This thesis examines the potential utility of magnetic resonance (MR) quantitative imaging biomarkers (QIBs) of knee osteoarthritis (OA) for rapid assessment of treatment efficacy in experimental medicine studies.

The development of treatments able to modify disease in OA is hampered by an inability to evaluate treatment response over a timeframe relevant to clinical trials. There are particular challenges in the experimental medicine setting due to the small numbers of participants and short follow-up duration relative to the expected time course of OA development and progression. Multiple MR QIBs of OA exist which may help address the problem of early evaluation of treatment response. However, their use in early phase studies has remained limited. Possible reasons for this include incomplete characterisation of the performance of QIBs in this setting and lack of head-to-head comparison of candidate QIBs to determine which would be optimal.

This thesis aims to address these shortcomings and provide new information on the likely utility of MR QIBs in the setting of experimental medicine studies, as well as their potential for improving our general understanding of OA pathophysiology.

I start by examining the reliability and ability to discriminate between OA and healthy knees of cartilage compositional MR imaging in a systematic review and meta-analysis. I then describe the development and validation of a novel semi-automatic surface-based method for analysing articular cartilage composition and morphology at the knee which may offer improved responsiveness and spatial localisation of change. Moving to QIBs of subchondral bone, I evaluate the association between measures of subchondral bone architecture derived from MR texture analysis and OA progression in the Osteoarthritis Initiative. The remainder of the thesis describes a prospective observational study where the utility of MR QIBs of synovium, subchondral bone and cartilage in experimental medicine studies is assessed.

In summary, this thesis will inform decisions regarding the use of MR-based QIBs in future longitudinal and interventional studies. Their inclusion in experimental medicine studies may allow early assessment of treatment efficacy at a structural level and improve efficiency of treatment development pipelines.