Glycogen is the primary glucose storage mechanism in in living systems and plays a central role in systemic glucose homeostasis. The study of muscle glycogen concentrations in vivo still largely relies on tissue sampling methods via needle biopsy. However, muscle biopsies are invasive and limit the frequency of measurements and the number of sites that can be assessed. Non-invasive methods for quantifying glycogen in vivo are therefore desirable in order to understand the pathophysiology of common diseases with dysregulated glycogen metabolism such as obesity, insulin resistance, and diabetes, as well as glycogen metabolism in sports physiology. Chemical Exchange Saturation Transfer (CEST) MRI has emerged as a non-invasive contrast enhancement technique that enables detection of molecules, like glycogen, whose concentrations are too low to impact the contrast of standard MR imaging. CEST imaging is performed by selectively saturating hydrogen nuclei of the metabolites that are in chemical exchange with those of water molecules and detecting a reduction in MRI signal in the water pool resulting from continuous chemical exchange. However, CEST signal can easily be compromised by artifacts. Since CEST is based on chemical shift, it is very sensitive to field inhomogeneity which may arise from poor initial shimming, subject respiration, heating of shim iron, mechanical vibrations or subject motion. This is a particular problem for molecules that resonate close to water, such as - OH protons in glycogen, where small variations in chemical shift cause misinterpretation of CEST data. The purpose of this thesis was to optimize the CEST MRI sequence for glycogen detection and implement a real-time simultaneous motion and shim correction and measurement method. First, analytical solution of the Bloch-McConnell equations was used to find optimal continuous wave RF pulse parameters for glycogen detection, and results were validated on a phantom with varying glycogen concentrations and in vivo on human calf muscle. Next, the CEST sequence was modified with double volumetric navigators (DvNavs) to measure pose changes and update field of view and zero- and first-order shim parameters. Finally, the impact of B0 field fluctuations on the scan-rescan reproducibility of CEST was evaluated in vivo in 9 volunteers across 10 different scans. Simulation results showed an optimal RF saturation power of 1.5µT and duration of 1s for glycoCEST. These parameters were validated experimentally in vivo and the ability to detect varying glycogen concentrations was demonstrated in a phantom. Phantom data showed that the DvNav-CEST sequence accurately estimates system frequency and linear shim gradient changes due to motion and corrects resulting image distortions. In addition, DvNav-CEST was shown to yield improved CEST quantification in vivo in the presence of motion and motion-induced field inhomogeneity. B0 field fluctuations were found to lower the reproducibility of CEST measures: the mean coefficient of variation (CoV) for repeated scans was 83.70 ± 70.79 % without shim correction. However, the DvNav-CEST sequence was able to measure and correct B0 variations, reducing the CoV to 2.6 ± 1.37 %. The study confirms the possibility of detecting glycogen using CEST MRI at 3 T and shows the potential of the real-time shim and motion navigated CEST sequence for producing repeatable results in vivo by reducing the effect of B0 field fluctuations.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uct/oai:localhost:11427/30039 |
| Date | 07 May 2019 |
| Creators | Simegn, Gizeaddis Lamesgin |
| Contributors | Robertson, Frances |
| Publisher | Faculty of Health Sciences, Department of Human Biology |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Doctoral Thesis, Doctoral, PhD |
| Format | application/pdf |
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