OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 3, Iss. 9 — Sep. 1, 2012
  • pp: 1978–1992

Monitoring airway mucus flow and ciliary activity with optical coherence tomography

Amy L. Oldenburg, Raghav K. Chhetri, David B. Hill, and Brian Button  »View Author Affiliations

Biomedical Optics Express, Vol. 3, Issue 9, pp. 1978-1992 (2012)

View Full Text Article

Enhanced HTML    Acrobat PDF (4823 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



Muco-ciliary transport in the human airway is a crucial defense mechanism for removing inhaled pathogens. Optical coherence tomography (OCT) is well-suited to monitor functional dynamics of cilia and mucus on the airway epithelium. Here we demonstrate several OCT-based methods upon an actively transporting in vitro bronchial epithelial model and ex vivo mouse trachea. We show quantitative flow imaging of optically turbid mucus, semi-quantitative analysis of the ciliary beat frequency, and functional imaging of the periciliary layer. These may translate to clinical methods for endoscopic monitoring of muco-ciliary transport in diseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD).

© 2012 OSA

OCIS Codes
(110.6150) Imaging systems : Speckle imaging
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.4500) Medical optics and biotechnology : Optical coherence tomography
(110.0113) Imaging systems : Imaging through turbid media
(170.2655) Medical optics and biotechnology : Functional monitoring and imaging
(110.4153) Imaging systems : Motion estimation and optical flow

ToC Category:
Optical Coherence Tomography

Original Manuscript: May 21, 2012
Revised Manuscript: July 6, 2012
Manuscript Accepted: July 6, 2012
Published: August 1, 2012

Amy L. Oldenburg, Raghav K. Chhetri, David B. Hill, and Brian Button, "Monitoring airway mucus flow and ciliary activity with optical coherence tomography," Biomed. Opt. Express 3, 1978-1992 (2012)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. A. Wanner, M. Salathé, and T. G. O’Riordan, “Mucociliary clearance in the airways,” Am. J. Respir. Crit. Care Med.154(6 Pt 1), 1868–1902 (1996). [PubMed]
  2. J. A. Regnis, M. Robinson, D. L. Bailey, P. Cook, P. Hooper, H. K. Chan, I. Gonda, G. Bautovich, and P. T. Bye, “Mucociliary clearance in patients with cystic fibrosis and in normal subjects,” Am. J. Respir. Crit. Care Med.150(1), 66–71 (1994). [PubMed]
  3. G. C. Smaldone, W. M. Foster, T. G. O’Riordan, M. S. Messina, R. J. Perry, and E. G. Langenback, “Regional impairment of mucociliary clearance in chronic obstructive pulmonary disease,” Chest103(5), 1390–1396 (1993). [CrossRef] [PubMed]
  4. M. R. Knowles and R. C. Boucher, “Mucus clearance as a primary innate defense mechanism for mammalian airways,” J. Clin. Invest.109(5), 571–577 (2002). [PubMed]
  5. M. B. Antunes and N. A. Cohen, “Mucociliary clearance--a critical upper airway host defense mechanism and methods of assessment,” Curr. Opin. Allergy Clin. Immunol.7(1), 5–10 (2007). [CrossRef] [PubMed]
  6. C. Pitris, M. E. Brezinski, B. E. Bouma, G. J. Tearney, J. F. Southern, and J. G. Fujimoto, “High resolution imaging of the upper respiratory tract with optical coherence tomography: a feasibility study,” Am. J. Respir. Crit. Care Med.157(5 Pt 1), 1640–1644 (1998). [PubMed]
  7. H. O. Coxson, B. Quiney, D. D. Sin, L. Xing, A. M. McWilliams, J. R. Mayo, and S. Lam, “Airway wall thickness assessed using computed tomography and optical coherence tomography,” Am. J. Respir. Crit. Care Med.177(11), 1201–1206 (2008). [CrossRef] [PubMed]
  8. S. Lam, B. Standish, C. Baldwin, A. McWilliams, J. leRiche, A. Gazdar, A. I. Vitkin, V. Yang, N. Ikeda, and C. MacAulay, “In vivo optical coherence tomography imaging of preinvasive bronchial lesions,” Clin. Cancer Res.14(7), 2006–2011 (2008). [CrossRef] [PubMed]
  9. J. P. Williamson, R. A. McLaughlin, W. J. Noffsinger, A. L. James, V. A. Baker, A. Curatolo, J. J. Armstrong, A. Regli, K. L. Shepherd, G. B. Marks, D. D. Sampson, D. R. Hillman, and P. R. Eastwood, “Elastic properties of the central airways in obstructive lung diseases measured using anatomical optical coherence tomography,” Am. J. Respir. Crit. Care Med.183(5), 612–619 (2011). [CrossRef] [PubMed]
  10. J. Su, J. Zhang, L. Yu, H. G Colt, M. Brenner, and Z. Chen, “Real-time swept source optical coherence tomography imaging of the human airway using a microelectromechanical system endoscope and digital signal processor,” J. Biomed. Opt.13(3), 030506 (2008). [CrossRef] [PubMed]
  11. R. G. Michel, G. T. Kinasewitz, K. M. Fung, and J. I. Keddissi, “Optical coherence tomography as an adjunct to flexible bronchoscopy in the diagnosis of lung cancer: a pilot study,” Chest138(4), 984–988 (2010). [CrossRef] [PubMed]
  12. K. Jeong, J. J. Turek, and D. D. Nolte, “Speckle fluctuation spectroscopy of intracellular motion in living tissue using coherence-domain digital holography,” J. Biomed. Opt.15(3), 030514 (2010). [CrossRef] [PubMed]
  13. D. D. Nolte, R. An, J. Turek, and K. Jeong, “Holographic tissue dynamics spectroscopy,” J. Biomed. Opt.16(8), 087004 (2011). [CrossRef] [PubMed]
  14. S. Jonas, D. Bhattacharya, M. K. Khokha, and M. A. Choma, “Microfluidic characterization of cilia-driven fluid flow using optical coherence tomography-based particle tracking velocimetry,” Biomed. Opt. Express2(7), 2022–2034 (2011). [CrossRef] [PubMed]
  15. J. C. Hogg, F. Chu, S. Utokaparch, R. Woods, W. M. Elliott, L. Buzatu, R. M. Cherniack, R. M. Rogers, F. C. Sciurba, H. O. Coxson, and P. D. Paré, “The nature of small-airway obstruction in chronic obstructive pulmonary disease,” N. Engl. J. Med.350(26), 2645–2653 (2004). [CrossRef] [PubMed]
  16. T. Aikawa, S. Shimura, H. Sasaki, M. Ebina, and T. Takishima, “Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack,” Chest101(4), 916–921 (1992). [CrossRef] [PubMed]
  17. R. M. Shah, W. Sexauer, B. J. Ostrum, S. B. Fiel, and A. C. Friedman, “High-resolution CT in the acute exacerbation of cystic fibrosis: evaluation of acute findings, reversibility of those findings, and clinical correlation,” AJR Am. J. Roentgenol.169(2), 375–380 (1997). [PubMed]
  18. S. H. Donaldson, W. D. Bennett, K. L. Zeman, M. R. Knowles, R. Tarran, and R. C. Boucher, “Mucus clearance and lung function in cystic fibrosis with hypertonic saline,” N. Engl. J. Med.354(3), 241–250 (2006). [CrossRef] [PubMed]
  19. L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011). [CrossRef] [PubMed]
  20. B. Povazay, K. Bizheva, A. Unterhuber, B. Hermann, H. Sattmann, A. F. Fercher, W. Drexler, A. Apolonski, W. J. Wadsworth, J. C. Knight, P. S. J. Russell, M. Vetterlein, and E. Scherzer, “Submicrometer axial resolution optical coherence tomography,” Opt. Lett.27(20), 1800–1802 (2002). [CrossRef] [PubMed]
  21. M. L. Fulcher, S. Gabriel, K. A. Burns, J. R. Yankaskas, and S. H. Randell, “Well-differentiated human airway epithelial cell cultures,” Methods Mol. Med.107, 183–206 (2005). [PubMed]
  22. J. H. Raphael, D. A. Selwyn, S. D. Mottram, J. A. Langton, and C. O’Callaghan, “Effects of 3 MAC of halothane, enflurane and isoflurane on cilia beat frequency of human nasal epithelium in vitro,” Br. J. Anaesth.76(1), 116–121 (1996). [CrossRef] [PubMed]
  23. A. L. Oldenburg, C. M. Gallippi, F. Tsui, T. C. Nichols, K. N. Beicker, R. K. Chhetri, D. Spivak, A. Richardson, and T. H. Fischer, “Magnetic and contrast properties of labeled platelets for magnetomotive optical coherence tomography,” Biophys. J.99(7), 2374–2383 (2010). [CrossRef] [PubMed]
  24. A. L. Oldenburg, V. Crecea, S. A. Rinne, and S. A. Boppart, “Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues,” Opt. Express16(15), 11525–11539 (2008). [PubMed]
  25. A. L. Oldenburg and R. K. Chhetri, “Digital dispersion compensation for ultrabroad-bandwidth single-camera spectral-domain polarization-sensitive OCT,” Proc. SPIE7889, 78891V (2011).
  26. D. L. Marks, A. L. Oldenburg, J. J. Reynolds, and S. A. Boppart, “Digital algorithm for dispersion correction in optical coherence tomography for homogeneous and stratified media,” Appl. Opt.42(2), 204–217 (2003). [CrossRef] [PubMed]
  27. B. White, M. Pierce, N. Nassif, B. Cense, B. Park, G. Tearney, B. Bouma, T. Chen, and J. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express11(25), 3490–3497 (2003). [CrossRef] [PubMed]
  28. J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch, “In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography,” Opt. Lett.22(18), 1439–1441 (1997). [CrossRef] [PubMed]
  29. V. J. Srinivasan, H. Radhakrishnan, E. H. Lo, E. T. Mandeville, J. Y. Jiang, S. Barry, and A. E. Cable, “OCT methods for capillary velocimetry,” Biomed. Opt. Express3(3), 612–629 (2012). [CrossRef] [PubMed]
  30. L. N. Bohs and G. E. Trahey, “A novel method for angle independent ultrasonic imaging of blood flow and tissue motion,” IEEE Trans. Biomed. Eng.38(3), 280–286 (1991). [CrossRef] [PubMed]
  31. I. A. Hein and W. R. O’Brien, “Current time-domain methods for assessing tissue motion by analysis from reflected ultrasound echoes-a review,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control40(2), 84–102 (1993). [CrossRef] [PubMed]
  32. E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “In vivo retinal imaging by optical coherence tomography,” Opt. Lett.18(21), 1864–1866 (1993). [CrossRef] [PubMed]
  33. J. Schmitt, “OCT elastography: imaging microscopic deformation and strain of tissue,” Opt. Express3(6), 199–211 (1998). [CrossRef] [PubMed]
  34. H. Matsui, B. R. Grubb, R. Tarran, S. H. Randell, J. T. Gatzy, C. W. Davis, and R. C. Boucher, “Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease,” Cell95(7), 1005–1015 (1998). [CrossRef] [PubMed]
  35. S. Gueron, K. Levit-Gurevich, N. Liron, and J. J. Blum, “Cilia internal mechanism and metachronal coordination as the result of hydrodynamical coupling,” Proc. Natl. Acad. Sci. U.S.A.94(12), 6001–6006 (1997). [CrossRef] [PubMed]
  36. A. B. Lansley, M. J. Sanderson, and E. R. Dirksen, “Control of the beat cycle of respiratory tract cilia by Ca2+ and cAMP,” Am. J. Physiol.263(2 Pt 1), L232–L242 (1992). [PubMed]
  37. D. B. Hill, V. Swaminathan, A. Estes, J. Cribb, E. T. O’Brien, C. W. Davis, and R. Superfine, “Force generation and dynamics of individual cilia under external loading,” Biophys. J.98(1), 57–66 (2010). [CrossRef] [PubMed]
  38. Y. Zhao, Z. Chen, C. Saxer, Q. Shen, S. Xiang, J. F. de Boer, and J. S. Nelson, “Doppler standard deviation imaging for clinical monitoring of in vivo human skin blood flow,” Opt. Lett.25(18), 1358–1360 (2000). [CrossRef] [PubMed]
  39. G. Liu, L. Chou, W. Jia, W. Qi, B. Choi, and Z. Chen, “Intensity-based modified Doppler variance algorithm: application to phase instable and phase stable optical coherence tomography systems,” Opt. Express19(12), 11429–11440 (2011). [CrossRef] [PubMed]
  40. Y. Wang and R. Wang, “Autocorrelation optical coherence tomography for mapping transverse particle-flow velocity,” Opt. Lett.35(21), 3538–3540 (2010). [CrossRef] [PubMed]
  41. W. M. Foster, E. Langenback, and E. H. Bergofsky, “Measurement of tracheal and bronchial mucus velocities in man: relation to lung clearance,” J. Appl. Physiol.48(6), 965–971 (1980). [PubMed]
  42. H. Matsui, S. H. Randell, S. W. Peretti, C. W. Davis, and R. C. Boucher, “Coordinated clearance of periciliary liquid and mucus from airway surfaces,” J. Clin. Invest.102(6), 1125–1131 (1998). [CrossRef] [PubMed]
  43. Z. Y. Shen, M. Wang, Y. H. Ji, Y. H. He, X. S. Dai, P. Li, and H. Ma, “Transverse flow velocity quantification using optical coherence tomography with correlation,” Laser Phys. Lett.8(4), 318–323 (2011). [CrossRef]
  44. E. Puchelle, J. M. Zahm, and D. Quemada, “Rheological properties controlling mucociliary frequency and respiratory mucus transport,” Biorheology24(6), 557–563 (1987). [PubMed]
  45. A. Robertson, W. Stannard, C. Passant, C. O’Callaghan, and A. Banerjee, “What effect does isoflurane have upon ciliary beat pattern: an in vivo study,” Clin. Otolaryngol. Allied Sci.29(2), 157–160 (2004). [CrossRef] [PubMed]
  46. B. R. Manawadu, S. R. Mostow, and F. M. LaForce, “Impairment of tracheal ring ciliary activity by halothane,” Anesth. Analg.58(6), 500–504 (1979). [CrossRef] [PubMed]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

Supplementary Material

» Media 1: AVI (3330 KB)     
» Media 2: AVI (3170 KB)     
» Media 3: AVI (2439 KB)     
» Media 4: AVI (3867 KB)     
» Media 5: AVI (2205 KB)     
» Media 6: AVI (1959 KB)     
» Media 7: AVI (4147 KB)     

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited