4.6 Article

Rapid, automated imaging of mouse articular cartilage by microCT for early detection of osteoarthritis and finite element modelling of joint mechanics

Journal

OSTEOARTHRITIS AND CARTILAGE
Volume 22, Issue 10, Pages 1419-1428

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2014.07.014

Keywords

Mouse articular cartilage; Destabilisation of medial meniscus model; Micro computed tomography; High-throughput automated image analysis; 3-dimensional quantitative imaging

Funding

  1. Wellcome Trust/EPSRC Centre of Excellence in Engineering Solutions for the Management of Osteoarthritis [088844/Z/09/Z]

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Objective: Mouse articular cartilage (AC) is mostly assessed by histopathology and its mechanics is poorly characterised. In this study: (1) we developed non-destructive imaging for quantitative assessment of AC morphology and (2) evaluated the mechanical implications of AC structural changes. Methods: Knee joints obtained from naive mice and from mice with osteoarthritis (OA) induced by destabilization of medial meniscus (DMM) for 4 and 12 weeks, were imaged by phosphotungstic acid (PTA) contrast enhanced micro-computed tomography (PTA-CT) and scored by conventional histopathology. Our software (Matlab) automatically segmented tibial AC, drew two regions centred on each tibial condyle and evaluated the volumes included. A finite element (FE) model of the whole mouse joint was implemented to evaluate AC mechanics. Results: Our method achieved rapid, automated analysis of mouse AC (structural parameters in <10 h from knee dissection) and was able to localise AC loss in the central region of the medial tibial condyle. AC thickness decreased by 15% at 4 weeks and 25% at 12 weeks post DMM surgery, whereas histopathology scores were significantly increased only at 12 weeks. FE simulations estimated that AC thinning at early-stages in the DMM model (4 weeks) increases contact pressures (+39%) and Tresca stresses (+43%) in AC. Conclusion: PTA-CT imaging is a fast and simple method to assess OA in murine models. Once applied more extensively to confirm its robustness, our approach will be useful for rapidly phenotyping genetically modified mice used for OA research and to improve the current understanding of mouse cartilage mechanics. (C) 2014 The Authors. Published by Elsevier Ltd and Osteoarthritis Research Society International.

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