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Multiphase micro-computed tomography reconstructions provide dynamic respiratory function in a mouse lung fibrosis

Francesca Pennati1, Sasha Belenkov2, Martina Buccardi3

  • 1Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.

Iscience
|March 4, 2024
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Four-dimensional (4D) micro-CT imaging visualizes lung dynamics during breathing. This novel approach accurately captures respiratory changes in lung disease models, aiding therapeutic discovery.

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Area of Science:

  • Pulmonary Medicine
  • Medical Imaging
  • Biomarker Discovery

Background:

  • Micro-computed tomography (micro-CT) offers functional biomarkers for lung disease research, complementing traditional histomorphometry and enabling longitudinal studies.
  • Existing methods lack the ability to visualize dynamic lung function throughout a complete respiratory cycle.

Purpose of the Study:

  • To develop and validate a four-dimensional (4D) micro-CT imaging approach for visualizing lung dynamics across a full respiratory cycle.
  • To assess the utility of 4D micro-CT in a bleomycin-induced lung fibrosis model and evaluate the effects of the antifibrotic drug nintedanib.

Main Methods:

  • Implementation of a 4D micro-CT imaging technique with 30 reconstructed volumes per respiratory cycle.
  • Application of deep-learning-assisted segmentation for precise lung volume analysis.
  • Utilizing a bleomycin-induced lung fibrosis model in conjunction with nintedanib treatment.

Main Results:

  • 4D micro-CT accurately described inhalatory and exhalatory lung dynamics under resting conditions.
  • An inflammation-related obstructive pattern was observed at day 7, transitioning to a restrictive pattern by day 21 due to fibrosis.
  • Nintedanib treatment resulted in a milder restrictive pattern and reduced fibrotic pathology.

Conclusions:

  • 4D micro-CT provides a powerful tool for visualizing dynamic lung function and disease progression.
  • The technique accurately captures respiratory patterns, including obstructive and restrictive changes, in lung fibrosis models.
  • 4D micro-CT shows significant potential as an exploratory tool for identifying clinically relevant therapeutic compounds.