Pennati Francesca, Belenkov Sasha, Buccardi Martina, Ferrini Erica, Sverzellati Nicola, Villetti Gino, Aliverti Andrea, Stellari Franco Fabio
Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
PerkinElmer, Inc, Waltham, MA, USA.
iScience. 2024 Feb 16;27(3):109262. doi: 10.1016/j.isci.2024.109262. eCollection 2024 Mar 15.
Micro-computed tomography derived functional biomarkers used in lung disease research can significantly complement end-stage histomorphometric measures while also allowing for longitudinal studies. However, no approach for visualizing lung dynamics across a full respiratory cycle has yet been described. Using bleomycin-induced lung fibrosis and the antifibrotic drug nintedanib as a test model, we implemented a four-dimensional (4D) micro-CT imaging approach consisting of 30 reconstructed volumes per respiratory cycle, coupled with deep-learning-assisted segmentation of lung volumes. 4D micro-CT provided an accurate description of inhalatory and exhalatory lung dynamics under resting conditions and revealed an inflammation-related obstructive pattern at day 7, followed by a restrictive pattern associated with fibrosis development at day 21. A milder restriction and fibrotic pathology resulted from nintedanib treatment. The similarity of 4D micro-CT data with those produced by diagnostic measurements, also points to its great potential as an exploratory tool for the discovery of clinically relevant therapeutic compounds.
用于肺部疾病研究的微计算机断层扫描衍生功能生物标志物可以显著补充终末期组织形态计量学测量，同时还能进行纵向研究。然而，尚未有描述在整个呼吸周期可视化肺动力学的方法。使用博来霉素诱导的肺纤维化和抗纤维化药物尼达尼布作为测试模型，我们实施了一种四维（4D）微CT成像方法，每个呼吸周期由30个重建体积组成，并结合深度学习辅助的肺体积分割。4D微CT准确描述了静息状态下吸气和呼气时的肺动力学，并在第7天揭示了与炎症相关的阻塞模式，随后在第21天出现了与纤维化发展相关的限制性模式。尼达尼布治疗导致了较轻的限制性和纤维化病理。4D微CT数据与诊断测量产生的数据的相似性，也表明其作为发现临床相关治疗化合物的探索工具具有巨大潜力。
