Analysis of Subchondral Bone and Microvessels Using a Novel Vascular Perfusion Contrast Agent and Optimized Dual-Energy Computed Tomography

Osteoarthritis (OA), is a chronic debilitating disease that affects millions of individuals and is characterized by the degeneration of joint subchondral bone and cartilage. These tissue degenerations manifest as joint pain, limited range of joint motion, and overall diminished quality of life. Currently, the exact mechanism(s) and cause(s) by which OA initiates and progresses remain unknown. The multi-factorial complex nature of OA (i.e. age, diabetes, obesity, and prior injuries have all been shown to play a role in OA) contributes to the current lack of a cure or effective long-term treatment for OA. One re-emerging and interesting hypothesis revolves around the delicate homeostatic microvascular environment around the cartilage – an avascular tissue. The absence of blood vessels within cartilage stresses the importance of nutrient and oxygen delivery from the neighbouring synovium and subchondral bone. Currently, the effects of changes in the subchondral bone microvessel density on cartilage health remain unknown due to the difficulties in simultaneously studying dense bone and the associated small microvessels. Computed tomography (CT) is widely used in the diagnosis of OA, as the use of x-rays provide detailed images of the bone degeneration associated with OA. However, the study of microvessels using CT has been exceptionally difficult due to their small (\u3c 10 µm) size, lack of contrast from neighbouring soft tissues, and proximity to dense bone. The purpose of this thesis was to develop a novel dual-energy micro-computed tomography (DECT) compatible vascular perfusion contrast agent and the associated instrumentation to optimize DECT on pre-clinical, cone-beam micro-CT scanners. The combination of these two techniques would facilitate the simultaneous visualization and quantification of subchondral bone and microvessels within the bone underlining the cartilage (i.e. distal femoral epiphysis and proximal tibial epiphysis) of rats that have undergone an OA-induced surgery. Results gained from this study will further provide information into the role that microvessels may play in OA