Johnston, Edward William; (2017) Developing multiparametric and novel magnetic resonance imaging biomarkers for prostate cancer. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Whilst biomarker research is gaining momentum within the cancer sciences, disappointingly few biomarkers are successfully translated into clinical practice, which is partly due to lack of rigorous methodology. In this thesis, I aim to systematically study several quantitative magnetic resonance imaging (MRI) biomarkers (QIBs), at various stages of biomarker development for use as tools in the assessment of local and metastatic prostate cancer according to clinical need. I initially focus on QIBs derived from conventional multiparametric (mp) prostate MRI sequences, namely T2 weighted (T2W), apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE). Firstly, by optimising analytical methods used throughout the thesis, deciding which approach is more reliable between single-slice region-of-interest vs. contouring the whole tumour volume using two different software packages. I then consider whether metric reproducibility can be improved by normalisation to different anatomical structures, and assess whether it is preferable to use statistics derived from imaging histograms rather than the current convention of using mean values. I combine multiple QIBs in a logistic regression model to predict a Gleason 4 component in known prostate cancer, which represents an unmet clinical need, as noninvasive tools to distinguish these more aggressive tumours do not currently exist. I subsequently ‘technically validate’ a novel microstructural diffusion-weighted MRI technique called VERDICT (Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumours) to detect aggressive prostate cancer as part of a prospective cohort study. I assess the image quality, contrast-to-noise ratio, repeatability and performance of quantitative parametric VERDICT maps to discriminate between Gleason grades vs. the current best performing, but still imperfect tool of ADC. In the final two results chapters, motivated by the limited diagnostic accuracy of the prostate cancer staging modalities in current clinical use, I investigate the ability of mp whole-body (WB) MRI to stage aggressive cancer outside the prostate in patients with a high risk of metastases at primary diagnosis, and in biochemical failure following prostatectomy.

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