Laboratory for Skeletal Development and Joint Disorders, Department of Development and Regeneration, KU Leuven, Leuven, Belgium. Ellen. elanghe@u leuven.be
PLoS One. 2012;7(8):e43123. doi: 10.1371/journal.pone.0043123. Epub 2012 Aug 13.
In vivo high-resolution micro-computed tomography allows for longitudinal image-based measurements in animal models of lung disease. The combination of repetitive high resolution imaging with fully automated quantitative image analysis in mouse models of lung fibrosis lung benefits preclinical research. This study aimed to develop and validate such an automated micro-computed tomography analysis algorithm for quantification of aerated lung volume in mice; an indicator of pulmonary fibrosis and emphysema severity.
Mice received an intratracheal instillation of bleomycin (n = 8), elastase (0.25 U elastase n = 9, 0.5 U elastase n = 8) or saline control (n = 6 for fibrosis, n = 5 for emphysema). A subset of mice was scanned without intervention, to evaluate potential radiation-induced toxicity (n = 4). Some bleomycin-instilled mice were treated with imatinib for proof of concept (n = 8). Mice were scanned weekly, until four weeks after induction, when they underwent pulmonary function testing, lung histology and collagen quantification. Aerated lung volumes were calculated with our automated algorithm.
Our automated image-based aerated lung volume quantification method is reproducible with low intra-subject variability. Bleomycin-treated mice had significantly lower scan-derived aerated lung volumes, compared to controls. Aerated lung volume correlated with the histopathological fibrosis score and total lung collagen content. Inversely, a dose-dependent increase in lung volume was observed in elastase-treated mice. Serial scanning of individual mice is feasible and visualized dynamic disease progression. No radiation-induced toxicity was observed. Three-dimensional images provided critical topographical information.
We report on a high resolution in vivo micro-computed tomography image analysis algorithm that runs fully automated and allows quantification of aerated lung volume in mice. This method is reproducible with low inherent measurement variability. We show that it is a reliable quantitative tool to investigate experimental lung fibrosis and emphysema in mice. Its non-invasive nature has the unique benefit to allow dynamic 4D evaluation of disease processes and therapeutic interventions.
体内高分辨率微计算机断层扫描允许对肺部疾病动物模型进行基于图像的纵向测量。在肺纤维化的小鼠模型中，重复高分辨率成像与全自动定量图像分析的结合有益于临床前研究。本研究旨在开发和验证一种用于量化小鼠充气肺容积的自动微计算机断层扫描分析算法；这是肺纤维化和肺气肿严重程度的一个指标。
将博来霉素（n = 8）、弹性蛋白酶（0.25 U 弹性蛋白酶 n = 9，0.5 U 弹性蛋白酶 n = 8）或生理盐水对照（纤维化 n = 6，肺气肿 n = 5）经气管内滴注到小鼠体内。一部分小鼠在未干预的情况下进行扫描，以评估潜在的辐射诱导毒性（n = 4）。一些博来霉素处理的小鼠接受伊马替尼治疗，以验证概念（n = 8）。每周对小鼠进行扫描，直到诱导后 4 周，此时对其进行肺功能测试、肺组织学和胶原蛋白定量。使用我们的自动算法计算充气肺容积。
我们的基于图像的自动充气肺容积定量方法具有低的个体内变异性，重复性好。与对照组相比，博来霉素处理的小鼠的扫描衍生充气肺容积显著降低。充气肺容积与组织病理学纤维化评分和总肺胶原蛋白含量相关。相反，在弹性蛋白酶处理的小鼠中观察到剂量依赖性的肺容积增加。对单个小鼠的连续扫描是可行的，并可直观地显示疾病进展的动态变化。未观察到辐射诱导的毒性。三维图像提供了重要的地形信息。
我们报告了一种高分辨率的体内微计算机断层扫描图像分析算法，该算法可全自动运行，并可量化小鼠的充气肺容积。该方法具有低固有测量变异性的重复性。我们表明，它是一种可靠的定量工具，可用于研究小鼠的实验性肺纤维化和肺气肿。其非侵入性的特点具有独特的优势，可以动态地 4D 评估疾病过程和治疗干预。
