Abstract

Deep tissue multiphoton imaging requires high peak power to enhance signal and low average power to prevent thermal damage. Both goals can be advantageously achieved through laser repetition rate tuning instead of simply adjusting the average power. We show that the ideal repetition rate for deep two-photon imaging in the mouse brain is between 1 and 10 MHz, and we present a fiber-based source with an arbitrarily tunable repetition rate within this range. The performance of the new source is compared to a mode-locked Ti:Sapphire (Ti:S) laser for in vivo imaging of mouse brain vasculature. At 2.5 MHz, the fiber source requires 5.1 times less average power to obtain the same signal as a standard Ti:S laser operating at 80 MHz.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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2017 (2)

2016 (3)

N. Linz, S. Freidank, X.-X. Liang, and A. Vogel, “Wavelength dependence of femtosecond laser-induced breakdown in water and implications for laser surgery,” Phys. Rev. B 94(2), 024113 (2016).
[Crossref]

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

K. Podgorski and G. Ranganathan, “Brain heating induced by near-infrared lasers during multiphoton microscopy,” J. Neurophysiol. 116(3), 1012–1023 (2016).
[Crossref] [PubMed]

2015 (4)

C. Tischbirek, A. Birkner, H. Jia, B. Sakmann, and A. Konnerth, “Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator,” Proc. Natl. Acad. Sci. U.S.A. 112(36), 11377–11382 (2015).
[Crossref] [PubMed]

V. Gautam, J. Drury, J. M. C. Choy, C. Stricker, H.-A. Bachor, and V. R. Daria, “Improved two-photon imaging of living neurons in brain tissue through temporal gating,” Biomed. Opt. Express 6(10), 4027–4036 (2015).
[Crossref] [PubMed]

D. J. L. Graham, S. F. Tseng, J. T. Hsieh, D. J. Chen, and G. Alexandrakis, “Dependence of Two-Photon eGFP Bleaching on Femtosecond Pulse Spectral Amplitude and Phase,” J. Fluoresc. 25(6), 1775–1785 (2015).
[Crossref] [PubMed]

D. Sinefeld, H. P. Paudel, D. G. Ouzounov, T. G. Bifano, and C. Xu, “Adaptive optics in multiphoton microscopy: comparison of two, three and four photon fluorescence,” Opt. Express 23(24), 31472–31483 (2015).
[Crossref] [PubMed]

2014 (1)

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20, 6800311 (2014).

2013 (1)

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

2011 (1)

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. D. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

2010 (3)

2009 (1)

2008 (4)

J. H. Lee, J. van Howe, X. Liu, and C. Xu, “Soliton self-frequency shift: experimental demonstrations and applications,” IEEE J. Sel. Top. Quantum Electron. 14(3), 713–723 (2008).
[Crossref] [PubMed]

G. Olivié, D. Giguère, F. Vidal, T. Ozaki, J.-C. Kieffer, O. Nada, and I. Brunette, “Wavelength dependence of femtosecond laser ablation threshold of corneal stroma,” Opt. Express 16(6), 4121–4129 (2008).
[Crossref] [PubMed]

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

N. Ji, J. C. Magee, and E. Betzig, “High-speed, low-photodamage nonlinear imaging using passive pulse splitters,” Nat. Methods 5(2), 197–202 (2008).
[Crossref] [PubMed]

2007 (3)

G. Donnert, C. Eggeling, and S. W. Hell, “Major signal increase in fluorescence microscopy through dark-state relaxation,” Nat. Methods 4(1), 81–86 (2007).
[Crossref] [PubMed]

R. Le Harzic, I. Riemann, K. König, C. Wüllner, and C. Donitzky, “Influence of femtosecond laser pulse irradiation on the viability of cells at 1035, 517, and 345 nm,” J. Appl. Phys. 102, 114701 (2007).

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

2005 (1)

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

2003 (1)

2002 (1)

2001 (1)

A. Hopt and E. Neher, “Highly nonlinear photodamage in two-photon fluorescence microscopy,” Biophys. J. 80(4), 2029–2036 (2001).
[Crossref] [PubMed]

2000 (1)

G. H. Patterson and D. W. Piston, “Photobleaching in two-photon excitation microscopy,” Biophys. J. 78(4), 2159–2162 (2000).
[Crossref] [PubMed]

1996 (2)

C. Xu and W. W. Webb, “Measurement of two-photon excitation cross sections of molecular fluorophores with data from 690 to 1050 nm,” J. Opt. Soc. Am. B 13(3), 481–491 (1996).
[Crossref]

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

1995 (1)

1987 (1)

P. Beaud, W. Hodel, B. Zysset, and H. P. Weber, “Ultrashort pulse propagation, pulse breakup, and fundamental soliton formation in a single-mode optical fiber,” IEEE J. Quantum Electron. 23(11), 1938–1946 (1987).
[Crossref]

1986 (1)

Adelman, T. L.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Alexandrakis, G.

D. J. L. Graham, S. F. Tseng, J. T. Hsieh, D. J. Chen, and G. Alexandrakis, “Dependence of Two-Photon eGFP Bleaching on Femtosecond Pulse Spectral Amplitude and Phase,” J. Fluoresc. 25(6), 1775–1785 (2015).
[Crossref] [PubMed]

Andegeko, Y.

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Bachor, H.-A.

Baltuska, A.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Beaud, P.

P. Beaud, W. Hodel, B. Zysset, and H. P. Weber, “Ultrashort pulse propagation, pulse breakup, and fundamental soliton formation in a single-mode optical fiber,” IEEE J. Quantum Electron. 23(11), 1938–1946 (1987).
[Crossref]

Bethge, P.

Betzig, E.

N. Ji, J. C. Magee, and E. Betzig, “High-speed, low-photodamage nonlinear imaging using passive pulse splitters,” Nat. Methods 5(2), 197–202 (2008).
[Crossref] [PubMed]

Bifano, T. G.

Birkner, A.

C. Tischbirek, A. Birkner, H. Jia, B. Sakmann, and A. Konnerth, “Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator,” Proc. Natl. Acad. Sci. U.S.A. 112(36), 11377–11382 (2015).
[Crossref] [PubMed]

Boppart, S. A.

H. Tu and S. A. Boppart, “Versatile photonic crystal fiber-enabled source for multi-modality biophotonic imaging beyond conventional multiphoton microscopy,” Proc. SPIE 7569, 75692D (2010).
[Crossref]

Brunette, I.

Carriles, R.

Carta, S.

Chandler, E. V.

Charan, K.

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20, 6800311 (2014).

Chen, D. J.

D. J. L. Graham, S. F. Tseng, J. T. Hsieh, D. J. Chen, and G. Alexandrakis, “Dependence of Two-Photon eGFP Bleaching on Femtosecond Pulse Spectral Amplitude and Phase,” J. Fluoresc. 25(6), 1775–1785 (2015).
[Crossref] [PubMed]

Choy, J. M. C.

Clark, C. G.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Clark, T. A.

Collman, F.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Czubayko, U.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. D. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Dantus, M.

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Daria, V. R.

Dela Cruz, J. M.

Delcour, J. E.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Denk, W.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. D. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

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

P. Theer, M. T. Hasan, and W. Denk, “Two-photon imaging to a depth of 1000 µm in living brains by use of a Ti:Al2O3 regenerative amplifier,” Opt. Lett. 28(12), 1022–1024 (2003).
[Crossref] [PubMed]

C. Xu, J. Guild, W. Webb, and W. Denk, “Determination of absolute two-photon excitation cross sections by in situ second-order autocorrelation,” Opt. Lett. 20(23), 2372 (1995).
[Crossref] [PubMed]

Dombeck, D. A.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Donitzky, C.

R. Le Harzic, I. Riemann, K. König, C. Wüllner, and C. Donitzky, “Influence of femtosecond laser pulse irradiation on the viability of cells at 1035, 517, and 345 nm,” J. Appl. Phys. 102, 114701 (2007).

Donnert, G.

G. Donnert, C. Eggeling, and S. W. Hell, “Major signal increase in fluorescence microscopy through dark-state relaxation,” Nat. Methods 4(1), 81–86 (2007).
[Crossref] [PubMed]

Drury, J.

Dunn, A. K.

Durst, M. E.

Eggeling, C.

G. Donnert, C. Eggeling, and S. W. Hell, “Major signal increase in fluorescence microscopy through dark-state relaxation,” Nat. Methods 4(1), 81–86 (2007).
[Crossref] [PubMed]

Emaury, F.

Fernández, A.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Field, J. J.

Freidank, S.

N. Linz, S. Freidank, X.-X. Liang, and A. Vogel, “Wavelength dependence of femtosecond laser-induced breakdown in water and implications for laser surgery,” Phys. Rev. B 94(2), 024113 (2016).
[Crossref]

Gautam, V.

Giguère, D.

Golshani, P.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Gordon, J. P.

Graham, D. J. L.

D. J. L. Graham, S. F. Tseng, J. T. Hsieh, D. J. Chen, and G. Alexandrakis, “Dependence of Two-Photon eGFP Bleaching on Femtosecond Pulse Spectral Amplitude and Phase,” J. Fluoresc. 25(6), 1775–1785 (2015).
[Crossref] [PubMed]

Guild, J.

Hagan, K.

Hasan, M. T.

Hassan, A. M.

Hell, S. W.

G. Donnert, C. Eggeling, and S. W. Hell, “Major signal increase in fluorescence microscopy through dark-state relaxation,” Nat. Methods 4(1), 81–86 (2007).
[Crossref] [PubMed]

Helmchen, F.

Herb, J. T.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. D. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Hodel, W.

P. Beaud, W. Hodel, B. Zysset, and H. P. Weber, “Ultrashort pulse propagation, pulse breakup, and fundamental soliton formation in a single-mode optical fiber,” IEEE J. Quantum Electron. 23(11), 1938–1946 (1987).
[Crossref]

Hoover, E. E.

Hopt, A.

A. Hopt and E. Neher, “Highly nonlinear photodamage in two-photon fluorescence microscopy,” Biophys. J. 80(4), 2029–2036 (2001).
[Crossref] [PubMed]

Horton, N. G.

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20, 6800311 (2014).

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Hsieh, J. T.

D. J. L. Graham, S. F. Tseng, J. T. Hsieh, D. J. Chen, and G. Alexandrakis, “Dependence of Two-Photon eGFP Bleaching on Femtosecond Pulse Spectral Amplitude and Phase,” J. Fluoresc. 25(6), 1775–1785 (2015).
[Crossref] [PubMed]

Huang, B. S.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Hughes, T. E.

Jarrett, J. W.

Ji, N.

N. Ji, J. C. Magee, and E. Betzig, “High-speed, low-photodamage nonlinear imaging using passive pulse splitters,” Nat. Methods 5(2), 197–202 (2008).
[Crossref] [PubMed]

Jia, H.

C. Tischbirek, A. Birkner, H. Jia, B. Sakmann, and A. Konnerth, “Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator,” Proc. Natl. Acad. Sci. U.S.A. 112(36), 11377–11382 (2015).
[Crossref] [PubMed]

Jones, R. J.

Jones, T. A.

Keller, U.

Kerr, J. N. D.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. D. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Khabbaz, A. N.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Kieffer, J.-C.

Kleinfeld, D.

Kobat, D.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

D. Kobat, M. E. Durst, N. Nishimura, A. W. Wong, C. B. Schaffer, and C. Xu, “Deep tissue multiphoton microscopy using longer wavelength excitation,” Opt. Express 17(16), 13354–13364 (2009).
[Crossref] [PubMed]

König, K.

R. Le Harzic, I. Riemann, K. König, C. Wüllner, and C. Donitzky, “Influence of femtosecond laser pulse irradiation on the viability of cells at 1035, 517, and 345 nm,” J. Appl. Phys. 102, 114701 (2007).

Konnerth, A.

C. Tischbirek, A. Birkner, H. Jia, B. Sakmann, and A. Konnerth, “Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator,” Proc. Natl. Acad. Sci. U.S.A. 112(36), 11377–11382 (2015).
[Crossref] [PubMed]

Le Harzic, R.

R. Le Harzic, I. Riemann, K. König, C. Wüllner, and C. Donitzky, “Influence of femtosecond laser pulse irradiation on the viability of cells at 1035, 517, and 345 nm,” J. Appl. Phys. 102, 114701 (2007).

Lee, J. H.

J. H. Lee, J. van Howe, X. Liu, and C. Xu, “Soliton self-frequency shift: experimental demonstrations and applications,” IEEE J. Sel. Top. Quantum Electron. 14(3), 713–723 (2008).
[Crossref] [PubMed]

Liang, X.-X.

N. Linz, S. Freidank, X.-X. Liang, and A. Vogel, “Wavelength dependence of femtosecond laser-induced breakdown in water and implications for laser surgery,” Phys. Rev. B 94(2), 024113 (2016).
[Crossref]

Link, S. M.

Linz, N.

N. Linz, S. Freidank, X.-X. Liang, and A. Vogel, “Wavelength dependence of femtosecond laser-induced breakdown in water and implications for laser surgery,” Phys. Rev. B 94(2), 024113 (2016).
[Crossref]

Liu, X.

J. H. Lee, J. van Howe, X. Liu, and C. Xu, “Soliton self-frequency shift: experimental demonstrations and applications,” IEEE J. Sel. Top. Quantum Electron. 14(3), 713–723 (2008).
[Crossref] [PubMed]

Looger, L. L.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. D. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Lozovoy, V. V.

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Magee, J. C.

N. Ji, J. C. Magee, and E. Betzig, “High-speed, low-photodamage nonlinear imaging using passive pulse splitters,” Nat. Methods 5(2), 197–202 (2008).
[Crossref] [PubMed]

McMullen, J. D.

Medina, F. A.

Miller, D. R.

Mitschke, F. M.

Mittmann, W.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. D. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Mollenauer, L. F.

Nada, O.

Neher, E.

A. Hopt and E. Neher, “Highly nonlinear photodamage in two-photon fluorescence microscopy,” Biophys. J. 80(4), 2029–2036 (2001).
[Crossref] [PubMed]

Nishimura, N.

Nöbauer, T.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Olivié, G.

Ouzounov, D. G.

Ozaki, T.

Patterson, G. H.

G. H. Patterson and D. W. Piston, “Photobleaching in two-photon excitation microscopy,” Biophys. J. 78(4), 2159–2162 (2000).
[Crossref] [PubMed]

Paudel, H. P.

Perillo, E. P.

Pernía-Andrade, A. J.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Piston, D. W.

G. H. Patterson and D. W. Piston, “Photobleaching in two-photon excitation microscopy,” Biophys. J. 78(4), 2159–2162 (2000).
[Crossref] [PubMed]

Podgorski, K.

K. Podgorski and G. Ranganathan, “Brain heating induced by near-infrared lasers during multiphoton microscopy,” J. Neurophysiol. 116(3), 1012–1023 (2016).
[Crossref] [PubMed]

Prevedel, R.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Ranganathan, G.

K. Podgorski and G. Ranganathan, “Brain heating induced by near-infrared lasers during multiphoton microscopy,” J. Neurophysiol. 116(3), 1012–1023 (2016).
[Crossref] [PubMed]

Riemann, I.

R. Le Harzic, I. Riemann, K. König, C. Wüllner, and C. Donitzky, “Influence of femtosecond laser pulse irradiation on the viability of cells at 1035, 517, and 345 nm,” J. Appl. Phys. 102, 114701 (2007).

Sakmann, B.

C. Tischbirek, A. Birkner, H. Jia, B. Sakmann, and A. Konnerth, “Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator,” Proc. Natl. Acad. Sci. U.S.A. 112(36), 11377–11382 (2015).
[Crossref] [PubMed]

Schaefer, A. T.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. D. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Schaffer, C. B.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

D. Kobat, M. E. Durst, N. Nishimura, A. W. Wong, C. B. Schaffer, and C. Xu, “Deep tissue multiphoton microscopy using longer wavelength excitation,” Opt. Express 17(16), 13354–13364 (2009).
[Crossref] [PubMed]

Shams Kazmi, S. M.

Shear, J. B.

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

Sheetz, K. E.

Sinefeld, D.

Squier, J. A.

Stricker, C.

Sullender, C. T.

Sylvester, A. W.

Tank, D. W.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Theer, P.

Tillo, S. E.

Tischbirek, C.

C. Tischbirek, A. Birkner, H. Jia, B. Sakmann, and A. Konnerth, “Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator,” Proc. Natl. Acad. Sci. U.S.A. 112(36), 11377–11382 (2015).
[Crossref] [PubMed]

Tseng, S. F.

D. J. L. Graham, S. F. Tseng, J. T. Hsieh, D. J. Chen, and G. Alexandrakis, “Dependence of Two-Photon eGFP Bleaching on Femtosecond Pulse Spectral Amplitude and Phase,” J. Fluoresc. 25(6), 1775–1785 (2015).
[Crossref] [PubMed]

Tu, H.

H. Tu and S. A. Boppart, “Versatile photonic crystal fiber-enabled source for multi-modality biophotonic imaging beyond conventional multiphoton microscopy,” Proc. SPIE 7569, 75692D (2010).
[Crossref]

van der Bourg, A.

van Howe, J.

J. H. Lee, J. van Howe, X. Liu, and C. Xu, “Soliton self-frequency shift: experimental demonstrations and applications,” IEEE J. Sel. Top. Quantum Electron. 14(3), 713–723 (2008).
[Crossref] [PubMed]

Vaziri, A.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Verhoef, A. J.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Vidal, F.

Vogel, A.

N. Linz, S. Freidank, X.-X. Liang, and A. Vogel, “Wavelength dependence of femtosecond laser-induced breakdown in water and implications for laser surgery,” Phys. Rev. B 94(2), 024113 (2016).
[Crossref]

Voigt, F. F.

Waldburger, D.

Wallace, D. J.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. D. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Wang, K.

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20, 6800311 (2014).

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Webb, W.

Webb, W. W.

C. Xu and W. W. Webb, “Measurement of two-photon excitation cross sections of molecular fluorophores with data from 690 to 1050 nm,” J. Opt. Soc. Am. B 13(3), 481–491 (1996).
[Crossref]

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

Weber, H. P.

P. Beaud, W. Hodel, B. Zysset, and H. P. Weber, “Ultrashort pulse propagation, pulse breakup, and fundamental soliton formation in a single-mode optical fiber,” IEEE J. Quantum Electron. 23(11), 1938–1946 (1987).
[Crossref]

Weisel, L. R.

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Weisenburger, S.

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

Williams, R. M.

J. M. Dela Cruz, J. D. McMullen, R. M. Williams, and W. R. Zipfel, “Feasibility of using multiphoton excited tissue autofluorescence for in vivo human histopathology,” Biomed. Opt. Express 1(5), 1320–1330 (2010).
[Crossref] [PubMed]

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

Wise, F. W.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Wong, A. W.

Wüllner, C.

R. Le Harzic, I. Riemann, K. König, C. Wüllner, and C. Donitzky, “Influence of femtosecond laser pulse irradiation on the viability of cells at 1035, 517, and 345 nm,” J. Appl. Phys. 102, 114701 (2007).

Xi, P.

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Xu, C.

D. Sinefeld, H. P. Paudel, D. G. Ouzounov, T. G. Bifano, and C. Xu, “Adaptive optics in multiphoton microscopy: comparison of two, three and four photon fluorescence,” Opt. Express 23(24), 31472–31483 (2015).
[Crossref] [PubMed]

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20, 6800311 (2014).

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

D. Kobat, M. E. Durst, N. Nishimura, A. W. Wong, C. B. Schaffer, and C. Xu, “Deep tissue multiphoton microscopy using longer wavelength excitation,” Opt. Express 17(16), 13354–13364 (2009).
[Crossref] [PubMed]

J. H. Lee, J. van Howe, X. Liu, and C. Xu, “Soliton self-frequency shift: experimental demonstrations and applications,” IEEE J. Sel. Top. Quantum Electron. 14(3), 713–723 (2008).
[Crossref] [PubMed]

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

C. Xu and W. W. Webb, “Measurement of two-photon excitation cross sections of molecular fluorophores with data from 690 to 1050 nm,” J. Opt. Soc. Am. B 13(3), 481–491 (1996).
[Crossref]

C. Xu, J. Guild, W. Webb, and W. Denk, “Determination of absolute two-photon excitation cross sections by in situ second-order autocorrelation,” Opt. Lett. 20(23), 2372 (1995).
[Crossref] [PubMed]

Ye, J.

Zemelman, B. V.

Zipfel, W.

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

Zipfel, W. R.

Zysset, B.

P. Beaud, W. Hodel, B. Zysset, and H. P. Weber, “Ultrashort pulse propagation, pulse breakup, and fundamental soliton formation in a single-mode optical fiber,” IEEE J. Quantum Electron. 23(11), 1938–1946 (1987).
[Crossref]

Biomed. Opt. Express (4)

Biophys. J. (2)

G. H. Patterson and D. W. Piston, “Photobleaching in two-photon excitation microscopy,” Biophys. J. 78(4), 2159–2162 (2000).
[Crossref] [PubMed]

A. Hopt and E. Neher, “Highly nonlinear photodamage in two-photon fluorescence microscopy,” Biophys. J. 80(4), 2029–2036 (2001).
[Crossref] [PubMed]

IEEE J. Quantum Electron. (1)

P. Beaud, W. Hodel, B. Zysset, and H. P. Weber, “Ultrashort pulse propagation, pulse breakup, and fundamental soliton formation in a single-mode optical fiber,” IEEE J. Quantum Electron. 23(11), 1938–1946 (1987).
[Crossref]

IEEE J. Sel. Top. Quantum Electron. (2)

J. H. Lee, J. van Howe, X. Liu, and C. Xu, “Soliton self-frequency shift: experimental demonstrations and applications,” IEEE J. Sel. Top. Quantum Electron. 14(3), 713–723 (2008).
[Crossref] [PubMed]

K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20, 6800311 (2014).

J. Appl. Phys. (1)

R. Le Harzic, I. Riemann, K. König, C. Wüllner, and C. Donitzky, “Influence of femtosecond laser pulse irradiation on the viability of cells at 1035, 517, and 345 nm,” J. Appl. Phys. 102, 114701 (2007).

J. Fluoresc. (1)

D. J. L. Graham, S. F. Tseng, J. T. Hsieh, D. J. Chen, and G. Alexandrakis, “Dependence of Two-Photon eGFP Bleaching on Femtosecond Pulse Spectral Amplitude and Phase,” J. Fluoresc. 25(6), 1775–1785 (2015).
[Crossref] [PubMed]

J. Neurophysiol. (1)

K. Podgorski and G. Ranganathan, “Brain heating induced by near-infrared lasers during multiphoton microscopy,” J. Neurophysiol. 116(3), 1012–1023 (2016).
[Crossref] [PubMed]

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

Nat. Methods (4)

R. Prevedel, A. J. Verhoef, A. J. Pernía-Andrade, S. Weisenburger, B. S. Huang, T. Nöbauer, A. Fernández, J. E. Delcour, P. Golshani, A. Baltuska, and A. Vaziri, “Fast volumetric calcium imaging across multiple cortical layers using sculpted light,” Nat. Methods 13(12), 1021–1028 (2016).
[Crossref] [PubMed]

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

G. Donnert, C. Eggeling, and S. W. Hell, “Major signal increase in fluorescence microscopy through dark-state relaxation,” Nat. Methods 4(1), 81–86 (2007).
[Crossref] [PubMed]

N. Ji, J. C. Magee, and E. Betzig, “High-speed, low-photodamage nonlinear imaging using passive pulse splitters,” Nat. Methods 5(2), 197–202 (2008).
[Crossref] [PubMed]

Nat. Neurosci. (1)

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. D. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Nat. Photonics (1)

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Neuron (1)

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Opt. Commun. (1)

P. Xi, Y. Andegeko, L. R. Weisel, V. V. Lozovoy, and M. Dantus, “Greater signal, increased depth, and less photobleaching in two-photon microscopy with 10 fs pulses,” Opt. Commun. 281(7), 1841–1849 (2008).
[Crossref]

Opt. Express (4)

Opt. Lett. (4)

Phys. Rev. B (1)

N. Linz, S. Freidank, X.-X. Liang, and A. Vogel, “Wavelength dependence of femtosecond laser-induced breakdown in water and implications for laser surgery,” Phys. Rev. B 94(2), 024113 (2016).
[Crossref]

Proc. Natl. Acad. Sci. U.S.A. (2)

C. Tischbirek, A. Birkner, H. Jia, B. Sakmann, and A. Konnerth, “Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator,” Proc. Natl. Acad. Sci. U.S.A. 112(36), 11377–11382 (2015).
[Crossref] [PubMed]

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

Proc. SPIE (1)

H. Tu and S. A. Boppart, “Versatile photonic crystal fiber-enabled source for multi-modality biophotonic imaging beyond conventional multiphoton microscopy,” Proc. SPIE 7569, 75692D (2010).
[Crossref]

Other (2)

Spectra-Physics, “Femtosource XL.”

Coherent, “Mira-900 with pulse switch accessory.”

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Figures (5)

Fig. 1
Fig. 1 Tunable repetition rate source for two-photon imaging.
Fig. 2
Fig. 2 a) SSFS spectra after the PC Rod at various repetition rates when pumped at 7W of average power at 1550 nm. A 1600-nm long pass filter was used to remove the residual pump light. Spectra are offset vertically for clarity. Second order interferometric autocorrelations for the 1880 nm soliton (b, deconvolution factor = 1.54) and the 940 nm frequency-doubled pulse (c, deconvolution factor = 1.4).
Fig. 3
Fig. 3 Fluorescence signal intensity as a function of the inverse of the source repetition rate at the constant average power of 0.08 mW on the sample. The solid circles are the measured data, and the dashed line is a linear fit to the data.
Fig. 4
Fig. 4 Second order autocorrelation traces recorded after the microscope for the 940 nm pulse from (a) the soliton and (b) the Ti:S oscillator (GaAsP photodiode, deconvolution factor = 1.4) Signal from the soliton source and Ti:S laser (c) in a fluorescein dye-pool and (d) as a function of imaging depth for in vivo mouse brain imaging.
Fig. 5
Fig. 5 Fluorescein-labeled mouse brain vasculature recorded with both sources. Images were recorded at comparable fluorescence levels, and have been further normalized to emphasize that there is no difference in image quality. (a),(c) Ti:S laser; (b),(d) Soliton source. Imaging depth from surface of the brain is 680 μm for (a) and (b) and 30 μm for (c) and (d).

Tables (1)

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Table 1 Saturation pulse energy Esat and the optimum repetition rate, f0, for imaging at depths of 4 and 5 attenuation lengths (la) for some common green and yellow fluorescent dyes.*

Equations (2)

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f 0 P surface E focus exp( z l a )
E sat = λ 2 πN A 2 τ g p (2) σ 2

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