Abstract

We present an easily implemented wavefront correction scheme that has been specifically designed for in-vivo brain imaging. The system can be implemented with a single liquid crystal spatial light modulator (LCSLM), which makes it compatible with existing patterned illumination setups, and provides measurable signal improvements even after a few seconds of optimization. The optimization scheme is signal-based and does not require exogenous guide-stars, repeated image acquisition or beam constraint. The unconstrained beam approach allows the use of Zernike functions for aberration correction and Hadamard functions for scattering correction. Low order corrections performed in mouse brain were found to be valid up to hundreds of microns away from the correction location.

© 2015 Optical Society of America

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References

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2014 (3)

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[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]

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]

2013 (2)

X. Tao, A. Norton, M. Kissel, O. Azucena, and J. Kubby, “Adaptive optical two-photon microscopy using autofluorescent guide stars,” Opt. Lett. 38(23), 5075–5078 (2013).
[Crossref] [PubMed]

C. Mathiesen, A. Brazhe, K. Thomsen, and M. Lauritzen, “Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen,” J. Cereb. Blood Flow Metab. 33(2), 161–169 (2013).
[Crossref] [PubMed]

2012 (4)

2011 (4)

A. F. H. McCaslin, B. R. Chen, A. J. Radosevich, B. Cauli, and E. M. C. Hillman, “In vivo 3D morphology of astrocyte-vasculature interactions in the somatosensory cortex: implications for neurovascular coupling,” J. Cereb. Blood Flow Metab. 31(3), 795–806 (2011).
[Crossref] [PubMed]

L. E. Grosberg, A. J. Radosevich, S. Asfaha, T. C. Wang, and E. M. Hillman, “Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral two-photon microscopy,” PLoS One 6(5), e19925 (2011).
[Crossref] [PubMed]

A. Thayil, T. Watanabe, A. Jesacher, T. Wilson, S. Srinivas, and M. Booth, “Long-term imaging of mouse embryos using adaptive harmonic generation microscopy,” J. Biomed. Opt. 16, 046018 (2011).

O. Katz, E. Small, Y. Bromberg, and Y. Silberberg, “Focusing and compression of ultrashort pulses through scattering media,” Nat. Photonics 5(6), 372–377 (2011).
[Crossref]

2010 (3)

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]

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. C. Boccara, and S. Gigan, “Measuring the Transmission Matrix in Optics: An Approach to the Study and Control of Light Propagation in Disordered Media,” Phys. Rev. Lett. 104(10), 100601 (2010).
[Crossref] [PubMed]

M. Dal Maschio, F. Difato, R. Beltramo, A. Blau, F. Benfenati, and T. Fellin, “Simultaneous two-photon imaging and photo-stimulation with structured light illumination,” Opt. Express 18(18), 18720–18731 (2010).
[Crossref] [PubMed]

2009 (1)

2008 (2)

A. J. Radosevich, M. B. Bouchard, S. A. Burgess, B. R. Chen, and E. M. C. Hillman, “Hyperspectral in vivo two-photon microscopy of intrinsic contrast,” Opt. Lett. 33(18), 2164–2166 (2008).
[Crossref] [PubMed]

V. Nikolenko, B. O. Watson, R. Araya, A. Woodruff, D. S. Peterka, and R. Yuste, “SLM microscopy: scanless two-photon imaging and photostimulation with spatial light modulators,” Front. Neural Circuits 2, 5 (2008).
[Crossref] [PubMed]

2007 (1)

2004 (1)

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).
[Crossref] [PubMed]

2002 (1)

L. N. Thibos, R. A. Applegate, J. T. Schwiegerling, R. Webb, and VSIA Standards Taskforce Members. Vision science and its applications, “Standards for reporting the optical aberrations of eyes,” J. Refract. Surg. 18(5), S652–S660 (2002).
[PubMed]

2000 (1)

M. J. Booth and T. Wilson, “Strategies for the compensation of specimen-induced spherical aberration in confocal microscopy of skin,” J. Microsc. 200(1), 68–74 (2000).
[Crossref] [PubMed]

1998 (1)

M. J. Booth, M. A. A. Neil, and T. Wilson, “Aberration correction for confocal imaging in refractive-index-mismatched media,” J. Microsc. 192(2), 90–98 (1998).
[Crossref]

1997 (2)

D. H. Brainard, “The psychophysics toolbox,” Spat. Vis. 10(4), 433–436 (1997).
[Crossref] [PubMed]

D. G. Pelli, “The VideoToolbox software for visual psychophysics: transforming numbers into movies,” Spat. Vis. 10(4), 437–442 (1997).
[Crossref] [PubMed]

1993 (1)

M. Firbank and D. T. Delpy, “A design for a stable and reproducible phantom for use in near infra-red imaging and spectroscopy,” Phys. Med. Biol. 38(6), 847–853 (1993).
[Crossref]

1982 (1)

Aoki, I.

K. Masamoto, Y. Tomita, H. Toriumi, I. Aoki, M. Unekawa, H. Takuwa, Y. Itoh, N. Suzuki, and I. Kanno, “Repeated longitudinal in vivo imaging of neuro-glio-vascular unit at the peripheral boundary of ischemia in mouse cerebral cortex,” Neuroscience 212, 190–200 (2012).
[Crossref] [PubMed]

Applegate, R. A.

L. N. Thibos, R. A. Applegate, J. T. Schwiegerling, R. Webb, and VSIA Standards Taskforce Members. Vision science and its applications, “Standards for reporting the optical aberrations of eyes,” J. Refract. Surg. 18(5), S652–S660 (2002).
[PubMed]

Araya, R.

V. Nikolenko, B. O. Watson, R. Araya, A. Woodruff, D. S. Peterka, and R. Yuste, “SLM microscopy: scanless two-photon imaging and photostimulation with spatial light modulators,” Front. Neural Circuits 2, 5 (2008).
[Crossref] [PubMed]

Asfaha, S.

L. E. Grosberg, A. J. Radosevich, S. Asfaha, T. C. Wang, and E. M. Hillman, “Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral two-photon microscopy,” PLoS One 6(5), e19925 (2011).
[Crossref] [PubMed]

Azucena, O.

Beaurepaire, E.

Beltramo, R.

Benfenati, F.

Betzig, E.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (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]

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proceedings of the National Academy of Sciences (2011).

Blau, A.

Boccara, A. C.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. C. Boccara, and S. Gigan, “Measuring the Transmission Matrix in Optics: An Approach to the Study and Control of Light Propagation in Disordered Media,” Phys. Rev. Lett. 104(10), 100601 (2010).
[Crossref] [PubMed]

Booth, M.

A. Thayil, T. Watanabe, A. Jesacher, T. Wilson, S. Srinivas, and M. Booth, “Long-term imaging of mouse embryos using adaptive harmonic generation microscopy,” J. Biomed. Opt. 16, 046018 (2011).

Booth, M. J.

D. Débarre, E. J. Botcherby, T. Watanabe, S. Srinivas, M. J. Booth, and T. Wilson, “Image-based adaptive optics for two-photon microscopy,” Opt. Lett. 34(16), 2495–2497 (2009).
[Crossref] [PubMed]

M. J. Booth and T. Wilson, “Strategies for the compensation of specimen-induced spherical aberration in confocal microscopy of skin,” J. Microsc. 200(1), 68–74 (2000).
[Crossref] [PubMed]

M. J. Booth, M. A. A. Neil, and T. Wilson, “Aberration correction for confocal imaging in refractive-index-mismatched media,” J. Microsc. 192(2), 90–98 (1998).
[Crossref]

Botcherby, E. J.

Bouchard, M. B.

Brainard, D. H.

D. H. Brainard, “The psychophysics toolbox,” Spat. Vis. 10(4), 433–436 (1997).
[Crossref] [PubMed]

Brazhe, A.

C. Mathiesen, A. Brazhe, K. Thomsen, and M. Lauritzen, “Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen,” J. Cereb. Blood Flow Metab. 33(2), 161–169 (2013).
[Crossref] [PubMed]

Bromberg, Y.

O. Katz, E. Small, Y. Bromberg, and Y. Silberberg, “Focusing and compression of ultrashort pulses through scattering media,” Nat. Photonics 5(6), 372–377 (2011).
[Crossref]

Bronner, M. E.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[Crossref] [PubMed]

Burgess, S. A.

Carminati, R.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. C. Boccara, and S. Gigan, “Measuring the Transmission Matrix in Optics: An Approach to the Study and Control of Light Propagation in Disordered Media,” Phys. Rev. Lett. 104(10), 100601 (2010).
[Crossref] [PubMed]

Cauli, B.

A. F. H. McCaslin, B. R. Chen, A. J. Radosevich, B. Cauli, and E. M. C. Hillman, “In vivo 3D morphology of astrocyte-vasculature interactions in the somatosensory cortex: implications for neurovascular coupling,” J. Cereb. Blood Flow Metab. 31(3), 795–806 (2011).
[Crossref] [PubMed]

Chen, B. R.

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]

Cooper, P. R.

Cui, M.

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proceedings of the National Academy of Sciences (2012).
[Crossref]

Dal Maschio, M.

Débarre, D.

Delpy, D. T.

M. Firbank and D. T. Delpy, “A design for a stable and reproducible phantom for use in near infra-red imaging and spectroscopy,” Phys. Med. Biol. 38(6), 847–853 (1993).
[Crossref]

Difato, F.

Engerer, P.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[Crossref] [PubMed]

Facomprez, A.

Fellin, T.

Fink, M.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. C. Boccara, and S. Gigan, “Measuring the Transmission Matrix in Optics: An Approach to the Study and Control of Light Propagation in Disordered Media,” Phys. Rev. Lett. 104(10), 100601 (2010).
[Crossref] [PubMed]

Firbank, M.

M. Firbank and D. T. Delpy, “A design for a stable and reproducible phantom for use in near infra-red imaging and spectroscopy,” Phys. Med. Biol. 38(6), 847–853 (1993).
[Crossref]

Germain, R. N.

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proceedings of the National Academy of Sciences (2012).
[Crossref]

Gigan, S.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. C. Boccara, and S. Gigan, “Measuring the Transmission Matrix in Optics: An Approach to the Study and Control of Light Propagation in Disordered Media,” Phys. Rev. Lett. 104(10), 100601 (2010).
[Crossref] [PubMed]

Grosberg, L. E.

L. E. Grosberg, B. R. Chen, and E. M. C. Hillman, “Simultaneous multiplane in vivo nonlinear microscopy using spectral encoding,” Opt. Lett. 37(14), 2967–2969 (2012).
[Crossref] [PubMed]

L. E. Grosberg, A. J. Radosevich, S. Asfaha, T. C. Wang, and E. M. Hillman, “Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral two-photon microscopy,” PLoS One 6(5), e19925 (2011).
[Crossref] [PubMed]

Guan, Y.

Helmchen, F.

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).
[Crossref] [PubMed]

Hillman, E. M.

L. E. Grosberg, A. J. Radosevich, S. Asfaha, T. C. Wang, and E. M. Hillman, “Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral two-photon microscopy,” PLoS One 6(5), e19925 (2011).
[Crossref] [PubMed]

Hillman, E. M. C.

Itoh, Y.

K. Masamoto, Y. Tomita, H. Toriumi, I. Aoki, M. Unekawa, H. Takuwa, Y. Itoh, N. Suzuki, and I. Kanno, “Repeated longitudinal in vivo imaging of neuro-glio-vascular unit at the peripheral boundary of ischemia in mouse cerebral cortex,” Neuroscience 212, 190–200 (2012).
[Crossref] [PubMed]

Jesacher, A.

A. Thayil, T. Watanabe, A. Jesacher, T. Wilson, S. Srinivas, and M. Booth, “Long-term imaging of mouse embryos using adaptive harmonic generation microscopy,” J. Biomed. Opt. 16, 046018 (2011).

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]

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proceedings of the National Academy of Sciences (2011).

Kanno, I.

K. Masamoto, Y. Tomita, H. Toriumi, I. Aoki, M. Unekawa, H. Takuwa, Y. Itoh, N. Suzuki, and I. Kanno, “Repeated longitudinal in vivo imaging of neuro-glio-vascular unit at the peripheral boundary of ischemia in mouse cerebral cortex,” Neuroscience 212, 190–200 (2012).
[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, Y. Bromberg, and Y. Silberberg, “Focusing and compression of ultrashort pulses through scattering media,” Nat. Photonics 5(6), 372–377 (2011).
[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.

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).
[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]

Kirchhoff, F.

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).
[Crossref] [PubMed]

Kissel, M.

Kubby, J.

Lauritzen, M.

C. Mathiesen, A. Brazhe, K. Thomsen, and M. Lauritzen, “Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen,” J. Cereb. Blood Flow Metab. 33(2), 161–169 (2013).
[Crossref] [PubMed]

Lerosey, G.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. C. Boccara, and S. Gigan, “Measuring the Transmission Matrix in Optics: An Approach to the Study and Control of Light Propagation in Disordered Media,” Phys. Rev. Lett. 104(10), 100601 (2010).
[Crossref] [PubMed]

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]

Mahou, P.

Masamoto, K.

K. Masamoto, Y. Tomita, H. Toriumi, I. Aoki, M. Unekawa, H. Takuwa, Y. Itoh, N. Suzuki, and I. Kanno, “Repeated longitudinal in vivo imaging of neuro-glio-vascular unit at the peripheral boundary of ischemia in mouse cerebral cortex,” Neuroscience 212, 190–200 (2012).
[Crossref] [PubMed]

Mathiesen, C.

C. Mathiesen, A. Brazhe, K. Thomsen, and M. Lauritzen, “Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen,” J. Cereb. Blood Flow Metab. 33(2), 161–169 (2013).
[Crossref] [PubMed]

McCaslin, A. F. H.

A. F. H. McCaslin, B. R. Chen, A. J. Radosevich, B. Cauli, and E. M. C. Hillman, “In vivo 3D morphology of astrocyte-vasculature interactions in the somatosensory cortex: implications for neurovascular coupling,” J. Cereb. Blood Flow Metab. 31(3), 795–806 (2011).
[Crossref] [PubMed]

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]

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (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]

Misgeld, T.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[Crossref] [PubMed]

Mosk, A. P.

Mumm, J.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[Crossref] [PubMed]

Neil, M. A. A.

M. J. Booth, M. A. A. Neil, and T. Wilson, “Aberration correction for confocal imaging in refractive-index-mismatched media,” J. Microsc. 192(2), 90–98 (1998).
[Crossref]

Nikolenko, V.

V. Nikolenko, B. O. Watson, R. Araya, A. Woodruff, D. S. Peterka, and R. Yuste, “SLM microscopy: scanless two-photon imaging and photostimulation with spatial light modulators,” Front. Neural Circuits 2, 5 (2008).
[Crossref] [PubMed]

Nimmerjahn, A.

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).
[Crossref] [PubMed]

Norton, A.

Pelli, D. G.

D. G. Pelli, “The VideoToolbox software for visual psychophysics: transforming numbers into movies,” Spat. Vis. 10(4), 437–442 (1997).
[Crossref] [PubMed]

Peterka, D. S.

V. Nikolenko, B. O. Watson, R. Araya, A. Woodruff, D. S. Peterka, and R. Yuste, “SLM microscopy: scanless two-photon imaging and photostimulation with spatial light modulators,” Front. Neural Circuits 2, 5 (2008).
[Crossref] [PubMed]

Popoff, S. M.

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. C. Boccara, and S. Gigan, “Measuring the Transmission Matrix in Optics: An Approach to the Study and Control of Light Propagation in Disordered Media,” Phys. Rev. Lett. 104(10), 100601 (2010).
[Crossref] [PubMed]

Radosevich, A. J.

L. E. Grosberg, A. J. Radosevich, S. Asfaha, T. C. Wang, and E. M. Hillman, “Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral two-photon microscopy,” PLoS One 6(5), e19925 (2011).
[Crossref] [PubMed]

A. F. H. McCaslin, B. R. Chen, A. J. Radosevich, B. Cauli, and E. M. C. Hillman, “In vivo 3D morphology of astrocyte-vasculature interactions in the somatosensory cortex: implications for neurovascular coupling,” J. Cereb. Blood Flow Metab. 31(3), 795–806 (2011).
[Crossref] [PubMed]

A. J. Radosevich, M. B. Bouchard, S. A. Burgess, B. R. Chen, and E. M. C. Hillman, “Hyperspectral in vivo two-photon microscopy of intrinsic contrast,” Opt. Lett. 33(18), 2164–2166 (2008).
[Crossref] [PubMed]

Sato, T. R.

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proceedings of the National Academy of Sciences (2011).

Saxena, A.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[Crossref] [PubMed]

Schanne-Klein, M.-C.

Schwiegerling, J. T.

L. N. Thibos, R. A. Applegate, J. T. Schwiegerling, R. Webb, and VSIA Standards Taskforce Members. Vision science and its applications, “Standards for reporting the optical aberrations of eyes,” J. Refract. Surg. 18(5), S652–S660 (2002).
[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, Y. Bromberg, and Y. Silberberg, “Focusing and compression of ultrashort pulses through scattering media,” Nat. Photonics 5(6), 372–377 (2011).
[Crossref]

Small, E.

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, Y. Bromberg, and Y. Silberberg, “Focusing and compression of ultrashort pulses through scattering media,” Nat. Photonics 5(6), 372–377 (2011).
[Crossref]

Srinivas, S.

A. Thayil, T. Watanabe, A. Jesacher, T. Wilson, S. Srinivas, and M. Booth, “Long-term imaging of mouse embryos using adaptive harmonic generation microscopy,” J. Biomed. Opt. 16, 046018 (2011).

D. Débarre, E. J. Botcherby, T. Watanabe, S. Srinivas, M. J. Booth, and T. Wilson, “Image-based adaptive optics for two-photon microscopy,” Opt. Lett. 34(16), 2495–2497 (2009).
[Crossref] [PubMed]

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]

Suzuki, N.

K. Masamoto, Y. Tomita, H. Toriumi, I. Aoki, M. Unekawa, H. Takuwa, Y. Itoh, N. Suzuki, and I. Kanno, “Repeated longitudinal in vivo imaging of neuro-glio-vascular unit at the peripheral boundary of ischemia in mouse cerebral cortex,” Neuroscience 212, 190–200 (2012).
[Crossref] [PubMed]

Takuwa, H.

K. Masamoto, Y. Tomita, H. Toriumi, I. Aoki, M. Unekawa, H. Takuwa, Y. Itoh, N. Suzuki, and I. Kanno, “Repeated longitudinal in vivo imaging of neuro-glio-vascular unit at the peripheral boundary of ischemia in mouse cerebral cortex,” Neuroscience 212, 190–200 (2012).
[Crossref] [PubMed]

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,” Proceedings of the National Academy of Sciences (2012).
[Crossref]

Tao, X.

Thayil, A.

A. Thayil, T. Watanabe, A. Jesacher, T. Wilson, S. Srinivas, and M. Booth, “Long-term imaging of mouse embryos using adaptive harmonic generation microscopy,” J. Biomed. Opt. 16, 046018 (2011).

Thibos, L. N.

L. N. Thibos, R. A. Applegate, J. T. Schwiegerling, R. Webb, and VSIA Standards Taskforce Members. Vision science and its applications, “Standards for reporting the optical aberrations of eyes,” J. Refract. Surg. 18(5), S652–S660 (2002).
[PubMed]

Thomsen, K.

C. Mathiesen, A. Brazhe, K. Thomsen, and M. Lauritzen, “Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen,” J. Cereb. Blood Flow Metab. 33(2), 161–169 (2013).
[Crossref] [PubMed]

Tomita, Y.

K. Masamoto, Y. Tomita, H. Toriumi, I. Aoki, M. Unekawa, H. Takuwa, Y. Itoh, N. Suzuki, and I. Kanno, “Repeated longitudinal in vivo imaging of neuro-glio-vascular unit at the peripheral boundary of ischemia in mouse cerebral cortex,” Neuroscience 212, 190–200 (2012).
[Crossref] [PubMed]

Toriumi, H.

K. Masamoto, Y. Tomita, H. Toriumi, I. Aoki, M. Unekawa, H. Takuwa, Y. Itoh, N. Suzuki, and I. Kanno, “Repeated longitudinal in vivo imaging of neuro-glio-vascular unit at the peripheral boundary of ischemia in mouse cerebral cortex,” Neuroscience 212, 190–200 (2012).
[Crossref] [PubMed]

Unekawa, M.

K. Masamoto, Y. Tomita, H. Toriumi, I. Aoki, M. Unekawa, H. Takuwa, Y. Itoh, N. Suzuki, and I. Kanno, “Repeated longitudinal in vivo imaging of neuro-glio-vascular unit at the peripheral boundary of ischemia in mouse cerebral cortex,” Neuroscience 212, 190–200 (2012).
[Crossref] [PubMed]

Vellekoop, I. M.

Wang, C.

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]

Wang, K.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[Crossref] [PubMed]

Wang, T. C.

L. E. Grosberg, A. J. Radosevich, S. Asfaha, T. C. Wang, and E. M. Hillman, “Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral two-photon microscopy,” PLoS One 6(5), e19925 (2011).
[Crossref] [PubMed]

Watanabe, T.

A. Thayil, T. Watanabe, A. Jesacher, T. Wilson, S. Srinivas, and M. Booth, “Long-term imaging of mouse embryos using adaptive harmonic generation microscopy,” J. Biomed. Opt. 16, 046018 (2011).

D. Débarre, E. J. Botcherby, T. Watanabe, S. Srinivas, M. J. Booth, and T. Wilson, “Image-based adaptive optics for two-photon microscopy,” Opt. Lett. 34(16), 2495–2497 (2009).
[Crossref] [PubMed]

Watson, B. O.

V. Nikolenko, B. O. Watson, R. Araya, A. Woodruff, D. S. Peterka, and R. Yuste, “SLM microscopy: scanless two-photon imaging and photostimulation with spatial light modulators,” Front. Neural Circuits 2, 5 (2008).
[Crossref] [PubMed]

Webb, R.

L. N. Thibos, R. A. Applegate, J. T. Schwiegerling, R. Webb, and VSIA Standards Taskforce Members. Vision science and its applications, “Standards for reporting the optical aberrations of eyes,” J. Refract. Surg. 18(5), S652–S660 (2002).
[PubMed]

Wilson, T.

A. Thayil, T. Watanabe, A. Jesacher, T. Wilson, S. Srinivas, and M. Booth, “Long-term imaging of mouse embryos using adaptive harmonic generation microscopy,” J. Biomed. Opt. 16, 046018 (2011).

D. Débarre, E. J. Botcherby, T. Watanabe, S. Srinivas, M. J. Booth, and T. Wilson, “Image-based adaptive optics for two-photon microscopy,” Opt. Lett. 34(16), 2495–2497 (2009).
[Crossref] [PubMed]

M. J. Booth and T. Wilson, “Strategies for the compensation of specimen-induced spherical aberration in confocal microscopy of skin,” J. Microsc. 200(1), 68–74 (2000).
[Crossref] [PubMed]

M. J. Booth, M. A. A. Neil, and T. Wilson, “Aberration correction for confocal imaging in refractive-index-mismatched media,” J. Microsc. 192(2), 90–98 (1998).
[Crossref]

Woodruff, A.

V. Nikolenko, B. O. Watson, R. Araya, A. Woodruff, D. S. Peterka, and R. Yuste, “SLM microscopy: scanless two-photon imaging and photostimulation with spatial light modulators,” Front. Neural Circuits 2, 5 (2008).
[Crossref] [PubMed]

Yuste, R.

V. Nikolenko, B. O. Watson, R. Araya, A. Woodruff, D. S. Peterka, and R. Yuste, “SLM microscopy: scanless two-photon imaging and photostimulation with spatial light modulators,” Front. Neural Circuits 2, 5 (2008).
[Crossref] [PubMed]

Zeng, J.

Appl. Opt. (1)

Biomed. Opt. Express (1)

Front. Neural Circuits (1)

V. Nikolenko, B. O. Watson, R. Araya, A. Woodruff, D. S. Peterka, and R. Yuste, “SLM microscopy: scanless two-photon imaging and photostimulation with spatial light modulators,” Front. Neural Circuits 2, 5 (2008).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

A. Thayil, T. Watanabe, A. Jesacher, T. Wilson, S. Srinivas, and M. Booth, “Long-term imaging of mouse embryos using adaptive harmonic generation microscopy,” J. Biomed. Opt. 16, 046018 (2011).

J. Cereb. Blood Flow Metab. (2)

A. F. H. McCaslin, B. R. Chen, A. J. Radosevich, B. Cauli, and E. M. C. Hillman, “In vivo 3D morphology of astrocyte-vasculature interactions in the somatosensory cortex: implications for neurovascular coupling,” J. Cereb. Blood Flow Metab. 31(3), 795–806 (2011).
[Crossref] [PubMed]

C. Mathiesen, A. Brazhe, K. Thomsen, and M. Lauritzen, “Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen,” J. Cereb. Blood Flow Metab. 33(2), 161–169 (2013).
[Crossref] [PubMed]

J. Microsc. (2)

M. J. Booth, M. A. A. Neil, and T. Wilson, “Aberration correction for confocal imaging in refractive-index-mismatched media,” J. Microsc. 192(2), 90–98 (1998).
[Crossref]

M. J. Booth and T. Wilson, “Strategies for the compensation of specimen-induced spherical aberration in confocal microscopy of skin,” J. Microsc. 200(1), 68–74 (2000).
[Crossref] [PubMed]

J. Refract. Surg. (1)

L. N. Thibos, R. A. Applegate, J. T. Schwiegerling, R. Webb, and VSIA Standards Taskforce Members. Vision science and its applications, “Standards for reporting the optical aberrations of eyes,” J. Refract. Surg. 18(5), S652–S660 (2002).
[PubMed]

Nat. Methods (4)

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[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]

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]

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods 1(1), 31–37 (2004).
[Crossref] [PubMed]

Nat. Photonics (1)

O. Katz, E. Small, Y. Bromberg, and Y. Silberberg, “Focusing and compression of ultrashort pulses through scattering media,” Nat. Photonics 5(6), 372–377 (2011).
[Crossref]

Neuroscience (1)

K. Masamoto, Y. Tomita, H. Toriumi, I. Aoki, M. Unekawa, H. Takuwa, Y. Itoh, N. Suzuki, and I. Kanno, “Repeated longitudinal in vivo imaging of neuro-glio-vascular unit at the peripheral boundary of ischemia in mouse cerebral cortex,” Neuroscience 212, 190–200 (2012).
[Crossref] [PubMed]

Opt. Express (2)

Opt. Lett. (5)

Optica (1)

Phys. Med. Biol. (1)

M. Firbank and D. T. Delpy, “A design for a stable and reproducible phantom for use in near infra-red imaging and spectroscopy,” Phys. Med. Biol. 38(6), 847–853 (1993).
[Crossref]

Phys. Rev. Lett. (1)

S. M. Popoff, G. Lerosey, R. Carminati, M. Fink, A. C. Boccara, and S. Gigan, “Measuring the Transmission Matrix in Optics: An Approach to the Study and Control of Light Propagation in Disordered Media,” Phys. Rev. Lett. 104(10), 100601 (2010).
[Crossref] [PubMed]

PLoS One (1)

L. E. Grosberg, A. J. Radosevich, S. Asfaha, T. C. Wang, and E. M. Hillman, “Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral two-photon microscopy,” PLoS One 6(5), e19925 (2011).
[Crossref] [PubMed]

Spat. Vis. (2)

D. G. Pelli, “The VideoToolbox software for visual psychophysics: transforming numbers into movies,” Spat. Vis. 10(4), 437–442 (1997).
[Crossref] [PubMed]

D. H. Brainard, “The psychophysics toolbox,” Spat. Vis. 10(4), 433–436 (1997).
[Crossref] [PubMed]

Other (6)

M. Kleiner, D. Brainard, and D. Pelli, “What’s new in Psychtoolbox-3?” Perception 36 (2007).

M. Born, E. Wolf, A. B. Bhatia, D. Gabor, A. R. Stokes, A. M. Taylor, P. A. Wayman, and W. L. Wilcock, Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light (Pergamon Press, 1987), pp. 464–490.

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proceedings of the National Academy of Sciences (2011).

J. Tang, R. N. Germain, and M. Cui, “Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique,” Proceedings of the National Academy of Sciences (2012).
[Crossref]

C. Xu and W. W. Webb, “Multiphoton excitation of molecular fluorophores and nonlinear laser microscopy,” in Topics in Fluorescence Spectroscopy (Springer, 2002), pp. 471–540.

M. J. Erickson, “Introduction to combinatorics,” in Wiley-Interscience Series in Discrete Mathematics and Optimization (Wiley, New York, 1996), pp. 170–176.

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Figures (8)

Fig. 1
Fig. 1

Optical Setup. The x and y galvanometer mirrors (G), the spatial light modulator (LCSLM) and the back aperture of the objective (OBJ) are in conjugate planes.

Fig. 2
Fig. 2

Wavefront Optimization Scheme. At the beginning, the basis index i and the scale factor j are set to 1. Steps 1,2: A set of correction functions and parameters W (maximum weight), ∆W (step size), and α (acceptance threshold are chosen). Step 3: N weight values wn (which includes 0) are generated based on the parameters set in step 2. These weight values are scaled by an integer j based on the results of the previous iteration. Step 4: The ith basis function is loaded and scaled by the weight values generated above to generate N functions. Step 5: The N functions generated in the previous step are summed with the correction of the previous iteration and phase wrapped to generate N trial solutions Φn. Step 6: The functions are up-scaled and addressed one by one and the corresponding 2PEF signal Si is recorded. Step 7: The ratio between the maximum signal Smax to the signal S0 corresponding to a weight of 0 is compared to α. Step 9: (optional) attempts to detect incorrect decisions caused by signal fluctuations. Step 10-11: If step 7 yielded a positive result, the function corresponding to the maximum signal is set as the current correction and the scaling factor j is incremented by 1. This causes the scheme to perform another optimization cycle using the same basis function but with the weight values scaled by 1/j. Step 8: If step 7 did not yield a positive result, the variable i is incremented and the scale-factor j is reset so that the scheme moves on to the next basis function.

Fig. 3
Fig. 3

In and out-of-focus corrections: Aberration correction performed on a 4 micron diameter bead embedded in a scattering epoxy phantom at a depth of ~100 μm with the bead initially in-focus (left panel) and out-of-focus (right panel). Axial stacks were acquired with and without the correction applied. Optimization was achieved for both the in-focus and out-of-focus bead. In both cases, the optimized focus was formed near the center of the bead. (A,B) Schematics showing the optimization process. (C,D) Max intensity projections of the axial stack to the x-y plane (MIP-xy). (E,G) Peak signal measured at each plane with and without the correction applied as a function of depth. ‘^’ marks the approximate location of the focus prior to optimization. (F,H) Final correction applied to the LCSLM. (I) Schematic of the sample. Scale bars = 10 µm. λ = 755 nm. Configuration: Sweeping Beam.

Fig. 4
Fig. 4

Comparing bases for scattering corrections: Comparing optimization performed with Zernike vs. Hadamard functions on a scattered excitation beam. Short optimization: Correcting function set Z16 (Zernike) and H256-16 (Hadamard). Long Optimization: Correcting function set Z60 (Zernike) and H256-60 (Hadamard). (A-E) are maximum intensity projections to the x-y plane (MIP-xy). (A) Uncorrected. (B) After fast optimization using Zernike and (C) Hadamard functions. (D) After slow optimization with Zernike and (E) Hadamard functions. (F-I) are the corrections corresponding to (B-E) respectively. (J) shows the sample setup and (K) shows the axial peak signal variation with depth before and after correction. λ = 850 nm. Configuration: Standing Beam. Scale bars = 10 µm.

Fig. 5
Fig. 5

Comparison of optimizations performed on 4 micron diameter beads embedded in various samples: The functions were picked to match the expected wavefront error. (A) System and coverslip correction. (B) Spherical aberration correction. (C) Scattering induced by chicken tissue. Axial stacks were acquired with and without the correction applied. Each column shows the sample schematic (row 1), maximum intensity projection to the x-y plane (MIP-xy) (row 2), peak signal variation with depth (row 3) and the correction applied to the LCSLM (row 4). λ = 755 nm (A, B) and λ = 850 nm (C). Configuration: Sweeping Beam (A,B) and Standing Beam (C). Scale bars = 10 µm.

Fig. 6
Fig. 6

Cranial window corrections: A correction was performed using a 4 µm diameter bead placed underneath the window on the surface of the dura. The correction obtained using the bead was applied to image astrocytes near the surface of the brain. Axial stacks were acquired with and without the correction applied. (A) Schematic showing the sample setup. (B) Maximum intensity projections to the x-z plane of the bead used for optimization. (C) Peak signal variation with depth for the bead. (D) The final correction applied to the LCSLM. (E,G) Max intensity projections to the x-y plane of astrocytes at a z≈65 µm with and without correction. (F,H) Signal variation along the dashed lines in (E) and (G). Optimization time was 18 seconds. λ = 850 nm. Configuration: Sweeping Beam. Scale bars = 10 µm.

Fig. 7
Fig. 7

In-vivo corrections using astrocytes at various depths: (A) A correction was performed using the astrocyte at the center of the field of view (indicated by a ‘*’ in A0). An axial stack of this field of view (approximately 120x120x19 µm) was then acquired with and without this correction. (A0) shows the max-intensity projection to the x-y plane (MIP-xy). (A1-A3) shows the MIP–xy and signal cross sections of three astrocytes in the volume located at z≈35 µm, z≈40 µm and z≈25 µm respectively, showing that the correction remains valid across the volume. In (B,C,D), a correction was performed on the same astrocyte as imaged, for a range of astrocytes at different depths. The final LCSLM correction pattern is shown next to the signal variation plot. Function sets used for optimization were: (A) Z16, (B) Z16 followed by ZR, (C) ZR and (D) ZR. Optimization time was (A) 19 seconds, (B) 37 seconds, (C) 6 seconds and (D) 6 seconds. λ = 850 nm. Configuration: Sweeping Beam. Scale bars = 10 µm.

Fig. 8
Fig. 8

Spatial applicability of a single correction. Lateral: The image on the top left is a 3-D rendering showing the imaged volume indicating three astrocytes and a blood vessel (outlined in dashed white lines). A correction generated using an astrocyte (A) was applied to the same astrocyte (A), two nearby astrocytes (hidden by a vessel) (B,C), and another astrocyte ~478 µm away laterally (D). The corresponding correction is (E). Optimization time was 22 seconds. Axial: A correction generated at z = 30 µm was applied at two other depths (G,H). The corresponding correction is shown in Fig. 7(A). λ = 850 nm. Configuration: Sweeping Beam. Scale bars = 10 µm.

Tables (1)

Tables Icon

Table 1 Functions used for optimization

Equations (6)

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

I peak = 2 P ave τ p fπ w 0 2
Z n m ={ N n m R n | m | (ρ)cos(mθ);m0 N n m R n | m | (ρ)sin(mθ);m<0
R n | m | (ρ)= s=0 (n| m |)/2 (1) s (ns)! s![0.5(n+| m |s]![0.5(n| m |)s]! ρ n2s
k= n(n+2)+m 2
H n H n T =n I n
H 2n =[ H n H n H n H n ]

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