Abstract

Otitis media (OM) is the most common illness in children in the United States. Three-fourths of children under the age of three have OM at least once. Children with chronic OM, including OM with effusion and recurrent OM, will often have conductive hearing loss and communication difficulties, and need surgical treatment. Recent clinical studies provide evidence that almost all chronic OM cases are accompanied by a bacterial biofilm behind the tympanic membrane (eardrum) and within the middle ear. Biofilms are typically very thin, and cannot be recognized using a regular otoscope. Here we demonstrate how optical low coherence interferometry (LCI) noninvasively depth-ranges into the middle ear to detect and quantify biofilm microstructure. A portable diagnostic system integrating LCI with a standard video otoscope was constructed and used to detect and quantify the presence of biofilms in a newly-developed pre-clinical animal model for this condition. Using a novel classification algorithm for acquired LCI data, the system identified the presence of a biofilm with 86% sensitivity and 90% specificity, compared to histological findings. This new information on the presence of a biofilm, its structure, and its response to antibiotic treatment, will not only provide better understanding of fundamental principles that govern biofilm formation, growth, and eradication, but may also provide much needed clinical data to direct and monitor protocols for the successful management of otitis media.

© 2010 OSA

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. J. O. Klein, “Otitis media,” Clin. Infect. Dis. 19(5), 823–833 (1994).
    [PubMed]
  2. J. E. Roberts, R. M. Rosenfeld, and S. A. Zeisel, “Otitis media and speech and language: a meta-analysis of prospective studies,” Pediatrics 113(3), e238–e248 (2004).
    [CrossRef] [PubMed]
  3. S. M. Pransky, “Surgical strategies for otitis media,” J. Otolaryngol. 27(Suppl 2), 37–42 (1998).
    [PubMed]
  4. J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
    [PubMed]
  5. P. Shekelle, G. Takata, L. S. Chan, R. Mangione-Smith, P. M. Corley, T. Morphew, and S. Morton, “Diagnosis, natural history, and late effects of otitis media with effusion,” Agency for Healthcare Research and Quality Publication No. 03–E023 (2003).
  6. P. K. Harris, K. M. Hutchinson, and J. Moravec, “The use of tympanometry and pneumatic otoscopy for predicting middle ear disease,” Am. J. Audiol. 14(1), 3–13 (2005).
    [CrossRef] [PubMed]
  7. L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
    [CrossRef] [PubMed]
  8. J. E. Dohar, P. A. Hebda, R. Veeh, M. Awad, J. W. Costerton, J. Hayes, and G. D. Ehrlich, “Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of chronic suppurative otitis media,” Laryngoscope 115(8), 1469–1472 (2005).
    [CrossRef] [PubMed]
  9. M. Allegrucci, F. Z. Hu, K. Shen, J. Hayes, G. D. Ehrlich, J. C. Post, and K. Sauer, “Phenotypic characterization of Streptococcus pneumoniae biofilm development,” J. Bacteriol. 188(7), 2325–2335 (2006).
    [CrossRef] [PubMed]
  10. C. Potera, “Forging a link between biofilms and disease,” Science 283(5409), 1837–1839, 1839 (1999).
    [CrossRef] [PubMed]
  11. J. W. Costerton, P. S. Stewart, and E. P. Greenberg, “Bacterial biofilms: a common cause of persistent infections,” Science 284(5418), 1318–1322 (1999).
    [CrossRef] [PubMed]
  12. W. Drexler, and J. Fujimoto, Optical Coherence Tomography: Technology and Applications, (Springer, New York, 2008).
  13. A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
    [CrossRef] [PubMed]
  14. C. Pitris, K. T. Saunders, J. G. Fujimoto, and M. E. Brezinski, “High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study,” Arch. Otolaryngol. Head Neck Surg. 127(6), 637–642 (2001).
    [PubMed]
  15. H. R. Djalilian, J. Ridgway, M. Tam, A. Sepehr, Z. Chen, and B. J. Wong, “Imaging the human tympanic membrane using optical coherence tomography in vivo,” Otol. Neurotol. 29(8), 1091–1094 (2008).
    [CrossRef] [PubMed]
  16. C. Xi, D. L. Marks, S. Schlachter, W. Luo, and S. A. Boppart, “High-resolution three-dimensional imaging of biofilm development using optical coherence tomography,” J. Biomed. Opt. 11(3), 034001 (2006).
    [CrossRef] [PubMed]
  17. W. Jung, D. T. McCormick, Y. C. Ahn, A. Sepehr, M. Brenner, B. Wong, N. C. Tien, and Z. Chen, “In vivo three-dimensional spectral domain endoscopic optical coherence tomography using a microelectromechanical system mirror,” Opt. Lett. 32(22), 3239–3241 (2007).
    [CrossRef] [PubMed]
  18. D. T. McCormick, W. Jung, Y. C. Ahn, V. Milanović, Z. Chen, and N. C. Tien, “A MEMS based optical coherence tomography imaging system and optical biopsy probes for real-time, high resolution in-vivo and in-vitro 2-D or 3-D imaging,” in Proceedings of 2006 IEEE/LEOS International Conference on Optical MEMS and their Applications (August 2006) pp. 2.
  19. A. M. Zysk and S. A. Boppart, “Computational methods for analysis of human breast tumor tissue in optical coherence tomography images,” J. Biomed. Opt. 11(5), 054015 (2006).
    [CrossRef] [PubMed]
  20. B. D. Goldberg, N. V. Iftimia, J. E. Bressner, M. B. Pitman, E. Halpern, B. E. Bouma, and G. J. Tearney, “Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance,” J. Biomed. Opt. 13(1), 014014 (2008).
    [CrossRef] [PubMed]
  21. E. L. Tonnaer, E. A. Sanders, and J. H. Curfs, “Bacterial otitis media: a new non-invasive rat model,” Vaccine 21(31), 4539–4544 (2003).
    [CrossRef] [PubMed]
  22. O. B. Piltcher, J. D. Swarts, K. Magnuson, C. M. Alper, W. J. Doyle, and P. A. Hebda, “A rat model of otitis media with effusion caused by eustachian tube obstruction with and without S. pneumoniae infection: Methods and disease course,” Otolaryngol. Head Neck Surg. 126(5), 490–498 (2002).
    [CrossRef] [PubMed]
  23. M. Hoa, M. Syamal, L. Sachdeva, R. Berk, and J. Coticchia, “Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media,” Ann. Otol. Rhinol. Laryngol. 118(4), 292–298 (2009).
    [PubMed]
  24. W. Jung, W. Benalcazar, U. Shamar, A. Ahmad, H. Tu, and S. A. Boppart, “Numerical analysis of GRIN lens-based OCT imaging probes,” J. Biomed. Opt. under review.
  25. J. Canny, “A computational approach to edge detection,” IEEE Trans. Pattern Anal. Mach. Intell. 8(6), 679–698 (1986).
    [CrossRef]
  26. R. Deriche, “Using Canny's criteria to derive a recursively implemented optimal edge detector,” Int. J. Comput. Vis. 1(2), 167–187 (1987).
    [CrossRef]
  27. D. J. Lim, “Structure and function of the tympanic membrane: a review,” Acta Otorhinolaryngol. Belg. 49(2), 101–115 (1995).
    [PubMed]

2009 (1)

M. Hoa, M. Syamal, L. Sachdeva, R. Berk, and J. Coticchia, “Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media,” Ann. Otol. Rhinol. Laryngol. 118(4), 292–298 (2009).
[PubMed]

2008 (2)

H. R. Djalilian, J. Ridgway, M. Tam, A. Sepehr, Z. Chen, and B. J. Wong, “Imaging the human tympanic membrane using optical coherence tomography in vivo,” Otol. Neurotol. 29(8), 1091–1094 (2008).
[CrossRef] [PubMed]

B. D. Goldberg, N. V. Iftimia, J. E. Bressner, M. B. Pitman, E. Halpern, B. E. Bouma, and G. J. Tearney, “Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance,” J. Biomed. Opt. 13(1), 014014 (2008).
[CrossRef] [PubMed]

2007 (2)

W. Jung, D. T. McCormick, Y. C. Ahn, A. Sepehr, M. Brenner, B. Wong, N. C. Tien, and Z. Chen, “In vivo three-dimensional spectral domain endoscopic optical coherence tomography using a microelectromechanical system mirror,” Opt. Lett. 32(22), 3239–3241 (2007).
[CrossRef] [PubMed]

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

2006 (4)

C. Xi, D. L. Marks, S. Schlachter, W. Luo, and S. A. Boppart, “High-resolution three-dimensional imaging of biofilm development using optical coherence tomography,” J. Biomed. Opt. 11(3), 034001 (2006).
[CrossRef] [PubMed]

A. M. Zysk and S. A. Boppart, “Computational methods for analysis of human breast tumor tissue in optical coherence tomography images,” J. Biomed. Opt. 11(5), 054015 (2006).
[CrossRef] [PubMed]

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

M. Allegrucci, F. Z. Hu, K. Shen, J. Hayes, G. D. Ehrlich, J. C. Post, and K. Sauer, “Phenotypic characterization of Streptococcus pneumoniae biofilm development,” J. Bacteriol. 188(7), 2325–2335 (2006).
[CrossRef] [PubMed]

2005 (2)

J. E. Dohar, P. A. Hebda, R. Veeh, M. Awad, J. W. Costerton, J. Hayes, and G. D. Ehrlich, “Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of chronic suppurative otitis media,” Laryngoscope 115(8), 1469–1472 (2005).
[CrossRef] [PubMed]

P. K. Harris, K. M. Hutchinson, and J. Moravec, “The use of tympanometry and pneumatic otoscopy for predicting middle ear disease,” Am. J. Audiol. 14(1), 3–13 (2005).
[CrossRef] [PubMed]

2004 (1)

J. E. Roberts, R. M. Rosenfeld, and S. A. Zeisel, “Otitis media and speech and language: a meta-analysis of prospective studies,” Pediatrics 113(3), e238–e248 (2004).
[CrossRef] [PubMed]

2003 (1)

E. L. Tonnaer, E. A. Sanders, and J. H. Curfs, “Bacterial otitis media: a new non-invasive rat model,” Vaccine 21(31), 4539–4544 (2003).
[CrossRef] [PubMed]

2002 (1)

O. B. Piltcher, J. D. Swarts, K. Magnuson, C. M. Alper, W. J. Doyle, and P. A. Hebda, “A rat model of otitis media with effusion caused by eustachian tube obstruction with and without S. pneumoniae infection: Methods and disease course,” Otolaryngol. Head Neck Surg. 126(5), 490–498 (2002).
[CrossRef] [PubMed]

2001 (1)

C. Pitris, K. T. Saunders, J. G. Fujimoto, and M. E. Brezinski, “High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study,” Arch. Otolaryngol. Head Neck Surg. 127(6), 637–642 (2001).
[PubMed]

1999 (2)

C. Potera, “Forging a link between biofilms and disease,” Science 283(5409), 1837–1839, 1839 (1999).
[CrossRef] [PubMed]

J. W. Costerton, P. S. Stewart, and E. P. Greenberg, “Bacterial biofilms: a common cause of persistent infections,” Science 284(5418), 1318–1322 (1999).
[CrossRef] [PubMed]

1998 (1)

S. M. Pransky, “Surgical strategies for otitis media,” J. Otolaryngol. 27(Suppl 2), 37–42 (1998).
[PubMed]

1997 (1)

J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
[PubMed]

1995 (1)

D. J. Lim, “Structure and function of the tympanic membrane: a review,” Acta Otorhinolaryngol. Belg. 49(2), 101–115 (1995).
[PubMed]

1994 (1)

J. O. Klein, “Otitis media,” Clin. Infect. Dis. 19(5), 823–833 (1994).
[PubMed]

1987 (1)

R. Deriche, “Using Canny's criteria to derive a recursively implemented optimal edge detector,” Int. J. Comput. Vis. 1(2), 167–187 (1987).
[CrossRef]

1986 (1)

J. Canny, “A computational approach to edge detection,” IEEE Trans. Pattern Anal. Mach. Intell. 8(6), 679–698 (1986).
[CrossRef]

Ahmad, A.

W. Jung, W. Benalcazar, U. Shamar, A. Ahmad, H. Tu, and S. A. Boppart, “Numerical analysis of GRIN lens-based OCT imaging probes,” J. Biomed. Opt. under review.

Ahn, Y. C.

Allegrucci, M.

M. Allegrucci, F. Z. Hu, K. Shen, J. Hayes, G. D. Ehrlich, J. C. Post, and K. Sauer, “Phenotypic characterization of Streptococcus pneumoniae biofilm development,” J. Bacteriol. 188(7), 2325–2335 (2006).
[CrossRef] [PubMed]

Alper, C. M.

O. B. Piltcher, J. D. Swarts, K. Magnuson, C. M. Alper, W. J. Doyle, and P. A. Hebda, “A rat model of otitis media with effusion caused by eustachian tube obstruction with and without S. pneumoniae infection: Methods and disease course,” Otolaryngol. Head Neck Surg. 126(5), 490–498 (2002).
[CrossRef] [PubMed]

Awad, M.

J. E. Dohar, P. A. Hebda, R. Veeh, M. Awad, J. W. Costerton, J. Hayes, and G. D. Ehrlich, “Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of chronic suppurative otitis media,” Laryngoscope 115(8), 1469–1472 (2005).
[CrossRef] [PubMed]

Benalcazar, W.

W. Jung, W. Benalcazar, U. Shamar, A. Ahmad, H. Tu, and S. A. Boppart, “Numerical analysis of GRIN lens-based OCT imaging probes,” J. Biomed. Opt. under review.

Berk, R.

M. Hoa, M. Syamal, L. Sachdeva, R. Berk, and J. Coticchia, “Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media,” Ann. Otol. Rhinol. Laryngol. 118(4), 292–298 (2009).
[PubMed]

Boppart, S. A.

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

C. Xi, D. L. Marks, S. Schlachter, W. Luo, and S. A. Boppart, “High-resolution three-dimensional imaging of biofilm development using optical coherence tomography,” J. Biomed. Opt. 11(3), 034001 (2006).
[CrossRef] [PubMed]

A. M. Zysk and S. A. Boppart, “Computational methods for analysis of human breast tumor tissue in optical coherence tomography images,” J. Biomed. Opt. 11(5), 054015 (2006).
[CrossRef] [PubMed]

W. Jung, W. Benalcazar, U. Shamar, A. Ahmad, H. Tu, and S. A. Boppart, “Numerical analysis of GRIN lens-based OCT imaging probes,” J. Biomed. Opt. under review.

Bouma, B. E.

B. D. Goldberg, N. V. Iftimia, J. E. Bressner, M. B. Pitman, E. Halpern, B. E. Bouma, and G. J. Tearney, “Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance,” J. Biomed. Opt. 13(1), 014014 (2008).
[CrossRef] [PubMed]

Brenner, M.

Bressner, J. E.

B. D. Goldberg, N. V. Iftimia, J. E. Bressner, M. B. Pitman, E. Halpern, B. E. Bouma, and G. J. Tearney, “Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance,” J. Biomed. Opt. 13(1), 014014 (2008).
[CrossRef] [PubMed]

Brezinski, M. E.

C. Pitris, K. T. Saunders, J. G. Fujimoto, and M. E. Brezinski, “High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study,” Arch. Otolaryngol. Head Neck Surg. 127(6), 637–642 (2001).
[PubMed]

Burrows, A.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Canny, J.

J. Canny, “A computational approach to edge detection,” IEEE Trans. Pattern Anal. Mach. Intell. 8(6), 679–698 (1986).
[CrossRef]

Chen, Z.

H. R. Djalilian, J. Ridgway, M. Tam, A. Sepehr, Z. Chen, and B. J. Wong, “Imaging the human tympanic membrane using optical coherence tomography in vivo,” Otol. Neurotol. 29(8), 1091–1094 (2008).
[CrossRef] [PubMed]

W. Jung, D. T. McCormick, Y. C. Ahn, A. Sepehr, M. Brenner, B. Wong, N. C. Tien, and Z. Chen, “In vivo three-dimensional spectral domain endoscopic optical coherence tomography using a microelectromechanical system mirror,” Opt. Lett. 32(22), 3239–3241 (2007).
[CrossRef] [PubMed]

Costerton, J. W.

J. E. Dohar, P. A. Hebda, R. Veeh, M. Awad, J. W. Costerton, J. Hayes, and G. D. Ehrlich, “Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of chronic suppurative otitis media,” Laryngoscope 115(8), 1469–1472 (2005).
[CrossRef] [PubMed]

J. W. Costerton, P. S. Stewart, and E. P. Greenberg, “Bacterial biofilms: a common cause of persistent infections,” Science 284(5418), 1318–1322 (1999).
[CrossRef] [PubMed]

Coticchia, J.

M. Hoa, M. Syamal, L. Sachdeva, R. Berk, and J. Coticchia, “Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media,” Ann. Otol. Rhinol. Laryngol. 118(4), 292–298 (2009).
[PubMed]

Culpepper, L.

J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
[PubMed]

Curfs, J. H.

E. L. Tonnaer, E. A. Sanders, and J. H. Curfs, “Bacterial otitis media: a new non-invasive rat model,” Vaccine 21(31), 4539–4544 (2003).
[CrossRef] [PubMed]

DeMelker, R. A.

J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
[PubMed]

Deriche, R.

R. Deriche, “Using Canny's criteria to derive a recursively implemented optimal edge detector,” Int. J. Comput. Vis. 1(2), 167–187 (1987).
[CrossRef]

Dice, B.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Djalilian, H. R.

H. R. Djalilian, J. Ridgway, M. Tam, A. Sepehr, Z. Chen, and B. J. Wong, “Imaging the human tympanic membrane using optical coherence tomography in vivo,” Otol. Neurotol. 29(8), 1091–1094 (2008).
[CrossRef] [PubMed]

Dohar, J. E.

J. E. Dohar, P. A. Hebda, R. Veeh, M. Awad, J. W. Costerton, J. Hayes, and G. D. Ehrlich, “Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of chronic suppurative otitis media,” Laryngoscope 115(8), 1469–1472 (2005).
[CrossRef] [PubMed]

Doyle, W. J.

O. B. Piltcher, J. D. Swarts, K. Magnuson, C. M. Alper, W. J. Doyle, and P. A. Hebda, “A rat model of otitis media with effusion caused by eustachian tube obstruction with and without S. pneumoniae infection: Methods and disease course,” Otolaryngol. Head Neck Surg. 126(5), 490–498 (2002).
[CrossRef] [PubMed]

Ehrlich, G. D.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

M. Allegrucci, F. Z. Hu, K. Shen, J. Hayes, G. D. Ehrlich, J. C. Post, and K. Sauer, “Phenotypic characterization of Streptococcus pneumoniae biofilm development,” J. Bacteriol. 188(7), 2325–2335 (2006).
[CrossRef] [PubMed]

J. E. Dohar, P. A. Hebda, R. Veeh, M. Awad, J. W. Costerton, J. Hayes, and G. D. Ehrlich, “Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of chronic suppurative otitis media,” Laryngoscope 115(8), 1469–1472 (2005).
[CrossRef] [PubMed]

Forbes, M.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Froom, J.

J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
[PubMed]

Fujimoto, J. G.

C. Pitris, K. T. Saunders, J. G. Fujimoto, and M. E. Brezinski, “High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study,” Arch. Otolaryngol. Head Neck Surg. 127(6), 637–642 (2001).
[PubMed]

Gieseke, A.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Goldberg, B. D.

B. D. Goldberg, N. V. Iftimia, J. E. Bressner, M. B. Pitman, E. Halpern, B. E. Bouma, and G. J. Tearney, “Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance,” J. Biomed. Opt. 13(1), 014014 (2008).
[CrossRef] [PubMed]

Green, L. A.

J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
[PubMed]

Greenberg, D. P.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Greenberg, E. P.

J. W. Costerton, P. S. Stewart, and E. P. Greenberg, “Bacterial biofilms: a common cause of persistent infections,” Science 284(5418), 1318–1322 (1999).
[CrossRef] [PubMed]

Grob, P.

J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
[PubMed]

Hall-Stoodley, L.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Halpern, E.

B. D. Goldberg, N. V. Iftimia, J. E. Bressner, M. B. Pitman, E. Halpern, B. E. Bouma, and G. J. Tearney, “Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance,” J. Biomed. Opt. 13(1), 014014 (2008).
[CrossRef] [PubMed]

Harris, P. K.

P. K. Harris, K. M. Hutchinson, and J. Moravec, “The use of tympanometry and pneumatic otoscopy for predicting middle ear disease,” Am. J. Audiol. 14(1), 3–13 (2005).
[CrossRef] [PubMed]

Hayes, J.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

M. Allegrucci, F. Z. Hu, K. Shen, J. Hayes, G. D. Ehrlich, J. C. Post, and K. Sauer, “Phenotypic characterization of Streptococcus pneumoniae biofilm development,” J. Bacteriol. 188(7), 2325–2335 (2006).
[CrossRef] [PubMed]

J. E. Dohar, P. A. Hebda, R. Veeh, M. Awad, J. W. Costerton, J. Hayes, and G. D. Ehrlich, “Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of chronic suppurative otitis media,” Laryngoscope 115(8), 1469–1472 (2005).
[CrossRef] [PubMed]

Hebda, P. A.

J. E. Dohar, P. A. Hebda, R. Veeh, M. Awad, J. W. Costerton, J. Hayes, and G. D. Ehrlich, “Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of chronic suppurative otitis media,” Laryngoscope 115(8), 1469–1472 (2005).
[CrossRef] [PubMed]

O. B. Piltcher, J. D. Swarts, K. Magnuson, C. M. Alper, W. J. Doyle, and P. A. Hebda, “A rat model of otitis media with effusion caused by eustachian tube obstruction with and without S. pneumoniae infection: Methods and disease course,” Otolaryngol. Head Neck Surg. 126(5), 490–498 (2002).
[CrossRef] [PubMed]

Heeren, T.

J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
[PubMed]

Hoa, M.

M. Hoa, M. Syamal, L. Sachdeva, R. Berk, and J. Coticchia, “Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media,” Ann. Otol. Rhinol. Laryngol. 118(4), 292–298 (2009).
[PubMed]

Hu, F. Z.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

M. Allegrucci, F. Z. Hu, K. Shen, J. Hayes, G. D. Ehrlich, J. C. Post, and K. Sauer, “Phenotypic characterization of Streptococcus pneumoniae biofilm development,” J. Bacteriol. 188(7), 2325–2335 (2006).
[CrossRef] [PubMed]

Hutchinson, K. M.

P. K. Harris, K. M. Hutchinson, and J. Moravec, “The use of tympanometry and pneumatic otoscopy for predicting middle ear disease,” Am. J. Audiol. 14(1), 3–13 (2005).
[CrossRef] [PubMed]

Iftimia, N. V.

B. D. Goldberg, N. V. Iftimia, J. E. Bressner, M. B. Pitman, E. Halpern, B. E. Bouma, and G. J. Tearney, “Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance,” J. Biomed. Opt. 13(1), 014014 (2008).
[CrossRef] [PubMed]

Jacobs, M.

J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
[PubMed]

Jung, W.

Kerschner, J. E.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Klein, J. O.

J. O. Klein, “Otitis media,” Clin. Infect. Dis. 19(5), 823–833 (1994).
[PubMed]

Lim, D. J.

D. J. Lim, “Structure and function of the tympanic membrane: a review,” Acta Otorhinolaryngol. Belg. 49(2), 101–115 (1995).
[PubMed]

Luo, W.

C. Xi, D. L. Marks, S. Schlachter, W. Luo, and S. A. Boppart, “High-resolution three-dimensional imaging of biofilm development using optical coherence tomography,” J. Biomed. Opt. 11(3), 034001 (2006).
[CrossRef] [PubMed]

Magnuson, K.

O. B. Piltcher, J. D. Swarts, K. Magnuson, C. M. Alper, W. J. Doyle, and P. A. Hebda, “A rat model of otitis media with effusion caused by eustachian tube obstruction with and without S. pneumoniae infection: Methods and disease course,” Otolaryngol. Head Neck Surg. 126(5), 490–498 (2002).
[CrossRef] [PubMed]

Marks, D. L.

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

C. Xi, D. L. Marks, S. Schlachter, W. Luo, and S. A. Boppart, “High-resolution three-dimensional imaging of biofilm development using optical coherence tomography,” J. Biomed. Opt. 11(3), 034001 (2006).
[CrossRef] [PubMed]

McCormick, D. T.

Moravec, J.

P. K. Harris, K. M. Hutchinson, and J. Moravec, “The use of tympanometry and pneumatic otoscopy for predicting middle ear disease,” Am. J. Audiol. 14(1), 3–13 (2005).
[CrossRef] [PubMed]

Nguyen, D.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Nguyen, F. T.

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

Nistico, L.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Oldenburg, A. L.

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

Piltcher, O. B.

O. B. Piltcher, J. D. Swarts, K. Magnuson, C. M. Alper, W. J. Doyle, and P. A. Hebda, “A rat model of otitis media with effusion caused by eustachian tube obstruction with and without S. pneumoniae infection: Methods and disease course,” Otolaryngol. Head Neck Surg. 126(5), 490–498 (2002).
[CrossRef] [PubMed]

Pitman, M. B.

B. D. Goldberg, N. V. Iftimia, J. E. Bressner, M. B. Pitman, E. Halpern, B. E. Bouma, and G. J. Tearney, “Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance,” J. Biomed. Opt. 13(1), 014014 (2008).
[CrossRef] [PubMed]

Pitris, C.

C. Pitris, K. T. Saunders, J. G. Fujimoto, and M. E. Brezinski, “High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study,” Arch. Otolaryngol. Head Neck Surg. 127(6), 637–642 (2001).
[PubMed]

Post, J. C.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

M. Allegrucci, F. Z. Hu, K. Shen, J. Hayes, G. D. Ehrlich, J. C. Post, and K. Sauer, “Phenotypic characterization of Streptococcus pneumoniae biofilm development,” J. Bacteriol. 188(7), 2325–2335 (2006).
[CrossRef] [PubMed]

Potera, C.

C. Potera, “Forging a link between biofilms and disease,” Science 283(5409), 1837–1839, 1839 (1999).
[CrossRef] [PubMed]

Pransky, S. M.

S. M. Pransky, “Surgical strategies for otitis media,” J. Otolaryngol. 27(Suppl 2), 37–42 (1998).
[PubMed]

Ridgway, J.

H. R. Djalilian, J. Ridgway, M. Tam, A. Sepehr, Z. Chen, and B. J. Wong, “Imaging the human tympanic membrane using optical coherence tomography in vivo,” Otol. Neurotol. 29(8), 1091–1094 (2008).
[CrossRef] [PubMed]

Roberts, J. E.

J. E. Roberts, R. M. Rosenfeld, and S. A. Zeisel, “Otitis media and speech and language: a meta-analysis of prospective studies,” Pediatrics 113(3), e238–e248 (2004).
[CrossRef] [PubMed]

Rosenfeld, R. M.

J. E. Roberts, R. M. Rosenfeld, and S. A. Zeisel, “Otitis media and speech and language: a meta-analysis of prospective studies,” Pediatrics 113(3), e238–e248 (2004).
[CrossRef] [PubMed]

Sachdeva, L.

M. Hoa, M. Syamal, L. Sachdeva, R. Berk, and J. Coticchia, “Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media,” Ann. Otol. Rhinol. Laryngol. 118(4), 292–298 (2009).
[PubMed]

Sanders, E. A.

E. L. Tonnaer, E. A. Sanders, and J. H. Curfs, “Bacterial otitis media: a new non-invasive rat model,” Vaccine 21(31), 4539–4544 (2003).
[CrossRef] [PubMed]

Sauer, K.

M. Allegrucci, F. Z. Hu, K. Shen, J. Hayes, G. D. Ehrlich, J. C. Post, and K. Sauer, “Phenotypic characterization of Streptococcus pneumoniae biofilm development,” J. Bacteriol. 188(7), 2325–2335 (2006).
[CrossRef] [PubMed]

Saunders, K. T.

C. Pitris, K. T. Saunders, J. G. Fujimoto, and M. E. Brezinski, “High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study,” Arch. Otolaryngol. Head Neck Surg. 127(6), 637–642 (2001).
[PubMed]

Schlachter, S.

C. Xi, D. L. Marks, S. Schlachter, W. Luo, and S. A. Boppart, “High-resolution three-dimensional imaging of biofilm development using optical coherence tomography,” J. Biomed. Opt. 11(3), 034001 (2006).
[CrossRef] [PubMed]

Sepehr, A.

H. R. Djalilian, J. Ridgway, M. Tam, A. Sepehr, Z. Chen, and B. J. Wong, “Imaging the human tympanic membrane using optical coherence tomography in vivo,” Otol. Neurotol. 29(8), 1091–1094 (2008).
[CrossRef] [PubMed]

W. Jung, D. T. McCormick, Y. C. Ahn, A. Sepehr, M. Brenner, B. Wong, N. C. Tien, and Z. Chen, “In vivo three-dimensional spectral domain endoscopic optical coherence tomography using a microelectromechanical system mirror,” Opt. Lett. 32(22), 3239–3241 (2007).
[CrossRef] [PubMed]

Shamar, U.

W. Jung, W. Benalcazar, U. Shamar, A. Ahmad, H. Tu, and S. A. Boppart, “Numerical analysis of GRIN lens-based OCT imaging probes,” J. Biomed. Opt. under review.

Shen, K.

M. Allegrucci, F. Z. Hu, K. Shen, J. Hayes, G. D. Ehrlich, J. C. Post, and K. Sauer, “Phenotypic characterization of Streptococcus pneumoniae biofilm development,” J. Bacteriol. 188(7), 2325–2335 (2006).
[CrossRef] [PubMed]

Stewart, P. S.

J. W. Costerton, P. S. Stewart, and E. P. Greenberg, “Bacterial biofilms: a common cause of persistent infections,” Science 284(5418), 1318–1322 (1999).
[CrossRef] [PubMed]

Stoodley, P.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Swarts, J. D.

O. B. Piltcher, J. D. Swarts, K. Magnuson, C. M. Alper, W. J. Doyle, and P. A. Hebda, “A rat model of otitis media with effusion caused by eustachian tube obstruction with and without S. pneumoniae infection: Methods and disease course,” Otolaryngol. Head Neck Surg. 126(5), 490–498 (2002).
[CrossRef] [PubMed]

Syamal, M.

M. Hoa, M. Syamal, L. Sachdeva, R. Berk, and J. Coticchia, “Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media,” Ann. Otol. Rhinol. Laryngol. 118(4), 292–298 (2009).
[PubMed]

Tam, M.

H. R. Djalilian, J. Ridgway, M. Tam, A. Sepehr, Z. Chen, and B. J. Wong, “Imaging the human tympanic membrane using optical coherence tomography in vivo,” Otol. Neurotol. 29(8), 1091–1094 (2008).
[CrossRef] [PubMed]

Tearney, G. J.

B. D. Goldberg, N. V. Iftimia, J. E. Bressner, M. B. Pitman, E. Halpern, B. E. Bouma, and G. J. Tearney, “Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance,” J. Biomed. Opt. 13(1), 014014 (2008).
[CrossRef] [PubMed]

Tien, N. C.

Tonnaer, E. L.

E. L. Tonnaer, E. A. Sanders, and J. H. Curfs, “Bacterial otitis media: a new non-invasive rat model,” Vaccine 21(31), 4539–4544 (2003).
[CrossRef] [PubMed]

Tu, H.

W. Jung, W. Benalcazar, U. Shamar, A. Ahmad, H. Tu, and S. A. Boppart, “Numerical analysis of GRIN lens-based OCT imaging probes,” J. Biomed. Opt. under review.

van Buchem, L.

J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
[PubMed]

Veeh, R.

J. E. Dohar, P. A. Hebda, R. Veeh, M. Awad, J. W. Costerton, J. Hayes, and G. D. Ehrlich, “Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of chronic suppurative otitis media,” Laryngoscope 115(8), 1469–1472 (2005).
[CrossRef] [PubMed]

Wackym, P. A.

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Wong, B.

Wong, B. J.

H. R. Djalilian, J. Ridgway, M. Tam, A. Sepehr, Z. Chen, and B. J. Wong, “Imaging the human tympanic membrane using optical coherence tomography in vivo,” Otol. Neurotol. 29(8), 1091–1094 (2008).
[CrossRef] [PubMed]

Xi, C.

C. Xi, D. L. Marks, S. Schlachter, W. Luo, and S. A. Boppart, “High-resolution three-dimensional imaging of biofilm development using optical coherence tomography,” J. Biomed. Opt. 11(3), 034001 (2006).
[CrossRef] [PubMed]

Zeisel, S. A.

J. E. Roberts, R. M. Rosenfeld, and S. A. Zeisel, “Otitis media and speech and language: a meta-analysis of prospective studies,” Pediatrics 113(3), e238–e248 (2004).
[CrossRef] [PubMed]

Zysk, A. M.

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

A. M. Zysk and S. A. Boppart, “Computational methods for analysis of human breast tumor tissue in optical coherence tomography images,” J. Biomed. Opt. 11(5), 054015 (2006).
[CrossRef] [PubMed]

Acta Otorhinolaryngol. Belg. (1)

D. J. Lim, “Structure and function of the tympanic membrane: a review,” Acta Otorhinolaryngol. Belg. 49(2), 101–115 (1995).
[PubMed]

Am. J. Audiol. (1)

P. K. Harris, K. M. Hutchinson, and J. Moravec, “The use of tympanometry and pneumatic otoscopy for predicting middle ear disease,” Am. J. Audiol. 14(1), 3–13 (2005).
[CrossRef] [PubMed]

Ann. Otol. Rhinol. Laryngol. (1)

M. Hoa, M. Syamal, L. Sachdeva, R. Berk, and J. Coticchia, “Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media,” Ann. Otol. Rhinol. Laryngol. 118(4), 292–298 (2009).
[PubMed]

Arch. Otolaryngol. Head Neck Surg. (1)

C. Pitris, K. T. Saunders, J. G. Fujimoto, and M. E. Brezinski, “High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study,” Arch. Otolaryngol. Head Neck Surg. 127(6), 637–642 (2001).
[PubMed]

BMJ (1)

J. Froom, L. Culpepper, M. Jacobs, R. A. DeMelker, L. A. Green, L. van Buchem, P. Grob, and T. Heeren, “Antimicrobials for acute otitis media? A review from the International Primary Care Network,” BMJ 315(7100), 98–102 (1997).
[PubMed]

Clin. Infect. Dis. (1)

J. O. Klein, “Otitis media,” Clin. Infect. Dis. 19(5), 823–833 (1994).
[PubMed]

IEEE Trans. Pattern Anal. Mach. Intell. (1)

J. Canny, “A computational approach to edge detection,” IEEE Trans. Pattern Anal. Mach. Intell. 8(6), 679–698 (1986).
[CrossRef]

Int. J. Comput. Vis. (1)

R. Deriche, “Using Canny's criteria to derive a recursively implemented optimal edge detector,” Int. J. Comput. Vis. 1(2), 167–187 (1987).
[CrossRef]

J. Bacteriol. (1)

M. Allegrucci, F. Z. Hu, K. Shen, J. Hayes, G. D. Ehrlich, J. C. Post, and K. Sauer, “Phenotypic characterization of Streptococcus pneumoniae biofilm development,” J. Bacteriol. 188(7), 2325–2335 (2006).
[CrossRef] [PubMed]

J. Biomed. Opt. (5)

C. Xi, D. L. Marks, S. Schlachter, W. Luo, and S. A. Boppart, “High-resolution three-dimensional imaging of biofilm development using optical coherence tomography,” J. Biomed. Opt. 11(3), 034001 (2006).
[CrossRef] [PubMed]

A. M. Zysk, F. T. Nguyen, A. L. Oldenburg, D. L. Marks, and S. A. Boppart, “Optical coherence tomography: a review of clinical development from bench to bedside,” J. Biomed. Opt. 12(5), 051403 (2007).
[CrossRef] [PubMed]

W. Jung, W. Benalcazar, U. Shamar, A. Ahmad, H. Tu, and S. A. Boppart, “Numerical analysis of GRIN lens-based OCT imaging probes,” J. Biomed. Opt. under review.

A. M. Zysk and S. A. Boppart, “Computational methods for analysis of human breast tumor tissue in optical coherence tomography images,” J. Biomed. Opt. 11(5), 054015 (2006).
[CrossRef] [PubMed]

B. D. Goldberg, N. V. Iftimia, J. E. Bressner, M. B. Pitman, E. Halpern, B. E. Bouma, and G. J. Tearney, “Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance,” J. Biomed. Opt. 13(1), 014014 (2008).
[CrossRef] [PubMed]

J. Otolaryngol. (1)

S. M. Pransky, “Surgical strategies for otitis media,” J. Otolaryngol. 27(Suppl 2), 37–42 (1998).
[PubMed]

JAMA (1)

L. Hall-Stoodley, F. Z. Hu, A. Gieseke, L. Nistico, D. Nguyen, J. Hayes, M. Forbes, D. P. Greenberg, B. Dice, A. Burrows, P. A. Wackym, P. Stoodley, J. C. Post, G. D. Ehrlich, and J. E. Kerschner, “Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media,” JAMA 296(2), 202–211 (2006).
[CrossRef] [PubMed]

Laryngoscope (1)

J. E. Dohar, P. A. Hebda, R. Veeh, M. Awad, J. W. Costerton, J. Hayes, and G. D. Ehrlich, “Mucosal biofilm formation on middle-ear mucosa in a nonhuman primate model of chronic suppurative otitis media,” Laryngoscope 115(8), 1469–1472 (2005).
[CrossRef] [PubMed]

Opt. Lett. (1)

Otol. Neurotol. (1)

H. R. Djalilian, J. Ridgway, M. Tam, A. Sepehr, Z. Chen, and B. J. Wong, “Imaging the human tympanic membrane using optical coherence tomography in vivo,” Otol. Neurotol. 29(8), 1091–1094 (2008).
[CrossRef] [PubMed]

Otolaryngol. Head Neck Surg. (1)

O. B. Piltcher, J. D. Swarts, K. Magnuson, C. M. Alper, W. J. Doyle, and P. A. Hebda, “A rat model of otitis media with effusion caused by eustachian tube obstruction with and without S. pneumoniae infection: Methods and disease course,” Otolaryngol. Head Neck Surg. 126(5), 490–498 (2002).
[CrossRef] [PubMed]

Pediatrics (1)

J. E. Roberts, R. M. Rosenfeld, and S. A. Zeisel, “Otitis media and speech and language: a meta-analysis of prospective studies,” Pediatrics 113(3), e238–e248 (2004).
[CrossRef] [PubMed]

Science (2)

C. Potera, “Forging a link between biofilms and disease,” Science 283(5409), 1837–1839, 1839 (1999).
[CrossRef] [PubMed]

J. W. Costerton, P. S. Stewart, and E. P. Greenberg, “Bacterial biofilms: a common cause of persistent infections,” Science 284(5418), 1318–1322 (1999).
[CrossRef] [PubMed]

Vaccine (1)

E. L. Tonnaer, E. A. Sanders, and J. H. Curfs, “Bacterial otitis media: a new non-invasive rat model,” Vaccine 21(31), 4539–4544 (2003).
[CrossRef] [PubMed]

Other (3)

W. Drexler, and J. Fujimoto, Optical Coherence Tomography: Technology and Applications, (Springer, New York, 2008).

P. Shekelle, G. Takata, L. S. Chan, R. Mangione-Smith, P. M. Corley, T. Morphew, and S. Morton, “Diagnosis, natural history, and late effects of otitis media with effusion,” Agency for Healthcare Research and Quality Publication No. 03–E023 (2003).

D. T. McCormick, W. Jung, Y. C. Ahn, V. Milanović, Z. Chen, and N. C. Tien, “A MEMS based optical coherence tomography imaging system and optical biopsy probes for real-time, high resolution in-vivo and in-vitro 2-D or 3-D imaging,” in Proceedings of 2006 IEEE/LEOS International Conference on Optical MEMS and their Applications (August 2006) pp. 2.

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (5)

Fig. 1
Fig. 1

Portable LCI otoscope system. (a) Diagram and (b) photograph of the portable system. (c,d) Integration of the LCI fiber-based micro-optic probe into the otoscope head. (e) Schematic and beam profile of the long working distance LCI probe.

Fig. 2
Fig. 2

Signal processing flow-chart for the axial scan classification algorithm.

Fig. 3
Fig. 3

Typical in vivo data of normal rat TM acquired with LCI otoscope system. (a) Video image of middle ear. (b) LCI axial scan of TM. (c) Validation data from 2-D OCT image acquired ex vivo. (d) Corresponding histology (M, Malleus). The thin membrane is representative of the TMs from normal rats.

Fig. 4
Fig. 4

Typical in vivo data of infected rat TM acquired with LCI otoscope system. (a) Video image of middle ear. (b) LCI axial scan of TM. (c) Validation data from 2-D OCT image acquired ex vivo. (d) Corresponding histology. Note the increased thickness of the TM and biofilm structures in LCI, OCT, and histology images (blue arrows). The prominent areas with TM perforations filled by blood, as seen in (a), are also recognized in OCT and histology (red squares).

Fig. 5
Fig. 5

Acquired and classified axial scan data represented by thickness and intensity. Acquired (a) ex vivo OCT data and (c) in vivo LCI data. Classified (b) ex vivo OCT data and (d) in vivo LCI data, the cross symbols represent the misclassified axial scans.

Metrics