Abstract

We demonstrate high speed, swept source optical coherence microscopy (OCM) using a MEMS tunable vertical cavity surface-emitting laser (VCSEL) light source. The light source had a sweep rate of 280 kHz, providing a bidirectional axial scan rate of 560 kHz. The sweep bandwidth was 117 nm centered at 1310 nm, corresponding to an axial resolution of 13.1 µm in air, corresponding to 8.1 µm (9.6 µm spectrally shaped) in tissue. Dispersion mismatch from different objectives was compensated numerically, enabling magnification and field of view to be easily changed. OCM images were acquired with transverse resolutions between 0.86 µm - 3.42 µm using interchangeable 40X, 20X and 10X objectives with ~600 µm x 600 µm, ~1 mm x 1 mm and ~2 mm x 2 mm field-of-view (FOV), respectively. Parasitic variations in path length with beam scanning were corrected numerically. These features enable swept source OCM to be integrated with a wide range of existing scanning microscopes. Large FOV mosaics were generated by serially acquiring adjacent overlapping microscopic fields and combining them in post-processing. Fresh human colon, thyroid and kidney specimens were imaged ex vivo and compared to matching histology sections, demonstrating the ability of OCM to image tissue specimens.

© 2013 OSA

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2012 (4)

H. C. Lee, C. Zhou, D. W. Cohen, A. E. Mondelblatt, Y. Wang, A. D. Aguirre, D. Shen, Y. Sheikine, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and optical coherence microscopy imaging of ex vivo human renal tissues,” J. Urol.187(2), 691–699 (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]

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]

G. Liu, W. Jia, V. Sun, B. Choi, and Z. Chen, “High-resolution imaging of microvasculature in human skin in-vivo with optical coherence tomography,” Opt. Express20(7), 7694–7705 (2012).
[CrossRef] [PubMed]

2011 (1)

S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt.16(5), 050504 (2011).
[CrossRef] [PubMed]

2010 (5)

A. D. Aguirre, Y. Chen, B. Bryan, H. Mashimo, Q. Huang, J. L. Connolly, and J. G. Fujimoto, “Cellular resolution ex vivo imaging of gastrointestinal tissues with optical coherence microscopy,” J. Biomed. Opt.15(1), 016025 (2010).
[CrossRef] [PubMed]

C. Zhou, D. W. Cohen, Y. Wang, H.-C. Lee, A. E. Mondelblatt, T.-H. Tsai, A. D. Aguirre, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and microscopy for ex vivo multiscale evaluation of human breast tissues,” Cancer Res.70(24), 10071–10079 (2010).
[CrossRef] [PubMed]

C. Zhou, Y. Wang, A. D. Aguirre, T. H. Tsai, D. W. Cohen, J. L. Connolly, and J. G. Fujimoto, “Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy,” J. Biomed. Opt.15(1), 016001 (2010).
[CrossRef] [PubMed]

J. F. Xi, L. Huo, J. S. Li, and X. D. Li, “Generic real-time uniform K-space sampling method for high-speed swept-Source optical coherence tomography,” Opt. Express18(9), 9511–9517 (2010).
[CrossRef] [PubMed]

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]

2009 (1)

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

2007 (4)

2006 (5)

C. Y. Xu, C. Vinegoni, T. S. Ralston, W. Luo, W. Tan, and S. A. Boppart, “Spectroscopic spectral-domain optical coherence microscopy,” Opt. Lett.31(8), 1079–1081 (2006).
[CrossRef] [PubMed]

M. A. Choma, A. K. Ellerbee, S. Yazdanfar, and J. A. Izatt, “Doppler flow imaging of cytoplasmic streaming using spectral domain phase microscopy,” J. Biomed. Opt.11(2), 024014 (2006).
[CrossRef] [PubMed]

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett.88(5), 053901 (2006).
[CrossRef]

R. Szeliski, “Image alignment and stitching: a tutorial,” Found. Trends. Comput. Graph. Vis.2(1), 1–104 (2006).
[CrossRef]

S. Tang, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source,” J. Biomed. Opt.11(2), 020502 (2006).
[CrossRef] [PubMed]

2004 (3)

A. Agarwala, M. Dontcheva, M. Agrawala, S. Drucker, A. Colburn, B. Curless, D. Salesin, and M. Cohen, “Interactive digital photomontage,” ACM Trans. Graphic23(3), 294–302 (2004).
[CrossRef]

M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, “Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation,” Opt. Express12(11), 2404–2422 (2004).
[CrossRef] [PubMed]

F. J. Fleming, A. D. K. Hill, E. W. Mc Dermott, A. O’Doherty, N. J. O’Higgins, and C. M. Quinn, “Intraoperative margin assessment and re-excision rate in breast conserving surgery,” Eur. J. Surg. Oncol.30(3), 233–237 (2004).
[CrossRef] [PubMed]

2003 (2)

2000 (3)

B. M. Hoeling, A. D. Fernandez, R. C. Haskell, E. Huang, W. R. Myers, D. C. Petersen, S. E. Ungersma, R. Y. Wang, M. E. Williams, and S. E. Fraser, “An optical coherence microscope for 3-dimensional imaging in developmental biology,” Opt. Express6(7), 136–146 (2000).
[CrossRef] [PubMed]

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol.182(5), 1135–1139 (2000).
[CrossRef] [PubMed]

J. W. Hettinger, M. de la Peña Mattozzi, W. R. Myers, M. E. Williams, A. Reeves, R. L. Parsons, R. C. Haskell, D. C. Petersen, R. Wang, and J. I. Medford, “Optical coherence microscopy. a technology for rapid, in vivo, non-destructive visualization of plants and plant cells,” Plant Physiol.123(1), 3–16 (2000).
[CrossRef] [PubMed]

1999 (1)

1994 (1)

1993 (1)

K. Kayser, E. Anyanwu, H. G. Bauer, and I. Vogt-Moykopf, “Tumor Presence at Resection Boundaries and Lymph-Node Metastasis in Bronchial Carcinoma Patients,” Thorac. Cardiovasc. Surg.41(5), 308–311 (1993).
[CrossRef] [PubMed]

Abdoh, A. A.

A. Binahmed, R. W. Nason, and A. A. Abdoh, “The clinical significance of the positive surgical margin in oral cancer,” Oral Oncol.43(8), 780–784 (2007).
[CrossRef] [PubMed]

Abeytunge, S.

S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt.16(5), 050504 (2011).
[CrossRef] [PubMed]

Adie, S. G.

Adler, D. C.

Agarwala, A.

A. Agarwala, M. Dontcheva, M. Agrawala, S. Drucker, A. Colburn, B. Curless, D. Salesin, and M. Cohen, “Interactive digital photomontage,” ACM Trans. Graphic23(3), 294–302 (2004).
[CrossRef]

Agrawala, M.

A. Agarwala, M. Dontcheva, M. Agrawala, S. Drucker, A. Colburn, B. Curless, D. Salesin, and M. Cohen, “Interactive digital photomontage,” ACM Trans. Graphic23(3), 294–302 (2004).
[CrossRef]

Aguirre, A. D.

H. C. Lee, C. Zhou, D. W. Cohen, A. E. Mondelblatt, Y. Wang, A. D. Aguirre, D. Shen, Y. Sheikine, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and optical coherence microscopy imaging of ex vivo human renal tissues,” J. Urol.187(2), 691–699 (2012).
[CrossRef] [PubMed]

C. Zhou, D. W. Cohen, Y. Wang, H.-C. Lee, A. E. Mondelblatt, T.-H. Tsai, A. D. Aguirre, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and microscopy for ex vivo multiscale evaluation of human breast tissues,” Cancer Res.70(24), 10071–10079 (2010).
[CrossRef] [PubMed]

A. D. Aguirre, Y. Chen, B. Bryan, H. Mashimo, Q. Huang, J. L. Connolly, and J. G. Fujimoto, “Cellular resolution ex vivo imaging of gastrointestinal tissues with optical coherence microscopy,” J. Biomed. Opt.15(1), 016025 (2010).
[CrossRef] [PubMed]

C. Zhou, Y. Wang, A. D. Aguirre, T. H. Tsai, D. W. Cohen, J. L. Connolly, and J. G. Fujimoto, “Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy,” J. Biomed. Opt.15(1), 016001 (2010).
[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. Express15(10), 6210–6217 (2007).
[CrossRef] [PubMed]

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]

Anderson, R. R.

Anyanwu, E.

K. Kayser, E. Anyanwu, H. G. Bauer, and I. Vogt-Moykopf, “Tumor Presence at Resection Boundaries and Lymph-Node Metastasis in Bronchial Carcinoma Patients,” Thorac. Cardiovasc. Surg.41(5), 308–311 (1993).
[CrossRef] [PubMed]

Barry, S.

Bartlett, L. A.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

Bauer, H. G.

K. Kayser, E. Anyanwu, H. G. Bauer, and I. Vogt-Moykopf, “Tumor Presence at Resection Boundaries and Lymph-Node Metastasis in Bronchial Carcinoma Patients,” Thorac. Cardiovasc. Surg.41(5), 308–311 (1993).
[CrossRef] [PubMed]

Binahmed, A.

A. Binahmed, R. W. Nason, and A. A. Abdoh, “The clinical significance of the positive surgical margin in oral cancer,” Oral Oncol.43(8), 780–784 (2007).
[CrossRef] [PubMed]

Boppart, S. A.

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]

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

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett.88(5), 053901 (2006).
[CrossRef]

C. Y. Xu, C. Vinegoni, T. S. Ralston, W. Luo, W. Tan, and S. A. Boppart, “Spectroscopic spectral-domain optical coherence microscopy,” Opt. Lett.31(8), 1079–1081 (2006).
[CrossRef] [PubMed]

Bouma, B. E.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

Brookner, C. K.

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol.182(5), 1135–1139 (2000).
[CrossRef] [PubMed]

Brown, M.

S. Winder, G. Hua, and M. Brown, “Picking the best DAISY,” in IEEE Conference on Computer Vision and Pattern Recognition, 2009, pp. 178–185.

Bryan, B.

A. D. Aguirre, Y. Chen, B. Bryan, H. Mashimo, Q. Huang, J. L. Connolly, and J. G. Fujimoto, “Cellular resolution ex vivo imaging of gastrointestinal tissues with optical coherence microscopy,” J. Biomed. Opt.15(1), 016025 (2010).
[CrossRef] [PubMed]

Cable, A. E.

Carney, P. S.

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]

Chen, Y.

A. D. Aguirre, Y. Chen, B. Bryan, H. Mashimo, Q. Huang, J. L. Connolly, and J. G. Fujimoto, “Cellular resolution ex vivo imaging of gastrointestinal tissues with optical coherence microscopy,” J. Biomed. Opt.15(1), 016025 (2010).
[CrossRef] [PubMed]

Chen, Z.

Choi, B.

Choma, M. A.

M. A. Choma, A. K. Ellerbee, S. Yazdanfar, and J. A. Izatt, “Doppler flow imaging of cytoplasmic streaming using spectral domain phase microscopy,” J. Biomed. Opt.11(2), 024014 (2006).
[CrossRef] [PubMed]

Cohen, D. W.

H. C. Lee, C. Zhou, D. W. Cohen, A. E. Mondelblatt, Y. Wang, A. D. Aguirre, D. Shen, Y. Sheikine, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and optical coherence microscopy imaging of ex vivo human renal tissues,” J. Urol.187(2), 691–699 (2012).
[CrossRef] [PubMed]

C. Zhou, D. W. Cohen, Y. Wang, H.-C. Lee, A. E. Mondelblatt, T.-H. Tsai, A. D. Aguirre, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and microscopy for ex vivo multiscale evaluation of human breast tissues,” Cancer Res.70(24), 10071–10079 (2010).
[CrossRef] [PubMed]

C. Zhou, Y. Wang, A. D. Aguirre, T. H. Tsai, D. W. Cohen, J. L. Connolly, and J. G. Fujimoto, “Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy,” J. Biomed. Opt.15(1), 016001 (2010).
[CrossRef] [PubMed]

Cohen, M.

A. Agarwala, M. Dontcheva, M. Agrawala, S. Drucker, A. Colburn, B. Curless, D. Salesin, and M. Cohen, “Interactive digital photomontage,” ACM Trans. Graphic23(3), 294–302 (2004).
[CrossRef]

Colburn, A.

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S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt.16(5), 050504 (2011).
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[CrossRef] [PubMed]

S. Tang, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source,” J. Biomed. Opt.11(2), 020502 (2006).
[CrossRef] [PubMed]

Tsai, T. H.

C. Zhou, Y. Wang, A. D. Aguirre, T. H. Tsai, D. W. Cohen, J. L. Connolly, and J. G. Fujimoto, “Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy,” J. Biomed. Opt.15(1), 016001 (2010).
[CrossRef] [PubMed]

Tsai, T.-H.

C. Zhou, D. W. Cohen, Y. Wang, H.-C. Lee, A. E. Mondelblatt, T.-H. Tsai, A. D. Aguirre, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and microscopy for ex vivo multiscale evaluation of human breast tissues,” Cancer Res.70(24), 10071–10079 (2010).
[CrossRef] [PubMed]

Tyrrell, J. A.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

Ungersma, S. E.

Vakoc, B. J.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

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C. Y. Xu, C. Vinegoni, T. S. Ralston, W. Luo, W. Tan, and S. A. Boppart, “Spectroscopic spectral-domain optical coherence microscopy,” Opt. Lett.31(8), 1079–1081 (2006).
[CrossRef] [PubMed]

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett.88(5), 053901 (2006).
[CrossRef]

Vogt-Moykopf, I.

K. Kayser, E. Anyanwu, H. G. Bauer, and I. Vogt-Moykopf, “Tumor Presence at Resection Boundaries and Lymph-Node Metastasis in Bronchial Carcinoma Patients,” Thorac. Cardiovasc. Surg.41(5), 308–311 (1993).
[CrossRef] [PubMed]

Wang, R.

J. W. Hettinger, M. de la Peña Mattozzi, W. R. Myers, M. E. Williams, A. Reeves, R. L. Parsons, R. C. Haskell, D. C. Petersen, R. Wang, and J. I. Medford, “Optical coherence microscopy. a technology for rapid, in vivo, non-destructive visualization of plants and plant cells,” Plant Physiol.123(1), 3–16 (2000).
[CrossRef] [PubMed]

Wang, R. Y.

Wang, Y.

H. C. Lee, C. Zhou, D. W. Cohen, A. E. Mondelblatt, Y. Wang, A. D. Aguirre, D. Shen, Y. Sheikine, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and optical coherence microscopy imaging of ex vivo human renal tissues,” J. Urol.187(2), 691–699 (2012).
[CrossRef] [PubMed]

C. Zhou, D. W. Cohen, Y. Wang, H.-C. Lee, A. E. Mondelblatt, T.-H. Tsai, A. D. Aguirre, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and microscopy for ex vivo multiscale evaluation of human breast tissues,” Cancer Res.70(24), 10071–10079 (2010).
[CrossRef] [PubMed]

C. Zhou, Y. Wang, A. D. Aguirre, T. H. Tsai, D. W. Cohen, J. L. Connolly, and J. G. Fujimoto, “Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy,” J. Biomed. Opt.15(1), 016001 (2010).
[CrossRef] [PubMed]

Wax, A.

Webb, R. H.

Williams, M. E.

B. M. Hoeling, A. D. Fernandez, R. C. Haskell, E. Huang, W. R. Myers, D. C. Petersen, S. E. Ungersma, R. Y. Wang, M. E. Williams, and S. E. Fraser, “An optical coherence microscope for 3-dimensional imaging in developmental biology,” Opt. Express6(7), 136–146 (2000).
[CrossRef] [PubMed]

J. W. Hettinger, M. de la Peña Mattozzi, W. R. Myers, M. E. Williams, A. Reeves, R. L. Parsons, R. C. Haskell, D. C. Petersen, R. Wang, and J. I. Medford, “Optical coherence microscopy. a technology for rapid, in vivo, non-destructive visualization of plants and plant cells,” Plant Physiol.123(1), 3–16 (2000).
[CrossRef] [PubMed]

Winder, S.

S. Winder, G. Hua, and M. Brown, “Picking the best DAISY,” in IEEE Conference on Computer Vision and Pattern Recognition, 2009, pp. 178–185.

Wojtkowski, M.

Xi, J. F.

Xu, C. Y.

Yang, C. H.

Yazdanfar, S.

M. A. Choma, A. K. Ellerbee, S. Yazdanfar, and J. A. Izatt, “Doppler flow imaging of cytoplasmic streaming using spectral domain phase microscopy,” J. Biomed. Opt.11(2), 024014 (2006).
[CrossRef] [PubMed]

Zhou, C.

H. C. Lee, C. Zhou, D. W. Cohen, A. E. Mondelblatt, Y. Wang, A. D. Aguirre, D. Shen, Y. Sheikine, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and optical coherence microscopy imaging of ex vivo human renal tissues,” J. Urol.187(2), 691–699 (2012).
[CrossRef] [PubMed]

C. Zhou, D. W. Cohen, Y. Wang, H.-C. Lee, A. E. Mondelblatt, T.-H. Tsai, A. D. Aguirre, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and microscopy for ex vivo multiscale evaluation of human breast tissues,” Cancer Res.70(24), 10071–10079 (2010).
[CrossRef] [PubMed]

C. Zhou, Y. Wang, A. D. Aguirre, T. H. Tsai, D. W. Cohen, J. L. Connolly, and J. G. Fujimoto, “Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy,” J. Biomed. Opt.15(1), 016001 (2010).
[CrossRef] [PubMed]

ACM Trans. Graphic (1)

A. Agarwala, M. Dontcheva, M. Agrawala, S. Drucker, A. Colburn, B. Curless, D. Salesin, and M. Cohen, “Interactive digital photomontage,” ACM Trans. Graphic23(3), 294–302 (2004).
[CrossRef]

Am. J. Obstet. Gynecol. (1)

R. A. Drezek, T. Collier, C. K. Brookner, A. Malpica, R. Lotan, R. R. Richards-Kortum, and M. Follen, “Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid,” Am. J. Obstet. Gynecol.182(5), 1135–1139 (2000).
[CrossRef] [PubMed]

Appl. Opt. (1)

Appl. Phys. Lett. (1)

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett.88(5), 053901 (2006).
[CrossRef]

Cancer Res. (1)

C. Zhou, D. W. Cohen, Y. Wang, H.-C. Lee, A. E. Mondelblatt, T.-H. Tsai, A. D. Aguirre, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and microscopy for ex vivo multiscale evaluation of human breast tissues,” Cancer Res.70(24), 10071–10079 (2010).
[CrossRef] [PubMed]

Eur. J. Surg. Oncol. (1)

F. J. Fleming, A. D. K. Hill, E. W. Mc Dermott, A. O’Doherty, N. J. O’Higgins, and C. M. Quinn, “Intraoperative margin assessment and re-excision rate in breast conserving surgery,” Eur. J. Surg. Oncol.30(3), 233–237 (2004).
[CrossRef] [PubMed]

Found. Trends. Comput. Graph. Vis. (1)

R. Szeliski, “Image alignment and stitching: a tutorial,” Found. Trends. Comput. Graph. Vis.2(1), 1–104 (2006).
[CrossRef]

IEEE J. Sel. Top. Quantum Electron. (1)

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]

J. Biomed. Opt. (5)

S. Tang, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source,” J. Biomed. Opt.11(2), 020502 (2006).
[CrossRef] [PubMed]

A. D. Aguirre, Y. Chen, B. Bryan, H. Mashimo, Q. Huang, J. L. Connolly, and J. G. Fujimoto, “Cellular resolution ex vivo imaging of gastrointestinal tissues with optical coherence microscopy,” J. Biomed. Opt.15(1), 016025 (2010).
[CrossRef] [PubMed]

M. A. Choma, A. K. Ellerbee, S. Yazdanfar, and J. A. Izatt, “Doppler flow imaging of cytoplasmic streaming using spectral domain phase microscopy,” J. Biomed. Opt.11(2), 024014 (2006).
[CrossRef] [PubMed]

C. Zhou, Y. Wang, A. D. Aguirre, T. H. Tsai, D. W. Cohen, J. L. Connolly, and J. G. Fujimoto, “Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy,” J. Biomed. Opt.15(1), 016001 (2010).
[CrossRef] [PubMed]

S. Abeytunge, Y. Li, B. Larson, R. Toledo-Crow, and M. Rajadhyaksha, “Rapid confocal imaging of large areas of excised tissue with strip mosaicing,” J. Biomed. Opt.16(5), 050504 (2011).
[CrossRef] [PubMed]

J. Urol. (1)

H. C. Lee, C. Zhou, D. W. Cohen, A. E. Mondelblatt, Y. Wang, A. D. Aguirre, D. Shen, Y. Sheikine, J. G. Fujimoto, and J. L. Connolly, “Integrated optical coherence tomography and optical coherence microscopy imaging of ex vivo human renal tissues,” J. Urol.187(2), 691–699 (2012).
[CrossRef] [PubMed]

Nat. Med. (1)

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

Nat. Phys. (1)

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]

Opt. Express (6)

Opt. Lett. (6)

Oral Oncol. (1)

A. Binahmed, R. W. Nason, and A. A. Abdoh, “The clinical significance of the positive surgical margin in oral cancer,” Oral Oncol.43(8), 780–784 (2007).
[CrossRef] [PubMed]

Plant Physiol. (1)

J. W. Hettinger, M. de la Peña Mattozzi, W. R. Myers, M. E. Williams, A. Reeves, R. L. Parsons, R. C. Haskell, D. C. Petersen, R. Wang, and J. I. Medford, “Optical coherence microscopy. a technology for rapid, in vivo, non-destructive visualization of plants and plant cells,” Plant Physiol.123(1), 3–16 (2000).
[CrossRef] [PubMed]

Thorac. Cardiovasc. Surg. (1)

K. Kayser, E. Anyanwu, H. G. Bauer, and I. Vogt-Moykopf, “Tumor Presence at Resection Boundaries and Lymph-Node Metastasis in Bronchial Carcinoma Patients,” Thorac. Cardiovasc. Surg.41(5), 308–311 (1993).
[CrossRef] [PubMed]

Other (5)

V. Jayaraman, J. Jiang, H. Li, P. Heim, G. Cole, B. Potsaid, J. G. Fujimoto, and A. Cable, “OCT imaging up to 760kHz axial scan rate using single-mode 1310nm MEMS-tunable VCSELs with> 100nm tuning range,” in CLEO: Science and Innovations (Optical Society of America, 2011).

V. Jayaraman, J. Jiang, B. Potsaid, G. Cole, J. Fujimoto, and A. Cable, “Design and performance of broadly tunable, narrow line-width, high repetition rate 1310nm VCSELs for swept source optical coherence tomography,” in Proc. of SPIE Vol, 2012), 82760D–82761.
[CrossRef]

B. Potsaid, V. Jayaraman, J. G. Fujimoto, J. Jiang, P. J. S. Heim, and A. E. Cable, “MEMS tunable VCSEL light source for ultrahigh speed 60kHz-1MHz axial scan rate and long range centimeter class OCT imaging,” in SPIE BiOS, (International Society for Optics and Photonics, 2012), 82130M–82130M–82138.

A. D. Aguirre, “Advances in Optical Coherence Tomography and Microscopy for endoscopic applications and functional neuroimaging,” Ph D (Harvard-MIT Division of Health Sciences and Technology, 2008).

S. Winder, G. Hua, and M. Brown, “Picking the best DAISY,” in IEEE Conference on Computer Vision and Pattern Recognition, 2009, pp. 178–185.

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Figures (9)

Fig. 1
Fig. 1

Schematic of the VCSEL SS-OCM System. Data was acquired using a dual-balanced detector with 200 MHz bandwidth. DAQ: Data acquisition card. DAQ-C: External clock channel. DAQ-I: Acquisition channel. DMG: Dispersion matching glass. IA: Iris attenuator. DBT: Dual balanced detector. PS: Pulse shaper. I: Isolator, PC: Polarization controller. Focal lengths of collimating, scan and tube lenses are fs = 11 mm, fs = 37.5 mm and ft = 85 mm, respectively.

Fig. 2
Fig. 2

System characterization. A) OCM image of a USAF 1951 resolution test chart acquired with the 40X water immersion objective. B) Spectrum of the VCSEL measured with an optical spectrum analyzer showing a 117 nm tuning range. C) Mirror fringe signal acquired using optical clocking. D) Spectrally reshaped fringe signal. E) Axial PSF of the raw fringe (blue line) with 11.4 µm resolution in air (~8.1 µm in tissue), and spectrally reshaped fringe (red line) with 13.5 µm resolution in air (~9.6 µm in tissue). F) Sensitivity fall-off of the VCSEL swept source obtained from the raw fringes and spectrally reshaped fringes (G), showing no significant change in the signal sensitivity across the imaging range.

Fig. 3
Fig. 3

Correction of delay variation with scanning demonstrated in images of fresh human colon obtained ex vivo. (A) and (B) are from two different depths from the same data set, where (C) is the calibrated image. (D) shows a surface plot of the cover slip surface taken with the 40X/W objective. Dashed lines in (A) and (B) indicate the regions that are in focus for that particular depth. Arrows point to goblet cells.

Fig. 4
Fig. 4

Ex vivo OCM images (A-C) and corresponding histology (G) of fresh human colon specimen obtained using the 10X/W, 20X/W and 40X/W objectives. (D-F) Show the corresponding simulated confocal images. Arrows point to goblet cells.

Fig. 5
Fig. 5

Ex vivo OCM images (A-C) and corresponding histology (D) of a fresh normal human thyroid specimen obtained using the 10X/W, 20X/W and 40X/W objectives.

Fig. 6
Fig. 6

Depth resolved OCM with the 10X/W objective imaging a fresh ex vivo human thyroid specimen. (A) Volume rendering emphasizing that arbitrary planes can be selected for visualization. For the imaging planes indicated by the colored lines, reconstructed cross sectional and en face images are shown in (B-E). (C-E) are en face images from 50 µm, 130 µm and 180 µm below the surface of the specimen, respectively. The cross sectional image in (B) is displayed using logarithmic scale, whereas (C-E) are displayed using square root scale.

Fig. 7
Fig. 7

Ex vivo OCM images (A-D) and corresponding histology (E) from fresh thyroid specimen with a histological diagnosis of multinodular goiter, obtained using the 20X/air and 40X/W objectives.

Fig. 8
Fig. 8

Ex vivo OCM images (A-C) and corresponding histology (D-F) from fresh normal human kidney (A, B, D, E) and clear cell renal cell carcinoma specimens (C, F) obtained using the 40X/W (A,C) and 20X/W (B) objectives. (A, D, C, F) are from renal cortex, whereas (B, E) are from renal medulla. CT: Convoluted tubules, G: Glomerulus, T: Collecting ducts.

Fig. 9
Fig. 9

Large field mosaic OCM image of a normal human kidney specimen. Image is constructed by merging 30 frames taken with the 40X/W objective producing a total field of 1.8 mm x 2.1 mm. (B) shows a zoomed view for the region shown with dashed lines in (A). CT: Convoluted tubules, G: Glomerulus.

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