Abstract

We report on a miniature fiber-optic multiphoton microscopy (MPM) system based on a frequency-doubled femtosecond Er-doped fiber laser. The femtosecond pulses from the laser source are delivered to the miniature fiber-optic probe at 1.58 µm wavelength, where a standard single mode fiber is used for delivery without the need of free-space dispersion compensation components. The beam is frequency-doubled inside the probe by a periodically poled MgO:LiNbO3 crystal. Frequency-doubled pulses at 786 nm with a maximum power of 80 mW and a pulsewidth of 150 fs are obtained and applied to excite intrinsic signals from tissues. A MEMS scanner, a miniature objective, and a multimode collection fiber are further used to make the probe compact. The miniature fiber-optic MPM system is highly portable and robust. Ex vivo multiphoton imaging of mammalian skins demonstrates the capability of the system in imaging biological tissues. The results show that the miniature fiber-optic MPM system using frequency-doubled femtosecond fiber laser can potentially bring the MPM imaging for clinical applications.

© 2016 Optical Society of America

Full Article  |  PDF Article
OSA Recommended Articles
Characterization and application of chirped photonic crystal fiber in multiphoton imaging

Jiali Yu, Haishan Zeng, Harvey Lui, Julia S. Skibina, Günter Steinmeyer, and Shuo Tang
Opt. Express 22(9) 10366-10379 (2014)

Energetic ultrafast fiber laser sources tunable in 1030–1215 nm for deep tissue multi-photon microscopy

Wei Liu, Shih-Hsuan Chia, Hsiang-Yu Chung, Rüdiger Greinert, Franz X. Kärtner, and Guoqing Chang
Opt. Express 25(6) 6822-6831 (2017)

Miniaturized probe based on a microelectromechanical system mirror for multiphoton microscopy

Woonggyu Jung, Suo Tang, Daniel T. McCormic, Tiquiang Xie, Yeh-Chan Ahn, Jianping Su, Ivan V. Tomov, Tatiana B. Krasieva, Bruce J. Tromberg, and Zhongping Chen
Opt. Lett. 33(12) 1324-1326 (2008)

References

  • View by:
  • |
  • |
  • |

  1. T. G. Oertner, “Functional imaging of single synapses in brain slices,” Exp. Physiol. 87(6), 733–736 (2002).
    [Crossref] [PubMed]
  2. T. Ladewig, P. Kloppenburg, P. M. Lalley, W. R. Zipfel, W. W. Webb, and B. U. Keller, “Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse,” J. Physiol. 547(3), 775–787 (2003).
    [Crossref] [PubMed]
  3. E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, and R. K. Jain, “In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy,” Nat. Med. 7(7), 864–868 (2001).
    [Crossref] [PubMed]
  4. D. M. McDonald and P. L. Choyke, “Imaging of angiogenesis: from microscope to clinic,” Nat. Med. 9(6), 713–725 (2003).
    [Crossref] [PubMed]
  5. W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
    [Crossref] [PubMed]
  6. F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
    [Crossref] [PubMed]
  7. B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, and M. J. Schnitzer, “In vivo brain imaging using a portable 3.9 gram two-photon fluorescence microendoscope,” Opt. Lett. 30(17), 2272–2274 (2005).
    [Crossref] [PubMed]
  8. J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
    [Crossref] [PubMed]
  9. S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).
  10. Y. Wu, Y. Leng, J. Xi, and X. Li, “Scanning all-fiber-optic endomicroscopy system for 3D nonlinear optical imaging of biological tissues,” Opt. Express 17(10), 7907–7915 (2009).
    [Crossref] [PubMed]
  11. D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
    [Crossref] [PubMed]
  12. C. L. Hoy, O. Ferhanoğlu, M. Yildirim, W. Piyawattanametha, H. Ra, O. Solgaard, and A. Ben-Yakar, “Optical design and imaging performance testing of a 9.6-mm diameter femtosecond laser microsurgery probe,” Opt. Express 19(11), 10536–10552 (2011).
    [Crossref] [PubMed]
  13. C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
    [Crossref] [PubMed]
  14. D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3(5), 1077–1085 (2012).
    [Crossref] [PubMed]
  15. F. Helmchen, W. Denk, and J. N. Kerr, “Miniaturization of two-photon microscopy for imaging in freely moving animals,” Cold Spring Harb. Protoc. 2013(10), 904–913 (2013).
    [Crossref] [PubMed]
  16. S. Tang, J. Liu, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 14(3), 030508 (2009).
    [Crossref] [PubMed]
  17. G. Liu, K. Kieu, F. W. Wise, and Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J. Biophotonics 4(1-2), 34–39 (2011).
    [Crossref] [PubMed]
  18. K. Murari, Y. Zhang, S. Li, Y. Chen, M.-J. Li, and X. Li, “Compensation-free, all-fiber-optic, two-photon endomicroscopy at 1.55 μm,” Opt. Lett. 36(7), 1299–1301 (2011).
    [Crossref] [PubMed]
  19. W. Göbel, A. Nimmerjahn, and F. Helmchen, “Distortion-free delivery of nanojoule femtosecond pulses from a Ti:sapphire laser through a hollow-core photonic crystal fiber,” Opt. Lett. 29(11), 1285–1287 (2004).
    [Crossref] [PubMed]
  20. J. Yu, H. Zeng, H. Lui, J. S. Skibina, G. Steinmeyer, and S. Tang, “Characterization and application of chirped photonic crystal fiber in multiphoton imaging,” Opt. Express 22(9), 10366–10379 (2014).
    [Crossref] [PubMed]
  21. W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
    [Crossref] [PubMed]
  22. J. R. Unruh, E. S. Price, R. G. Molla, L. Stehno-Bittel, C. K. Johnson, and R. Hui, “Two-photon microscopy with wavelength switchable fiber laser excitation,” Opt. Express 14(21), 9825–9831 (2006).
    [Crossref] [PubMed]
  23. W. Chun, D. Do, and D.-G. Gweon, “Design and demonstration of multimodal optical scanning microscopy for confocal and two-photon imaging,” Rev. Sci. Instrum. 84(1), 013701 (2013).
    [Crossref] [PubMed]
  24. D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
    [Crossref] [PubMed]
  25. M. Hofer, M. E. Fermann, F. Haberl, M. H. Ober, and A. J. Schmidt, “Mode locking with cross-phase and self-phase modulation,” Opt. Lett. 16(7), 502–504 (1991).
    [Crossref] [PubMed]
  26. K. Tamura, L. Nelson, H. Haus, and E. Ippen, “Soliton versus nonsoliton operation of fiber ring lasers,” Appl. Phys. Lett. 64(2), 149–151 (1994).
    [Crossref]
  27. L. E. Myers, R. Eckardt, M. Fejer, R. Byer, W. Bosenberg, and J. Pierce, “Quasi-phase-matched optical parametric oscillators in bulk periodically poled LiNbO3,” J. Opt. Soc. Am. B 12(11), 2102–2116 (1995).
    [Crossref]
  28. G. D. Boyd and D. A. Kleinman, “Parametric Interaction of Focused Gaussian Light Beams,” J. Appl. Phys. 39(8), 3597–3639 (1968).
    [Crossref]
  29. K. Moutzouris, E. Adler, F. Sotier, D. Träutlein, and A. Leitenstorfer, “Multimilliwatt ultrashort pulses continuously tunable in the visible from a compact fiber source,” Opt. Lett. 31(8), 1148–1150 (2006).
    [Crossref] [PubMed]
  30. L. Gruner-Nielsen, M. Wandel, P. Kristensen, C. Jorgensen, L. V. Jorgensen, B. Edvold, B. Palsdottir, and D. Jakobsen, “Dispersion-compensating fibers,” J. Lightwave Technol. 23(11), 3566–3579 (2005).
    [Crossref]
  31. P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
    [Crossref]

2014 (2)

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

J. Yu, H. Zeng, H. Lui, J. S. Skibina, G. Steinmeyer, and S. Tang, “Characterization and application of chirped photonic crystal fiber in multiphoton imaging,” Opt. Express 22(9), 10366–10379 (2014).
[Crossref] [PubMed]

2013 (2)

W. Chun, D. Do, and D.-G. Gweon, “Design and demonstration of multimodal optical scanning microscopy for confocal and two-photon imaging,” Rev. Sci. Instrum. 84(1), 013701 (2013).
[Crossref] [PubMed]

F. Helmchen, W. Denk, and J. N. Kerr, “Miniaturization of two-photon microscopy for imaging in freely moving animals,” Cold Spring Harb. Protoc. 2013(10), 904–913 (2013).
[Crossref] [PubMed]

2012 (2)

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3(5), 1077–1085 (2012).
[Crossref] [PubMed]

2011 (4)

K. Murari, Y. Zhang, S. Li, Y. Chen, M.-J. Li, and X. Li, “Compensation-free, all-fiber-optic, two-photon endomicroscopy at 1.55 μm,” Opt. Lett. 36(7), 1299–1301 (2011).
[Crossref] [PubMed]

C. L. Hoy, O. Ferhanoğlu, M. Yildirim, W. Piyawattanametha, H. Ra, O. Solgaard, and A. Ben-Yakar, “Optical design and imaging performance testing of a 9.6-mm diameter femtosecond laser microsurgery probe,” Opt. Express 19(11), 10536–10552 (2011).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

G. Liu, K. Kieu, F. W. Wise, and Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J. Biophotonics 4(1-2), 34–39 (2011).
[Crossref] [PubMed]

2009 (4)

S. Tang, J. Liu, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 14(3), 030508 (2009).
[Crossref] [PubMed]

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).

Y. Wu, Y. Leng, J. Xi, and X. Li, “Scanning all-fiber-optic endomicroscopy system for 3D nonlinear optical imaging of biological tissues,” Opt. Express 17(10), 7907–7915 (2009).
[Crossref] [PubMed]

2006 (2)

2005 (3)

2004 (1)

2003 (4)

T. Ladewig, P. Kloppenburg, P. M. Lalley, W. R. Zipfel, W. W. Webb, and B. U. Keller, “Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse,” J. Physiol. 547(3), 775–787 (2003).
[Crossref] [PubMed]

D. M. McDonald and P. L. Choyke, “Imaging of angiogenesis: from microscope to clinic,” Nat. Med. 9(6), 713–725 (2003).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [PubMed]

2002 (1)

T. G. Oertner, “Functional imaging of single synapses in brain slices,” Exp. Physiol. 87(6), 733–736 (2002).
[Crossref] [PubMed]

2001 (1)

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, and R. K. Jain, “In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy,” Nat. Med. 7(7), 864–868 (2001).
[Crossref] [PubMed]

2000 (1)

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

1995 (1)

1994 (1)

K. Tamura, L. Nelson, H. Haus, and E. Ippen, “Soliton versus nonsoliton operation of fiber ring lasers,” Appl. Phys. Lett. 64(2), 149–151 (1994).
[Crossref]

1991 (1)

1968 (1)

G. D. Boyd and D. A. Kleinman, “Parametric Interaction of Focused Gaussian Light Beams,” J. Appl. Phys. 39(8), 3597–3639 (1968).
[Crossref]

Adler, E.

Ahn, Y. C.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).

Anderson, E. P.

Ben-Yakar, A.

Bosenberg, W.

Boyd, G. D.

G. D. Boyd and D. A. Kleinman, “Parametric Interaction of Focused Gaussian Light Beams,” J. Appl. Phys. 39(8), 3597–3639 (1968).
[Crossref]

Brown, C. M.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3(5), 1077–1085 (2012).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

Brown, E. B.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, and R. K. Jain, “In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy,” Nat. Med. 7(7), 864–868 (2001).
[Crossref] [PubMed]

Byer, R.

Campbell, R. B.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, and R. K. Jain, “In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy,” Nat. Med. 7(7), 864–868 (2001).
[Crossref] [PubMed]

Carmeliet, P.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, and R. K. Jain, “In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy,” Nat. Med. 7(7), 864–868 (2001).
[Crossref] [PubMed]

Chen, J.

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Chen, Y.

Chen, Z.

G. Liu, K. Kieu, F. W. Wise, and Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J. Biophotonics 4(1-2), 34–39 (2011).
[Crossref] [PubMed]

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).

S. Tang, J. Liu, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 14(3), 030508 (2009).
[Crossref] [PubMed]

Cheng, P. C.

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Choyke, P. L.

D. M. McDonald and P. L. Choyke, “Imaging of angiogenesis: from microscope to clinic,” Nat. Med. 9(6), 713–725 (2003).
[Crossref] [PubMed]

Christie, R.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [PubMed]

Chun, W.

W. Chun, D. Do, and D.-G. Gweon, “Design and demonstration of multimodal optical scanning microscopy for confocal and two-photon imaging,” Rev. Sci. Instrum. 84(1), 013701 (2013).
[Crossref] [PubMed]

Cocker, E. D.

Denk, W.

F. Helmchen, W. Denk, and J. N. Kerr, “Miniaturization of two-photon microscopy for imaging in freely moving animals,” Cold Spring Harb. Protoc. 2013(10), 904–913 (2013).
[Crossref] [PubMed]

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[Crossref] [PubMed]

Do, D.

W. Chun, D. Do, and D.-G. Gweon, “Design and demonstration of multimodal optical scanning microscopy for confocal and two-photon imaging,” Rev. Sci. Instrum. 84(1), 013701 (2013).
[Crossref] [PubMed]

Eckardt, R.

Edvold, B.

Fejer, M.

Ferhanoglu, O.

Fermann, M. E.

Flusberg, B. A.

Fukumura, D.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, and R. K. Jain, “In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy,” Nat. Med. 7(7), 864–868 (2001).
[Crossref] [PubMed]

Göbel, W.

Greenberg, D. S.

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

Grossmann, S.

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

Gruner-Nielsen, L.

Gweon, D.-G.

W. Chun, D. Do, and D.-G. Gweon, “Design and demonstration of multimodal optical scanning microscopy for confocal and two-photon imaging,” Rev. Sci. Instrum. 84(1), 013701 (2013).
[Crossref] [PubMed]

Haberl, F.

Harya, D. S.

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

Haus, H.

K. Tamura, L. Nelson, H. Haus, and E. Ippen, “Soliton versus nonsoliton operation of fiber ring lasers,” Appl. Phys. Lett. 64(2), 149–151 (1994).
[Crossref]

Helmchen, F.

F. Helmchen, W. Denk, and J. N. Kerr, “Miniaturization of two-photon microscopy for imaging in freely moving animals,” Cold Spring Harb. Protoc. 2013(10), 904–913 (2013).
[Crossref] [PubMed]

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[Crossref] [PubMed]

W. Göbel, A. Nimmerjahn, and F. Helmchen, “Distortion-free delivery of nanojoule femtosecond pulses from a Ti:sapphire laser through a hollow-core photonic crystal fiber,” Opt. Lett. 29(11), 1285–1287 (2004).
[Crossref] [PubMed]

Hofer, M.

Howard, S. S.

Hoy, C. L.

Huang, M. K.

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Hui, R.

Huland, D. M.

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3(5), 1077–1085 (2012).
[Crossref] [PubMed]

Hyman, B. T.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [PubMed]

Ippen, E.

K. Tamura, L. Nelson, H. Haus, and E. Ippen, “Soliton versus nonsoliton operation of fiber ring lasers,” Appl. Phys. Lett. 64(2), 149–151 (1994).
[Crossref]

Jain, M.

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

Jain, R. K.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, and R. K. Jain, “In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy,” Nat. Med. 7(7), 864–868 (2001).
[Crossref] [PubMed]

Jakobsen, D.

Johnson, C. K.

Johnson, I.

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Jorgensen, C.

Jorgensen, L. V.

Jung, J. C.

Jung, W.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).

Kao, F. J.

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Keller, B. U.

T. Ladewig, P. Kloppenburg, P. M. Lalley, W. R. Zipfel, W. W. Webb, and B. U. Keller, “Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse,” J. Physiol. 547(3), 775–787 (2003).
[Crossref] [PubMed]

Kerr, J. N.

F. Helmchen, W. Denk, and J. N. Kerr, “Miniaturization of two-photon microscopy for imaging in freely moving animals,” Cold Spring Harb. Protoc. 2013(10), 904–913 (2013).
[Crossref] [PubMed]

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

Kieu, K.

G. Liu, K. Kieu, F. W. Wise, and Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J. Biophotonics 4(1-2), 34–39 (2011).
[Crossref] [PubMed]

Kleinman, D. A.

G. D. Boyd and D. A. Kleinman, “Parametric Interaction of Focused Gaussian Light Beams,” J. Appl. Phys. 39(8), 3597–3639 (1968).
[Crossref]

Kloppenburg, P.

T. Ladewig, P. Kloppenburg, P. M. Lalley, W. R. Zipfel, W. W. Webb, and B. U. Keller, “Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse,” J. Physiol. 547(3), 775–787 (2003).
[Crossref] [PubMed]

Kobat, D.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

Krasieva, T. B.

S. Tang, J. Liu, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 14(3), 030508 (2009).
[Crossref] [PubMed]

Kristensen, P.

Ladewig, T.

T. Ladewig, P. Kloppenburg, P. M. Lalley, W. R. Zipfel, W. W. Webb, and B. U. Keller, “Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse,” J. Physiol. 547(3), 775–787 (2003).
[Crossref] [PubMed]

Lalley, P. M.

T. Ladewig, P. Kloppenburg, P. M. Lalley, W. R. Zipfel, W. W. Webb, and B. U. Keller, “Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse,” J. Physiol. 547(3), 775–787 (2003).
[Crossref] [PubMed]

Leitenstorfer, A.

Leng, Y.

Li, M.-J.

Li, S.

Li, X.

Lin, B. L.

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Liu, G.

G. Liu, K. Kieu, F. W. Wise, and Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J. Biophotonics 4(1-2), 34–39 (2011).
[Crossref] [PubMed]

Liu, J.

S. Tang, J. Liu, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 14(3), 030508 (2009).
[Crossref] [PubMed]

Liu, T. M.

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Lui, H.

McCormick, D.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).

McDonald, D. M.

D. M. McDonald and P. L. Choyke, “Imaging of angiogenesis: from microscope to clinic,” Nat. Med. 9(6), 713–725 (2003).
[Crossref] [PubMed]

Mohanan, S.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

Molla, R. G.

Moutzouris, K.

Murari, K.

Myers, L. E.

Nelson, L.

K. Tamura, L. Nelson, H. Haus, and E. Ippen, “Soliton versus nonsoliton operation of fiber ring lasers,” Appl. Phys. Lett. 64(2), 149–151 (1994).
[Crossref]

Nikitin, A. Y.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [PubMed]

Nimmerjahn, A.

Ober, M. H.

Oertner, T. G.

T. G. Oertner, “Functional imaging of single synapses in brain slices,” Exp. Physiol. 87(6), 733–736 (2002).
[Crossref] [PubMed]

Ouzounov, D. G.

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3(5), 1077–1085 (2012).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

Palsdottir, B.

Pavlova, I.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3(5), 1077–1085 (2012).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

Pierce, J.

Piyawattanametha, W.

Price, E. S.

Ra, H.

Rivera, D. R.

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3(5), 1077–1085 (2012).
[Crossref] [PubMed]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

Robinson, B. D.

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

Sawinski, J.

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

Schmidt, A. J.

Schnitzer, M. J.

Shevchuk, M. M.

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

Singhal, P.

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

Skibina, J. S.

Solgaard, O.

Sotier, F.

Stehno-Bittel, L.

Steinmeyer, G.

Su, J.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).

Sun, C. K.

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Tamura, K.

K. Tamura, L. Nelson, H. Haus, and E. Ippen, “Soliton versus nonsoliton operation of fiber ring lasers,” Appl. Phys. Lett. 64(2), 149–151 (1994).
[Crossref]

Tang, S.

J. Yu, H. Zeng, H. Lui, J. S. Skibina, G. Steinmeyer, and S. Tang, “Characterization and application of chirped photonic crystal fiber in multiphoton imaging,” Opt. Express 22(9), 10366–10379 (2014).
[Crossref] [PubMed]

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).

S. Tang, J. Liu, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 14(3), 030508 (2009).
[Crossref] [PubMed]

Tewari, A. K.

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

Träutlein, D.

Tromberg, B. J.

S. Tang, J. Liu, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 14(3), 030508 (2009).
[Crossref] [PubMed]

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).

Tsuzuki, Y.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, and R. K. Jain, “In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy,” Nat. Med. 7(7), 864–868 (2001).
[Crossref] [PubMed]

Unruh, J. R.

Wallace, D. J.

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

Wandel, M.

Wang, K.

Wang, Y.

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Wang, Y. S.

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Webb, W. W.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3(5), 1077–1085 (2012).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

T. Ladewig, P. Kloppenburg, P. M. Lalley, W. R. Zipfel, W. W. Webb, and B. U. Keller, “Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse,” J. Physiol. 547(3), 775–787 (2003).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [PubMed]

Williams, R. M.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Williams, W. O.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

Wise, F. W.

G. Liu, K. Kieu, F. W. Wise, and Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J. Biophotonics 4(1-2), 34–39 (2011).
[Crossref] [PubMed]

Wu, Y.

Xi, J.

Xie, T.

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).

Xu, C.

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3(5), 1077–1085 (2012).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

Xu, L.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, and R. K. Jain, “In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy,” Nat. Med. 7(7), 864–868 (2001).
[Crossref] [PubMed]

Yildirim, M.

Yu, J.

Zeng, H.

Zhang, Y.

Zipfel, W. R.

T. Ladewig, P. Kloppenburg, P. M. Lalley, W. R. Zipfel, W. W. Webb, and B. U. Keller, “Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse,” J. Physiol. 547(3), 775–787 (2003).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [PubMed]

Appl. Phys. Lett. (1)

K. Tamura, L. Nelson, H. Haus, and E. Ippen, “Soliton versus nonsoliton operation of fiber ring lasers,” Appl. Phys. Lett. 64(2), 149–151 (1994).
[Crossref]

Biomed. Opt. Express (1)

Cold Spring Harb. Protoc. (1)

F. Helmchen, W. Denk, and J. N. Kerr, “Miniaturization of two-photon microscopy for imaging in freely moving animals,” Cold Spring Harb. Protoc. 2013(10), 904–913 (2013).
[Crossref] [PubMed]

Exp. Physiol. (1)

T. G. Oertner, “Functional imaging of single synapses in brain slices,” Exp. Physiol. 87(6), 733–736 (2002).
[Crossref] [PubMed]

J. Appl. Phys. (1)

G. D. Boyd and D. A. Kleinman, “Parametric Interaction of Focused Gaussian Light Beams,” J. Appl. Phys. 39(8), 3597–3639 (1968).
[Crossref]

J. Biomed. Opt. (4)

D. M. Huland, M. Jain, D. G. Ouzounov, B. D. Robinson, D. S. Harya, M. M. Shevchuk, P. Singhal, C. Xu, and A. K. Tewari, “Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo,” J. Biomed. Opt. 19(11), 116011 (2014).
[Crossref] [PubMed]

S. Tang, J. Liu, T. B. Krasieva, Z. Chen, and B. J. Tromberg, “Developing compact multiphoton systems using femtosecond fiber lasers,” J. Biomed. Opt. 14(3), 030508 (2009).
[Crossref] [PubMed]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref] [PubMed]

S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y. C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).

J. Biophotonics (1)

G. Liu, K. Kieu, F. W. Wise, and Z. Chen, “Multiphoton microscopy system with a compact fiber-based femtosecond-pulse laser and handheld probe,” J. Biophotonics 4(1-2), 34–39 (2011).
[Crossref] [PubMed]

J. Lightwave Technol. (1)

J. Opt. Soc. Am. B (1)

J. Physiol. (1)

T. Ladewig, P. Kloppenburg, P. M. Lalley, W. R. Zipfel, W. W. Webb, and B. U. Keller, “Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse,” J. Physiol. 547(3), 775–787 (2003).
[Crossref] [PubMed]

Nat. Biotechnol. (1)

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Nat. Med. (2)

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, and R. K. Jain, “In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy,” Nat. Med. 7(7), 864–868 (2001).
[Crossref] [PubMed]

D. M. McDonald and P. L. Choyke, “Imaging of angiogenesis: from microscope to clinic,” Nat. Med. 9(6), 713–725 (2003).
[Crossref] [PubMed]

Nat. Methods (1)

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[Crossref] [PubMed]

Opt. Express (4)

Opt. Lett. (5)

Proc. Natl. Acad. Sci. U.S.A. (3)

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003).
[Crossref] [PubMed]

J. Sawinski, D. J. Wallace, D. S. Greenberg, S. Grossmann, W. Denk, and J. N. Kerr, “Visually evoked activity in cortical cells imaged in freely moving animals,” Proc. Natl. Acad. Sci. U.S.A. 106(46), 19557–19562 (2009).
[Crossref] [PubMed]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, and C. Xu, “Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue,” Proc. Natl. Acad. Sci. U.S.A. 108(43), 17598–17603 (2011).
[Crossref] [PubMed]

Proc. SPIE (1)

P. C. Cheng, B. L. Lin, F. J. Kao, C. K. Sun, Y. S. Wang, T. M. Liu, Y. Wang, J. Chen, M. K. Huang, and I. Johnson, “Multiphoton fluorescence spectroscopy of flourescent bioprobes and biomolecules,” Proc. SPIE 4082, 87–91 (2000).
[Crossref]

Rev. Sci. Instrum. (1)

W. Chun, D. Do, and D.-G. Gweon, “Design and demonstration of multimodal optical scanning microscopy for confocal and two-photon imaging,” Rev. Sci. Instrum. 84(1), 013701 (2013).
[Crossref] [PubMed]

Cited By

OSA participates in Crossref's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (6)

Fig. 1
Fig. 1

Schematic the compact fiber laser based MPM system. EDF: Er-doped fiber; HWP: half-wave plate; QWP: quarter-wave plate; BP: birefringent plate; FI: faraday isolator; CL: collimating lens; WDM: wavelength division multiplexer; PC: polarization controller; SMF: single mode fiber; L: lens; PPLN: periodically poled MgO:LiNbO3 crystal; F: filter; MEMS: micro-electro-mechanical scanning mirror; DM: Dichroic mirror; OBJ: objective lens; MMF: multimode fiber; PMT: photomultiplier tube.

Fig. 2
Fig. 2

Spectra of the (a) fundamental and the (c) frequency-doubled pulse and their corresponding autocorrelation traces in (b) and (d).

Fig. 3
Fig. 3

A photograph of the miniature fiber-optic MPM probe. SMF: single mode fiber; CL: collimating lens; HWP: half-wave plate; QWP: quarter-wave plate; L: lens; PPLN: periodically poled MgO:LiNbO3 crystal; F: filter; MEMS: micro-electro-mechanical scanning mirror; DM: Dichroic mirror; OBJ: objective; MMF: multimode fiber. The Loonie shown has a diameter of 26.5 mm.

Fig. 4
Fig. 4

The normalized spectrum of the second order generation signal and third order generation signal of PPLN.

Fig. 5
Fig. 5

The lateral two-photon PSF plot for a 0.1-µm-diameter fluorescent bead. Experimental data (black dots) and results of the Gaussian fit (in blue) are shown.

Fig. 6
Fig. 6

Images acquired by the miniature fiber-optic MPM probe system. (a) SHG image of a porcine skin. (b) SHG image of a leporine skin. (c) TPEF image of a murine skin averaged over 10 frames. Scale bar is 20 μm.

Metrics