Abstract

Fiber delivery of ultrashort pulses is important for multiphoton endoscopy. A chirped photonic crystal fiber (CPCF) is first characterized for its transmission bandwidth, propagation loss, and dispersion properties. Its extremely low dispersion (~150fs2/m) enables the delivery of sub-30 fs pulses through a ~1 m-long CPCF. The CPCF is then incorporated into a multiphoton imaging system and its performance is demonstrated by imaging various biological samples including yew leaf, mouse tendon, and human skin. The imaging quality is further compared with images acquired by a multiphoton imaging system with free-space or hollow-core photonic band-gap fiber (PBF) delivery of pulses. Compared with free-space system, the CPCF delivered system maintains the same ultrashort pulsewidth and the image qualities are comparable. Compared with the PBF delivery, CPCF provides a 35 times shorter pulsewidth at the sample location, which results in a ~12 and 50 times improvement in two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) signals respectively. Our results show that CPCF has great potential for fiber delivery of ultrashort pulses for multiphoton endoscopy.

© 2014 Optical Society of America

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2013 (1)

2012 (2)

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M. J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (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, 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 (3)

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, 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]

C. Lefort, T. Mansuryan, F. Louradour, A. Barthelemy, “Pulse compression and fiber delivery of 45 fs Fourier transform limited pulses at 830 nm,” Opt. Lett. 36(2), 292–294 (2011).
[CrossRef] [PubMed]

Yu. S. Skibina, V. V. Tuchin, V. I. Beloglazov, G. Steinmeyer, J. Bethge, R. Wedell, N. Langhoff, “Photonic crystal fibres in biomedical investigations,” Quantum Electron. 41(4), 284–301 (2011).
[CrossRef]

2009 (2)

2008 (2)

C. L. Hoy, N. J. Durr, P. Chen, W. Piyawattanametha, H. Ra, O. Solgaard, A. Ben-Yakar, “Miniaturized probe for femtosecond laser microsurgery and two-photon imaging,” Opt. Express 16(13), 9996–10005 (2008).
[CrossRef] [PubMed]

J. S. Skibina, R. Iliew, J. Bethge, M. Bock, D. Fischer, V. I. Beloglasov, R. Wedell, G. Steinmeyer, “A chirped photonic-crystal fibre,” Nat. Photonics 2(11), 679–683 (2008).
[CrossRef]

2006 (2)

S. Tang, T. B. Krasieva, Z. Chen, G. Tempea, B. J. Tromberg, “Effect of pulse duration on two-photon excited fluorescence and second harmonic generation in nonlinear optical microscopy,” J. Biomed. Opt. 11(2), 020501 (2006).
[CrossRef] [PubMed]

M. T. Myaing, D. J. MacDonald, X. Li, “Fiber-optic scanning two-photon fluorescence endoscope,” Opt. Lett. 31(8), 1076–1078 (2006).
[CrossRef] [PubMed]

2005 (4)

B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, 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]

L. Fu, X. Gan, M. Gu, “Nonlinear optical microscopy based on double-clad photonic crystal fibers,” Opt. Express 13(14), 5528–5534 (2005).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[CrossRef] [PubMed]

R. M. Williams, W. R. Zipfel, W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005).
[CrossRef] [PubMed]

2004 (2)

2003 (2)

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

C. Stosiek, O. Garaschuk, K. Holthoff, A. Konnerth, “In vivo two-photon calcium imaging of neuronal networks,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7319–7324 (2003).
[CrossRef] [PubMed]

2002 (2)

A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002).
[CrossRef] [PubMed]

D. Bird, M. Gu, “Fibre-optic two-photon scanning fluorescence microscopy,” J. Microsc. 208(1), 35–48 (2002).
[CrossRef] [PubMed]

2001 (2)

F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, 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]

1998 (1)

M. Müller, J. Squier, R. Wolleschensky, U. Simon, G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[CrossRef] [PubMed]

1990 (1)

W. Denk, J. H. Strickler, W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

1987 (1)

O. Martinez, “3000 times grating compressor with positive group velocity dispersion: Application to fiber compensation in 1.3-1.6 µm region,” IEEE J. Quantum Electron. 23(1), 59–64 (1987).
[CrossRef]

1984 (1)

Ahmad, F. R.

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

Akins, M. L.

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M. J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

Anderson, E. P.

Andresen, E. R.

Barthelemy, A.

Beloglasov, V. I.

J. S. Skibina, R. Iliew, J. Bethge, M. Bock, D. Fischer, V. I. Beloglasov, R. Wedell, G. Steinmeyer, “A chirped photonic-crystal fibre,” Nat. Photonics 2(11), 679–683 (2008).
[CrossRef]

Beloglazov, V. I.

Yu. S. Skibina, V. V. Tuchin, V. I. Beloglazov, G. Steinmeyer, J. Bethge, R. Wedell, N. Langhoff, “Photonic crystal fibres in biomedical investigations,” Quantum Electron. 41(4), 284–301 (2011).
[CrossRef]

Ben-Yakar, A.

Bethge, J.

Yu. S. Skibina, V. V. Tuchin, V. I. Beloglazov, G. Steinmeyer, J. Bethge, R. Wedell, N. Langhoff, “Photonic crystal fibres in biomedical investigations,” Quantum Electron. 41(4), 284–301 (2011).
[CrossRef]

J. Bethge, G. Steinmeyer, S. Burger, F. Lederer, R. Iliew, “Guiding Properties of Chirped Photonic Crystal Fibers,” J. Lightwave Technol. 27(11), 1698–1706 (2009).
[CrossRef]

J. S. Skibina, R. Iliew, J. Bethge, M. Bock, D. Fischer, V. I. Beloglasov, R. Wedell, G. Steinmeyer, “A chirped photonic-crystal fibre,” Nat. Photonics 2(11), 679–683 (2008).
[CrossRef]

Bird, D.

D. Bird, M. Gu, “Fibre-optic two-photon scanning fluorescence microscopy,” J. Microsc. 208(1), 35–48 (2002).
[CrossRef] [PubMed]

Bock, M.

J. S. Skibina, R. Iliew, J. Bethge, M. Bock, D. Fischer, V. I. Beloglasov, R. Wedell, G. Steinmeyer, “A chirped photonic-crystal fibre,” Nat. Photonics 2(11), 679–683 (2008).
[CrossRef]

Bouwmans, G.

Brakenhoff, G. J.

M. Müller, J. Squier, R. Wolleschensky, U. Simon, G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[CrossRef] [PubMed]

Brown, C. M.

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, 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, 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, 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]

Burger, S.

Campbell, R. B.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, 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, 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]

Chan, M. C.

Chen, L. J.

Chen, P.

Chen, Z.

S. Tang, T. B. Krasieva, Z. Chen, G. Tempea, B. J. Tromberg, “Effect of pulse duration on two-photon excited fluorescence and second harmonic generation in nonlinear optical microscopy,” J. Biomed. Opt. 11(2), 020501 (2006).
[CrossRef] [PubMed]

Cheung, E. L. M.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[CrossRef] [PubMed]

Cocker, E. D.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[CrossRef] [PubMed]

B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, 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]

Denk, W.

F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Durr, N. J.

Fee, M. S.

F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

Fischer, D.

J. S. Skibina, R. Iliew, J. Bethge, M. Bock, D. Fischer, V. I. Beloglasov, R. Wedell, G. Steinmeyer, “A chirped photonic-crystal fibre,” Nat. Photonics 2(11), 679–683 (2008).
[CrossRef]

Flusberg, B. A.

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[CrossRef] [PubMed]

B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, 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]

Fork, R. L.

Fu, L.

Fukumura, D.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, 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]

Gaeta, A. L.

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

Gallagher, M. T.

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

Gan, X.

Garaschuk, O.

C. Stosiek, O. Garaschuk, K. Holthoff, A. Konnerth, “In vivo two-photon calcium imaging of neuronal networks,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7319–7324 (2003).
[CrossRef] [PubMed]

Göbel, W.

Gordon, J. P.

Gu, M.

Guol, S. H.

Helmchen, F.

W. Göbel, A. Nimmerjahn, 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]

F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

Holthoff, K.

C. Stosiek, O. Garaschuk, K. Holthoff, A. Konnerth, “In vivo two-photon calcium imaging of neuronal networks,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7319–7324 (2003).
[CrossRef] [PubMed]

Howard, S. S.

Hoy, C. L.

Huland, D. M.

Iliew, R.

J. Bethge, G. Steinmeyer, S. Burger, F. Lederer, R. Iliew, “Guiding Properties of Chirped Photonic Crystal Fibers,” J. Lightwave Technol. 27(11), 1698–1706 (2009).
[CrossRef]

J. S. Skibina, R. Iliew, J. Bethge, M. Bock, D. Fischer, V. I. Beloglasov, R. Wedell, G. Steinmeyer, “A chirped photonic-crystal fibre,” Nat. Photonics 2(11), 679–683 (2008).
[CrossRef]

Jain, R. K.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, 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]

Jung, J. C.

B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, 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]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[CrossRef] [PubMed]

Kobat, D.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, 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]

Koch, K. W.

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

König, K.

Konnerth, A.

C. Stosiek, O. Garaschuk, K. Holthoff, A. Konnerth, “In vivo two-photon calcium imaging of neuronal networks,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7319–7324 (2003).
[CrossRef] [PubMed]

Krasieva, T. B.

S. Tang, T. B. Krasieva, Z. Chen, G. Tempea, B. J. Tromberg, “Effect of pulse duration on two-photon excited fluorescence and second harmonic generation in nonlinear optical microscopy,” J. Biomed. Opt. 11(2), 020501 (2006).
[CrossRef] [PubMed]

Langhoff, N.

Yu. S. Skibina, V. V. Tuchin, V. I. Beloglazov, G. Steinmeyer, J. Bethge, R. Wedell, N. Langhoff, “Photonic crystal fibres in biomedical investigations,” Quantum Electron. 41(4), 284–301 (2011).
[CrossRef]

Le Harzic, R.

Lederer, F.

Lefort, C.

Li, M. J.

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M. J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

Li, X.

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M. J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

M. T. Myaing, D. J. MacDonald, X. Li, “Fiber-optic scanning two-photon fluorescence endoscope,” Opt. Lett. 31(8), 1076–1078 (2006).
[CrossRef] [PubMed]

Louradour, F.

Luby-Phelps, K.

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M. J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

MacDonald, D. J.

Mahendroo, M.

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M. J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

Mansuryan, T.

Martinez, O.

O. Martinez, “3000 times grating compressor with positive group velocity dispersion: Application to fiber compensation in 1.3-1.6 µm region,” IEEE J. Quantum Electron. 23(1), 59–64 (1987).
[CrossRef]

Martinez, O. E.

Messerschmidt, B.

Monneret, S.

Müller, D.

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

Müller, M.

M. Müller, J. Squier, R. Wolleschensky, U. Simon, G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[CrossRef] [PubMed]

Murari, K.

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M. J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

Myaing, M. T.

Nimmerjahn, A.

Ouzounov, D. G.

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, 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, 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]

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

Pavlova, I.

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, 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, 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]

Piyawattanametha, W.

C. L. Hoy, N. J. Durr, P. Chen, W. Piyawattanametha, H. Ra, O. Solgaard, A. Ben-Yakar, “Miniaturized probe for femtosecond laser microsurgery and two-photon imaging,” Opt. Express 16(13), 9996–10005 (2008).
[CrossRef] [PubMed]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[CrossRef] [PubMed]

Ra, H.

Riemann, I.

Rigneault, 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, 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, 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]

Schnitzer, M. J.

B. A. Flusberg, J. C. Jung, E. D. Cocker, E. P. Anderson, 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]

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[CrossRef] [PubMed]

Silcox, J.

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

Simon, U.

M. Müller, J. Squier, R. Wolleschensky, U. Simon, G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[CrossRef] [PubMed]

Skibina, J. S.

J. S. Skibina, R. Iliew, J. Bethge, M. Bock, D. Fischer, V. I. Beloglasov, R. Wedell, G. Steinmeyer, “A chirped photonic-crystal fibre,” Nat. Photonics 2(11), 679–683 (2008).
[CrossRef]

Skibina, Yu. S.

Yu. S. Skibina, V. V. Tuchin, V. I. Beloglazov, G. Steinmeyer, J. Bethge, R. Wedell, N. Langhoff, “Photonic crystal fibres in biomedical investigations,” Quantum Electron. 41(4), 284–301 (2011).
[CrossRef]

Solgaard, O.

Squier, J.

M. Müller, J. Squier, R. Wolleschensky, U. Simon, G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[CrossRef] [PubMed]

Steinmeyer, G.

Yu. S. Skibina, V. V. Tuchin, V. I. Beloglazov, G. Steinmeyer, J. Bethge, R. Wedell, N. Langhoff, “Photonic crystal fibres in biomedical investigations,” Quantum Electron. 41(4), 284–301 (2011).
[CrossRef]

J. Bethge, G. Steinmeyer, S. Burger, F. Lederer, R. Iliew, “Guiding Properties of Chirped Photonic Crystal Fibers,” J. Lightwave Technol. 27(11), 1698–1706 (2009).
[CrossRef]

J. S. Skibina, R. Iliew, J. Bethge, M. Bock, D. Fischer, V. I. Beloglasov, R. Wedell, G. Steinmeyer, “A chirped photonic-crystal fibre,” Nat. Photonics 2(11), 679–683 (2008).
[CrossRef]

Stosiek, C.

C. Stosiek, O. Garaschuk, K. Holthoff, A. Konnerth, “In vivo two-photon calcium imaging of neuronal networks,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7319–7324 (2003).
[CrossRef] [PubMed]

Strickler, J. H.

W. Denk, J. H. Strickler, W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Sun, C. K.

Tai, S. P.

Tang, S.

S. Tang, T. B. Krasieva, Z. Chen, G. Tempea, B. J. Tromberg, “Effect of pulse duration on two-photon excited fluorescence and second harmonic generation in nonlinear optical microscopy,” J. Biomed. Opt. 11(2), 020501 (2006).
[CrossRef] [PubMed]

Tank, D. W.

F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

Tempea, G.

S. Tang, T. B. Krasieva, Z. Chen, G. Tempea, B. J. Tromberg, “Effect of pulse duration on two-photon excited fluorescence and second harmonic generation in nonlinear optical microscopy,” J. Biomed. Opt. 11(2), 020501 (2006).
[CrossRef] [PubMed]

Thomas, M. G.

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

Tromberg, B. J.

S. Tang, T. B. Krasieva, Z. Chen, G. Tempea, B. J. Tromberg, “Effect of pulse duration on two-photon excited fluorescence and second harmonic generation in nonlinear optical microscopy,” J. Biomed. Opt. 11(2), 020501 (2006).
[CrossRef] [PubMed]

A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002).
[CrossRef] [PubMed]

Tsai, T. H.

Tsuzuki, Y.

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, 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]

Tuchin, V. V.

Yu. S. Skibina, V. V. Tuchin, V. I. Beloglazov, G. Steinmeyer, J. Bethge, R. Wedell, N. Langhoff, “Photonic crystal fibres in biomedical investigations,” Quantum Electron. 41(4), 284–301 (2011).
[CrossRef]

Venkataraman, N.

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

Wang, K.

Webb, W. W.

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, 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, 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]

R. M. Williams, W. R. Zipfel, W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Wedell, R.

Yu. S. Skibina, V. V. Tuchin, V. I. Beloglazov, G. Steinmeyer, J. Bethge, R. Wedell, N. Langhoff, “Photonic crystal fibres in biomedical investigations,” Quantum Electron. 41(4), 284–301 (2011).
[CrossRef]

J. S. Skibina, R. Iliew, J. Bethge, M. Bock, D. Fischer, V. I. Beloglasov, R. Wedell, G. Steinmeyer, “A chirped photonic-crystal fibre,” Nat. Photonics 2(11), 679–683 (2008).
[CrossRef]

Weinigel, M.

Williams, R. M.

R. M. Williams, W. R. Zipfel, W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005).
[CrossRef] [PubMed]

Wolleschensky, R.

M. Müller, J. Squier, R. Wolleschensky, U. Simon, G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[CrossRef] [PubMed]

Xi, J.

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M. J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

Xu, C.

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, 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, 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, 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]

Yeh, A.

A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002).
[CrossRef] [PubMed]

Zhang, Y.

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M. J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

Zipfel, W. R.

R. M. Williams, W. R. Zipfel, W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005).
[CrossRef] [PubMed]

Zoumi, A.

A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002).
[CrossRef] [PubMed]

Appl. Opt. (1)

Biomed. Opt. Express (1)

Biophys. J. (1)

R. M. Williams, W. R. Zipfel, W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88(2), 1377–1386 (2005).
[CrossRef] [PubMed]

IEEE J. Quantum Electron. (1)

O. Martinez, “3000 times grating compressor with positive group velocity dispersion: Application to fiber compensation in 1.3-1.6 µm region,” IEEE J. Quantum Electron. 23(1), 59–64 (1987).
[CrossRef]

J. Biomed. Opt. (1)

S. Tang, T. B. Krasieva, Z. Chen, G. Tempea, B. J. Tromberg, “Effect of pulse duration on two-photon excited fluorescence and second harmonic generation in nonlinear optical microscopy,” J. Biomed. Opt. 11(2), 020501 (2006).
[CrossRef] [PubMed]

J. Lightwave Technol. (1)

J. Microsc. (2)

M. Müller, J. Squier, R. Wolleschensky, U. Simon, G. J. Brakenhoff, “Dispersion pre-compensation of 15 femtosecond optical pulses for high-numerical-aperture objectives,” J. Microsc. 191(2), 141–150 (1998).
[CrossRef] [PubMed]

D. Bird, M. Gu, “Fibre-optic two-photon scanning fluorescence microscopy,” J. Microsc. 208(1), 35–48 (2002).
[CrossRef] [PubMed]

Nat. Photonics (1)

J. S. Skibina, R. Iliew, J. Bethge, M. Bock, D. Fischer, V. I. Beloglasov, R. Wedell, G. Steinmeyer, “A chirped photonic-crystal fibre,” Nat. Photonics 2(11), 679–683 (2008).
[CrossRef]

Nat. Med. (1)

E. B. Brown, R. B. Campbell, Y. Tsuzuki, L. Xu, P. Carmeliet, D. Fukumura, 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]

Nat. Methods (1)

B. A. Flusberg, E. D. Cocker, W. Piyawattanametha, J. C. Jung, E. L. M. Cheung, M. J. Schnitzer, “Fiber-optic fluorescence imaging,” Nat. Methods 2(12), 941–950 (2005).
[CrossRef] [PubMed]

Neuron (1)

F. Helmchen, M. S. Fee, D. W. Tank, W. Denk, “A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals,” Neuron 31(6), 903–912 (2001).
[CrossRef] [PubMed]

Opt. Express (4)

Opt. Lett. (5)

Proc. Natl. Acad. Sci. U.S.A. (1)

D. R. Rivera, C. M. Brown, D. G. Ouzounov, I. Pavlova, D. Kobat, W. W. Webb, 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. Natl. Acad. Sci. U.S.A. (3)

Y. Zhang, M. L. Akins, K. Murari, J. Xi, M. J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, “A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy,” Proc. Natl. Acad. Sci. U.S.A. 109(32), 12878–12883 (2012).
[CrossRef] [PubMed]

A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 99(17), 11014–11019 (2002).
[CrossRef] [PubMed]

C. Stosiek, O. Garaschuk, K. Holthoff, A. Konnerth, “In vivo two-photon calcium imaging of neuronal networks,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7319–7324 (2003).
[CrossRef] [PubMed]

Quantum Electron. (1)

Yu. S. Skibina, V. V. Tuchin, V. I. Beloglazov, G. Steinmeyer, J. Bethge, R. Wedell, N. Langhoff, “Photonic crystal fibres in biomedical investigations,” Quantum Electron. 41(4), 284–301 (2011).
[CrossRef]

Science (2)

D. G. Ouzounov, F. R. Ahmad, D. Müller, N. Venkataraman, M. T. Gallagher, M. G. Thomas, J. Silcox, K. W. Koch, A. L. Gaeta, “Generation of Megawatt optical solitons in hollow-core photonic band-gap fibers,” Science 301(5640), 1702–1704 (2003).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Other (2)

G. P. Agrawal, Nonlinear Fiber Optics (Academic Press, 2007), Chap. 1.

J. Diels and W. Rudolph, Ultrashort Laser Pulse Phenomena (Academic Press, 2006), Chap. 1.

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Figures (10)

Fig. 1
Fig. 1

Optical micrograph of the structure of a CPCF. Scale bar is 30µm.

Fig. 2
Fig. 2

(a) Measurement of transmission window of ~1 m CPCF by using white light source; (b) Spectra of the laser light before and after passing through ~1 m CPCF. The insertion in (b) shows the far-field beam profile after ~1 m CPCF delivery.

Fig. 3
Fig. 3

Intensity autocorrelation measurements for three cases without the dispersion compensation. The blue curve shows the pulse directly at the laser output; the red line shows the laser pulse after passing through the coupling and collimation lenses; the green line shows the pulse after passing through ~0.5 m CPCF in addition to the coupling and collimation lenses.

Fig. 4
Fig. 4

Measurement of bending loss of CPCF.

Fig. 5
Fig. 5

Fiber-delivered MPM system configuration. Dotted box shows the dispersion pre-compensation unit and dash-dotted box shows the MPM imaging sub-system; M, mirror; P, prism; ND, variable neutral density filter; FL, Focusing lens; CL, collimation lens; Obj, objective lens; F, filter; PMT, photomultiplier tube. In this setup, CPCF and PBF are bent in ~90 degrees with ~13 cm bending radius.

Fig. 6
Fig. 6

Intensity autocorrelation measurements at sample location before (top) and after (bottom) implementing pre-compensation with three pulse-delivery configurations. (a) and (d), With free-space delivery. (b) and (e), With ~1 m of CPCF fiber delivery in the system. (c) and (f), With ~0.5 m of PBF fiber delivery in the system.

Fig. 7
Fig. 7

MPM images of yew leaf (a) and mouse tail tendon (b) when excitation light is delivered by the CPCF. Images are in false color, with TPEF in red and SHG in green. Power on the sample is about 4 mW. Pixel dwell time is 10 μs for both images. The scale bar is 50 µm.

Fig. 8
Fig. 8

MPM images of human skin when excitation light is delivered by CPCF. From (a) to (f), the images are acquired at different depths where the distance to the skin surface is denoted on each image. The arrows in (f) indicate the elastin fibers. Power on the sample is 5 mW. Pixel dwell time is 10 μs for all the images. The scale bar is 50 µm.

Fig.
								9
Fig. 9

Comparison of MPM images of fluorescent beads and fish scale when excitation light is delivered by CPCF (top row) and free-space (bottom row). (a) and (c), TPEF images of 6 µm fluorescent beads with 0.06 mW power on the sample. (b) and (d), SHG images of fish scale with 4 mW power on the sample. Pixel dwell time remains the same as 10 μs for all the images with and without the fiber delivery. The scale bar is 50 µm.

Fig. 10
Fig. 10

Comparison of MPM images of fluorescent beads, fish scale, and human skin where excitation light is delivered by CPCF (top row) and HC-800-01 (bottom row). Image brightness in the bottom row is enhanced by 10 × to make the images discernible. (a) and (d), TPEF images of 2 µm fluorescent beads with 0.1 mW excitation power. (b) and (e), SHG images of fish scale with 4 mW excitation power. (c) and (f), MPM images from dermis layer of human skin with 5 mW excitation power. The scale bar is 50 µm.

Equations (3)

Equations on this page are rendered with MathJax. Learn more.

Δ t out = ( Δt ) 4 +16 ( ln2 ) 2 ( φ 2 ) 2 / Δt
Δt= C B / Δν = C B / ( c Δλ / λ 0 2 )
φ 2_CPCF = φ 2_(CPCF+Lenses) φ 2_Lenses = k 2_CPCF l CPCF

Metrics