Objectives: Knee injury often triggers post-traumatic osteoarthritis (PTOA) that affects articular cartilage (AC), subchondral bone and other joint tissues. PTOA is often detected late past the ‘treatment window’ due to the limitations in diagnostic imaging methods, which also results in an incomplete understanding of early PTOA. The objectives of the present study were: (1) to enhance the analytical capabilities of quantitative MRI for early detection of PTOA; and (2) to identify the tissue alteration pathway leading from the initial knee injury towards symptomatic PTOA.

Methods: The rat knee meniscectomy (MSX) model, where PTOA is initiated by removing the meniscus, was used. The state of the joints was assessed at weekly time points via micro-MRI over the course of 8 weeks and by histology at weeks 0, 4 and 8. Cartilage thickness, its T₂ values and the volume fraction of cortical bone (VFCB) within the tibial epiphysis were measured from T₂-weighted images and T₂ maps.

Results: The knee joints subjected to MSX exhibited a strong correlation (Spearman’s rank order correlation, p < 0.05) between cartilage thickness (corrected for the partial-effect) and its T₂; both quantities gradually increased from week 1 to week 7 and decreased at week 8. The increase in T₂ at week 4 corresponded to the reduced proteoglycan content. Decreased cartilage thickness and T₂ at week 8 corresponded to cartilage erosion. Changes in the VFCB exhibited an initial minor decrease (weeks 1-2), which was followed by a significant increase over weeks 3-8.

Conclusion: An MRI-based protocol suitable for early detection of PTOA by whole-knee assessment was established. The key finding resulting from the longitudinal observation of the knee joints was the following pathogenesis cascade found to precede advanced PTOA: meniscal injury → AC swelling → subchondral bone remodelling → proteoglycan depletion → free water influx → cartilage erosion.