We have developed a white-light interference microscope for ultrahigh-resolution full-field optical coherence tomography of biological media. The experimental setup is based on a Linnik-type interferometer illuminated by a tungsten halogen lamp. En face tomographic images are calculated by a combination of interferometric images recorded by a high-speed CCD camera. Spatial resolution of 1.8 μm × 0.9 μm (transverse × axial) is achieved owing to the extremely short coherence length of the source, the compensation of dispersion mismatch in the interferometer arms, and the use of relatively high-numerical-aperture microscope objectives. A shot-noise-limited detection sensitivity of 90 dB is obtained in an acquisition time per image of 4 s. Subcellular-level images of plant, animal, and human tissues are presented.

© 2004 Optical Society of America

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46. P. A. Moulin, “A wavelet regularization method for diffuse radar-target imaging and speckle-noise reduction,” J. Math. Imaging Vision 3, 123–134 (1993).
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52. C. A. Puliafito, M. R. Hee, C. P. Lin, E. Reichel, J. S. Schuman, J. S. Duker, J. A. Izatt, E. A. Swanson, and J. G. Fujimoto, “Imaging of macular diseases with optical coherence tomography,” Ophthalmology 102, 217–229 (1995).
53. M. R. Hee, J. A. Izatt, E. A. Swanson, D. Huang, J. S. Schuman, C. P. Lin, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography of the human retina,” Arch. Ophthalmol. 113, 325–332 (1995).
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55. J. S. Schuman, M. R. Hee, C. A. Puliafito, C. Wong, T. Pedut-Kloizman, C. P. Lin, E. Hertzmark, J. A. Izatt, E. A. Swanson, and J. G. Fujimoto, “Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography,” Arch. Ophthalmol. 113, 586–596 (1995).
56. J. R. Wilkins, C. A. Puliafito, M. R. Hee, J. S. Duker, E. Reichel, J. G. Coker, J. S. Schuman, E. A. Swanson, and J. G. Fujimoto, “Characterization of epiretinal membranes using optical coherence tomography,” Ophthalmology 103, 2142–2151 (1996).
57. M. R. Hee, C. A. Puliafito, J. S. Duker, E. Reichel, J. G. Coker, J. R. Wilkins, J. S. Schuman, E. A. Swanson, and J. G. Fujimoto, “Topography of diabetic macular edema with optical coherence tomography,” Ophthalmology 105, 360–370 (1998).
58. H. Hoerauf and R. Birngruber, “Optical coherence tomography in the anterior segment of the eye,” in Handbook of Optical Coherence Tomography, B. E. Bouma and G. J. Tearney, eds. (Marcel Dekker, New York, 2002), pp. 487–503.
59. G. J. Tearney, B. E. Bouma, S. A. Boppart, B. Golubovic, E. A. Swanson, and J. G. Fujimoto, “Rapid acquisition of in vivo biological images by use of optical coherence tomography,” Opt. Lett. 21, 1408–1410 (1996).
60. G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, “In vivo endoscopic optical biopsy with optical coherence tomography,” Science 276, 2037–2039 (1995).
61. G. J. Tearney, M. E. Brezinski, J. F. Southern, B. E. Bouma, S. A. Boppart, and J. G. Fujimoto, “Optical biopsy in human urologic tissue using optical coherence tomography,” J. Urol. 75, 1915–1920 (1997).
62. F. I. Feldchtein, V. M. Gelikonov, G. V. Gelikonov, R. V. Kuranov, A. M. Sergeev, N. D. Gladkova, A. V. Shakhov, N. M. Shakhova, L. B. Snopova, A. B. Teerenteva, E. V. Zagainova, Y. P. Chumakov, and I. A. Kuznetzova, “Endoscopic applications of optical coherence tomography,” Opt. Express 3, 257–262 (1998).
63. J. G. Fujimoto, S. A. Boppart, G. J. Tearney, B. E. Bouma, C. Pitris, and M. E. Brezinski, “High resolution in vivo intra-arterial imaging with optical coherence tomography,” Heart 82, 128–133 (1999).
64. A. M. Sergeev, V. M. Gelikonov, G. V. Gelikono, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzova, A. N. Denisenko, V. V. Pochinko, Y. P. Chumakov, and O. S. Streltzova, “In vivo endoscopic OCT imaging of precancer and cancer states of human mucosa,” Opt. Express 1, 432–440 (1997).
65. C. Pitris, A. Goodman, S. A. Boppart, J. J. Libus, J. G. Fujimoto, and M. E. Brezinski, “High-resolution imaging of gynecologic neoplasms using optical coherence tomography,” Obstet. Gynecol. 93, 135–139 (1999).
66. J. Welzel, E. Lankenau, R. Birngruber, and R. Egelhardt, “Optical coherence tomography of the human skin,” J. Am. Acad. Dermatol. 37, 958–963 (1997).
67. A. M. Rollins, A. Chak, C. K. Wong, K. Kobayashi, M. V. Sivak, R. Ung-arunyawee, and J. A. Izatt, “Real-time in vivo imaging of gastrointestinal ultrastructures using optical coherence tomography with a novel efficient interferometer design,” Opt. Lett. 24, 1358–1360 (1999).

Appl. Opt.

• P. Parsa, S. L. Jacques, and N. S. Nishioka, “Optical properties of rat liver between 350 and 2200 nm,” Appl. Opt. 28, 2325–2330 (1989).
• A. Dubois, L. Vabre, A. C. Boccara, and E. Beaurepaire, “High-resolution full-field optical coherence tomography with a Linnik microscope,” Appl. Opt. 41, 805–812 (2002).
• E. Bordenave, E. Abraham, G. Jonusauskas, N. Tsurumachi, J. Oberlé, C. Rullière, P. E. Minot, M. Lassègues, and J. E. Surlève Bazeille, “Wide-field optical coherence tomography: imaging of biological tissues,” Appl. Opt. 41, 2059–2064 (2002).
• B. Laude, A. De Martino, B. Drévillon, L. Benattar, and L. Schwartz, “Full-field optical coherence tomography with thermal light,” Appl. Opt. 41, 2059–2064 (2002).
• G. S. Kino and S. C. Chim, “Mirau correlation microscope,” Appl. Opt. 29, 3775–3783 (1990).

Arch. Ophthalmol.

• M. R. Hee, J. A. Izatt, E. A. Swanson, D. Huang, J. S. Schuman, C. P. Lin, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography of the human retina,” Arch. Ophthalmol. 113, 325–332 (1995).
• J. A. Izatt, M. R. Hee, E. A. Swanson, C. P. Lin, D. Huang, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography,” Arch. Ophthalmol. 112, 1584–1589 (1994).
• J. S. Schuman, M. R. Hee, C. A. Puliafito, C. Wong, T. Pedut-Kloizman, C. P. Lin, E. Hertzmark, J. A. Izatt, E. A. Swanson, and J. G. Fujimoto, “Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography,” Arch. Ophthalmol. 113, 586–596 (1995).

Biomed. Eng. Appl. Basis Commun.

• S. H. Xiang and Y. T. Zhang, “Sensitivity enhancement using nonlinear optical wavelet thresholding for two-dimensional medical ultrasound transducer,” Biomed. Eng. Appl. Basis Commun. 9, 91–100 (1997).

Electron. Lett.

• M. D. Kulkarni, C. W. Thomas, and J. A. Izatt, “Image enhancement in optical coherence tomography using deconvolution,” Electron. Lett. 33, 1365–1367 (1997).

Heart

• J. G. Fujimoto, S. A. Boppart, G. J. Tearney, B. E. Bouma, C. Pitris, and M. E. Brezinski, “High resolution in vivo intra-arterial imaging with optical coherence tomography,” Heart 82, 128–133 (1999).

IEEE Trans. Circuits Syst.

• R. Berstein, “Adaptative nonlinear filters for simultaneous removal of different kinds of noise in images,” IEEE Trans. Circuits Syst. 34, 1275–1291 (1987).

IEEE Trans. Pattern Anal. Mach. Intell.

• D. T. Kuan, A. A. Sawchuk, T. C. Strand, and P. Chavel, “Adaptative noise smoothing for images with signal-dependent noise,” IEEE Trans. Pattern Anal. Mach. Intell. 7, 165–177 (1985).

J. Am. Acad. Dermatol.

• J. Welzel, E. Lankenau, R. Birngruber, and R. Egelhardt, “Optical coherence tomography of the human skin,” J. Am. Acad. Dermatol. 37, 958–963 (1997).

J. Biomed. Opt.

• K. M. Yung and J. M. Schmitt, “Phase-domain processing of optical coherence tomography images,” J. Biomed. Opt. 4, 125–136 (1996).
• J. M. Schmitt, “Restoration of optical coherence images of living tissue using the CLEAN algorithm,” J. Biomed. Opt. 3, 66–75 (1998).
• C. K. Hitzenberger, A. Baumgartner, W. Drexler, and A. F. Fercher, “Dispersion effects in partial coherence interferometry: implications for intraocular ranging,” J. Biomed. Opt. 4, 144–151 (1999).
• A. F. Fercher, “Optical coherence tomography,” J. Biomed. Opt. 1, 157–173 (1996).

J. Math. Imaging Vision

• P. A. Moulin, “A wavelet regularization method for diffuse radar-target imaging and speckle-noise reduction,” J. Math. Imaging Vision 3, 123–134 (1993).

J. Opt. Soc. Am. A

• G. Franceschetti, V. Pascazio, and G. Schirinzi, “Iterative homomorphic technique for speckle reduction in synthetic-aperture imaging,” J. Opt. Soc. Am. A 12, 686–694 (1995).
• J. M. Schmitt and A. Knuttel, “Model of optical coherence tomography of heterogeneous tissue,” J. Opt. Soc. Am. A 14, 1231–1242 (1997).
• K. G. Larkin, “Efficient nonlinear algorithm for envelope detection in white light interferometry,” J. Opt. Soc. Am. A 13, 832–843 (1996).

J. Urol.

• G. J. Tearney, M. E. Brezinski, J. F. Southern, B. E. Bouma, S. A. Boppart, and J. G. Fujimoto, “Optical biopsy in human urologic tissue using optical coherence tomography,” J. Urol. 75, 1915–1920 (1997).

Nat. Med.

• J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. E. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med. 1, 970–972 (1995).
• S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, “In vivo cellular optical coherence tomography imaging,” Nat. Med. 4, 861–865 (1998).

Obstet. Gynecol.

• C. Pitris, A. Goodman, S. A. Boppart, J. J. Libus, J. G. Fujimoto, and M. E. Brezinski, “High-resolution imaging of gynecologic neoplasms using optical coherence tomography,” Obstet. Gynecol. 93, 135–139 (1999).

Ophthalmic Surg. Lasers

• H. Ishikawa, R. Gürses-Özden, S. T. Hoh, H. L. Dou, J. M. Liebmann, and R. Ritch, “Grayscale and proportion-corrected optical coherence tomography images,” Ophthalmic Surg. Lasers 31, 223–228 (2000).

Ophthalmology

• J. R. Wilkins, C. A. Puliafito, M. R. Hee, J. S. Duker, E. Reichel, J. G. Coker, J. S. Schuman, E. A. Swanson, and J. G. Fujimoto, “Characterization of epiretinal membranes using optical coherence tomography,” Ophthalmology 103, 2142–2151 (1996).
• M. R. Hee, C. A. Puliafito, J. S. Duker, E. Reichel, J. G. Coker, J. R. Wilkins, J. S. Schuman, E. A. Swanson, and J. G. Fujimoto, “Topography of diabetic macular edema with optical coherence tomography,” Ophthalmology 105, 360–370 (1998).
• C. A. Puliafito, M. R. Hee, C. P. Lin, E. Reichel, J. S. Schuman, J. S. Duker, J. A. Izatt, E. A. Swanson, and J. G. Fujimoto, “Imaging of macular diseases with optical coherence tomography,” Ophthalmology 102, 217–229 (1995).

Opt. Commun.

• A. F. Fercher, C. K. Hitzenberger, M. Sticker, E. Moreno-Barriuso, R. Leitgeb, W. Drexler, and H. Sattmann, “A thermal light source technique for optical coherence tomography,” Opt. Commun. 185, 57–64 (2000).

Opt. Express

• A. G. Podoleanu, J. A. Rogers, D. A. Jackson, and S. Dunne, “Three dimensional OCT images from retina and skin,” Opt. Express 7, 292–298 (2000).
• C. K. Hitzenberger, P. Trost, P. W. Lo, and Q. Zhou, “Three-dimensional imaging of the human retina by high-speed optical coherence tomography,” Opt. Express 11, 2753–2761 (2003).
• A. M. Sergeev, V. M. Gelikonov, G. V. Gelikono, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzova, A. N. Denisenko, V. V. Pochinko, Y. P. Chumakov, and O. S. Streltzova, “In vivo endoscopic OCT imaging of precancer and cancer states of human mucosa,” Opt. Express 1, 432–440 (1997).
• F. I. Feldchtein, V. M. Gelikonov, G. V. Gelikonov, R. V. Kuranov, A. M. Sergeev, N. D. Gladkova, A. V. Shakhov, N. M. Shakhova, L. B. Snopova, A. B. Teerenteva, E. V. Zagainova, Y. P. Chumakov, and I. A. Kuznetzova, “Endoscopic applications of optical coherence tomography,” Opt. Express 3, 257–262 (1998).

Opt. Lett.

• G. J. Tearney, B. E. Bouma, S. A. Boppart, B. Golubovic, E. A. Swanson, and J. G. Fujimoto, “Rapid acquisition of in vivo biological images by use of optical coherence tomography,” Opt. Lett. 21, 1408–1410 (1996).
• A. M. Rollins, A. Chak, C. K. Wong, K. Kobayashi, M. V. Sivak, R. Ung-arunyawee, and J. A. Izatt, “Real-time in vivo imaging of gastrointestinal ultrastructures using optical coherence tomography with a novel efficient interferometer design,” Opt. Lett. 24, 1358–1360 (1999).
• 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, 1864–1866 (1993).
• M. Bashkansky and J. Reintjes, “Statistics and reduction of speckle in optical coherence tomography,” Opt. Lett. 25, 545–547 (2000).
• G. J. Tearney, M. E. Brezinski, J. F. Southern, B. E. Bouma, M. R. Hee, and J. G. Fujimoto, “Determination of the refractive index of highly scattering human tissue by optical coherence tomography,” Opt. Lett. 20, 2258–2260 (1995).
• L. Vabre, A. Dubois, and A. C. Boccara, “Thermal-light full-field optical coherence tomography,” Opt. Lett. 27, 530–533 (2002).
• 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, 590–593 (1994).
• A. G. Podoleanu, G. M. Dobre, D. J. Webb, and D. A. Jackson, “Simultaneous en-face imaging of two layers in the human retina by low-coherence reflectometry,” Opt. Lett. 22, 1039–1041 (1997).
• A. G. Podoleanu, G. M. Dobre, and D. A. Jackson, “En-face coherence imaging using galvanometer scanner modulation,” Opt. Lett. 23, 147–149 (1998).
• W. Drexler, U. Morgner, F. X. Kärtner, C. Pitris, S. A. Boppart, X. D. Li, E. P. Ippen, and J. G. Fujimoto, “In vivo ultrahigh-resolution optical coherence tomography,” Opt. Lett. 24, 1221–1223 (1999).
• B. Považay, K. Bizheva, A. Unterhuber, B. Hermann, H. Sattmann, A. F. Fercher, A. Apolonski, W. J. Wadsworth, J. C. Knight, P. St. J. Russell, M. Vetterlein, E. Scherzer, and W. Drexler, “Submicrometer axial resolution optical coherence tomography,” Opt. Lett. 20, 1800–1802 (2002).
• E. Beaurepaire, A. C. Boccara, M. Lebec, L. Blanchot, and H. Saint-Jalmes, “Full-field optical coherence microscopy,” Opt. Lett. 23, 244–246 (1998).
• S. Bourquin, P. Seitz, R. P. Salathé, “Optical coherence topography based on a two-dimensional smart detector array,” Opt. Lett. 26, 512–514 (2001).
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