학술논문

Multiphase micro-computed tomography reconstructions provide dynamic respiratory function in a mouse lung fibrosis model.
Document Type
Academic Journal
Author
Pennati F; Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.; Belenkov S; PerkinElmer, Inc, Waltham, MA, USA.; Buccardi M; Department of Mathematical, Physical and Computer Sciences, University of Parma, Parma, Italy.; Ferrini E; Department of Veterinary Science, University of Parma, Parma, Italy.; Sverzellati N; Department of Medicine and Surgery, University of Parma, Parma, Italy.; Villetti G; Pharmacology and Toxicology Department Corporate Pre-Clinical R&D, Chiesi Farmaceutici S.p.A., Parma, Italy.; Aliverti A; Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.; Stellari FF; Pharmacology and Toxicology Department Corporate Pre-Clinical R&D, Chiesi Farmaceutici S.p.A., Parma, Italy.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
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.
Competing Interests: F.F.S. and G.V. are employees of Chiesi Farmaceutici S.p.A., that supported the research work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be perceived as a potential conflict of interest.
(© 2024 The Author(s).)