Abstract

We report a mechanistic analysis of photodamage in coherent anti-Stokes Raman scattering (CARS) microscopy. Photodamage to the myelin sheath in spinal tissues is induced by using the point scan mode and is featured by myelin splitting and shockwaves with broadband emission. Our measurement of photodamage rate versus the excitation power reveals that both linear and nonlinear mechanisms are involved. Moreover, we show that vibrational absorption induced by coherent Raman processes significantly contributes to the nonlinear damage at high peak powers. For CARS imaging of cultured cells, the photodamage is characterized by plasma membrane blebbing and is dominated by a second order mechanism. Our study suggests that for dense samples such as the myelin sheath, CARS imaging induced photodamage can be minimized by using laser beams with relatively long near IR wavelengths and a repetition rate of a few MHz. For less dense samples such as cultured cells, laser pulses of higher repetition rates are preferred.

© 2006 Optical Society of America

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    [CrossRef] [PubMed]
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  42. K. König, H. Liang, M. W. Berns, and B. J. Tromberg, "Cell damage in near-infrared multimode optical traps as a result of multiphoton absorption," Opt. Lett. 21, 1090-1092 (1996).
    [CrossRef] [PubMed]
  43. M. L. Cunningham, J. S. Johnson, S. M. Giovanazzi, and M. J. Peak, "Photosensitized production of superoxide anion by monochromatic (290-405 nm) ultraviolet irradiation of NADH and NADPH coenzymes," Photochem. Photobiol. 42, 125-128 (1985).
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2005 (8)

L. Li, H. Wang, and J. X. Cheng, "Quantitative coherent anti-Stokes Raman scattering imaging of lipid distribution in co-existing domains," Biophys. J. 89,3480-3490 (2005).
[CrossRef] [PubMed]

G. W. H. Wurpel, H. A. Rinia, and M. Müller, "Imaging orientational order and lipid density in multilamellar vesicles with multiplex CARS microscopy," J. Microsc. 218,37-45 (2005).
[CrossRef] [PubMed]

E. O. Potma and X. S. Xie, "Direct visualization of lipid phase segregation in single lipid bilayers with coherent anti-Stokes Raman scattering microscopy," Chem. Phys. Chem. 6, 77-79 (2005).
[CrossRef] [PubMed]

J. S. Bredfeldt, C. Vinegoni, D. L. Marks, and S. A. Boppart, "Molecular sensitivity optical coherence tomography," Opt. Lett. 30,495-497 (2005).
[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," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

A. P. Kennedy, J. Sutcliffe, and J. X. Cheng, "Molecular composition and orientation of myelin figures characterized by coherent anti-Stokes Raman scattering microscopy," Langmuir 21, 6478-6486 (2005).
[CrossRef] [PubMed]

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J. X. Cheng, "Coherent anti-Stokes Raman scattering imaging of live spinal tissues," Biophys. J. 89, 581-591 (2005).
[CrossRef] [PubMed]

H. Wang, Y. Fu, and J. X. Cheng, "Light-matter energy exchange in coherent Raman microscopy," Phys. Rev. A, submitted (2005).

2004 (5)

B. R. Masters, P. T. C. So, C. Buehler, N. Barry, J. D. Sutin, W. W. Mantulin, and E. Gratton, "Mitigating thermal mechanical damage potential during two-photon dermal imaging," J. Biomed. Opt. 9, 1265-1270 (2004).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, and X. S. Xie, "Coherent anti-Stokes Raman scattering spectral interferometry:determination of the real and imaginary components of nonlinear susceptibility χ(3) for vibrational microscopy," Opt. Lett. 29,2923-2925 (2004).
[CrossRef]

K. P. Knutsen, J. C. Johnson, A. E. Miller, P. B. Petersen, and R. J. Saykally, "High spectral resolution multiplex CARS spectroscopy using chirped pulses," Chem. Phys. Lett. 387,436-441 (2004).
[CrossRef]

T. Ichimura, N. Hayazawa, M. Hashimoto, Y. Inouye, and S. Kawata, "Tip-enhanced coherent anti-Stokes Raman scattering for vibrational nanoimaging," Phys. Rev. Lett. 92,220801 (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]

2003 (3)

P. J. Campagnola and L. M. Loew, "Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms," Nat. Biotech. 21, 1356-1360 (2003).
[CrossRef]

X. Nan, J. X. Cheng, and X. S. Xie, "Vibrational imaging of lipid droplets in live fibroblast cells using coherent anti-Stokes Raman microscopy," J. Lipid Res. 40,2202-2208 (2003).
[CrossRef]

J. X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, "Ordering of water molecules between phospholipid bilayers visualized by coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 100, 9826-9830 (2003).
[CrossRef] [PubMed]

2002 (4)

A. Vogel, J. Noack, G. Huettmann, and G. Paltauf, "Femtosecond-laser-produced low-density plasmas in transparent biological media: a tool for the creation of chemical, thermal, and thermomechanical effects below the optical breakdown threshold," Proc. SPIE 4633A,1-15 (2002).

G. W. H. Wurpel, J. M. Schins, and M. Müller, "Chemical specificity in three-dimensional imaging with multiplex coherent anti-Stokes Raman scattering microscopy," Opt. Lett. 27, 1093-1095 (2002).
[CrossRef]

J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19,1363-1375 (2002).
[CrossRef]

N. Dudovich, D. Oron, and Y. Silberberg, "Single-pulse coherently controlled nonlinear Raman spectroscopy and microscopy," Nature 418,512-514 (2002).
[CrossRef] [PubMed]

2001 (4)

J. X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, "An epi-detected coherent anti-Stokes Raman scattering (E-CARS) microscope with high spectral resolution and high sensitivity," J. Phys. Chem. B 105, 1277-1280 (2001).
[CrossRef]

A. Volkmer, J. X. Cheng, and X. S. Xie, "Vibrational imaging with high sensitivity via epi-detected coherent anti-Stokes Raman scattering microscopy," Phys. Rev. Lett. 87, 023901 (2001).
[CrossRef]

E. O. Potma, W. P. D. Boeij, P. J. M. v. Haastert, and D. A. Wiersma, "Real-time visualization of intracellular hydrodynamics in single living cells," Proc. Natl. Acad. Sci. USA 98,1577-1582 (2001).
[CrossRef] [PubMed]

A. Hopt and E. Neher, "Highly nonlinear photodamage in two-photon fluorescence microscopy," Biophys. J. 80, 2029-2036 (2001).
[CrossRef] [PubMed]

2000 (2)

K. König, "Laser tweezers and multiphoton microscopes in life sciences," Histochem. Cell Biol. 114, 79-92 (2000).
[PubMed]

L. Moreaux, O. Sandre, and J. Mertz, "Membrane imaging by second-harmonic generation microscopy," J. Opt. Soc. Am. B 17, 1685-1694 (2000).
[CrossRef]

1999 (4)

K. König, T. W. Becker, P. Fischer, I. Riemann, and K.-J. Halbhuber, "Pulse-length dependence of cellular response to intense near-infrared laser pulses in multiphoton microscopes," Opt. Lett. 24, 113-115 (1999).
[CrossRef]

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: signal and photodamge," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, and S. M. Block, "Characterization of photodamage to Escherichia coli in optical traps," Biophys. J. 77, 2856-2863 (1999).
[CrossRef] [PubMed]

A. Zumbusch, G. R. Holtom, and X. S. Xie, "Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering," Phys. Rev. Lett. 82, 4142-4145 (1999).
[CrossRef]

1996 (3)

Y. Liu, G. J. Sonek, M. W. Berns, and B. J. Tromberg, "Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry," Biophys. J. 71, 2158-2167 (1996).
[CrossRef] [PubMed]

K. König, H. Liang, M. W. Berns, and B. J. Tromberg, "Cell damage in near-infrared multimode optical traps as a result of multiphoton absorption," Opt. Lett. 21, 1090-1092 (1996).
[CrossRef] [PubMed]

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, "Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy," Proc. Natl. Acad. Sci. USA 93, 10763-10768 (1996).
[CrossRef] [PubMed]

1990 (1)

W. Denk, J. H. Strickler, and W. W. Webb, "Two-Photon Laser Scanning Fluorescence Microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

1985 (1)

M. L. Cunningham, J. S. Johnson, S. M. Giovanazzi, and M. J. Peak, "Photosensitized production of superoxide anion by monochromatic (290-405 nm) ultraviolet irradiation of NADH and NADPH coenzymes," Photochem. Photobiol. 42, 125-128 (1985).
[CrossRef] [PubMed]

1982 (1)

1965 (1)

P. D. Maker and R. W. Terhune, "Study of Optical effects Due to an Induced Polarization Third Order in the Electric Field Strength," Phys. Rev. 137,A801-818 (1965).
[CrossRef]

Barry, N.

B. R. Masters, P. T. C. So, C. Buehler, N. Barry, J. D. Sutin, W. W. Mantulin, and E. Gratton, "Mitigating thermal mechanical damage potential during two-photon dermal imaging," J. Biomed. Opt. 9, 1265-1270 (2004).
[CrossRef] [PubMed]

Baur, D.

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: signal and photodamge," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

Becker, T. W.

Bergman, K.

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, and S. M. Block, "Characterization of photodamage to Escherichia coli in optical traps," Biophys. J. 77, 2856-2863 (1999).
[CrossRef] [PubMed]

Berns, M. W.

Y. Liu, G. J. Sonek, M. W. Berns, and B. J. Tromberg, "Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry," Biophys. J. 71, 2158-2167 (1996).
[CrossRef] [PubMed]

K. König, H. Liang, M. W. Berns, and B. J. Tromberg, "Cell damage in near-infrared multimode optical traps as a result of multiphoton absorption," Opt. Lett. 21, 1090-1092 (1996).
[CrossRef] [PubMed]

Block, S. M.

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, and S. M. Block, "Characterization of photodamage to Escherichia coli in optical traps," Biophys. J. 77, 2856-2863 (1999).
[CrossRef] [PubMed]

Boeij, W. P. D.

E. O. Potma, W. P. D. Boeij, P. J. M. v. Haastert, and D. A. Wiersma, "Real-time visualization of intracellular hydrodynamics in single living cells," Proc. Natl. Acad. Sci. USA 98,1577-1582 (2001).
[CrossRef] [PubMed]

Book, L. D.

J. X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, "An epi-detected coherent anti-Stokes Raman scattering (E-CARS) microscope with high spectral resolution and high sensitivity," J. Phys. Chem. B 105, 1277-1280 (2001).
[CrossRef]

Boppart, S. A.

Bredfeldt, J. S.

Buehler, C.

B. R. Masters, P. T. C. So, C. Buehler, N. Barry, J. D. Sutin, W. W. Mantulin, and E. Gratton, "Mitigating thermal mechanical damage potential during two-photon dermal imaging," J. Biomed. Opt. 9, 1265-1270 (2004).
[CrossRef] [PubMed]

Campagnola, P. J.

P. J. Campagnola and L. M. Loew, "Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms," Nat. Biotech. 21, 1356-1360 (2003).
[CrossRef]

Chadd, E. H.

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, and S. M. Block, "Characterization of photodamage to Escherichia coli in optical traps," Biophys. J. 77, 2856-2863 (1999).
[CrossRef] [PubMed]

Cheng, J. X.

H. Wang, Y. Fu, and J. X. Cheng, "Light-matter energy exchange in coherent Raman microscopy," Phys. Rev. A, submitted (2005).

A. P. Kennedy, J. Sutcliffe, and J. X. Cheng, "Molecular composition and orientation of myelin figures characterized by coherent anti-Stokes Raman scattering microscopy," Langmuir 21, 6478-6486 (2005).
[CrossRef] [PubMed]

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J. X. Cheng, "Coherent anti-Stokes Raman scattering imaging of live spinal tissues," Biophys. J. 89, 581-591 (2005).
[CrossRef] [PubMed]

L. Li, H. Wang, and J. X. Cheng, "Quantitative coherent anti-Stokes Raman scattering imaging of lipid distribution in co-existing domains," Biophys. J. 89,3480-3490 (2005).
[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, J. X. Cheng, and X. S. Xie, "Vibrational imaging of lipid droplets in live fibroblast cells using coherent anti-Stokes Raman microscopy," J. Lipid Res. 40,2202-2208 (2003).
[CrossRef]

J. X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, "Ordering of water molecules between phospholipid bilayers visualized by coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 100, 9826-9830 (2003).
[CrossRef] [PubMed]

J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19,1363-1375 (2002).
[CrossRef]

A. Volkmer, J. X. Cheng, and X. S. Xie, "Vibrational imaging with high sensitivity via epi-detected coherent anti-Stokes Raman scattering microscopy," Phys. Rev. Lett. 87, 023901 (2001).
[CrossRef]

J. X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, "An epi-detected coherent anti-Stokes Raman scattering (E-CARS) microscope with high spectral resolution and high sensitivity," J. Phys. Chem. B 105, 1277-1280 (2001).
[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," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Cunningham, M. L.

M. L. Cunningham, J. S. Johnson, S. M. Giovanazzi, and M. J. Peak, "Photosensitized production of superoxide anion by monochromatic (290-405 nm) ultraviolet irradiation of NADH and NADPH coenzymes," Photochem. Photobiol. 42, 125-128 (1985).
[CrossRef] [PubMed]

Denk, W.

W. Denk, J. H. Strickler, and W. W. Webb, "Two-Photon Laser Scanning Fluorescence Microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Dudovich, N.

N. Dudovich, D. Oron, and Y. Silberberg, "Single-pulse coherently controlled nonlinear Raman spectroscopy and microscopy," Nature 418,512-514 (2002).
[CrossRef] [PubMed]

Duncan, M. D.

Evans, C. L.

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," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, and X. S. Xie, "Coherent anti-Stokes Raman scattering spectral interferometry:determination of the real and imaginary components of nonlinear susceptibility χ(3) for vibrational microscopy," Opt. Lett. 29,2923-2925 (2004).
[CrossRef]

Fischer, P.

Fu, Y.

H. Wang, Y. Fu, and J. X. Cheng, "Light-matter energy exchange in coherent Raman microscopy," Phys. Rev. A, submitted (2005).

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J. X. Cheng, "Coherent anti-Stokes Raman scattering imaging of live spinal tissues," Biophys. J. 89, 581-591 (2005).
[CrossRef] [PubMed]

Giovanazzi, S. M.

M. L. Cunningham, J. S. Johnson, S. M. Giovanazzi, and M. J. Peak, "Photosensitized production of superoxide anion by monochromatic (290-405 nm) ultraviolet irradiation of NADH and NADPH coenzymes," Photochem. Photobiol. 42, 125-128 (1985).
[CrossRef] [PubMed]

Gratton, E.

B. R. Masters, P. T. C. So, C. Buehler, N. Barry, J. D. Sutin, W. W. Mantulin, and E. Gratton, "Mitigating thermal mechanical damage potential during two-photon dermal imaging," J. Biomed. Opt. 9, 1265-1270 (2004).
[CrossRef] [PubMed]

Halbhuber, K.-J.

Hashimoto, M.

T. Ichimura, N. Hayazawa, M. Hashimoto, Y. Inouye, and S. Kawata, "Tip-enhanced coherent anti-Stokes Raman scattering for vibrational nanoimaging," Phys. Rev. Lett. 92,220801 (2004).
[CrossRef] [PubMed]

Hayazawa, N.

T. Ichimura, N. Hayazawa, M. Hashimoto, Y. Inouye, and S. Kawata, "Tip-enhanced coherent anti-Stokes Raman scattering for vibrational nanoimaging," Phys. Rev. Lett. 92,220801 (2004).
[CrossRef] [PubMed]

Hell, S. W.

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: signal and photodamge," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

Holtom, G. R.

A. Zumbusch, G. R. Holtom, and X. S. Xie, "Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering," Phys. Rev. Lett. 82, 4142-4145 (1999).
[CrossRef]

Hopt, A.

A. Hopt and E. Neher, "Highly nonlinear photodamage in two-photon fluorescence microscopy," Biophys. J. 80, 2029-2036 (2001).
[CrossRef] [PubMed]

Huettmann, G.

A. Vogel, J. Noack, G. Huettmann, and G. Paltauf, "Femtosecond-laser-produced low-density plasmas in transparent biological media: a tool for the creation of chemical, thermal, and thermomechanical effects below the optical breakdown threshold," Proc. SPIE 4633A,1-15 (2002).

Ichimura, T.

T. Ichimura, N. Hayazawa, M. Hashimoto, Y. Inouye, and S. Kawata, "Tip-enhanced coherent anti-Stokes Raman scattering for vibrational nanoimaging," Phys. Rev. Lett. 92,220801 (2004).
[CrossRef] [PubMed]

Inouye, Y.

T. Ichimura, N. Hayazawa, M. Hashimoto, Y. Inouye, and S. Kawata, "Tip-enhanced coherent anti-Stokes Raman scattering for vibrational nanoimaging," Phys. Rev. Lett. 92,220801 (2004).
[CrossRef] [PubMed]

Johnson, J. C.

K. P. Knutsen, J. C. Johnson, A. E. Miller, P. B. Petersen, and R. J. Saykally, "High spectral resolution multiplex CARS spectroscopy using chirped pulses," Chem. Phys. Lett. 387,436-441 (2004).
[CrossRef]

Johnson, J. S.

M. L. Cunningham, J. S. Johnson, S. M. Giovanazzi, and M. J. Peak, "Photosensitized production of superoxide anion by monochromatic (290-405 nm) ultraviolet irradiation of NADH and NADPH coenzymes," Photochem. Photobiol. 42, 125-128 (1985).
[CrossRef] [PubMed]

Kawata, S.

T. Ichimura, N. Hayazawa, M. Hashimoto, Y. Inouye, and S. Kawata, "Tip-enhanced coherent anti-Stokes Raman scattering for vibrational nanoimaging," Phys. Rev. Lett. 92,220801 (2004).
[CrossRef] [PubMed]

Kennedy, A. P.

A. P. Kennedy, J. Sutcliffe, and J. X. Cheng, "Molecular composition and orientation of myelin figures characterized by coherent anti-Stokes Raman scattering microscopy," Langmuir 21, 6478-6486 (2005).
[CrossRef] [PubMed]

Knutsen, K. P.

K. P. Knutsen, J. C. Johnson, A. E. Miller, P. B. Petersen, and R. J. Saykally, "High spectral resolution multiplex CARS spectroscopy using chirped pulses," Chem. Phys. Lett. 387,436-441 (2004).
[CrossRef]

Koester, H. J.

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: signal and photodamge," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

König, K.

Li, L.

L. Li, H. Wang, and J. X. Cheng, "Quantitative coherent anti-Stokes Raman scattering imaging of lipid distribution in co-existing domains," Biophys. J. 89,3480-3490 (2005).
[CrossRef] [PubMed]

Liang, H.

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," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Liou, G. F.

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, and S. M. Block, "Characterization of photodamage to Escherichia coli in optical traps," Biophys. J. 77, 2856-2863 (1999).
[CrossRef] [PubMed]

Liu, Y.

Y. Liu, G. J. Sonek, M. W. Berns, and B. J. Tromberg, "Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry," Biophys. J. 71, 2158-2167 (1996).
[CrossRef] [PubMed]

Loew, L. M.

P. J. Campagnola and L. M. Loew, "Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms," Nat. Biotech. 21, 1356-1360 (2003).
[CrossRef]

Maker, P. D.

P. D. Maker and R. W. Terhune, "Study of Optical effects Due to an Induced Polarization Third Order in the Electric Field Strength," Phys. Rev. 137,A801-818 (1965).
[CrossRef]

Mantulin, W. W.

B. R. Masters, P. T. C. So, C. Buehler, N. Barry, J. D. Sutin, W. W. Mantulin, and E. Gratton, "Mitigating thermal mechanical damage potential during two-photon dermal imaging," J. Biomed. Opt. 9, 1265-1270 (2004).
[CrossRef] [PubMed]

Manuccia, T. J.

Marks, D. L.

Masters, B. R.

B. R. Masters, P. T. C. So, C. Buehler, N. Barry, J. D. Sutin, W. W. Mantulin, and E. Gratton, "Mitigating thermal mechanical damage potential during two-photon dermal imaging," J. Biomed. Opt. 9, 1265-1270 (2004).
[CrossRef] [PubMed]

Mertz, J.

Miller, A. E.

K. P. Knutsen, J. C. Johnson, A. E. Miller, P. B. Petersen, and R. J. Saykally, "High spectral resolution multiplex CARS spectroscopy using chirped pulses," Chem. Phys. Lett. 387,436-441 (2004).
[CrossRef]

Moreaux, L.

Müller, M.

G. W. H. Wurpel, H. A. Rinia, and M. Müller, "Imaging orientational order and lipid density in multilamellar vesicles with multiplex CARS microscopy," J. Microsc. 218,37-45 (2005).
[CrossRef] [PubMed]

G. W. H. Wurpel, J. M. Schins, and M. Müller, "Chemical specificity in three-dimensional imaging with multiplex coherent anti-Stokes Raman scattering microscopy," Opt. Lett. 27, 1093-1095 (2002).
[CrossRef]

Nan, X.

X. Nan, J. X. Cheng, and X. S. Xie, "Vibrational imaging of lipid droplets in live fibroblast cells using coherent anti-Stokes Raman microscopy," J. Lipid Res. 40,2202-2208 (2003).
[CrossRef]

Neher, E.

A. Hopt and E. Neher, "Highly nonlinear photodamage in two-photon fluorescence microscopy," Biophys. J. 80, 2029-2036 (2001).
[CrossRef] [PubMed]

Neuman, K. C.

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, and S. M. Block, "Characterization of photodamage to Escherichia coli in optical traps," Biophys. J. 77, 2856-2863 (1999).
[CrossRef] [PubMed]

Noack, J.

A. Vogel, J. Noack, G. Huettmann, and G. Paltauf, "Femtosecond-laser-produced low-density plasmas in transparent biological media: a tool for the creation of chemical, thermal, and thermomechanical effects below the optical breakdown threshold," Proc. SPIE 4633A,1-15 (2002).

Oron, D.

N. Dudovich, D. Oron, and Y. Silberberg, "Single-pulse coherently controlled nonlinear Raman spectroscopy and microscopy," Nature 418,512-514 (2002).
[CrossRef] [PubMed]

Paltauf, G.

A. Vogel, J. Noack, G. Huettmann, and G. Paltauf, "Femtosecond-laser-produced low-density plasmas in transparent biological media: a tool for the creation of chemical, thermal, and thermomechanical effects below the optical breakdown threshold," Proc. SPIE 4633A,1-15 (2002).

Pautot, S.

J. X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, "Ordering of water molecules between phospholipid bilayers visualized by coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 100, 9826-9830 (2003).
[CrossRef] [PubMed]

Peak, M. J.

M. L. Cunningham, J. S. Johnson, S. M. Giovanazzi, and M. J. Peak, "Photosensitized production of superoxide anion by monochromatic (290-405 nm) ultraviolet irradiation of NADH and NADPH coenzymes," Photochem. Photobiol. 42, 125-128 (1985).
[CrossRef] [PubMed]

Petersen, P. B.

K. P. Knutsen, J. C. Johnson, A. E. Miller, P. B. Petersen, and R. J. Saykally, "High spectral resolution multiplex CARS spectroscopy using chirped pulses," Chem. Phys. Lett. 387,436-441 (2004).
[CrossRef]

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," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

E. O. Potma and X. S. Xie, "Direct visualization of lipid phase segregation in single lipid bilayers with coherent anti-Stokes Raman scattering microscopy," Chem. Phys. Chem. 6, 77-79 (2005).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, and X. S. Xie, "Coherent anti-Stokes Raman scattering spectral interferometry:determination of the real and imaginary components of nonlinear susceptibility χ(3) for vibrational microscopy," Opt. Lett. 29,2923-2925 (2004).
[CrossRef]

E. O. Potma, W. P. D. Boeij, P. J. M. v. Haastert, and D. A. Wiersma, "Real-time visualization of intracellular hydrodynamics in single living cells," Proc. Natl. Acad. Sci. USA 98,1577-1582 (2001).
[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," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Reintjes, J.

Riemann, I.

Rinia, H. A.

G. W. H. Wurpel, H. A. Rinia, and M. Müller, "Imaging orientational order and lipid density in multilamellar vesicles with multiplex CARS microscopy," J. Microsc. 218,37-45 (2005).
[CrossRef] [PubMed]

Sandre, O.

Saykally, R. J.

K. P. Knutsen, J. C. Johnson, A. E. Miller, P. B. Petersen, and R. J. Saykally, "High spectral resolution multiplex CARS spectroscopy using chirped pulses," Chem. Phys. Lett. 387,436-441 (2004).
[CrossRef]

Schins, J. M.

Shear, J. B.

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, "Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy," Proc. Natl. Acad. Sci. USA 93, 10763-10768 (1996).
[CrossRef] [PubMed]

Shi, R.

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J. X. Cheng, "Coherent anti-Stokes Raman scattering imaging of live spinal tissues," Biophys. J. 89, 581-591 (2005).
[CrossRef] [PubMed]

Silberberg, Y.

N. Dudovich, D. Oron, and Y. Silberberg, "Single-pulse coherently controlled nonlinear Raman spectroscopy and microscopy," Nature 418,512-514 (2002).
[CrossRef] [PubMed]

So, P. T. C.

B. R. Masters, P. T. C. So, C. Buehler, N. Barry, J. D. Sutin, W. W. Mantulin, and E. Gratton, "Mitigating thermal mechanical damage potential during two-photon dermal imaging," J. Biomed. Opt. 9, 1265-1270 (2004).
[CrossRef] [PubMed]

Sonek, G. J.

Y. Liu, G. J. Sonek, M. W. Berns, and B. J. Tromberg, "Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry," Biophys. J. 71, 2158-2167 (1996).
[CrossRef] [PubMed]

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, "Two-Photon Laser Scanning Fluorescence Microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Sutcliffe, J.

A. P. Kennedy, J. Sutcliffe, and J. X. Cheng, "Molecular composition and orientation of myelin figures characterized by coherent anti-Stokes Raman scattering microscopy," Langmuir 21, 6478-6486 (2005).
[CrossRef] [PubMed]

Sutin, J. D.

B. R. Masters, P. T. C. So, C. Buehler, N. Barry, J. D. Sutin, W. W. Mantulin, and E. Gratton, "Mitigating thermal mechanical damage potential during two-photon dermal imaging," J. Biomed. Opt. 9, 1265-1270 (2004).
[CrossRef] [PubMed]

Terhune, R. W.

P. D. Maker and R. W. Terhune, "Study of Optical effects Due to an Induced Polarization Third Order in the Electric Field Strength," Phys. Rev. 137,A801-818 (1965).
[CrossRef]

Tromberg, B. J.

Y. Liu, G. J. Sonek, M. W. Berns, and B. J. Tromberg, "Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry," Biophys. J. 71, 2158-2167 (1996).
[CrossRef] [PubMed]

K. König, H. Liang, M. W. Berns, and B. J. Tromberg, "Cell damage in near-infrared multimode optical traps as a result of multiphoton absorption," Opt. Lett. 21, 1090-1092 (1996).
[CrossRef] [PubMed]

Uhl, R.

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: signal and photodamge," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

Vinegoni, C.

Vogel, A.

A. Vogel, J. Noack, G. Huettmann, and G. Paltauf, "Femtosecond-laser-produced low-density plasmas in transparent biological media: a tool for the creation of chemical, thermal, and thermomechanical effects below the optical breakdown threshold," Proc. SPIE 4633A,1-15 (2002).

Volkmer, A.

J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19,1363-1375 (2002).
[CrossRef]

A. Volkmer, J. X. Cheng, and X. S. Xie, "Vibrational imaging with high sensitivity via epi-detected coherent anti-Stokes Raman scattering microscopy," Phys. Rev. Lett. 87, 023901 (2001).
[CrossRef]

J. X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, "An epi-detected coherent anti-Stokes Raman scattering (E-CARS) microscope with high spectral resolution and high sensitivity," J. Phys. Chem. B 105, 1277-1280 (2001).
[CrossRef]

Wang, H.

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J. X. Cheng, "Coherent anti-Stokes Raman scattering imaging of live spinal tissues," Biophys. J. 89, 581-591 (2005).
[CrossRef] [PubMed]

L. Li, H. Wang, and J. X. Cheng, "Quantitative coherent anti-Stokes Raman scattering imaging of lipid distribution in co-existing domains," Biophys. J. 89,3480-3490 (2005).
[CrossRef] [PubMed]

H. Wang, Y. Fu, and J. X. Cheng, "Light-matter energy exchange in coherent Raman microscopy," Phys. Rev. A, submitted (2005).

Webb, W. W.

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, "Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy," Proc. Natl. Acad. Sci. USA 93, 10763-10768 (1996).
[CrossRef] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, "Two-Photon Laser Scanning Fluorescence Microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Weitz, D. A.

J. X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, "Ordering of water molecules between phospholipid bilayers visualized by coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 100, 9826-9830 (2003).
[CrossRef] [PubMed]

Williams, R. M.

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, "Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy," Proc. Natl. Acad. Sci. USA 93, 10763-10768 (1996).
[CrossRef] [PubMed]

Wurpel, G. W. H.

G. W. H. Wurpel, H. A. Rinia, and M. Müller, "Imaging orientational order and lipid density in multilamellar vesicles with multiplex CARS microscopy," J. Microsc. 218,37-45 (2005).
[CrossRef] [PubMed]

G. W. H. Wurpel, J. M. Schins, and M. Müller, "Chemical specificity in three-dimensional imaging with multiplex coherent anti-Stokes Raman scattering microscopy," Opt. Lett. 27, 1093-1095 (2002).
[CrossRef]

Xie, X. S.

E. O. Potma and X. S. Xie, "Direct visualization of lipid phase segregation in single lipid bilayers with coherent anti-Stokes Raman scattering microscopy," Chem. Phys. Chem. 6, 77-79 (2005).
[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," Proc. Natl. Acad. Sci. USA 102, 16807-16812 (2005).
[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]

C. L. Evans, E. O. Potma, and X. S. Xie, "Coherent anti-Stokes Raman scattering spectral interferometry:determination of the real and imaginary components of nonlinear susceptibility χ(3) for vibrational microscopy," Opt. Lett. 29,2923-2925 (2004).
[CrossRef]

X. Nan, J. X. Cheng, and X. S. Xie, "Vibrational imaging of lipid droplets in live fibroblast cells using coherent anti-Stokes Raman microscopy," J. Lipid Res. 40,2202-2208 (2003).
[CrossRef]

J. X. Cheng, S. Pautot, D. A. Weitz, and X. S. Xie, "Ordering of water molecules between phospholipid bilayers visualized by coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. USA 100, 9826-9830 (2003).
[CrossRef] [PubMed]

J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19,1363-1375 (2002).
[CrossRef]

A. Volkmer, J. X. Cheng, and X. S. Xie, "Vibrational imaging with high sensitivity via epi-detected coherent anti-Stokes Raman scattering microscopy," Phys. Rev. Lett. 87, 023901 (2001).
[CrossRef]

J. X. Cheng, A. Volkmer, L. D. Book, and X. S. Xie, "An epi-detected coherent anti-Stokes Raman scattering (E-CARS) microscope with high spectral resolution and high sensitivity," J. Phys. Chem. B 105, 1277-1280 (2001).
[CrossRef]

A. Zumbusch, G. R. Holtom, and X. S. Xie, "Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering," Phys. Rev. Lett. 82, 4142-4145 (1999).
[CrossRef]

Xu, C.

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, "Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy," Proc. Natl. Acad. Sci. USA 93, 10763-10768 (1996).
[CrossRef] [PubMed]

Zickmund, P.

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J. X. Cheng, "Coherent anti-Stokes Raman scattering imaging of live spinal tissues," Biophys. J. 89, 581-591 (2005).
[CrossRef] [PubMed]

Zipfel, W.

C. Xu, W. Zipfel, J. B. Shear, R. M. Williams, and W. W. Webb, "Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy," Proc. Natl. Acad. Sci. USA 93, 10763-10768 (1996).
[CrossRef] [PubMed]

Zumbusch, A.

A. Zumbusch, G. R. Holtom, and X. S. Xie, "Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering," Phys. Rev. Lett. 82, 4142-4145 (1999).
[CrossRef]

Biophys. J. (6)

L. Li, H. Wang, and J. X. Cheng, "Quantitative coherent anti-Stokes Raman scattering imaging of lipid distribution in co-existing domains," Biophys. J. 89,3480-3490 (2005).
[CrossRef] [PubMed]

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J. X. Cheng, "Coherent anti-Stokes Raman scattering imaging of live spinal tissues," Biophys. J. 89, 581-591 (2005).
[CrossRef] [PubMed]

H. J. Koester, D. Baur, R. Uhl, and S. W. Hell, "Ca2+ fluorescence imaging with pico- and femtosecond two-photon excitation: signal and photodamge," Biophys. J. 77, 2226-2236 (1999).
[CrossRef] [PubMed]

A. Hopt and E. Neher, "Highly nonlinear photodamage in two-photon fluorescence microscopy," Biophys. J. 80, 2029-2036 (2001).
[CrossRef] [PubMed]

K. C. Neuman, E. H. Chadd, G. F. Liou, K. Bergman, and S. M. Block, "Characterization of photodamage to Escherichia coli in optical traps," Biophys. J. 77, 2856-2863 (1999).
[CrossRef] [PubMed]

Y. Liu, G. J. Sonek, M. W. Berns, and B. J. Tromberg, "Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry," Biophys. J. 71, 2158-2167 (1996).
[CrossRef] [PubMed]

Chem. Phys. Chem. (1)

E. O. Potma and X. S. Xie, "Direct visualization of lipid phase segregation in single lipid bilayers with coherent anti-Stokes Raman scattering microscopy," Chem. Phys. Chem. 6, 77-79 (2005).
[CrossRef] [PubMed]

Chem. Phys. Lett. (1)

K. P. Knutsen, J. C. Johnson, A. E. Miller, P. B. Petersen, and R. J. Saykally, "High spectral resolution multiplex CARS spectroscopy using chirped pulses," Chem. Phys. Lett. 387,436-441 (2004).
[CrossRef]

Histochem. Cell Biol. (1)

K. König, "Laser tweezers and multiphoton microscopes in life sciences," Histochem. Cell Biol. 114, 79-92 (2000).
[PubMed]

J. Biomed. Opt. (1)

B. R. Masters, P. T. C. So, C. Buehler, N. Barry, J. D. Sutin, W. W. Mantulin, and E. Gratton, "Mitigating thermal mechanical damage potential during two-photon dermal imaging," J. Biomed. Opt. 9, 1265-1270 (2004).
[CrossRef] [PubMed]

J. Lipid Res. (1)

X. Nan, J. X. Cheng, and X. S. Xie, "Vibrational imaging of lipid droplets in live fibroblast cells using coherent anti-Stokes Raman microscopy," J. Lipid Res. 40,2202-2208 (2003).
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A. P. Kennedy, J. Sutcliffe, and J. X. Cheng, "Molecular composition and orientation of myelin figures characterized by coherent anti-Stokes Raman scattering microscopy," Langmuir 21, 6478-6486 (2005).
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Figures (6)

Fig. 1.
Fig. 1.

CARS images of myelin sheath in spinal tissue. (a) Normal myelin sheath wrapping five parallel axons labeled as “ax”. The middle axon displays a node of Ranvier (NR). Bar = 10 μm. (b) A Schmidt-Lanterman incisure. Bar = 5 μm. The images in (a-b) were acquired with the peak pump and Stokes power of 323 W and 129 W, respectively. (c) E-CARS image of a damaged site acquired after x-y scanning for 22 s. (d) E-CARS and (e) F-CARS images of the same damaged site as in (c) acquired after x-y scanning for 25 s. The damage shown in (c-e) was induced with peak pump and Stokes power of 74 W and 60 W, respectively. f = 39 MHz. Bar = 5 μm for images (c-e).

Fig. 2.
Fig. 2.

CARS images of single myelin sheath before and after photodamage induced by point scanning. The x-y imaging and point scanning were carried out at the same condition. (a-b) results with high peak power of the pump (308 W) and Stokes (149 W) beams. f = 0.65 MHz. (e) Intensity trace of point scanning at the position indicated by the red star in (a). (c-d) results with low peak power of the pump (38 W) and Stokes (19 W) beams. f = 15.6 MHz. (f) Intensity trace of point scanning at the position indicated by the red cross in (c). For all images, bar = 5 μm.

Fig. 3.
Fig. 3.

Dependence of photodamage rate on the total excitation peak power on the sample. f = 3.9 MHz. The power ratio of pump to Stokes lasers was kept constant at 3.2. The peak power of the pump and Stokes beams were adjusted from 74 W to 277 W and from 23 W to 86 W, respectively.

Fig. 4.
Fig. 4.

Dependence of photodamage rate on the Raman shift. The pump wavelength was fixed at 701 nm and the Stokes beam was tuned to generate different Raman shifts. (a) Significant dependence observed with high peak powers of pump (338 W) and Stokes (203 W) beams at f = 1.3 MHz. (b) No dependence observed at low peak powers of pump (32 W) and Stokes (19 W) beams at f = 15.6 MHz.

Fig. 5.
Fig. 5.

(a) Dependence of photodamage rate on the pump to Stokes power ratio under the condition of constant CARS signal. f = 3.9 MHz. (b) Dependence of photodamage rate on the repetition rate under the condition of constant CARS signal. The power ratio of pump to Stokes was fixed at 2. f was varied from 0.65 to 39 MHz. To maintain the same CARS signal at different repetition rates, the pump peak power was changed from 286 W to 52 W and the Stokes peak power from 143 W to 26 W accordingly.

Fig. 6.
Fig. 6.

Photodamage in CARS imaging of live KB cells. (a) CARS image of a KB cell under normal conditions. (b) CARS image of the same KB cell after 3min of scanning with the pump peak power 373W and Stokes peak power 101W. Bar = 10 μm. (c) Dependence of photodamage rate on the total excitation peak power. f = 7.8 MHz. The power ratio of pump to Stokes lasers was kept at 3.8. The peak power of the pump and Stokes beams were adjusted from 138.4 W to 373 W and from 36 W to 101 W, respectively.

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