Multiscale biochemical mapping of the brain through deep-learning-enhanced high-throughput mass spectrometry.

Spatial omics technologies can reveal the molecular intricacy of the brain. While mass spectrometry imaging (MSI) provides spatial localization of compounds, comprehensive biochemical profiling at a brain-wide scale in three dimensions by MSI with single-cell resolution has not been achieved. We demonstrate complementary brain-wide and single-cell biochemical mapping using MEISTER, an integrative experimental and computational mass spectrometry (MS) framework. Our framework integrates a deep-learning-based reconstruction that accelerates high-mass-resolving MS by 15-fold, multimodal registration creating three-dimensional (3D) molecular distributions and a data integration method fitting cell-specific mass spectra to 3D datasets. We imaged detailed lipid profiles in tissues with millions of pixels and in large single-cell populations acquired from the rat brain. We identified region-specific lipid contents and cell-specific localizations of lipids depending on both cell subpopulations and anatomical origins of the cells. Our workflow establishes a blueprint for future development of multiscale technologies for biochemical characterization of the brain.

Epigenetic MRI: Noninvasive imaging of DNA methylation in the brain.

Both neuronal and genetic mechanisms regulate brain function. While there are excellent methods to study neuronal activity in vivo, there are no nondestructive methods to measure global gene expression in living brains. Here, we present a method, epigenetic MRI (eMRI), that overcomes this limitation via direct imaging of DNA methylation, a major gene-expression regulator. eMRI exploits the methionine metabolic pathways for DNA methylation to label genomic DNA through 13C-enriched diets. A 13C magnetic resonance spectroscopic imaging method then maps the spatial distribution of labeled DNA. We validated eMRI using pigs, whose brains have stronger similarity to humans in volume and anatomy than rodents, and confirmed efficient 13C-labeling of brain DNA. We also discovered strong regional differences in global DNA methylation. Just as functional MRI measurements of regional neuronal activity have had a transformational effect on neuroscience, we expect that the eMRI signal, both as a measure of regional epigenetic activity and as a possible surrogate for regional gene expression, will enable many new investigations of human brain function, behavior, and disease.

High-resolution 1H-MRSI at 9.4 T by integrating relaxation enhancement and subspace imaging.

Achieving high-resolution and high signal-to-noise ratio (SNR) in vivo metabolic imaging via fast magnetic resonance spectroscopic imaging (MRSI) has been a longstanding challenge. This study combines the methods of relaxation enhancement (RE) and subspace imaging for the first time, enabling high-resolution and high-SNR in vivo MRSI of rodent brains at 9.4 T. Specifically, an RE-based chemical shift imaging sequence, which combines a frequency-selective pulse to excite only the metabolite frequencies with minimum perturbation of the water spins and a pair of adiabatic pulses to spatially localize the slice of interest, is designed and evaluated in vivo. This strategy effectively shortens the apparent T1 of metabolites, thereby increasing the SNR during relatively short repetition time ((TR) compared with acquisitions with only spatially selective wideband excitations, and does not require water suppression. The SNR was further enhanced via a state-of-the-art subspace reconstruction method. A novel subspace learning strategy tailored for 9.4 T and RE acquisitions is developed. In vivo, high-resolution (e.g., voxel size of 0.6 × 0.6 × 1.5 mm3) MRSI of both healthy mouse brains and a glioma-bearing mouse brain in 12.5 min has been demonstrated.

High-Dimensional MR Spatiospectral Imaging by Integrating Physics-Based Modeling and Data-Driven Machine Learning: Current progress and future directions.

Magnetic resonance spectroscopic imaging (MRSI) offers a unique molecular window into the physiological and pathological processes in the human body. However, the applications of MRSI have been limited by a number of long-standing technical challenges due to high dimensionality and low signal-to-noise ratio (SNR). Recent technological developments integrating physics-based modeling and data-driven machine learning that exploit unique physical and mathematical properties of MRSI signals have demonstrated impressive performance in addressing these challenges for rapid, high-resolution, quantitative MRSI. This paper provides a systematic review of these progresses in the context of MRSI physics and offers perspectives on promising future directions.

Enhancing the Throughput of FT Mass Spectrometry Imaging Using Joint Compressed Sensing and Subspace Modeling.

Mass spectrometry imaging (MSI) allows for untargeted mapping of the chemical composition of tissues with attomole detection limits. MSI using Fourier transform (FT)-based mass spectrometers, such as FT-ion cyclotron resonance (FT-ICR), grants the ability to examine the chemical space with unmatched mass resolution and mass accuracy. However, direct imaging of large tissue samples using FT-ICR is slow. In this work, we present an approach that combines the subspace modeling of ICR temporal signals with compressed sensing to accelerate high-resolution FT-ICR MSI. A joint subspace and spatial sparsity constrained model computationally reconstructs high-resolution MSI data from the sparsely sampled transients with reduced duration, allowing a significant reduction in imaging time. Simulation studies and experimental implementation of the proposed method in investigation of brain tissues demonstrate a 10-fold enhancement in throughput of FT-ICR MSI, without the need for instrumental or hardware modifications.

High-resolution, 3D multi-TE 1 H MRSI using fast spatiospectral encoding and subspace imaging.

PURPOSE: To develop a novel method to achieve fast, high-resolution, 3D multi-TE 1 H-MRSI of the brain. METHODS: A new multi-TE MRSI acquisition strategy was developed that integrates slab selective excitation with adiabatic refocusing for better volume coverage, rapid spatiospectral encoding, sparse multi-TE sampling, and interleaved water navigators for field mapping and calibration. Special data processing strategies were developed to interpolate the sparsely sampled data, remove nuisance signals, and reconstruct multi-TE spatiospectral distributions with high SNR. Phantom and in vivo experiments have been carried out to demonstrate the capability of the proposed method. RESULTS: The proposed acquisition can produce multi-TE 1 H-MRSI data with three TEs at a nominal spatial resolution of 3.4 × 3.4 × 5.3 mm3 in around 20 min. High-SNR brain metabolite spatiospectral reconstructions can be obtained from both a metabolite phantom and in vivo experiments by the proposed method. CONCLUSION: High-resolution, 3D multi-TE 1 H-MRSI of the brain can be achieved within clinically feasible time. This capability, with further optimizations, could be translated to clinical applications and neuroscience studies where simultaneously mapping metabolites and neurotransmitters and TE-dependent molecular spectral changes are of interest.

DeepSENSE: Learning coil sensitivity functions for SENSE reconstruction using deep learning.

PURPOSE: To improve the estimation of coil sensitivity functions from limited auto-calibration signals (ACS) in SENSE-based reconstruction for brain imaging. METHODS: We propose to use deep learning to estimate coil sensitivity functions by leveraging information from previous scans obtained using the same RF receiver system. Specifically, deep convolutional neural networks were designed to learn an end-to-end mapping from the initial sensitivity to the high-resolution counterpart. Sensitivity alignment was further proposed to reduce the geometric variation caused by different subject positions and imaging FOVs. Cross-validation with a small set of datasets was performed to validate the learned neural network. Iterative SENSE reconstruction was adopted to evaluate the utility of the sensitivity functions from the proposed and conventional methods. RESULTS: The proposed method produced improved sensitivity estimates and SENSE reconstructions compared to the conventional methods in terms of aliasing and noise suppression with very limited ACS data. Cross-validation with a small set of data demonstrated the feasibility of learning coil sensitivity functions for brain imaging. The network learned on the spoiled GRE data can be applied to predict sensitivity functions for spin-echo and MPRAGE datasets. CONCLUSION: A deep learning-based method has been proposed for improving the estimation of coil sensitivity functions. Experimental results have demonstrated the feasibility and potential of the proposed method for improving SENSE-based reconstructions especially when the ACS data are limited.

Intravoxel B0 inhomogeneity corrected reconstruction using a low-rank encoding operator.

PURPOSE: To present a general and efficient method for macroscopic intravoxel B0 inhomogeneity corrected reconstruction from multi-TE acquisitions. THEORY AND METHODS: A signal encoding model for multi-TE gradient echo (GRE) acquisitions that incorporates 3D intravoxel B0 field variations is derived, and a low-rank approximation to the encoding operator is introduced under piecewise linear B0 assumption. The low-rank approximation enables very efficient computation and memory usage, and allows the proposed signal model to be integrated into general inverse problem formulations that are compatible with multi-coil and undersampling acquisitions as well as different regularization functions. RESULTS: Experimental multi-echo GRE data were acquired to evaluate the proposed method. Effective reduction of macroscopic intravoxel B0 inhomogeneity induced artifacts was demonstrated. Improved R2∗ estimation from the corrected reconstruction over standard Fourier reconstruction has also been obtained. CONCLUSIONS: The proposed method can effectively correct the effects of intravoxel B0 inhomogeneity, and can be useful for various imaging applications involving GRE-based acquisitions, including fMRI, quantitative R2∗ and susceptibility mapping, and MR spectroscopic imaging.

Ultrafast magnetic resonance spectroscopic imaging using SPICE with learned subspaces.

PURPOSE: To develop a subspace learning method for the recently proposed subspace-based MRSI approach known as SPICE, and achieve ultrafast 1 H-MRSI of the brain. THEORY AND METHODS: A novel strategy is formulated to learn a low-dimensional subspace representation of MR spectra from specially acquired training data and use the learned subspace for general MRSI experiments. Specifically, the subspace learning problem is formulated as learning "empirical" distributions of molecule-specific spectral parameters (e.g., concentrations, lineshapes, and frequency shifts) by integrating physics-based model and the training data. The learned spectral parameters and quantum mechanical simulation basis can then be combined to construct acquisition-specific subspace for spatiospectral encoding and processing. High-resolution MRSI acquisitions combining ultrashort-TE/short-TR excitation, sparse sampling, and the elimination of water suppression have been performed to evaluate the feasibility of the proposed method. RESULTS: The accuracy of the learned subspace and the capability of the proposed method in producing high-resolution 3D 1 H metabolite maps and high-quality spatially resolved spectra (with a nominal resolution of ∼2.4 × 2.4 × 3 mm3 in 5 minutes) were demonstrated using phantom and in vivo studies. By eliminating water suppression, we are also able to extract valuable information from the water signals for data processing ( B0 map, frequency drift, and coil sensitivity) as well as for mapping tissue susceptibility and relaxation parameters. CONCLUSIONS: The proposed method enables ultrafast 1 H-MRSI of the brain using a learned subspace, eliminating the need of acquiring subject-dependent navigator data (known as D1 ) in the original SPICE technique. It represents a new way to perform MRSI experiments and an important step toward practical applications of high-resolution MRSI.

Macromolecule mapping of the brain using ultrashort-TE acquisition and reference-based metabolite removal.

PURPOSE: To develop a practical method for mapping macromolecule distribution in the brain using ultrashort-TE MRSI data. METHODS: An FID-based chemical shift imaging acquisition without metabolite-nulling pulses was used to acquire ultrashort-TE MRSI data that capture the macromolecule signals with high signal-to-noise-ratio (SNR) efficiency. To remove the metabolite signals from the ultrashort-TE data, single voxel spectroscopy data were obtained to determine a set of high-quality metabolite reference spectra. These spectra were then incorporated into a generalized series (GS) model to represent general metabolite spatiospectral distributions. A time-segmented algorithm was developed to back-extrapolate the GS model-based metabolite distribution from truncated FIDs and remove it from the MRSI data. Numerical simulations and in vivo experiments have been performed to evaluate the proposed method. RESULTS: Simulation results demonstrate accurate metabolite signal extrapolation by the proposed method given a high-quality reference. For in vivo experiments, the proposed method is able to produce spatiospectral distributions of macromolecules in the brain with high SNR from data acquired in about 10 minutes. We further demonstrate that the high-dimensional macromolecule spatiospectral distribution resides in a low-dimensional subspace. This finding provides a new opportunity to use subspace models for quantification and accelerated macromolecule mapping. Robustness of the proposed method is also demonstrated using multiple data sets from the same and different subjects. CONCLUSION: The proposed method is able to obtain macromolecule distributions in the brain from ultrashort-TE acquisitions. It can also be used for acquiring training data to determine a low-dimensional subspace to represent the macromolecule signals for subspace-based MRSI. Magn Reson Med 79:2460-2469, 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 1 H-MRSI of the brain using short-TE SPICE.

PURPOSE: To improve signal-to-noise ratio (SNR) for high-resolution spectroscopic imaging using a subspace-based technique known as SPectroscopic Imaging by exploiting spatiospectral CorrElation (SPICE). METHODS: The proposed method is based on a union-of-subspaces model of MRSI signals, which exploits the partial separability properties of water, lipid, baseline and metabolite signals. Enabled by this model, a special scheme is used for accelerated data acquisition, which includes a double-echo CSI component used to collect a "training" dataset (for determination of the basis functions) and a short-TE EPSI component used to collect a sparse "imaging" dataset (for determination of the overall spatiospectral distributions). A set of signal processing algorithms are developed to remove the water and lipid signals and jointly reconstruct the metabolite and baseline signals. RESULTS: In vivo 1 H-MRSI results show that the proposed method can effectively remove the remaining water and lipid signals from sparse MRSI data acquired at 20 ms TE. Spatiospectral distributions of metabolite signals at 2 mm in-plane resolution with good SNR were obtained in a 15.5 min scan. CONCLUSIONS: The proposed method can effectively remove nuisance signals and reconstruct high-resolution spatiospectral functions from sparse data to make short-TE SPICE possible. The method should prove useful for high-resolution 1 H-MRSI of the brain. Magn Reson Med 77:467-479, 2017. © 2016 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.

Removal of nuisance signals from limited and sparse 1H MRSI data using a union-of-subspaces model.

PURPOSE: To remove nuisance signals (e.g., water and lipid signals) for (1) H MRSI data collected from the brain with limited and/or sparse (k, t)-space coverage. METHODS: A union-of-subspace model is proposed for removing nuisance signals. The model exploits the partial separability of both the nuisance signals and the metabolite signal, and decomposes an MRSI dataset into several sets of generalized voxels that share the same spectral distributions. This model enables the estimation of the nuisance signals from an MRSI dataset that has limited and/or sparse (k, t)-space coverage. RESULTS: The proposed method has been evaluated using in vivo MRSI data. For conventional chemical shift imaging data with limited k-space coverage, the proposed method produced "lipid-free" spectra without lipid suppression during data acquisition at 130 ms echo time. For sparse (k, t)-space data acquired with conventional pulses for water and lipid suppression, the proposed method was also able to remove the remaining water and lipid signals with negligible residuals. CONCLUSION: Nuisance signals in (1) H MRSI data reside in low-dimensional subspaces. This property can be utilized for estimation and removal of nuisance signals from (1) H MRSI data even when they have limited and/or sparse coverage of (k, t)-space. The proposed method should prove useful especially for accelerated high-resolution (1) H MRSI of the brain.

High-resolution (1) H-MRSI of the brain using SPICE: Data acquisition and image reconstruction.

PURPOSE: To develop data acquisition and image reconstruction methods to enable high-resolution (1) H MR spectroscopic imaging (MRSI) of the brain, using the recently proposed subspace-based spectroscopic imaging framework called SPICE (SPectroscopic Imaging by exploiting spatiospectral CorrElation). THEORY AND METHODS: SPICE is characterized by the use of a subspace model for both data acquisition and image reconstruction. For data acquisition, we propose a novel spatiospectral encoding scheme that provides hybrid data sets for determining the subspace structure and for image reconstruction using the subspace model. More specifically, we use a hybrid chemical shift imaging /echo-planar spectroscopic imaging sequence for two-dimensional (2D) MRSI and a dual-density, dual-speed echo-planar spectroscopic imaging sequence for three-dimensional (3D) MRSI. For image reconstruction, we propose a method that can determine the subspace structure and the high-resolution spatiospectral reconstruction from the hybrid data sets generated by the proposed sequences, incorporating field inhomogeneity correction and edge-preserving regularization. RESULTS: Phantom and in vivo brain experiments were performed to evaluate the performance of the proposed method. For 2D MRSI experiments, SPICE is able to produce high-SNR spatiospectral distributions with an approximately 3 mm nominal in-plane resolution from a 10-min acquisition. For 3D MRSI experiments, SPICE is able to achieve an approximately 3 mm in-plane and 4 mm through-plane resolution in about 25 min. CONCLUSION: Special data acquisition and reconstruction methods have been developed for high-resolution (1) H-MRSI of the brain using SPICE. Using these methods, SPICE is able to produce spatiospectral distributions of (1) H metabolites in the brain with high spatial resolution, while maintaining a good SNR. These capabilities should prove useful for practical applications of SPICE. Magn Reson Med 76:1059-1070, 2016. © 2015 Wiley Periodicals, Inc.

A fast algorithm for denoising magnitude diffusion-weighted images with rank and edge constraints.

PURPOSE: To accelerate denoising of magnitude diffusion-weighted images subject to joint rank and edge constraints. METHODS: We extend a previously proposed majorize-minimize method for statistical estimation that involves noncentral χ distributions to incorporate joint rank and edge constraints. A new algorithm is derived which decomposes the constrained noncentral χ denoising problem into a series of constrained Gaussian denoising problems each of which is then solved using an efficient alternating minimization scheme. RESULTS: The performance of the proposed algorithm has been evaluated using both simulated and experimental data. Results from simulations based on ex vivo data show that the new algorithm achieves about a factor of 10 speed up over the original Quasi-Newton-based algorithm. This improvement in computational efficiency enabled denoising of large datasets containing many diffusion-encoding directions. The denoising performance of the new efficient algorithm is found to be comparable to or even better than that of the original slow algorithm. For an in vivo high-resolution Q-ball acquisition, comparison of fiber tracking results around hippocampus region before and after denoising will also be shown to demonstrate the denoising effects of the new algorithm. CONCLUSION: The optimization problem associated with denoising noncentral χ distributed diffusion-weighted images subject to joint rank and edge constraints can be solved efficiently using a majorize-minimize-based algorithm.

Accelerated MR parameter mapping with low-rank and sparsity constraints.

PURPOSE: To enable accurate magnetic resonance (MR) parameter mapping with accelerated data acquisition, utilizing recent advances in constrained imaging with sparse sampling. THEORY AND METHODS: A new constrained reconstruction method based on low-rank and sparsity constraints is proposed to accelerate MR parameter mapping. More specifically, the proposed method simultaneously imposes low-rank and joint sparse structures on contrast-weighted image sequences within a unified mathematical formulation. With a pre-estimated subspace, this formulation results in a convex optimization problem, which is solved using an efficient numerical algorithm based on the alternating direction method of multipliers. RESULTS: To evaluate the performance of the proposed method, two application examples were considered: (i) T2 mapping of the human brain and (ii) T1 mapping of the rat brain. For each application, the proposed method was evaluated at both moderate and high acceleration levels. Additionally, the proposed method was compared with two state-of-the-art methods that only use a single low-rank or joint sparsity constraint. The results demonstrate that the proposed method can achieve accurate parameter estimation with both moderately and highly undersampled data. Although all methods performed fairly well with moderately undersampled data, the proposed method achieved much better performance (e.g., more accurate parameter values) than the other two methods with highly undersampled data. CONCLUSIONS: Simultaneously imposing low-rank and sparsity constraints can effectively improve the accuracy of fast MR parameter mapping with sparse sampling.

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.

Denoising diffusion-weighted magnitude MR images using rank and edge constraints.

PURPOSE: To improve signal-to-noise ratio for diffusion-weighted magnetic resonance images. METHODS: A new method is proposed for denoising diffusion-weighted magnitude images. The proposed method formulates the denoising problem as an maximum a posteriori} estimation problem based on Rician/noncentral χ likelihood models, incorporating an edge prior and a low-rank model. The resulting optimization problem is solved efficiently using a half-quadratic method with an alternating minimization scheme. RESULTS: The performance of the proposed method has been validated using simulated and experimental data. Diffusion-weighted images and noisy data were simulated based on the diffusion tensor imaging model and Rician/noncentral χ distributions. The simulation study (with known gold standard) shows substantial improvements in single-to-noise ratio and diffusion tensor estimation after denoising. In vivo diffusion imaging data at different b-values were acquired. Based on the experimental data, qualitative improvement in image quality and quantitative improvement in diffusion tensor estimation were demonstrated. Additionally, the proposed method is shown to outperform one of the state-of-the-art nonlocal means-based denoising algorithms, both qualitatively and quantitatively. CONCLUSION: The single-to-noise ratio of diffusion-weighted images can be effectively improved with rank and edge constraints, resulting in an improvement in diffusion parameter estimation accuracy.

Multi-Parametric Molecular Imaging of the Brain Using Optimized Multi-TE Subspace MRSI.

OBJECTIVE: To develop a novel multi-TE MR spectroscopic imaging (MRSI) approach to enable label-free, simultaneous, high-resolution mapping of several molecules and their biophysical parameters in the brain. METHODS: The proposed method uniquely integrated an augmented molecular-component-specific subspace model for multi-TE 1H-MRSI signals, an estimation-theoretic experiment optimization (nonuniform TE selection) for molecule separation and parameter estimation, a physics-driven subspace learning strategy for spatiospectral reconstruction and molecular quantification, and a new accelerated multi-TE MRSI acquisition for generating high-resolution data in clinically relevant times. Numerical studies, phantom and in vivo experiments were conducted to validate the optimized experiment design and demonstrate the imaging capability offered by the proposed method. RESULTS: The proposed TE optimization improved estimation of metabolites, neurotransmitters and their T2's over conventional TE choices, e.g., reducing variances of neurotransmitter concentration by  âˆ¼  40% and metabolite T2 by  âˆ¼  60%. Simultaneous metabolite and neurotransmitter mapping of the brain can be achieved at a nominal resolution of 3.4 × 3.4 × 6.4 mm 3. High-resolution, 3D metabolite T2 mapping was made possible for the first time. The translational potential of the proposed method was demonstrated by mapping biochemical abnormality in a post-traumatic epilepsy (PTE) patient. CONCLUSION: The feasibility for high-resolution mapping of metabolites/neurotransmitters and metabolite T2's within clinically relevant time was demonstrated. We expect our method to offer richer information for revealing and understanding metabolic alterations in neurological diseases. SIGNIFICANCE: A novel multi-TE MRSI approach was presented that enhanced the technological capability of multi-parametric molecular imaging of the brain. The proposed method presents new technology development and application opportunities for providing richer molecular level information to uncover and comprehend metabolic changes relevant in various neurological applications.