Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis.
OBJECTIVE
The degradation of articular cartilage, which characterises osteoarthritis (OA), is usually paired with excessive bone remodelling, including subchondral bone sclerosis, cysts, and osteophyte formation. Experimental models of OA are widely used to investigate pathogenesis, yet few validated methodologies for assessing periarticular bone morphology exist and quantitative measurements are limited by manual segmentation of micro-CT scans. The aim of this work was to chart the temporal changes in periarticular bone in murine OA by novel, automated micro-CT methods.


METHODS
OA was induced by destabilisation of the medial meniscus (DMM) in 10-week old male mice and disease assessed cross-sectionally from 1- to 20-weeks post-surgery. A novel approach was developed to automatically segment subchondral bone compartments into plate and trabecular bone in micro-CT scans of tibial epiphyses. Osteophyte volume, as assessed by shape differences using 3D image registration, and by measuring total epiphyseal volume was performed.


RESULTS
Significant linear and volumetric structural modifications in subchondral bone compartments and osteophytes were measured from 4-weeks post-surgery and showed progressive changes at all time points; by 20 weeks, medial subchondral bone plate thickness increased by 160±19.5 μm and the medial osteophyte grew by 0.124±0.028 μm3. Excellent agreement was found when automated measurements were compared with manual assessments.


CONCLUSIONS
Our automated methods for assessing bone changes in murine periarticular bone are rapid, quantitative, and highly accurate, and promise to be a useful tool in future preclinical studies of OA progression and treatment. The current approaches were developed specifically for cross-sectional micro-CT studies but could be applied to longitudinal studies.
Department of Bioengineering, Imperial College London, London, United Kingdom.
Patricia
http://orcid.org/0000-0001-5656-273X
P
Das Neves Borges
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.
Tonia L
TL
Vincent
Department of Bioengineering, Imperial College London, London, United Kingdom.|Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.
Massimo
M
Marenzana
D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000473:pathology*; D004838:Epiphyses / Q000000981:diagnostic imaging / Q000473:pathology; D021621:Imaging, Three-Dimensional / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054850:Osteophyte / Q000000981:diagnostic imaging / Q000473:pathology; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology*; D055114:X-Ray Microtomography