Multi-Resolution Study of Topographical and Zonal Properties of Osteoarthritis in Articular Cartilage Using Microscopic MRI and Polarized Light Microscopy

Articular cartilage is a thin layer of connective tissue found in diarthrodial joints that overlay the opposing ends of bones and acts as lubricating surfaces to distribute stress and reduce friction with the help of synovial fluid. Hyaline cartilage contains an abundance of water molecules that are essential to the behavior and function of cartilage, the negatively charged proteoglycans that influence the biomechanical properties of the tissue, and the collagen fibers that act as the rebar or reinforcement bars to preserve the structural integrity of the tissue. Cartilage supports the applied load and distributes stress based on its intrinsic material properties, together with its underlying bone. At different surface locations of any single diarthrodial joint, the properties of cartilage are prone to have many morphological and molecular variations topographically, which are mainly due to the patterns of mechanical loading for any specific joint. Any change in the morphological and molecular properties of the cartilage and bone is likely to directly impact the clinical diagnoses of joint diseases such as osteoarthritis (OA). In addition to the topographical variations, cartilage also has a number of depth-dependent variations over its thin thickness, which begins in the non-calcified cartilage with articular laminae and the unequal thickness of sub-tissue zones. Conceptually, the non-calcified cartilage is commonly subdivided based on the orientations of collagen fibers and chondrocytes, into three histological zones. They are the superficial (SZ), transitional (TZ), and radial (RZ) zones. The non-calcified cartilage interfaces with the calcified cartilage and subchondral bone plate (SBP) through the tidemark (TM). This dissertation has seven chapters, which describe a number of multi-resolution projects that use high-resolution imaging to determine the topographical and depth-dependent variations in cartilage, in order to diagnose OA at its earliest stages. The dissertation begins with a brief introduction of background and literature review (Chapters 1-2), continues with the description of the materials and methods (Chapter 3), and summarizes three published peer-reviewed journal articles (Chapters 4-6). The dissertation ends with a summary and comments on future directions (Chapter 7). Among the three research projects described in this dissertation, the first project (Chapter 4) investigates the improvement in the OA detection in cartilage by the interpolation of T2 images, in the situation when the native MRI resolution is insufficient to resolve the depth-dependent T2 characteristics in articular cartilage. The second project (Chapter 5) establishes the topographical and zonal T2 patterns of multi-resolution MRI in medial tibial cartilage in a canine model of OA, initiated by an anterior cruciate ligament (ACL) transection surgery, which was studied after 8-weeks and 12-weeks post-surgery. The third project (Chapter 6) quantifies the interface region between the non-calcified cartilage and the subchondral bone plate, which includes the deep portion of the non-calcified articular cartilage and the zone of calcified cartilage (ZCC) using a dual-modality microscopic imaging study.