Das Neves Borges Patricia, Vincent Tonia L, Marenzana Massimo
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.
PLoS One. 2017 Mar 23;12(3):e0174294. doi: 10.1371/journal.pone.0174294. eCollection 2017.
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.
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.
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.
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.
骨关节炎(OA)的特征是关节软骨退化,通常还伴有过度的骨重塑,包括软骨下骨硬化、囊肿和骨赘形成。OA的实验模型被广泛用于研究发病机制,但目前用于评估关节周围骨形态的有效方法较少,且定量测量受限于微CT扫描的手动分割。本研究旨在通过新颖的自动微CT方法描绘小鼠OA关节周围骨的时间变化。
对10周龄雄性小鼠进行内侧半月板不稳定(DMM)诱导OA,并在术后1至20周进行横断面疾病评估。开发了一种新方法,可在胫骨骨骺的微CT扫描中自动将软骨下骨区域分割为骨板和小梁骨。通过使用3D图像配准的形状差异评估骨赘体积,并测量总骨骺体积。
术后4周开始测量软骨下骨区域和骨赘的显著线性和体积结构变化,且在所有时间点均呈现渐进性变化;到20周时,内侧软骨下骨板厚度增加了160±19.5μm,内侧骨赘增长了0.124±0.028μm³。将自动测量结果与手动评估结果进行比较时,发现两者具有极好的一致性。
我们用于评估小鼠关节周围骨变化的自动方法快速、定量且高度准确,有望成为未来OA进展和治疗临床前研究中的有用工具。当前方法专为横断面微CT研究而开发,但也可应用于纵向研究。