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Title: Characterisation of cycling tumour hypoxia with magnetic resonance imaging
Author: Goncalves, M. R.
ISNI:       0000 0004 8503 4102
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Hypoxia is defined by a low oxygen concentration state in biological tissue, resulting from an imbalance between oxygen supply and demand. Greater understanding of hypoxia in tumours is essential, as it is associated with disease progression and resistance to therapy, leading therefore to a poorer prognosis. Tumour hypoxia can be classified into two types: chronic and cycling, and this thesis focuses on characterising cycling hypoxia in colorectal carcinoma tumours in mice. For that, magnetic resonance imaging (MRI) was used, as it provides a non-invasive method to dynamically map blood oxygenation changes due to the different magnetic properties of oxygenated and deoxygenated blood. The first approach to characterise cycling tumour hypoxia consisted of a longitudinal study in which the influence of the tumour size on the occurrence, frequency and amplitude of cycling events was investigated. These observations were complemented with tumour vascular properties, inferred from applied vasoactive gas challenges, with blood sampling assessments, and with histological assessments. The influence of systemic variations in blood oxygenation in cycling tumour hypoxia was demonstrated through simultaneous acquisition of MRI and blood oxygen saturation trends. In particular, the computational implementation of independent component analysis (ICA) allowed the identification of the tumour regions that were simultaneously suffering from systemic and tumour-specific effects, and revealed links to tumour pathophysiology. The effect of a therapy on cycling tumour hypoxia was also assessed under the hypothesis of a "vascular normalisation" effect of the drug. In addition, the effects of the therapy on gas challenge response and on histological distributions were studied. This dynamic MRI technique and the ICA protocol were ultimately adapted to a translational study, where cycling hypoxia was investigated as a biomarker for early detection of prostate tumours. Overall, this thesis revealed that the stage of the tumour development can influence some aspects related to cycling hypoxia, and that its occurrence has a contribution of local and systemic effects. Also, it drew attention to the regional effects a therapy can have in tumours and provided a starting point to assess cycling tumour hypoxia in the clinic.
Supervisor: Walker-Samuel, S. ; Lythgoe, M. ; Pedley, R. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available