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

Karl Ludger Radke; Vera Grotheer; Benedikt Kamp; Anja Müller-Lutz; Justus Kertscher; Rosanna Strunk; Petros Martirosian; Birte Valentin; Hans-Jörg Wittsack; Martin Sager; Joachim Windolf; Gerald Antoch; Erik Schiffner; Pascal Jungbluth; Miriam Frenken

doi:10.21037/qims-23-570

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

Quant Imaging Med Surg. 2023 Nov 1;13(11):7467-7483. doi: 10.21037/qims-23-570. Epub 2023 Oct 13.

Authors

Affiliations

¹ Department of Diagnostic and Interventional Radiology, Faculty of Medicine, University Hospital Düsseldorf, Düsseldorf, Germany.
² Department of Orthopedics and Trauma Surgery, Heinrich Heine University Hospital Düsseldorf, Düsseldorf, Germany.
³ Department of Diagnostic and Interventional Radiology, Faculty of Medicine, University Hospital Tübingen, Tübingen, Germany.
⁴ Central Unit for Animal Research and Animal Welfare Affairs, University Hospital, Heinrich Heine University, Düsseldorf, Germany.

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 T₁, T₂, T₂*, 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 T₂ 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, T₁, T₂*, 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, T₂ 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.

Keywords: Cartilage regeneration therapy; adipose-derived stromal cells (ASC); bone marrow-derived mesenchymal stromal cells (BMSC); compositional magnetic resonance imaging (MRI).