title: Three-Dimensional Quantitative Morphometric Analysis (QMA) for In Situ Joint and Tissue Assessment of Osteoarthritis in a Preclinical Rabbit Disease Model.
abstract: 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.
authors.affiliation: Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.|SCANCO Medical AG, Bruttisellen, Switzerland.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Stok
authors.affiliation: Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Besler
authors.affiliation: Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Steiner
authors.affiliation: Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
authors.forename: Ana V
authors.initials: AV
authors.lastname: Villarreal Escudero
authors.affiliation: SCANCO Medical AG, Bruttisellen, Switzerland.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Zulliger
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Wilke
authors.affiliation: Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
authors.forename: Kailash
authors.initials: K
authors.lastname: Atal
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Quintin
authors.affiliation: SCANCO Medical AG, Bruttisellen, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Koller
authors.affiliation: Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Dobrila
authors.initials: D
authors.lastname: Nesic
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000503:physiopathology*; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011817:Rabbits; D015203:Reproducibility of Results; D055114:X-Ray Microtomography