Abstract

A spatial overlap modulation (SPOM) technique is a nonlinear optical microscopy technique which enhances the three-dimensional spatial resolution and rejects the out-of-focus background limiting the imaging depth inside a highly scattering sample. Here, we report on the implementation of SPOM in which beam pointing modulation is achieved by an electro-optic deflector. The modulation and demodulation frequencies are enhanced to 200 kHz and 400 kHz, respectively, resulting in a 200-fold enhancement compared with the previously reported system. The resolution enhancement and suppression of the out-of-focus background are demonstrated by sum-frequency-generation imaging of pounded granulated sugar and deep imaging of fluorescent beads in a tissue-like phantom, respectively.

© 2013 OSA

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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]

2012 (4)

2011 (3)

J. Miyazu, T. Imai, S. Toyoda, M. Sasaura, S. Yagi, K. Kato, Y. Sasaki, and K. Fujiura, “New beam scanning model for high-speed operation using KTa1-xNbxO3 Crystals,” Appl. Phys. Express 4(11), 111501 (2011).
[Crossref]

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt. 16(10), 106014 (2011).
[Crossref] [PubMed]

2010 (2)

2009 (3)

2008 (3)

K. Isobe, T. Kawasumi, T. Tamaki, S. Kataoka, Y. Ozeki, and K. Itoh, “Three-dimensional profiling of refractive index distribution inside transparent materials by use of nonresonant four-wave mixing microscopy,” Appl. Phys. Express 1, 022006 (2008).
[Crossref]

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

N. Chen, C.-H. Wong, and C. J. R. Sheppard, “Focal modulation microscopy,” Opt. Express 16(23), 18764–18769 (2008).
[Crossref] [PubMed]

2007 (2)

D. Fu, T. Ye, T. E. Matthews, G. Yurtsever, and W. S. Warren, “Two-color, two-photon, and excited-state absorption microscopy,” J. Biomed. Opt. 12(5), 054004 (2007).
[Crossref] [PubMed]

D. Fu, T. Ye, T. E. Matthews, B. J. Chen, G. Yurtserver, and W. S. Warren, “High-resolution in vivo imaging of blood vessels without labeling,” Opt. Lett. 32(18), 2641–2643 (2007).
[Crossref] [PubMed]

2006 (3)

2005 (2)

2003 (3)

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

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[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]

2001 (1)

J. Squier and M. Müller, “High resolution nonlinear microscopy: A review of sources and methods for achieving optimal imaging,” Rev. Sci. Instrum. 72(7), 2855–2867 (2001).
[Crossref]

2000 (1)

K. König, “Multiphoton microscopy in life sciences,” J. Microsc. 200(2), 83–104 (2000).
[Crossref] [PubMed]

1999 (1)

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[Crossref]

1997 (2)

Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[Crossref]

M. A. A. Neil, R. Juskaitis, and T. Wilson, “Method of obtaining optical sectioning by using structured light in a conventional microscope,” Opt. Lett. 22(24), 1905–1907 (1997).
[Crossref] [PubMed]

1990 (1)

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

1982 (1)

Barad, Y.

Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[Crossref]

Betzig, E.

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[Crossref] [PubMed]

Campagnola, P. J.

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[Crossref] [PubMed]

Chen, B. J.

Chen, N.

Chen, Z.

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]

Dake, F.

Denk, W.

Duncan, M. D.

Durst, M.

Durst, M. E.

Eisenberg, H.

Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[Crossref]

Fischer, M. C.

Freudiger, C. W.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Fu, D.

D. Fu, T. Ye, T. E. Matthews, G. Yurtsever, and W. S. Warren, “Two-color, two-photon, and excited-state absorption microscopy,” J. Biomed. Opt. 12(5), 054004 (2007).
[Crossref] [PubMed]

D. Fu, T. Ye, T. E. Matthews, B. J. Chen, G. Yurtserver, and W. S. Warren, “High-resolution in vivo imaging of blood vessels without labeling,” Opt. Lett. 32(18), 2641–2643 (2007).
[Crossref] [PubMed]

Fujiura, K.

J. Miyazu, T. Imai, S. Toyoda, M. Sasaura, S. Yagi, K. Kato, Y. Sasaki, and K. Fujiura, “New beam scanning model for high-speed operation using KTa1-xNbxO3 Crystals,” Appl. Phys. Express 4(11), 111501 (2011).
[Crossref]

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

Fukui, K.

Hasan, M. T.

Hashimoto, H.

He, C.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Higashi, T.

Holtom, G. R.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[Crossref]

Horowitz, M.

Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (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. Photonics 7(3), 205–209 (2013).
[Crossref]

D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt. 16(10), 106014 (2011).
[Crossref] [PubMed]

Imai, T.

J. Miyazu, T. Imai, S. Toyoda, M. Sasaura, S. Yagi, K. Kato, Y. Sasaki, and K. Fujiura, “New beam scanning model for high-speed operation using KTa1-xNbxO3 Crystals,” Appl. Phys. Express 4(11), 111501 (2011).
[Crossref]

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

Ishibashi, S.

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

Isobe, K.

Itoh, K.

Ji, N.

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[Crossref] [PubMed]

Juskaitis, R.

Kajiyama, S.

Kang, J. X.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Kannari, F.

Kataoka, S.

K. Isobe, T. Kawasumi, T. Tamaki, S. Kataoka, Y. Ozeki, and K. Itoh, “Three-dimensional profiling of refractive index distribution inside transparent materials by use of nonresonant four-wave mixing microscopy,” Appl. Phys. Express 1, 022006 (2008).
[Crossref]

K. Isobe, S. Kataoka, R. Murase, W. Watanabe, T. Higashi, S. Kawakami, S. Matsunaga, K. Fukui, and K. Itoh, “Stimulated parametric emission microscopy,” Opt. Express 14(2), 786–793 (2006).
[Crossref] [PubMed]

Kato, K.

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

J. Miyazu, T. Imai, S. Toyoda, M. Sasaura, S. Yagi, K. Kato, Y. Sasaki, and K. Fujiura, “New beam scanning model for high-speed operation using KTa1-xNbxO3 Crystals,” Appl. Phys. Express 4(11), 111501 (2011).
[Crossref]

Kawakami, S.

Kawano, H.

Kawasumi, T.

K. Isobe, T. Kawasumi, T. Tamaki, S. Kataoka, Y. Ozeki, and K. Itoh, “Three-dimensional profiling of refractive index distribution inside transparent materials by use of nonresonant four-wave mixing microscopy,” Appl. Phys. Express 1, 022006 (2008).
[Crossref]

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]

D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt. 16(10), 106014 (2011).
[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.

K. König, “Multiphoton microscopy in life sciences,” J. Microsc. 200(2), 83–104 (2000).
[Crossref] [PubMed]

Kovalev, A.

P. Nandakumar, A. Kovalev, and A. Volkmer, “Vibrational imaging based on stimulated Raman scattering microscopy,” New J. Phys. 11(3), 033026 (2009).
[Crossref]

Kumagai, A.

Leray, A.

Li, B.

Loew, L. M.

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[Crossref] [PubMed]

Lu, S.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Manuccia, T. J.

Matsunaga, S.

Matthews, T. E.

D. Fu, T. Ye, T. E. Matthews, B. J. Chen, G. Yurtserver, and W. S. Warren, “High-resolution in vivo imaging of blood vessels without labeling,” Opt. Lett. 32(18), 2641–2643 (2007).
[Crossref] [PubMed]

D. Fu, T. Ye, T. E. Matthews, G. Yurtsever, and W. S. Warren, “Two-color, two-photon, and excited-state absorption microscopy,” J. Biomed. Opt. 12(5), 054004 (2007).
[Crossref] [PubMed]

Mertz, J.

Midorikawa, K.

Milkie, D. E.

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[Crossref] [PubMed]

Min, W.

Z. Chen, L. Wei, X. Zhu, and W. Min, “Extending the fundamental imaging-depth limit of multi-photon microscopy by imaging with photo-activatable fluorophores,” Opt. Express 20(17), 18525–18536 (2012).
[Crossref] [PubMed]

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Miyawaki, A.

Miyazu, J.

J. Miyazu, T. Imai, S. Toyoda, M. Sasaura, S. Yagi, K. Kato, Y. Sasaki, and K. Fujiura, “New beam scanning model for high-speed operation using KTa1-xNbxO3 Crystals,” Appl. Phys. Express 4(11), 111501 (2011).
[Crossref]

Mizuno, H.

Müller, M.

J. Squier and M. Müller, “High resolution nonlinear microscopy: A review of sources and methods for achieving optimal imaging,” Rev. Sci. Instrum. 72(7), 2855–2867 (2001).
[Crossref]

Murase, R.

Naganuma, K.

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

Nandakumar, P.

P. Nandakumar, A. Kovalev, and A. Volkmer, “Vibrational imaging based on stimulated Raman scattering microscopy,” New J. Phys. 11(3), 033026 (2009).
[Crossref]

Neil, M. A. A.

Nishimura, N.

Oron, D.

Ozeki, Y.

Y. Ozeki, F. Dake, S. Kajiyama, K. Fukui, and K. Itoh, “Analysis and experimental assessment of the sensitivity of stimulated Raman scattering microscopy,” Opt. Express 17(5), 3651–3658 (2009).
[Crossref] [PubMed]

K. Isobe, T. Kawasumi, T. Tamaki, S. Kataoka, Y. Ozeki, and K. Itoh, “Three-dimensional profiling of refractive index distribution inside transparent materials by use of nonresonant four-wave mixing microscopy,” Appl. Phys. Express 1, 022006 (2008).
[Crossref]

Reintjes, J.

Saar, B. G.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Samineni, P.

Sasaki, Y.

J. Miyazu, T. Imai, S. Toyoda, M. Sasaura, S. Yagi, K. Kato, Y. Sasaki, and K. Fujiura, “New beam scanning model for high-speed operation using KTa1-xNbxO3 Crystals,” Appl. Phys. Express 4(11), 111501 (2011).
[Crossref]

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

Sasaura, M.

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

J. Miyazu, T. Imai, S. Toyoda, M. Sasaura, S. Yagi, K. Kato, Y. Sasaki, and K. Fujiura, “New beam scanning model for high-speed operation using KTa1-xNbxO3 Crystals,” Appl. Phys. Express 4(11), 111501 (2011).
[Crossref]

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]

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]

Sheppard, C. J. R.

Shibata, Y.

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

Silberberg, Y.

D. Oron, E. Tal, and Y. Silberberg, “Scanningless depth-resolved microscopy,” Opt. Express 13(5), 1468–1476 (2005).
[Crossref] [PubMed]

Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[Crossref]

Squier, J.

J. Squier and M. Müller, “High resolution nonlinear microscopy: A review of sources and methods for achieving optimal imaging,” Rev. Sci. Instrum. 72(7), 2855–2867 (2001).
[Crossref]

Strickler, J. H.

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

Suda, A.

Takeda, T.

Tal, E.

Tamaki, T.

K. Isobe, T. Kawasumi, T. Tamaki, S. Kataoka, Y. Ozeki, and K. Itoh, “Three-dimensional profiling of refractive index distribution inside transparent materials by use of nonresonant four-wave mixing microscopy,” Appl. Phys. Express 1, 022006 (2008).
[Crossref]

Theer, P.

Toyoda, S.

J. Miyazu, T. Imai, S. Toyoda, M. Sasaura, S. Yagi, K. Kato, Y. Sasaki, and K. Fujiura, “New beam scanning model for high-speed operation using KTa1-xNbxO3 Crystals,” Appl. Phys. Express 4(11), 111501 (2011).
[Crossref]

Tsai, J. C.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

van Howe, J.

Volkmer, A.

P. Nandakumar, A. Kovalev, and A. Volkmer, “Vibrational imaging based on stimulated Raman scattering microscopy,” New J. Phys. 11(3), 033026 (2009).
[Crossref]

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. Photonics 7(3), 205–209 (2013).
[Crossref]

Warren, W. S.

Watanabe, W.

Webb, W. W.

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

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

Wei, L.

Williams, R. M.

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

Wilson, J. W.

Wilson, T.

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]

Wong, A. W.

Wong, C.-H.

Xie, X. S.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[Crossref]

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. Photonics 7(3), 205–209 (2013).
[Crossref]

D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt. 16(10), 106014 (2011).
[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]

G. Zhu, J. van Howe, M. Durst, W. Zipfel, and C. Xu, “Simultaneous spatial and temporal focusing of femtosecond pulses,” Opt. Express 13(6), 2153–2159 (2005).
[Crossref] [PubMed]

Yagi, S.

J. Miyazu, T. Imai, S. Toyoda, M. Sasaura, S. Yagi, K. Kato, Y. Sasaki, and K. Fujiura, “New beam scanning model for high-speed operation using KTa1-xNbxO3 Crystals,” Appl. Phys. Express 4(11), 111501 (2011).
[Crossref]

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

Ye, T.

D. Fu, T. Ye, T. E. Matthews, G. Yurtsever, and W. S. Warren, “Two-color, two-photon, and excited-state absorption microscopy,” J. Biomed. Opt. 12(5), 054004 (2007).
[Crossref] [PubMed]

D. Fu, T. Ye, T. E. Matthews, B. J. Chen, G. Yurtserver, and W. S. Warren, “High-resolution in vivo imaging of blood vessels without labeling,” Opt. Lett. 32(18), 2641–2643 (2007).
[Crossref] [PubMed]

Yurtserver, G.

Yurtsever, G.

D. Fu, T. Ye, T. E. Matthews, G. Yurtsever, and W. S. Warren, “Two-color, two-photon, and excited-state absorption microscopy,” J. Biomed. Opt. 12(5), 054004 (2007).
[Crossref] [PubMed]

Zhu, G.

Zhu, X.

Zipfel, W.

Zipfel, W. R.

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

Zumbusch, A.

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[Crossref]

Appl. Phys. Express (2)

K. Isobe, T. Kawasumi, T. Tamaki, S. Kataoka, Y. Ozeki, and K. Itoh, “Three-dimensional profiling of refractive index distribution inside transparent materials by use of nonresonant four-wave mixing microscopy,” Appl. Phys. Express 1, 022006 (2008).
[Crossref]

J. Miyazu, T. Imai, S. Toyoda, M. Sasaura, S. Yagi, K. Kato, Y. Sasaki, and K. Fujiura, “New beam scanning model for high-speed operation using KTa1-xNbxO3 Crystals,” Appl. Phys. Express 4(11), 111501 (2011).
[Crossref]

Appl. Phys. Lett. (1)

Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, “Nonlinear scanning laser microscopy by third harmonic generation,” Appl. Phys. Lett. 70(8), 922–924 (1997).
[Crossref]

Biomed. Opt. Express (3)

J. Biomed. Opt. (2)

D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt. 16(10), 106014 (2011).
[Crossref] [PubMed]

D. Fu, T. Ye, T. E. Matthews, G. Yurtsever, and W. S. Warren, “Two-color, two-photon, and excited-state absorption microscopy,” J. Biomed. Opt. 12(5), 054004 (2007).
[Crossref] [PubMed]

J. Microsc. (1)

K. König, “Multiphoton microscopy in life sciences,” J. Microsc. 200(2), 83–104 (2000).
[Crossref] [PubMed]

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

Nat. Biotechnol. (2)

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

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003).
[Crossref] [PubMed]

Nat. Methods (1)

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[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]

New J. Phys. (1)

P. Nandakumar, A. Kovalev, and A. Volkmer, “Vibrational imaging based on stimulated Raman scattering microscopy,” New J. Phys. 11(3), 033026 (2009).
[Crossref]

Opt. Express (8)

Y. Ozeki, F. Dake, S. Kajiyama, K. Fukui, and K. Itoh, “Analysis and experimental assessment of the sensitivity of stimulated Raman scattering microscopy,” Opt. Express 17(5), 3651–3658 (2009).
[Crossref] [PubMed]

K. Isobe, S. Kataoka, R. Murase, W. Watanabe, T. Higashi, S. Kawakami, S. Matsunaga, K. Fukui, and K. Itoh, “Stimulated parametric emission microscopy,” Opt. Express 14(2), 786–793 (2006).
[Crossref] [PubMed]

G. Zhu, J. van Howe, M. Durst, W. Zipfel, and C. Xu, “Simultaneous spatial and temporal focusing of femtosecond pulses,” Opt. Express 13(6), 2153–2159 (2005).
[Crossref] [PubMed]

D. Oron, E. Tal, and Y. Silberberg, “Scanningless depth-resolved microscopy,” Opt. Express 13(5), 1468–1476 (2005).
[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]

N. Chen, C.-H. Wong, and C. J. R. Sheppard, “Focal modulation microscopy,” Opt. Express 16(23), 18764–18769 (2008).
[Crossref] [PubMed]

A. Leray and J. Mertz, “Rejection of two-photon fluorescence background in thick tissue by differential aberration imaging,” Opt. Express 14(22), 10565–10573 (2006).
[Crossref] [PubMed]

Z. Chen, L. Wei, X. Zhu, and W. Min, “Extending the fundamental imaging-depth limit of multi-photon microscopy by imaging with photo-activatable fluorophores,” Opt. Express 20(17), 18525–18536 (2012).
[Crossref] [PubMed]

Opt. Lett. (5)

Phys. Rev. Lett. (1)

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999).
[Crossref]

Proc. SPIE (1)

S. Yagi, K. Naganuma, T. Imai, Y. Shibata, S. Ishibashi, Y. Sasaki, M. Sasaura, K. Fujiura, and K. Kato, “A mechanical-free 150-kHz repetition swept light source incorporated a KTN electro-optic deflector,” Proc. SPIE 7889, 78891J, 78891J-6 (2011).
[Crossref]

Rev. Sci. Instrum. (1)

J. Squier and M. Müller, “High resolution nonlinear microscopy: A review of sources and methods for achieving optimal imaging,” Rev. Sci. Instrum. 72(7), 2855–2867 (2001).
[Crossref]

Science (2)

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

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008).
[Crossref] [PubMed]

Supplementary Material (1)

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Figures (5)

Fig. 1
Fig. 1

SPOM-NOM setup. PBS: polarizing beamsplitter, OPO: optical parametric oscillator, PC: prechirper, EOD: electro-optic deflector, DM: dichroic mirror, OB: objective lens, SPF: shortpass filter, BPF: band-pass filter, PMT: photomultiplier tube.

Fig. 2
Fig. 2

SNRs at demodulation frequencies of (red square) 400 kHz and (black circk) 2 kHz.

Fig. 3
Fig. 3

TPEF images of tissue-like phantom obtained by (a) conventional TPEF microscopy and (b) SPOM-NOM.

Fig. 4
Fig. 4

(a, b) TPEF intensity of fluorescent beads in the focal plane (signal, red squares), background TPEF intensity (black circles) and input power from the Ti:sapphire oscillator and the OPO (solid blue line) as a function of penetration depth in a tissue-like phantom. (c) Contrast ratio between TPEF intensity of fluorescent beads in the focal plane and background TPEF intensity for conventional TPEF microscopy (black circles) and SPOM-NOM (red squares) as a function of penetration depth in a tissue-like phantom. The solid lines represent best fits to the data.

Fig. 5
Fig. 5

Enhancement of the spatial resolution in SFG imaging by SPOM-NOM. (a, b) SFG images of granulated sugar pounded in a mortar obtained by (a) conventional microscopy and (b) SPOM-NOM. (c-e) Normalized signal profiles along the lateral and axial directions indicated by (c) blue, (d) green, (e) red, (f) yellow, (g) pink arrows in (a) and (b).

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