Quantitative imaging of murine osteoarthritic cartilage by phase contrast micro-computed tomography

Abstract

Objective—Mouse is an optimal model organism in which gene-environment interactions can be studied for the pathogenesis of osteoarthritis. The gold standard in arthritis research in mice is based on histopathology and immunohistochemistry, which are labor intensive, prone to sampling bias and technical variability, and limited in throughput. This study aims to develop a new technique that assesses mouse cartilage by integrating quantitative volumetric imaging techniques. Methods—A novel mouse model of osteoarthritis was generated by cruciate ligament transection (CLT) and evaluated by histopathology and immunohistochemistry. Knee joint samples were then imaged by a novel technique that combines high resolution μ CT and phase-contrast optics followed by quantitative analyses. A comparative analysis was also performed on a previously established mouse model of osteoarthritis generated by destabilization of medial meniscus (DMM). Results—Phase contrast μ CT achieved cellular resolution of chondrocytes and quantitative assessment of parameters such as articular cartilage volume and surface area. In mouse models of OA generated by either CLT or DMM, we showed that phase contrast μ CT distinguished control and OA cartilage by providing quantitative measures with high reproducibility and minimal variability. Features of OA at the cellular or tissue levels could also be observed in images generated by phase contrast μ CT. Conclusion—We established an imaging technology that comprehensively assessed and quantified the 2 and 3 dimensional changes of articular cartilage. Application of this technology will facilitate the rapid and high throughput assessment of genetic and therapeutic models of OA in mice.