Center for Pulmonary Imaging Research, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
Department of Physics, Washington University in St. Louis , St. Louis, Missouri.
J Appl Physiol (1985). 2019 Apr 1;126(4):1138-1149. doi: 10.1152/japplphysiol.00993.2018. Epub 2019 Feb 7.
To longitudinally monitor progressive fibrosis in the transforming growth factor-α (TGF-α) transgenic mouse model of lung fibrosis, we used retrospective self-gating ultrashort echo time (UTE) magnetic resonance imaging (MRI) to image mouse lung at baseline and after 4 and 8 wk of fibrosis initiation via doxycycline administration. Only bitransgenic mice were used in this study and divided into two cohorts: six mice were fed doxycycline food to induce lung fibrosis (referred to as Dox cohort), and five other mice were fed normal food (referred to as control cohort). Lung mechanics, histology, and hydroxyproline were assessed after the final MRI. A linear mixed-effects model was used to analyze MRI-derived longitudinal lung-function parameters. Tidal volume decreased at a rate of -0.016 ± 0.002 ml/week [χ(1) = 16.48, < 0.001] for Dox cohort and increased at a rate of 0.010 ± 0.003 ml/week [χ(1) = 6.37, = 0.01] for control cohort. Minute ventilation decreased at a rate of -1.71 ± 0.26 ml·min·wk [χ(1) = 14.04, < 0.001] for Dox cohort but did not change significantly over time for control cohort. High-density lung volume percentage increased at a rate of 3.9 ± 0.7%/wk for Dox cohort [χ(1) = 11.47, < 0.001] but did not change significantly over time for control cohort. MRI-derived lung structure and function parameters were strongly correlated with pleural thickness, hydroxyproline content, lung compliance, airway resistance, and airway elastance. We conclude that self-gating UTE MRI could be used to longitudinally monitor lung fibrosis in the TGF-α transgenic mouse model. Self-gating UTE MRI was used to monitor morphology and physiology in lung fibrosis in a transforming growth factor-α transgenic mouse model. Tidal volume was shown for the first time to correlate strongly with conventional metrics of fibrosis such as hydroxyproline and pleural thickness.
为了纵向监测转化生长因子-α（TGF-α）转基因肺纤维化小鼠模型中的进行性纤维化，我们使用回顾性自门控超短回波时间（UTE）磁共振成像（MRI）在通过强力霉素给药启动纤维化后 4 周和 8 周时对小鼠肺进行成像。本研究仅使用双转基因小鼠，并分为两个队列：六只小鼠喂食强力霉素食物以诱导肺纤维化（称为 Dox 队列），另外五只喂食正常食物（称为对照组）。在最后一次 MRI 后评估肺力学、组织学和羟脯氨酸。使用线性混合效应模型分析 MRI 衍生的纵向肺功能参数。对于 Dox 队列，潮气量以 -0.016 ± 0.002 ml/周的速度下降[χ(1) = 16.48， < 0.001]，而对于对照组，潮气量以 0.010 ± 0.003 ml/周的速度增加[χ(1) = 6.37， = 0.01]。每分钟通气量以 -1.71 ± 0.26 ml·min·wk 的速度下降[χ(1) = 14.04， < 0.001]对于 Dox 队列，但对照组随时间推移没有明显变化。高密度肺容积百分比以 3.9 ± 0.7%/wk 的速度增加[χ(1) = 11.47， < 0.001]对于 Dox 队列，但对照组随时间推移没有明显变化。MRI 衍生的肺结构和功能参数与胸膜厚度、羟脯氨酸含量、肺顺应性、气道阻力和气道弹性密切相关。我们得出结论，自门控 UTE MRI 可用于纵向监测 TGF-α 转基因小鼠模型中的肺纤维化。自门控 UTE MRI 用于监测转化生长因子-α转基因小鼠模型中的肺纤维化的形态和生理学。首次显示潮气量与羟脯氨酸和胸膜厚度等纤维化的常规指标密切相关。
