Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla.

Introduction: Nicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for in vivo measurement and imaging. Methods: In this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI)-based NAD assay at ultrahigh field (7 Tesla), in combination with a probabilistic subspace-based processing method. Results: The processing method achieved about a 10-fold reduction in noise over raw measurements, resulting in remarkably reduced estimation errors of NAD. Quantified NAD levels, observed at approximately 0.4 mM, exhibited good reproducibility within repeated scans on the same subject and good consistency across subjects in group data (2.3 cc nominal resolution). One set of higher-resolution data (1.0 cc nominal resolution) unveiled potential for assessing tissue metabolic heterogeneity, showing similar NAD distributions in white and gray matter. Preliminary analysis of age dependence suggested that the NAD level decreases with age. Discussion: These results illustrate favorable outcomes of our first attempt to use ultrahigh field 31P-MRSI and advanced processing techniques to generate a whole-brain map of low-concentration intracellular NAD content in the human brain.

High-fidelity intravoxel incoherent motion parameter mapping using locally low-rank and subspace modeling.

PURPOSE: Intravoxel incoherent motion (IVIM) is a quantitative magnetic resonance imaging (MRI) method used to quantify perfusion properties of tissue non-invasively without contrast. However, clinical applications are limited by unreliable parameter estimates, particularly for the perfusion fraction (f) and pseudodiffusion coefficient (D*). This study aims to develop a high-fidelity reconstruction for reliable estimation of IVIM parameters. The proposed method is versatile and amenable to various acquisition schemes and fitting methods. METHODS: To address current challenges with IVIM, we adapted several advanced reconstruction techniques. We used a low-rank approximation of IVIM images and temporal subspace modeling to constrain the magnetization dynamics of the bi-exponential diffusion signal decay. In addition, motion-induced phase variations were corrected between diffusion directions and b-values, facilitating the use of high SNR real-valued diffusion data. The proposed method was evaluated in simulations and in vivo brain acquisitions in six healthy subjects and six individuals with a history of SARS-CoV-2 infection and compared with the conventionally reconstructed magnitude data. Following reconstruction, IVIM parameters were estimated voxel-wise. RESULTS: Our proposed method reduced noise contamination in simulations, resulting in a 60%, 58.9%, and 83.9% reduction in the NRMSE for D, f, and D*, respectively, compared to the conventional reconstruction. In vivo, anisotropic properties of D, f, and D* were preserved with the proposed method, highlighting microvascular differences in gray matter between individuals with a history of COVID-19 and those without (p = 0.0210), which wasn't observed with the conventional reconstruction. CONCLUSION: The proposed method yielded a more reliable estimation of IVIM parameters with less noise than the conventional reconstruction. Further, the proposed method preserved anisotropic properties of IVIM parameter estimates and demonstrated differences in microvascular perfusion in COVID-affected subjects, which weren't observed with conventional reconstruction methods.

Linear optimal transport subspaces for point set classification.

Learning from point sets is an essential component in many computer vision and machine learning applications. Native, unordered, and permutation invariant set structure space is challenging to model, particularly for point set classification under spatial deformations. Here we propose a framework for classifying point sets experiencing certain types of spatial deformations, with a particular emphasis on datasets featuring affine deformations. Our approach employs the Linear Optimal Transport (LOT) transform to obtain a linear embedding of set-structured data. Utilizing the mathematical properties of the LOT transform, we demonstrate its capacity to accommodate variations in point sets by constructing a convex data space, effectively simplifying point set classification problems. Our method, which employs a nearest-subspace algorithm in the LOT space, demonstrates label efficiency, non-iterative behavior, and requires no hyper-parameter tuning. It achieves competitive accuracies compared to state-of-the-art methods across various point set classification tasks. Furthermore, our approach exhibits robustness in out-of-distribution scenarios where training and test distributions vary in terms of deformation magnitudes.

B1 mapping using pre-learned subspaces for quantitative brain imaging.

PURPOSE: To develop a machine learning-based method for estimation of both transmitter and receiver B1 fields desired for correction of the B1 inhomogeneity effects in quantitative brain imaging. THEORY AND METHODS: A subspace model-based machine learning method was proposed for estimation of B1t and B1r fields. Probabilistic subspace models were used to capture scan-dependent variations in the B1 fields; the subspace basis and coefficient distributions were learned from pre-scanned training data. Estimation of the B1 fields for new experimental data was achieved by solving a linear optimization problem with prior distribution constraints. We evaluated the performance of the proposed method for B1 inhomogeneity correction in quantitative brain imaging scenarios, including T1 and proton density (PD) mapping from variable-flip-angle spoiled gradient-echo (SPGR) data as well as neurometabolic mapping from MRSI data, using phantom, healthy subject and brain tumor patient data. RESULTS: In both phantom and healthy subject data, the proposed method produced high-quality B1 maps. B1 correction on SPGR data using the estimated B1 maps produced significantly improved T1 and PD maps. In brain tumor patients, the proposed method produced more accurate and robust B1 estimation and correction results than conventional methods. The B1 maps were also applied to MRSI data from tumor patients and produced improved neurometabolite maps, with better separation between pathological and normal tissues. CONCLUSION: This work presents a novel method to estimate B1 variations using probabilistic subspace models and machine learning. The proposed method may make correction of B1 inhomogeneity effects more robust in practical applications.

T 2 ' mapping of the brain from water-unsuppressed 1 H-MRSI and turbo spin-echo data.

PURPOSE: To obtain high-quality T 2 ' $$ {\mathrm{T}}_2^{\prime } $$ maps of brain tissues from water-unsuppressed magnetic resonance spectroscopic imaging (MRSI) and turbo spin-echo (TSE) data. METHODS: T 2 ' $$ {\mathrm{T}}_2^{\prime } $$ mapping can be achieved using T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping from water-unsuppressed MRSI data and T 2 $$ {\mathrm{T}}_2 $$ mapping from TSE data. However, T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping often suffers from signal dephasing and distortions caused by B 0 $$ {\mathrm{B}}_0 $$ field inhomogeneity; T 2 $$ {\mathrm{T}}_2 $$ measurements may be biased due to system imperfections, especially for T 2 $$ {\mathrm{T}}_2 $$ -weighted image with small number of TEs. In this work, we corrected the B 0 $$ {\mathrm{B}}_0 $$ field inhomogeneity effect on T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping using a subspace model-based method, incorporating pre-learned spectral basis functions of the water signals. T 2 $$ {\mathrm{T}}_2 $$ estimation bias was corrected using a TE-adjustment method, which modeled the deviation between measured and reference T 2 $$ {\mathrm{T}}_2 $$ decays as TE shifts. RESULTS: In vivo experiments were performed to evaluate the performance of the proposed method. High-quality T 2 * $$ {\mathrm{T}}_2^{\ast } $$ maps were obtained in the presence of large field inhomogeneity in the prefrontal cortex. Bias in T 2 $$ {\mathrm{T}}_2 $$ measurements obtained from TSE data was effectively reduced. Based on the T 2 * $$ {\mathrm{T}}_2^{\ast } $$ and T 2 $$ {\mathrm{T}}_2 $$ measurements produced by the proposed method, high-quality T 2 ' $$ {\mathrm{T}}_2^{\prime } $$ maps were obtained, along with neurometabolite maps, from MRSI and TSE data that were acquired in about 9 min. The results obtained from acute stroke and glioma patients demonstrated the feasibility of the proposed method in the clinical setting. CONCLUSIONS: High-quality T 2 ' $$ {\mathrm{T}}_2^{\prime } $$ maps can be obtained from water-unsuppressed 1 H-MRSI and TSE data using the proposed method. With further development, this method may lay a foundation for simultaneously imaging oxygenation and neurometabolic alterations of brain disorders.

Simultaneous QSM and metabolic imaging of the brain using SPICE: Further improvements in data acquisition and processing.

PURPOSE: To achieve high-resolution mapping of brain tissue susceptibility in simultaneous QSM and metabolic imaging. METHODS: Simultaneous QSM and metabolic imaging was first achieved using SPICE (spectroscopic imaging by exploiting spatiospectral correlation), but the QSM maps thus obtained were at relatively low-resolution (2.0 × 3.0 × 3.0 mm3 ). We overcome this limitation using an improved SPICE data acquisition method with the following novel features: 1) sampling (k, t)-space in dual densities, 2) sampling central k-space fully to achieve nominal spatial resolution of 3.0 × 3.0 × 3.0 mm3 for metabolic imaging, and 3) sampling outer k-space sparsely to achieve spatial resolution of 1.0 × 1.0 × 1.9 mm3 for QSM. To keep the scan time short, we acquired spatiospectral encodings in echo-planar spectroscopic imaging trajectories in central k-space but in CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) trajectories in outer k-space using blipped phase encodings. For data processing and image reconstruction, a union-of-subspaces model was used, effectively incorporating sensitivity encoding, spatial priors, and spectral priors of individual molecules. RESULTS: In vivo experiments were carried out to evaluate the feasibility and potential of the proposed method. In a 6-min scan, QSM maps at 1.0 × 1.0 × 1.9 mm3 resolution and metabolic maps at 3.0 × 3.0 × 3.0 mm3 nominal resolution were obtained simultaneously. Compared with the original method, the QSM maps obtained using the new method reveal fine-scale brain structures more clearly. CONCLUSION: We demonstrated the feasibility of achieving high-resolution QSM simultaneously with metabolic imaging using a modified SPICE acquisition method. The improved capability of SPICE may further enhance its practical utility in brain mapping.

GRASP-Pro: imProving GRASP DCE-MRI through self-calibrating subspace-modeling and contrast phase automation.

PURPOSE: To propose a highly accelerated, high-resolution dynamic contrast-enhanced MRI (DCE-MRI) technique called GRASP-Pro (golden-angle radial sparse parallel imaging with imProved performance) through a joint sparsity and self-calibrating subspace constraint with automated selection of contrast phases. METHODS: GRASP-Pro reconstruction enforces a combination of an explicit low-rank subspace-constraint and a temporal sparsity constraint. The temporal basis used to construct the subspace is learned from an intermediate reconstruction step using the low-resolution portion of radial k-space, which eliminates the need for generating the basis using auxiliary data or a physical signal model. A convolutional neural network was trained to generate the contrast enhancement curve in the artery, from which clinically relevant contrast phases are automatically selected for evaluation. The performance of GRASP-Pro was demonstrated for high spatiotemporal resolution DCE-MRI of the prostate and was compared against standard GRASP in terms of overall image quality, image sharpness, and residual streaks and/or noise level. RESULTS: Compared to GRASP, GRASP-Pro reconstructed dynamic images with enhanced sharpness, less residual streaks and/or noise, and finer delineation of the prostate without prolonging reconstruction time. The image quality improvement reached statistical significance (P < 0.05) in all the assessment categories. The neural network successfully generated contrast enhancement curves in the artery, and corresponding peak enhancement indexes correlated well with that from the manual selection. CONCLUSION: GRASP-Pro is a promising method for rapid and continuous DCE-MRI. It enables superior reconstruction performance over standard GRASP and allows reliable generation of artery enhancement curve to guide the selection of desired contrast phases for improving the efficiency of GRASP MRI workflow.

Improved magnetic resonance fingerprinting reconstruction with low-rank and subspace modeling.

PURPOSE: This article introduces a constrained imaging method based on low-rank and subspace modeling to improve the accuracy and speed of MR fingerprinting (MRF). THEORY AND METHODS: A new model-based imaging method is developed for MRF to reconstruct high-quality time-series images and accurate tissue parameter maps (e.g., T1 , T2 , and spin density maps). Specifically, the proposed method exploits low-rank approximations of MRF time-series images, and further enforces temporal subspace constraints to capture magnetization dynamics. This allows the time-series image reconstruction problem to be formulated as a simple linear least-squares problem, which enables efficient computation. After image reconstruction, tissue parameter maps are estimated via dictionary-based pattern matching, as in the conventional approach. RESULTS: The effectiveness of the proposed method was evaluated with in vivo experiments. Compared with the conventional MRF reconstruction, the proposed method reconstructs time-series images with significantly reduced aliasing artifacts and noise contamination. Although the conventional approach exhibits some robustness to these corruptions, the improved time-series image reconstruction in turn provides more accurate tissue parameter maps. The improvement is pronounced especially when the acquisition time becomes short. CONCLUSIONS: The proposed method significantly improves the accuracy of MRF, and also reduces data acquisition time. Magn Reson Med 79:933-942, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Simultaneous QSM and metabolic imaging of the brain using SPICE.

PURPOSE: To map brain metabolites and tissue magnetic susceptibility simultaneously using a single three-dimensional 1 H-MRSI acquisition without water suppression. METHODS: The proposed technique builds on a subspace imaging method called spectroscopic imaging by exploiting spatiospectral correlation (SPICE), which enables ultrashort echo time (TE)/short pulse repetition time (TR) acquisitions for 1 H-MRSI without water suppression. This data acquisition scheme simultaneously captures both the spectral information of brain metabolites and the phase information of the water signals that is directly related to tissue magnetic susceptibility variations. In extending this scheme for simultaneous QSM and metabolic imaging, we increase k-space coverage by using dual density sparse sampling and ramp sampling to achieve spatial resolution often required by QSM, while maintaining a reasonable signal-to-noise ratio (SNR) for the spatiospectral data used for metabolite mapping. In data processing, we obtain high-quality QSM from the unsuppressed water signals by taking advantage of the larger number of echoes acquired and any available anatomical priors; metabolite spatiospectral distributions are reconstructed using a union-of-subspaces model. RESULTS: In vivo experimental results demonstrate that the proposed method can produce susceptibility maps at a resolution higher than 1.8 × 1.8 × 2.4 mm3 along with metabolite spatiospectral distributions at a nominal spatial resolution of 2.4 × 2.4 × 2.4 mm3 from a single 7-min MRSI scan. The estimated susceptibility values are consistent with those obtained using the conventional QSM method with 3D multi-echo gradient echo acquisitions. CONCLUSION: This article reports a new capability for simultaneous susceptibility mapping and metabolic imaging of the brain from a single 1 H-MRSI scan, which has potential for a wide range of applications. Magn Reson Med 79:13-21, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

High-resolution dynamic 31 P-MRSI using a low-rank tensor model.

PURPOSE: To develop a rapid 31 P-MRSI method with high spatiospectral resolution using low-rank tensor-based data acquisition and image reconstruction. METHODS: The multidimensional image function of 31 P-MRSI is represented by a low-rank tensor to capture the spatial-spectral-temporal correlations of data. A hybrid data acquisition scheme is used for sparse sampling, which consists of a set of "training" data with limited k-space coverage to capture the subspace structure of the image function, and a set of sparsely sampled "imaging" data for high-resolution image reconstruction. An explicit subspace pursuit approach is used for image reconstruction, which estimates the bases of the subspace from the "training" data and then reconstructs a high-resolution image function from the "imaging" data. RESULTS: We have validated the feasibility of the proposed method using phantom and in vivo studies on a 3T whole-body scanner and a 9.4T preclinical scanner. The proposed method produced high-resolution static 31 P-MRSI images (i.e., 6.9 × 6.9 × 10 mm3 nominal resolution in a 15-min acquisition at 3T) and high-resolution, high-frame-rate dynamic 31 P-MRSI images (i.e., 1.5 × 1.5 × 1.6 mm3 nominal resolution, 30 s/frame at 9.4T). CONCLUSIONS: Dynamic spatiospectral variations of 31 P-MRSI signals can be efficiently represented by a low-rank tensor. Exploiting this mathematical structure for data acquisition and image reconstruction can lead to fast 31 P-MRSI with high resolution, frame-rate, and SNR. Magn Reson Med 78:419-428, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Sparse and dense hybrid representation via subspace modeling for dynamic MRI.

Recent theoretical results on compressed sensing and low-rank matrix recovery have inspired significant interest in joint sparse and low rank modeling of dynamic magnetic resonance imaging (dMRI). Existing approaches usually describe these two respective prior information with different formulations. In this paper, we present a novel sparse and dense hybrid representation (SDR) model which describes the sparse plus low rank properties by a unified way. More specifically, under the learned dictionary consisting of temporal basis functions, SDR models the spatial coefficients in two subspaces with Laplacian and Gaussian prior distributions, respectively. This results in the objective function consisting of L1-L2 hybrid penalty term for the coefficients and Frobenius norm term for the dictionary. An efficient algorithm utilizing alternating direction technique is developed to solve the proposed model. Extensive experiments under a variety of test images and a comprehensive evaluation against existing state-of-the-art methods consistently demonstrate the potential of the proposed model and algorithm, in terms of reconstruction and separation comparisons.

A subspace approach to high-resolution spectroscopic imaging.

PURPOSE: To accelerate spectroscopic imaging using sparse sampling of (k,t)-space and subspace (or low-rank) modeling to enable high-resolution metabolic imaging with good signal-to-noise ratio. METHODS: The proposed method, called SPectroscopic Imaging by exploiting spatiospectral CorrElation, exploits a unique property known as partial separability of spectroscopic signals. This property indicates that high-dimensional spectroscopic signals reside in a very low-dimensional subspace and enables special data acquisition and image reconstruction strategies to be used to obtain high-resolution spatiospectral distributions with good signal-to-noise ratio. More specifically, a hybrid chemical shift imaging/echo-planar spectroscopic imaging pulse sequence is proposed for sparse sampling of (k,t)-space, and a low-rank model-based algorithm is proposed for subspace estimation and image reconstruction from sparse data with the capability to incorporate prior information and field inhomogeneity correction. RESULTS: The performance of the proposed method has been evaluated using both computer simulations and phantom studies, which produced very encouraging results. For two-dimensional spectroscopic imaging experiments on a metabolite phantom, a factor of 10 acceleration was achieved with a minimal loss in signal-to-noise ratio compared to the long chemical shift imaging experiments and with a significant gain in signal-to-noise ratio compared to the accelerated echo-planar spectroscopic imaging experiments. CONCLUSION: The proposed method, SPectroscopic Imaging by exploiting spatiospectral CorrElation, is able to significantly accelerate spectroscopic imaging experiments, making high-resolution metabolic imaging possible.