in a fraction of the time required by state-of-the-art quantitative susceptibility mapping methods. Magn Reson Med 80:814-821, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

While many useful microstructural indices, as well as orientation distribution functions, can be obtained from multi-shell dMRI data, there is growing interest in exploring the richer set of microstructural features that can be extracted from the full ensemble average propagator (EAP). The EAP can be readily computed from diffusion spectrum imaging (DSI) data, at the cost of a very lengthy acquisition. Compressed sensing (CS) has been used to make DSI more practical by reducing its acquisition time. CS applied to DSI (CS-DSI) attempts to reconstruct the EAP from significantly undersampled q-space data. We present a post mortem validation study where we evaluate the ability of CS-DSI to approximate not only fully sampled DSI but also multi-shell acquisitions with high fidelity. Human brain samples are imaged with high-resolution DSI at 9.4T and with polarization-sensitive optical coherence tomography (PSOCT). The latter provides direct measurements of axonal orientations at microscopic resolutions, allowing us to evaluate the mesoscopic orientation estimates obtained from diffusion MRI, in terms of their angular error and the presence of spurious peaks. We test two fast, dictionary-based, L2-regularized algorithms for CS-DSI reconstruction. We find that, for a CS acceleration factor of R=3, i.e., an acquisition with 171 gradient directions, one of these methods is able to achieve both low angular error and low number of spurious peaks. With a scan length similar to that of high angular resolution multi-shell acquisition schemes, this CS-DSI approach is able to approximate both fully sampled DSI and multi-shell data with high accuracy. Thus it is suitable for orientation reconstruction and microstructural modeling techniques that require either grid- or shell-based acquisitions. We find that the signal-to-noise ratio (SNR) of the training data used to construct the dictionary can have an impact on the accuracy of CS-DSI, but that there is substantial robustness to loss of SNR in the test data. Finally, we show that, as the CS acceleration factor increases beyond R=3, the accuracy of these reconstruction methods degrade, either in terms of the angular error, or in terms of the number of spurious peaks. Our results provide useful benchmarks for the future development of even more efficient q-space acceleration techniques.

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.

Purpose The aim of the 2016 quantitative susceptibility mapping (QSM) reconstruction challenge was to test the ability of various QSM algorithms to recover the underlying susceptibility from phase data faithfully. Methods Gradient-echo images of a healthy volunteer acquired at 3T in a single orientation with 1.06 mm isotropic resolution. A reference susceptibility map was provided, which was computed using the susceptibility tensor imaging algorithm on data acquired at 12 head orientations. Susceptibility maps calculated from the single orientation data were compared against the reference susceptibility map. Deviations were quantified using the following metrics: root mean squared error (RMSE), structure similarity index (SSIM), high-frequency error norm (HFEN), and the error in selected white and gray matter regions. Results Twenty-seven submissions were evaluated. Most of the best scoring approaches estimated the spatial frequency content in the ill-conditioned domain of the dipole kernel using compressed sensing strategies. The top 10 maps in each category had similar error metrics but substantially different visual appearance. Conclusion Because QSM algorithms were optimized to minimize error metrics, the resulting susceptibility maps suffered from over-smoothing and conspicuity loss in fine features such as vessels. As such, the challenge highlighted the need for better numerical image quality criteria. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

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.

Purpose To describe a model-based reconstruction strategy for single-shot echo planar imaging (EPI) that intrinsically accounts for k-space nonuniformity, Nyquist ghosting, and geometric distortions during rather than before or after image reconstruction. Methods Ramp sampling and inhomogeneous B0 field-induced distortion cause the EPI samples to lie on a non-Cartesian grid, thus requiring the nonuniform fast Fourier transform. Additionally, a 2D Nyquist ghost phase correction without the need for extra navigator acquisition is included in the proposed reconstruction. Coil compression is also incorporated to reduce the computational load. The proposed method is applied to phantom and human brain MRI data. Results The results demonstrate that Nyquist ghosting and geometric distortions are reduced by the proposed reconstruction. The proposed 2D phase correction is superior to a conventional 1D correction. The reductions of both artifacts lead to improved temporal signal-to-noise ratio (tSNR). The virtual coil results suggest that the processing time can be reduced by up to 75%, with a mean tSNR loss of only 3.2% when using 8-virtual instead of 32-physical coils for twofold undersampled data. Conclusion The proposed reconstruction improves the quality (ghosting, geometry, and tSNR) of EPI without requiring calibration data for Nyquist ghost correction. Magn Reson Med 78:2250–2264, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

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

Purpose: To rapidly obtain high isotropic-resolution T2 maps with whole-brain coverage and high geometric fidelity. Methods: A T2 blip-up/down echo planar imaging (EPI) acquisition with generalized Slice-dithered enhanced resolution (T2-BUDA-gSlider) is proposed. A radiofrequency (RF)-encoded multi-slab spin-echo EPI acquisition with multiple echo times (TEs) was developed to obtain high SNR efficiency with reduced repetition time (TR). This was combined with an interleaved 2-shot EPI acquisition using blip-up/down phase encoding. An estimated field map was incorporated into the joint multi-shot EPI reconstruction with a structured low rank constraint to achieve distortion-free and robust reconstruction for each slab without navigation. A Bloch simulated subspace model was integrated into gSlider reconstruction and utilized for T2 quantification. Results: In vivo results demonstrated that the T2 values estimated by the proposed method were consistent with gold standard spin-echo acquisition. Compared to the reference 3D fast spin echo (FSE) images, distortion caused by off-resonance and eddy current effects were effectively mitigated. Conclusion: BUDA-gSlider SE-EPI acquisition and gSlider-subspace joint reconstruction enabled distortion-free whole-brain T2 mapping in 2 min at ~1 mm3 isotropic resolution, which could bring significant benefits to related clinical and neuroscience applications., 20 pages, 7 figures

Multi-shot echo planar imaging (msEPI) is a promising approach to achieve high in-plane resolution with high sampling efficiency and low T2* blurring. However, due to the geometric distortion, shot-to-shot phase variations and potential subject motion, msEPI continues to be a challenge in MRI. In this work, we introduce acquisition and reconstruction strategies for robust, high-quality msEPI without phase navigators. We propose Blip Up-Down Acquisition (BUDA) using interleaved blip-up and -down phase encoding, and incorporate B0 forward-modeling into Hankel structured low-rank model to enable distortion- and navigator-free msEPI. We improve the acquisition efficiency and reconstruction quality by incorporating simultaneous multi-slice acquisition and virtual-coil reconstruction into the BUDA technique. We further combine BUDA with the novel RF-encoded gSlider acquisition, dubbed BUDA-gSlider, to achieve rapid high isotropic-resolution MRI. Deploying BUDA-gSlider with model-based reconstruction allows for distortion-free whole-brain 1mm isotropic T2 mapping in about 1 minute. It also provides whole-brain 1mm isotropic diffusion imaging with high geometric fidelity and SNR efficiency. We finally incorporate sinusoidal wave gradients during the EPI readout to better use coil sensitivity encoding with controlled aliasing., Comment: 13 pages, 10 figures