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Title: Development of magnetic resonance spectroscopic imaging methods to assess tumour metabolism
Author: Kreis, Felix Karl
ISNI:       0000 0004 7972 9258
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2019
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Proton detection of hyperpolarized low gamma nuclei. Hyperpolarized molecules labelled with low gamma nuclei such as 15N and 13C have been proposed as magnetic resonance spectroscopic imaging (MRSI) agents for investigating metabolism, perfusion and pH in tumours. However, the sensitivity of direct detection is limited by the low gyromagnetic ratios of these nuclei. Sensitivity can be increased by transferring the hyperpolarization to spin coupled protons provided that there is not significant polarization loss during the transfer. To exploit both the slow relaxation offered by storing the hyperpolarization in the low gamma nucleus and the higher sensitivity of 1H detection, polarization transfer pulse sequences for full and partial transfer of polarization were developed. The possible sensitivity improvement with those MRSI pulse sequences was evaluated in experiments and simulations using hyperpolarized [1-13C]pyruvate, [2-13C]pyruvate, [1-13C]lactate and [15N2]urea. Glycolytic flux measurements in vivo using 2H magnetic resonance spectroscopic imaging. Tumour cells frequently show high rates of aerobic glycolysis, which provides the glycolytic intermediates needed for the increased biosynthetic demands of rapid cell growth and proliferation. These high rates of glycolysis have enabled disease detection and treatment response monitoring using Positron Emission Tomography measurements of 2-([18F]fluoro)-2- deoxy-D-glucose uptake (FDG-PET) and 13C magnetic resonance spectroscopic imaging of hyperpolarized [1-13C]pyruvate metabolism. However, neither of these techniques allows quantitative mapping of metabolic fluxes. A fast 3D deuterium MRSI sequence for dynamic imaging of [6,6'-2H2]glucose metabolism was developed and used to map glycolytic flux in a murine tumour model, demonstrating heterogeneity in glycolytic rate an early decrease following treatment.
Supervisor: Wright, Alan ; Brindle, Kevin Michael Sponsor: European Union's Horizon 2020 Research and Innovation Program
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Magnetic Resonance Imaging ; Cancer Metabolism ; Deuterium Metabolic Imaging ; Hyperpolarization