In vivo imaging of airway cilia and mucus clearance with micro-optical coherence tomography

Kengyeh K Chu; Carolin Unglert; Tim N Ford; Dongyao Cui; Robert W Carruth; Kanwarpal Singh; Linbo Liu; Susan E Birket; George M Solomon; Steven M Rowe; Guillermo J Tearney

doi:10.1364/BOE.7.002494

In vivo imaging of airway cilia and mucus clearance with micro-optical coherence tomography

Biomed Opt Express. 2016 Jun 2;7(7):2494-505. doi: 10.1364/BOE.7.002494. eCollection 2016 Jul 1.

Authors

Affiliations

¹ Wellman Center for Photomedicine, Department of Determatology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA; Contributed equally as co-authors.
² Wellman Center for Photomedicine, Department of Determatology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA.
³ Department of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, MCLM 706, 1918 University Blvd, Birmingham, AL, 35294-0005, USA.
⁴ Department of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, MCLM 706, 1918 University Blvd, Birmingham, AL, 35294-0005, USA; Contributed equally as senior authors.
⁵ Wellman Center for Photomedicine, Department of Determatology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA; Contributed equally as senior authors.

Abstract

We have designed and fabricated a 4 mm diameter rigid endoscopic probe to obtain high resolution micro-optical coherence tomography (µOCT) images from the tracheal epithelium of living swine. Our common-path fiber-optic probe used gradient-index focusing optics, a selectively coated prism reflector to implement a circular-obscuration apodization for depth-of-focus enhancement, and a common-path reference arm and an ultra-broadbrand supercontinuum laser to achieve high axial resolution. Benchtop characterization demonstrated lateral and axial resolutions of 3.4 μm and 1.7 μm, respectively (in tissue). Mechanical standoff rails flanking the imaging window allowed the epithelial surface to be maintained in focus without disrupting mucus flow. During in vivo imaging, relative motion was mitigated by inflating an airway balloon to hold the standoff rails on the epithelium. Software implemented image stabilization was also implemented during post-processing. The resulting image sequences yielded co-registered quantitative outputs of airway surface liquid and periciliary liquid layer thicknesses, ciliary beat frequency, and mucociliary transport rate, metrics that directly indicate airway epithelial function that have dominated in vitro research in diseases such as cystic fibrosis, but have not been available in vivo.

Keywords: (170.1610) Clinical applications; (170.2150) Endoscopic imaging; (170.4500) Optical coherence tomography; (170.4580) Optical diagnostics for medicine.

Abstract

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