ULTRASOUND IMAGING OF SYNOVITIS: RELATIONSHIP TO PATHOBIOLOGY AND RESPONSE TO THERAPY

PhdUltrasound (US) imaging has made significant progress over the past 20 years in relation to its role in inflammatory arthritis, and in particular, Rheumatoid Arthritis. Modern US machines provide crisp, detailed images of superficial anatomical structures which has facilitated the uptake of US imaging as an important assessment tool within the Rheumatology department. Diagnostic and prognostic information can now assist clinicians decisions with the goal of improving patient treatment and subsequent outcome. In addition, 3D US imaging has recently been suggested as an additional imaging modality with potential benefits in the assessment of in?ammatory arthritis. Recent work has focused on providing a reliable, responsive US joint count which can be assimilated into routine care as well as providing a platform for clinical research. Thus, my first aim was to show that a defined limited US data set, including 2D and 3D imaging, shows acceptable reliability. I demonstrate that both imaging modalities are reliable in terms of reading and image acquisition when restricted to a limited US data set. My second aim, was to demonstrate that a limited US data set is responsive. Using both a physiological and pharmacological trigger, I demonstrate that both 2D and 3D imaging are responsive and that combining US endpoints with DAS28 (Disease Activity Score - 28) increased the effect size and identifies treatment effects early. Despite notable advances in musculoskeletal US research, there is still need for better understanding of the pathophysiological correlates of ultrasound imaging. Therefore my final aim was to examine the relationship of Power Doppler Signal (PDS) and gray-scale synovial thickening with histological features of synovitis at a single joint level and with an extended joint US data set. I Firstly show that the harvesting of synovial tissue, using a minimally invasive US-guided biopsy technique, is safe and well tolerated by patients and that the quality of tissue and RNA extracted is good. Using this tissue collection method, I demonstrate a good correlation of US and histological parameters of synovitis (specifically CD68+ sub-lining macrophages) at a single joint level, in both an early and established RA cohort. This relationship is maintained if the US assessment is extended to a discrete US joint data set. Furthermore, within the knee joint I demonstrated that PDS correlates well with synovial tissue expression of inflammatory mediators of neoangiogenesis and histological assessment of synovial vascular area