Redox imaging and optical coherence tomography of the respiratory ciliated epithelium

Optical coherence tomography (OCT) is an emerging technology for in vivo airway and lung imaging. However, OCT lacks sensitivity to the metabolic changes caused by inflammation, which drives chronic respiratory diseases such as asthma and chronic obstructive pulmonary disorder. Redox imaging (RI) is a label-free technique that uses the autofluorescence of the metabolic coenzymes NAD(P)H and flavin adenine dinucleotide (FAD) to probe cellular metabolism and could provide complimentary information to OCT for airway and lung imaging. We demonstrate OCT and RI of respiratory ciliated epithelial function in ex vivo mouse tracheae. We applied RI to measure cellular metabolism via the redox ratio [intensity of NAD(P)H divided by FAD] and particle tracking velocimetry OCT to quantify cilia-driven fluid flow. To model mitochondrial dysfunction, a key aspect of the inflammatory process, cyanide was used to inhibit oxidative metabolism and reduce ciliary motility. Cyanide exposure over 20 min significantly increased the redox ratio and reversed cilia-driven fluid flow. We propose that RI provides complementary information to OCT to assess inflammation in the airway and lungs.