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

Abstract

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.

Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography

“…Miniaturization of the μOCT probe may allow in vivo imaging of ciliary motion in the human nasal passages for rapid noninvasive assessment of ciliary dynamics for PCD diagnosis in the future; initial attempts are already in progress (32). Another limitation is our use of murine models, which do not express the glandular structures of the human airway, which alters mucus content.…”

Flexible, high-resolution micro-optical coherence tomography endobronchial probe toward in vivo imaging of cilia

“…The recent development of micro-optical coherence tomography (μOCT) has further improved resolution in both axial and lateral directions by an order of magnitude compared to traditional techniques, allowing cellular and sub-cellular microstructures of biological tissues to be resolved with applications in a variety of organ systems [4,5]. In particular, our group has applied μOCT to the dynamic imaging of respiratory cilia [6–8], the organelles on airway epithelia that are responsible for mucus clearance. Other OCT approaches to ciliary imaging and mucociliary transport have also been recently developed [9–11].…”

“…Much research has been devoted to high-resolution OCT probe development [12–15]. We recently reported the development of a rigid, 4 mm diameter μOCT probe and demonstrated its ability to capture high-resolution images and measure mucociliary function in swine in vivo [8]. However, the clinical utility of this probe was limited by its relatively large diameter and the fact that it was rigid.…”

“…The optical core of the probe was a common-path, circular-obscuration apodization design, similar to [8]. The common-path design minimized material dispersion, and the beam apodization extended DOF as reported in [5,8] [Fig.…”

Direct monitoring of pulmonary disease treatment biomarkers using plasmonic gold nanorods with diffusion-sensitive OCT

“…By directly monitoring mucus wt% changes in real-time during treatment we may develop more accurate, rapid and reliable outcome measures. OCT is a promising technology toward this end, as it has already proven useful for studying MCC-related metrics including cilia-driven flow rates 12, 13 , collapse of cilia under a mucus load 14 , and ciliary beat frequency 13, 15 , with recent developments toward in vivo measurements 16 . Here, we introduce DS-OCT for non-invasive quantification of mucus wt% in situ on epithelium and in real-time during mucus-hydrating therapy.…”