Qualitative and quantitative whole-body MRI assessment of metastatic disease in patients with radio-recurrent prostate cancer

The thesis provides an overview of my research on the evaluation of whole-body magnetic resonance imaging (WB-MRI) as a single step imaging technique for assessment of metastasis in patients presenting with radio-recurrent prostate cancer (PCa). The work presented is the interim analysis of the LOCATE (localising occult prostate cancer metastasis with advanced imaging techniques) prospective clinical trial (study REC number: 15/LO/0776) Chapter 1 provides a literature review of available clinical and research imaging techniques for evaluation of metastatic disease in the radio-recurrent prostate cancer setting. It introduces the WB-MRI techniques employed in chapters 2-5, provides an overview of pathophysiological basis for WB-MRI signal changes and a review of current WB-MRI literature related to PCa. Chapter 2 presents the first part of my research, addressing the repeatability of lymph node and bone lesion size measurements conducted on various sequences on WB- MRI studies. This critical piece of work underpins the development of the reference standard applied for WB-MRI qualitative and quantitative analysis presented in chapters 3 and 4 respectively. Chapter 3 addresses quantitative imaging biomarkers namely signal fat fraction (sFF), apparent diffusion co-efficient (ADC) and signal enhancement ratio (SER) obtained from WB-MRI and assesses each as a classifier of nodal & bony metastatic disease status. Chapter 4 addresses the diagnostic accuracy of WB- MRI as a qualitative imaging modality evaluated by expert radiologists; compared against an enhanced reference standard (involving clinical and imaging 1-year follow-up). Sensitivity/specificity of WB- MRI is determined on a per-patient basis. Sensitivity/specificity analyses of conventional imaging is also provided. Finally, in this chapter, locked sequential read analysis for the whole-body MRI sequences is presented. Chapter 5 is a health economic analysis of imaging techniques evaluated in chapter 3. It was done in collaboration with the health economics team, in order to carry out a cost comparison analyses between whole body MRI and conventional imaging. Chapter 6 is a summary of main findings and discussions from chapters in this thesis. It also dwells on potential applications and future perspectives on some of the imaging techniques explored in this thesis.