Abstract

We present the design, implementation and performance analysis of a compact multi-photon endoscope based on a piezo electric scanning tube. A miniature objective lens with a long working distance and a high numerical aperture (≈ 0.5) is designed to provide a diffraction limited spot size. Furthermore, a 1700 nm wavelength femtosecond fiber laser is used as an excitation source to overcome the scattering of biological tissues and reduce water absorption. Therefore, the novel optical system along with the unique wavelength allows us to increase the imaging depth. We demonstrate that the endoscope is capable of performing third and second harmonic generation (THG/SHG) and three-photon excitation fluorescence (3PEF) imaging over a large field of view (> 400 μm) with high lateral resolution (2.2 μm). The compact and lightweight probe design makes it suitable for minimally-invasive in-vivo imaging as a potential alternative to surgical biopsies.

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

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References

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    [Crossref] [PubMed]
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2017 (2)

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt, M. Schmitt, and J. Popp, “Endoscopic fiber probe for nonlinear spectroscopic imaging,” Optica. 4, 496–501 (2017).
[Crossref]

2016 (4)

2015 (2)

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of bv-2 microglia cells,” J. Struct. Bio. 189, 105–113 (2015).
[Crossref]

2014 (2)

D. Do, H. Yoo, and D.-G. Gweon, “Fiber-optic raster scanning two-photon endomicroscope using a tubular piezoelectric actuator,” J. Biomed. Opt. 19, 066010 (2014).
[Crossref] [PubMed]

E. Anashkina, A. Andrianov, M. Y. Koptev, S. Muravyev, and A. Kim, “Generating femtosecond optical pulses tunable from 2 to 3 μm with a silica-based all-fiber laser system,” Opt. Lett. 39, 2963–2966 (2014).
[Crossref] [PubMed]

2013 (6)

T. N. Nguyen, K. Kieu, D. Churin, T. Ota, M. Miyawaki, and N. Peyghambarian, “High power soliton self-frequency shift with improved flatness ranging from 1.6 to 1.78 μm,” IEEE Photonics Technol. Lett. 25, 1893–1896 (2013).
[Crossref]

C. Xu and F. Wise, “Recent advances in fibre lasers for nonlinear microscopy,” Nat. Photon. 7, 875–882 (2013).
[Crossref]

W.-J. Madore, E. De Montigny, O. Ouellette, S. Lemire-Renaud, M. Leduc, X. Daxhelet, N. Godbout, and C. Boudoux, “Asymmetric double-clad fiber couplers for endoscopy,” Opt. Lett. 38, 4514–4517 (2013).
[Crossref] [PubMed]

K. Kieu, S. Mehravar, R. Gowda, R. A. Norwood, and N. Peyghambarian, “Label-free multi-photon imaging using a compact femtosecond fiber laser mode-locked by carbon nanotube saturable absorber,” Biomed. Opt. Express 4, 2187–2195 (2013).
[Crossref] [PubMed]

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. Photon. 7, 205 (2013).
[Crossref]

D. M. Huland, K. Charan, D. G. Ouzounov, J. S. Jones, N. Nishimura, and C. Xu, “Three-photon excited fluorescence imaging of unstained tissue using a grin lens endoscope,” Biomed. Opt. Express 4, 652–658 (2013).
[Crossref] [PubMed]

2012 (2)

2011 (2)

K. Wang and C. Xu, “Tunable high-energy soliton pulse generation from a large-mode-area fiber and its application to third harmonic generation microscopy,” Appl. Phys. Lett. 99, 071112 (2011).
[Crossref]

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

2010 (2)

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, and P. Loza-Alvarez, “Third-harmonic generation for the study of caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15, 046020 (2010).
[Crossref] [PubMed]

Y. Zhao, H. Nakamura, and R. J. Gordon, “Development of a versatile two-photon endoscope for biological imaging,” Biomed. Opt. Express 1, 1159–1172 (2010).
[Crossref]

2009 (2)

G. Liu, T. Xie, I. V. Tomov, J. Su, L. Yu, J. Zhang, B. J. Tromberg, and Z. Chen, “Rotational multiphoton endoscopy with a 1 μm fiber laser system,” Opt. Lett. 34, 2249–2251 (2009).
[Crossref] [PubMed]

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

2006 (2)

2005 (1)

S. Nioka, S. Wen, J. Zhang, J. Du, X. Intes, Z. Zhao, and B. Chance, “Simulation study of breast tissue hemodynamics during pressure perturbation,” Oxyg. Transp. to Tissue 26, pp. 17–22 (2005).
[Crossref]

1997 (1)

K. Shiraishi, H. Ohnuki, N. Hiraguri, K. Matsumura, I. Ohishi, H. Morichi, and H. Kazami, “A lensed-fiber coupling scheme utilizing a graded-index fiber and a hemispherically ended coreless fiber tip,” J. Light. Tech. 15, 356–363 (1997).
[Crossref]

1996 (1)

1990 (1)

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

Abdeladim, L.

P. Cadroas, L. V. Kotov, L. Abdeladim, M. E. Likhachev, D. Lipatov, W. Supatto, J. Livet, E. Beaurepaire, and S. Février, “Three-photon microscopy with a monolithic all-fiber format laser emitting at 1650 nm,” in “Specialty Optical Fibers” (Optical Society of America, 2016), pp. SoM4F–4.
[Crossref]

Ahn, Y.-C.

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

Alonso-Ortega, C.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, and P. Loza-Alvarez, “Third-harmonic generation for the study of caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15, 046020 (2010).
[Crossref] [PubMed]

Amirsolaimani, B.

Anashkina, E.

Andrianov, A.

Artigas, D.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, and P. Loza-Alvarez, “Third-harmonic generation for the study of caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15, 046020 (2010).
[Crossref] [PubMed]

Athanassakis, I.

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of bv-2 microglia cells,” J. Struct. Bio. 189, 105–113 (2015).
[Crossref]

Aviles-Espinosa, R.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, and P. Loza-Alvarez, “Third-harmonic generation for the study of caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15, 046020 (2010).
[Crossref] [PubMed]

Baayen, J.

Bae, H.

A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt, M. Schmitt, and J. Popp, “Endoscopic fiber probe for nonlinear spectroscopic imaging,” Optica. 4, 496–501 (2017).
[Crossref]

Baker, R. D.

Banerjee, B.

Batrin, R.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Beaurepaire, E.

P. Cadroas, L. V. Kotov, L. Abdeladim, M. E. Likhachev, D. Lipatov, W. Supatto, J. Livet, E. Beaurepaire, and S. Février, “Three-photon microscopy with a monolithic all-fiber format laser emitting at 1650 nm,” in “Specialty Optical Fibers” (Optical Society of America, 2016), pp. SoM4F–4.
[Crossref]

Boudoux, C.

Bourg-Heckly, G.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Braud, F.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Brevier, J.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Brodschelm, A.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, and P. Loza-Alvarez, “Third-harmonic generation for the study of caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15, 046020 (2010).
[Crossref] [PubMed]

Brown, C. M.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, W. W. Webb, and C. Xu, “Multifocal multiphoton endoscope,” Opt. Lett. 37, 1349–1351 (2012).
[Crossref] [PubMed]

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

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

E. J. Seibel, M. Fauver, J. L. Crossman-Bosworth, Q. Y. Smithwick, and C. M. Brown, “Microfabricated optical fiber with microlens that produces large field-of-view video-rate optical beam scanning for microendoscopy applications,” in “Optical Fibers and Sensors for Medical Applications III” (International Society for Optics and Photonics, 2003), vol. 4957, pp. 46–56.
[Crossref]

Cadroas, P.

P. Cadroas, L. V. Kotov, L. Abdeladim, M. E. Likhachev, D. Lipatov, W. Supatto, J. Livet, E. Beaurepaire, and S. Février, “Three-photon microscopy with a monolithic all-fiber format laser emitting at 1650 nm,” in “Specialty Optical Fibers” (Optical Society of America, 2016), pp. SoM4F–4.
[Crossref]

Chance, B.

S. Nioka, S. Wen, J. Zhang, J. Du, X. Intes, Z. Zhao, and B. Chance, “Simulation study of breast tissue hemodynamics during pressure perturbation,” Oxyg. Transp. to Tissue 26, pp. 17–22 (2005).
[Crossref]

Charan, K.

Chatrath, H.

Chen, Z.

G. Liu, T. Xie, I. V. Tomov, J. Su, L. Yu, J. Zhang, B. J. Tromberg, and Z. Chen, “Rotational multiphoton endoscopy with a 1 μm fiber laser system,” Opt. Lett. 34, 2249–2251 (2009).
[Crossref] [PubMed]

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

Churin, D.

T. N. Nguyen, K. Kieu, D. Churin, T. Ota, M. Miyawaki, and N. Peyghambarian, “High power soliton self-frequency shift with improved flatness ranging from 1.6 to 1.78 μm,” IEEE Photonics Technol. Lett. 25, 1893–1896 (2013).
[Crossref]

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. Photon. 7, 205 (2013).
[Crossref]

Cranfield, C.

Crossman-Bosworth, J. L.

E. J. Seibel, M. Fauver, J. L. Crossman-Bosworth, Q. Y. Smithwick, and C. M. Brown, “Microfabricated optical fiber with microlens that produces large field-of-view video-rate optical beam scanning for microendoscopy applications,” in “Optical Fibers and Sensors for Medical Applications III” (International Society for Optics and Photonics, 2003), vol. 4957, pp. 46–56.
[Crossref]

Daxhelet, X.

De Montigny, E.

de Witt Hamer, P.

Denk, W.

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

Dickensheets, D.

Do, D.

D. Do, H. Yoo, and D.-G. Gweon, “Fiber-optic raster scanning two-photon endomicroscope using a tubular piezoelectric actuator,” J. Biomed. Opt. 19, 066010 (2014).
[Crossref] [PubMed]

Dochow, S.

A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt, M. Schmitt, and J. Popp, “Endoscopic fiber probe for nonlinear spectroscopic imaging,” Optica. 4, 496–501 (2017).
[Crossref]

Du, J.

S. Nioka, S. Wen, J. Zhang, J. Du, X. Intes, Z. Zhao, and B. Chance, “Simulation study of breast tissue hemodynamics during pressure perturbation,” Oxyg. Transp. to Tissue 26, pp. 17–22 (2005).
[Crossref]

Ducourthial, G.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Fabert, M.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Fauver, M.

E. J. Seibel, M. Fauver, J. L. Crossman-Bosworth, Q. Y. Smithwick, and C. M. Brown, “Microfabricated optical fiber with microlens that produces large field-of-view video-rate optical beam scanning for microendoscopy applications,” in “Optical Fibers and Sensors for Medical Applications III” (International Society for Optics and Photonics, 2003), vol. 4957, pp. 46–56.
[Crossref]

Février, S.

P. Cadroas, L. V. Kotov, L. Abdeladim, M. E. Likhachev, D. Lipatov, W. Supatto, J. Livet, E. Beaurepaire, and S. Février, “Three-photon microscopy with a monolithic all-fiber format laser emitting at 1650 nm,” in “Specialty Optical Fibers” (Optical Society of America, 2016), pp. SoM4F–4.
[Crossref]

Filippidis, G.

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of bv-2 microglia cells,” J. Struct. Bio. 189, 105–113 (2015).
[Crossref]

Fotakis, C.

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of bv-2 microglia cells,” J. Struct. Bio. 189, 105–113 (2015).
[Crossref]

Fu, L.

Galgano, G.

Gavgiotaki, E.

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of bv-2 microglia cells,” J. Struct. Bio. 189, 105–113 (2015).
[Crossref]

Giessen, H.

T. Gissibl, S. Thiele, A. Herkommer, and H. Giessen, “Two-photon direct laser writing of ultracompact multi-lens objectives,” Nat. Photon. 10, 554–560 (2016).
[Crossref]

Gissibl, T.

T. Gissibl, S. Thiele, A. Herkommer, and H. Giessen, “Two-photon direct laser writing of ultracompact multi-lens objectives,” Nat. Photon. 10, 554–560 (2016).
[Crossref]

Godbout, N.

Gordon, R. J.

Gowda, R.

Groot, M.

Gu, M.

Gweon, D.-G.

D. Do, H. Yoo, and D.-G. Gweon, “Fiber-optic raster scanning two-photon endomicroscope using a tubular piezoelectric actuator,” J. Biomed. Opt. 19, 066010 (2014).
[Crossref] [PubMed]

Habert, R.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Harpel, K.

Herkommer, A.

T. Gissibl, S. Thiele, A. Herkommer, and H. Giessen, “Two-photon direct laser writing of ultracompact multi-lens objectives,” Nat. Photon. 10, 554–560 (2016).
[Crossref]

Hiraguri, N.

K. Shiraishi, H. Ohnuki, N. Hiraguri, K. Matsumura, I. Ohishi, H. Morichi, and H. Kazami, “A lensed-fiber coupling scheme utilizing a graded-index fiber and a hemispherically ended coreless fiber tip,” J. Light. Tech. 15, 356–363 (1997).
[Crossref]

Horton, N. 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. Photon. 7, 205 (2013).
[Crossref]

Howard, S. S.

Hu, Y.

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Huland, D. M.

Intes, X.

S. Nioka, S. Wen, J. Zhang, J. Du, X. Intes, Z. Zhao, and B. Chance, “Simulation study of breast tissue hemodynamics during pressure perturbation,” Oxyg. Transp. to Tissue 26, pp. 17–22 (2005).
[Crossref]

Jain, A.

Jones, J. S.

Jung, W.

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

Kaenders, W. G.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, and P. Loza-Alvarez, “Third-harmonic generation for the study of caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15, 046020 (2010).
[Crossref] [PubMed]

Kalognomou, M.

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of bv-2 microglia cells,” J. Struct. Bio. 189, 105–113 (2015).
[Crossref]

Kazami, H.

K. Shiraishi, H. Ohnuki, N. Hiraguri, K. Matsumura, I. Ohishi, H. Morichi, and H. Kazami, “A lensed-fiber coupling scheme utilizing a graded-index fiber and a hemispherically ended coreless fiber tip,” J. Light. Tech. 15, 356–363 (1997).
[Crossref]

Kieu, K.

Kim, A.

Kino, G.

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. Photon. 7, 205 (2013).
[Crossref]

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

Koptev, M. Y.

Kotov, L. V.

P. Cadroas, L. V. Kotov, L. Abdeladim, M. E. Likhachev, D. Lipatov, W. Supatto, J. Livet, E. Beaurepaire, and S. Février, “Three-photon microscopy with a monolithic all-fiber format laser emitting at 1650 nm,” in “Specialty Optical Fibers” (Optical Society of America, 2016), pp. SoM4F–4.
[Crossref]

Kuzmin, N.

Latka, I.

A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt, M. Schmitt, and J. Popp, “Endoscopic fiber probe for nonlinear spectroscopic imaging,” Optica. 4, 496–501 (2017).
[Crossref]

Leclerc, P.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Leduc, M.

Lemire-Renaud, S.

Li, J.

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Li, M.

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Li, X.

Li, Y.

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Likhachev, M. E.

P. Cadroas, L. V. Kotov, L. Abdeladim, M. E. Likhachev, D. Lipatov, W. Supatto, J. Livet, E. Beaurepaire, and S. Février, “Three-photon microscopy with a monolithic all-fiber format laser emitting at 1650 nm,” in “Specialty Optical Fibers” (Optical Society of America, 2016), pp. SoM4F–4.
[Crossref]

Lipatov, D.

P. Cadroas, L. V. Kotov, L. Abdeladim, M. E. Likhachev, D. Lipatov, W. Supatto, J. Livet, E. Beaurepaire, and S. Février, “Three-photon microscopy with a monolithic all-fiber format laser emitting at 1650 nm,” in “Specialty Optical Fibers” (Optical Society of America, 2016), pp. SoM4F–4.
[Crossref]

Liu, G.

Livet, J.

P. Cadroas, L. V. Kotov, L. Abdeladim, M. E. Likhachev, D. Lipatov, W. Supatto, J. Livet, E. Beaurepaire, and S. Février, “Three-photon microscopy with a monolithic all-fiber format laser emitting at 1650 nm,” in “Specialty Optical Fibers” (Optical Society of America, 2016), pp. SoM4F–4.
[Crossref]

Loza-Alvarez, P.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, and P. Loza-Alvarez, “Third-harmonic generation for the study of caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15, 046020 (2010).
[Crossref] [PubMed]

Lu, Y.

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Lukic, A.

A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt, M. Schmitt, and J. Popp, “Endoscopic fiber probe for nonlinear spectroscopic imaging,” Optica. 4, 496–501 (2017).
[Crossref]

MacDonald, D. J.

Madore, W.-J.

Mansuryan, T.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Mansvelder, H.

Matsumura, K.

K. Shiraishi, H. Ohnuki, N. Hiraguri, K. Matsumura, I. Ohishi, H. Morichi, and H. Kazami, “A lensed-fiber coupling scheme utilizing a graded-index fiber and a hemispherically ended coreless fiber tip,” J. Light. Tech. 15, 356–363 (1997).
[Crossref]

Matsunaga, T. O.

Matz, G.

A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt, M. Schmitt, and J. Popp, “Endoscopic fiber probe for nonlinear spectroscopic imaging,” Optica. 4, 496–501 (2017).
[Crossref]

McCormick, D.

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

Mehravar, S.

Messerschmidt, B.

A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt, M. Schmitt, and J. Popp, “Endoscopic fiber probe for nonlinear spectroscopic imaging,” Optica. 4, 496–501 (2017).
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T. N. Nguyen, K. Kieu, D. Churin, T. Ota, M. Miyawaki, and N. Peyghambarian, “High power soliton self-frequency shift with improved flatness ranging from 1.6 to 1.78 μm,” IEEE Photonics Technol. Lett. 25, 1893–1896 (2013).
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Morichi, H.

K. Shiraishi, H. Ohnuki, N. Hiraguri, K. Matsumura, I. Ohishi, H. Morichi, and H. Kazami, “A lensed-fiber coupling scheme utilizing a graded-index fiber and a hemispherically ended coreless fiber tip,” J. Light. Tech. 15, 356–363 (1997).
[Crossref]

Muravyev, S.

Myaing, M. T.

Nakamura, H.

Nguyen, T. N.

T. N. Nguyen, K. Kieu, D. Churin, T. Ota, M. Miyawaki, and N. Peyghambarian, “High power soliton self-frequency shift with improved flatness ranging from 1.6 to 1.78 μm,” IEEE Photonics Technol. Lett. 25, 1893–1896 (2013).
[Crossref]

Nioka, S.

S. Nioka, S. Wen, J. Zhang, J. Du, X. Intes, Z. Zhao, and B. Chance, “Simulation study of breast tissue hemodynamics during pressure perturbation,” Oxyg. Transp. to Tissue 26, pp. 17–22 (2005).
[Crossref]

Nishimura, N.

Norwood, R. A.

Noske, D.

Ohishi, I.

K. Shiraishi, H. Ohnuki, N. Hiraguri, K. Matsumura, I. Ohishi, H. Morichi, and H. Kazami, “A lensed-fiber coupling scheme utilizing a graded-index fiber and a hemispherically ended coreless fiber tip,” J. Light. Tech. 15, 356–363 (1997).
[Crossref]

Ohnuki, H.

K. Shiraishi, H. Ohnuki, N. Hiraguri, K. Matsumura, I. Ohishi, H. Morichi, and H. Kazami, “A lensed-fiber coupling scheme utilizing a graded-index fiber and a hemispherically ended coreless fiber tip,” J. Light. Tech. 15, 356–363 (1997).
[Crossref]

Ota, T.

T. N. Nguyen, K. Kieu, D. Churin, T. Ota, M. Miyawaki, and N. Peyghambarian, “High power soliton self-frequency shift with improved flatness ranging from 1.6 to 1.78 μm,” IEEE Photonics Technol. Lett. 25, 1893–1896 (2013).
[Crossref]

Ouellette, O.

Ouzounov, D. G.

Patel, C.

Patel, K.

Pavlova, I.

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

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

Peyghambarian, N.

Popp, J.

A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt, M. Schmitt, and J. Popp, “Endoscopic fiber probe for nonlinear spectroscopic imaging,” Optica. 4, 496–501 (2017).
[Crossref]

Rivera, D. R.

Rong, H.

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Santos, S. I.

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, and P. Loza-Alvarez, “Third-harmonic generation for the study of caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15, 046020 (2010).
[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. Photon. 7, 205 (2013).
[Crossref]

Schmitt, M.

A. Lukic, S. Dochow, H. Bae, G. Matz, I. Latka, B. Messerschmidt, M. Schmitt, and J. Popp, “Endoscopic fiber probe for nonlinear spectroscopic imaging,” Optica. 4, 496–501 (2017).
[Crossref]

Seibel, E. J.

E. J. Seibel, M. Fauver, J. L. Crossman-Bosworth, Q. Y. Smithwick, and C. M. Brown, “Microfabricated optical fiber with microlens that produces large field-of-view video-rate optical beam scanning for microendoscopy applications,” in “Optical Fibers and Sensors for Medical Applications III” (International Society for Optics and Photonics, 2003), vol. 4957, pp. 46–56.
[Crossref]

Shiraishi, K.

K. Shiraishi, H. Ohnuki, N. Hiraguri, K. Matsumura, I. Ohishi, H. Morichi, and H. Kazami, “A lensed-fiber coupling scheme utilizing a graded-index fiber and a hemispherically ended coreless fiber tip,” J. Light. Tech. 15, 356–363 (1997).
[Crossref]

Skordos, I.

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of bv-2 microglia cells,” J. Struct. Bio. 189, 105–113 (2015).
[Crossref]

Smithwick, Q. Y.

E. J. Seibel, M. Fauver, J. L. Crossman-Bosworth, Q. Y. Smithwick, and C. M. Brown, “Microfabricated optical fiber with microlens that produces large field-of-view video-rate optical beam scanning for microendoscopy applications,” in “Optical Fibers and Sensors for Medical Applications III” (International Society for Optics and Photonics, 2003), vol. 4957, pp. 46–56.
[Crossref]

Strickler, J. H.

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

Su, J.

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

G. Liu, T. Xie, I. V. Tomov, J. Su, L. Yu, J. Zhang, B. J. Tromberg, and Z. Chen, “Rotational multiphoton endoscopy with a 1 μm fiber laser system,” Opt. Lett. 34, 2249–2251 (2009).
[Crossref] [PubMed]

Supatto, W.

P. Cadroas, L. V. Kotov, L. Abdeladim, M. E. Likhachev, D. Lipatov, W. Supatto, J. Livet, E. Beaurepaire, and S. Février, “Three-photon microscopy with a monolithic all-fiber format laser emitting at 1650 nm,” in “Specialty Optical Fibers” (Optical Society of America, 2016), pp. SoM4F–4.
[Crossref]

Tang, S.

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

Thiele, S.

T. Gissibl, S. Thiele, A. Herkommer, and H. Giessen, “Two-photon direct laser writing of ultracompact multi-lens objectives,” Nat. Photon. 10, 554–560 (2016).
[Crossref]

Tomov, I. V.

Tromberg, B. J.

G. Liu, T. Xie, I. V. Tomov, J. Su, L. Yu, J. Zhang, B. J. Tromberg, and Z. Chen, “Rotational multiphoton endoscopy with a 1 μm fiber laser system,” Opt. Lett. 34, 2249–2251 (2009).
[Crossref] [PubMed]

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

Tsouko, A.

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of bv-2 microglia cells,” J. Struct. Bio. 189, 105–113 (2015).
[Crossref]

Vagner, J.

Vever-Bizet, C.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
[Crossref] [PubMed]

Wang, K.

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. Photon. 7, 205 (2013).
[Crossref]

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

K. Wang and C. Xu, “Tunable high-energy soliton pulse generation from a large-mode-area fiber and its application to third harmonic generation microscopy,” Appl. Phys. Lett. 99, 071112 (2011).
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Webb, W. W.

D. R. Rivera, C. M. Brown, D. G. Ouzounov, W. W. Webb, and C. Xu, “Multifocal multiphoton endoscope,” Opt. Lett. 37, 1349–1351 (2012).
[Crossref] [PubMed]

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

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

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

Wen, S.

S. Nioka, S. Wen, J. Zhang, J. Du, X. Intes, Z. Zhao, and B. Chance, “Simulation study of breast tissue hemodynamics during pressure perturbation,” Oxyg. Transp. to Tissue 26, pp. 17–22 (2005).
[Crossref]

Wesseling, P.

Wise, F.

C. Xu and F. Wise, “Recent advances in fibre lasers for nonlinear microscopy,” Nat. Photon. 7, 875–882 (2013).
[Crossref]

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. Photon. 7, 205 (2013).
[Crossref]

Wu, H.

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Wu, R.

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Xie, H.

Xie, T.

G. Liu, T. Xie, I. V. Tomov, J. Su, L. Yu, J. Zhang, B. J. Tromberg, and Z. Chen, “Rotational multiphoton endoscopy with a 1 μm fiber laser system,” Opt. Lett. 34, 2249–2251 (2009).
[Crossref] [PubMed]

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

Xu, C.

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. Photon. 7, 205 (2013).
[Crossref]

C. Xu and F. Wise, “Recent advances in fibre lasers for nonlinear microscopy,” Nat. Photon. 7, 875–882 (2013).
[Crossref]

D. M. Huland, K. Charan, D. G. Ouzounov, J. S. Jones, N. Nishimura, and C. Xu, “Three-photon excited fluorescence imaging of unstained tissue using a grin lens endoscope,” Biomed. Opt. Express 4, 652–658 (2013).
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D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express 3, 1077–1085 (2012).
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D. R. Rivera, C. M. Brown, D. G. Ouzounov, W. W. Webb, and C. Xu, “Multifocal multiphoton endoscope,” Opt. Lett. 37, 1349–1351 (2012).
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K. Wang and C. Xu, “Tunable high-energy soliton pulse generation from a large-mode-area fiber and its application to third harmonic generation microscopy,” Appl. Phys. Lett. 99, 071112 (2011).
[Crossref]

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

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Yoo, H.

D. Do, H. Yoo, and D.-G. Gweon, “Fiber-optic raster scanning two-photon endomicroscope using a tubular piezoelectric actuator,” J. Biomed. Opt. 19, 066010 (2014).
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Yu, L.

Zhang, J.

G. Liu, T. Xie, I. V. Tomov, J. Su, L. Yu, J. Zhang, B. J. Tromberg, and Z. Chen, “Rotational multiphoton endoscopy with a 1 μm fiber laser system,” Opt. Lett. 34, 2249–2251 (2009).
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[Crossref]

Zhao, Y.

Zhao, Z.

S. Nioka, S. Wen, J. Zhang, J. Du, X. Intes, Z. Zhao, and B. Chance, “Simulation study of breast tissue hemodynamics during pressure perturbation,” Oxyg. Transp. to Tissue 26, pp. 17–22 (2005).
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Zong, W.

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Appl. Phys. Lett. (1)

K. Wang and C. Xu, “Tunable high-energy soliton pulse generation from a large-mode-area fiber and its application to third harmonic generation microscopy,” Appl. Phys. Lett. 99, 071112 (2011).
[Crossref]

Biomed. Opt. Express (7)

K. Kieu, S. Mehravar, R. Gowda, R. A. Norwood, and N. Peyghambarian, “Label-free multi-photon imaging using a compact femtosecond fiber laser mode-locked by carbon nanotube saturable absorber,” Biomed. Opt. Express 4, 2187–2195 (2013).
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Y. Zhao, H. Nakamura, and R. J. Gordon, “Development of a versatile two-photon endoscope for biological imaging,” Biomed. Opt. Express 1, 1159–1172 (2010).
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S. Mehravar, B. Banerjee, H. Chatrath, B. Amirsolaimani, K. Patel, C. Patel, R. A. Norwood, N. Peyghambarian, and K. Kieu, “Label-free multi-photon imaging of dysplasia in Barrett’s esophagus,” Biomed. Opt. Express 7, 148–157 (2016).
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K. Harpel, R. D. Baker, B. Amirsolaimani, S. Mehravar, J. Vagner, T. O. Matsunaga, B. Banerjee, and K. Kieu, “Imaging of targeted lipid microbubbles to detect cancer cells using third harmonic generation microscopy,” Biomed. Opt. Express 7, 2849–2860 (2016).
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N. Kuzmin, P. Wesseling, P. de Witt Hamer, D. Noske, G. Galgano, H. Mansvelder, J. Baayen, and M. Groot, “Third harmonic generation imaging for fast, label-free pathology of human brain tumors,” Biomed. Opt. Express 7, 1889–1904 (2016).
[Crossref] [PubMed]

D. M. Huland, K. Charan, D. G. Ouzounov, J. S. Jones, N. Nishimura, and C. Xu, “Three-photon excited fluorescence imaging of unstained tissue using a grin lens endoscope,” Biomed. Opt. Express 4, 652–658 (2013).
[Crossref] [PubMed]

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

IEEE Photonics Technol. Lett. (1)

T. N. Nguyen, K. Kieu, D. Churin, T. Ota, M. Miyawaki, and N. Peyghambarian, “High power soliton self-frequency shift with improved flatness ranging from 1.6 to 1.78 μm,” IEEE Photonics Technol. Lett. 25, 1893–1896 (2013).
[Crossref]

J. Biomed. Opt. (3)

R. Aviles-Espinosa, S. I. Santos, A. Brodschelm, W. G. Kaenders, C. Alonso-Ortega, D. Artigas, and P. Loza-Alvarez, “Third-harmonic generation for the study of caenorhabditis elegans embryogenesis,” J. Biomed. Opt. 15, 046020 (2010).
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S. Tang, W. Jung, D. McCormick, T. Xie, J. Su, Y.-C. Ahn, B. J. Tromberg, and Z. Chen, “Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning,” J. Biomed. Opt. 14, 034005 (2009).
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D. Do, H. Yoo, and D.-G. Gweon, “Fiber-optic raster scanning two-photon endomicroscope using a tubular piezoelectric actuator,” J. Biomed. Opt. 19, 066010 (2014).
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J. Light. Tech. (1)

K. Shiraishi, H. Ohnuki, N. Hiraguri, K. Matsumura, I. Ohishi, H. Morichi, and H. Kazami, “A lensed-fiber coupling scheme utilizing a graded-index fiber and a hemispherically ended coreless fiber tip,” J. Light. Tech. 15, 356–363 (1997).
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J. Struct. Bio. (1)

E. Gavgiotaki, G. Filippidis, M. Kalognomou, A. Tsouko, I. Skordos, C. Fotakis, and I. Athanassakis, “Third harmonic generation microscopy as a reliable diagnostic tool for evaluating lipid body modification during cell activation: the example of bv-2 microglia cells,” J. Struct. Bio. 189, 105–113 (2015).
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Nat. Meth. (1)

W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, and et al., “Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice,” Nat. Meth. 14, 713 (2017).
[Crossref]

Nat. Photon. (3)

T. Gissibl, S. Thiele, A. Herkommer, and H. Giessen, “Two-photon direct laser writing of ultracompact multi-lens objectives,” Nat. Photon. 10, 554–560 (2016).
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C. Xu and F. Wise, “Recent advances in fibre lasers for nonlinear microscopy,” Nat. Photon. 7, 875–882 (2013).
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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. Photon. 7, 205 (2013).
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Opt. Express (1)

Opt. Lett. (6)

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Oxyg. Transp. to Tissue (1)

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[Crossref]

Proc. Natl. Acad. Sci. (1)

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

Sci. Rep. (1)

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, and et al., “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5, 18303 (2015).
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Science (1)

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Other (3)

GRINTECH Lens Systems for Medical Applications, “High-NA Endomicroscopic Imaging Objective for 2-Photon Microscopy,” http://www.grintech.de/downloads.html?file=tl_files/content/downloads/GRIN_High-NA_Objective_2Photon_Microscopy.pdf . 2017-01-23.

P. Cadroas, L. V. Kotov, L. Abdeladim, M. E. Likhachev, D. Lipatov, W. Supatto, J. Livet, E. Beaurepaire, and S. Février, “Three-photon microscopy with a monolithic all-fiber format laser emitting at 1650 nm,” in “Specialty Optical Fibers” (Optical Society of America, 2016), pp. SoM4F–4.
[Crossref]

E. J. Seibel, M. Fauver, J. L. Crossman-Bosworth, Q. Y. Smithwick, and C. M. Brown, “Microfabricated optical fiber with microlens that produces large field-of-view video-rate optical beam scanning for microendoscopy applications,” in “Optical Fibers and Sensors for Medical Applications III” (International Society for Optics and Photonics, 2003), vol. 4957, pp. 46–56.
[Crossref]

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Figures (5)

Fig. 1
Fig. 1 Schematic diagram and final prototype of the compact fiber-based multi-photon endoscope. The spectrum and autocorrelation trace of the shifted soliton are also shown. MLL: mode-locked fiber laser, DM: dichroic mirror, PZT: piezo electric tube, PMT: photomultiplier tube, DAQ: data acquisition board.
Fig. 2
Fig. 2 (a) Customized objective design with two aspheric lenses and a fused silica spacer. (b) 3D view of the objective lens attached to the fiber using optical epoxy. (c) On-axis spot diagram generated using Zemax which shows that the spherical aberration is within diffraction limit. (d) Spot diagram of a single ball lens with the same working distance which can be made at the tip of the coreless fiber (for comparison). (e) Image nonuniformity due to constant sampling across the field. (f) Uniform image is achieved by implementing a dynamic sampling.
Fig. 3
Fig. 3 (a) THG image of a silicon nano-waveguide and ring resonator with FOV = 200 μm. Since the waveguide width and depth are about 200 nm and 100 nm respectively, it can be used to determine the endoscope resolution. (b) THG signal across a section of the ring resonator. The corresponding Gaussian fit shows a FWHM of 2.2 μm which is considered as the lateral resolution. (c) THG signal from the ring resonator as we move the endoscope in Z direction. The corresponding Gaussian fit shows an axial resolution of 12.7 μm. The scale bar is 25 μm.
Fig. 4
Fig. 4 (a, c) THG image of a GaAs chip surface for two different FOV. (b, d) Relative intensity across the field of view. Considering FWHM criteria, the FOV about 800 μm. (e) GaAs spectrum show a peak at around 567 nm wavelength which corresponds to third harmonic of 1700 nm excitation wavelength. The scale bar is 100 μm.
Fig. 5
Fig. 5 3PEF (orange) from a thin section of (a) stained mouse kidney and (b) rabbit lung. (c) 3PEF from a stained human inflammation of colon. (d) SHG (red) and THG (green) from an indoor plant leaf (unstained). (e) A strong THG signal from a lens cleaning tissue (unstained). (f) 3D view of THG image acquired from a male mosquito eye with 200 μm depth (unstained). The scale bar is 80 μm.

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