Quantification of lung fibrosis and emphysema in mice using automated micro-computed tomography.
Quantification of lung fibrosis and emphysema in mice using automated micro-computed tomography.
复制标题
DOI：
10.1371/journal.pone.0043123
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lories RJ
中科院分区：
文献类型：
--
作者：
De Langhe E;Vande Velde G;Hostens J;Himmelreich U;Nemery B;Luyten FP;Vanoirbeek J;Lories RJ
体内高分辨率微计算机断层扫描允许在肺部疾病的动物模型中进行基于图像的纵向测量。在肺纤维化小鼠模型中，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这种自动化微计算机断层扫描分析算法，用于定量小鼠的充气肺体积;肺纤维化和肺气肿严重程度的指标。小鼠接受博莱霉素（n = 8）、弹性蛋白酶（0.25U弹性蛋白酶n = 9，0.5U弹性蛋白酶n = 8）或盐水对照（对于纤维化n=6，对于肺气肿n=5）的腹膜内滴注。 在没有干预的情况下扫描小鼠亚组，以评价潜在的辐射诱导毒性（n = 4）。 一些博来霉素滴注的小鼠用伊马替尼处理以验证概念（n = 8）。 每周对小鼠进行扫描，直到诱导后四周，此时它们进行肺功能测试、肺组织学和胶原定量。用我们的自动算法计算充气肺体积。我们的自动化基于图像的充气肺容积定量方法是可重复的，受试者内变异性低。与对照组相比，博来霉素治疗的小鼠具有显著更低的扫描衍生的充气肺体积。充气肺容积与组织病理学纤维化评分和肺总胶原含量相关。因此，在弹性蛋白酶处理的小鼠中观察到肺体积的剂量依赖性增加。单个小鼠的连续扫描是可行的并且可视化动态疾病进展。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，该算法完全自动运行，并允许量化小鼠的充气肺体积。该方法具有较低的固有测量变异性，具有重现性。我们表明，这是一个可靠的定量工具，研究实验性肺纤维化和肺气肿小鼠。它的非侵入性性质具有独特的优势，可以对疾病过程和治疗干预进行动态4D评估。
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 (0.25U elastase n = 9, 0.5U 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.
登录
查看更多内容
影响因子：
4.8
作者：
Cavanaugh, Dawn;Travis, Elizabeth L.;Cody, Dianna D.
通讯作者：
Cody, Dianna D.
影响因子：
3.9
作者：
WOESSNER, JF
通讯作者：
WOESSNER, JF
影响因子：
5.8
作者：
Rodt T;von Falck C;Dettmer S;Halter R;Maus R;Ask K;Kolb M;Gauldie J;Länger F;Hoy L;Welte T;Galanski M;Maus UA;Borlak J
通讯作者：
Borlak J
影响因子：
1.7
作者：
Shofer, Scott;Badea, Cristian;Johnson, G. Allan
通讯作者：
Johnson, G. Allan
影响因子：
5.7
作者：
Fushiki, Hiroshi;Kanoh-Azuma, Tomoko;Hayakawa, Yoshihiro
通讯作者：
Hayakawa, Yoshihiro