Faculty of Medicine, Lund University BioImaging Centre, Lund University, Lund, Sweden.
Department of Translational Medicine, Medical Radiation Physics, Lund University, Malmö, Sweden.
PLoS One. 2024 Sep 27;19(9):e0310643. doi: 10.1371/journal.pone.0310643. eCollection 2024.
Identifying biomarkers in fibrotic lung disease is key for early anti-fibrotic intervention. Dynamic contrast-enhanced (DCE) MRI offers valuable perfusion-related insights in fibrosis but adapting human MRI methods to rodents poses challenges. Here, we explored these translational challenges for the inflammatory and fibrotic phase of a bleomycin lung injury model in rats. Eleven male Sprague-Dawley rats received a single intratracheal dose of bleomycin (1000iU), four control rats received saline. Imaging was performed on days 7 and 28 post-induction. Ultra-short echo time imaging was used to image the lung for 7 minutes after which Clariscan was injected intravenously. Lung signal changes were measured for an additional 21 minutes. Images were reconstructed with a sliding-window approach, providing a temporal resolution of 10 seconds per image. After imaging on day 28, animals were euthanized, and lungs were collected for histology. Bleomycin-exposed rats initially exhibited reduced body weight, recovering to control levels after 20 days. Lung volume increased in bleomycin animals from 4.4±0.9 ml in controls to 5.5±0.5 ml and 6.5±1.2 ml on day 7 and 28. DCE-MRI showed no change of initial gradient of relative enhancement in the curves between controls and bleomycin animals on day 7 and 28 post-induction. On day 7, the DCE-MRI washout phase in bleomycin animals had higher signals than the saline group and than observed at a later time point. Lung pixels were binned in 7 enhancement classes. On day 28, the size of low relative enhancement bins almost doubled in volume compared to controls and animals on day 7 post-induction. Histology on day 28 suggests that findings could be explained by changes in lung tissue density due to lung volume increase. Adapting this clinical MRI method to rodents at 9.4T remains a challenge. Future studies may benefit from lower field strength MRI combined with higher temporal resolution DCE-MRI.
在纤维化肺部疾病中识别生物标志物是进行早期抗纤维化干预的关键。动态对比增强(DCE)MRI 为纤维化提供了有价值的灌注相关见解,但将人类 MRI 方法应用于啮齿动物存在挑战。在这里,我们探索了这种方法在博莱霉素肺损伤模型的炎症和纤维化阶段的转化挑战。11 只雄性 Sprague-Dawley 大鼠接受单次气管内博莱霉素(1000iU)剂量,4 只对照大鼠接受生理盐水。在诱导后第 7 天和第 28 天进行成像。使用超短回波时间成像对肺部进行成像 7 分钟,然后静脉注射 Clariscan。测量肺部信号变化另外 21 分钟。使用滑动窗口方法重建图像,每个图像的时间分辨率为 10 秒。在第 28 天成像后,处死动物并收集肺组织进行组织学检查。博莱霉素暴露的大鼠最初体重减轻,20 天后恢复到对照水平。博莱霉素动物的肺体积从对照动物的 4.4±0.9ml 增加到第 7 天的 5.5±0.5ml 和第 28 天的 6.5±1.2ml。DCE-MRI 显示,在诱导后第 7 天和第 28 天,对照动物和博莱霉素动物的曲线初始增强梯度无变化。在第 7 天,博莱霉素动物的 DCE-MRI 洗脱阶段的信号高于盐水组,也高于稍后时间点的信号。将肺像素分为 7 个增强类。在第 28 天,与对照组和诱导后第 7 天相比,低相对增强类别的肺像素体积几乎增加了一倍。第 28 天的组织学表明,这些发现可以通过由于肺体积增加导致的肺组织密度变化来解释。在 9.4T 下将这种临床 MRI 方法应用于啮齿动物仍然是一个挑战。未来的研究可能受益于低场强 MRI 结合更高时间分辨率的 DCE-MRI。