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Murine articular cartilage morphology and compositional quantification with high resolution cationic
Maleeha Mashiatulla1,2, Meghan M Moran1, Deva Chan3
1Department of Cell & Molecular Medicine, Rush University Medical Center, 600 South Paulina, Suite 507, Chicago, Illinois, 60612.
Summary
A new contrast agent, CA4+, enhances microcomputed tomography (μCT) imaging for assessing mouse articular cartilage degeneration and proteoglycan content. This high-resolution imaging method offers improved sensitivity for detecting cartilage composition changes in preclinical research.
Area of Science:
- Orthopaedic Research
- Medical Imaging
- Biomedical Engineering
Background:
- Articular cartilage degeneration is a hallmark of osteoarthritis, necessitating advanced imaging techniques for preclinical assessment.
- Microcomputed tomography (μCT) is valuable for 3D mapping of cartilage structure and composition, but challenges exist with small animal models.
- Previous studies utilized Hexabrix contrast agent with μCT for mouse articular cartilage, but 6 μm voxel size was limited.
Purpose of the Study:
- To evaluate the efficacy of a novel cationic contrast agent, CA4+, for high-resolution (3 μm voxel) μCT imaging of mouse articular cartilage.
- To compare the sensitivity of CA4+ and anionic Hexabrix in quantifying cartilage morphology and composition, specifically proteoglycan (PG) content.
- To assess the utility of CA4+ in detecting age-related cartilage degeneration in mice.
Main Methods:
- High-resolution (3 μm voxel) contrast-enhanced μCT imaging was performed on mouse articular cartilage using CA4+.
- Histology was used to validate μCT-derived measurements of cartilage thickness.
- Comparison of CA4+ and Hexabrix was conducted for sensitivity in detecting cartilage degeneration and PG content differences.
Main Results:
- CA4+ demonstrated a strong correlation between μCT and histology for non-calcified articular cartilage thickness (R² = 0.72).
- Significant cartilage degeneration (decreased volume, thickness, PG content) was observed in 34-week-old mice compared to younger groups.
- CA4+ provided higher sensitivity for assessing PG content compared to Hexabrix, with excellent measurement precision (CVs < 7.4%).
Conclusions:
- CA4+ is a valuable tool for high-resolution μCT assessment of mouse articular cartilage morphology and composition.
- The improved sensitivity of CA4+ for PG content is beneficial for preclinical studies of cartilage degeneration and regeneration.
- This advanced imaging approach aids in understanding osteoarthritis progression and evaluating therapeutic interventions in mouse models.

