Abstract

Although temporally focused wide-field two-photon microscopy (TFM) can perform depth resolved wide field imaging, it cannot avoid the image degradation due to scattering of excitation and emission photons when imaging in a turbid medium. Further, its axial resolution is inferior to standard point-scanning two-photon microscopy. We implemented a structured light illumination for TFM and have shown that it can effectively reject the out-of-focus scattered emission photons improving image contrast. Further, the depth resolution of the improved system is dictated by the spatial frequency of the structure light with the potential of attaining depth resolution better than point-scanning two-photon microscopy.

© 2013 OSA

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2013 (2)

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, “Functional patterned multiphoton excitation deep inside scattering tissue,” Nat. Photonics7(4), 274–278 (2013).
[CrossRef]

H. Dana, N. Kruger, A. Ellman, and S. Shoham, “Line temporal focusing characteristics in transparent and scattering media,” Opt. Express21(5), 5677–5687 (2013).
[CrossRef] [PubMed]

2012 (7)

Y. C. Li, L. C. Cheng, C. Y. Chang, C. H. Lien, P. J. Campagnola, and S. J. Chen, “Fast multiphoton microfabrication of freeform polymer microstructures by spatiotemporal focusing and patterned excitation,” Opt. Express20(17), 19030–19038 (2012).
[CrossRef] [PubMed]

H. Choi, D. S. Tzeranis, J. W. Cha, P. Clémenceau, S. J. de Jong, L. K. van Geest, J. H. Moon, I. V. Yannas, and P. T. So, “3D-resolved fluorescence and phosphorescence lifetime imaging using temporal focusing wide-field two-photon excitation,” Opt. Express20(24), 26219–26235 (2012).
[CrossRef] [PubMed]

D. Bhattacharya, V. R. Singh, C. Zhi, P. T. C. So, P. Matsudaira, and G. Barbastathis, “Three dimensional HiLo-based structured illumination for a digital scanned laser sheet microscopy (DSLM) in thick tissue imaging,” Opt. Express20(25), 27337–27347 (2012).
[CrossRef] [PubMed]

L. C. Cheng, C. Y. Chang, W. C. Yen, and S. J. Chen, “Spatiotemporal focusing-based widefield multiphoton microscopy for fast optical sectioning of thick tissues,” Proc. SPIE8520, 85200N, 85200N-8 (2012).
[CrossRef]

J. Michaelson, H. J. Choi, P. So, and H. D. Huang, “Depth-resolved cellular microrheology using HiLo microscopy,” Biomed. Opt. Express3(6), 1241–1255 (2012).
[CrossRef] [PubMed]

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt.17(2), 021105 (2012).
[CrossRef] [PubMed]

L. C. Cheng, C. Y. Chang, C. Y. Lin, K. C. Cho, W. C. Yen, N. S. Chang, C. Xu, C. Y. Dong, and S. J. Chen, “Spatiotemporal focusing-based widefield multiphoton microscopy for fast optical sectioning,” Opt. Express20(8), 8939–8948 (2012).
[CrossRef] [PubMed]

2011 (4)

E. Y. S. Yew, H. J. Choi, D. Kim, and P. T. C. So, “Wide-field two-photon microscopy with temporal focusing and HiLo background rejection,” Proc. SPIE7903, 79031O, 79031O-6 (2011).
[CrossRef]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt.16(1), 016014 (2011).
[CrossRef] [PubMed]

O. D. Therrien, B. Aubé, S. Pagès, P. D. Koninck, and D. Côté, “Wide-field multiphoton imaging of cellular dynamics in thick tissue by temporal focusing and patterned illumination,” Biomed. Opt. Express2(3), 696–704 (2011).
[CrossRef] [PubMed]

H. Dana and S. Shoham, “Numerical evaluation of temporal focusing characteristics in transparent and scattering media,” Opt. Express19(6), 4937–4948 (2011).
[CrossRef] [PubMed]

2010 (6)

A. Vaziri and C. V. Shank, “Ultrafast widefield optical sectioning microscopy by multifocal temporal focusing,” Opt. Express18(19), 19645–19655 (2010).
[CrossRef] [PubMed]

B. K. Andrasfalvy, B. V. Zemelman, J. Y. Tang, and A. Vaziri, “Two-photon single-cell optogenetic control of neuronal activity by sculpted light,” Proc. Natl. Acad. Sci. U.S.A.107(26), 11981–11986 (2010).
[CrossRef] [PubMed]

E. Papagiakoumou, F. Anselmi, A. Bègue, V. de Sars, J. Glückstad, E. Y. Isacoff, and V. Emiliani, “Scanless two-photon excitation of channelrhodopsin-2,” Nat. Methods7(10), 848–854 (2010).
[CrossRef] [PubMed]

D. Kim and P. T. C. So, “High-throughput three-dimensional lithographic microfabrication,” Opt. Lett.35(10), 1602–1604 (2010).
[CrossRef] [PubMed]

J. Mertz and J. Kim, “Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection,” J. Biomed. Opt.15(1), 016027 (2010).
[CrossRef] [PubMed]

P. Sun and Y. Wang, “Measurements of optical parameters of phantom solution and bulk animal tissues in vitro at 650 nm,” Opt. Laser Technol.42(1), 1–7 (2010).
[CrossRef]

2009 (2)

E. Papagiakoumou, V. de Sars, V. Emiliani, and D. Oron, “Temporal focusing with spatially modulated excitation,” Opt. Express17(7), 5391–5401 (2009).
[CrossRef] [PubMed]

A. Weigel, D. Schild, and A. Zeug, “Resolution in the ApoTome and the confocal laser scanning microscope: comparison,” J. Biomed. Opt.14(1), 014022 (2009).
[CrossRef] [PubMed]

2008 (5)

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett.33(16), 1819–1821 (2008).
[CrossRef] [PubMed]

A. Vaziri, J. Y. Tang, H. Shroff, and C. V. Shank, “Multilayer three-dimensional super resolution imaging of thick biological samples,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20221–20226 (2008).
[CrossRef] [PubMed]

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, “Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination,” Biophys. J.94(12), 4957–4970 (2008).
[CrossRef] [PubMed]

N. Ji, J. C. Magee, and E. Betzig, “High-speed, low-photodamage nonlinear imaging using passive pulse splitters,” Nat. Methods5(2), 197–202 (2008).
[CrossRef] [PubMed]

D. Karadaglić and T. Wilson, “Image formation in structured illumination wide-field fluorescence microscopy,” Micron39(7), 808–818 (2008).
[CrossRef] [PubMed]

2007 (1)

2006 (1)

2005 (2)

2003 (1)

C. Y. Dong, K. Koenig, and P. So, “Characterizing point spread functions of two-photon fluorescence microscopy in turbid medium,” J. Biomed. Opt.8(3), 450–459 (2003).
[CrossRef] [PubMed]

1997 (1)

1991 (1)

1990 (1)

C. J. R. Sheppard and M. Gu, “Image formation in two-photon fluorescence microscopy,” Optik (Stuttg.)86, 104–106 (1990).

1969 (1)

Agard, D. A.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, “Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination,” Biophys. J.94(12), 4957–4970 (2008).
[CrossRef] [PubMed]

Andrasfalvy, B. K.

B. K. Andrasfalvy, B. V. Zemelman, J. Y. Tang, and A. Vaziri, “Two-photon single-cell optogenetic control of neuronal activity by sculpted light,” Proc. Natl. Acad. Sci. U.S.A.107(26), 11981–11986 (2010).
[CrossRef] [PubMed]

Anselmi, F.

E. Papagiakoumou, F. Anselmi, A. Bègue, V. de Sars, J. Glückstad, E. Y. Isacoff, and V. Emiliani, “Scanless two-photon excitation of channelrhodopsin-2,” Nat. Methods7(10), 848–854 (2010).
[CrossRef] [PubMed]

Aubé, B.

Bahlmann, K.

Barbastathis, G.

Begue, A.

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, “Functional patterned multiphoton excitation deep inside scattering tissue,” Nat. Photonics7(4), 274–278 (2013).
[CrossRef]

Bègue, A.

E. Papagiakoumou, F. Anselmi, A. Bègue, V. de Sars, J. Glückstad, E. Y. Isacoff, and V. Emiliani, “Scanless two-photon excitation of channelrhodopsin-2,” Nat. Methods7(10), 848–854 (2010).
[CrossRef] [PubMed]

Betzig, E.

N. Ji, J. C. Magee, and E. Betzig, “High-speed, low-photodamage nonlinear imaging using passive pulse splitters,” Nat. Methods5(2), 197–202 (2008).
[CrossRef] [PubMed]

Bhattacharya, D.

Bradley, J.

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, “Functional patterned multiphoton excitation deep inside scattering tissue,” Nat. Photonics7(4), 274–278 (2013).
[CrossRef]

Buehler, C.

Campagnola, P. J.

Cande, W. Z.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, “Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination,” Biophys. J.94(12), 4957–4970 (2008).
[CrossRef] [PubMed]

Carlton, P. M.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, “Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination,” Biophys. J.94(12), 4957–4970 (2008).
[CrossRef] [PubMed]

Cha, J. W.

Chang, C. Y.

Chang, N. S.

Chen, S. J.

Cheng, L. C.

Cho, K. C.

Choi, H.

Choi, H. J.

J. Michaelson, H. J. Choi, P. So, and H. D. Huang, “Depth-resolved cellular microrheology using HiLo microscopy,” Biomed. Opt. Express3(6), 1241–1255 (2012).
[CrossRef] [PubMed]

E. Y. S. Yew, H. J. Choi, D. Kim, and P. T. C. So, “Wide-field two-photon microscopy with temporal focusing and HiLo background rejection,” Proc. SPIE7903, 79031O, 79031O-6 (2011).
[CrossRef]

Chu, K. K.

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt.16(1), 016014 (2011).
[CrossRef] [PubMed]

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett.33(16), 1819–1821 (2008).
[CrossRef] [PubMed]

Clémenceau, P.

Côté, D.

Dana, H.

de Jong, S. J.

de Sars, V.

E. Papagiakoumou, F. Anselmi, A. Bègue, V. de Sars, J. Glückstad, E. Y. Isacoff, and V. Emiliani, “Scanless two-photon excitation of channelrhodopsin-2,” Nat. Methods7(10), 848–854 (2010).
[CrossRef] [PubMed]

E. Papagiakoumou, V. de Sars, V. Emiliani, and D. Oron, “Temporal focusing with spatially modulated excitation,” Opt. Express17(7), 5391–5401 (2009).
[CrossRef] [PubMed]

Dong, C. Y.

Durst, M.

Durst, M. E.

Ellman, A.

Emiliani, V.

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, “Functional patterned multiphoton excitation deep inside scattering tissue,” Nat. Photonics7(4), 274–278 (2013).
[CrossRef]

E. Papagiakoumou, F. Anselmi, A. Bègue, V. de Sars, J. Glückstad, E. Y. Isacoff, and V. Emiliani, “Scanless two-photon excitation of channelrhodopsin-2,” Nat. Methods7(10), 848–854 (2010).
[CrossRef] [PubMed]

E. Papagiakoumou, V. de Sars, V. Emiliani, and D. Oron, “Temporal focusing with spatially modulated excitation,” Opt. Express17(7), 5391–5401 (2009).
[CrossRef] [PubMed]

Fantini, S.

Ford, T. N.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt.17(2), 021105 (2012).
[CrossRef] [PubMed]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt.16(1), 016014 (2011).
[CrossRef] [PubMed]

Glückstad, J.

E. Papagiakoumou, F. Anselmi, A. Bègue, V. de Sars, J. Glückstad, E. Y. Isacoff, and V. Emiliani, “Scanless two-photon excitation of channelrhodopsin-2,” Nat. Methods7(10), 848–854 (2010).
[CrossRef] [PubMed]

Golubovskaya, I. N.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, “Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination,” Biophys. J.94(12), 4957–4970 (2008).
[CrossRef] [PubMed]

Gu, M.

C. J. R. Sheppard and M. Gu, “Image formation in two-photon fluorescence microscopy,” Optik (Stuttg.)86, 104–106 (1990).

Gustafsson, M. G. L.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, “Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination,” Biophys. J.94(12), 4957–4970 (2008).
[CrossRef] [PubMed]

Heffer, E. L.

Huang, H. D.

Isacoff, E. Y.

E. Papagiakoumou, F. Anselmi, A. Bègue, V. de Sars, J. Glückstad, E. Y. Isacoff, and V. Emiliani, “Scanless two-photon excitation of channelrhodopsin-2,” Nat. Methods7(10), 848–854 (2010).
[CrossRef] [PubMed]

Ji, N.

N. Ji, J. C. Magee, and E. Betzig, “High-speed, low-photodamage nonlinear imaging using passive pulse splitters,” Nat. Methods5(2), 197–202 (2008).
[CrossRef] [PubMed]

Juskaitis, R.

Karadaglic, D.

D. Karadaglić and T. Wilson, “Image formation in structured illumination wide-field fluorescence microscopy,” Micron39(7), 808–818 (2008).
[CrossRef] [PubMed]

Kim, D.

E. Y. S. Yew, H. J. Choi, D. Kim, and P. T. C. So, “Wide-field two-photon microscopy with temporal focusing and HiLo background rejection,” Proc. SPIE7903, 79031O, 79031O-6 (2011).
[CrossRef]

D. Kim and P. T. C. So, “High-throughput three-dimensional lithographic microfabrication,” Opt. Lett.35(10), 1602–1604 (2010).
[CrossRef] [PubMed]

Kim, J.

J. Mertz and J. Kim, “Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection,” J. Biomed. Opt.15(1), 016027 (2010).
[CrossRef] [PubMed]

Kim, K. H.

Koenig, K.

C. Y. Dong, K. Koenig, and P. So, “Characterizing point spread functions of two-photon fluorescence microscopy in turbid medium,” J. Biomed. Opt.8(3), 450–459 (2003).
[CrossRef] [PubMed]

Koninck, P. D.

Kruger, N.

Lee, W. C. A.

Leshem, B.

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, “Functional patterned multiphoton excitation deep inside scattering tissue,” Nat. Photonics7(4), 274–278 (2013).
[CrossRef]

Li, Y. C.

Lien, C. H.

Lim, D.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt.17(2), 021105 (2012).
[CrossRef] [PubMed]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt.16(1), 016014 (2011).
[CrossRef] [PubMed]

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett.33(16), 1819–1821 (2008).
[CrossRef] [PubMed]

Lin, C. Y.

Magee, J. C.

N. Ji, J. C. Magee, and E. Betzig, “High-speed, low-photodamage nonlinear imaging using passive pulse splitters,” Nat. Methods5(2), 197–202 (2008).
[CrossRef] [PubMed]

Matsudaira, P.

Mertz, J.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt.17(2), 021105 (2012).
[CrossRef] [PubMed]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt.16(1), 016014 (2011).
[CrossRef] [PubMed]

J. Mertz and J. Kim, “Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection,” J. Biomed. Opt.15(1), 016027 (2010).
[CrossRef] [PubMed]

D. Lim, K. K. Chu, and J. Mertz, “Wide-field fluorescence sectioning with hybrid speckle and uniform-illumination microscopy,” Opt. Lett.33(16), 1819–1821 (2008).
[CrossRef] [PubMed]

Michaelson, J.

Moes, C. J.

Moon, J. H.

Nedivi, E.

Neil, M. A. A.

Oron, D.

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, “Functional patterned multiphoton excitation deep inside scattering tissue,” Nat. Photonics7(4), 274–278 (2013).
[CrossRef]

E. Papagiakoumou, V. de Sars, V. Emiliani, and D. Oron, “Temporal focusing with spatially modulated excitation,” Opt. Express17(7), 5391–5401 (2009).
[CrossRef] [PubMed]

D. Oron, E. Tal, and Y. Silberberg, “Scanningless depth-resolved microscopy,” Opt. Express13(5), 1468–1476 (2005).
[CrossRef] [PubMed]

Pagès, S.

Papagiakoumou, E.

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, “Functional patterned multiphoton excitation deep inside scattering tissue,” Nat. Photonics7(4), 274–278 (2013).
[CrossRef]

E. Papagiakoumou, F. Anselmi, A. Bègue, V. de Sars, J. Glückstad, E. Y. Isacoff, and V. Emiliani, “Scanless two-photon excitation of channelrhodopsin-2,” Nat. Methods7(10), 848–854 (2010).
[CrossRef] [PubMed]

E. Papagiakoumou, V. de Sars, V. Emiliani, and D. Oron, “Temporal focusing with spatially modulated excitation,” Opt. Express17(7), 5391–5401 (2009).
[CrossRef] [PubMed]

Prahl, S. A.

Ragan, T.

Schild, D.

A. Weigel, D. Schild, and A. Zeug, “Resolution in the ApoTome and the confocal laser scanning microscope: comparison,” J. Biomed. Opt.14(1), 014022 (2009).
[CrossRef] [PubMed]

Schwartz, O.

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, “Functional patterned multiphoton excitation deep inside scattering tissue,” Nat. Photonics7(4), 274–278 (2013).
[CrossRef]

Sedat, J. W.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, “Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination,” Biophys. J.94(12), 4957–4970 (2008).
[CrossRef] [PubMed]

Shank, C. V.

A. Vaziri and C. V. Shank, “Ultrafast widefield optical sectioning microscopy by multifocal temporal focusing,” Opt. Express18(19), 19645–19655 (2010).
[CrossRef] [PubMed]

A. Vaziri, J. Y. Tang, H. Shroff, and C. V. Shank, “Multilayer three-dimensional super resolution imaging of thick biological samples,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20221–20226 (2008).
[CrossRef] [PubMed]

Shao, L.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, “Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination,” Biophys. J.94(12), 4957–4970 (2008).
[CrossRef] [PubMed]

Sheppard, C. J. R.

C. J. R. Sheppard and M. Gu, “Image formation in two-photon fluorescence microscopy,” Optik (Stuttg.)86, 104–106 (1990).

Shoham, S.

Shroff, H.

A. Vaziri, J. Y. Tang, H. Shroff, and C. V. Shank, “Multilayer three-dimensional super resolution imaging of thick biological samples,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20221–20226 (2008).
[CrossRef] [PubMed]

Silberberg, Y.

Singh, V. R.

So, P.

J. Michaelson, H. J. Choi, P. So, and H. D. Huang, “Depth-resolved cellular microrheology using HiLo microscopy,” Biomed. Opt. Express3(6), 1241–1255 (2012).
[CrossRef] [PubMed]

C. Y. Dong, K. Koenig, and P. So, “Characterizing point spread functions of two-photon fluorescence microscopy in turbid medium,” J. Biomed. Opt.8(3), 450–459 (2003).
[CrossRef] [PubMed]

So, P. T.

So, P. T. C.

Stell, B. M.

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, “Functional patterned multiphoton excitation deep inside scattering tissue,” Nat. Photonics7(4), 274–278 (2013).
[CrossRef]

Stokseth, P. A.

Sun, P.

P. Sun and Y. Wang, “Measurements of optical parameters of phantom solution and bulk animal tissues in vitro at 650 nm,” Opt. Laser Technol.42(1), 1–7 (2010).
[CrossRef]

Tal, E.

Tang, J. Y.

B. K. Andrasfalvy, B. V. Zemelman, J. Y. Tang, and A. Vaziri, “Two-photon single-cell optogenetic control of neuronal activity by sculpted light,” Proc. Natl. Acad. Sci. U.S.A.107(26), 11981–11986 (2010).
[CrossRef] [PubMed]

A. Vaziri, J. Y. Tang, H. Shroff, and C. V. Shank, “Multilayer three-dimensional super resolution imaging of thick biological samples,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20221–20226 (2008).
[CrossRef] [PubMed]

Therrien, O. D.

Tzeranis, D. S.

van Geest, L. K.

van Gemert, M. J.

van Howe, J.

van Marie, J.

van Staveren, H. J.

Vaziri, A.

A. Vaziri and C. V. Shank, “Ultrafast widefield optical sectioning microscopy by multifocal temporal focusing,” Opt. Express18(19), 19645–19655 (2010).
[CrossRef] [PubMed]

B. K. Andrasfalvy, B. V. Zemelman, J. Y. Tang, and A. Vaziri, “Two-photon single-cell optogenetic control of neuronal activity by sculpted light,” Proc. Natl. Acad. Sci. U.S.A.107(26), 11981–11986 (2010).
[CrossRef] [PubMed]

A. Vaziri, J. Y. Tang, H. Shroff, and C. V. Shank, “Multilayer three-dimensional super resolution imaging of thick biological samples,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20221–20226 (2008).
[CrossRef] [PubMed]

Wang, C. J. R.

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, “Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination,” Biophys. J.94(12), 4957–4970 (2008).
[CrossRef] [PubMed]

Wang, Y.

P. Sun and Y. Wang, “Measurements of optical parameters of phantom solution and bulk animal tissues in vitro at 650 nm,” Opt. Laser Technol.42(1), 1–7 (2010).
[CrossRef]

Weigel, A.

A. Weigel, D. Schild, and A. Zeug, “Resolution in the ApoTome and the confocal laser scanning microscope: comparison,” J. Biomed. Opt.14(1), 014022 (2009).
[CrossRef] [PubMed]

Wilson, T.

D. Karadaglić and T. Wilson, “Image formation in structured illumination wide-field fluorescence microscopy,” Micron39(7), 808–818 (2008).
[CrossRef] [PubMed]

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]

Xu, C.

Yannas, I. V.

Yen, W. C.

L. C. Cheng, C. Y. Chang, C. Y. Lin, K. C. Cho, W. C. Yen, N. S. Chang, C. Xu, C. Y. Dong, and S. J. Chen, “Spatiotemporal focusing-based widefield multiphoton microscopy for fast optical sectioning,” Opt. Express20(8), 8939–8948 (2012).
[CrossRef] [PubMed]

L. C. Cheng, C. Y. Chang, W. C. Yen, and S. J. Chen, “Spatiotemporal focusing-based widefield multiphoton microscopy for fast optical sectioning of thick tissues,” Proc. SPIE8520, 85200N, 85200N-8 (2012).
[CrossRef]

Yew, E. Y. S.

E. Y. S. Yew, H. J. Choi, D. Kim, and P. T. C. So, “Wide-field two-photon microscopy with temporal focusing and HiLo background rejection,” Proc. SPIE7903, 79031O, 79031O-6 (2011).
[CrossRef]

Zemelman, B. V.

B. K. Andrasfalvy, B. V. Zemelman, J. Y. Tang, and A. Vaziri, “Two-photon single-cell optogenetic control of neuronal activity by sculpted light,” Proc. Natl. Acad. Sci. U.S.A.107(26), 11981–11986 (2010).
[CrossRef] [PubMed]

Zeug, A.

A. Weigel, D. Schild, and A. Zeug, “Resolution in the ApoTome and the confocal laser scanning microscope: comparison,” J. Biomed. Opt.14(1), 014022 (2009).
[CrossRef] [PubMed]

Zhi, C.

Zhu, G. H.

Zipfel, W.

Appl. Opt. (1)

Biomed. Opt. Express (2)

Biophys. J. (1)

M. G. L. Gustafsson, L. Shao, P. M. Carlton, C. J. R. Wang, I. N. Golubovskaya, W. Z. Cande, D. A. Agard, and J. W. Sedat, “Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination,” Biophys. J.94(12), 4957–4970 (2008).
[CrossRef] [PubMed]

J. Biomed. Opt. (5)

C. Y. Dong, K. Koenig, and P. So, “Characterizing point spread functions of two-photon fluorescence microscopy in turbid medium,” J. Biomed. Opt.8(3), 450–459 (2003).
[CrossRef] [PubMed]

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt.17(2), 021105 (2012).
[CrossRef] [PubMed]

A. Weigel, D. Schild, and A. Zeug, “Resolution in the ApoTome and the confocal laser scanning microscope: comparison,” J. Biomed. Opt.14(1), 014022 (2009).
[CrossRef] [PubMed]

D. Lim, T. N. Ford, K. K. Chu, and J. Mertz, “Optically sectioned in vivo imaging with speckle illumination HiLo microscopy,” J. Biomed. Opt.16(1), 016014 (2011).
[CrossRef] [PubMed]

J. Mertz and J. Kim, “Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection,” J. Biomed. Opt.15(1), 016027 (2010).
[CrossRef] [PubMed]

J. Opt. Soc. Am. (1)

Micron (1)

D. Karadaglić and T. Wilson, “Image formation in structured illumination wide-field fluorescence microscopy,” Micron39(7), 808–818 (2008).
[CrossRef] [PubMed]

Nat. Methods (2)

N. Ji, J. C. Magee, and E. Betzig, “High-speed, low-photodamage nonlinear imaging using passive pulse splitters,” Nat. Methods5(2), 197–202 (2008).
[CrossRef] [PubMed]

E. Papagiakoumou, F. Anselmi, A. Bègue, V. de Sars, J. Glückstad, E. Y. Isacoff, and V. Emiliani, “Scanless two-photon excitation of channelrhodopsin-2,” Nat. Methods7(10), 848–854 (2010).
[CrossRef] [PubMed]

Nat. Photonics (1)

E. Papagiakoumou, A. Begue, B. Leshem, O. Schwartz, B. M. Stell, J. Bradley, D. Oron, and V. Emiliani, “Functional patterned multiphoton excitation deep inside scattering tissue,” Nat. Photonics7(4), 274–278 (2013).
[CrossRef]

Opt. Express (12)

A. Vaziri and C. V. Shank, “Ultrafast widefield optical sectioning microscopy by multifocal temporal focusing,” Opt. Express18(19), 19645–19655 (2010).
[CrossRef] [PubMed]

H. Dana and S. Shoham, “Numerical evaluation of temporal focusing characteristics in transparent and scattering media,” Opt. Express19(6), 4937–4948 (2011).
[CrossRef] [PubMed]

H. Dana, N. Kruger, A. Ellman, and S. Shoham, “Line temporal focusing characteristics in transparent and scattering media,” Opt. Express21(5), 5677–5687 (2013).
[CrossRef] [PubMed]

K. H. Kim, C. Buehler, K. Bahlmann, T. Ragan, W. C. A. Lee, E. Nedivi, E. L. Heffer, S. Fantini, and P. T. C. So, “Multifocal multiphoton microscopy based on multianode photomultiplier tubes,” Opt. Express15(18), 11658–11678 (2007).
[CrossRef] [PubMed]

H. Choi, D. S. Tzeranis, J. W. Cha, P. Clémenceau, S. J. de Jong, L. K. van Geest, J. H. Moon, I. V. Yannas, and P. T. So, “3D-resolved fluorescence and phosphorescence lifetime imaging using temporal focusing wide-field two-photon excitation,” Opt. Express20(24), 26219–26235 (2012).
[CrossRef] [PubMed]

D. Oron, E. Tal, and Y. Silberberg, “Scanningless depth-resolved microscopy,” Opt. Express13(5), 1468–1476 (2005).
[CrossRef] [PubMed]

G. H. Zhu, J. van Howe, M. Durst, W. Zipfel, and C. Xu, “Simultaneous spatial and temporal focusing of femtosecond pulses,” Opt. Express13(6), 2153–2159 (2005).
[CrossRef] [PubMed]

E. Papagiakoumou, V. de Sars, V. Emiliani, and D. Oron, “Temporal focusing with spatially modulated excitation,” Opt. Express17(7), 5391–5401 (2009).
[CrossRef] [PubMed]

D. Bhattacharya, V. R. Singh, C. Zhi, P. T. C. So, P. Matsudaira, and G. Barbastathis, “Three dimensional HiLo-based structured illumination for a digital scanned laser sheet microscopy (DSLM) in thick tissue imaging,” Opt. Express20(25), 27337–27347 (2012).
[CrossRef] [PubMed]

Y. C. Li, L. C. Cheng, C. Y. Chang, C. H. Lien, P. J. Campagnola, and S. J. Chen, “Fast multiphoton microfabrication of freeform polymer microstructures by spatiotemporal focusing and patterned excitation,” Opt. Express20(17), 19030–19038 (2012).
[CrossRef] [PubMed]

L. C. Cheng, C. Y. Chang, C. Y. Lin, K. C. Cho, W. C. Yen, N. S. Chang, C. Xu, C. Y. Dong, and S. J. Chen, “Spatiotemporal focusing-based widefield multiphoton microscopy for fast optical sectioning,” Opt. Express20(8), 8939–8948 (2012).
[CrossRef] [PubMed]

M. E. Durst, G. H. Zhu, and C. Xu, “Simultaneous spatial and temporal focusing for axial scanning,” Opt. Express14(25), 12243–12254 (2006).
[CrossRef] [PubMed]

Opt. Laser Technol. (1)

P. Sun and Y. Wang, “Measurements of optical parameters of phantom solution and bulk animal tissues in vitro at 650 nm,” Opt. Laser Technol.42(1), 1–7 (2010).
[CrossRef]

Opt. Lett. (3)

Optik (Stuttg.) (1)

C. J. R. Sheppard and M. Gu, “Image formation in two-photon fluorescence microscopy,” Optik (Stuttg.)86, 104–106 (1990).

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

A. Vaziri, J. Y. Tang, H. Shroff, and C. V. Shank, “Multilayer three-dimensional super resolution imaging of thick biological samples,” Proc. Natl. Acad. Sci. U.S.A.105(51), 20221–20226 (2008).
[CrossRef] [PubMed]

B. K. Andrasfalvy, B. V. Zemelman, J. Y. Tang, and A. Vaziri, “Two-photon single-cell optogenetic control of neuronal activity by sculpted light,” Proc. Natl. Acad. Sci. U.S.A.107(26), 11981–11986 (2010).
[CrossRef] [PubMed]

Proc. SPIE (2)

E. Y. S. Yew, H. J. Choi, D. Kim, and P. T. C. So, “Wide-field two-photon microscopy with temporal focusing and HiLo background rejection,” Proc. SPIE7903, 79031O, 79031O-6 (2011).
[CrossRef]

L. C. Cheng, C. Y. Chang, W. C. Yen, and S. J. Chen, “Spatiotemporal focusing-based widefield multiphoton microscopy for fast optical sectioning of thick tissues,” Proc. SPIE8520, 85200N, 85200N-8 (2012).
[CrossRef]

Other (1)

D. A. Boas, C. Pitris, and N. Ramanujam, eds., Handbook of Biomedical Optics (CRC Press, 2011), Chap. 5.

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Figures (6)

Fig. 1
Fig. 1

Generating SLI is possible through either an interferometer or a grid. The interferometric setup shown here is much simplified for grid projection where the components in the dotted box are bypassed and the light goes directly from RDG through the f = 200mm and f = 100mm lenses before passing through the grid and onwards. BE: beam expander, RDG: reflective diffraction grating, NPB: non-polarizing beam splitter, M: mirror, ExTL: excitation tube lens, EmTL: emission tube lens, DM: dichroic mirror, Obj: objective, BFP: back focal plane, FFP: front focal plane, GP: grid projection, FP: fringe projection.

Fig. 2
Fig. 2

(a) The profile of the illumination fringe pattern of FP predicted by Eq. (1). (b) The profile of the illumination fringe pattern of GP predicted by Eq. (2). λ = 780nm, θf = 13.2 degree, θg = 27.2 degree, α = 2/π (c) The experimentally measured contrast of the coherent illumination fringe pattern and the incoherent detection fringe pattern of both FP and GP. Standard deviations are small compared to averages and not well visible in the plot.

Fig. 3
Fig. 3

(a) Contrast decay of fringe pattern of the spatial period of Tg = 0.43, 0.85, 1.71, 3.42 µm as a function of the defocus (distance from focal plane). (b) Normalized intensity of SLI and TPLSM as a function of the normalized defocus unit.

Fig. 4
Fig. 4

(a) Axial resolution measured with the thin Rhodamine solution. Fringe period of SLI is 1.71µm (red) TFM HiLo at 0% intralipid (blue) TFM HiLo at 2% intralipid (green) TFM at 0% intralipid (black) TFM at 2% intralipid (orange) TPLSM in Fig. 3(b) convoluted with 2 µm thick Rhodamine solution. (b) Averages and standard deviations of FWHM of 10 measurements for 0% and 2% scattering condition of both TFM and HiLo TFM.

Fig. 5
Fig. 5

xz sections of the fine glomeruli and convoluted tubules structure in a mouse kidney sample acquired with TFM without SLI, HiLo processed TFM with fringe period of 3.42µm, 1.71µm, 0.85µm, respectively. The thickness of the imaged portion is 14µm. Intensity increases from purple to red. The cross sectional intensity plot along the line indicated by the yellow arrow is also shown on the right side. Further details on the sample can be found in http://products.invitrogen.com/ivgn/product/F24630.

Fig. 6
Fig. 6

Unprocessed images in scattering conditions (a) 0% v/v, (c) 3% v/v, and (e) 5%v/v Lipofundin-20. Processed images are (b), (d), and (f) for the same scattering conditions, respectively. Each image represents a 90µm x 70µm.

Tables (1)

Tables Icon

Table 1 Reduced Scattering Coefficients

Equations (7)

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

I Fringe =1+cos(2ksin θ f y)
I Grid =1+4αcos(ksin θ g y)cos( k( cos θ g 1 )z )+2 α 2 ( 1+cos(2ksin θ g y) )
Contrast= I max I min I max + I min
f(y)= 1 2 (1+Mcos(ky))exp( y 2 2 σ 2 )
F(m)=[ 1 2 δ(m)+ 1 4 Mδ(mk)+ 1 4 Mδ(m+k) ][ σ 2π exp( σ 2 m 2 2 ) ]
M=2 F(m=±k) F(m=0)
C( u,m )=f( m ){ 2 J 1 ( um[ 1m/2 ] ) um[ 1m/2 ] }

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