Abstract

We describe a dual-modality laser scanning endomicroscope that provides simultaneous fluorescence contrast based on confocal laser endomicroscopy (CLE) and phase-gradient contrast based on scanning oblique back-scattering microscopy (sOBM). The probe consists of a 2.6mm-diameter micro-objective attached to a 30,000-core flexible fiber bundle. The dual contrasts are inherently co-registered, providing complementary information on labeled and un-labeled sample structure. Proof of principle demonstrations are presented with ex-vivo mouse colon tissue.

© 2016 Optical Society of America

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  40. D. Cunefare, R. F. Cooper, B. Higgins, D. F. Katz, A. Dubra, J. Carroll, and S. Farsiu, “Automatic detection of cone photoreceptors in split detector adaptive optics scanning light ophthalmoscope images,” Biomed. Opt. Express 7, 2036–2050 (2012).
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2015 (1)

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

2014 (4)

H. Li, Y. Li, L. Cui, B. Wang, W. Cui, M. Li, and Y. Cheng, “Monitoring pancreatic carcinogenesis by the molecular imaging of cathepsin E in vivo using confocal laser endomicroscopy,” PloS One 9, e106566 (2014).
[Crossref] [PubMed]

W. A. Welge, a. T. DeMarco, J. M. Watson, P. S. Rice, J. K. Barton, and M. A. Kupinski, “Diagnostic potential of multimodal imaging of ovarian tissue using optical coherence tomography and second-harmonic generation microscopy,” J. Med. Imaging 1, 025501 (2014).
[Crossref]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments In Vivo Imaging of Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55, 4244–4251 (2014).
[Crossref] [PubMed]

J. Mertz, A. Gasecka, A. Daradich, I. Davison, and D. Coté, “Phase-gradient contrast in thick tissue with a scanning microscope,” Biomed. Opt. Express 5, 407–416 (2014).
[Crossref] [PubMed]

2013 (4)

X. Ou, R. Horstmeyer, C. Yang, and G. Zheng, “Quantitative phase imaging via Fourier ptychographic microscopy,” Opt. Lett. 38, 4845–4848 (2013).
[Crossref] [PubMed]

T. Y. Chui, T. J. Gast, and S. A. Burns, “Imaging of Vascular Wall Fine Structure in the Human Retina Using Adaptive Optics Scanning Laser Ophthalmoscopy Vascular Wall Imaging Using AOSLO,” Invest. Ophthalmol. Vis. Sci. 54, 7115–7124 (2013).
[Crossref] [PubMed]

T. N. Ford and J. Mertz, “Video-rate imaging of microcirculation with single-exposure oblique back-illumination microscopy,” J. Biomed. Opt. 18, 066007 (2013).
[Crossref] [PubMed]

Q. T. Nguyen and R. Y. Tsien, “Fluorescence-guided surgery with live molecular navigation - a new cutting edge,” Nat. Rev. Cancer 13, 653–662 (2013).
[Crossref] [PubMed]

2012 (6)

2011 (1)

2010 (1)

K. C. Lee, S. Sharma, J. B. Tuttle, and W. D. Steers, “Origin and characterization of retrograde labeled neurons supplying the rat urethra using fiberoptic confocal fluorescent microscopy in vivo and immunohistochemistry,” J. Urology 184, 1550–1554 (2010).
[Crossref]

2009 (3)

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101, 2015–2022 (2009).
[Crossref] [PubMed]

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14, 030502 (2009).
[Crossref] [PubMed]

S. B. Mehta and C. J. R. Sheppard, “Quantitative phase-gradient imaging at high resolution with asymmetric illumination-based differential phase contrast,” Opt. Lett. 34, 1924–1926 (2009).
[Crossref] [PubMed]

2008 (3)

N. Bozinovic, C. Ventalon, T. Ford, and J. Mertz, “Fluorescence endomicroscopy with structured illumination,” Opt. Express 16, 8016–8025 (2008).
[Crossref] [PubMed]

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med. 14, 454–458 (2008).
[Crossref] [PubMed]

M. C. Pierce, D. J. Javier, and R. Richards-Kortum, “Optical contrast agents and imaging systems for detection and diagnosis of cancer,” Int. J. Cancer 123, 1979–1990 (2008).
[Crossref] [PubMed]

2007 (4)

P. S. P. Thong, M. Olivo, K. W. Kho, W. Zheng, K. Mancer, M. Harris, and K. C. Soo, “Laser confocal endomicroscopy as a novel technique for fluorescence diagnostic imaging of the oral cavity,” J. Biomed. Opt. 12, 014007 (2007).
[Crossref] [PubMed]

C. Joo, K. H. Kim, and J. F. de Boer, “Spectral-domain optical coherence phase and multiphoton microscopy,” Opt. Lett. 32, 623–625 (2007).
[Crossref] [PubMed]

T. J. Muldoon, M. C. Pierce, D. L. Nida, M. D. Williams, A. Gillenwater, and R. Richards-Kortum, “Subcellular-resolution molecular imaging within living tissue by fiber microendoscopy,” Opt. Express 15, 16413–16423 (2007).
[Crossref] [PubMed]

D. C. Adler, Y. Chen, R. Huber, J. Schmitt, J. Connolly, and G. J. Fujimoto, “Three-dimensional endomicroscopy using optical coherence tomography,” Nat. Photon. 1, 709–716 (2007).
[Crossref]

2006 (2)

R. Yi, K. K. Chu, and J. Mertz, “Graded-field microscopy with white light,” Opt. Express 14, 5191–5200 (2006).
[Crossref] [PubMed]

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg Med 38, 305–313 (2006).
[Crossref] [PubMed]

2005 (1)

2004 (1)

2003 (1)

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210, 166–175 (2003).
[Crossref] [PubMed]

2001 (1)

1997 (1)

1996 (1)

1993 (1)

1984 (1)

D. K. Hamilton and C. J. R. Sheppard, “Differential phase contrast in scanning optical microscopy,” J. Microscopy 133, 27–39 (1984).
[Crossref]

1955 (1)

G. Nomarski, “Differential microinterferometer with polarized waves,” J. Phys. Radium 16, 9S–11S (1955).

1942 (1)

F. Zernike, “Phase contrast, a new method for the microscopic observation of transparent objects,” Physica 9, 686–698 (1942).
[Crossref]

Abrat, B.

B. Viellerobe, A. Osdoit, C. Cavé, F. Lacombe, S. Loiseau, and B. Abrat, “Mauna Kea technologies’ F400 prototype: a new tool for in vivo microscopic imaging during endoscopy,” in Biomedical Optics 2006, 60820C. International Society for Optics and Photonics, 2006.

Adler, D. C.

D. C. Adler, Y. Chen, R. Huber, J. Schmitt, J. Connolly, and G. J. Fujimoto, “Three-dimensional endomicroscopy using optical coherence tomography,” Nat. Photon. 1, 709–716 (2007).
[Crossref]

Akkin, T.

Amos, W. B.

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210, 166–175 (2003).
[Crossref] [PubMed]

Aziz, D.

Barton, J. K.

W. A. Welge, a. T. DeMarco, J. M. Watson, P. S. Rice, J. K. Barton, and M. A. Kupinski, “Diagnostic potential of multimodal imaging of ovarian tissue using optical coherence tomography and second-harmonic generation microscopy,” J. Med. Imaging 1, 025501 (2014).
[Crossref]

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg Med 38, 305–313 (2006).
[Crossref] [PubMed]

Bartoo, A. C.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14, 030502 (2009).
[Crossref] [PubMed]

Batrin, R.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Besselsen, D. G.

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg Med 38, 305–313 (2006).
[Crossref] [PubMed]

Bourg-Heckly, G.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Bozinovic, N.

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14, 030502 (2009).
[Crossref] [PubMed]

N. Bozinovic, C. Ventalon, T. Ford, and J. Mertz, “Fluorescence endomicroscopy with structured illumination,” Opt. Express 16, 8016–8025 (2008).
[Crossref] [PubMed]

Braud, F.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Brevier, J.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Brown, C. M.

Burns, S. A.

T. Y. Chui, T. J. Gast, and S. A. Burns, “Imaging of Vascular Wall Fine Structure in the Human Retina Using Adaptive Optics Scanning Laser Ophthalmoscopy Vascular Wall Imaging Using AOSLO,” Invest. Ophthalmol. Vis. Sci. 54, 7115–7124 (2013).
[Crossref] [PubMed]

Carroll, J.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments In Vivo Imaging of Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55, 4244–4251 (2014).
[Crossref] [PubMed]

D. Cunefare, R. F. Cooper, B. Higgins, D. F. Katz, A. Dubra, J. Carroll, and S. Farsiu, “Automatic detection of cone photoreceptors in split detector adaptive optics scanning light ophthalmoscope images,” Biomed. Opt. Express 7, 2036–2050 (2012).
[Crossref]

Cattermole, D. M.

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210, 166–175 (2003).
[Crossref] [PubMed]

Cavé, C.

B. Viellerobe, A. Osdoit, C. Cavé, F. Lacombe, S. Loiseau, and B. Abrat, “Mauna Kea technologies’ F400 prototype: a new tool for in vivo microscopic imaging during endoscopy,” in Biomedical Optics 2006, 60820C. International Society for Optics and Photonics, 2006.

Celli, J. P.

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101, 2015–2022 (2009).
[Crossref] [PubMed]

Chen, Y.

Cheng, Y.

H. Li, Y. Li, L. Cui, B. Wang, W. Cui, M. Li, and Y. Cheng, “Monitoring pancreatic carcinogenesis by the molecular imaging of cathepsin E in vivo using confocal laser endomicroscopy,” PloS One 9, e106566 (2014).
[Crossref] [PubMed]

Chu, K. K.

T. N. Ford, K. K. Chu, and J. Mertz, “Phase-gradient microscopy in thick tissue with oblique back-illumination,” Nat. Methods 9, 1195–1197 (2012).
[Crossref] [PubMed]

A. B. Parthasarathy, K. K. Chu, T. N. Ford, and J. Mertz, “Quantitative phase imaging using a partitioned detection aperture,” Opt. Lett. 37, 4062–4064 (2012).
[Crossref] [PubMed]

S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14, 030502 (2009).
[Crossref] [PubMed]

R. Yi, K. K. Chu, and J. Mertz, “Graded-field microscopy with white light,” Opt. Express 14, 5191–5200 (2006).
[Crossref] [PubMed]

Chui, T. Y.

T. Y. Chui, T. J. Gast, and S. A. Burns, “Imaging of Vascular Wall Fine Structure in the Human Retina Using Adaptive Optics Scanning Laser Ophthalmoscopy Vascular Wall Imaging Using AOSLO,” Invest. Ophthalmol. Vis. Sci. 54, 7115–7124 (2013).
[Crossref] [PubMed]

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H. Li, Y. Li, L. Cui, B. Wang, W. Cui, M. Li, and Y. Cheng, “Monitoring pancreatic carcinogenesis by the molecular imaging of cathepsin E in vivo using confocal laser endomicroscopy,” PloS One 9, e106566 (2014).
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L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg Med 38, 305–313 (2006).
[Crossref] [PubMed]

Tuttle, J. B.

K. C. Lee, S. Sharma, J. B. Tuttle, and W. D. Steers, “Origin and characterization of retrograde labeled neurons supplying the rat urethra using fiberoptic confocal fluorescent microscopy in vivo and immunohistochemistry,” J. Urology 184, 1550–1554 (2010).
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L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg Med 38, 305–313 (2006).
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Wang, B.

H. Li, Y. Li, L. Cui, B. Wang, W. Cui, M. Li, and Y. Cheng, “Monitoring pancreatic carcinogenesis by the molecular imaging of cathepsin E in vivo using confocal laser endomicroscopy,” PloS One 9, e106566 (2014).
[Crossref] [PubMed]

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P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med. 14, 454–458 (2008).
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W. A. Welge, a. T. DeMarco, J. M. Watson, P. S. Rice, J. K. Barton, and M. A. Kupinski, “Diagnostic potential of multimodal imaging of ovarian tissue using optical coherence tomography and second-harmonic generation microscopy,” J. Med. Imaging 1, 025501 (2014).
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P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med. 14, 454–458 (2008).
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Xu., C.

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P. S. P. Thong, M. Olivo, K. W. Kho, W. Zheng, K. Mancer, M. Harris, and K. C. Soo, “Laser confocal endomicroscopy as a novel technique for fluorescence diagnostic imaging of the oral cavity,” J. Biomed. Opt. 12, 014007 (2007).
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W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101, 2015–2022 (2009).
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Appl. Opt. (1)

Biomed. Opt. Express (3)

Br. J. Cancer (1)

W. Zhong, J. P. Celli, I. Rizvi, Z. Mai, B. Q. Spring, S. H. Yun, and T. Hasan, “In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring,” Br. J. Cancer 101, 2015–2022 (2009).
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T. Y. Chui, T. J. Gast, and S. A. Burns, “Imaging of Vascular Wall Fine Structure in the Human Retina Using Adaptive Optics Scanning Laser Ophthalmoscopy Vascular Wall Imaging Using AOSLO,” Invest. Ophthalmol. Vis. Sci. 54, 7115–7124 (2013).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments In Vivo Imaging of Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55, 4244–4251 (2014).
[Crossref] [PubMed]

J. Biomed. Opt. (4)

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17, 0211051 (2012).
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P. S. P. Thong, M. Olivo, K. W. Kho, W. Zheng, K. Mancer, M. Harris, and K. C. Soo, “Laser confocal endomicroscopy as a novel technique for fluorescence diagnostic imaging of the oral cavity,” J. Biomed. Opt. 12, 014007 (2007).
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S. Santos, K. K. Chu, D. Lim, N. Bozinovic, T. N. Ford, C. Hourtoule, A. C. Bartoo, S. K. Singh, and J. Mertz, “Optically sectioned fluorescence endomicroscopy with hybrid-illumination imaging through a flexible fiber bundle,” J. Biomed. Opt. 14, 030502 (2009).
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T. N. Ford and J. Mertz, “Video-rate imaging of microcirculation with single-exposure oblique back-illumination microscopy,” J. Biomed. Opt. 18, 066007 (2013).
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J. Med. Imaging (1)

W. A. Welge, a. T. DeMarco, J. M. Watson, P. S. Rice, J. K. Barton, and M. A. Kupinski, “Diagnostic potential of multimodal imaging of ovarian tissue using optical coherence tomography and second-harmonic generation microscopy,” J. Med. Imaging 1, 025501 (2014).
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J. Microsc. (1)

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210, 166–175 (2003).
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[Crossref]

Lasers Surg Med (1)

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg Med 38, 305–313 (2006).
[Crossref] [PubMed]

Nat. Med. (1)

P. L. Hsiung, J. Hardy, S. Friedland, R. Soetikno, C. B. Du, A. P. Wu, P. Sahbaie, J. M. Crawford, A. W. Lowe, C. H. Contag, and T. D. Wang, “Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal microendoscopy,” Nat. Med. 14, 454–458 (2008).
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Nat. Photon. (1)

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Nat. Rev. Cancer (1)

Q. T. Nguyen and R. Y. Tsien, “Fluorescence-guided surgery with live molecular navigation - a new cutting edge,” Nat. Rev. Cancer 13, 653–662 (2013).
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Physica (1)

F. Zernike, “Phase contrast, a new method for the microscopic observation of transparent objects,” Physica 9, 686–698 (1942).
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PloS One (1)

H. Li, Y. Li, L. Cui, B. Wang, W. Cui, M. Li, and Y. Cheng, “Monitoring pancreatic carcinogenesis by the molecular imaging of cathepsin E in vivo using confocal laser endomicroscopy,” PloS One 9, e106566 (2014).
[Crossref] [PubMed]

Sci. Rep. (1)

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Other (2)

B. Viellerobe, A. Osdoit, C. Cavé, F. Lacombe, S. Loiseau, and B. Abrat, “Mauna Kea technologies’ F400 prototype: a new tool for in vivo microscopic imaging during endoscopy,” in Biomedical Optics 2006, 60820C. International Society for Optics and Photonics, 2006.

V. Tuchin, Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnosis, Vol. 13, (SPIE press, Bellingham2007).
[Crossref]

Supplementary Material (2)

NameDescription
» Visualization 1: AVI (249 KB)      Video acquired with micro-objective
» Visualization 2: AVI (4506 KB)      Video acquired with no probe

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Figures (5)

Fig. 1
Fig. 1 Principle of sOBM based on differential split detection. In-focus phase gradients at the laser focus deflect the laser beam and lead to an asymmetric distribution of the back-scattered light with respect to the focus axis. This imbalance is detected by a differential split detector. To obtain an image, the sample must be scanned, or the laser light must be scanned and de-scanned (see setup).

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Fig. 2
Fig. 2 Schematic of our dual modality endomicroscope. PBS, polarized beam splitter; GM, galvanometric mirrors; OBJ, microscope objective; FB, fiber bundle; μOBJ, micro-objective; RP, reflective pinhole; EF, emission filter; PMT, photomultiplier tube; LP, linear polarizer; ND, neutral density filter; QD, quadrant detector.

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Fig. 3
Fig. 3 Simultaneous fluorescence (left) and sOBM (right) images of 20μm beads in a scattering phantom, acquired with a 2.5× micro-objective. Top and bottom panels correspond to images before and after the application of segmentation-interpolation to remove patterning artifacts due to the fiber bundle cores (scale bar 24μm).

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Fig. 4
Fig. 4 Top row from left to right: fluorescence, phase-gradient and combined images of mouse colon tissue labeled with acridine orange, acquired with 2.5× micro-objective (scale bar 24μm). See also Visualization 1 for a video recorded with a frame rate of 2 fps. Bottom row from left to right, fluorescence, phase-gradient and combined images of the same sample acquired with 1× micro-objective (scale bar 60μm).

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Fig. 5
Fig. 5 From left to right: fluorescence, phase-gradient and combined images of labeled mouse colon tissue acquired directly through the microscope objective with no fiber probe (scale bar 60μm). These span the same FoV as the bottom row images in Fig. 4 and can be used to evaluate the degradation caused by the fiber probe. Also see Visualization 2 for a video recorded with this setup.

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