Torrealdea, F;
(2016)
Investigation of brain tumour metabolism using naturally occurring chemical exchange saturation transfer agents with magnetic resonance imaging.
Doctoral thesis , UCL (University College London).
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Abstract
This thesis presents a thorough study on the newly developed glucoCEST magnetic resonance imaging (MRI) technique and its application for the assessment of malignant brain tumours. The key asset of glucoCEST is that it allows the detection of small concentration of glucose with standard MRI scanners and has the potential to provide a novel imaging tool to investigate diseases in which glucose metabolism is affected, in particular cancer. The physical principles and the rationale behind the glucoCEST technique are described in detail and factors influencing the measurements (both physiological and hardware related) are analysed using computer simulations and evaluated with in vitro experiments. Special attention is given to the analysis of the first four sugars along the glycolytic pathway i.e. glucose, glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-biphosphate as contributors to the overall observed signal. The results of this analysis give grounds for the argument of the intracellular origin of the glucoCEST signal, which opens the possibility of characterising tumours based on their metabolism with MRI. A preclinical glucoCEST study on mice bearing human xenograft glioblastoma is also presented in which cancers with diverse phenotype are scanned longitudinally throughout the different stages of tumour development. While not conclusive, the results suggest that the glucoCEST technique is able to identify the presence of cancer at an earlier stage than standard MRI methods.
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