Multimodal Imaging Assessment of Post-traumatic Osteoarthritis Progression

Abstract

Osteoarthritis (OA) is a complex joint disease that can cause progressive damage that leads to chronic pain, stiffness, and functional impairment, which can severely affect the quality of a person’s life. The primary reason for the development of OA is the degeneration of articular cartilage which acts as a smooth load-bearing surface in diarthrodial joints. Post-traumatic osteoarthritis (PTOA) is a specific form of OA that occurs after joint injury. The architecture and operation of articular cartilage are special and depend on its dense extracellular matrix (ECM); PTOA results in significant ECM changes which lead to cartilage degradation and structural failure. Due to the avascular nature of cartilage, its self-repair capacity remains limited, thus its degradation will benefit from early detection and intervention. The study of PTOA progression is critically dependent on advanced imaging methods. For example, magnetic resonance imaging (MRI) is a sensitive tool for detailed assessment of cartilage health and can assist in the early detection of disease; polarized light microscopy (PLM) is effective for the detailed assessment of collagen fiber orientation and structural integrity of the cartilage; and computed tomography (CT) imaging can measure subchondral bone remodeling. These imaging techniques probe different aspects of cartilage degradation; when used in combination, they can help to better understand OA progression which can lead to early diagnosis and more effective intervention.This dissertation consists of eight chapters that investigate PTOA progression through high-resolution imaging. The first three chapters introduce this dissertation research by explaining knee joint OA while reviewing literature about its pathophysiology and advanced imaging capabilities for detecting early disease changes. The experimental design and imaging approaches for studying topographical and depth-dependent cartilage changes are explained in Chapter Four. The dissertation presents three peer-reviewed journal articles in chapters five through seven, offering new insights into cartilage degeneration in OA. Chapter Five explores the progression of PTOA and biomechanical factors involved in PTOA progression using μMRI imaging of the whole knee joint. Chapter Six investigates zonal structural changes in articular cartilage following a mechanical injury utilizing high-resolution μMRI imaging of cartilage blocks. Chapter seven examines the effects of an impact injury on articular cartilage and subchondral bone through PLM and μCT imaging. The final chapter summarizes results of this dissertation study and discusses potential future research directions.