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Three-dimensional quantitative morphometric analysis (QMA) for in situ joint and tissue assessment of osteoarthritis in a preclinical rabbit disease model


Stok, KS and Besler, BA and Steiner, TH and Villarreal Escudero, AV and Zulliger, MA and Wilke, M and Atal, K and Quintin, A and Koller, B and Muller, R and Nesic, D, Three-dimensional quantitative morphometric analysis (QMA) for in situ joint and tissue assessment of osteoarthritis in a preclinical rabbit disease model, PLoS ONE, 11, (1) pp. e0147564. ISSN 1932-6203 (2016) [Refereed Article]


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Copyright 2016 Stok et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1371/journal.pone.0147564


This work utilises advances in multi-tissue imaging, and incorporates new metrics which define in situ joint changes and individual tissue changes in osteoarthritis (OA). The aims are to (1) demonstrate a protocol for processing intact animal joints for microCT to visualise relevant joint, bone and cartilage structures for understanding OA in a preclinical rabbit model, and (2) introduce a comprehensive three-dimensional (3D) quantitative morphometric analysis (QMA), including an assessment of reproducibility. Sixteen rabbit joints with and without transection of the anterior cruciate ligament were scanned with microCT and contrast agents, and processed for histology. Semi-quantitative evaluation was performed on matching two-dimensional (2D) histology and microCT images. Subsequently, 3D QMA was performed; including measures of cartilage, subchondral cortical and epiphyseal bone, and novel tibio-femoral joint metrics. Reproducibility of the QMA was tested on seven additional joints. A significant correlation was observed in cartilage thickness from matching histology-microCT pairs. The lateral compartment of operated joints had larger joint space width, thicker femoral cartilage and reduced bone volume, while osteophytes could be detected quantitatively. Measures between the in situ tibia and femur indicated an altered loading scenario. High measurement reproducibility was observed for all new parameters; with ICC ranging from 0.754 to 0.998. In conclusion, this study provides a novel 3D QMA to quantify macro and micro tissue measures in the joint of a rabbit OA model. New metrics were established consisting of: an angle to quantitatively measure osteophytes (σ), an angle to indicate erosion between the lateral and medial femoral condyles (ρ), a vector defining altered angulation (λ, α, β, γ) and a twist angle (τ) measuring instability and tissue degeneration between the femur and tibia, a length measure of joint space width (JSW), and a slope and intercept (m, Χ) of joint contact to demonstrate altered loading with disease progression, as well as traditional bone and cartilage and histo-morphometry measures. We demonstrate correlation of microCT and histology, sensitive discrimination of OA change and robust reproducibility.

Item Details

Item Type:Refereed Article
Keywords:quantitative morphometric analysis, osteoarthritis, animal model
Research Division:Engineering
Research Group:Biomedical engineering
Research Field:Biomechanical engineering
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in engineering
UTAS Author:Stok, KS (Dr Kathryn Stok)
ID Code:133632
Year Published:2016
Web of Science® Times Cited:17
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-07-04
Last Modified:2019-08-06
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