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Mucociliary microscopy
Epithelial ion transport is dysfunctional in individuals with cystic fibrosis (CF), a disease caused by mutations in the CF transmembrane conductance regulator that results in increased mucus accumulation, infection, and loss of lung function. Leung et al. developed an intranasal optical imaging probe with subcellular resolution that detected alterations in airway mucociliary transport in individuals with CF. Along with increased reflectivity in mucus and thicker mucus layers, the authors found areas of the epithelium lacking cilia, thinning of the periciliary liquid layer, and delayed mucociliary transport rate. Results suggest that intranasal micro-optical coherence tomography could help monitor disease status in individuals with respiratory conditions.
Abstract
Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Although impairment of mucociliary clearance contributes to severe morbidity and mortality in people with CF, a clear understanding of the pathophysiology is lacking. This is, in part, due to the absence of clinical imaging techniques capable of capturing CFTR-dependent functional metrics at the cellular level. Here, we report the clinical translation of a 1-μm resolution micro-optical coherence tomography (μOCT) technology to quantitatively characterize the functional microanatomy of human upper airways. Using a minimally invasive intranasal imaging approach, we performed a clinical study on age- and sex-matched CF and control groups. We observed delayed mucociliary transport rate at the cellular level, depletion of periciliary liquid layer, and prevalent loss of ciliation in subjects with CF. Distinctive morphological differences in mucus and various forms of epithelial injury were also revealed by μOCT imaging and had prominent effects on the mucociliary transport apparatus. Elevated mucus reflectance intensity in CF, a proxy for viscosity in situ, had a dominant effect. These results demonstrate the utility of μOCT to determine epithelial function and monitor disease status of CF airways on a per-patient basis, with applicability for other diseases of mucus clearance.
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