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 femorotibial 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.