Concurrent Assessment of Cartilage Morphology and Bone Microarchitecture in the Human Knee Using Contrast-Enhanced HR-pQCT Imaging

Osteoarthritis (OA) is a prevalent articular disease characterized by whole joint degradation, including articular cartilage and bone. Presently, no single imaging modality is well suited to concurrently capture these changes. Recent ex vivo animal studies have demonstrated the efficacy of utilizing contrast agents in conjunction with micro-CT as a means of evaluating cartilage and bone alterations concurrently, though no work as of yet has been performed in large animal models or humans. This study sought to develop and validate a novel joint imaging technique, contrast enhanced high resolution peripheral quantitative computed tomography (CEHR-pQCT), to concurrently assess bone microarchitecture and cartilage morphology in the whole human knee. Fresh frozen cadaveric knees were harvested (n = 10) and scanned using magnetic resonance imaging (MRI), HR-pQCT without contrast, and HR- pQCT following intra-articular injection of nonionic contrast media. Cartilage morphology and bone microarchitecture were evaluated in weight bearing regions of interest in both the tibia and femur. Joints were then disarticulated, and the articular cartilage thickness measured by needle probe. Measures of cartilage morphology, thickness and volume, were found to be significantly less when measured by CEHR- pQCT compared to magnetic resonance imaging in all regions. Compared to needle probing, cartilage thickness measured by CEHR-pQCT was less in the lateral tibia and greater in the medial tibia. Bone microarchitecture was found to be significantly different when measured with CEHR-pQCT compared to HR-pQCT, where cortical bone mineral density (BMD) was depressed, and trabecular bone mineral density was greater. This study demonstrates that CEHR-pQCT can be used to concurrently measure cartilage morphology and bone microarchitecture; however, systematic errors impact both measures. This is the first study using contrast media in combination with HR-pQCT in whole joints. Additionally, all imaging parameters, as well as the contrast media, were selected to be directly transferable to in vivo studies, laying the foundation to perform in vivo scanning of knee cartilage and bone.