Abstract

We demonstrate adaptive optics system based on nonlinear feedback from 3- and 4-photon fluorescence. The system is based on femtosecond pulses created by soliton self-frequency shift of a 1550-nm fiber-based femtosecond laser together with micro-electro-mechanical system (MEMS) phase spatial light modulator (SLM). We perturb the 1020-segment SLM using an orthogonal Walsh sequence basis set with a modified version of three-point phase shifting interferometry. We show the improvement after aberrations correction in 3-photon signal from fluorescent beads. In addition, we compare the improvement obtained in the same adaptive optical system for 2-, 3- and 4-photon fluorescence using dye pool. We show that signal improvement resulting from aberration correction grows exponentially as a function of the order of nonlinearity.

© 2015 Optical Society of America

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2015 (2)

2014 (4)

L. C. Cheng, N. G. Horton, K. Wang, S. J. Chen, and C. Xu, “Measurements of multiphoton action cross sections for multiphoton microscopy,” Biomed. Opt. Express 5(10), 3427–3433 (2014).
[Crossref] [PubMed]

O. Katz, E. Small, Y. Guan, and Y. Silberberg, “Noninvasive nonlinear focusing and imaging through strongly scattering turbid layers,” Optica 1(3), 170–174 (2014).
[Crossref]

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

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
[Crossref] [PubMed]

2013 (2)

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

H. P. Paudel, C. Stockbridge, J. Mertz, and T. Bifano, “Focusing polychromatic light through strongly scattering media,” Opt. Express 21(14), 17299–17308 (2013).
[Crossref] [PubMed]

2012 (4)

C. Stockbridge, Y. Lu, J. Moore, S. Hoffman, R. Paxman, K. Toussaint, and T. Bifano, “Focusing through dynamic scattering media,” Opt. Express 20(14), 15086–15092 (2012).
[Crossref] [PubMed]

M. J. Booth, D. Débarre, and A. Jesacher, “Adaptive optics for biomedical microscopy,” Opt. Photonics News 23(1), 22–29 (2012).
[Crossref]

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proc. Natl. Acad. Sci. U.S.A. 109(22), 8434–8439 (2012).
[Crossref] [PubMed]

O. Katz, E. Small, and Y. Silberberg, “Looking around corners and through thin turbid layers in real time with scattered incoherent light,” Nat. Photonics 6(8), 549–553 (2012).
[Crossref]

2011 (4)

Editorial, “Nature photonics technology focus: adaptive optics,” Nat. Photonics 5, 15–28 (2011).

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]

F. Wang, “Utility transforms of optical fields employing deformable mirror,” Opt. Lett. 36(22), 4383–4385 (2011).
[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(7), 071112 (2011).
[Crossref]

2010 (3)

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, “Exploiting disorder for perfect focusing,” Nat. Photonics 4(5), 320–322 (2010).
[Crossref]

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

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]

2009 (1)

2008 (1)

J. N. D. Kerr and W. Denk, “Imaging in vivo: watching the brain in action,” Nat. Rev. Neurosci. 9(3), 195–205 (2008).
[Crossref] [PubMed]

2007 (2)

M. J. Booth, “Adaptive optics in microscopy,” Philos. Trans. A Math. Phys. Eng. Sci. 365(1861), 2829–2843 (2007).
[Crossref] [PubMed]

I. M. Vellekoop and A. P. Mosk, “Focusing coherent light through opaque strongly scattering media,” Opt. Lett. 32(16), 2309–2311 (2007).
[Crossref] [PubMed]

2004 (1)

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

2003 (2)

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]

T. A. Pologruto, B. L. Sabatini, and K. Svoboda, “ScanImage: flexible software for operating laser scanning microscopes,” Biomed. Eng. Online 2(1), 13 (2003).
[Crossref] [PubMed]

1996 (1)

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

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]

1976 (1)

Aksay, E.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

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]

Bewersdorf, J.

Bifano, T.

Booth, M. J.

D. Burke, B. Patton, F. Huang, J. Bewersdorf, and M. J. Booth, “Adaptive optics correction of specimen-induced aberrations in single-molecule switching microscopy,” Optica 2(2), 177–185 (2015).
[Crossref]

M. J. Booth, D. Débarre, and A. Jesacher, “Adaptive optics for biomedical microscopy,” Opt. Photonics News 23(1), 22–29 (2012).
[Crossref]

M. J. Booth, “Adaptive optics in microscopy,” Philos. Trans. A Math. Phys. Eng. Sci. 365(1861), 2829–2843 (2007).
[Crossref] [PubMed]

Burke, D.

Charan, K.

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

Chen, S. J.

Chen, T.-W.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
[Crossref] [PubMed]

Cheng, L. C.

Clark, C. G.

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

Cui, M.

L. Kong and M. Cui, “In vivo neuroimaging through the highly scattering tissue via iterative multi-photon adaptive compensation technique,” Opt. Express 23(5), 6145–6150 (2015).
[Crossref] [PubMed]

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proc. Natl. Acad. Sci. U.S.A. 109(22), 8434–8439 (2012).
[Crossref] [PubMed]

Débarre, D.

M. J. Booth, D. Débarre, and A. Jesacher, “Adaptive optics for biomedical microscopy,” Opt. Photonics News 23(1), 22–29 (2012).
[Crossref]

Denk, W.

J. N. D. Kerr and W. Denk, “Imaging in vivo: watching the brain in action,” Nat. Rev. Neurosci. 9(3), 195–205 (2008).
[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]

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

Dombeck, D. A.

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

Durst, M. E.

Editorial,

Editorial, “Nature photonics technology focus: adaptive optics,” Nat. Photonics 5, 15–28 (2011).

Germain, R. N.

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proc. Natl. Acad. Sci. U.S.A. 109(22), 8434–8439 (2012).
[Crossref] [PubMed]

Guan, Y.

Harvey, C. D.

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

Hasan, M. T.

Hoffman, S.

Horton, N. G.

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

L. C. Cheng, N. G. Horton, K. Wang, S. J. Chen, and C. Xu, “Measurements of multiphoton action cross sections for multiphoton microscopy,” Biomed. Opt. Express 5(10), 3427–3433 (2014).
[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. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

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]

Huang, F.

Jesacher, A.

M. J. Booth, D. Débarre, and A. Jesacher, “Adaptive optics for biomedical microscopy,” Opt. Photonics News 23(1), 22–29 (2012).
[Crossref]

Ji, N.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
[Crossref] [PubMed]

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]

Jung, J. C.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Katz, O.

O. Katz, E. Small, Y. Guan, and Y. Silberberg, “Noninvasive nonlinear focusing and imaging through strongly scattering turbid layers,” Optica 1(3), 170–174 (2014).
[Crossref]

O. Katz, E. Small, and Y. Silberberg, “Looking around corners and through thin turbid layers in real time with scattered incoherent light,” Nat. Photonics 6(8), 549–553 (2012).
[Crossref]

Kerlin, A.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
[Crossref] [PubMed]

Kerr, J. N. D.

J. N. D. Kerr and W. Denk, “Imaging in vivo: watching the brain in action,” Nat. Rev. Neurosci. 9(3), 195–205 (2008).
[Crossref] [PubMed]

Kim, D. S.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
[Crossref] [PubMed]

Kobat, D.

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

D. Kobat, 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]

Kong, L.

Lagendijk, A.

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, “Exploiting disorder for perfect focusing,” Nat. Photonics 4(5), 320–322 (2010).
[Crossref]

Liu, R.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
[Crossref] [PubMed]

Looger, L. L.

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

Lu, Y.

Mehta, A. D.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Mertz, J.

Milkie, D. E.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
[Crossref] [PubMed]

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]

Moore, J.

Mosk, A. P.

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, “Exploiting disorder for perfect focusing,” Nat. Photonics 4(5), 320–322 (2010).
[Crossref]

I. M. Vellekoop and A. P. Mosk, “Focusing coherent light through opaque strongly scattering media,” Opt. Lett. 32(16), 2309–2311 (2007).
[Crossref] [PubMed]

Nishimura, N.

Noll, R.

Patton, B.

Paudel, H. P.

Paxman, R.

Pologruto, T. A.

T. A. Pologruto, B. L. Sabatini, and K. Svoboda, “ScanImage: flexible software for operating laser scanning microscopes,” Biomed. Eng. Online 2(1), 13 (2003).
[Crossref] [PubMed]

Sabatini, B. L.

T. A. Pologruto, B. L. Sabatini, and K. Svoboda, “ScanImage: flexible software for operating laser scanning microscopes,” Biomed. Eng. Online 2(1), 13 (2003).
[Crossref] [PubMed]

Schaffer, C. B.

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

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

Schnitzer, M. J.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Shear, J. B.

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

Silberberg, Y.

O. Katz, E. Small, Y. Guan, and Y. Silberberg, “Noninvasive nonlinear focusing and imaging through strongly scattering turbid layers,” Optica 1(3), 170–174 (2014).
[Crossref]

O. Katz, E. Small, and Y. Silberberg, “Looking around corners and through thin turbid layers in real time with scattered incoherent light,” Nat. Photonics 6(8), 549–553 (2012).
[Crossref]

Small, E.

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[Crossref]

O. Katz, E. Small, and Y. Silberberg, “Looking around corners and through thin turbid layers in real time with scattered incoherent light,” Nat. Photonics 6(8), 549–553 (2012).
[Crossref]

Stepnoski, R.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Stockbridge, C.

Strickler, J. H.

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

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
[Crossref] [PubMed]

Svoboda, K.

T. A. Pologruto, B. L. Sabatini, and K. Svoboda, “ScanImage: flexible software for operating laser scanning microscopes,” Biomed. Eng. Online 2(1), 13 (2003).
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Tan, Z.

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
[Crossref] [PubMed]

Tang, J.

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proc. Natl. Acad. Sci. U.S.A. 109(22), 8434–8439 (2012).
[Crossref] [PubMed]

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D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
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Theer, P.

Tian, L.

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
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C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
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K. Wang, N. G. Horton, K. Charan, and C. Xu, “Advanced fiber soliton sources for nonlinear deep tissue imaging in biophotonics,” IEEE J. Sel. Top. Quantum Electron. 20, 6800311 (2014).

L. C. Cheng, N. G. Horton, K. Wang, S. J. Chen, and C. Xu, “Measurements of multiphoton action cross sections for multiphoton microscopy,” Biomed. Opt. Express 5(10), 3427–3433 (2014).
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C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
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Wong, A. W.

Xu, C.

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

L. C. Cheng, N. G. Horton, K. Wang, S. J. Chen, and C. Xu, “Measurements of multiphoton action cross sections for multiphoton microscopy,” Biomed. Opt. Express 5(10), 3427–3433 (2014).
[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. Photonics 7(3), 205–209 (2013).
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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]

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(7), 071112 (2011).
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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).
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C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, “Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy,” Proc. Natl. Acad. Sci. U.S.A. 93(20), 10763–10768 (1996).
[Crossref] [PubMed]

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(7), 071112 (2011).
[Crossref]

Biomed. Eng. Online (1)

T. A. Pologruto, B. L. Sabatini, and K. Svoboda, “ScanImage: flexible software for operating laser scanning microscopes,” Biomed. Eng. Online 2(1), 13 (2003).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

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

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

J. Biomed. Opt. (1)

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]

J. Neurophysiol. (1)

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

J. Opt. Soc. Am. (1)

Nat. Methods (2)

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]

C. Wang, R. Liu, D. E. Milkie, W. Sun, Z. Tan, A. Kerlin, T.-W. Chen, D. S. Kim, and N. Ji, “Multiplexed aberration measurement for deep tissue imaging in vivo,” Nat. Methods 11(10), 1037–1040 (2014).
[Crossref] [PubMed]

Nat. Neurosci. (1)

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

Nat. Photonics (4)

Editorial, “Nature photonics technology focus: adaptive optics,” Nat. Photonics 5, 15–28 (2011).

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

I. M. Vellekoop, A. Lagendijk, and A. P. Mosk, “Exploiting disorder for perfect focusing,” Nat. Photonics 4(5), 320–322 (2010).
[Crossref]

O. Katz, E. Small, and Y. Silberberg, “Looking around corners and through thin turbid layers in real time with scattered incoherent light,” Nat. Photonics 6(8), 549–553 (2012).
[Crossref]

Nat. Rev. Neurosci. (1)

J. N. D. Kerr and W. Denk, “Imaging in vivo: watching the brain in action,” Nat. Rev. Neurosci. 9(3), 195–205 (2008).
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Opt. Express (4)

Opt. Lett. (3)

Opt. Photonics News (1)

M. J. Booth, D. Débarre, and A. Jesacher, “Adaptive optics for biomedical microscopy,” Opt. Photonics News 23(1), 22–29 (2012).
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Optica (2)

Philos. Trans. A Math. Phys. Eng. Sci. (1)

M. J. Booth, “Adaptive optics in microscopy,” Philos. Trans. A Math. Phys. Eng. Sci. 365(1861), 2829–2843 (2007).
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Proc. Natl. Acad. Sci. U.S.A. (2)

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

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proc. Natl. Acad. Sci. U.S.A. 109(22), 8434–8439 (2012).
[Crossref] [PubMed]

Science (1)

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

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D. Ouzounov, N. Horton, T. Wang, D. Feng, N. Nishimura, and C. Xu, “In vivo three-photon calcium imaging of brain activity from layer 6 neurons in mouse brain,” in CLEO: 2014 Postdeadline Paper Digest, OSA Technical Digest (online) (Optical Society of America, 2014), paper STh4C.2.

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C. Xu and W. W. Webb, Topics in Fluorescence Spectroscopy, vol. 5 (Springer, 1997).

M. Born and E. Wolf, Principles of Optics, 7th ed. (Cambridge University Press, 1999).

J. C. Wyant and K. Creath, “Basic wavefront aberration theory for optical metrology,” in Applied Optics and Optical Engineering, J. C. Wyant, and R. R. Shannon, eds. (Academic Press, 1992), pp. 2−53.

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Figures (7)

Fig. 1
Fig. 1 (a) System description. The same excitation light is used for 2-, 3- and 4- photon fluorescence by changing the fluorescence dye, the PMT and the filter. (b) Second-order AC traces taken after the PC rod (top) and after the objective (bottom). The pulse FWHM values correspond to 115 fs (top) and 130 fs (bottom). (c) 4 Examples for Walsh binary phase patterns (out of 1024 patterns).
Fig. 2
Fig. 2 Aberration correction results for 3-photon fluorescence from 200 nm fluorescent beads. (a-b) compensation for system aberrations: (a) System phase correction as it applied on the SLM, (b) Axial response before and after system correction. (c-f) Phase correction for 1-m focal length cylindrical lens: (c) Algorithm convergence with 200 nm beads as the test sample. (d) Phase correction applied on the SLM (color bar is in wavelength unit scale). (e-f): 3-photon images of beads: before (e) and after (f) phase correction. (Image size: 25 × 25 μm).
Fig. 3
Fig. 3 The spectrum of the soliton-shifted excitation laser (black) and emission (dashed lines) and excitation (solid lines) spectra of Alexa Fluor 790, Sulforhodamine 101 and Fluorescein used for 2-, 3- and 4-photon fluorescence excitation, respectively. Data for the fluorescent dyes were obtained from Life Technologies, USA. http://www.lifetechnologies.com
Fig. 4
Fig. 4 (a) Power curves: Logarithmic plots of the dependence of 4-, 3-, and 2-photon excited fluorescence on excitation intensity for Alexa Fluor 790 (red square), Sulforhodamine 101 (green square) and Fluorescein (blue square). (b) Phase curves for N = 4, 3, and 2, obtained by applying alternating phase different with the chess pattern phase shown in the lower right part of Fig. 1. The results match the function: a + b × cos(ϕ/2)2N. The same signal levels were used for all experiments.
Fig. 5
Fig. 5 Phase correction for a 2-m-focal length cylindrical lens for 2-, 3- and 4- photon excited fluorescence of Alexa Fluor 790, Sulforhodamine 101 and Fluorescein. (a) Left – 4-photon fluorescence convergence curve showing a signal improvement factor of × 320. Right – final phase applied on the SLM (b) left – 3-photon fluorescence convergence curve showing a signal improvement factor of × 40. Right – final phase applied on the SLM. (c) Left – 2-photon fluorescence convergence curve showing a signal improvement factor of × 2.1. Right – final phase applied on the SLM. Color-bars are in wavelength unit scale.
Fig. 6
Fig. 6 (a-d) Final phases applied on the SLM for (a) system correction, (b) 10-m focal length cylindrical lens correction, (c) 5-m focal length cylindrical lens correction, and (d) 2-m focal length cylindrical lens correction (Color-bars are in wavelength unit scale). (e) Power curves for 4-photon fluorescence with 2-m focal length cylindrical lens showing the maximal signal (red), the original signal (blue) before system correction, the signal with the cylindrical lens (magenta), and after correction (green). (f-g) Comparison of aberration correction results for 10-m (red line), 5-m (green line) and 2-m (blue line) focal length cylindrical lenses placed above the objective aperture. (f) Signal degradation due to cylindrical lens aberration - excluding lens losses. (g) signal improvement by phase optimization.
Fig. 7
Fig. 7 Simulation results of signal losses due to aberrations for high order excitation. (a-f) Zernike phase maps of: (a) astigmatism, (b) 3rd order coma, (c) 3rd order spherical, (d) 5th order coma, (e) 5th order spherical. (f) Phase map of an arbitrary aberration combined from random coefficients of 25 Zernike orders. (g) Comparison of experimental results (marked with circles) to simulation results (lines) of cylindrical lens aberration for 2-, 5- and 10-m focal lengths. (h) Logarithmic plot of signal degradation due to aberrations as a function of the nonlinear order –N. Applying tilt or defocus terms does not change the result of the volume integral since they are equivalent to lateral or axial movements.

Tables (1)

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Table 1 Dye pool results summary

Equations (4)

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C i = tan 1 [ S i+ N S i N 2 S i N S i+ N S i N tan( π α ) ]
F ( N ) (t) = 1 N g P (N) ( fτ ) N1 ϕη σ N C n 0 a N (NA) 2N4 P(t) N 8 π 3N λ 2N3
ψ ( N ) = F ' ( N ) (t) F ( N ) (t) = g ' (N) τ ' N1 g (N) τ N1 a N (NA) 2N4 a ' N (NA') 2N4 a N (NA) 2N4 a ' N (NA') 2N4
log[ ψ ( N ) ]log[ a N a ' N ]+(2N4)log[ NA NA' ]

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