Ex vivo characterization of articular cartilage and bone lesions in a rabbit ACL transection model of osteoarthritis using MRI and micro-CT

Objective: To characterize the rabbit anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA) at various stages of disease using high-resolution 3-D medical imaging systems, which, in turn, will facilitate future longitudinal studies evaluating disease progression and response to therapy in live animals. Methods: Degenerative changes in temorotibial cartilage, volumetric bone mineral density (vBMD), bone volume fraction (BV/TV), and osteophyte volume were characterized ex vivo using 4-T magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) at 4, 8, and 12 weeks post-ACLT. These changes were subsequently correlated to macroscopic joint evaluation. Results: Macroscopic assessment demonstrated progressive cartilage degeneration post-surgery, which was significantly correlated to MRI evaluation (r = 0.82, P < 0.0001). Linear regression analysis indicated that vBMD and BV/TV are linearly related such that as vBMD increases, BV/TV increases (P < 0.0001). Micro-CT revealed bone loss at 4 and 8 weeks post-ACLT, but recovery to control values at 12 weeks post-ACLT. Volumetric BMD was not strongly correlated with macroscopic assessment of articular cartilage degeneration (r = -0.35, P < 0.0001). Quantitative measurement of osteophyte volume demonstrated a statistically significant difference (with respect to control groups) at both 8 and 12 weeks post-ACLT, but not at 4 weeks post-ACLT. Conclusions: The rabbit ACLT model of OA demonstrates progressive cartilage degeneration and intermediate bone changes at 4, 8, and 12 weeks post-surgery. Cartilage and bone lesions were characterized ex vivo using 4-T MRI and micro-CT, and MRI assessment of cartilage degeneration was correlated to macroscopic grading. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.