Linking optics and mechanics in an in vivo model of airway fibrosis and epithelial injury

Christopher B. Raub, Sari Mahon, Navneet Narula, Bruce J. Tromberg, Matthew Brenner, Steven George

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Chronic mucosal and submucosal injury can lead to persistent inflammation and tissue remodeling. We hypothesized that microstructural and mechanical properties of the airway wall could be derived from multiphoton images. New Zealand White rabbits were intubated, and the tracheal epithelium gently denuded every other day for five days (three injuries). Three days following the last injury, the tracheas were excised for multiphoton imaging, mechanical compression testing, and histological analysis. Multiphoton imaging and histology confirm epithelial denudation, mucosal ulceration, subepithelial thickening, collagen deposition, immune cell infiltration, and a disrupted elastin network. Elastase removes the elastin network and relaxes the collagen network. Purified collagenase removes epithelium with subtle subepithelial changes. Young's modulus [(E) measured in kiloPascal] was significantly elevated for the scrape injured (9.0±3.2) trachea, and both collagenase (2.6±0.4) and elastase (0.8±0.3) treatment significantly reduced E relative to control (4.1 ±0.7). E correlates strongly with second harmonic generation (SHG) signal depth decay for enzyme-treated and control tracheas (R 2 = 0.77), but not with scrape-injured tracheas. We conclude that E of subepithelial connective tissue increases on repeated epithelial wounding, due in part to changes in elastin and collagen microstructure and concentration. SHG depth decay is sensitive to changes in extracellular matrix content and correlates with bulk Young's modulus.

Original languageEnglish (US)
Article number015004
JournalJournal of Biomedical Optics
Volume15
Issue number1
DOIs
StatePublished - Dec 1 2010

Keywords

  • Collagen
  • Elastin
  • Fibrosis
  • Second harmonic
  • Two photon fluorescence

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering

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