Noise-reduction techniques for 1H-FID-MRSI at 14.1T: Monte-Carlo validation & in vivo application

Proton magnetic resonance spectroscopic imaging (1H-MRSI) is a powerful tool that enables the multidimensional non-invasive mapping of the neurochemical profile at high-resolution over the entire brain. The constant demand for higher spatial resolution in 1H-MRSI led to increased interest in post-processing-based denoising methods aimed at reducing noise variance. The aim of the present study was to implement two noise-reduction techniques, the Marchenko-Pastur principal component analysis (MP-PCA) based denoising and the low-rank total generalized variation (LR-TGV) reconstruction, and to test their potential and impact on preclinical 14.1T fast in vivo 1H-FID-MRSI datasets. Since there is no known ground truth for in vivo metabolite maps, additional evaluations of the performance of both noise-reduction strategies were conducted using Monte-Carlo simulations. Results showed that both denoising techniques increased the apparent signal-to-noise ratio SNR while preserving noise properties in each spectrum for both in vivo and Monte-Carlo datasets. Relative metabolite concentrations were not significantly altered by either methods and brain regional differences were preserved in both synthetic and in vivo datasets. Increased precision of metabolite estimates was observed for the two methods, with inconsistencies noted on lower concentrated metabolites. Our study provided a framework on how to evaluate the performance of MP-PCA and LR-TGV methods for preclinical 1H-FID MRSI data at 14.1T. While gains in apparent SNR and precision were observed, concentration estimations ought to be treated with care especially for low-concentrated metabolites.Comment: Brayan Alves and Dunja Simicic are joint first authors. Currently in revision for NMR in Biomedicin

A subspace method for reconstruction of time-series fMRI images from sparse data

Functional magnetic resonance imaging (fMRI) is a powerful imaging modality commonly used to study brain functions. It utilizes the difference in the oxygen content of brain tissues over time to produce functional connectivity maps, or visualizations of brain regions activated when a subject performs a task. As such, it provides invaluable insight into the inner workings of the brain and how disease changes its functionality. Unfortunately, fMRI sees limited use outside of research settings due to its long data acquisition time and the large amount of data required to generate useful results. Methods which reduce the amount of required data while maintaining acceptable results become necessary to allow the availability of fMRI in clinical settings. This thesis presents a novel method to reconstruct high-resolution spatiotemporal fMRI image sequences given highly undersampled data. It introduces a model which combines low-rank subspaces with prior information to produce results which outperform other state-of-the-art reconstruction techniques such as SENSE. A comparison of image quality and fMRI analyses over a wide variety of datasets shows the superiority of the proposed method

Dynamic Imaging of Glucose and Lactate Metabolism by C-13-MRS without Hyperpolarization

Abstract Metabolic reprogramming is one of the defining features of cancer and abnormal metabolism is associated with many other pathologies. Molecular imaging techniques capable of detecting such changes have become essential for cancer diagnosis, treatment planning, and surveillance. In particular, 18F-FDG (fluorodeoxyglucose) PET has emerged as an essential imaging modality for cancer because of its unique ability to detect a disturbed molecular pathway through measurements of glucose uptake. However, FDG-PET has limitations that restrict its usefulness in certain situations and the information gained is limited to glucose uptake only.13C magnetic resonance spectroscopy theoretically has certain advantages over FDG-PET, but its inherent low sensitivity has restricted its use mostly to single voxel measurements unless dissolution dynamic nuclear polarization (dDNP) is used to increase the signal, which brings additional complications for clinical use. We show here a new method of imaging glucose metabolism in vivo by MRI chemical shift imaging (CSI) experiments that relies on a simple, but robust and efficient, post-processing procedure by the higher dimensional analog of singular value decomposition, tensor decomposition. Using this procedure, we achieve an order of magnitude increase in signal to noise in both dDNP and non-hyperpolarized non-localized experiments without sacrificing accuracy. In CSI experiments an approximately 30-fold increase was observed, enough that the glucose to lactate conversion indicative of the Warburg effect can be imaged without hyper-polarization with a time resolution of 12s and an overall spatial resolution that compares favorably to 18F-FDG PET

Statistical characterization of residual noise in the low-rank approximation filter framework, general theory and application to hyperpolarized tracer spectroscopy

The use of low-rank approximation filters in the field of NMR is increasing due to their flexibility and effectiveness. Despite their ability to reduce the Mean Square Error between the processed signal and the true signal is well known, the statistical distribution of the residual noise is still undescribed. In this article, we show that low-rank approximation filters are equivalent to linear filters, and we calculate the mean and the covariance matrix of the processed data. We also show how to use this knowledge to build a maximum likelihood estimator, and we test the estimator's performance with a Montecarlo simulation of a 13C pyruvate metabolic tracer. While the article focuses on NMR spectroscopy experiment with hyperpolarized tracer, we also show that the results can be applied to tensorial data (e.g. using HOSVD) or 1D data (e.g. Cadzow filter).Comment: 26 pages, 7 figure

A subspace approach to high-resolution magnetic resonance spectroscopic imaging

With its unique capability to obtain spatially resolved biochemical profiles from the human body noninvasively, magnetic resonance spectroscopic imaging (MRSI) has been recognized as a powerful tool for in vivo metabolic studies. However, research and clinical applications of in vivo MRSI have been progressing more slowly than expected. The main reasons for this situation are the problems of long data acquisition time, poor spatial resolution and low signal-to-noise ratio (SNR) for this imaging modality. In the last four decades, significant efforts have been made to improve MRSI, resulting in a large number of fast pulse sequences and advanced image reconstruction methods. However, the existing techniques have yet to offer the levels of improvement in imaging time, spatial resolution and SNR necessary to significantly impact in vivo applications of MRSI. This thesis work develops a new subspace imaging approach to address these technical challenges to enable fast, high-resolution MRSI with high SNR. The proposed approach, coined SPICE (Spectroscopic Imaging by Exploiting Spatiospectral Correlation), is characterized by using a subspace model for integrative data acquisition, processing and image reconstruction. More specifically, SPICE represents the spectroscopic signals in MRSI using the partial separability (PS) model. The PS model implies that the high-dimensional spectroscopic signals reside in a low-dimensional subspace, which enables the design of special sparse sampling strategies for accelerated spatiospectral encoding and special image reconstruction strategies for determining the subspace and reconstructing the underlying spatiospectral function of interest from the sparse data. Using the SPICE framework, new data acquisition and image reconstruction methods are developed to enable high-resolution 1H-MRSI of the brain. We have evaluated SPICE using theoretical analysis, numerical simulations, phantom and in vivo experimental studies. Results obtained from these experiments demonstrate the unprecedented capability of SPICE in achieving accelerated MRSI with simultaneously very high resolution and SNR. We expect SPICE to provide a powerful tool for in vivo metabolic studies with many exciting applications. Furthermore, the SPICE framework also presents new opportunities for future developments in subspace-driven signal generation, signal encoding, data processing and image reconstruction methods to advance the research and clinical applications of high-resolution in vivo MRSI

Simultaneous fMRI and metabolic imaging of the brain using spice

In this thesis, we propose a novel approach to achieve simultaneous acquisition of high resolution MRSI and fMRI in a fast scan. The proposed acquisition scheme adds an EVI-based sequence module into a subspace-based imaging technique called SPICE (SPectroscopic Imaging by exploiting spatiospectral CorrElation). With the features of ultrashort TE/short TR, no water and lipid suppression, extended k-space coverage by prolonged EPSI readout and highly sparse sampling, the data acquisition captures both the spatiospectral information of brain metabolites and the dynamic information of brain functional activation. The data processing and reconstruction are based on the subspace modeling and involve pre-trained basis functions and spatial prior information. Moreover, the complementary information between fMRI and MRSI is utilized to further improve the quality of both fMRI and metabolic imaging. The in vivo experimental results demonstrate that the proposed method can achieve whole brain covered, simultaneous fMRI at spatial resolution of 3.0 × 3.0 × 1.8 mm, temporal resolution 3 seconds, along with metabolic imaging at nominal spatial resolution of 1.9 × 2.3 × 3.0 mm in a single 6-minute scan. The high-quality metabolic maps, spatially resolved spectra, resting-state functional networks and task time courses corresponding to the task events can all be obtained in the in vivo scans. This technique, when fully developed, will become a powerful tool to study the brain metabolism and function activities

Subspace estimation for subspace-based magnetic resonance spectroscopic imaging

Magnetic resonance spectroscopic imaging (MRSI) is a powerful technique that offers us the ability to non-invasively image chemical distributions within the human body. However, due to its inherently poor trade-off between imaging speed, resolution, and signal-to-noise ratio (SNR), MRSI has remained impractical for many research and clinical applications. A large body of work has been done to improve this trade-off. Recently new subspace-based imaging methods have also been proposed as a means of dramatically accelerating MRSI. By taking advantage of the properties of a partially separable (PS) signal model, subspace-based methods offer increased flexibility in acquisition as well as image reconstruction, and thereby allow high-resolution, high-SNR MRSI images to be obtained in a fraction of the time required by standard techniques. An important ingredient common to all subspace-based imaging methods is the estimation of the subspace structure of the high-dimensional image function. However, accurate subspace estimation in the presence of noise and inhomogeneity in the main magnetic field is challenging. To this end we propose a novel method for subspace estimation which utilizes a regularized-reconstruction approach to correct for the effects of field inhomogeneity and noise. Carefully designed numerical simulations and experimental studies have been performed to evaluate the performance of the proposed method in a variety of experimental conditions. Results from these data show that the proposed method is able to obtain an accurate subspace estimation, either in terms of a projection error metric or by inspecting the residual after projecting the fully sampled data onto the estimated subspaces. Additionally, in vivo MRSI data was acquired to illustrate that the subspace estimated by the proposed method leads to high-quality spatiospectral reconstructions

Superresolution Reconstruction for Magnetic Resonance Spectroscopic Imaging Exploiting Low-Rank Spatio-Spectral Structure

Magnetic resonance spectroscopic imaging (MRSI) is a rapidly developing medical imaging modality, capable of conferring both spatial and spectral information content, and has become a powerful clinical tool. The ability to non-invasively observe spatial maps of metabolite concentrations, for instance, in the human brain, can offer functional, as well as pathological insights, perhaps even before structural aberrations or behavioral symptoms are evinced. Despite its lofty clinical prospects, MRSI has traditionally remained encumbered by a number of practical limitations. Of primary concern are the vastly reduced concentrations of tissue metabolites when compared to that of water, which forms the basis for conventional MR imaging. Moreover, the protracted exam durations required by MRSI routinely approach the limits for patient compliance. Taken in conjunction, the above considerations effectively circumscribe the data collection process, ultimately translating to coarse image resolutions that are of diminished clinical utility. Such shortcomings are compounded by spectral contamination artifacts due to the system pointspread function, which arise as a natural consequence when reconstructing non-band-limited data by the inverse Fourier transform. These artifacts are especially pronounced near regions characterized by substantial discrepancies in signal intensity, for example, the interface between normal brain and adipose tissue, whereby the metabolite signals are inundated by the dominant lipid resonances. In recent years, concerted efforts have been made to develop alternative, non-Fourier MRSI reconstruction strategies that aim to surmount the aforementioned limitations. In this dissertation, we build upon the burgeoning medley of innovative and promising techniques, proffering a novel superresolution reconstruction framework predicated on the recent interest in low-rank signal modeling, along with state-of-the-art regularization methods. The proposed framework is founded upon a number of key tenets. Firstly, we proclaim that the underlying spatio-spectral distribution of the investigated object admits a bilinear representation, whereby spatial and spectral signal components can be effectively segregated. We further maintain that the dimensionality of the subspace spanned by the components is, in principle, bounded by a modest number of observable metabolites. Secondly, we assume that local susceptibility effects represent the primary sources of signal corruption that tend to disallow such representations. Finally, we assert that the spatial components belong to a class of real-valued, non-negative, and piecewise linear functions, compelled in part through the use of a total variation regularization penalty. After demonstrating superior spatial and spectral localization properties in both numerical and physical phantom data when compared against standard Fourier methods, we proceed to evaluate reconstruction performance in typical in vivo settings, whereby the method is extended in order to promote the recovery of signal variations throughout the MRSI slice thickness. Aside from the various technical obstacles, one of the cardinal prospective challenges for high-resolution MRSI reconstruction is the shortfall of reliable ground truth data prudent for validation, thereby prompting reservations surrounding the resulting experimental outcomes. [...