Abstract

We present an all-fiber-optic scanning multiphoton endomicroscope with 1.55μm excitation without the need for prechirping femtosecond pulses before the endomicroscope. The system consists of a 1.55μm femtosecond fiber laser, a customized double-clad fiber for light delivery and fluorescence collection, and a piezoelectric scan head. We demonstrate two-photon imaging of cultured cells and mouse tissue, both labeled with indocyanine green. Free-space multiphoton imaging with near-IR emission has previously shown benefits in reduced background fluorescence and lower attenuation for the fluorescence emission. For fiber-optic multiphoton imaging there is the additional advantage of using the soliton effect at the telecommunication wavelengths (1.31.6μm) in fibers, permitting dispersion-compensation-free, small-footprint systems. We expect these advantages will help transition multiphoton endomicroscopy to the clinic.

© 2011 Optical Society of America

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S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, and S. Achilefu, J Biomed. Opt. 15, 030505 (2010).
[CrossRef] [PubMed]

T. H. Kim, Y. P. Chen, C. W. Mount, W. R. Gombotz, X. D. Li, and S. H. Pun, Pharm. Res. 27, 1900 (2010).
[CrossRef] [PubMed]

2009

V. Andresen, S. Alexander, W. M. Heupel, M. Hirschberg, R. M. Hoffman, and P. Friedl, Curr. Opin. Biotechnol. 20, 54 (2009).
[CrossRef] [PubMed]

Y. C. Wu, J. F. Xi, M. J. Cobb, and X. D. Li, Opt. Lett. 34, 953 (2009).
[CrossRef] [PubMed]

2008

V. B. Rodriguez, S. M. Henry, A. S. Hoffman, P. S. Stayton, X. D. Li, and S. H. Pun, J. Biomed. Opt. 13, 014025 (2008).
[CrossRef] [PubMed]

2007

G. McConnell, Phys. Med. Biol. 52, 717 (2007).
[CrossRef] [PubMed]

2006

2001

1996

1995

K. C. Chan and H. F. Liu, IEEE J. Quantum Electron. 31, 2226 (1995).
[CrossRef]

1990

W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
[CrossRef] [PubMed]

1987

A. Gouveia-Neto, A. Gomes, and J. Taylor, IEEE J. Quantum Electron. 23, 1193 (1987).
[CrossRef]

1960

G. R. Cherrick, S. W. Stein, C. M. Leevy, and C. S. Davidson, J. Clin. Invest. 39, 592 (1960).
[CrossRef] [PubMed]

Achilefu, S.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, and S. Achilefu, J Biomed. Opt. 15, 030505 (2010).
[CrossRef] [PubMed]

Akers, W. J.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, and S. Achilefu, J Biomed. Opt. 15, 030505 (2010).
[CrossRef] [PubMed]

Alexander, S.

V. Andresen, S. Alexander, W. M. Heupel, M. Hirschberg, R. M. Hoffman, and P. Friedl, Curr. Opin. Biotechnol. 20, 54 (2009).
[CrossRef] [PubMed]

Andresen, V.

V. Andresen, S. Alexander, W. M. Heupel, M. Hirschberg, R. M. Hoffman, and P. Friedl, Curr. Opin. Biotechnol. 20, 54 (2009).
[CrossRef] [PubMed]

Berezin, M. Y.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, and S. Achilefu, J Biomed. Opt. 15, 030505 (2010).
[CrossRef] [PubMed]

Chan, K. C.

K. C. Chan and H. F. Liu, IEEE J. Quantum Electron. 31, 2226 (1995).
[CrossRef]

Chen, I. H.

Chen, P. C.

Chen, Y.

Y. Chen, T. G. Jabbour, and X. Li, in Biomedical Optics, OSA Technical Digest (CD) (Optical Society of America, 2010), paper BTuC6.
[PubMed]

Chen, Y. P.

T. H. Kim, Y. P. Chen, C. W. Mount, W. R. Gombotz, X. D. Li, and S. H. Pun, Pharm. Res. 27, 1900 (2010).
[CrossRef] [PubMed]

Cherrick, G. R.

G. R. Cherrick, S. W. Stein, C. M. Leevy, and C. S. Davidson, J. Clin. Invest. 39, 592 (1960).
[CrossRef] [PubMed]

Chu, S. W.

Cobb, M. J.

Cranfield, C.

Davidson, C. S.

G. R. Cherrick, S. W. Stein, C. M. Leevy, and C. S. Davidson, J. Clin. Invest. 39, 592 (1960).
[CrossRef] [PubMed]

Denk, W.

W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
[CrossRef] [PubMed]

Friedl, P.

V. Andresen, S. Alexander, W. M. Heupel, M. Hirschberg, R. M. Hoffman, and P. Friedl, Curr. Opin. Biotechnol. 20, 54 (2009).
[CrossRef] [PubMed]

Fu, L.

Gombotz, W. R.

T. H. Kim, Y. P. Chen, C. W. Mount, W. R. Gombotz, X. D. Li, and S. H. Pun, Pharm. Res. 27, 1900 (2010).
[CrossRef] [PubMed]

Gomes, A.

A. Gouveia-Neto, A. Gomes, and J. Taylor, IEEE J. Quantum Electron. 23, 1193 (1987).
[CrossRef]

Gouveia-Neto, A.

A. Gouveia-Neto, A. Gomes, and J. Taylor, IEEE J. Quantum Electron. 23, 1193 (1987).
[CrossRef]

Gu, M.

Henry, S. M.

V. B. Rodriguez, S. M. Henry, A. S. Hoffman, P. S. Stayton, X. D. Li, and S. H. Pun, J. Biomed. Opt. 13, 014025 (2008).
[CrossRef] [PubMed]

Heupel, W. M.

V. Andresen, S. Alexander, W. M. Heupel, M. Hirschberg, R. M. Hoffman, and P. Friedl, Curr. Opin. Biotechnol. 20, 54 (2009).
[CrossRef] [PubMed]

Hirschberg, M.

V. Andresen, S. Alexander, W. M. Heupel, M. Hirschberg, R. M. Hoffman, and P. Friedl, Curr. Opin. Biotechnol. 20, 54 (2009).
[CrossRef] [PubMed]

Hoffman, A. S.

V. B. Rodriguez, S. M. Henry, A. S. Hoffman, P. S. Stayton, X. D. Li, and S. H. Pun, J. Biomed. Opt. 13, 014025 (2008).
[CrossRef] [PubMed]

Hoffman, R. M.

V. Andresen, S. Alexander, W. M. Heupel, M. Hirschberg, R. M. Hoffman, and P. Friedl, Curr. Opin. Biotechnol. 20, 54 (2009).
[CrossRef] [PubMed]

Jabbour, T. G.

Y. Chen, T. G. Jabbour, and X. Li, in Biomedical Optics, OSA Technical Digest (CD) (Optical Society of America, 2010), paper BTuC6.
[PubMed]

Jain, A.

Joo, C.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, and S. Achilefu, J Biomed. Opt. 15, 030505 (2010).
[CrossRef] [PubMed]

Kim, T. H.

T. H. Kim, Y. P. Chen, C. W. Mount, W. R. Gombotz, X. D. Li, and S. H. Pun, Pharm. Res. 27, 1900 (2010).
[CrossRef] [PubMed]

Leevy, C. M.

G. R. Cherrick, S. W. Stein, C. M. Leevy, and C. S. Davidson, J. Clin. Invest. 39, 592 (1960).
[CrossRef] [PubMed]

Li, X.

Y. Chen, T. G. Jabbour, and X. Li, in Biomedical Optics, OSA Technical Digest (CD) (Optical Society of America, 2010), paper BTuC6.
[PubMed]

Li, X. D.

T. H. Kim, Y. P. Chen, C. W. Mount, W. R. Gombotz, X. D. Li, and S. H. Pun, Pharm. Res. 27, 1900 (2010).
[CrossRef] [PubMed]

Y. C. Wu, J. F. Xi, M. J. Cobb, and X. D. Li, Opt. Lett. 34, 953 (2009).
[CrossRef] [PubMed]

V. B. Rodriguez, S. M. Henry, A. S. Hoffman, P. S. Stayton, X. D. Li, and S. H. Pun, J. Biomed. Opt. 13, 014025 (2008).
[CrossRef] [PubMed]

M. T. Myaing, D. J. MacDonald, and X. D. Li, Opt. Lett. 31, 1076 (2006).
[CrossRef] [PubMed]

Lin, B. L.

Liu, H. F.

K. C. Chan and H. F. Liu, IEEE J. Quantum Electron. 31, 2226 (1995).
[CrossRef]

Liu, T. M.

MacDonald, D. J.

McConnell, G.

G. McConnell, Phys. Med. Biol. 52, 717 (2007).
[CrossRef] [PubMed]

Mount, C. W.

T. H. Kim, Y. P. Chen, C. W. Mount, W. R. Gombotz, X. D. Li, and S. H. Pun, Pharm. Res. 27, 1900 (2010).
[CrossRef] [PubMed]

Myaing, M. T.

Pun, S. H.

T. H. Kim, Y. P. Chen, C. W. Mount, W. R. Gombotz, X. D. Li, and S. H. Pun, Pharm. Res. 27, 1900 (2010).
[CrossRef] [PubMed]

V. B. Rodriguez, S. M. Henry, A. S. Hoffman, P. S. Stayton, X. D. Li, and S. H. Pun, J. Biomed. Opt. 13, 014025 (2008).
[CrossRef] [PubMed]

Rodriguez, V. B.

V. B. Rodriguez, S. M. Henry, A. S. Hoffman, P. S. Stayton, X. D. Li, and S. H. Pun, J. Biomed. Opt. 13, 014025 (2008).
[CrossRef] [PubMed]

Stayton, P. S.

V. B. Rodriguez, S. M. Henry, A. S. Hoffman, P. S. Stayton, X. D. Li, and S. H. Pun, J. Biomed. Opt. 13, 014025 (2008).
[CrossRef] [PubMed]

Stein, S. W.

G. R. Cherrick, S. W. Stein, C. M. Leevy, and C. S. Davidson, J. Clin. Invest. 39, 592 (1960).
[CrossRef] [PubMed]

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
[CrossRef] [PubMed]

Sun, C. K.

Taylor, J.

A. Gouveia-Neto, A. Gomes, and J. Taylor, IEEE J. Quantum Electron. 23, 1193 (1987).
[CrossRef]

Webb, W. W.

C. Xu and W. W. Webb, J. Opt. Soc. Am. B 13, 481 (1996).
[CrossRef]

W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
[CrossRef] [PubMed]

Wu, Y. C.

Xi, J. F.

Xie, H.

Xu, C.

Yazdanfar, S.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, and S. Achilefu, J Biomed. Opt. 15, 030505 (2010).
[CrossRef] [PubMed]

Zhan, C.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, and S. Achilefu, J Biomed. Opt. 15, 030505 (2010).
[CrossRef] [PubMed]

Curr. Opin. Biotechnol.

V. Andresen, S. Alexander, W. M. Heupel, M. Hirschberg, R. M. Hoffman, and P. Friedl, Curr. Opin. Biotechnol. 20, 54 (2009).
[CrossRef] [PubMed]

IEEE J. Quantum Electron.

K. C. Chan and H. F. Liu, IEEE J. Quantum Electron. 31, 2226 (1995).
[CrossRef]

A. Gouveia-Neto, A. Gomes, and J. Taylor, IEEE J. Quantum Electron. 23, 1193 (1987).
[CrossRef]

J Biomed. Opt.

S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, and S. Achilefu, J Biomed. Opt. 15, 030505 (2010).
[CrossRef] [PubMed]

J. Biomed. Opt.

V. B. Rodriguez, S. M. Henry, A. S. Hoffman, P. S. Stayton, X. D. Li, and S. H. Pun, J. Biomed. Opt. 13, 014025 (2008).
[CrossRef] [PubMed]

J. Clin. Invest.

G. R. Cherrick, S. W. Stein, C. M. Leevy, and C. S. Davidson, J. Clin. Invest. 39, 592 (1960).
[CrossRef] [PubMed]

J. Opt. Soc. Am. B

Opt. Express

Opt. Lett.

Pharm. Res.

T. H. Kim, Y. P. Chen, C. W. Mount, W. R. Gombotz, X. D. Li, and S. H. Pun, Pharm. Res. 27, 1900 (2010).
[CrossRef] [PubMed]

Phys. Med. Biol.

G. McConnell, Phys. Med. Biol. 52, 717 (2007).
[CrossRef] [PubMed]

Science

W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
[CrossRef] [PubMed]

Other

Y. Chen, T. G. Jabbour, and X. Li, in Biomedical Optics, OSA Technical Digest (CD) (Optical Society of America, 2010), paper BTuC6.
[PubMed]

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Figures (3)

Fig. 1
Fig. 1

System design and components: (a) block diagram of the 1.55 μm short-pulsed fiber laser, (b) detailed layout of the optical path, (c) micrograph of the double-clad fiber cross section.

Fig. 2
Fig. 2

(a) Spectra and (b) autocorrelation traces of the pulses at the laser output and at the endo microscope output.

Fig. 3
Fig. 3

Multiphoton fluorescence images (averaged five times) with 1.55 μm excitation. (a), (b) A431 cells targeted with anti-EGFR antibody conjugated ICG micelles, (c) ex vivo mouse bile duct after tail vein administration of 50 μL ICG solution ( 10 μM ), (d) skeletal muscle after i.m. administration of 50 μL ICG solution ( 10 μM ) showing characteristic striations.

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