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Extracellular matrix remodeling modifies structural responses to ventilator-induced lung injury : a multiscale correlative imaging study

Sagar, Md Motiur Rahman ; D’Amico, Lorenzo ; Deyhle, Richard T. LU ; Meyer, Ruth ; Fardin, Luca ; Mahmutovic Persson, Irma LU orcid ; Cercos-Pita, Jose Luis ; Perchiazzi, Gaetano ; Köster, Sarah and Benke, Claudia V. , et al. (2026) In Respiratory Research 27(1).
Abstract

Background: Mechanical ventilation (MV) can induce or exacerbate ventilator-induced lung injury (VILI), particularly in mechanically heterogeneous lungs with pre-existing injury. Methods: We investigated VILI in a rat model of bleomycin-induced lung injury and compared it with healthy controls using a combined in-vivo and ex-vivo imaging approach. Previously acquired in-vivo data from four-dimensional (4D) phase-contrast synchrotron micro-computed tomography (micro-CT) and forced oscillation measurements showed increased lung elastance and reduced local acinar deformation in bleomycin-induced injured lungs at baseline and after injurious MV. To identify structural and mechanical correlates, we performed automated three-dimensional (3D)... (More)

Background: Mechanical ventilation (MV) can induce or exacerbate ventilator-induced lung injury (VILI), particularly in mechanically heterogeneous lungs with pre-existing injury. Methods: We investigated VILI in a rat model of bleomycin-induced lung injury and compared it with healthy controls using a combined in-vivo and ex-vivo imaging approach. Previously acquired in-vivo data from four-dimensional (4D) phase-contrast synchrotron micro-computed tomography (micro-CT) and forced oscillation measurements showed increased lung elastance and reduced local acinar deformation in bleomycin-induced injured lungs at baseline and after injurious MV. To identify structural and mechanical correlates, we performed automated three-dimensional (3D) pore analysis and atomic force microscopy (AFM) on formalin-fixed, paraffin-embedded lung tissue, complemented by histology and spatial co-registration. Results: Ex-vivo analysis revealed pronounced airspace enlargement after both injurious MV of healthy lungs, and in bleomycin-injured lungs with inflammation and early fibrotic changes, with the strongest cumulative effect in combined bleomycin and VILI. AFM demonstrated region-specific mechanical responses, and correlation analyses linked pore geometry and nanoscale stiffness to in-vivo lung mechanics. Spatial analysis further showed co-localization of VILI-associated airspace damage with injured regions. Conclusions: Extracellular matrix remodelling modifies the lung’s response to injurious mechanical ventilation, with VILI-associated airspace damage preferentially co-localising with regions of pre-existing matrix injury. This multiscale correlative approach provides mechanistic insight into the interplay between lung injury and VILI and informs ventilation strategies in structurally altered lungs.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Correlative imaging, FFPE lung tissue, Lung fibrosis, Propagation-based imaging, Ventilator-induced lung injury
in
Respiratory Research
volume
27
issue
1
article number
287
publisher
BioMed Central (BMC)
external identifiers
  • pmid:42443903
  • scopus:105044767341
ISSN
1465-9921
DOI
10.1186/s12931-026-03807-y
language
English
LU publication?
yes
id
1b26eb65-2251-47ec-8554-76711ddefa70
date added to LUP
2026-09-30 13:25:13
date last changed
2026-10-01 03:00:02
@article{1b26eb65-2251-47ec-8554-76711ddefa70,
  abstract     = {{<p>Background: Mechanical ventilation (MV) can induce or exacerbate ventilator-induced lung injury (VILI), particularly in mechanically heterogeneous lungs with pre-existing injury. Methods: We investigated VILI in a rat model of bleomycin-induced lung injury and compared it with healthy controls using a combined in-vivo and ex-vivo imaging approach. Previously acquired in-vivo data from four-dimensional (4D) phase-contrast synchrotron micro-computed tomography (micro-CT) and forced oscillation measurements showed increased lung elastance and reduced local acinar deformation in bleomycin-induced injured lungs at baseline and after injurious MV. To identify structural and mechanical correlates, we performed automated three-dimensional (3D) pore analysis and atomic force microscopy (AFM) on formalin-fixed, paraffin-embedded lung tissue, complemented by histology and spatial co-registration. Results: Ex-vivo analysis revealed pronounced airspace enlargement after both injurious MV of healthy lungs, and in bleomycin-injured lungs with inflammation and early fibrotic changes, with the strongest cumulative effect in combined bleomycin and VILI. AFM demonstrated region-specific mechanical responses, and correlation analyses linked pore geometry and nanoscale stiffness to in-vivo lung mechanics. Spatial analysis further showed co-localization of VILI-associated airspace damage with injured regions. Conclusions: Extracellular matrix remodelling modifies the lung’s response to injurious mechanical ventilation, with VILI-associated airspace damage preferentially co-localising with regions of pre-existing matrix injury. This multiscale correlative approach provides mechanistic insight into the interplay between lung injury and VILI and informs ventilation strategies in structurally altered lungs.</p>}},
  author       = {{Sagar, Md Motiur Rahman and D’Amico, Lorenzo and Deyhle, Richard T. and Meyer, Ruth and Fardin, Luca and Mahmutovic Persson, Irma and Cercos-Pita, Jose Luis and Perchiazzi, Gaetano and Köster, Sarah and Benke, Claudia V. and Alves, Frauke and Tromba, Giuliana and Olsson, Lars E. and Bayat, Sam and Dullin, Christian}},
  issn         = {{1465-9921}},
  keywords     = {{Correlative imaging; FFPE lung tissue; Lung fibrosis; Propagation-based imaging; Ventilator-induced lung injury}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Respiratory Research}},
  title        = {{Extracellular matrix remodeling modifies structural responses to ventilator-induced lung injury : a multiscale correlative imaging study}},
  url          = {{http://dx.doi.org/10.1186/s12931-026-03807-y}},
  doi          = {{10.1186/s12931-026-03807-y}},
  volume       = {{27}},
  year         = {{2026}},
}