Swiss Light Source, Paul Scherrer Institut, Villigen 5232, Switzerland; Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich 8006, Switzerland.
Bone. 2013 Nov;57(1):142-54. doi: 10.1016/j.bone.2013.06.026. Epub 2013 Jul 18.
Assessing the role of osteocyte lacunae and the ways in which they communicate with one another is important for determining the function and viability of bone tissue. Osteocytes are able to play a significant role in bone development and remodeling because they can receive nourishment from, interact with, and communicate with other cells. In this sense the immediate environment of an osteocyte is crucial for understanding its function. Modern imaging techniques, ranging from synchrotron radiation-based computed tomography (SR CT) to confocal laser scanning microscopy, produce large volumes of high-quality imaging data of bone tissue on the micrometer scale in rapidly shortening times. These images often contain tens of thousands of osteocytes and their lacunae, void spaces which enclose the osteocytes. While theoretically possible, quantitative analysis of the osteocyte lacunar system is too time consuming to be practical without highly automated tools. Moreover, quantitative morphometry of the osteocyte lacunar system necessitates clearly defined, robust, and three-dimensional (3D) measures. Here, we introduce a framework for the quantitative characterization of millions of osteocyte lacunae and their spatial relationships in 3D. The metrics complement and expand previous works looking at shape and number density while providing novel measures for quantifying spatial distribution and alignment. We developed model, in silico systems to visualize and validate the metrics and provide a concrete example of the attribute being classified with each metric. We then illustrate the applicability to biological samples in a first study comparing two strains of mice and the effect of growth hormone. We found significant differences in shape and distribution between strains for alignment. The proposed quantitative framework can be used in future studies examining differences and treatment effects in bone microstructure at the cell scale. Furthermore, the proposed strategy for quantitative bone cell morphometry will allow investigating structure-function relationships in bone tissue, for example by linking cellular morphometry to bone remodeling.
评估骨细胞陷窝及其相互交流的方式对于确定骨组织的功能和活力非常重要。骨细胞能够在骨发育和重塑中发挥重要作用，因为它们能够从其他细胞中获取营养，与其他细胞相互作用并进行交流。从这个意义上说，骨细胞的直接环境对于理解其功能至关重要。现代成像技术，从同步辐射计算机断层扫描（SR CT）到共聚焦激光扫描显微镜，在极短的时间内产生大量高质量的骨组织微米尺度成像数据。这些图像通常包含成千上万的骨细胞及其陷窝，即包围骨细胞的空隙。虽然从理论上讲是可行的，但如果没有高度自动化的工具，对骨细胞陷窝系统进行定量分析太耗时耗力。此外，骨细胞陷窝系统的定量形态测量需要明确、稳健和三维（3D）的测量方法。在这里，我们引入了一个框架，用于对 3D 中数百万个骨细胞陷窝及其空间关系进行定量描述。这些指标补充并扩展了之前研究形状和数量密度的工作，同时提供了新的方法来量化空间分布和对准。我们开发了模型，在模拟系统中可视化和验证了这些指标，并提供了一个具体的例子来说明每个指标的分类属性。然后，我们通过比较两种小鼠品系和生长激素的影响的第一个研究来说明在生物样本中的适用性。我们发现，在对准方面，两种品系之间的形状和分布存在显著差异。所提出的定量框架可用于未来研究，在细胞尺度上检查骨微观结构的差异和治疗效果。此外，所提出的定量骨细胞形态测量策略将允许研究骨组织中的结构-功能关系，例如将细胞形态测量与骨重塑联系起来。
