- 144 views
- 343 downloads
Spectral Editing for Detection of Oncologically Relevant Metabolites with In-Vivo Magnetic Resonance Spectroscopy at 9.4 T
-
- Author / Creator
- Dobberthien, Brennen Jay
-
Short echo time (TE) magnetic resonance spectroscopy (MRS) techniques with spectral fitting are commonly employed approaches for brain metabolite quantification at 9.4 T. However, there is a significant overlap of peaks in short-TE spectra, even at 9.4 T. To better resolve resonances, spectral editing by optimal-TE Point RESolved Spectroscopy (PRESS), a readily available in-vivo MRS sequence, was used to improve the detection of some oncologically relevant brain metabolites in rat brain at 9.4 T. The metabolites include glycine (Gly), glutamine (Gln), glutamate (Glu), and γ-aminobutyric acid (GABA). 13C4-Glu was also measured with indirect 13C detection, using optimized PRESS timings, during [U-13C6]-glucose infusions. For Gly, a PRESS (TE1, TE2) combination of (60 ms, 100 ms) was found numerically to minimize the myo-inositol signal in the Gly spectral region resulting in a well resolved Gly resonance. LCModel was employed to analyze in-vivo spectra. Average Gly concentration (over three rats) was found to be 1.35 mM with an average Cramér-Rao Lower Bound (CRLB) of 17.5 %, agreeing with values in the literature. To simultaneously quantify Gln, Glu and GABA, a (TE1, TE2) combination of (106 ms, 16 ms) minimized the NAA signal in the Gln spectral region, while retaining macromolecule-free Gln, Glu, and GABA peaks. The efficacy of the timings were verified on phantom solutions and on rat brain in vivo. Average Gln, Glu, and GABA concentrations were found over five rats to be 3.39 mM, 11.43 mM, and 2.20 mM, with average CRLBs of 15.4 %, 5.0 %, and 17.8 %, respectively, within error of literature values. In addition, we evaluated short-TE spectra obtained from phantoms of known Gln, Glu and GABA concentrations, and demonstrated that errors can result due to overlapping signals. Specifically, concentrations were estimated from phantoms of known varying glutamine (Gln) concentrations, with other metabolites present in fixed known physiological concentration ratios, and it was found that errors in estimation were >39 %. The errors were reduced with the long-TE PRESS sequence. For the dynamic 13C indirect measures, a (TE1, TE2) combination of (20 ms, 106 ms) was found to be suitable for minimizing NAA signal in the ≈ 2.51 ppm 13C4-Glu proton spectral region, while retaining the ≈ 2.51 ppm 13C4-Glu proton satellite peak. The efficacy of the technique was verified on phantom solutions and on rat brain in vivo during an infusion of [U-13C6]-glucose. LCModel was again employed for analysis of the in-vivo spectra to quantify the ≈ 2.51 ppm proton 13C4-Glu signal to obtain Glu C4 fractional enrichment (FE) time courses during the infusions. Glutamate FE was found to be, on average, 0.59, for two rats at the end of infusion. The indirect 13C detection with optimized PRESS provides an alternative to subtraction techniques and techniques that require additional 13C capability.
In addition, rat kidney MRS was also investigated with short-TE PRESS at 9.4 T to non-invasively obtain in-vivo spectra of the kidney and quantify levels of Glx (Glu + Gln), myo-inositol, and taurine, relative to choline + betaine. The relative concentrations, found over four rats, were found to be, on average, 2.16, 1.40, and 2.17, for Glx, myo-inositol, and taurine, respectively. Previous MRS of rat kidney in vivo relied on surgical exposure. -
- Graduation date
- Fall 2019
-
- Type of Item
- Thesis
-
- Degree
- Doctor of Philosophy
-
- License
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.