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Fat Unsaturation Quantification, Including ω-3 Measures, with In-Vivo Magnetic Resonance Spectroscopy

  • Author / Creator
    Fallone, Clara Jodie Michele
  • Fat composition is relevant to disease and can be assessed non-invasively using Magnetic Resonance Spectroscopy (MRS). MRS studies do not usually account for the ω-3 (omega-3) fat content because of its low prevalence in human adipose tissue (≈ 1 %) and because the ω-3 (≈ 1.0 ppm) and non-ω-3 (≈ 0.9 ppm) methyl proton signals overlap at field strengths even as high as 9.4 T (Tesla). However, ω-3 fat content is altered in disease; therefore, there is motivation to quantify it non-invasively. Fat unsaturation can be estimated with MRS in vivo using the olefinic resonance (≈ 5.4 ppm). The thesis objectives are to enable relative ω-3 fat quantification at 9.4 T and 3 T and to enhance aspects of relative fat unsaturation assessment at 3 T. High field strengths including 9.4 T have been used to investigate animal fat composition. When employing standard short TE (echo time) in-vivo MRS pulse sequences, the ω-3 and non-ω-3 methyl resonances overlap at 9.4 T, rendering relative ω-3 fat quantification challenging. The presented research uses product operator formalism to establish a PRESS (Point RESolved Spectroscopy) TE of 109 ms that separately quantifies the two methyl resonances at 9.4 T (the TE minimized signal from the side peaks of the methyl triplets). The optimized method measured relative differences in ω-3 fat content in abdominal tissue of mice fed varying amounts of ω-3 fat. A coefficient of determination (R2) of 0.96 was calculated when assessing MRS results against the content measured with gas chromatography of excised mouse tissue. Relative ω-3 fat quantification was also investigated at the clinical field strength of 3 T. The more weakly-coupled ω-3 methyl triplet includes side peaks that vary sinusoidally with TE. The response of the methyl resonances as a function of PRESS and STEAM (STimulated Echo Acquisition Mode, TM (mixing time) of 20 ms) TE was investigated. It was found that a TE of 160 ms with both sequences yields ω-3 methyl side peaks that are positive in-phase and broaden the collective methyl linewidth, correlating methyl linewidth to relative ω-3 fat content in oil phantoms. The optimized methods yielded R2 values ≥ 0.9 when comparing to the expected oil compositions obtained using 16.5 T high field NMR. In addition, using MRS to quantify relative levels of fat unsaturation at 3 T in vivo was explored. PRESS (TE = 180 ms) and STEAM (TE = 120 ms, TM = 20 ms) yielded olefinic to methyl ratios that differed by 0.2 % and -1.8 %, respectively, from literature-obtained values for tibial bone marrow. The optimal timings depend on combined effects from J-coupling evolution and T2 relaxation. Apparent (including J-coupling effects) T2 relaxation times in several subjects were investigated in tibial bone marrow, subcutaneous and breast adipose tissue, to assess if the determined TE values in tibial bone marrow can be used to compare fat unsaturation measurements in the anatomical regions without applying correction factors for T2 relaxation. Olefinic proton T2 relaxation times were significantly higher in tibial bone marrow than in breast adipose. Fat unsaturation measures in the three tissues were also measured using olefinic to methylene (1.3 ppm) ratios. Fat unsaturation measures in breast have not been explored extensively. This thesis examined the use of an inversion recovery pulse prior to a PRESS sequence (delay = 613 ms, TE = 40 ms) for minimizing water contamination of the olefinic resonance when using a short TE. The technique yielded 5.9 times higher olefinic signal to noise ratio compared to using the previously determined long-TE of 200 ms, which relies on water T2 relaxation to resolve the olefinic resonance. Often, the glycerol CH (≈ 5.2 ppm) resonance contribution to that of the olefinic is ignored. This research estimates glycerol contaminations of ≈ 13 % for PRESS with a TE of 40 ms and ≈ 20 % for STEAM with a TE of 20 ms (TM = 20 ms) at 3 T. Furthermore, the response of the glycerol proton to PRESS and STEAM TE was studied to determine that PRESS with a TE of 200 ms and STEAM with a TE of 90 ms (TM = 20ms) minimizes the glycerol resonance area. The technique efficacies were verified on tibial bone marrow in vivo.

  • Subjects / Keywords
  • Graduation date
    Spring 2021
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/r3-e9vq-h485
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.