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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  1. W. Denk, J. H. Strickler, and W. W. Webb, Science 248, 73 (1990).
    [CrossRef] [PubMed]
  2. M. T. Myaing, D. J. MacDonald, and X. D. Li, Opt. Lett. 31, 1076 (2006).
    [CrossRef] [PubMed]
  3. L. Fu, A. Jain, H. Xie, C. Cranfield, and M. Gu, Opt. Express 14, 1027 (2006).
    [CrossRef] [PubMed]
  4. C. Xu and W. W. Webb, J. Opt. Soc. Am. B 13, 481 (1996).
    [CrossRef]
  5. S. W. Chu, I. H. Chen, T. M. Liu, P. C. Chen, C. K. Sun, and B. L. Lin, Opt. Lett. 26, 1909 (2001).
    [CrossRef]
  6. G. McConnell, Phys. Med. Biol. 52, 717 (2007).
    [CrossRef] [PubMed]
  7. V. Andresen, S. Alexander, W. M. Heupel, M. Hirschberg, R. M. Hoffman, and P. Friedl, Curr. Opin. Biotechnol. 20, 54 (2009).
    [CrossRef] [PubMed]
  8. S. Yazdanfar, C. Joo, C. Zhan, M. Y. Berezin, W. J. Akers, and S. Achilefu, J Biomed. Opt. 15, 030505 (2010).
    [CrossRef] [PubMed]
  9. K. C. Chan and H. F. Liu, IEEE J. Quantum Electron. 31, 2226 (1995).
    [CrossRef]
  10. A. Gouveia-Neto, A. Gomes, and J. Taylor, IEEE J. Quantum Electron. 23, 1193 (1987).
    [CrossRef]
  11. Y. C. Wu, J. F. Xi, M. J. Cobb, and X. D. Li, Opt. Lett. 34, 953 (2009).
    [CrossRef] [PubMed]
  12. 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]
  13. 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]
  14. Y. Chen, T. G. Jabbour, and X. Li, in Biomedical Optics, OSA Technical Digest (CD) (Optical Society of America, 2010), paper BTuC6.
    [PubMed]
  15. G. R. Cherrick, S. W. Stein, C. M. Leevy, and C. S. Davidson, J. Clin. Invest. 39, 592 (1960).
    [CrossRef] [PubMed]

2010 (2)

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 (2)

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

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

2008 (1)

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 (1)

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

2006 (2)

2001 (1)

1996 (1)

1995 (1)

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

1990 (1)

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

1987 (1)

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

1960 (1)

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. (1)

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. (2)

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. (1)

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. (1)

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. (1)

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 (1)

Opt. Express (1)

Opt. Lett. (3)

Pharm. Res. (1)

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. (1)

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

Science (1)

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

Other (1)

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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