Abstract

Optical coherence microscopy (OCM) is a promising technique for high resolution cellular imaging in human tissues. An OCM system for high-speed en face cellular resolution imaging was developed at 1060 nm wavelength at frame rates up to 5 Hz with resolutions of < 4 µm axial and < 2 µm transverse. The system utilized a novel polarization compensation method to combat wavelength dependent source polarization and achieve broadband electro-optic phase modulation compatible with ultrahigh axial resolution. In addition, the system incorporated an auto-focusing feature that enables precise, near real-time alignment of the confocal and coherence gates in tissue, allowing user-friendly optimization of image quality during the imaging procedure. Ex vivo cellular images of human esophagus, colon, and cervix as well as in vivo results from human skin are presented. Finally, the system design is demonstrated with a miniaturized piezoelectric fiber-scanning probe which can be adapted for laparoscopic and endoscopic imaging applications.

© 2010 OSA

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2008 (1)

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc. 68(4), 737–744 (2008).
[CrossRef] [PubMed]

2007 (7)

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol. 5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

S. W. Huang, A. D. Aguirre, R. A. Huber, D. C. Adler, and J. G. Fujimoto, “Swept source optical coherence microscopy using a Fourier domain mode-locked laser,” Opt. Express 15(10), 6210–6217 (2007).
[CrossRef] [PubMed]

Y. Chen, S. W. Huang, A. D. Aguirre, and J. G. Fujimoto, “High-resolution line-scanning optical coherence microscopy,” Opt. Lett. 32(14), 1971–1973 (2007).
[CrossRef] [PubMed]

A. D. Aguirre, P. R. Hertz, Y. Chen, J. G. Fujimoto, W. Piyawattanametha, L. Fan, and M. C. Wu, “Two-axis MEMS scanning catheter for ultrahigh resolution three-dimensional and en face imaging,” Opt. Express 15(5), 2445–2453 (2007).
[CrossRef] [PubMed]

J. T. Liu, M. J. Mandella, H. Ra, L. K. Wong, O. Solgaard, G. S. Kino, W. Piyawattanametha, C. H. Contag, and T. D. Wang, “Miniature near-infrared dual-axes confocal microscope utilizing a two-dimensional microelectromechanical systems scanner,” Opt. Lett. 32(3), 256–258 (2007).
[CrossRef] [PubMed]

K. H. Kim, B. H. Park, G. N. Maguluri, T. W. Lee, F. J. Rogomentich, M. G. Bancu, B. E. Bouma, J. F. de Boer, and J. J. Bernstein, “Two-axis magnetically-driven MEMS scanning catheter for endoscopic high-speed optical coherence tomography,” Opt. Express 15(26), 18130–18140 (2007).
[CrossRef] [PubMed]

J. Sawinski and W. Denk, “Miniature random-access fiber scanner for in vivo multiphoton imaging,” J. Appl. Phys. 102(3), 034701 (2007).
[CrossRef]

2006 (6)

2005 (4)

2004 (10)

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology 127(3), 706–713 (2004).
[CrossRef] [PubMed]

T. M. Fortier, S. T. Cundiff, I. T. Lima, B. S. Marks, C. R. Menyuk, and R. S. Windeler, “Nonlinear polarization evolution of ultrashort pulses in microstructure fiber,” Opt. Lett. 29(21), 2548–2550 (2004).
[CrossRef] [PubMed]

Z. M. Zhu and T. G. Brown, “Polarization properties of supercontinuum spectra generated in birefringent photonic crystal fibers,” J. Opt. Soc. Am. B 21(2), 249–257 (2004).
[CrossRef]

B. Qi, A. P. Himmer, L. M. Gordon, X. D. V. Yang, L. D. Dickensheets, and I. A. Vitkin, “Dynamic focus control in high-speed optical coherence tomography based on a microelectromechanical mirror,” Opt. Commun. 232(1-6), 123–128 (2004).
[CrossRef]

A. R. Rouse, A. Kano, J. A. Udovich, S. M. Kroto, and A. F. Gmitro, “Design and demonstration of a miniature catheter for a confocal microendoscope,” Appl. Opt. 43(31), 5763–5771 (2004).
[CrossRef] [PubMed]

A. Jain, A. Kopa, Y. T. Pan, G. K. Fedder, and H. K. Xie, “A two-axis electrothermal micromirror for endoscopic optical coherence tomography,” IEEE J. Sel. Top. Quan. Electron. 10(3), 636–642 (2004).
[CrossRef]

A. Dubois, K. Grieve, G. Moneron, R. Lecaque, L. Vabre, and C. Boccara, “Ultrahigh-resolution full-field optical coherence tomography,” Appl. Opt. 43(14), 2874–2883 (2004).
[CrossRef] [PubMed]

Y. C. Chen and X. D. Li, “Dispersion management up to the third order for real-time optical coherence tomography involving a phase or frequency modulator,” Opt. Express 12(24), 5968–5978 (2004).
[CrossRef] [PubMed]

A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
[CrossRef] [PubMed]

B. M. Hoeling, M. E. Peter, D. C. Petersen, and R. C. Haskell, “Improved phase modulation for an en-face scanning three-dimensional optical coherence microscope,” Rev. Sci. Instrum. 75(10), 3348–3350 (2004).
[CrossRef]

2003 (7)

A. D. Aguirre, P. Hsiung, T. H. Ko, I. Hartl, and J. G. Fujimoto, “High-resolution optical coherence microscopy for high-speed, in vivo cellular imaging,” Opt. Lett. 28(21), 2064–2066 (2003).
[CrossRef] [PubMed]

H. Miyajima, N. Asaoka, T. Isokawa, M. Ogata, Y. Aoki, M. Imai, O. Fujimori, M. Katashiro, and K. Matsumoto, “A MEMS electromagnetic optical scanner for a commercial confocal laser scanning microscope,” J. Microelectromech. Syst. 12(3), 243–251 (2003).
[CrossRef]

J. M. Zara, S. Yazdanfar, K. D. Rao, J. A. Izatt, and S. W. Smith, “Electrostatic micromachine scanning mirror for optical coherence tomography,” Opt. Lett. 28(8), 628–630 (2003).
[CrossRef] [PubMed]

C. K. Hitzenberger, P. Trost, P. W. Lo, and Q. Y. Zhou, “Three-dimensional imaging of the human retina by high-speed optical coherence tomography,” Opt. Express 11(21), 2753–2761 (2003).
[CrossRef] [PubMed]

T. Q. Xie, Z. G. Wang, and Y. T. Pan, “High-speed optical coherence tomography using fiberoptic acousto-optic phase modulation,” Opt. Express 11(24), 3210–3219 (2003).
[CrossRef] [PubMed]

A. V. Zvyagin, E. D. Smith, and D. D. Sampson, “Delay and dispersion characteristics of a frequency-domain optical delay line for scanning interferometry,” J. Opt. Soc. Am. A 20(2), 333–341 (2003).
[CrossRef]

S. Bourquin, A. D. Aguirre, I. Hartl, P. Hsiung, T. H. Ko, J. G. Fujimoto, T. A. Birks, W. J. Wadsworth, U. Bünting, and D. Kopf, “Ultrahigh resolution real time OCT imaging using a compact femtosecond Nd:Glass laser and nonlinear fiber,” Opt. Express 11(24), 3290–3297 (2003).
[CrossRef] [PubMed]

2002 (2)

A. E. Willner, “Chromatic dispersion and polarization-mode dispersion: managing key limitations in optical communication systems,” Opt. Photon. News 13, 16–21 (2002).

V. Westphal, S. Yazdanfar, A. M. Rollins, and J. A. Izatt, “Real-time, high velocity-resolution color Doppler optical coherence tomography,” Opt. Lett. 27(1), 34–36 (2002).
[CrossRef]

2001 (3)

2000 (2)

1999 (1)

F. Lexer, C. K. Hitzenberger, W. Drexler, S. Molebny, H. Sattmann, M. Sticker, and A. F. Fercher, “Dynamic coherent focus OCT with depth-independent transversal resolution,” J. Mod. Opt. 46, 541–553 (1999).

1998 (1)

D. L. Dickensheets and G. S. Kino, “Silicon-micromachined scanning confocal optical microscope,” J. Microelectromech. Syst. 7(1), 38–47 (1998).
[CrossRef]

1997 (3)

1996 (2)

M. Kempe, W. Rudolph, and E. Welsch, “Comparative study of confocal and heterodyne microscopy for imaging through scattering media,” J. Opt. Soc. Am. A 13(1), 46–52 (1996).
[CrossRef]

J. A. Izatt, M. D. Kulkarni, H.-W. Wang, K. Kobayashi, and M. V. Sivak., “Optical coherence tomography and microscopy in gastrointestinal tissues,” IEEE J. Sel. Top. Quan. Electron. 2(4), 1017–1028 (1996).
[CrossRef]

1995 (1)

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo Confocal Scanning Laser Microscopy of Human Skin: Melanin Provides Strong Contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

1994 (1)

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Adler, D. C.

Aguirre, A. D.

Alizadeh-Naderi, R.

A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
[CrossRef] [PubMed]

Anandasabapathy, S.

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc. 68(4), 737–744 (2008).
[CrossRef] [PubMed]

Anderson, R. R.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo Confocal Scanning Laser Microscopy of Human Skin: Melanin Provides Strong Contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

Aoki, Y.

H. Miyajima, N. Asaoka, T. Isokawa, M. Ogata, Y. Aoki, M. Imai, O. Fujimori, M. Katashiro, and K. Matsumoto, “A MEMS electromagnetic optical scanner for a commercial confocal laser scanning microscope,” J. Microelectromech. Syst. 12(3), 243–251 (2003).
[CrossRef]

Asaoka, N.

H. Miyajima, N. Asaoka, T. Isokawa, M. Ogata, Y. Aoki, M. Imai, O. Fujimori, M. Katashiro, and K. Matsumoto, “A MEMS electromagnetic optical scanner for a commercial confocal laser scanning microscope,” J. Microelectromech. Syst. 12(3), 243–251 (2003).
[CrossRef]

Bancu, M. G.

Barretto, R. P.

Bernstein, J. J.

Birks, T. A.

Boccara, C.

Boppart, S. A.

Boudoux, C.

Bouma, B. E.

Bourquin, S.

Brenner, M.

Brezinski, M. E.

Brown, T. G.

Bünting, U.

Burg, J.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology 127(3), 706–713 (2004).
[CrossRef] [PubMed]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Chen, Y.

Chen, Y. C.

Chen, Z.

Chen, Z. P.

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. P. Chen, “Three-dimensional endoscopic optical coherence tomography by use of a two-axis microelectromechanical scanning mirror,” Appl. Phys. Lett. 88(16), 163901 (2006).
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A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
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R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology 127(3), 706–713 (2004).
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Gnaendiger, J.

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B. Qi, A. P. Himmer, L. M. Gordon, X. D. V. Yang, L. D. Dickensheets, and I. A. Vitkin, “Dynamic focus control in high-speed optical coherence tomography based on a microelectromechanical mirror,” Opt. Commun. 232(1-6), 123–128 (2004).
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Grossman, M.

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Hartl, I.

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F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
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Himmer, A. P.

B. Qi, A. P. Himmer, L. M. Gordon, X. D. V. Yang, L. D. Dickensheets, and I. A. Vitkin, “Dynamic focus control in high-speed optical coherence tomography based on a microelectromechanical mirror,” Opt. Commun. 232(1-6), 123–128 (2004).
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B. M. Hoeling, M. E. Peter, D. C. Petersen, and R. C. Haskell, “Improved phase modulation for an en-face scanning three-dimensional optical coherence microscope,” Rev. Sci. Instrum. 75(10), 3348–3350 (2004).
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Hsiung, P. L.

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol. 5(11), 1300–1305 (2007).
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H. Miyajima, N. Asaoka, T. Isokawa, M. Ogata, Y. Aoki, M. Imai, O. Fujimori, M. Katashiro, and K. Matsumoto, “A MEMS electromagnetic optical scanner for a commercial confocal laser scanning microscope,” J. Microelectromech. Syst. 12(3), 243–251 (2003).
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H. Miyajima, N. Asaoka, T. Isokawa, M. Ogata, Y. Aoki, M. Imai, O. Fujimori, M. Katashiro, and K. Matsumoto, “A MEMS electromagnetic optical scanner for a commercial confocal laser scanning microscope,” J. Microelectromech. Syst. 12(3), 243–251 (2003).
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Kiesslich, R.

A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
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Lima, I. T.

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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J. T. Liu, M. J. Mandella, H. Ra, L. K. Wong, O. Solgaard, G. S. Kino, W. Piyawattanametha, C. H. Contag, and T. D. Wang, “Miniature near-infrared dual-axes confocal microscope utilizing a two-dimensional microelectromechanical systems scanner,” Opt. Lett. 32(3), 256–258 (2007).
[CrossRef] [PubMed]

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W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. P. Chen, “Three-dimensional endoscopic optical coherence tomography by use of a two-axis microelectromechanical scanning mirror,” Appl. Phys. Lett. 88(16), 163901 (2006).
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R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology 127(3), 706–713 (2004).
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A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
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Mukai, D.

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T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc. 68(4), 737–744 (2008).
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Nafe, B.

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Neurath, M. F.

A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
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Owen, G. M.

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B. M. Hoeling, M. E. Peter, D. C. Petersen, and R. C. Haskell, “Improved phase modulation for an en-face scanning three-dimensional optical coherence microscope,” Rev. Sci. Instrum. 75(10), 3348–3350 (2004).
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B. M. Hoeling, M. E. Peter, D. C. Petersen, and R. C. Haskell, “Improved phase modulation for an en-face scanning three-dimensional optical coherence microscope,” Rev. Sci. Instrum. 75(10), 3348–3350 (2004).
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Piyawattanametha, W.

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R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology 127(3), 706–713 (2004).
[CrossRef] [PubMed]

Polglase, A. L.

A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
[CrossRef] [PubMed]

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Qi, B.

B. Qi, A. P. Himmer, L. M. Gordon, X. D. V. Yang, L. D. Dickensheets, and I. A. Vitkin, “Dynamic focus control in high-speed optical coherence tomography based on a microelectromechanical mirror,” Opt. Commun. 232(1-6), 123–128 (2004).
[CrossRef]

Ra, H.

Rajadhyaksha, M.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo Confocal Scanning Laser Microscopy of Human Skin: Melanin Provides Strong Contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

Ralston, T. S.

Rao, K. D.

Richards-Kortum, R.

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc. 68(4), 737–744 (2008).
[CrossRef] [PubMed]

K. C. Maitland, H. J. Shin, H. Ra, D. Lee, O. Solgaard, and R. Richards-Kortum, “Single fiber confocal microscope with a two-axis gimbaled MEMS scanner for cellular imaging,” Opt. Express 14(19), 8604–8612 (2006).
[CrossRef] [PubMed]

A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
[CrossRef] [PubMed]

Rogomentich, F. J.

Rollins, A. M.

Rouse, A. R.

Rudolph, W.

Sahbaie, P.

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol. 5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Sampson, D. D.

Sattmann, H.

F. Lexer, C. K. Hitzenberger, W. Drexler, S. Molebny, H. Sattmann, M. Sticker, and A. F. Fercher, “Dynamic coherent focus OCT with depth-independent transversal resolution,” J. Mod. Opt. 46, 541–553 (1999).

Sawinski, J.

J. Sawinski and W. Denk, “Miniature random-access fiber scanner for in vivo multiphoton imaging,” J. Appl. Phys. 102(3), 034701 (2007).
[CrossRef]

Saxer, C.

Saxer, C. E.

Schmitt, J. M.

J. M. Schmitt, S. L. Lee, and K. M. Yung, “An optical coherence microscope with enhanced resolving power in thick tissue,” Opt. Commun. 142(4-6), 203–207 (1997).
[CrossRef]

Schnitzer, M. J.

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Shin, H. J.

Shishkov, M.

Sivak, M. V.

J. A. Izatt, M. D. Kulkarni, H.-W. Wang, K. Kobayashi, and M. V. Sivak., “Optical coherence tomography and microscopy in gastrointestinal tissues,” IEEE J. Sel. Top. Quan. Electron. 2(4), 1017–1028 (1996).
[CrossRef]

Skinner, S. A.

A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
[CrossRef] [PubMed]

Smeulders, A. W. M.

J. M. Geusebroek, F. Cornelissen, A. W. M. Smeulders, and H. Geerts, “Robust autofocusing in microscopy,” Cytometry 39(1), 1–9 (2000).
[CrossRef] [PubMed]

Smith, E. D.

Smith, S. W.

Soetikno, R.

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol. 5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Solgaard, O.

Sticker, M.

F. Lexer, C. K. Hitzenberger, W. Drexler, S. Molebny, H. Sattmann, M. Sticker, and A. F. Fercher, “Dynamic coherent focus OCT with depth-independent transversal resolution,” J. Mod. Opt. 46, 541–553 (1999).

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Swanson, E. A.

J. A. Izatt, M. R. Hee, G. M. Owen, E. A. Swanson, and J. G. Fujimoto, “Optical coherence microscopy in scattering media,” Opt. Lett. 19(8), 590–592 (1994).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Tan, W.

Tank, D. W.

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

Tearney, G. J.

Thomas, S.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology 127(3), 706–713 (2004).
[CrossRef] [PubMed]

Tien, N. C.

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. P. Chen, “Three-dimensional endoscopic optical coherence tomography by use of a two-axis microelectromechanical scanning mirror,” Appl. Phys. Lett. 88(16), 163901 (2006).
[CrossRef]

Trost, P.

Udovich, J. A.

Vabre, L.

Vieth, M.

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology 127(3), 706–713 (2004).
[CrossRef] [PubMed]

Vinegoni, C.

Vitkin, I. A.

B. Qi, A. P. Himmer, L. M. Gordon, X. D. V. Yang, L. D. Dickensheets, and I. A. Vitkin, “Dynamic focus control in high-speed optical coherence tomography based on a microelectromechanical mirror,” Opt. Commun. 232(1-6), 123–128 (2004).
[CrossRef]

Wadsworth, W. J.

Wang, H.-W.

J. A. Izatt, M. D. Kulkarni, H.-W. Wang, K. Kobayashi, and M. V. Sivak., “Optical coherence tomography and microscopy in gastrointestinal tissues,” IEEE J. Sel. Top. Quan. Electron. 2(4), 1017–1028 (1996).
[CrossRef]

Wang, L.

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. P. Chen, “Three-dimensional endoscopic optical coherence tomography by use of a two-axis microelectromechanical scanning mirror,” Appl. Phys. Lett. 88(16), 163901 (2006).
[CrossRef]

Wang, T. D.

J. T. Liu, M. J. Mandella, H. Ra, L. K. Wong, O. Solgaard, G. S. Kino, W. Piyawattanametha, C. H. Contag, and T. D. Wang, “Miniature near-infrared dual-axes confocal microscope utilizing a two-dimensional microelectromechanical systems scanner,” Opt. Lett. 32(3), 256–258 (2007).
[CrossRef] [PubMed]

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol. 5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Wang, Z. G.

Webb, R. H.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo Confocal Scanning Laser Microscopy of Human Skin: Melanin Provides Strong Contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

Welsch, E.

Westphal, V.

White, W. M.

Willner, A. E.

A. E. Willner, “Chromatic dispersion and polarization-mode dispersion: managing key limitations in optical communication systems,” Opt. Photon. News 13, 16–21 (2002).

Windeler, R. S.

Wong, L. K.

Wu, M. C.

Xiang, S.

Xie, H.

Xie, H. K.

A. Jain, A. Kopa, Y. T. Pan, G. K. Fedder, and H. K. Xie, “A two-axis electrothermal micromirror for endoscopic optical coherence tomography,” IEEE J. Sel. Top. Quan. Electron. 10(3), 636–642 (2004).
[CrossRef]

Xie, T.

Xie, T. Q.

Xu, C.

Yang, X. D. V.

B. Qi, A. P. Himmer, L. M. Gordon, X. D. V. Yang, L. D. Dickensheets, and I. A. Vitkin, “Dynamic focus control in high-speed optical coherence tomography based on a microelectromechanical mirror,” Opt. Commun. 232(1-6), 123–128 (2004).
[CrossRef]

Yazdanfar, S.

Yun, S. H.

Yung, K. M.

J. M. Schmitt, S. L. Lee, and K. M. Yung, “An optical coherence microscope with enhanced resolving power in thick tissue,” Opt. Commun. 142(4-6), 203–207 (1997).
[CrossRef]

Zara, J. M.

Zhang, J.

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. P. Chen, “Three-dimensional endoscopic optical coherence tomography by use of a two-axis microelectromechanical scanning mirror,” Appl. Phys. Lett. 88(16), 163901 (2006).
[CrossRef]

Zhao, Y.

Zhou, Q. Y.

Zhu, Z. M.

Zvyagin, A. V.

Appl. Opt. (4)

Appl. Phys. Lett. (1)

W. Jung, D. T. McCormick, J. Zhang, L. Wang, N. C. Tien, and Z. P. Chen, “Three-dimensional endoscopic optical coherence tomography by use of a two-axis microelectromechanical scanning mirror,” Appl. Phys. Lett. 88(16), 163901 (2006).
[CrossRef]

Clin. Gastroenterol. Hepatol. (1)

T. D. Wang, S. Friedland, P. Sahbaie, R. Soetikno, P. L. Hsiung, J. T. Liu, J. M. Crawford, and C. H. Contag, “Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology,” Clin. Gastroenterol. Hepatol. 5(11), 1300–1305 (2007).
[CrossRef] [PubMed]

Cytometry (1)

J. M. Geusebroek, F. Cornelissen, A. W. M. Smeulders, and H. Geerts, “Robust autofocusing in microscopy,” Cytometry 39(1), 1–9 (2000).
[CrossRef] [PubMed]

Gastroenterology (1)

R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology 127(3), 706–713 (2004).
[CrossRef] [PubMed]

Gastrointest. Endosc. (2)

A. L. Polglase, W. J. McLaren, S. A. Skinner, R. Kiesslich, M. F. Neurath, and P. M. Delaney, “A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract,” Gastrointest. Endosc. 62(5), 686–695 (2005).
[CrossRef] [PubMed]

T. J. Muldoon, S. Anandasabapathy, D. Maru, and R. Richards-Kortum, “High-resolution imaging in Barrett’s esophagus: a novel, low-cost endoscopic microscope,” Gastrointest. Endosc. 68(4), 737–744 (2008).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quan. Electron. (2)

J. A. Izatt, M. D. Kulkarni, H.-W. Wang, K. Kobayashi, and M. V. Sivak., “Optical coherence tomography and microscopy in gastrointestinal tissues,” IEEE J. Sel. Top. Quan. Electron. 2(4), 1017–1028 (1996).
[CrossRef]

A. Jain, A. Kopa, Y. T. Pan, G. K. Fedder, and H. K. Xie, “A two-axis electrothermal micromirror for endoscopic optical coherence tomography,” IEEE J. Sel. Top. Quan. Electron. 10(3), 636–642 (2004).
[CrossRef]

J. Appl. Phys. (1)

J. Sawinski and W. Denk, “Miniature random-access fiber scanner for in vivo multiphoton imaging,” J. Appl. Phys. 102(3), 034701 (2007).
[CrossRef]

J. Biomed. Opt. (1)

A. L. Clark, A. Gillenwater, R. Alizadeh-Naderi, A. K. El-Naggar, and R. Richards-Kortum, “Detection and diagnosis of oral neoplasia with an optical coherence microscope,” J. Biomed. Opt. 9(6), 1271–1280 (2004).
[CrossRef] [PubMed]

J. Invest. Dermatol. (1)

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo Confocal Scanning Laser Microscopy of Human Skin: Melanin Provides Strong Contrast,” J. Invest. Dermatol. 104(6), 946–952 (1995).
[CrossRef] [PubMed]

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D. L. Dickensheets and G. S. Kino, “Silicon-micromachined scanning confocal optical microscope,” J. Microelectromech. Syst. 7(1), 38–47 (1998).
[CrossRef]

H. Miyajima, N. Asaoka, T. Isokawa, M. Ogata, Y. Aoki, M. Imai, O. Fujimori, M. Katashiro, and K. Matsumoto, “A MEMS electromagnetic optical scanner for a commercial confocal laser scanning microscope,” J. Microelectromech. Syst. 12(3), 243–251 (2003).
[CrossRef]

J. Mod. Opt. (1)

F. Lexer, C. K. Hitzenberger, W. Drexler, S. Molebny, H. Sattmann, M. Sticker, and A. F. Fercher, “Dynamic coherent focus OCT with depth-independent transversal resolution,” J. Mod. Opt. 46, 541–553 (1999).

J. Opt. Soc. Am. A (2)

J. Opt. Soc. Am. B (1)

Neuron (1)

F. Helmchen, M. S. Fee, D. W. Tank, and W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

Opt. Commun. (2)

J. M. Schmitt, S. L. Lee, and K. M. Yung, “An optical coherence microscope with enhanced resolving power in thick tissue,” Opt. Commun. 142(4-6), 203–207 (1997).
[CrossRef]

B. Qi, A. P. Himmer, L. M. Gordon, X. D. V. Yang, L. D. Dickensheets, and I. A. Vitkin, “Dynamic focus control in high-speed optical coherence tomography based on a microelectromechanical mirror,” Opt. Commun. 232(1-6), 123–128 (2004).
[CrossRef]

Opt. Express (9)

C. K. Hitzenberger, P. Trost, P. W. Lo, and Q. Y. Zhou, “Three-dimensional imaging of the human retina by high-speed optical coherence tomography,” Opt. Express 11(21), 2753–2761 (2003).
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T. Q. Xie, Z. G. Wang, and Y. T. Pan, “High-speed optical coherence tomography using fiberoptic acousto-optic phase modulation,” Opt. Express 11(24), 3210–3219 (2003).
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S. Bourquin, A. D. Aguirre, I. Hartl, P. Hsiung, T. H. Ko, J. G. Fujimoto, T. A. Birks, W. J. Wadsworth, U. Bünting, and D. Kopf, “Ultrahigh resolution real time OCT imaging using a compact femtosecond Nd:Glass laser and nonlinear fiber,” Opt. Express 11(24), 3290–3297 (2003).
[CrossRef] [PubMed]

Y. C. Chen and X. D. Li, “Dispersion management up to the third order for real-time optical coherence tomography involving a phase or frequency modulator,” Opt. Express 12(24), 5968–5978 (2004).
[CrossRef] [PubMed]

C. Boudoux, S. H. Yun, W. Y. Oh, W. M. White, N. V. Iftimia, M. Shishkov, B. E. Bouma, and G. J. Tearney, “Rapid wavelength-swept spectrally encoded confocal microscopy,” Opt. Express 13(20), 8214–8221 (2005).
[CrossRef] [PubMed]

K. C. Maitland, H. J. Shin, H. Ra, D. Lee, O. Solgaard, and R. Richards-Kortum, “Single fiber confocal microscope with a two-axis gimbaled MEMS scanner for cellular imaging,” Opt. Express 14(19), 8604–8612 (2006).
[CrossRef] [PubMed]

A. D. Aguirre, P. R. Hertz, Y. Chen, J. G. Fujimoto, W. Piyawattanametha, L. Fan, and M. C. Wu, “Two-axis MEMS scanning catheter for ultrahigh resolution three-dimensional and en face imaging,” Opt. Express 15(5), 2445–2453 (2007).
[CrossRef] [PubMed]

S. W. Huang, A. D. Aguirre, R. A. Huber, D. C. Adler, and J. G. Fujimoto, “Swept source optical coherence microscopy using a Fourier domain mode-locked laser,” Opt. Express 15(10), 6210–6217 (2007).
[CrossRef] [PubMed]

K. H. Kim, B. H. Park, G. N. Maguluri, T. W. Lee, F. J. Rogomentich, M. G. Bancu, B. E. Bouma, J. F. de Boer, and J. J. Bernstein, “Two-axis magnetically-driven MEMS scanning catheter for endoscopic high-speed optical coherence tomography,” Opt. Express 15(26), 18130–18140 (2007).
[CrossRef] [PubMed]

Opt. Lett. (16)

Y. Chen, S. W. Huang, A. D. Aguirre, and J. G. Fujimoto, “High-resolution line-scanning optical coherence microscopy,” Opt. Lett. 32(14), 1971–1973 (2007).
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R. Huber, D. C. Adler, and J. G. Fujimoto, “Buffered Fourier domain mode locking: Unidirectional swept laser sources for optical coherence tomography imaging at 370,000 lines/s,” Opt. Lett. 31(20), 2975–2977 (2006).
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J. T. Liu, M. J. Mandella, H. Ra, L. K. Wong, O. Solgaard, G. S. Kino, W. Piyawattanametha, C. H. Contag, and T. D. Wang, “Miniature near-infrared dual-axes confocal microscope utilizing a two-dimensional microelectromechanical systems scanner,” Opt. Lett. 32(3), 256–258 (2007).
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M. T. Myaing, D. J. MacDonald, and X. D. Li, “Fiber-optic scanning two-photon fluorescence endoscope,” Opt. Lett. 31(8), 1076–1078 (2006).
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W. Piyawattanametha, R. P. Barretto, T. H. Ko, B. A. Flusberg, E. D. Cocker, H. Ra, D. Lee, O. Solgaard, and M. J. Schnitzer, “Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two- dimensional scanning mirror,” Opt. Lett. 31(13), 2018–2020 (2006).
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Y. Zhao, Z. Chen, C. Saxer, S. Xiang, J. F. de Boer, and J. S. Nelson, “Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity,” Opt. Lett. 25(2), 114–116 (2000).
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J. A. Izatt, M. R. Hee, G. M. Owen, E. A. Swanson, and J. G. Fujimoto, “Optical coherence microscopy in scattering media,” Opt. Lett. 19(8), 590–592 (1994).
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S. A. Boppart, B. E. Bouma, C. Pitris, G. J. Tearney, J. G. Fujimoto, and M. E. Brezinski, “Forward-imaging instruments for optical coherence tomography,” Opt. Lett. 22(21), 1618–1620 (1997).
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G. J. Tearney, B. E. Bouma, and J. G. Fujimoto, “High-speed phase- and group-delay scanning with a grating-based phase control delay line,” Opt. Lett. 22(23), 1811–1813 (1997).
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V. Westphal, S. Yazdanfar, A. M. Rollins, and J. A. Izatt, “Real-time, high velocity-resolution color Doppler optical coherence tomography,” Opt. Lett. 27(1), 34–36 (2002).
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Opt. Photon. News (1)

A. E. Willner, “Chromatic dispersion and polarization-mode dispersion: managing key limitations in optical communication systems,” Opt. Photon. News 13, 16–21 (2002).

Rev. Sci. Instrum. (1)

B. M. Hoeling, M. E. Peter, D. C. Petersen, and R. C. Haskell, “Improved phase modulation for an en-face scanning three-dimensional optical coherence microscope,” Rev. Sci. Instrum. 75(10), 3348–3350 (2004).
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Science (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, and et, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Supplementary Material (1)

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Figures (11)

Fig. 1
Fig. 1

High-speed OCM imaging system. The system operates at 1060 nm center wavelength using a broadband electro-optic waveguide phase modulator. TIA, transimpedance amplifier. BPF, bandpass filter. PD, photodiode. VGA, variable-gain amplifier. A/D, analog-to-digital converter. PC, personal computer. D/A, digital-to-analog converter. PM, polarization-maintaining. EOM, electro-optic modulator.

Fig. 2
Fig. 2

Schematic of the reference arm optical delay line used for dispersion compensation and path length scanning. FC, fiber collimator. DCG, dispersion compensating glass. QWP, quarter waveplate. M, mirror. R, retroreflector. CM, curved mirror. SM, stationary mirror. G, grating.

Fig. 3
Fig. 3

Dispersion-balanced axial coherence point spread function achieved with polarization management. The axial resolution (a) measured 4.3 µm in air, corresponding to 3.1 µm in tissue. The Fourier transform of the point spread function (b), measures ~137 nm in spectral full-width at half maximum

Fig. 4
Fig. 4

Resolution characterization for the OCM instrument. High lateral resolution of <2 µm is demonstrated by the visualization of the smallest elements on the 1951 USAF resolution target (a). Overlapped confocal and coherence gates show that the dominant axial sectioning is provided by the coherence gate (b).

Fig. 5
Fig. 5

Ex vivo OCM image of human esophagus and colon with corresponding histology. The OCM image of esophagus (a) shows cell membranes and individual nuclei in the squamous epithelium. The image of colon clearly delineates crypt architecture as well as individual goblet cells (gc) in the crypt epithelium. Correspondence with representative histology (b, d) demonstrates the ability for OCM to perform high-resolution imaging without the need for specimen processing. Notable shrinkage is evident from the OCM images of fresh tissue to the processed histology specimens. Scale bar, 100 µm.

Fig. 6
Fig. 6

Coregistered OCT and OCM images of human cervical epithelium ex vivo. Ultrahigh resolution OCT in (a) delineates the layered squamous epithelium (e) from the more highly scattering, heterogenous lamina propria (lp). En face OCM images (b, Media 1) and (c) corresponding to the region of the box in (a) demonstrate cellular and subcellular resolution below the tissue surface. Cell membranes (cm) as well as the junction between the basal layer and the underlying lamina propria (b) are distinguished. The inset in (c) demonstrates the small epithelial cells near the basal layer. The combination of OCT and OCM provides complementary information about tissue microstructure. Scale bars 500 µm (a), 100 µm (b,c). Media 1 - Video sequence of cellular features in human cervical epithelium ex vivo. Organized stratified squamous epithelial cells with progression to smaller size can be seen as the video scans from the surface to the basement membrane. Images deep into the lamina propria demonstrate the ability to image through the basement membrane into the underlying connective tissue layers

Fig. 7
Fig. 7

Measurement of confocal gate position in scattering tissue using coherence ranging. The OCM depth scanner was used to acquire a lateral priority cross-sectional image, which clearly shows the restricted depth of field resulting from high NA focusing (A). Averaging across lateral scans produced an average depth response, which is a measure of the confocal axial response in scattering tissue (B). Images obtained with the coherence and confocal gates misaligned (C,F and E,H) appear out of focus compared to the image obtained with the gates precisely aligned (D,G). Scale bars, 100 µm.

Fig. 8
Fig. 8

Algorithm for fast autofocusing in scattering tissues.

Fig. 9
Fig. 9

In vivo cellular resolution OCM images of human skin. A progression is shown from the stratum corneum (a-c) thru the epidermis (d-f) and into the dermis (g-i). Highly scattering corneocytes, c, are visible in the stratum corneum in images (a) and (b) while epidermal cells become evident in images (c-f). The transition regions between the stratum corneum and the epidermis and between the epidermis and the dermis can be appreciated in (c) and (g), respectively. Scale bar, 100 µm. Image depths range from the surface to approximately 400 µm below the surface.

Fig. 10
Fig. 10

Endoscope for OCM imaging. (a) Optical design. Tube lens focal length, fT. Back focal plane, BFP. Piezoelectric actuators, PZT’s. Illumination aperture, AI. (b) Endoscope package. (c) Sample arm containing the endoscope unit, air gap coupling, and drive electronics. (d) Scanner drive waveforms.

Fig. 11
Fig. 11

Endoscopic OCM imaging. (a) USAF target demonstrating scan field of view and lateral resolution <2 µm. (b,c) Ex vivo images of human colon acquired at 2 frames per second. Goblet cells, gc. (d) In vivo image of human skin acquired at 4 frames per second. Epidermal cells, ec. Scale bar, 50 µm.

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