Abstract

Inherent aberrations of gradient index (GRIN) lenses used in fluorescence endomicroscopes deteriorate imaging performance. Using adaptive optics, we characterized and corrected the on-axis and off-axis aberrations of a GRIN lens with NA 0.8 at multiple focal planes. We demonstrated a rotational-transformation-based correction procedure, which enlarged the imaging area with diffraction-limited resolution with only two aberration measurements. 204.8 × 204.8 µm2 images of fluorescent beads and brain slices before and after AO corrections were obtained, with evident improvements in both image sharpness and brightness after AO correction. These results show great promises of applying adaptive optical two-photon fluorescence endomicroscope to three-dimensional (3D) imaging.

© 2013 Optical Society of America

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References

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2013 (1)

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics7(3), 205–209 (2013).
[CrossRef]

2012 (6)

T. A. Murray and M. J. Levene, “Singlet gradient index lens for deep in vivo multiphoton microscopy,” J. Biomed. Opt.17(2), 021106 (2012).
[CrossRef] [PubMed]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt.17(4), 040505 (2012).
[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,” Proc. Natl. Acad. Sci. U.S.A.109(1), 22–27 (2012).
[CrossRef] [PubMed]

C. Grienberger and A. Konnerth, “Imaging calcium in neurons,” Neuron73(5), 862–885 (2012).
[CrossRef] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express3(5), 1077–1085 (2012).
[CrossRef] [PubMed]

C. Wang and N. Ji, “Pupil-segmentation-based adaptive optical correction of a high-numerical-aperture gradient refractive index lens for two-photon fluorescence endoscopy,” Opt. Lett.37(11), 2001–2003 (2012).
[CrossRef] [PubMed]

2011 (4)

W. M. Lee and S. H. Yun, “Adaptive aberration correction of GRIN lenses for confocal endomicroscopy,” Opt. Lett.36(23), 4608–4610 (2011).
[CrossRef] [PubMed]

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

F. Bortoletto, C. Bonoli, P. Panizzolo, C. D. Ciubotaru, and F. Mammano, “Multiphoton fluorescence microscopy with GRIN objective aberration correction by low order adaptive optics,” PLoS ONE6(7), e22321 (2011).
[CrossRef] [PubMed]

C. Wang, L. Qiao, F. He, Y. Cheng, and Z. Xu, “Extension of imaging depth in two-photon fluorescence microscopy using a long-wavelength high-pulse-energy femtosecond laser source,” J. Microsc.243(2), 179–183 (2011).
[CrossRef] [PubMed]

2010 (2)

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods7(2), 141–147 (2010).
[CrossRef] [PubMed]

P. Kner, J. W. Sedat, D. A. Agard, and Z. Kam, “High-resolution wide-field microscopy with adaptive opticsfor spherical aberration correction and motionless focusing,” J. Microsc-Oxford237(2), 136–147 (2010).
[CrossRef]

2009 (3)

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods6(7), 511–512 (2009).
[CrossRef] [PubMed]

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, and B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt.14(1), 010508 (2009).
[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. Express17(16), 13354–13364 (2009).
[CrossRef] [PubMed]

2008 (1)

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

2005 (1)

H. Alencar, U. Mahmood, Y. Kawano, T. Hirata, and R. Weissleder, “Novel multiwavelength microscopic scanner for mouse imaging,” Neoplasia7(11), 977–983 (2005).
[CrossRef] [PubMed]

2004 (2)

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol.91(4), 1908–1912 (2004).
[CrossRef] [PubMed]

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)

1986 (1)

Agard, D. A.

P. Kner, J. W. Sedat, D. A. Agard, and Z. Kam, “High-resolution wide-field microscopy with adaptive opticsfor spherical aberration correction and motionless focusing,” J. Microsc-Oxford237(2), 136–147 (2010).
[CrossRef]

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]

Alencar, H.

H. Alencar, U. Mahmood, Y. Kawano, T. Hirata, and R. Weissleder, “Novel multiwavelength microscopic scanner for mouse imaging,” Neoplasia7(11), 977–983 (2005).
[CrossRef] [PubMed]

Attardo, A.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Baldacchini, T.

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, and B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt.14(1), 010508 (2009).
[CrossRef] [PubMed]

Balu, M.

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, and B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt.14(1), 010508 (2009).
[CrossRef] [PubMed]

Barretto, R. P. J.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods6(7), 511–512 (2009).
[CrossRef] [PubMed]

Betzig, E.

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proc. Natl. Acad. Sci. U.S.A.109(1), 22–27 (2012).
[CrossRef] [PubMed]

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods7(2), 141–147 (2010).
[CrossRef] [PubMed]

Bonoli, C.

F. Bortoletto, C. Bonoli, P. Panizzolo, C. D. Ciubotaru, and F. Mammano, “Multiphoton fluorescence microscopy with GRIN objective aberration correction by low order adaptive optics,” PLoS ONE6(7), e22321 (2011).
[CrossRef] [PubMed]

Bortoletto, F.

F. Bortoletto, C. Bonoli, P. Panizzolo, C. D. Ciubotaru, and F. Mammano, “Multiphoton fluorescence microscopy with GRIN objective aberration correction by low order adaptive optics,” PLoS ONE6(7), e22321 (2011).
[CrossRef] [PubMed]

Brown, C. M.

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express3(5), 1077–1085 (2012).
[CrossRef] [PubMed]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt.17(4), 040505 (2012).
[CrossRef] [PubMed]

Capps, G.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Carter, J.

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, and B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt.14(1), 010508 (2009).
[CrossRef] [PubMed]

Cheng, Y.

C. Wang, L. Qiao, F. He, Y. Cheng, and Z. Xu, “Extension of imaging depth in two-photon fluorescence microscopy using a long-wavelength high-pulse-energy femtosecond laser source,” J. Microsc.243(2), 179–183 (2011).
[CrossRef] [PubMed]

Ciubotaru, C. D.

F. Bortoletto, C. Bonoli, P. Panizzolo, C. D. Ciubotaru, and F. Mammano, “Multiphoton fluorescence microscopy with GRIN objective aberration correction by low order adaptive optics,” PLoS ONE6(7), e22321 (2011).
[CrossRef] [PubMed]

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. Photonics7(3), 205–209 (2013).
[CrossRef]

Côté, D.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

Denk, W.

Dombeck, D. A.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol.91(4), 1908–1912 (2004).
[CrossRef] [PubMed]

Durst, M. E.

Grienberger, C.

C. Grienberger and A. Konnerth, “Imaging calcium in neurons,” Neuron73(5), 862–885 (2012).
[CrossRef] [PubMed]

Hasan, M. T.

He, F.

C. Wang, L. Qiao, F. He, Y. Cheng, and Z. Xu, “Extension of imaging depth in two-photon fluorescence microscopy using a long-wavelength high-pulse-energy femtosecond laser source,” J. Microsc.243(2), 179–183 (2011).
[CrossRef] [PubMed]

Hirata, T.

H. Alencar, U. Mahmood, Y. Kawano, T. Hirata, and R. Weissleder, “Novel multiwavelength microscopic scanner for mouse imaging,” Neoplasia7(11), 977–983 (2005).
[CrossRef] [PubMed]

Horton, N. G.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics7(3), 205–209 (2013).
[CrossRef]

Howard, S. S.

Huland, D. M.

Ji, N.

C. Wang and N. Ji, “Pupil-segmentation-based adaptive optical correction of a high-numerical-aperture gradient refractive index lens for two-photon fluorescence endoscopy,” Opt. Lett.37(11), 2001–2003 (2012).
[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,” Proc. Natl. Acad. Sci. U.S.A.109(1), 22–27 (2012).
[CrossRef] [PubMed]

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods7(2), 141–147 (2010).
[CrossRef] [PubMed]

Jung, J. C.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

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. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett.28(11), 902–904 (2003).
[CrossRef] [PubMed]

Kam, Z.

P. Kner, J. W. Sedat, D. A. Agard, and Z. Kam, “High-resolution wide-field microscopy with adaptive opticsfor spherical aberration correction and motionless focusing,” J. Microsc-Oxford237(2), 136–147 (2010).
[CrossRef]

Kasischke, K. A.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol.91(4), 1908–1912 (2004).
[CrossRef] [PubMed]

Kawano, Y.

H. Alencar, U. Mahmood, Y. Kawano, T. Hirata, and R. Weissleder, “Novel multiwavelength microscopic scanner for mouse imaging,” Neoplasia7(11), 977–983 (2005).
[CrossRef] [PubMed]

Kim, P.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

Kner, P.

P. Kner, J. W. Sedat, D. A. Agard, and Z. Kam, “High-resolution wide-field microscopy with adaptive opticsfor spherical aberration correction and motionless focusing,” J. Microsc-Oxford237(2), 136–147 (2010).
[CrossRef]

Ko, T. H.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[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. Photonics7(3), 205–209 (2013).
[CrossRef]

D. Kobat, M. E. Durst, N. Nishimura, A. W. Wong, C. B. Schaffer, and C. Xu, “Deep tissue multiphoton microscopy using longer wavelength excitation,” Opt. Express17(16), 13354–13364 (2009).
[CrossRef] [PubMed]

Konnerth, A.

C. Grienberger and A. Konnerth, “Imaging calcium in neurons,” Neuron73(5), 862–885 (2012).
[CrossRef] [PubMed]

Krasieva, T. B.

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, and B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt.14(1), 010508 (2009).
[CrossRef] [PubMed]

Lee, W. M.

Levene, M. J.

T. A. Murray and M. J. Levene, “Singlet gradient index lens for deep in vivo multiphoton microscopy,” J. Biomed. Opt.17(2), 021106 (2012).
[CrossRef] [PubMed]

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol.91(4), 1908–1912 (2004).
[CrossRef] [PubMed]

Lin, C. P.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

Mahmood, U.

H. Alencar, U. Mahmood, Y. Kawano, T. Hirata, and R. Weissleder, “Novel multiwavelength microscopic scanner for mouse imaging,” Neoplasia7(11), 977–983 (2005).
[CrossRef] [PubMed]

Mammano, F.

F. Bortoletto, C. Bonoli, P. Panizzolo, C. D. Ciubotaru, and F. Mammano, “Multiphoton fluorescence microscopy with GRIN objective aberration correction by low order adaptive optics,” PLoS ONE6(7), e22321 (2011).
[CrossRef] [PubMed]

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]

Messerschmidt, B.

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods6(7), 511–512 (2009).
[CrossRef] [PubMed]

Milkie, D. E.

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods7(2), 141–147 (2010).
[CrossRef] [PubMed]

Mohanan, S.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt.17(4), 040505 (2012).
[CrossRef] [PubMed]

Molloy, R. P.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol.91(4), 1908–1912 (2004).
[CrossRef] [PubMed]

Murray, T. A.

T. A. Murray and M. J. Levene, “Singlet gradient index lens for deep in vivo multiphoton microscopy,” J. Biomed. Opt.17(2), 021106 (2012).
[CrossRef] [PubMed]

Nishimura, N.

Ouzounov, D. G.

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express3(5), 1077–1085 (2012).
[CrossRef] [PubMed]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt.17(4), 040505 (2012).
[CrossRef] [PubMed]

Panizzolo, P.

F. Bortoletto, C. Bonoli, P. Panizzolo, C. D. Ciubotaru, and F. Mammano, “Multiphoton fluorescence microscopy with GRIN objective aberration correction by low order adaptive optics,” PLoS ONE6(7), e22321 (2011).
[CrossRef] [PubMed]

Pavlova, I.

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express3(5), 1077–1085 (2012).
[CrossRef] [PubMed]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt.17(4), 040505 (2012).
[CrossRef] [PubMed]

Puoris’haag, M.

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

Qiao, L.

C. Wang, L. Qiao, F. He, Y. Cheng, and Z. Xu, “Extension of imaging depth in two-photon fluorescence microscopy using a long-wavelength high-pulse-energy femtosecond laser source,” J. Microsc.243(2), 179–183 (2011).
[CrossRef] [PubMed]

Recht, L.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Rivera, D. R.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt.17(4), 040505 (2012).
[CrossRef] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express3(5), 1077–1085 (2012).
[CrossRef] [PubMed]

Sakamoto, T.

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,” Proc. Natl. Acad. Sci. U.S.A.109(1), 22–27 (2012).
[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. Photonics7(3), 205–209 (2013).
[CrossRef]

D. Kobat, M. E. Durst, N. Nishimura, A. W. Wong, C. B. Schaffer, and C. Xu, “Deep tissue multiphoton microscopy using longer wavelength excitation,” Opt. Express17(16), 13354–13364 (2009).
[CrossRef] [PubMed]

Schnitzer, M. J.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods6(7), 511–512 (2009).
[CrossRef] [PubMed]

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. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett.28(11), 902–904 (2003).
[CrossRef] [PubMed]

Sedat, J. W.

P. Kner, J. W. Sedat, D. A. Agard, and Z. Kam, “High-resolution wide-field microscopy with adaptive opticsfor spherical aberration correction and motionless focusing,” J. Microsc-Oxford237(2), 136–147 (2010).
[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]

Theer, P.

Tromberg, B. J.

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, and B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt.14(1), 010508 (2009).
[CrossRef] [PubMed]

Wang, C.

C. Wang and N. Ji, “Pupil-segmentation-based adaptive optical correction of a high-numerical-aperture gradient refractive index lens for two-photon fluorescence endoscopy,” Opt. Lett.37(11), 2001–2003 (2012).
[CrossRef] [PubMed]

C. Wang, L. Qiao, F. He, Y. Cheng, and Z. Xu, “Extension of imaging depth in two-photon fluorescence microscopy using a long-wavelength high-pulse-energy femtosecond laser source,” J. Microsc.243(2), 179–183 (2011).
[CrossRef] [PubMed]

Wang, K.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics7(3), 205–209 (2013).
[CrossRef]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express3(5), 1077–1085 (2012).
[CrossRef] [PubMed]

Wang, T. J.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Waters, A. C.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Webb, W. W.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt.17(4), 040505 (2012).
[CrossRef] [PubMed]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express3(5), 1077–1085 (2012).
[CrossRef] [PubMed]

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol.91(4), 1908–1912 (2004).
[CrossRef] [PubMed]

Weissleder, R.

H. Alencar, U. Mahmood, Y. Kawano, T. Hirata, and R. Weissleder, “Novel multiwavelength microscopic scanner for mouse imaging,” Neoplasia7(11), 977–983 (2005).
[CrossRef] [PubMed]

Williams, W. O.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt.17(4), 040505 (2012).
[CrossRef] [PubMed]

Wise, F. W.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics7(3), 205–209 (2013).
[CrossRef]

Wong, A. W.

Xu, C.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics7(3), 205–209 (2013).
[CrossRef]

D. M. Huland, C. M. Brown, S. S. Howard, D. G. Ouzounov, I. Pavlova, K. Wang, D. R. Rivera, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using long gradient index lens multiphoton endoscopic systems,” Biomed. Opt. Express3(5), 1077–1085 (2012).
[CrossRef] [PubMed]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt.17(4), 040505 (2012).
[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. Express17(16), 13354–13364 (2009).
[CrossRef] [PubMed]

Xu, Z.

C. Wang, L. Qiao, F. He, Y. Cheng, and Z. Xu, “Extension of imaging depth in two-photon fluorescence microscopy using a long-wavelength high-pulse-energy femtosecond laser source,” J. Microsc.243(2), 179–183 (2011).
[CrossRef] [PubMed]

Yun, S. H.

W. M. Lee and S. H. Yun, “Adaptive aberration correction of GRIN lenses for confocal endomicroscopy,” Opt. Lett.36(23), 4608–4610 (2011).
[CrossRef] [PubMed]

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

Zadoyan, R.

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, and B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt.14(1), 010508 (2009).
[CrossRef] [PubMed]

Ziv, Y.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Appl. Opt. (1)

Biomed. Opt. Express (1)

J. Biomed. Opt. (4)

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt.17(4), 040505 (2012).
[CrossRef] [PubMed]

P. Kim, M. Puoris’haag, D. Côté, C. P. Lin, and S. H. Yun, “In vivo confocal and multiphoton microendoscopy,” J. Biomed. Opt.13(1), 010501 (2008).
[CrossRef] [PubMed]

M. Balu, T. Baldacchini, J. Carter, T. B. Krasieva, R. Zadoyan, and B. J. Tromberg, “Effect of excitation wavelength on penetration depth in nonlinear optical microscopy of turbid media,” J. Biomed. Opt.14(1), 010508 (2009).
[CrossRef] [PubMed]

T. A. Murray and M. J. Levene, “Singlet gradient index lens for deep in vivo multiphoton microscopy,” J. Biomed. Opt.17(2), 021106 (2012).
[CrossRef] [PubMed]

J. Microsc-Oxford (1)

P. Kner, J. W. Sedat, D. A. Agard, and Z. Kam, “High-resolution wide-field microscopy with adaptive opticsfor spherical aberration correction and motionless focusing,” J. Microsc-Oxford237(2), 136–147 (2010).
[CrossRef]

J. Microsc. (1)

C. Wang, L. Qiao, F. He, Y. Cheng, and Z. Xu, “Extension of imaging depth in two-photon fluorescence microscopy using a long-wavelength high-pulse-energy femtosecond laser source,” J. Microsc.243(2), 179–183 (2011).
[CrossRef] [PubMed]

J. Neurophysiol. (2)

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol.91(4), 1908–1912 (2004).
[CrossRef] [PubMed]

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]

Nat. Med. (1)

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med.17(2), 223–228 (2011).
[CrossRef] [PubMed]

Nat. Methods (2)

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods6(7), 511–512 (2009).
[CrossRef] [PubMed]

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods7(2), 141–147 (2010).
[CrossRef] [PubMed]

Nat. Photonics (1)

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics7(3), 205–209 (2013).
[CrossRef]

Neoplasia (1)

H. Alencar, U. Mahmood, Y. Kawano, T. Hirata, and R. Weissleder, “Novel multiwavelength microscopic scanner for mouse imaging,” Neoplasia7(11), 977–983 (2005).
[CrossRef] [PubMed]

Neuron (1)

C. Grienberger and A. Konnerth, “Imaging calcium in neurons,” Neuron73(5), 862–885 (2012).
[CrossRef] [PubMed]

Opt. Express (1)

Opt. Lett. (4)

PLoS ONE (1)

F. Bortoletto, C. Bonoli, P. Panizzolo, C. D. Ciubotaru, and F. Mammano, “Multiphoton fluorescence microscopy with GRIN objective aberration correction by low order adaptive optics,” PLoS ONE6(7), e22321 (2011).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proc. Natl. Acad. Sci. U.S.A.109(1), 22–27 (2012).
[CrossRef] [PubMed]

Other (5)

GRINTECH, GmbH, “High NA for 2-photon microscopy,” http://www.grintech.de/grin-lens-systems-for-medical-applications.html?file=tl_files/content/downloads/GRIN_High-NA_Objective-2_Photon_Microscopy . pdf.

Olympus, “Microprobe objectives,” http://www.olympusamerica.com/seg_section/seg_microprobe_objectives.asp .

C. Gomez-Reino, M. V. Perez, and C. Bao, Gradient-Index Optics (Springer-Verlag, 2002).

J. Pawley, Handbook of Biological Confocal Microscopy (Springer, 2006).

D. B. Murphy and M. W. Davidson, Fundamentals of Light Microscopy and Electronic Imaging (Wiley, 2012).

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Figures (6)

Fig. 1
Fig. 1

Schematics and characterization of on-axis aberrations. (a) Schematic diagrams of a GRIN-lens-based endomicroscope, where the GRIN lens serves as a relay lens between the microscope objective and the sample, illustrating image working distance (WD), Δd, and image field position (FP). (b-d) Focal series images of a 2 μm diameter fluorescence bead at FP(0,0) before and after AO correction for (b) Δd = −100 µm, (c) Δd = 0 µm, (d) Δd = 100 µm, respectively. The corrective wavefronts in units of waves (λ = 900 nm) are (c) for the on-axis system aberration and (b, d) the additional corrective wavefronts (residue wavefronts) to the system aberration measured in (c). Images taken without AO are digitally enhanced so that the brightest pixel in the focal series has the same value as that after AO correction. (e) Zernike decomposition of the residue wavefronts shown in (b) and (d). Z1 piston, Z2 and Z3, tip and tilt; Z4 and Z6, astigmatism; Z5, defocus; Z7 and Z10, trefoil aberration; Z8 and Z9, coma; Z13, spherical aberration. Scale bars: 5 µm.

Fig. 2
Fig. 2

Characterization of off-axis aberrations. (a-c) Focal series images of a 2 µm fluorescence bead at FP(100 µm,0) for three different image WDs (a) Δd = −100µm, (b) Δd = 0 µm, (c) Δd = 100 µm before and after AO correction. Right panel of (c) shows the axial projections of the focal series at Δd = 100 µm before and after AO correction. Images taken without AO have their brightness digitally enhanced so that both focal series images for the same FP have the same maximal signal before and after AO correction. (d) Corrective wavefronts after system aberration subtraction at the three different image WDs in units of waves (λ = 900 nm). (e) Zernike decomposition of the three corrective patterns in (d). Z1 piston, Z2 and Z3, tip and tilt; Z4 and Z6, astigmatism; Z5, defocus; Z7 and Z10, trefoil aberration; Z8 and Z9, coma; Z13, spherical aberration. (f) Fluorescence beads imaged over a large FOV at all three Δd’s before AO correction. Scale bars: (a-d) 5 µm; (f) 20 µm.

Fig. 3
Fig. 3

Summary of the aberration correction results at FP(0,0), FP(75 μm,0), and FP(100 μm,0) for all three Δd’s. (a) Signal enhancement after AO correction at the focal plane with least blur. (b-d) Integrated signal of focal series images of a 2µm fluorescence bead plotted against their axial positions before and after AO correction at all three Δd’s for each FP.

Fig. 4
Fig. 4

Comparison of focal series images of a 2µm fluorescence bead without AO, with system aberration (SA) correction only, with correction obtained via the rotational-transformation-based procedure (R45°, R90°, and R180° denotes the rotation angle used for calculation), and with experimentally measured correction for (a) FP(53 µm, 53 µm), (b) FP(0, 75 µm), (c) FP(−75 µm, 0) with Δd = 100 µm. (d) Integrated signal of the focal series images in (a-c) plotted against their axial positions, respectively. Green dash line in the leftmost panel is the normalized axial profile from R45° correction. (e) Top panel: the off-axis corrective pattern (R0°) and its rotational-transformations (R45°, R90°, and R180°). Bottom panel: Final composite correction patterns obtained by adding the SA correction to the patterns in the top panel. Dashed black circle represents the back pupil of the objective, and the red square represents the border of the SLM. Scale bar: 5 µm.

Fig. 5
Fig. 5

(a) Maximal intensity projections from focal series images of 2 µm diameter fluorescence beads obtained with two measured corrective wavefronts (SA and AO R0°, yellow labels) and seven calculated corrective patterns (AO R45°, AO R90°, AO R135°, AO R180°, AO R225°, AO R270°, and AO R315°, white labels). (b) The calculated corrective patterns significantly improve image quality, as shown in the enlarged views of two sample areas (blue and green squares in (a)) imaged without AO, with calculated corrective patterns, and with corrective patterns experimentally measured at the center of each area. Intensity profiles shown in the top and bottom line figures were measured along the blue and green lines in the images, respectively. (c) Corrective pattern at FP(X,Y) improves image quality at the opposing FP(-X,-Y), as shown in two examples where images at FP(53 µm,-53 µm) and FP(−75 µm,0) were measured using the correction patterns calculated for its their opposite FPs (FP(−53 µm,53 µm) and FP(75 µm,0), R135° and R90°), as well as with the corrective patterns experimentally measured at FP(53 µm,-53 µm) and FP(−75 µm,0). Intensity profiles were measured along the orange lines in the images. (d) Maximal intensity projections of images over an area 204.8µm × 204.8 µm taken, from top to bottom, without AO, with five correction patterns (two measured, SA and AO R0°, and three calculated, AO R45°, AO R90°, and AO R135°), and with the nine correction patterns used in (a). Scale bar: 20 µm.

Fig. 6
Fig. 6

(a) Maximal intensity projections of 10-μm-thick focal series images of a brain slice of Thy-1 line 16 mouse taken with two measured (SA and AO R0°, yellow labels) and seven calculated corrective patterns (AO R45°, AO R90°, AO R135°, AO R180°, AO R225°, AO R270°, and AO R315°, white labels). (b-c) Enlarged views centering at two off-axis locations, FP(53 µm,-53 µm) and FP(0,75 µm) (orange and purple squares in (a)) without AO and with the calculated patterns, AO R315° and AO R90°, respectively. (d) Maximal intensity projections of images over an area 204.8µm × 204.8 µm taken, from top to bottom, without AO, with five correction patterns (two measured, SA and AO R0°, and three calculated, AO R45°, AO R90°, and AO R135°), and with the nine correction patterns used in (a), respectively. Scale bar: 20 µm.

Tables (1)

Tables Icon

Table 1 Signal enhancement and axial resolution at different image WD’s before and after AO correction for a singlet GRIN lens with NA 0.45 and 3.74mm length.

Metrics