Abstract

A novel, Yb-fiber laser based, handheld 2PEF/SHG microscope imaging system is introduced. It is suitable for in vivo imaging of murine skin at an average power level as low as 5 mW at 200 kHz sampling rate. Amplified and compressed laser pulses having a spectral bandwidth of 8 to 12 nm at around 1030 nm excite the biological samples at a ~1.89 MHz repetition rate, which explains how the high quality two-photon excitation fluorescence (2PEF) and second harmonic generation (SHG) images are obtained at the average power level of a laser pointer. The scanning, imaging and detection head, which comprises a conventional microscope objective for beam focusing, has a physical length of ~180 mm owing to the custom designed imaging telescope system between the laser scanner mirrors and the entrance aperture of the microscope objective. Operation of the all-fiber, all-normal dispersion Yb-fiber ring laser oscillator is electronically controlled by a two-channel polarization controller for Q-switching free mode-locked operation. The whole nonlinear microscope imaging system has the main advantages of the low price of the fs laser applied, fiber optics flexibility, a relatively small, light-weight scanning and detection head, and a very low risk of thermal or photochemical damage of the skin samples.

© 2016 Optical Society of America

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References

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2016 (2)

M. Klemp, M. C. Meinke, M. Weinigel, H. J. Röwert-Huber, K. König, M. Ulrich, J. Lademann, and M. E. Darvin, “Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography,” Exp. Dermatol. 25(3), 218–222 (2016).
[Crossref] [PubMed]

L. Huang, A. K. Mills, Y. Zhao, D. J. Jones, and S. Tang, “Miniature fiber-optic multiphoton microscopy system using frequency-doubled femtosecond Er-doped fiber laser,” Biomed. Opt. Express 7(5), 1948–1956 (2016).
[Crossref] [PubMed]

2015 (3)

M. Weinigel, H. G. Breunig, A. Uchugonova, and K. König, “Multipurpose nonlinear optical imaging system for in vivo and ex vivo multimodal histology,” J. Med. Imaging (Bellingham) 2(1), 016003 (2015).
[Crossref] [PubMed]

M. Balu, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, B. J. Tromberg, and K. M. Kelly, “In vivo multiphoton microscopy of basal cell carcinoma,” JAMA Dermatol. 151(10), 1068–1074 (2015).
[Crossref] [PubMed]

D. Haluszka, K. Lőrincz, G. Molnár, G. Tamás, A. Kolonics, R. Szipőcs, S. Kárpáti, and N. M. Wikonkál, “In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroblast cell function using an Yb-fiber laser-based CARS extension unit,” Microsc. Res. Tech. 78(9), 823–830 (2015).
[Crossref] [PubMed]

2014 (4)

A. Kolonics, Z. Csiszovszki, E. R. Tőke, O. Lőrincz, D. Haluszka, and R. Szipőcs, “In vivo study of targeted nanomedicine delivery into Langerhans cells by multiphoton laser scanning microscopy,” Exp. Dermatol. 23(8), 596–605 (2014).
[Crossref] [PubMed]

D. Haluszka, K. Lőrincz, R. Szipőcs, N. Gyöngyösi, A. Bánvölgyi, A. Keszeg, S. Kárpáti, and N. M. Wikonkál, “In vivo assessment of potential carcinogenicity of multi-photon microscopy as the function of wavelength in the near-infrared range,” J. Invest. Dermatol. 134, S86 (2014).

M. Balu, K. M. Kelly, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, A. J. Durkin, and B. J. Tromberg, “Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy,” Cancer Res. 74(10), 2688–2697 (2014).
[Crossref] [PubMed]

Z. Várallyay and R. Szipőcs, “Stored energy, transmission group delay and mode field distortion in optical fibers,” IEEE J. Sel. Top. Quantum Electron. 20, 0904206 (2014).

2013 (1)

M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan, and B. J. Tromberg, “In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin,” Biophys. J. 104(1), 258–267 (2013).
[Crossref] [PubMed]

2012 (2)

2011 (1)

2009 (1)

J. Fekete, A. Cserteg, and R. Szipőcs, “All-fiber, all-normal dispersion ytterbium ring oscillator,” Laser Phys. Lett. 6(1), 49–53 (2009).
[Crossref]

2008 (2)

2005 (2)

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]

A. Komarov, H. Leblond, and F. Sanchez, “Theoretical analysis of the operating regime of a passively-mode-locked fiber laser through nonlinear polarization rotation,” Phys. Rev. A 72(6), 063811 (2005).
[Crossref]

1997 (1)

Allen, J.

Anderson, E. P.

Antal, P.

P. Antal and R. Szipőcs, “Tunable, low-repetition-rate, cost-efficient femtosecond Ti:sapphire laser for nonlinear microscopy,” Appl. Phys. B 107(1), 17–22 (2012).
[Crossref]

Balu, M.

M. Balu, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, B. J. Tromberg, and K. M. Kelly, “In vivo multiphoton microscopy of basal cell carcinoma,” JAMA Dermatol. 151(10), 1068–1074 (2015).
[Crossref] [PubMed]

M. Balu, K. M. Kelly, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, A. J. Durkin, and B. J. Tromberg, “Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy,” Cancer Res. 74(10), 2688–2697 (2014).
[Crossref] [PubMed]

M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan, and B. J. Tromberg, “In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin,” Biophys. J. 104(1), 258–267 (2013).
[Crossref] [PubMed]

Bánvölgyi, A.

D. Haluszka, K. Lőrincz, R. Szipőcs, N. Gyöngyösi, A. Bánvölgyi, A. Keszeg, S. Kárpáti, and N. M. Wikonkál, “In vivo assessment of potential carcinogenicity of multi-photon microscopy as the function of wavelength in the near-infrared range,” J. Invest. Dermatol. 134, S86 (2014).

Bao, H.

Baumgartl, M.

Breunig, H. G.

M. Weinigel, H. G. Breunig, A. Uchugonova, and K. König, “Multipurpose nonlinear optical imaging system for in vivo and ex vivo multimodal histology,” J. Med. Imaging (Bellingham) 2(1), 016003 (2015).
[Crossref] [PubMed]

Chemnitz, M.

Cocker, E. D.

Cserteg, A.

J. Fekete, A. Cserteg, and R. Szipőcs, “All-fiber, all-normal dispersion ytterbium ring oscillator,” Laser Phys. Lett. 6(1), 49–53 (2009).
[Crossref]

Csiszovszki, Z.

A. Kolonics, Z. Csiszovszki, E. R. Tőke, O. Lőrincz, D. Haluszka, and R. Szipőcs, “In vivo study of targeted nanomedicine delivery into Langerhans cells by multiphoton laser scanning microscopy,” Exp. Dermatol. 23(8), 596–605 (2014).
[Crossref] [PubMed]

Darvin, M. E.

M. Klemp, M. C. Meinke, M. Weinigel, H. J. Röwert-Huber, K. König, M. Ulrich, J. Lademann, and M. E. Darvin, “Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography,” Exp. Dermatol. 25(3), 218–222 (2016).
[Crossref] [PubMed]

Dietzek, B.

Durkin, A. J.

M. Balu, K. M. Kelly, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, A. J. Durkin, and B. J. Tromberg, “Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy,” Cancer Res. 74(10), 2688–2697 (2014).
[Crossref] [PubMed]

Euteneuer, A.

Fekete, J.

J. Fekete, A. Cserteg, and R. Szipőcs, “All-fiber, all-normal dispersion ytterbium ring oscillator,” Laser Phys. Lett. 6(1), 49–53 (2009).
[Crossref]

Flusberg, B. A.

Freudiger, C. W.

Gu, M.

Gyöngyösi, N.

D. Haluszka, K. Lőrincz, R. Szipőcs, N. Gyöngyösi, A. Bánvölgyi, A. Keszeg, S. Kárpáti, and N. M. Wikonkál, “In vivo assessment of potential carcinogenicity of multi-photon microscopy as the function of wavelength in the near-infrared range,” J. Invest. Dermatol. 134, S86 (2014).

Haluszka, D.

D. Haluszka, K. Lőrincz, G. Molnár, G. Tamás, A. Kolonics, R. Szipőcs, S. Kárpáti, and N. M. Wikonkál, “In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroblast cell function using an Yb-fiber laser-based CARS extension unit,” Microsc. Res. Tech. 78(9), 823–830 (2015).
[Crossref] [PubMed]

A. Kolonics, Z. Csiszovszki, E. R. Tőke, O. Lőrincz, D. Haluszka, and R. Szipőcs, “In vivo study of targeted nanomedicine delivery into Langerhans cells by multiphoton laser scanning microscopy,” Exp. Dermatol. 23(8), 596–605 (2014).
[Crossref] [PubMed]

D. Haluszka, K. Lőrincz, R. Szipőcs, N. Gyöngyösi, A. Bánvölgyi, A. Keszeg, S. Kárpáti, and N. M. Wikonkál, “In vivo assessment of potential carcinogenicity of multi-photon microscopy as the function of wavelength in the near-infrared range,” J. Invest. Dermatol. 134, S86 (2014).

Harris, R. M.

M. Balu, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, B. J. Tromberg, and K. M. Kelly, “In vivo multiphoton microscopy of basal cell carcinoma,” JAMA Dermatol. 151(10), 1068–1074 (2015).
[Crossref] [PubMed]

M. Balu, K. M. Kelly, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, A. J. Durkin, and B. J. Tromberg, “Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy,” Cancer Res. 74(10), 2688–2697 (2014).
[Crossref] [PubMed]

Hayakawa, C. K.

M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan, and B. J. Tromberg, “In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin,” Biophys. J. 104(1), 258–267 (2013).
[Crossref] [PubMed]

Huang, L.

Jauregui, C.

Johnston, R. S.

Jones, D. J.

Jung, J. C.

Kárpáti, S.

D. Haluszka, K. Lőrincz, G. Molnár, G. Tamás, A. Kolonics, R. Szipőcs, S. Kárpáti, and N. M. Wikonkál, “In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroblast cell function using an Yb-fiber laser-based CARS extension unit,” Microsc. Res. Tech. 78(9), 823–830 (2015).
[Crossref] [PubMed]

D. Haluszka, K. Lőrincz, R. Szipőcs, N. Gyöngyösi, A. Bánvölgyi, A. Keszeg, S. Kárpáti, and N. M. Wikonkál, “In vivo assessment of potential carcinogenicity of multi-photon microscopy as the function of wavelength in the near-infrared range,” J. Invest. Dermatol. 134, S86 (2014).

Kelly, K. M.

M. Balu, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, B. J. Tromberg, and K. M. Kelly, “In vivo multiphoton microscopy of basal cell carcinoma,” JAMA Dermatol. 151(10), 1068–1074 (2015).
[Crossref] [PubMed]

M. Balu, K. M. Kelly, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, A. J. Durkin, and B. J. Tromberg, “Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy,” Cancer Res. 74(10), 2688–2697 (2014).
[Crossref] [PubMed]

Keszeg, A.

D. Haluszka, K. Lőrincz, R. Szipőcs, N. Gyöngyösi, A. Bánvölgyi, A. Keszeg, S. Kárpáti, and N. M. Wikonkál, “In vivo assessment of potential carcinogenicity of multi-photon microscopy as the function of wavelength in the near-infrared range,” J. Invest. Dermatol. 134, S86 (2014).

Kieu, K.

Klemp, M.

M. Klemp, M. C. Meinke, M. Weinigel, H. J. Röwert-Huber, K. König, M. Ulrich, J. Lademann, and M. E. Darvin, “Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography,” Exp. Dermatol. 25(3), 218–222 (2016).
[Crossref] [PubMed]

Kolonics, A.

D. Haluszka, K. Lőrincz, G. Molnár, G. Tamás, A. Kolonics, R. Szipőcs, S. Kárpáti, and N. M. Wikonkál, “In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroblast cell function using an Yb-fiber laser-based CARS extension unit,” Microsc. Res. Tech. 78(9), 823–830 (2015).
[Crossref] [PubMed]

A. Kolonics, Z. Csiszovszki, E. R. Tőke, O. Lőrincz, D. Haluszka, and R. Szipőcs, “In vivo study of targeted nanomedicine delivery into Langerhans cells by multiphoton laser scanning microscopy,” Exp. Dermatol. 23(8), 596–605 (2014).
[Crossref] [PubMed]

Komarov, A.

A. Komarov, H. Leblond, and F. Sanchez, “Theoretical analysis of the operating regime of a passively-mode-locked fiber laser through nonlinear polarization rotation,” Phys. Rev. A 72(6), 063811 (2005).
[Crossref]

König, K.

M. Klemp, M. C. Meinke, M. Weinigel, H. J. Röwert-Huber, K. König, M. Ulrich, J. Lademann, and M. E. Darvin, “Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography,” Exp. Dermatol. 25(3), 218–222 (2016).
[Crossref] [PubMed]

M. Weinigel, H. G. Breunig, A. Uchugonova, and K. König, “Multipurpose nonlinear optical imaging system for in vivo and ex vivo multimodal histology,” J. Med. Imaging (Bellingham) 2(1), 016003 (2015).
[Crossref] [PubMed]

M. Balu, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, B. J. Tromberg, and K. M. Kelly, “In vivo multiphoton microscopy of basal cell carcinoma,” JAMA Dermatol. 151(10), 1068–1074 (2015).
[Crossref] [PubMed]

M. Balu, K. M. Kelly, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, A. J. Durkin, and B. J. Tromberg, “Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy,” Cancer Res. 74(10), 2688–2697 (2014).
[Crossref] [PubMed]

M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan, and B. J. Tromberg, “In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin,” Biophys. J. 104(1), 258–267 (2013).
[Crossref] [PubMed]

Krasieva, T. B.

M. Balu, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, B. J. Tromberg, and K. M. Kelly, “In vivo multiphoton microscopy of basal cell carcinoma,” JAMA Dermatol. 151(10), 1068–1074 (2015).
[Crossref] [PubMed]

M. Balu, K. M. Kelly, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, A. J. Durkin, and B. J. Tromberg, “Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy,” Cancer Res. 74(10), 2688–2697 (2014).
[Crossref] [PubMed]

M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan, and B. J. Tromberg, “In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin,” Biophys. J. 104(1), 258–267 (2013).
[Crossref] [PubMed]

Lademann, J.

M. Klemp, M. C. Meinke, M. Weinigel, H. J. Röwert-Huber, K. König, M. Ulrich, J. Lademann, and M. E. Darvin, “Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography,” Exp. Dermatol. 25(3), 218–222 (2016).
[Crossref] [PubMed]

Leblond, H.

A. Komarov, H. Leblond, and F. Sanchez, “Theoretical analysis of the operating regime of a passively-mode-locked fiber laser through nonlinear polarization rotation,” Phys. Rev. A 72(6), 063811 (2005).
[Crossref]

Limpert, J.

Lorincz, K.

D. Haluszka, K. Lőrincz, G. Molnár, G. Tamás, A. Kolonics, R. Szipőcs, S. Kárpáti, and N. M. Wikonkál, “In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroblast cell function using an Yb-fiber laser-based CARS extension unit,” Microsc. Res. Tech. 78(9), 823–830 (2015).
[Crossref] [PubMed]

D. Haluszka, K. Lőrincz, R. Szipőcs, N. Gyöngyösi, A. Bánvölgyi, A. Keszeg, S. Kárpáti, and N. M. Wikonkál, “In vivo assessment of potential carcinogenicity of multi-photon microscopy as the function of wavelength in the near-infrared range,” J. Invest. Dermatol. 134, S86 (2014).

Lorincz, O.

A. Kolonics, Z. Csiszovszki, E. R. Tőke, O. Lőrincz, D. Haluszka, and R. Szipőcs, “In vivo study of targeted nanomedicine delivery into Langerhans cells by multiphoton laser scanning microscopy,” Exp. Dermatol. 23(8), 596–605 (2014).
[Crossref] [PubMed]

Mayer, E. J.

Mazhar, A.

M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan, and B. J. Tromberg, “In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin,” Biophys. J. 104(1), 258–267 (2013).
[Crossref] [PubMed]

Meinke, M. C.

M. Klemp, M. C. Meinke, M. Weinigel, H. J. Röwert-Huber, K. König, M. Ulrich, J. Lademann, and M. E. Darvin, “Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography,” Exp. Dermatol. 25(3), 218–222 (2016).
[Crossref] [PubMed]

Meyer, T.

Mills, A. K.

Mittal, R.

M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan, and B. J. Tromberg, “In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin,” Biophys. J. 104(1), 258–267 (2013).
[Crossref] [PubMed]

Möbius, J.

Molnár, G.

D. Haluszka, K. Lőrincz, G. Molnár, G. Tamás, A. Kolonics, R. Szipőcs, S. Kárpáti, and N. M. Wikonkál, “In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroblast cell function using an Yb-fiber laser-based CARS extension unit,” Microsc. Res. Tech. 78(9), 823–830 (2015).
[Crossref] [PubMed]

Pattie, R.

Popp, J.

Röwert-Huber, H. J.

M. Klemp, M. C. Meinke, M. Weinigel, H. J. Röwert-Huber, K. König, M. Ulrich, J. Lademann, and M. E. Darvin, “Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography,” Exp. Dermatol. 25(3), 218–222 (2016).
[Crossref] [PubMed]

Rühle, W. W.

Saar, B. G.

Sanchez, F.

A. Komarov, H. Leblond, and F. Sanchez, “Theoretical analysis of the operating regime of a passively-mode-locked fiber laser through nonlinear polarization rotation,” Phys. Rev. A 72(6), 063811 (2005).
[Crossref]

Schnitzer, M. J.

Seibel, E. J.

Szipocs, R.

D. Haluszka, K. Lőrincz, G. Molnár, G. Tamás, A. Kolonics, R. Szipőcs, S. Kárpáti, and N. M. Wikonkál, “In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroblast cell function using an Yb-fiber laser-based CARS extension unit,” Microsc. Res. Tech. 78(9), 823–830 (2015).
[Crossref] [PubMed]

A. Kolonics, Z. Csiszovszki, E. R. Tőke, O. Lőrincz, D. Haluszka, and R. Szipőcs, “In vivo study of targeted nanomedicine delivery into Langerhans cells by multiphoton laser scanning microscopy,” Exp. Dermatol. 23(8), 596–605 (2014).
[Crossref] [PubMed]

D. Haluszka, K. Lőrincz, R. Szipőcs, N. Gyöngyösi, A. Bánvölgyi, A. Keszeg, S. Kárpáti, and N. M. Wikonkál, “In vivo assessment of potential carcinogenicity of multi-photon microscopy as the function of wavelength in the near-infrared range,” J. Invest. Dermatol. 134, S86 (2014).

Z. Várallyay and R. Szipőcs, “Stored energy, transmission group delay and mode field distortion in optical fibers,” IEEE J. Sel. Top. Quantum Electron. 20, 0904206 (2014).

P. Antal and R. Szipőcs, “Tunable, low-repetition-rate, cost-efficient femtosecond Ti:sapphire laser for nonlinear microscopy,” Appl. Phys. B 107(1), 17–22 (2012).
[Crossref]

J. Fekete, A. Cserteg, and R. Szipőcs, “All-fiber, all-normal dispersion ytterbium ring oscillator,” Laser Phys. Lett. 6(1), 49–53 (2009).
[Crossref]

E. J. Mayer, J. Möbius, A. Euteneuer, W. W. Rühle, and R. Szipőcs, “Ultrabroadband chirped mirrors for femtosecond lasers,” Opt. Lett. 22(8), 528–530 (1997).
[Crossref] [PubMed]

Tamás, G.

D. Haluszka, K. Lőrincz, G. Molnár, G. Tamás, A. Kolonics, R. Szipőcs, S. Kárpáti, and N. M. Wikonkál, “In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroblast cell function using an Yb-fiber laser-based CARS extension unit,” Microsc. Res. Tech. 78(9), 823–830 (2015).
[Crossref] [PubMed]

Tang, S.

Toke, E. R.

A. Kolonics, Z. Csiszovszki, E. R. Tőke, O. Lőrincz, D. Haluszka, and R. Szipőcs, “In vivo study of targeted nanomedicine delivery into Langerhans cells by multiphoton laser scanning microscopy,” Exp. Dermatol. 23(8), 596–605 (2014).
[Crossref] [PubMed]

Tromberg, B. J.

M. Balu, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, B. J. Tromberg, and K. M. Kelly, “In vivo multiphoton microscopy of basal cell carcinoma,” JAMA Dermatol. 151(10), 1068–1074 (2015).
[Crossref] [PubMed]

M. Balu, K. M. Kelly, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, A. J. Durkin, and B. J. Tromberg, “Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy,” Cancer Res. 74(10), 2688–2697 (2014).
[Crossref] [PubMed]

M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan, and B. J. Tromberg, “In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin,” Biophys. J. 104(1), 258–267 (2013).
[Crossref] [PubMed]

Tünnermann, A.

Uchugonova, A.

M. Weinigel, H. G. Breunig, A. Uchugonova, and K. König, “Multipurpose nonlinear optical imaging system for in vivo and ex vivo multimodal histology,” J. Med. Imaging (Bellingham) 2(1), 016003 (2015).
[Crossref] [PubMed]

Ulrich, M.

M. Klemp, M. C. Meinke, M. Weinigel, H. J. Röwert-Huber, K. König, M. Ulrich, J. Lademann, and M. E. Darvin, “Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography,” Exp. Dermatol. 25(3), 218–222 (2016).
[Crossref] [PubMed]

Vance, R.

Várallyay, Z.

Z. Várallyay and R. Szipőcs, “Stored energy, transmission group delay and mode field distortion in optical fibers,” IEEE J. Sel. Top. Quantum Electron. 20, 0904206 (2014).

Venugopalan, V.

M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan, and B. J. Tromberg, “In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin,” Biophys. J. 104(1), 258–267 (2013).
[Crossref] [PubMed]

Weinigel, M.

M. Klemp, M. C. Meinke, M. Weinigel, H. J. Röwert-Huber, K. König, M. Ulrich, J. Lademann, and M. E. Darvin, “Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography,” Exp. Dermatol. 25(3), 218–222 (2016).
[Crossref] [PubMed]

M. Weinigel, H. G. Breunig, A. Uchugonova, and K. König, “Multipurpose nonlinear optical imaging system for in vivo and ex vivo multimodal histology,” J. Med. Imaging (Bellingham) 2(1), 016003 (2015).
[Crossref] [PubMed]

Wikonkál, N. M.

D. Haluszka, K. Lőrincz, G. Molnár, G. Tamás, A. Kolonics, R. Szipőcs, S. Kárpáti, and N. M. Wikonkál, “In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroblast cell function using an Yb-fiber laser-based CARS extension unit,” Microsc. Res. Tech. 78(9), 823–830 (2015).
[Crossref] [PubMed]

D. Haluszka, K. Lőrincz, R. Szipőcs, N. Gyöngyösi, A. Bánvölgyi, A. Keszeg, S. Kárpáti, and N. M. Wikonkál, “In vivo assessment of potential carcinogenicity of multi-photon microscopy as the function of wavelength in the near-infrared range,” J. Invest. Dermatol. 134, S86 (2014).

Wise, F. W.

Xie, X. S.

Zachary, C. B.

M. Balu, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, B. J. Tromberg, and K. M. Kelly, “In vivo multiphoton microscopy of basal cell carcinoma,” JAMA Dermatol. 151(10), 1068–1074 (2015).
[Crossref] [PubMed]

M. Balu, K. M. Kelly, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, A. J. Durkin, and B. J. Tromberg, “Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy,” Cancer Res. 74(10), 2688–2697 (2014).
[Crossref] [PubMed]

Zhao, Y.

Appl. Phys. B (1)

P. Antal and R. Szipőcs, “Tunable, low-repetition-rate, cost-efficient femtosecond Ti:sapphire laser for nonlinear microscopy,” Appl. Phys. B 107(1), 17–22 (2012).
[Crossref]

Biomed. Opt. Express (1)

Biophys. J. (1)

M. Balu, A. Mazhar, C. K. Hayakawa, R. Mittal, T. B. Krasieva, K. König, V. Venugopalan, and B. J. Tromberg, “In vivo multiphoton NADH fluorescence reveals depth-dependent keratinocyte metabolism in human skin,” Biophys. J. 104(1), 258–267 (2013).
[Crossref] [PubMed]

Cancer Res. (1)

M. Balu, K. M. Kelly, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, A. J. Durkin, and B. J. Tromberg, “Distinguishing between benign and malignant melanocytic nevi by in vivo multiphoton microscopy,” Cancer Res. 74(10), 2688–2697 (2014).
[Crossref] [PubMed]

Exp. Dermatol. (2)

M. Klemp, M. C. Meinke, M. Weinigel, H. J. Röwert-Huber, K. König, M. Ulrich, J. Lademann, and M. E. Darvin, “Comparison of morphologic criteria for actinic keratosis and squamous cell carcinoma using in vivo multiphoton tomography,” Exp. Dermatol. 25(3), 218–222 (2016).
[Crossref] [PubMed]

A. Kolonics, Z. Csiszovszki, E. R. Tőke, O. Lőrincz, D. Haluszka, and R. Szipőcs, “In vivo study of targeted nanomedicine delivery into Langerhans cells by multiphoton laser scanning microscopy,” Exp. Dermatol. 23(8), 596–605 (2014).
[Crossref] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (1)

Z. Várallyay and R. Szipőcs, “Stored energy, transmission group delay and mode field distortion in optical fibers,” IEEE J. Sel. Top. Quantum Electron. 20, 0904206 (2014).

J. Invest. Dermatol. (1)

D. Haluszka, K. Lőrincz, R. Szipőcs, N. Gyöngyösi, A. Bánvölgyi, A. Keszeg, S. Kárpáti, and N. M. Wikonkál, “In vivo assessment of potential carcinogenicity of multi-photon microscopy as the function of wavelength in the near-infrared range,” J. Invest. Dermatol. 134, S86 (2014).

J. Med. Imaging (Bellingham) (1)

M. Weinigel, H. G. Breunig, A. Uchugonova, and K. König, “Multipurpose nonlinear optical imaging system for in vivo and ex vivo multimodal histology,” J. Med. Imaging (Bellingham) 2(1), 016003 (2015).
[Crossref] [PubMed]

JAMA Dermatol. (1)

M. Balu, C. B. Zachary, R. M. Harris, T. B. Krasieva, K. König, B. J. Tromberg, and K. M. Kelly, “In vivo multiphoton microscopy of basal cell carcinoma,” JAMA Dermatol. 151(10), 1068–1074 (2015).
[Crossref] [PubMed]

Laser Phys. Lett. (1)

J. Fekete, A. Cserteg, and R. Szipőcs, “All-fiber, all-normal dispersion ytterbium ring oscillator,” Laser Phys. Lett. 6(1), 49–53 (2009).
[Crossref]

Microsc. Res. Tech. (1)

D. Haluszka, K. Lőrincz, G. Molnár, G. Tamás, A. Kolonics, R. Szipőcs, S. Kárpáti, and N. M. Wikonkál, “In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroblast cell function using an Yb-fiber laser-based CARS extension unit,” Microsc. Res. Tech. 78(9), 823–830 (2015).
[Crossref] [PubMed]

Opt. Express (2)

Opt. Lett. (4)

Phys. Rev. A (1)

A. Komarov, H. Leblond, and F. Sanchez, “Theoretical analysis of the operating regime of a passively-mode-locked fiber laser through nonlinear polarization rotation,” Phys. Rev. A 72(6), 063811 (2005).
[Crossref]

Other (2)

D. M. Huland, Ch. M. Brown, D. G. Ouzounov, I. Pavlova, D. R. Rivera, W. W. Webb, and Ch. Xu, “Compact and portable in vivo multiphoton GRIN endoscope,” in Biomedical Optics and Digital Holography and Three- Dimensional Imaging Conference, OSA Technical Digest Series (Optical Society of America, 2012), paper BTu3A.42.

D. Herrmann, J. Eastman, Ch. Alessi-Fox, and N. Boger, “Non-invasive in-vivo imaging of mechanoreceptors in human skin using confocal microscopy,” U.S. Patent 11/878,638 (2007).

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Figures (11)

Fig. 1
Fig. 1 Bloch scheme of the handheld 2PEF/SHG microscope imaging system comprising a 2 MHz mode-locked Yb-fiber laser.
Fig. 2
Fig. 2 (a) Photo of the 2 MHz Yb-fiber laser system comprising an AND type Yb-oscillator (FiberSource), a Pulse Picker (on the top) and a 2-stage Yb-fiber amplifier (CARS Stokes Unit). (b) Photo of the 2PEF/SHG imaging system with plastic housing and the control software interface. The plastic vacuum skin fixing unit including a 0.17 mm thick cover glass is removed in order to show the position of the microscope objective.
Fig. 3
Fig. 3 Setup of our AND type Yb-fiber seed oscillator.
Fig. 4
Fig. 4 Measured radio-frequency power spectra at different control voltages (vertical axis) at around the central frequency of the all-fiber, all-normal-dispersion Yb-fiber ring laser. Central frequency: 36.4 MHz, frequency span: 2 MHz.
Fig. 5
Fig. 5 (a) Measured signal power and (b) normalized noise power as the function of control voltage on the polarization controllers.
Fig. 6
Fig. 6 Demonstration of optical bistability of the all-fiber, all-normal dispersion Yb-fiber ring oscillator. Parameters are the same than in Fig. 5, but the data plotted were recorded for increasing and reducing quarter-wave plate control voltages for even and odd rows, respectively.
Fig. 7
Fig. 7 Optical design of the achromatic 1:3 imaging telescope (comprising two lens groups (2 and 3) between the scanner mirrors (1) and the entrance aperture of the microscope objective (5). A dichroic beamsplitter (4) is placed in front of the microscope objective.
Fig. 8
Fig. 8 Photo of the laser scanning 2PEF/SHG imaging system. The optical elements shown in the optical design (see Fig. 7) are fixed within the metallic tube between the two scanner mirrors (left) and the microscope objective (right).
Fig. 9
Fig. 9 SHG signal intensity as the function of repetition rate of the Yb-fiber laser. Average power: 5 mW (measured after the microscope objective). Pixel dwell time: 5 µs. Operation wavelength: 1030 nm. Fixed transmission grating distance of ~80 mm. Ex-vivo murine skin sample. Scale bar: 20 μm.
Fig. 10
Fig. 10 In vivo SHG image of collagen in a murine skin sample being measured by the use of an Yb-fiber laser operating at a 1.89 MHz repetition rate. The laser average power measured directly above the skin is 5 mW. Scale bar: 20 μm.
Fig. 11
Fig. 11 In vivo penetration measurement of Alexa-546 labelled nanoparticles (AF546-DV) in murine skin. Excitation wavelength: ~1030 nm, z-stack image (128x128 pixels/frame). Green: SHG signal of collagen. Red: fluorescence signal of AF546-labelled nanoparticles 1 hour after of the topical treatment by nanomedicine of the skin. One can observe that the Langerhans cells, which are a part of the immune system, accumulate the AF546-labelled nanoparticles [15]. Scale bar: 50 μm.

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