Automated assessment of bone changes in cross-sectional micro-CT studies of murine experimental osteoarthritis

ObjectiveThe 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.MethodsOA 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.ResultsSignificant 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.ConclusionOur 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.

研究目标
骨关节炎（osteoarthritis, OA）以关节软骨退变为特征，通常伴随过度骨重塑，包括软骨下骨硬化、囊肿形成及骨赘生成。现有骨关节炎实验模型被广泛用于探究其发病机制，但目前经验证的关节周骨形态学评估方法寥寥无几，且定量测量受限于显微CT（micro-CT）扫描的手动分割操作。本研究旨在通过新型自动化显微CT技术，系统刻画小鼠骨关节炎模型中关节周骨的时序变化规律。

研究方法
本研究对10周龄雄性小鼠实施内侧半月板失稳术（destabilisation of the medial meniscus, DMM）以诱导骨关节炎，并于术后1至20周开展横断面评估。我们开发了一种全新方法，可在胫骨骨骺的显微CT扫描图像中，自动将软骨下骨室分割为骨板与骨小梁两个亚区。同时通过三维图像配准（3D image registration）分析形态差异，以及测量骨骺总体积的方式，对骨赘体积进行定量评估。

研究结果
术后4周即可检测到软骨下骨室及骨赘出现显著的线性与体积结构改变，且各观测时间点均呈现进行性变化；至术后20周时，内侧软骨下骨板厚度增加160±19.5 μm，内侧骨赘体积增长0.124±0.028 μm³。自动化测量结果与手动评估结果具有极佳的一致性。

研究结论
本研究建立的小鼠关节周骨骨改变自动化评估方法快速、定量且准确度极高，有望成为未来骨关节炎进展与治疗相关临床前研究的实用工具。尽管本方法专为横断面显微CT研究开发，但同样可应用于纵向研究。