Advanced magnetic resonance spectroscopy techniques and applications

Abstract

Magnetic resonance (MR) is a well-known non-invasive technique that provides spectra (by MR spectroscopy, MRS) and images (by magnetic resonance imaging, MRI) of the examined tissue with detailed metabolic, structural, and functional information. This doctoral work is focused on advanced methodologies and applications of MRS for probing cellular and molecular changes in vivo. A single-voxel diffusion-weighted (DW) MRS method was first developed for monitoring the size changes of intramyocellular lipid droplets in vivo. This DWMRS technique was then utilized for exploring the vascular origins of the functional blood-oxygen-level-dependent (BOLD) signal. Magnetic resonance spectroscopic imaging (MRSI) enables simultaneous MRS acquisition in multiple voxels. However, MRSI is conventionally time-consuming. Therefore, a compressed sensing (CS) method was proposed in this thesis to accelerate the acquisition speed of the in vivo MRSI. It holds the potential for promoting the realization of multiple-voxel DW-MRS experiments, though the latter is still constrained by hardware in the present. The single-voxel DW-MRS method for probing lipid diffusion was first developed and evaluated in oil and muscle phantoms. The experimental sequence was demonstrated to be sensitive to diffusion restriction and free of significant artifacts. Experiments were then performed in rat hindlimb muscles in vivo. The restricted lipid diffusion behavior was characterized by apparent diffusion coefficient (ADC) changes and utilized for quantifying the sizes of intramyocellular lipid (IMCL) droplets in normal, fasting, diabetic and obese rats. The sizes of IMCL droplets reflect their vital roles in muscle energy metabolism. The IMCL droplet size estimated by ADC here was closely correlated with that measured by transmission electron microscopy. IMCL ADC was sensitive to metabolic alterations, decreasing in the fasting and diabetic groups while increasing in the obese group. These results clearly demonstrate DW MRS as a new means to examine the dynamics of IMCL metabolism in vivo. The DW-MRS technique was then utilized to characterize water ADC during neuronal activation to explore the vascular origins of the BOLD signal in rat brains. MRS experiments with acoustic stimulation were performed with a dynamic point-resolved spectroscopy (PRESS) acquisition on conditions with or without the diffusion gradient for blood suppression in the same voxel and same experimental session, which enabled the simultaneous T2/T2*/diffusion measurements. The T2*% changes with and without diffusion gradient showed no significant difference, while the spin echo (SE)-BOLD% (T2%) change significantly decreased after applying the diffusion gradient, suggesting an intravascular component in the SE-BOLD signal. This intravascular component was not venous blood, as the T2* of this component was comparable with the T2* of the brain tissue. These results provide new insights into the vascular origins of BOLD signals. A CS approach was developed to accelerate in vivo magnetic resonance spectroscopic imaging (MRSI) which enables multi-voxel MRS measurements. The CS undersampling was performed by acquiring a pseudo-random and density-varying subset of phase encodings. The proposed CS approach preserved the spectral and spatial resolution, while substantially reduced the number of phase encodings with accelerations up to seven fold for phantom and up to six fold for in vivo rat brains.