Abstract

Three-dimensional high-resolution imaging methods are important for cellular-level research. Optical coherence microscopy (OCM) is a low-coherence-based interferometry technology for cellular imaging with both high axial and lateral resolution. Using a high-numerical-aperture objective, OCM normally has a shallow depth of field and requires scanning the focus through the entire region of interest to perform volumetric imaging. With a higher-numerical-aperture objective, the image quality of OCM is affected by and more sensitive to aberrations. Interferometric synthetic aperture microscopy (ISAM) and computational adaptive optics (CAO) are computed imaging techniques that overcome the depth-of-field limitation and the effect of optical aberrations in optical coherence tomography (OCT), respectively. In this work we combine OCM with ISAM and CAO to achieve high-speed volumetric cellular imaging. Experimental imaging results of ex vivo human breast tissue, ex vivo mouse brain tissue, in vitro fibroblast cells in 3D scaffolds, and in vivo human skin demonstrate the significant potential of this technique for high-speed volumetric cellular imaging.

© 2014 Optical Society of America

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2014 (1)

2013 (4)

J. Mo, M. de Groot, and J. F. de Boer, “Focus-extension by depth-encoded synthetic aperture in optical coherence tomography,” Opt. Express21(8), 10048–10061 (2013).
[CrossRef] [PubMed]

A. Ahmad, N. D. Shemonski, S. G. Adie, H. S. Kim, W. M. Hwu, P. S. Carney, and S. A. Boppart, “Real-time in vivo computed optical interferometric tomography,” Nat. Photonics7(6), 444–448 (2013).
[CrossRef] [PubMed]

Y. Jian, R. J. Zawadzki, and M. V. Sarunic, “Adaptive optics optical coherence tomography for in vivo mouse retinal imaging,” J. Biomed. Opt.18(5), 056007 (2013).
[CrossRef] [PubMed]

A. Kumar, W. Drexler, and R. A. Leitgeb, “Subaperture correlation based digital adaptive optics for full field optical coherence tomography,” Opt. Express21(9), 10850–10866 (2013).
[CrossRef] [PubMed]

2012 (5)

S. G. Adie, B. W. Graf, A. Ahmad, P. S. Carney, and S. A. Boppart, “Computational adaptive optics for broadband optical interferometric tomography of biological tissue,” Proc. Natl. Acad. Sci. U.S.A.109(19), 7175–7180 (2012).
[CrossRef] [PubMed]

S. G. Adie, N. D. Shemonski, B. W. Graf, A. Ahmad, P. Scott Carney, and S. A. Boppart, “Guide-star-based computational adaptive optics for broadband interferometric tomography,” Appl. Phys. Lett.101(22), 221117 (2012).
[CrossRef] [PubMed]

Y. Zhao, B. W. Graf, E. J. Chaney, Z. Mahmassani, E. Antoniadou, R. Devolder, H. Kong, M. D. Boppart, and S. A. Boppart, “Integrated multimodal optical microscopy for structural and functional imaging of engineered and natural skin,” J. Biophotonics5(5-6), 437–448 (2012).
[CrossRef] [PubMed]

V. J. Srinivasan, H. Radhakrishnan, J. Y. Jiang, S. Barry, and A. E. Cable, “Optical coherence microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast,” Opt. Express20(3), 2220–2239 (2012).
[CrossRef] [PubMed]

B. W. Graf and S. A. Boppart, “Multimodal in vivo skin imaging with integrated optical coherence and multiphoton microscopy,” IEEE J. Sel. Top. Quantum Electron.18(4), 1280–1286 (2012).
[CrossRef]

2011 (4)

S. G. Adie, B. W. Grafa, A. Ahmad, B. Dabarsyah, S. A. Boppart, and P. S. Carney, “The impact of aberrations on object reconstruction with interferometric synthetic aperture microscopy,” Proc. SPIE7889, 78891O (2011).
[CrossRef]

V. Lakshminarayanan and A. Fleck, “Zernike polynomials: a guide,” J. Mod. Opt.58(7), 545–561 (2011).
[CrossRef]

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
[CrossRef] [PubMed]

D. Hillmann, C. Lührs, T. Bonin, P. Koch, and G. Hüttmann, “Holoscopy--holographic optical coherence tomography,” Opt. Lett.36(13), 2390–2392 (2011).
[CrossRef] [PubMed]

2010 (6)

2009 (1)

2008 (1)

2007 (7)

2006 (2)

2005 (2)

W. Lo, Y. Sun, S.-J. Lin, S.-H. Jee, and C.-Y. Dong, “Spherical aberration correction in multiphoton fluorescence imaging using objective correction collar,” J. Biomed. Opt.10(3), 034006 (2005).
[CrossRef] [PubMed]

R. Huber, M. Wojtkowski, J. G. Fujimoto, J. Y. Jiang, and A. E. Cable, “Three-dimensional and C-mode OCT imaging with a compact, frequency swept laser source at 1300 nm,” Opt. Express13(26), 10523–10538 (2005).
[CrossRef] [PubMed]

2003 (2)

J. R. Fienup and J. J. Miller, “Aberration correction by maximizing generalized sharpness metrics,” J. Opt. Soc. Am. A20(4), 609–620 (2003).
[CrossRef] [PubMed]

G. Partadiredja, R. Miller, and D. E. Oorschot, “The number, size, and type of axons in rat subcortical white matter on left and right sides: a stereological, ultrastructural study,” J. Neurocytol.32(9), 1165–1179 (2003).
[CrossRef] [PubMed]

2002 (1)

2001 (1)

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med.7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

1998 (1)

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(7), 861–865 (1998).
[CrossRef] [PubMed]

1996 (1)

J. A. Izatt, M. D. Kulkarni, K. Kobayashi, and M. V. Sivak, “Optical coherence tomography and microscopy in gastrointestinal tissues,” IEEE J. Sel. Top. Quantum 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)

1993 (1)

P. Corcuff, C. Bertrand, and J. L. Leveque, “Morphometry of human epidermis in vivo by real-time confocal microscopy,” Arch. Dermatol. Res.285(8), 475–481 (1993).
[CrossRef] [PubMed]

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, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Adie, S. G.

A. Ahmad, N. D. Shemonski, S. G. Adie, H. S. Kim, W. M. Hwu, P. S. Carney, and S. A. Boppart, “Real-time in vivo computed optical interferometric tomography,” Nat. Photonics7(6), 444–448 (2013).
[CrossRef] [PubMed]

S. G. Adie, B. W. Graf, A. Ahmad, P. S. Carney, and S. A. Boppart, “Computational adaptive optics for broadband optical interferometric tomography of biological tissue,” Proc. Natl. Acad. Sci. U.S.A.109(19), 7175–7180 (2012).
[CrossRef] [PubMed]

S. G. Adie, N. D. Shemonski, B. W. Graf, A. Ahmad, P. Scott Carney, and S. A. Boppart, “Guide-star-based computational adaptive optics for broadband interferometric tomography,” Appl. Phys. Lett.101(22), 221117 (2012).
[CrossRef] [PubMed]

S. G. Adie, B. W. Grafa, A. Ahmad, B. Dabarsyah, S. A. Boppart, and P. S. Carney, “The impact of aberrations on object reconstruction with interferometric synthetic aperture microscopy,” Proc. SPIE7889, 78891O (2011).
[CrossRef]

B. W. Graf, S. G. Adie, and S. A. Boppart, “Correction of coherence gate curvature in high numerical aperture optical coherence imaging,” Opt. Lett.35(18), 3120–3122 (2010).
[CrossRef] [PubMed]

T. S. Ralston, S. G. Adie, D. L. Marks, S. A. Boppart, and P. S. Carney, “Cross-validation of interferometric synthetic aperture microscopy and optical coherence tomography,” Opt. Lett.35(10), 1683–1685 (2010).
[CrossRef] [PubMed]

Aguirre, A. D.

Ahmad, A.

A. Ahmad, N. D. Shemonski, S. G. Adie, H. S. Kim, W. M. Hwu, P. S. Carney, and S. A. Boppart, “Real-time in vivo computed optical interferometric tomography,” Nat. Photonics7(6), 444–448 (2013).
[CrossRef] [PubMed]

S. G. Adie, N. D. Shemonski, B. W. Graf, A. Ahmad, P. Scott Carney, and S. A. Boppart, “Guide-star-based computational adaptive optics for broadband interferometric tomography,” Appl. Phys. Lett.101(22), 221117 (2012).
[CrossRef] [PubMed]

S. G. Adie, B. W. Graf, A. Ahmad, P. S. Carney, and S. A. Boppart, “Computational adaptive optics for broadband optical interferometric tomography of biological tissue,” Proc. Natl. Acad. Sci. U.S.A.109(19), 7175–7180 (2012).
[CrossRef] [PubMed]

S. G. Adie, B. W. Grafa, A. Ahmad, B. Dabarsyah, S. A. Boppart, and P. S. Carney, “The impact of aberrations on object reconstruction with interferometric synthetic aperture microscopy,” Proc. SPIE7889, 78891O (2011).
[CrossRef]

Akiba, M.

M. Akiba and K. P. Chan, “In vivo video-rate cellular-level full-field optical coherence tomography,” J. Biomed. Opt.12(6), 064024 (2007).
[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]

Antoniadou, E.

Y. Zhao, B. W. Graf, E. J. Chaney, Z. Mahmassani, E. Antoniadou, R. Devolder, H. Kong, M. D. Boppart, and S. A. Boppart, “Integrated multimodal optical microscopy for structural and functional imaging of engineered and natural skin,” J. Biophotonics5(5-6), 437–448 (2012).
[CrossRef] [PubMed]

Bachmann, A. H.

Backman, V.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med.7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

Badizadegan, K.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med.7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

Barry, S.

Bertrand, C.

P. Corcuff, C. Bertrand, and J. L. Leveque, “Morphometry of human epidermis in vivo by real-time confocal microscopy,” Arch. Dermatol. Res.285(8), 475–481 (1993).
[CrossRef] [PubMed]

Betzig, E.

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods7(2), 141–147 (2010).
[CrossRef] [PubMed]

Bonin, T.

Boppart, M. D.

Y. Zhao, B. W. Graf, E. J. Chaney, Z. Mahmassani, E. Antoniadou, R. Devolder, H. Kong, M. D. Boppart, and S. A. Boppart, “Integrated multimodal optical microscopy for structural and functional imaging of engineered and natural skin,” J. Biophotonics5(5-6), 437–448 (2012).
[CrossRef] [PubMed]

Boppart, S. A.

A. Ahmad, N. D. Shemonski, S. G. Adie, H. S. Kim, W. M. Hwu, P. S. Carney, and S. A. Boppart, “Real-time in vivo computed optical interferometric tomography,” Nat. Photonics7(6), 444–448 (2013).
[CrossRef] [PubMed]

S. G. Adie, N. D. Shemonski, B. W. Graf, A. Ahmad, P. Scott Carney, and S. A. Boppart, “Guide-star-based computational adaptive optics for broadband interferometric tomography,” Appl. Phys. Lett.101(22), 221117 (2012).
[CrossRef] [PubMed]

S. G. Adie, B. W. Graf, A. Ahmad, P. S. Carney, and S. A. Boppart, “Computational adaptive optics for broadband optical interferometric tomography of biological tissue,” Proc. Natl. Acad. Sci. U.S.A.109(19), 7175–7180 (2012).
[CrossRef] [PubMed]

B. W. Graf and S. A. Boppart, “Multimodal in vivo skin imaging with integrated optical coherence and multiphoton microscopy,” IEEE J. Sel. Top. Quantum Electron.18(4), 1280–1286 (2012).
[CrossRef]

Y. Zhao, B. W. Graf, E. J. Chaney, Z. Mahmassani, E. Antoniadou, R. Devolder, H. Kong, M. D. Boppart, and S. A. Boppart, “Integrated multimodal optical microscopy for structural and functional imaging of engineered and natural skin,” J. Biophotonics5(5-6), 437–448 (2012).
[CrossRef] [PubMed]

S. G. Adie, B. W. Grafa, A. Ahmad, B. Dabarsyah, S. A. Boppart, and P. S. Carney, “The impact of aberrations on object reconstruction with interferometric synthetic aperture microscopy,” Proc. SPIE7889, 78891O (2011).
[CrossRef]

B. W. Graf, S. G. Adie, and S. A. Boppart, “Correction of coherence gate curvature in high numerical aperture optical coherence imaging,” Opt. Lett.35(18), 3120–3122 (2010).
[CrossRef] [PubMed]

T. S. Ralston, S. G. Adie, D. L. Marks, S. A. Boppart, and P. S. Carney, “Cross-validation of interferometric synthetic aperture microscopy and optical coherence tomography,” Opt. Lett.35(10), 1683–1685 (2010).
[CrossRef] [PubMed]

D. L. Marks, B. J. Davis, S. A. Boppart, and P. Carney, “Partially coherent illumination in full-field interferometric synthetic aperture microscopy,” J. Opt. Soc. Am. A26(2), 376–386 (2009).
[CrossRef] [PubMed]

T. S. Ralston, D. L. Marks, P. S. Carney, and S. A. Boppart, “Real-time interferometric synthetic aperture microscopy,” Opt. Express16(4), 2555–2569 (2008).
[CrossRef] [PubMed]

B. J. Davis, S. C. Schlachter, D. L. Marks, T. S. Ralston, S. A. Boppart, and P. S. Carney, “Nonparaxial vector-field modeling of optical coherence tomography and interferometric synthetic aperture microscopy,” J. Opt. Soc. Am. A24(9), 2527–2542 (2007).
[CrossRef] [PubMed]

D. L. Marks, T. S. Ralston, S. A. Boppart, and P. S. Carney, “Inverse scattering for frequency-scanned full-field optical coherence tomography,” J. Opt. Soc. Am. A24(4), 1034–1041 (2007).
[CrossRef] [PubMed]

T. S. Ralston, D. L. Marks, P. S. Carney, and S. A. Boppart, “Interferometric synthetic aperture microscopy,” Nat. Phys.3(2), 129–134 (2007).
[CrossRef]

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S. G. Adie, B. W. Grafa, A. Ahmad, B. Dabarsyah, S. A. Boppart, and P. S. Carney, “The impact of aberrations on object reconstruction with interferometric synthetic aperture microscopy,” Proc. SPIE7889, 78891O (2011).
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Chen, Z.

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Dabarsyah, B.

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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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Gabarda, S.

Georgakoudi, I.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med.7(11), 1245–1248 (2001).
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S. G. Adie, B. W. Graf, A. Ahmad, P. S. Carney, and S. A. Boppart, “Computational adaptive optics for broadband optical interferometric tomography of biological tissue,” Proc. Natl. Acad. Sci. U.S.A.109(19), 7175–7180 (2012).
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Y. Zhao, B. W. Graf, E. J. Chaney, Z. Mahmassani, E. Antoniadou, R. Devolder, H. Kong, M. D. Boppart, and S. A. Boppart, “Integrated multimodal optical microscopy for structural and functional imaging of engineered and natural skin,” J. Biophotonics5(5-6), 437–448 (2012).
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F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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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).
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Gurjar, R. S.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med.7(11), 1245–1248 (2001).
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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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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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Huber, R.

Hüttmann, G.

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A. Ahmad, N. D. Shemonski, S. G. Adie, H. S. Kim, W. M. Hwu, P. S. Carney, and S. A. Boppart, “Real-time in vivo computed optical interferometric tomography,” Nat. Photonics7(6), 444–448 (2013).
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Itzkan, I.

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W. Lo, Y. Sun, S.-J. Lin, S.-H. Jee, and C.-Y. Dong, “Spherical aberration correction in multiphoton fluorescence imaging using objective correction collar,” J. Biomed. Opt.10(3), 034006 (2005).
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Y. Jian, R. J. Zawadzki, and M. V. Sarunic, “Adaptive optics optical coherence tomography for in vivo mouse retinal imaging,” J. Biomed. Opt.18(5), 056007 (2013).
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Kim, H. S.

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J. A. Izatt, M. D. Kulkarni, K. Kobayashi, and M. V. Sivak, “Optical coherence tomography and microscopy in gastrointestinal tissues,” IEEE J. Sel. Top. Quantum Electron.2(4), 1017–1028 (1996).
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Kong, H.

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J. A. Izatt, M. D. Kulkarni, K. Kobayashi, and M. V. Sivak, “Optical coherence tomography and microscopy in gastrointestinal tissues,” IEEE J. Sel. Top. Quantum Electron.2(4), 1017–1028 (1996).
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Lakshminarayanan, V.

V. Lakshminarayanan and A. Fleck, “Zernike polynomials: a guide,” J. Mod. Opt.58(7), 545–561 (2011).
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Lee, K. K. C.

B. A. Standish, K. K. C. Lee, A. Mariampillai, N. R. Munce, M. K. K. Leung, V. X. D. Yang, and I. A. Vitkin, “In vivo endoscopic multi-beam optical coherence tomography,” Phys. Med. Biol.55(3), 615–622 (2010).
[CrossRef] [PubMed]

Lee, K. S.

Leitgeb, R. A.

Leung, M. K. K.

B. A. Standish, K. K. C. Lee, A. Mariampillai, N. R. Munce, M. K. K. Leung, V. X. D. Yang, and I. A. Vitkin, “In vivo endoscopic multi-beam optical coherence tomography,” Phys. Med. Biol.55(3), 615–622 (2010).
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P. Corcuff, C. Bertrand, and J. L. Leveque, “Morphometry of human epidermis in vivo by real-time confocal microscopy,” Arch. Dermatol. Res.285(8), 475–481 (1993).
[CrossRef] [PubMed]

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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

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W. Lo, Y. Sun, S.-J. Lin, S.-H. Jee, and C.-Y. Dong, “Spherical aberration correction in multiphoton fluorescence imaging using objective correction collar,” J. Biomed. Opt.10(3), 034006 (2005).
[CrossRef] [PubMed]

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Liu, L.

Lo, W.

W. Lo, Y. Sun, S.-J. Lin, S.-H. Jee, and C.-Y. Dong, “Spherical aberration correction in multiphoton fluorescence imaging using objective correction collar,” J. Biomed. Opt.10(3), 034006 (2005).
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Mahmassani, Z.

Y. Zhao, B. W. Graf, E. J. Chaney, Z. Mahmassani, E. Antoniadou, R. Devolder, H. Kong, M. D. Boppart, and S. A. Boppart, “Integrated multimodal optical microscopy for structural and functional imaging of engineered and natural skin,” J. Biophotonics5(5-6), 437–448 (2012).
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Mariampillai, A.

B. A. Standish, K. K. C. Lee, A. Mariampillai, N. R. Munce, M. K. K. Leung, V. X. D. Yang, and I. A. Vitkin, “In vivo endoscopic multi-beam optical coherence tomography,” Phys. Med. Biol.55(3), 615–622 (2010).
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Meemon, P.

Milkie, D. E.

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods7(2), 141–147 (2010).
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Munce, N. R.

B. A. Standish, K. K. C. Lee, A. Mariampillai, N. R. Munce, M. K. K. Leung, V. X. D. Yang, and I. A. Vitkin, “In vivo endoscopic multi-beam optical coherence tomography,” Phys. Med. Biol.55(3), 615–622 (2010).
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Nakamura, Y.

Nelson, J. S.

Oorschot, D. E.

G. Partadiredja, R. Miller, and D. E. Oorschot, “The number, size, and type of axons in rat subcortical white matter on left and right sides: a stereological, ultrastructural study,” J. Neurocytol.32(9), 1165–1179 (2003).
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Owen, G. M.

Partadiredja, G.

G. Partadiredja, R. Miller, and D. E. Oorschot, “The number, size, and type of axons in rat subcortical white matter on left and right sides: a stereological, ultrastructural study,” J. Neurocytol.32(9), 1165–1179 (2003).
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R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, “Imaging human epithelial properties with polarized light-scattering spectroscopy,” Nat. Med.7(11), 1245–1248 (2001).
[CrossRef] [PubMed]

Pitris, C.

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(7), 861–865 (1998).
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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, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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Radhakrishnan, 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).
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Rao, B.

Ren, H.

Robles, F. E.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
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Sando, Y.

Sarunic, M. V.

Y. Jian, R. J. Zawadzki, and M. V. Sarunic, “Adaptive optics optical coherence tomography for in vivo mouse retinal imaging,” J. Biomed. Opt.18(5), 056007 (2013).
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Schlachter, S. C.

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, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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S. G. Adie, N. D. Shemonski, B. W. Graf, A. Ahmad, P. Scott Carney, and S. A. Boppart, “Guide-star-based computational adaptive optics for broadband interferometric tomography,” Appl. Phys. Lett.101(22), 221117 (2012).
[CrossRef] [PubMed]

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A. Ahmad, N. D. Shemonski, S. G. Adie, H. S. Kim, W. M. Hwu, P. S. Carney, and S. A. Boppart, “Real-time in vivo computed optical interferometric tomography,” Nat. Photonics7(6), 444–448 (2013).
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S. G. Adie, N. D. Shemonski, B. W. Graf, A. Ahmad, P. Scott Carney, and S. A. Boppart, “Guide-star-based computational adaptive optics for broadband interferometric tomography,” Appl. Phys. Lett.101(22), 221117 (2012).
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Sivak, M. V.

J. A. Izatt, M. D. Kulkarni, K. Kobayashi, and M. V. Sivak, “Optical coherence tomography and microscopy in gastrointestinal tissues,” IEEE J. Sel. Top. Quantum Electron.2(4), 1017–1028 (1996).
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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(7), 861–865 (1998).
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Standish, B. A.

B. A. Standish, K. K. C. Lee, A. Mariampillai, N. R. Munce, M. K. K. Leung, V. X. D. Yang, and I. A. Vitkin, “In vivo endoscopic multi-beam optical coherence tomography,” Phys. Med. Biol.55(3), 615–622 (2010).
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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, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
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Sugisaka, J.-I.

Sun, Y.

W. Lo, Y. Sun, S.-J. Lin, S.-H. Jee, and C.-Y. Dong, “Spherical aberration correction in multiphoton fluorescence imaging using objective correction collar,” J. Biomed. Opt.10(3), 034006 (2005).
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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).
[CrossRef] [PubMed]

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Villiger, M.

Vitkin, I. A.

B. A. Standish, K. K. C. Lee, A. Mariampillai, N. R. Munce, M. K. K. Leung, V. X. D. Yang, and I. A. Vitkin, “In vivo endoscopic multi-beam optical coherence tomography,” Phys. Med. Biol.55(3), 615–622 (2010).
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Wax, A.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
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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).
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F. E. Robles, C. Wilson, G. Grant, and A. Wax, “Molecular imaging true-colour spectroscopic optical coherence tomography,” Nat. Photonics5(12), 744–747 (2011).
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Wojtkowski, M.

Yang, V. X. D.

B. A. Standish, K. K. C. Lee, A. Mariampillai, N. R. Munce, M. K. K. Leung, V. X. D. Yang, and I. A. Vitkin, “In vivo endoscopic multi-beam optical coherence tomography,” Phys. Med. Biol.55(3), 615–622 (2010).
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Yatagai, T.

Yu, L.

Zawadzki, R. J.

Y. Jian, R. J. Zawadzki, and M. V. Sarunic, “Adaptive optics optical coherence tomography for in vivo mouse retinal imaging,” J. Biomed. Opt.18(5), 056007 (2013).
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Supplementary Material (1)

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Figures (9)

Fig. 1
Fig. 1

Schematic of the inverted spectral-domain optical coherence microscope (SD-OCM) system operating with ISAM and CAO.

Fig. 2
Fig. 2

System characterization. OCM image of a USAF resolution target where the smallest element 3 bars in group 9 can be observed.

Fig. 3
Fig. 3

Tissue phantom imaging (a) Experimental measurement of PSF (FWHM) versus distance from the focus for OCT, ISAM, and the combination of ISAM and CAO. (b)-(d) Cross-sectional images of the reconstructions of OCM, ISAM, the combination of ISAM and CAO. (e)-(g) En face plane reconstructions of OCM, ISAM, the combination of ISAM and CAO, at 28 µm below the focus. Spherical aberration can be seen clearly in the (e) OCM and (f) ISAM results. The insets show the zoomed-in images of selected particles in (e)-(g). All the images have the same gamma correction. The color scales indicate the displayed range of relative signal amplitudes. The scale bar denotes 20 µm.

Fig. 4
Fig. 4

OCM (1st row) and ISAM (2nd row) in ex vivo human breast tissue. En face planes of OCM at (a) the focal plane, a plane (b) 22 µm (5.8 Rayleigh lengths) and (c) 67 µm (17.6 Rayleigh lengths) above the focus plane. (d)-(f) ISAM reconstruction of the same en face planes of (a)-(c). The bright and highly scattering nuclei are indicated by the arrows. The scale bar in (a) denotes 50 µm, and applies to all images.

Fig. 5
Fig. 5

Image metrics for quantitatively evaluating the image quality of ex vivo human breast tissue along the depth. (a) Depth-dependent SNR improvement, based on subtracting the SNR between ISAM and OCM. (b) Image anisotropy measurement.

Fig. 6
Fig. 6

En face planes from highly scattering ex vivo mouse brain tissue at a depth ~6 Rayleigh lengths above the focus, showing (a) OCM, (b) Uncorrected ISAM, and (c) CAO aberration-corrected ISAM. The blue arrows indicate the cell bodies of neurons, and the green arrows indicate the myelinated axons. The insets show the profile and FWHM of the myelinated axons. The scale bar denotes 20 µm.

Fig. 7
Fig. 7

En face plane reconstructions of the 3D scaffold at a depth of about 11.5 Rayleigh lengths above the focus from (a) OCM, (b) ISAM without aberration correction, and (c) CAO and ISAM. The images in (f) and (g) show the same zoomed-in structures as in (d) and (e), but show the results of correcting the aberrations. The scale bar denotes 30 µm.

Fig. 8
Fig. 8

Time lapse results of mouse dermal fibroblasts in a 3D macroporous alginate hydrogel scaffold (Media 1). Images (a-f) and (g-l) are the results for t = 0 min (start) and 112 min, respectively. The columns (a, d, g, j) are at the depth of about 12 Rayleigh lengths above the focus, and (b, e, h, k) are at the depth of about 5 Rayleigh lengths above the focus. Images (c, f, i, l) are at the focal plane. The top row images (a, b, c, g, h, i) are the OCM results while the bottom row images (d, e, f, j, k, l) show the results from applying the combination of ISAM and CAO. The green arrows indicate the filopodia. The scale bar denotes 30 µm.

Fig. 9
Fig. 9

Cellular resolution images of different layers in in vivo human skin. The 1st row are OCM results without Z-stacks, and the 2nd row are the results from the combination of ISAM and CAO. (a, f) Depth about 62 µm beneath the surface and 24 Rayleigh lengths above the focus, where the junction between the stratum corneum and the epidermis is located. The boundary of this junction is indicated by the arrow in (f). (b, g) Epidermis layer. The nuclei of granular cells are visible in ISAM/CAO results (arrow) while they are not present in the OCM result. (c, h) Superficial dermis layer. An arrow shows the dermal papillae. (d, i) Junction between epidermis and dermis. The basal cells are visualized and indicated by an arrow. (e, j) Deep in the dermis, which is about 11 Rayleigh lengths below the focus. Probable collagen fiber bundles are indicated by the arrow in the ISAM/CAO reconstruction. The scale bar in (a) denotes 40 µm, and applies to all images.

Equations (5)

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S ˜ ˜ ˜ ( q x , q y , k ) = H ( q x , q y , k ) η ˜ ˜ ˜ [ q x , q y , ( 2 k ) 2 ( q x 2 + q y 2 ) ] ,
η ˜ ˜ ˜ + ( q x , q y , q z ) S ˜ ˜ ˜ ( q x , q y , k ) | k = 1 2 q z 2 + q x 2 + q y 2
η ( x , y , z ) = F 1 [ η ˜ ˜ ˜ + ( q x , q y , q z ) ]
S ˜ ˜ ˜ A ( q x , q y , k ) = H A ( q x , q y , k ) H ( q x , q y , k ) η ˜ ˜ ˜ [ q x , q y , ( 2 k ) 2 ( q x 2 + q y 2 ) ]
S ˜ ˜ ˜ A C ( q x , q y , k ) = H A C ( q x , q y , k ) S ˜ ˜ ˜ A ( q x , q y , k )

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