Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1.

Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1.
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DOI:
10.1186/1465-9921-11-181
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发表时间:
2010-12-22
影响因子:
5.8
通讯作者:
Borlak J
Borlak J
中科院分区:
医学2区
文献类型:
--
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

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微型计算机断层扫描(micro-CT)是一种监测小型实验动物急慢性疾病状态的新工具。它在评估小鼠进行性肺纤维化方面的价值迄今尚未报道。在这里,我们研究了体内微ct作为评估小鼠肺纤维化进展的非侵入性工具的重要性。通过气管内递送编码生物活性TGF-ß1 (AdTGF-ß1)的腺病毒基因载体诱导小鼠肺纤维化。在肺腺病毒基因或控制载体递送后1、2、3和4周进行呼吸门控和非门控微ct扫描,然后与小鼠肺纤维化的组织病理学Ashcroft评分相关联。由3名观察员对图像质量和实变进行视觉评估,并采用半自动量化算法对充气肺体积进行量化,作为肺纤维化的逆替代指标。我们发现经典Ashcroft评分与使用视觉评估和半自动量化算法的微ct评估之间存在显著相关性。微ct可以清晰地检测到肺纤维化,呼吸门控检查的图像质量值更高,但差异不显著。在评估纤维化方面,呼吸门控检查和非门控检查没有显著差异。总之,我们表明micro-CT是评估小鼠肺纤维化的有力工具,使用视觉评估和半自动量化算法。这些数据可能是重要的,考虑到临床前药物干预治疗肺纤维化的小实验动物。
Micro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time. Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis. We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed. Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.