Comparison of compositional MRI techniques to quantify the regenerative potential of articular cartilage: a preclinical minipig model after osteochondral defect treatments with autologous mesenchymal stromal cells and unseeded scaffolds

Abstract

Background The field of orthopedics seeks effective, safer methods for evaluating articular cartilage regeneration. Despite various treatment innovations, non-invasive, contrast-free full quantitative assessments of hyaline articular cartilage’s regenerative potential using compositional magnetic resonance (MR) sequences remain challenging. In this context, our aim was to investigate the effectiveness of different MR sequences for quantitative assessment of cartilage and to compare them with the current gold standard delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) measurements. Methods We employed ex vivo imaging in a preclinical minipig model to assess knee cartilage regeneration. Standardized osteochondral defects were drilled in the proximal femur of the specimens (n=14), which were divided into four groups. Porcine collagen scaffolds seeded with autologous adipose-derived stromal cells (ASC), autologous bone marrow stromal cells (BMSC), and unseeded scaffolds (US) were implanted in femoral defects. Furthermore, there was a defect group which received no treatment. After 6 months, the specimens were examined using different compositional MR methods, including the gold standard dGEMRIC as well as T 1 , T 2 , T 2 *, and T 1ρ techniques. The statistical evaluation involved comparing the defect region with the uninjured tibia and femur cartilage layers and all measurements were performed on a clinical 3T MR Scanner. Results In the untreated defect group, we observed significant differences in the defect region, with dGEMRIC values significantly lower (404.86±64.2 ms, P=0.018) and T 2 times significantly higher (44.24±2.75 ms, P<0.001). Contrastingly, in all three treatment groups (ASC, BMSC, US), there were no significant differences among the three regions in the dGEMRIC sequence, suggesting successful cartilage regeneration. However, T 1 , T 2 *, and T 1ρ sequences failed to detect such differences, highlighting their lower sensitivity for cartilage regeneration. Conclusions As expected, dGEMRIC is well suited for monitoring cartilage regeneration. Interestingly, T 2 imaging also proved to be a reliable cartilage imaging technique and thus offers a contrast agent-free alternative to the former gold standard for subsequent in vivo studies investigating the cartilage regeneration potential of different treatment modalities.