Johnson, SP; (2015) Multimodality Imaging of Tumour Pathophysiology and Response to Pharmacological Intervention. Doctoral thesis , UCL (University College London).

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Abstract

This thesis describes the need for imaging the tumour pathophysiological microenvironment in order to understand response to treatment. Specifically looking at tumour vascularisation in in vivo murine xenograft models of disease, response to treatment with vascular disruption is assessed via photoacoustic tomography (PAT) and magnetic resonance imaging (MRI). Photoacoustic imaging is a novel imaging modality based on the detection of ultrasound waves created by the absorption of nano-second pulsed laser energy within tissue chromophores. It has the spectral specificity of optical techniques whilst also achieving the high resolution of ultrasound. Haemoglobin is the main chromophore found in biological tissue and this modality is therefore ideally suited to imaging tumour vascularisation. Using a Fabry-Perot interferometer this thesis demonstrates for the first time the feasibility of using PAT for re-clinical research and the characterisation of typical tumour vascular features in a non-invasive non-ionising manner. Response to different concentrations of a vascular disrupting drug is then demonstrated, with novel insights in to how tumours recover from vascular damage observed. MRI of response to vascular disruption is also presented. As MRI is widely used in the clinic it can serve as a translational tool of novel imaging biomarkers, and serves to further understand the differences in response of pathologically vascularised of tumours. This thesis looks at markers associated with disruption of haemodynamics, using apparent diffusion (ADC) to elucidate onset of necrosis, increase in haemoglobin concentration (R2*) as indication of impaired flow, and arterial spin labelling (ASL) as a marker of tumour blood perfusion. This is shown in both subcutaneous and clinically relevant liver metastasis models. Taken as whole, the results from this thesis indicate that whilst understanding the response of the tumour vasculature to pharmacological intervention is complex, novel imaging techniques can provide invaluable translational information on the pathophysiology of tumours.

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