Abstract

We report the use of adaptive optics with coherent anti-Stokes Raman scattering (CARS) microscopy for label-free deep tissue imaging based on molecular vibrational spectroscopy. The setup employs a deformable membrane mirror and a random search optimization algorithm to improve signal intensity and image quality at large sample depths. We demonstrate the ability to correct for both system and sample-induced aberrations in test samples as well as in muscle tissue in order to enhance the CARS signal. The combined system and sample-induced aberration correction increased the signal by an average factor of ~3x for the test samples at a depth of 700 µm and ~6x for muscle tissue at a depth of 260 µm. The enhanced signal and higher penetration depth offered by adaptive optics will augment CARS microscopy as an in vivo and in situ biomedical imaging modality.

© 2007 Optical Society of America

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2007

2006

F. Ganikhanov, S. Carrasco, X. S. Xie, M. Katz, W. Seitz, D. Kopf, "Broadly tunable dual-wavelength light source for coherent anti-Stokes Raman scattering microscopy," Opt. Lett.,  31, 1292-1294 (2006).
[CrossRef] [PubMed]

F. Ganikhanov, C. L. Evans, B. G. Saar, and X. S. Xie, "High sensitivity vibrational imaging with frequency modulation coherent anti-Stokes Raman scattering (FM-CARS) microscopy," Opt. Lett. 31, 1872-1874 (2006).
[CrossRef] [PubMed]

X. Nan, A. M. Tonary, A. Stolow, X. S. Xie, J. P. Pezacki, "Intracellular Imaging of HCV RNA and Cellular Lipids by Using Simultaneous Two-Photon Fluorescence and Coherent Anti-Stokes Raman Scattering Microscopies," ChemBioChem 7, 1895-1897 (2006).
[CrossRef] [PubMed]

M. Rueckel, J. A. Mack-Bucher, and W. Denk, "Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing," PNAS 103, 17137 (2006).
[CrossRef] [PubMed]

S. Tang, T. B. Krasieva, Z. Chen, and B. J. Tromberg, "Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source," J. Biomed. Opt. 11,020502, (2006).
[CrossRef] [PubMed]

2005

J. J. Dirckx, L. C. Kuypers, and W. F. Decraemer, "Refractive index of tissue measured with confocal microscopy," J. Biomed. Opt. 4044014 (2005).
[CrossRef]

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côté, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," PNAS 102, 16807-16812 (2005).
[CrossRef] [PubMed]

F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2,932-940 (2005).
[CrossRef] [PubMed]

E. Dalimier and C. Dainty, "Comparative analysis of deformable mirrors for ocular adaptive optics," Opt. Express 13, 4275-4285 (2005).
[CrossRef] [PubMed]

A. J. Wright, B. A. Patterson, S. P. Poland, J. M. Girkin, G. M. Gibson, and M. J. Padgett, "Dynamic closed-loop system for focus tracking using a spatial light modulator and a deformable membrane mirror," Opt. Express 14,222-228 (2005)
[CrossRef]

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, "Exploration of the Optimisation Algorithms used in the implementation of Adaptive Optics in Confocal and Multiphoton Microscopy," Microsc. Res. Tech. 67, 36-44 (2005).
[CrossRef] [PubMed]

2004

M. Schwertner, M. J. Booth, and T. Wilson, "Characterizing specimen induced aberrations for high NA adaptive optics microscopy," Opt. Express 12,6540-6552 (2004).
[CrossRef] [PubMed]

J. X. Cheng and X. S. Xie, "Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications," J. Phys. Chem. B 108,827-840 (2004).
[CrossRef]

X. Nan, W. Y. Yan, and X. S. Xie, "CARS Microscopy: Lights Up Lipids in Living Cells," Bioph. Int. 11, 44-47 (2004).

2003

J. X. Cheng, S. Pautot, A. D. Weitz, and X. S. Xie, "Ordering of Water Molecules Between Phospholipid Bilayers Visualized by Coherent anti-Stokes Raman Scattering Microscopy," PNAS 100, 9826-9830 (2003).
[CrossRef] [PubMed]

W. R Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotech.  21,1369 - 1377 (2003)
[CrossRef]

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Real-time imaging of lymphocytes in vivo," Curr. Opin. Immunol. 15,372-377 (2003)
[CrossRef] [PubMed]

E. J. Fernández and P. Artal, "Membrane deformation mirror for adaptive optics: performance limits in visual optics," Opt. Express 11, 1056-1069 (2003).
[CrossRef] [PubMed]

P. Marsh, D. Burns, and J. Girkin, "Practical implementation of adaptive optics in multiphoton microscopy," Opt. Express 11, 1123-1130 (2003).
[CrossRef] [PubMed]

2002

J. X. Cheng, A. Volkmer, L. D. Book, X. S. Xie, "Multiplex Coherent Anti-Stokes Raman Scattering Microspectroscopy and Study of Lipid Vesicles," J. Phys. Chem. B 106, 8493 (2002).
[CrossRef]

M. J. Booth, M. A. A. Neil, R. Juskaitis, and T. Wilson, "Adaptive aberration correction in a confocal microscope," PNAS 99, 5788 (2002).
[CrossRef] [PubMed]

L. Sherman, J. Y. Ye, O. Albert, and T. B. Norris, "Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror" J. Microscopy 206, 65-71 (2002).
[CrossRef]

2001

2000

1999

L. Zhu, P.-C. Sun, D.-U. Bartsch, W. R. Freeman, and Y. Fainman, "Wave-front generation of Zernike polynomial modes with a micromachined membrane deformable mirror," App. Opt. 38, 6019-6026 (1999).
[CrossRef]

1997

G. Marques, L. Wang, S. P. Lin, S. L. Jacques, F. K. Tittel, S. L. Thomsen and J. Schwartz, "Measurement of Absorption and Scattering Spectra of Chicken Breast with Oblique Incidence Reflectometry," Proc. SPIE 2976,306-317 (1997)
[CrossRef]

Albert, O.

L. Sherman, J. Y. Ye, O. Albert, and T. B. Norris, "Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror" J. Microscopy 206, 65-71 (2002).
[CrossRef]

Artal, P.

Bartsch, D.-U.

L. Zhu, P.-C. Sun, D.-U. Bartsch, W. R. Freeman, and Y. Fainman, "Wave-front generation of Zernike polynomial modes with a micromachined membrane deformable mirror," App. Opt. 38, 6019-6026 (1999).
[CrossRef]

Book, L. D.

J. X. Cheng, A. Volkmer, L. D. Book, X. S. Xie, "Multiplex Coherent Anti-Stokes Raman Scattering Microspectroscopy and Study of Lipid Vesicles," J. Phys. Chem. B 106, 8493 (2002).
[CrossRef]

Booth, M. J.

Burns, D.

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, "Exploration of the Optimisation Algorithms used in the implementation of Adaptive Optics in Confocal and Multiphoton Microscopy," Microsc. Res. Tech. 67, 36-44 (2005).
[CrossRef] [PubMed]

P. Marsh, D. Burns, and J. Girkin, "Practical implementation of adaptive optics in multiphoton microscopy," Opt. Express 11, 1123-1130 (2003).
[CrossRef] [PubMed]

Cahalan, M. D.

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Real-time imaging of lymphocytes in vivo," Curr. Opin. Immunol. 15,372-377 (2003)
[CrossRef] [PubMed]

Carrasco, S.

Chen, Z.

S. Tang, T. B. Krasieva, Z. Chen, and B. J. Tromberg, "Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source," J. Biomed. Opt. 11,020502, (2006).
[CrossRef] [PubMed]

Cheng, J. X.

J. X. Cheng and X. S. Xie, "Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications," J. Phys. Chem. B 108,827-840 (2004).
[CrossRef]

J. X. Cheng, S. Pautot, A. D. Weitz, and X. S. Xie, "Ordering of Water Molecules Between Phospholipid Bilayers Visualized by Coherent anti-Stokes Raman Scattering Microscopy," PNAS 100, 9826-9830 (2003).
[CrossRef] [PubMed]

J. X. Cheng, A. Volkmer, L. D. Book, X. S. Xie, "Multiplex Coherent Anti-Stokes Raman Scattering Microspectroscopy and Study of Lipid Vesicles," J. Phys. Chem. B 106, 8493 (2002).
[CrossRef]

Côté, D.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côté, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," PNAS 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Dainty, C.

Dalimier, E.

Decraemer, W. F.

J. J. Dirckx, L. C. Kuypers, and W. F. Decraemer, "Refractive index of tissue measured with confocal microscopy," J. Biomed. Opt. 4044014 (2005).
[CrossRef]

Denk, W.

M. Rueckel, J. A. Mack-Bucher, and W. Denk, "Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing," PNAS 103, 17137 (2006).
[CrossRef] [PubMed]

F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2,932-940 (2005).
[CrossRef] [PubMed]

Dirckx, J. J.

J. J. Dirckx, L. C. Kuypers, and W. F. Decraemer, "Refractive index of tissue measured with confocal microscopy," J. Biomed. Opt. 4044014 (2005).
[CrossRef]

Evans, C. L.

Fainman, Y.

L. Zhu, P.-C. Sun, D.-U. Bartsch, W. R. Freeman, and Y. Fainman, "Wave-front generation of Zernike polynomial modes with a micromachined membrane deformable mirror," App. Opt. 38, 6019-6026 (1999).
[CrossRef]

Fernández, E. J.

Freeman, W. R.

L. Zhu, P.-C. Sun, D.-U. Bartsch, W. R. Freeman, and Y. Fainman, "Wave-front generation of Zernike polynomial modes with a micromachined membrane deformable mirror," App. Opt. 38, 6019-6026 (1999).
[CrossRef]

Ganikhanov, F.

Gibson, G. M.

Girkin, J.

Girkin, J. M.

A. J. Wright, B. A. Patterson, S. P. Poland, J. M. Girkin, G. M. Gibson, and M. J. Padgett, "Dynamic closed-loop system for focus tracking using a spatial light modulator and a deformable membrane mirror," Opt. Express 14,222-228 (2005)
[CrossRef]

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, "Exploration of the Optimisation Algorithms used in the implementation of Adaptive Optics in Confocal and Multiphoton Microscopy," Microsc. Res. Tech. 67, 36-44 (2005).
[CrossRef] [PubMed]

Helmchen, F.

F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2,932-940 (2005).
[CrossRef] [PubMed]

Jacques, S. L.

G. Marques, L. Wang, S. P. Lin, S. L. Jacques, F. K. Tittel, S. L. Thomsen and J. Schwartz, "Measurement of Absorption and Scattering Spectra of Chicken Breast with Oblique Incidence Reflectometry," Proc. SPIE 2976,306-317 (1997)
[CrossRef]

Juskaitis, R.

M. J. Booth, M. A. A. Neil, R. Juskaitis, and T. Wilson, "Adaptive aberration correction in a confocal microscope," PNAS 99, 5788 (2002).
[CrossRef] [PubMed]

Katz, M.

Kesari, S.

Kopf, D.

Krasieva, T. B.

S. Tang, T. B. Krasieva, Z. Chen, and B. J. Tromberg, "Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source," J. Biomed. Opt. 11,020502, (2006).
[CrossRef] [PubMed]

Kuypers, L. C.

J. J. Dirckx, L. C. Kuypers, and W. F. Decraemer, "Refractive index of tissue measured with confocal microscopy," J. Biomed. Opt. 4044014 (2005).
[CrossRef]

Lin, C. P.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côté, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," PNAS 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Lin, S. P.

G. Marques, L. Wang, S. P. Lin, S. L. Jacques, F. K. Tittel, S. L. Thomsen and J. Schwartz, "Measurement of Absorption and Scattering Spectra of Chicken Breast with Oblique Incidence Reflectometry," Proc. SPIE 2976,306-317 (1997)
[CrossRef]

Mack-Bucher, J. A.

M. Rueckel, J. A. Mack-Bucher, and W. Denk, "Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing," PNAS 103, 17137 (2006).
[CrossRef] [PubMed]

Marques, G.

G. Marques, L. Wang, S. P. Lin, S. L. Jacques, F. K. Tittel, S. L. Thomsen and J. Schwartz, "Measurement of Absorption and Scattering Spectra of Chicken Breast with Oblique Incidence Reflectometry," Proc. SPIE 2976,306-317 (1997)
[CrossRef]

Marsh, P.

Masters, B. R.

Miller, M. J.

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Real-time imaging of lymphocytes in vivo," Curr. Opin. Immunol. 15,372-377 (2003)
[CrossRef] [PubMed]

Nan, X.

X. Nan, A. M. Tonary, A. Stolow, X. S. Xie, J. P. Pezacki, "Intracellular Imaging of HCV RNA and Cellular Lipids by Using Simultaneous Two-Photon Fluorescence and Coherent Anti-Stokes Raman Scattering Microscopies," ChemBioChem 7, 1895-1897 (2006).
[CrossRef] [PubMed]

X. Nan, W. Y. Yan, and X. S. Xie, "CARS Microscopy: Lights Up Lipids in Living Cells," Bioph. Int. 11, 44-47 (2004).

Neil, M. A. A.

M. J. Booth, M. A. A. Neil, R. Juskaitis, and T. Wilson, "Adaptive aberration correction in a confocal microscope," PNAS 99, 5788 (2002).
[CrossRef] [PubMed]

M. A. A. Neil, M. J. Booth, and T. Wilson, "Closed-loop aberration correction by use of a modal Zernike wave-front sensor," Opt. Lett. 25,1083-1085, (2000).
[CrossRef]

Norris, T. B.

L. Sherman, J. Y. Ye, O. Albert, and T. B. Norris, "Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror" J. Microscopy 206, 65-71 (2002).
[CrossRef]

Padgett, M. J.

Parker, I.

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Real-time imaging of lymphocytes in vivo," Curr. Opin. Immunol. 15,372-377 (2003)
[CrossRef] [PubMed]

Patterson, B. A.

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, "Exploration of the Optimisation Algorithms used in the implementation of Adaptive Optics in Confocal and Multiphoton Microscopy," Microsc. Res. Tech. 67, 36-44 (2005).
[CrossRef] [PubMed]

A. J. Wright, B. A. Patterson, S. P. Poland, J. M. Girkin, G. M. Gibson, and M. J. Padgett, "Dynamic closed-loop system for focus tracking using a spatial light modulator and a deformable membrane mirror," Opt. Express 14,222-228 (2005)
[CrossRef]

Pautot, S.

J. X. Cheng, S. Pautot, A. D. Weitz, and X. S. Xie, "Ordering of Water Molecules Between Phospholipid Bilayers Visualized by Coherent anti-Stokes Raman Scattering Microscopy," PNAS 100, 9826-9830 (2003).
[CrossRef] [PubMed]

Pezacki, J. P.

X. Nan, A. M. Tonary, A. Stolow, X. S. Xie, J. P. Pezacki, "Intracellular Imaging of HCV RNA and Cellular Lipids by Using Simultaneous Two-Photon Fluorescence and Coherent Anti-Stokes Raman Scattering Microscopies," ChemBioChem 7, 1895-1897 (2006).
[CrossRef] [PubMed]

Poland, S. P.

A. J. Wright, B. A. Patterson, S. P. Poland, J. M. Girkin, G. M. Gibson, and M. J. Padgett, "Dynamic closed-loop system for focus tracking using a spatial light modulator and a deformable membrane mirror," Opt. Express 14,222-228 (2005)
[CrossRef]

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, "Exploration of the Optimisation Algorithms used in the implementation of Adaptive Optics in Confocal and Multiphoton Microscopy," Microsc. Res. Tech. 67, 36-44 (2005).
[CrossRef] [PubMed]

Potma, E. O.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côté, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," PNAS 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Puoris'haag, M.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côté, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," PNAS 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Rueckel, M.

M. Rueckel, J. A. Mack-Bucher, and W. Denk, "Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing," PNAS 103, 17137 (2006).
[CrossRef] [PubMed]

Saar, B. G.

Schwartz, J.

G. Marques, L. Wang, S. P. Lin, S. L. Jacques, F. K. Tittel, S. L. Thomsen and J. Schwartz, "Measurement of Absorption and Scattering Spectra of Chicken Breast with Oblique Incidence Reflectometry," Proc. SPIE 2976,306-317 (1997)
[CrossRef]

Schwertner, M.

Seitz, W.

Sherman, L.

L. Sherman, J. Y. Ye, O. Albert, and T. B. Norris, "Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror" J. Microscopy 206, 65-71 (2002).
[CrossRef]

So, P. T. C.

Stolow, A.

X. Nan, A. M. Tonary, A. Stolow, X. S. Xie, J. P. Pezacki, "Intracellular Imaging of HCV RNA and Cellular Lipids by Using Simultaneous Two-Photon Fluorescence and Coherent Anti-Stokes Raman Scattering Microscopies," ChemBioChem 7, 1895-1897 (2006).
[CrossRef] [PubMed]

Sun, P.-C.

L. Zhu, P.-C. Sun, D.-U. Bartsch, W. R. Freeman, and Y. Fainman, "Wave-front generation of Zernike polynomial modes with a micromachined membrane deformable mirror," App. Opt. 38, 6019-6026 (1999).
[CrossRef]

Tang, S.

S. Tang, T. B. Krasieva, Z. Chen, and B. J. Tromberg, "Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source," J. Biomed. Opt. 11,020502, (2006).
[CrossRef] [PubMed]

Thomsen, S. L.

G. Marques, L. Wang, S. P. Lin, S. L. Jacques, F. K. Tittel, S. L. Thomsen and J. Schwartz, "Measurement of Absorption and Scattering Spectra of Chicken Breast with Oblique Incidence Reflectometry," Proc. SPIE 2976,306-317 (1997)
[CrossRef]

Tittel, F. K.

G. Marques, L. Wang, S. P. Lin, S. L. Jacques, F. K. Tittel, S. L. Thomsen and J. Schwartz, "Measurement of Absorption and Scattering Spectra of Chicken Breast with Oblique Incidence Reflectometry," Proc. SPIE 2976,306-317 (1997)
[CrossRef]

Tonary, A. M.

X. Nan, A. M. Tonary, A. Stolow, X. S. Xie, J. P. Pezacki, "Intracellular Imaging of HCV RNA and Cellular Lipids by Using Simultaneous Two-Photon Fluorescence and Coherent Anti-Stokes Raman Scattering Microscopies," ChemBioChem 7, 1895-1897 (2006).
[CrossRef] [PubMed]

Tromberg, B. J.

S. Tang, T. B. Krasieva, Z. Chen, and B. J. Tromberg, "Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source," J. Biomed. Opt. 11,020502, (2006).
[CrossRef] [PubMed]

Valentine, G. J.

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, "Exploration of the Optimisation Algorithms used in the implementation of Adaptive Optics in Confocal and Multiphoton Microscopy," Microsc. Res. Tech. 67, 36-44 (2005).
[CrossRef] [PubMed]

Volkmer, A.

J. X. Cheng, A. Volkmer, L. D. Book, X. S. Xie, "Multiplex Coherent Anti-Stokes Raman Scattering Microspectroscopy and Study of Lipid Vesicles," J. Phys. Chem. B 106, 8493 (2002).
[CrossRef]

Wang, L.

G. Marques, L. Wang, S. P. Lin, S. L. Jacques, F. K. Tittel, S. L. Thomsen and J. Schwartz, "Measurement of Absorption and Scattering Spectra of Chicken Breast with Oblique Incidence Reflectometry," Proc. SPIE 2976,306-317 (1997)
[CrossRef]

Webb, W. W.

W. R Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotech.  21,1369 - 1377 (2003)
[CrossRef]

Wei, S. H.

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Real-time imaging of lymphocytes in vivo," Curr. Opin. Immunol. 15,372-377 (2003)
[CrossRef] [PubMed]

Weitz, A. D.

J. X. Cheng, S. Pautot, A. D. Weitz, and X. S. Xie, "Ordering of Water Molecules Between Phospholipid Bilayers Visualized by Coherent anti-Stokes Raman Scattering Microscopy," PNAS 100, 9826-9830 (2003).
[CrossRef] [PubMed]

Williams, R. M.

W. R Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotech.  21,1369 - 1377 (2003)
[CrossRef]

Wilson, T.

Wong, S. T.C.

Wright, A. J.

A. J. Wright, B. A. Patterson, S. P. Poland, J. M. Girkin, G. M. Gibson, and M. J. Padgett, "Dynamic closed-loop system for focus tracking using a spatial light modulator and a deformable membrane mirror," Opt. Express 14,222-228 (2005)
[CrossRef]

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, "Exploration of the Optimisation Algorithms used in the implementation of Adaptive Optics in Confocal and Multiphoton Microscopy," Microsc. Res. Tech. 67, 36-44 (2005).
[CrossRef] [PubMed]

Xie, X. S.

C. L. Evans, X. Xu, S. Kesari, X. S. Xie, S. T.C. Wong and G. S. Young, "Chemically-selective imaging of brain structures with CARS microscopy," Opt. Express 15,12076-12087 (2007)
[CrossRef] [PubMed]

X. Nan, A. M. Tonary, A. Stolow, X. S. Xie, J. P. Pezacki, "Intracellular Imaging of HCV RNA and Cellular Lipids by Using Simultaneous Two-Photon Fluorescence and Coherent Anti-Stokes Raman Scattering Microscopies," ChemBioChem 7, 1895-1897 (2006).
[CrossRef] [PubMed]

F. Ganikhanov, C. L. Evans, B. G. Saar, and X. S. Xie, "High sensitivity vibrational imaging with frequency modulation coherent anti-Stokes Raman scattering (FM-CARS) microscopy," Opt. Lett. 31, 1872-1874 (2006).
[CrossRef] [PubMed]

F. Ganikhanov, S. Carrasco, X. S. Xie, M. Katz, W. Seitz, D. Kopf, "Broadly tunable dual-wavelength light source for coherent anti-Stokes Raman scattering microscopy," Opt. Lett.,  31, 1292-1294 (2006).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côté, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," PNAS 102, 16807-16812 (2005).
[CrossRef] [PubMed]

X. Nan, W. Y. Yan, and X. S. Xie, "CARS Microscopy: Lights Up Lipids in Living Cells," Bioph. Int. 11, 44-47 (2004).

J. X. Cheng and X. S. Xie, "Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications," J. Phys. Chem. B 108,827-840 (2004).
[CrossRef]

J. X. Cheng, S. Pautot, A. D. Weitz, and X. S. Xie, "Ordering of Water Molecules Between Phospholipid Bilayers Visualized by Coherent anti-Stokes Raman Scattering Microscopy," PNAS 100, 9826-9830 (2003).
[CrossRef] [PubMed]

J. X. Cheng, A. Volkmer, L. D. Book, X. S. Xie, "Multiplex Coherent Anti-Stokes Raman Scattering Microspectroscopy and Study of Lipid Vesicles," J. Phys. Chem. B 106, 8493 (2002).
[CrossRef]

Xu, X.

Yan, W. Y.

X. Nan, W. Y. Yan, and X. S. Xie, "CARS Microscopy: Lights Up Lipids in Living Cells," Bioph. Int. 11, 44-47 (2004).

Ye, J. Y.

L. Sherman, J. Y. Ye, O. Albert, and T. B. Norris, "Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror" J. Microscopy 206, 65-71 (2002).
[CrossRef]

Young, G. S.

Zhu, L.

L. Zhu, P.-C. Sun, D.-U. Bartsch, W. R. Freeman, and Y. Fainman, "Wave-front generation of Zernike polynomial modes with a micromachined membrane deformable mirror," App. Opt. 38, 6019-6026 (1999).
[CrossRef]

Zipfel, W. R

W. R Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotech.  21,1369 - 1377 (2003)
[CrossRef]

App. Opt.

L. Zhu, P.-C. Sun, D.-U. Bartsch, W. R. Freeman, and Y. Fainman, "Wave-front generation of Zernike polynomial modes with a micromachined membrane deformable mirror," App. Opt. 38, 6019-6026 (1999).
[CrossRef]

Bioph. Int.

X. Nan, W. Y. Yan, and X. S. Xie, "CARS Microscopy: Lights Up Lipids in Living Cells," Bioph. Int. 11, 44-47 (2004).

ChemBioChem

X. Nan, A. M. Tonary, A. Stolow, X. S. Xie, J. P. Pezacki, "Intracellular Imaging of HCV RNA and Cellular Lipids by Using Simultaneous Two-Photon Fluorescence and Coherent Anti-Stokes Raman Scattering Microscopies," ChemBioChem 7, 1895-1897 (2006).
[CrossRef] [PubMed]

Curr. Opin. Immunol.

M. D. Cahalan, I. Parker, S. H. Wei, and M. J. Miller, "Real-time imaging of lymphocytes in vivo," Curr. Opin. Immunol. 15,372-377 (2003)
[CrossRef] [PubMed]

J. Biomed. Opt.

S. Tang, T. B. Krasieva, Z. Chen, and B. J. Tromberg, "Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source," J. Biomed. Opt. 11,020502, (2006).
[CrossRef] [PubMed]

J. J. Dirckx, L. C. Kuypers, and W. F. Decraemer, "Refractive index of tissue measured with confocal microscopy," J. Biomed. Opt. 4044014 (2005).
[CrossRef]

J. Microscopy

L. Sherman, J. Y. Ye, O. Albert, and T. B. Norris, "Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror" J. Microscopy 206, 65-71 (2002).
[CrossRef]

J. Phys. Chem. B

J. X. Cheng and X. S. Xie, "Coherent anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications," J. Phys. Chem. B 108,827-840 (2004).
[CrossRef]

J. X. Cheng, A. Volkmer, L. D. Book, X. S. Xie, "Multiplex Coherent Anti-Stokes Raman Scattering Microspectroscopy and Study of Lipid Vesicles," J. Phys. Chem. B 106, 8493 (2002).
[CrossRef]

Microsc. Res. Tech.

A. J. Wright, D. Burns, B. A. Patterson, S. P. Poland, G. J. Valentine, and J. M. Girkin, "Exploration of the Optimisation Algorithms used in the implementation of Adaptive Optics in Confocal and Multiphoton Microscopy," Microsc. Res. Tech. 67, 36-44 (2005).
[CrossRef] [PubMed]

Nat. Biotech.

W. R Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotech.  21,1369 - 1377 (2003)
[CrossRef]

Nat. Methods

F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2,932-940 (2005).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

PNAS

J. X. Cheng, S. Pautot, A. D. Weitz, and X. S. Xie, "Ordering of Water Molecules Between Phospholipid Bilayers Visualized by Coherent anti-Stokes Raman Scattering Microscopy," PNAS 100, 9826-9830 (2003).
[CrossRef] [PubMed]

M. J. Booth, M. A. A. Neil, R. Juskaitis, and T. Wilson, "Adaptive aberration correction in a confocal microscope," PNAS 99, 5788 (2002).
[CrossRef] [PubMed]

M. Rueckel, J. A. Mack-Bucher, and W. Denk, "Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing," PNAS 103, 17137 (2006).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côté, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," PNAS 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Proc. SPIE

G. Marques, L. Wang, S. P. Lin, S. L. Jacques, F. K. Tittel, S. L. Thomsen and J. Schwartz, "Measurement of Absorption and Scattering Spectra of Chicken Breast with Oblique Incidence Reflectometry," Proc. SPIE 2976,306-317 (1997)
[CrossRef]

Other

A. J. Wright, S. P. Poland, J. Vijverberg, and J. M. Girkin, "A practical implementation of adaptive optics for aberration compensation in optical microscopy," Proc. 6th International Workshop on Adaptive Optics for Industry and Medicine, paper [30] (2007)

R. K. Tyson, "Principles of adaptive optics," Principles of adaptive optics, Edition: 2nd ed., Publisher: Boston, MA: Academic Press, 1998, ISBN: 0127059024 (1998).

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Figures (7)

Fig. 1.
Fig. 1.

Adaptive CARS setup. The signal and idler pulse trains exit the optical parametric oscillator (OPO) collinearly and overlapped in time. A set of achromatic lenses (L1, L2) expand and collimate the beam. The polarizing beam splitter cube (PBS) and quarterwaveplate form a double-pass configuration such that beams deflected by the deformable membrane mirror (DMM) are redirected to the microscope. A photomultiplier tube (PMT) collects the forward CARS signal.

Fig. 2.
Fig. 2.

Non-resonant CARS image obtained by raster-scanning of tightly focused collinear pump-and Stokes-beams with N.A. 0.75 air objective at an glass-air interface. a) Image without DMM correction. b) Image taken after optimizing DMM with a centered pump-and Stokes-beam. c) Horizontal cross-sections of a) and b) through the maximum, showing 2.2x CARS signal enhancement due to wavefront correction. Gaussian fits are added.

Fig. 3.
Fig. 3.

Adaptive optics improvement of CARS intensity from a 734 µm thick agarose-bead sample. Graphs are smoothed at 25µm intervals to average laser intensity fluctuations that occurred while the xyz-stack was taken. a) Averaged CARS intensity as a function of depth using different look up tables. b) Enhancement factors (corrected intensity/uncorrected intensity) as a function of depth.

Fig. 4.
Fig. 4.

CARS images of a polystyrene bead fixed in agarose gel at 592 µm depth in the sample a) without aberration correction b) with the system-induced aberration corrected using the DMM mirror-shape from the LUT for 0µm depth and c) with the system and sample-induced aberrations corrected using the LUT recorded at a depth of 460µm.

Fig. 5.
Fig. 5.

Adipose globular deposit imaged with CARS microscopy at 260 µm depth in white chicken muscle. Top: Comparison of image a) without correction, b) with the system-induced aberrations corrected and c) with the system and sample-induced aberrations corrected for the globule marked by the arrow. Bottom: Horizontal linescans through the tip of the arrow, intensity-averaged over 3 adjacent lines.

Fig. 6.
Fig. 6.

DMM shapes required to compensate for a) the system aberrations, b) the system and sample aberrations and c) the sample only aberrations. The scale bar represents DMM deformation in microns and each image shows the 15mm diameter mirror.

Fig. 7.
Fig. 7.

Radial enhancement function displaying the average signal enhancement factor with standard deviations from adipose deposit at 260 µm depth as a function of the distance from the point of optimization (arrow in Fig. 5). The localized optimization on the deposit decays due to the heterogeneous distribution of the refraction index in tissue. The mirror-shape taken from the LUT for system-induced aberration correction gave an on average flat enhancement as it is not optimized for a particular position in the sample.

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