Abstract

Third-harmonic generation (THG) imaging of thick samples or large organisms requires TH light to be epicollected through the focusing objective. In this study we first estimate the amount of backward-to-forward TH radiation created by an isolated object as a function of size and spatial frequencies in the object. Theory and model experiments indicate that no significant signal can be epidetected from a (biological) dielectric structure embedded in a transparent medium. In contrast, backward emission is observed from metal nanoparticles where THG is partly a surface effect. We then address the case of an object embedded in a turbid medium. Experiments and Monte Carlo simulations show that epidetection is possible when the absorption mean free path of harmonic light in the medium exceeds its reduced scattering length, and that epicollection efficiency critically depends on the microscope field-of-view even at shallow depths, because backscattered light is essentially diffusive. These observations provide guidelines for optimizing epidetection in third-harmonic, second-harmonic, or CARS imaging of thick tissues.

© 2007 Optical Society of America

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  1. W. R. Zipfel, R. M. Williams and W. W. Webb, "Nonlinear magic:multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1369-1377 (2003).
    [CrossRef] [PubMed]
  2. K. Svoboda, W. Denk, D. Kleinfeld and D. W. Tank, "In vivo dendritic calcium dynamics in neocortical pyramidal neurons," Nature 385, 161-165 (1997).
    [CrossRef] [PubMed]
  3. F. Helmchen and W. Denk, "New developments in multiphoton microscopy", Curr. Opin. Neurobiol. 12, 593-601 (2002).
    [CrossRef] [PubMed]
  4. S. Charpak, J. Mertz, E. Beaurepaire, L. Moreaux and K. Delaney, "Odor-evoked calcium signals in dendrites of rat mitral cells," Proc. Nat. Acad. Sci. USA 98, 1230-1234 (2001).
    [CrossRef] [PubMed]
  5. 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]
  6. S. Hugues, L. Fetler, L. Bonifaz, J. Helft, F. Amblard and S. Amigorena, "Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity," Nat. Immunol. 5, 1235-42 (2004).
    [CrossRef] [PubMed]
  7. W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
    [PubMed]
  8. J. M. Squirrell, D. L. Wokosin, J. G. White and B. D. Bavister, "Long-term two photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
    [CrossRef] [PubMed]
  9. W. Supatto, D. Débarre, B. Moulia, E. Brouzés, J.-L. Martin, E. Farge and E. Beaurepaire, "In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses," Proc. Nat. Acad. Sci. USA 102, 1047-1052 (2005).
    [CrossRef] [PubMed]
  10. E. Beaurepaire and J. Mertz, "Epifluorescence collection in two-photon microscopy," Appl. Opt. 41, 5376-5382 (2002).
    [CrossRef] [PubMed]
  11. M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz and S. Charpak, "Two-photon microscopy in brain tissue: parameters influencing the imaging depth," J. Neurosci. Methods 111, 29-37 (2001).
    [CrossRef] [PubMed]
  12. D. Vučinić, T. M. BartolJr. and T. J. Sejnowski, "Hybrid reflecting objectives for functional multiphoton microscopy in turbid media," Opt. Lett. 31, 2447-2449 (2006).
    [CrossRef] [PubMed]
  13. Y. Barad, H. Eisenberg, M. Horowitz and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," Appl. Phys. Lett. 70, 922-924 (1997).
    [CrossRef]
  14. M. Müller, J. Squier, K. R. Wilson and G. J. Brakenhoff, "3D-microscopy of transparent objects using third-harmonic generation," J. Microsc. 191, 266-274 (1998).
    [CrossRef] [PubMed]
  15. D. Yelin and Y. Silberberg, "Laser scanning third-harmonic generation microscopy in biology," Opt. Express 5, 169-175 (1999).
    [CrossRef] [PubMed]
  16. D. Oron, D. Yelin, E. Tal, S. Raz, R. Fachima and Y. Silberberg, "Depth-resolved structural imaging by third-harmonic generation microscopy," J. Struct. Biol. 147, 3-11 (2004).
    [CrossRef] [PubMed]
  17. D. Débarre, W. Supatto, E. Farge, B. Moulia, M.-C. Schanne-Klein and E. Beaurepaire, "Velocimetric third-harmonic generation microscopy: micrometer-scale quantification of morphogenetic movements in unstained embryos," Opt. Lett. 29, 2881-2883 (2004).
    [CrossRef]
  18. D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
    [CrossRef]
  19. C.-K. Sun, C.-C. Chen, S.-W. Chu, T.-H. Tsai, Y.-C. Chen and B.-L. Lin, "Multiharmonic generation biopsy of skin," Opt. Lett. 28, 2488-2490 (2003).
    [CrossRef] [PubMed]
  20. S.-P. Tai, W.-J. Lee, D.-B. Shieh, P.-C. Wu, H.-Y. Huang, C.-H. Yu and C.-K. Sun, "In vivo optical biopsy of hamster oral cavity with epi-third-harmonic generation microscopy," Opt. Express 14, 6178-6187 (2006).
    [CrossRef] [PubMed]
  21. J.-X. Cheng and X. S. Xie, "Green's function formulation for third harmonic generation microscopy," J. Opt. Soc. Am. B 19, 1604-1610 (2002).
    [CrossRef]
  22. L. Moreaux, O. Sandre and J. Mertz, "Membrane imaging by second-harmonic generation microscopy," J. Opt. Soc. Am. B 17, 1685-1694 (2000).
    [CrossRef]
  23. J. Mertz and L. Moreaux, "Second-harmonic generation by focused excitation of inhomogeneously distributed scatterers," Opt. Commun. 196, 325-330 (2001).
    [CrossRef]
  24. R. M. Williams, W. R. Zipfel and W. W. Webb, "Interpreting second-harmonic images of collagen I fibrils," Biophys. J. 88, 1377-1386 (2005).
    [CrossRef]
  25. O. Nadiarnykh, R. Lacomb, P. J. Campagnola and W. A. Mohler, "Coherent and incoherent SHG in fibrillar cellulose matrices," Opt. Express 15, 3348-3360 (2007).
    [CrossRef] [PubMed]
  26. 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, 1328-1347 (2002).
    [CrossRef]
  27. 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. Nat. Acad. Sci. USA 102, 16807-12 (2005).
    [CrossRef] [PubMed]
  28. R. W. Boyd, Nonlinear Optics, 2nd ed., (Academic Press, 2003).
  29. S.-P. Tai, T.-H. Tsai, W.-J. Lee, D.-B. Shieh, Y.-H. Liao, H.-Y. Huang, K. Y. J. Zhang, H.-L. Liu and C.-K. Sun, "Optical biopsy of fixed human skin with backward-collected optical harmonics signals," Opt. Express 13, 8231-8242 (2005).
    [CrossRef] [PubMed]
  30. D. Débarre, W. Supatto and E. Beaurepaire, "Structure sensitivity in third-harmonic generation microscopy," Opt. Lett. 30, 2134-2136 (2005).
    [CrossRef] [PubMed]
  31. B. Richards and E. Wolf, "Electromagnetic diffraction in optical systems II. Structure of the image field in an aplanetic system," Proc. Royal Soc. London Ser. A 253, 358-379 (1959).
    [CrossRef]
  32. M. LippitzM. A. van Dijk.and M. Orrit, "Third-harmonic generation from single gold nanoparticules," Nano Lett. 5, 799-802 (2005).
    [CrossRef] [PubMed]
  33. S. V. Popruzhenko, D. F. Zaretsky and W. Becker, "Third-harmonic generation by small clusters in a dielectric medium," J. Phys. B. 39, 4933-4943 (2006).
    [CrossRef]
  34. J. J. Mock, M. Barbic, D. R. Smith, D. A. Schultz and S. Schultz, "Shape effects in plasmon resonance of individual silver nanoparticles," J. Chem. Phys. 116, 6755-6759 (2002).
    [CrossRef]
  35. M. H. Niemz, Laser-tissue interactions - Fundamentals and Applications - Third ed., (Springer, 2004).
  36. S. A. Prahl, M. Keijzer, S. L. Jacques and A. J. Welch, "A Monte Carlo model of light propagation in tissue," SPIE Institute Series 5, 102-111 (1989).
  37. C. G. Bohren and D. R. Huffman, Absorption and scattering of light by small particles, (Wiley, New York, 1983).
  38. V. Barzda, C. Greenhalgh, J. Aus-der-Au and S. Elmore, "Visualization of mitochondria in cardiomyocytes by simultaneous harmonic generation and fluorescence microscopy," Opt. Express 13, 8263-8276 (2006).
    [CrossRef]
  39. O. G. Clay, A. C. Millard, C. B. Schaffer, J. Aus-Der-Au, P. S. Tsai, J. A. Squier and D. Kleinfeld, "Spectroscopy of third harmonic generation: evidence for resonances in model compounds and ligated hemoglobin," J. Opt. Soc. Am. B 23, 932-950 (2006).
    [CrossRef]
  40. N. Djaker, D. Gachet, N. Sandeau, P.-F. Lenne and H. Rigneault, "Refractive effects in coherent anti-Stokes Raman scattering microscopy," Appl. Opt. 45, 7005-7011 (2006).
    [CrossRef] [PubMed]

2007

2006

S. V. Popruzhenko, D. F. Zaretsky and W. Becker, "Third-harmonic generation by small clusters in a dielectric medium," J. Phys. B. 39, 4933-4943 (2006).
[CrossRef]

V. Barzda, C. Greenhalgh, J. Aus-der-Au and S. Elmore, "Visualization of mitochondria in cardiomyocytes by simultaneous harmonic generation and fluorescence microscopy," Opt. Express 13, 8263-8276 (2006).
[CrossRef]

O. G. Clay, A. C. Millard, C. B. Schaffer, J. Aus-Der-Au, P. S. Tsai, J. A. Squier and D. Kleinfeld, "Spectroscopy of third harmonic generation: evidence for resonances in model compounds and ligated hemoglobin," J. Opt. Soc. Am. B 23, 932-950 (2006).
[CrossRef]

N. Djaker, D. Gachet, N. Sandeau, P.-F. Lenne and H. Rigneault, "Refractive effects in coherent anti-Stokes Raman scattering microscopy," Appl. Opt. 45, 7005-7011 (2006).
[CrossRef] [PubMed]

S.-P. Tai, W.-J. Lee, D.-B. Shieh, P.-C. Wu, H.-Y. Huang, C.-H. Yu and C.-K. Sun, "In vivo optical biopsy of hamster oral cavity with epi-third-harmonic generation microscopy," Opt. Express 14, 6178-6187 (2006).
[CrossRef] [PubMed]

D. Vučinić, T. M. BartolJr. and T. J. Sejnowski, "Hybrid reflecting objectives for functional multiphoton microscopy in turbid media," Opt. Lett. 31, 2447-2449 (2006).
[CrossRef] [PubMed]

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

2005

W. Supatto, D. Débarre, B. Moulia, E. Brouzés, J.-L. Martin, E. Farge and E. Beaurepaire, "In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses," Proc. Nat. Acad. Sci. USA 102, 1047-1052 (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. Nat. Acad. Sci. USA 102, 16807-12 (2005).
[CrossRef] [PubMed]

S.-P. Tai, T.-H. Tsai, W.-J. Lee, D.-B. Shieh, Y.-H. Liao, H.-Y. Huang, K. Y. J. Zhang, H.-L. Liu and C.-K. Sun, "Optical biopsy of fixed human skin with backward-collected optical harmonics signals," Opt. Express 13, 8231-8242 (2005).
[CrossRef] [PubMed]

D. Débarre, W. Supatto and E. Beaurepaire, "Structure sensitivity in third-harmonic generation microscopy," Opt. Lett. 30, 2134-2136 (2005).
[CrossRef] [PubMed]

R. M. Williams, W. R. Zipfel and W. W. Webb, "Interpreting second-harmonic images of collagen I fibrils," Biophys. J. 88, 1377-1386 (2005).
[CrossRef]

M. LippitzM. A. van Dijk.and M. Orrit, "Third-harmonic generation from single gold nanoparticules," Nano Lett. 5, 799-802 (2005).
[CrossRef] [PubMed]

2004

S. Hugues, L. Fetler, L. Bonifaz, J. Helft, F. Amblard and S. Amigorena, "Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity," Nat. Immunol. 5, 1235-42 (2004).
[CrossRef] [PubMed]

D. Oron, D. Yelin, E. Tal, S. Raz, R. Fachima and Y. Silberberg, "Depth-resolved structural imaging by third-harmonic generation microscopy," J. Struct. Biol. 147, 3-11 (2004).
[CrossRef] [PubMed]

D. Débarre, W. Supatto, E. Farge, B. Moulia, M.-C. Schanne-Klein and E. Beaurepaire, "Velocimetric third-harmonic generation microscopy: micrometer-scale quantification of morphogenetic movements in unstained embryos," Opt. Lett. 29, 2881-2883 (2004).
[CrossRef]

2003

C.-K. Sun, C.-C. Chen, S.-W. Chu, T.-H. Tsai, Y.-C. Chen and B.-L. Lin, "Multiharmonic generation biopsy of skin," Opt. Lett. 28, 2488-2490 (2003).
[CrossRef] [PubMed]

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]

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

2002

F. Helmchen and W. Denk, "New developments in multiphoton microscopy", Curr. Opin. Neurobiol. 12, 593-601 (2002).
[CrossRef] [PubMed]

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

E. Beaurepaire and J. Mertz, "Epifluorescence collection in two-photon microscopy," Appl. Opt. 41, 5376-5382 (2002).
[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, 1328-1347 (2002).
[CrossRef]

J. J. Mock, M. Barbic, D. R. Smith, D. A. Schultz and S. Schultz, "Shape effects in plasmon resonance of individual silver nanoparticles," J. Chem. Phys. 116, 6755-6759 (2002).
[CrossRef]

J.-X. Cheng and X. S. Xie, "Green's function formulation for third harmonic generation microscopy," J. Opt. Soc. Am. B 19, 1604-1610 (2002).
[CrossRef]

2001

J. Mertz and L. Moreaux, "Second-harmonic generation by focused excitation of inhomogeneously distributed scatterers," Opt. Commun. 196, 325-330 (2001).
[CrossRef]

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz and S. Charpak, "Two-photon microscopy in brain tissue: parameters influencing the imaging depth," J. Neurosci. Methods 111, 29-37 (2001).
[CrossRef] [PubMed]

S. Charpak, J. Mertz, E. Beaurepaire, L. Moreaux and K. Delaney, "Odor-evoked calcium signals in dendrites of rat mitral cells," Proc. Nat. Acad. Sci. USA 98, 1230-1234 (2001).
[CrossRef] [PubMed]

2000

1999

D. Yelin and Y. Silberberg, "Laser scanning third-harmonic generation microscopy in biology," Opt. Express 5, 169-175 (1999).
[CrossRef] [PubMed]

J. M. Squirrell, D. L. Wokosin, J. G. White and B. D. Bavister, "Long-term two photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef] [PubMed]

1998

M. Müller, J. Squier, K. R. Wilson and G. J. Brakenhoff, "3D-microscopy of transparent objects using third-harmonic generation," J. Microsc. 191, 266-274 (1998).
[CrossRef] [PubMed]

1997

Y. Barad, H. Eisenberg, M. Horowitz and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," Appl. Phys. Lett. 70, 922-924 (1997).
[CrossRef]

K. Svoboda, W. Denk, D. Kleinfeld and D. W. Tank, "In vivo dendritic calcium dynamics in neocortical pyramidal neurons," Nature 385, 161-165 (1997).
[CrossRef] [PubMed]

1989

S. A. Prahl, M. Keijzer, S. L. Jacques and A. J. Welch, "A Monte Carlo model of light propagation in tissue," SPIE Institute Series 5, 102-111 (1989).

1959

B. Richards and E. Wolf, "Electromagnetic diffraction in optical systems II. Structure of the image field in an aplanetic system," Proc. Royal Soc. London Ser. A 253, 358-379 (1959).
[CrossRef]

Amblard, F.

S. Hugues, L. Fetler, L. Bonifaz, J. Helft, F. Amblard and S. Amigorena, "Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity," Nat. Immunol. 5, 1235-42 (2004).
[CrossRef] [PubMed]

Amigorena, S.

S. Hugues, L. Fetler, L. Bonifaz, J. Helft, F. Amblard and S. Amigorena, "Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity," Nat. Immunol. 5, 1235-42 (2004).
[CrossRef] [PubMed]

Aus-der-Au, J.

Barad, Y.

Y. Barad, H. Eisenberg, M. Horowitz and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," Appl. Phys. Lett. 70, 922-924 (1997).
[CrossRef]

Barbic, M.

J. J. Mock, M. Barbic, D. R. Smith, D. A. Schultz and S. Schultz, "Shape effects in plasmon resonance of individual silver nanoparticles," J. Chem. Phys. 116, 6755-6759 (2002).
[CrossRef]

Bartol, T. M.

Barzda, V.

Bavister, B. D.

J. M. Squirrell, D. L. Wokosin, J. G. White and B. D. Bavister, "Long-term two photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef] [PubMed]

Beaurepaire, E.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

D. Débarre, W. Supatto and E. Beaurepaire, "Structure sensitivity in third-harmonic generation microscopy," Opt. Lett. 30, 2134-2136 (2005).
[CrossRef] [PubMed]

W. Supatto, D. Débarre, B. Moulia, E. Brouzés, J.-L. Martin, E. Farge and E. Beaurepaire, "In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses," Proc. Nat. Acad. Sci. USA 102, 1047-1052 (2005).
[CrossRef] [PubMed]

D. Débarre, W. Supatto, E. Farge, B. Moulia, M.-C. Schanne-Klein and E. Beaurepaire, "Velocimetric third-harmonic generation microscopy: micrometer-scale quantification of morphogenetic movements in unstained embryos," Opt. Lett. 29, 2881-2883 (2004).
[CrossRef]

E. Beaurepaire and J. Mertz, "Epifluorescence collection in two-photon microscopy," Appl. Opt. 41, 5376-5382 (2002).
[CrossRef] [PubMed]

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz and S. Charpak, "Two-photon microscopy in brain tissue: parameters influencing the imaging depth," J. Neurosci. Methods 111, 29-37 (2001).
[CrossRef] [PubMed]

S. Charpak, J. Mertz, E. Beaurepaire, L. Moreaux and K. Delaney, "Odor-evoked calcium signals in dendrites of rat mitral cells," Proc. Nat. Acad. Sci. USA 98, 1230-1234 (2001).
[CrossRef] [PubMed]

Becker, W.

S. V. Popruzhenko, D. F. Zaretsky and W. Becker, "Third-harmonic generation by small clusters in a dielectric medium," J. Phys. B. 39, 4933-4943 (2006).
[CrossRef]

Bonifaz, L.

S. Hugues, L. Fetler, L. Bonifaz, J. Helft, F. Amblard and S. Amigorena, "Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity," Nat. Immunol. 5, 1235-42 (2004).
[CrossRef] [PubMed]

Bottinger, E. P.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

Brakenhoff, G. J.

M. Müller, J. Squier, K. R. Wilson and G. J. Brakenhoff, "3D-microscopy of transparent objects using third-harmonic generation," J. Microsc. 191, 266-274 (1998).
[CrossRef] [PubMed]

Brouzés, E.

W. Supatto, D. Débarre, B. Moulia, E. Brouzés, J.-L. Martin, E. Farge and E. Beaurepaire, "In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses," Proc. Nat. Acad. Sci. USA 102, 1047-1052 (2005).
[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]

Campagnola, P. J.

Cermak, L.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

Chaigneau, E.

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz and S. Charpak, "Two-photon microscopy in brain tissue: parameters influencing the imaging depth," J. Neurosci. Methods 111, 29-37 (2001).
[CrossRef] [PubMed]

Charpak, S.

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz and S. Charpak, "Two-photon microscopy in brain tissue: parameters influencing the imaging depth," J. Neurosci. Methods 111, 29-37 (2001).
[CrossRef] [PubMed]

S. Charpak, J. Mertz, E. Beaurepaire, L. Moreaux and K. Delaney, "Odor-evoked calcium signals in dendrites of rat mitral cells," Proc. Nat. Acad. Sci. USA 98, 1230-1234 (2001).
[CrossRef] [PubMed]

Chen, C.-C.

Chen, Y.-C.

Cheng, J.-X.

J.-X. Cheng and X. S. Xie, "Green's function formulation for third harmonic generation microscopy," J. Opt. Soc. Am. B 19, 1604-1610 (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, 1328-1347 (2002).
[CrossRef]

Chu, S.-W.

Clay, O. G.

Combettes, L.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Condeelis, J. S.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

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. Nat. Acad. Sci. USA 102, 16807-12 (2005).
[CrossRef] [PubMed]

Débarre, D.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

D. Débarre, W. Supatto and E. Beaurepaire, "Structure sensitivity in third-harmonic generation microscopy," Opt. Lett. 30, 2134-2136 (2005).
[CrossRef] [PubMed]

W. Supatto, D. Débarre, B. Moulia, E. Brouzés, J.-L. Martin, E. Farge and E. Beaurepaire, "In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses," Proc. Nat. Acad. Sci. USA 102, 1047-1052 (2005).
[CrossRef] [PubMed]

D. Débarre, W. Supatto, E. Farge, B. Moulia, M.-C. Schanne-Klein and E. Beaurepaire, "Velocimetric third-harmonic generation microscopy: micrometer-scale quantification of morphogenetic movements in unstained embryos," Opt. Lett. 29, 2881-2883 (2004).
[CrossRef]

Delaney, K.

S. Charpak, J. Mertz, E. Beaurepaire, L. Moreaux and K. Delaney, "Odor-evoked calcium signals in dendrites of rat mitral cells," Proc. Nat. Acad. Sci. USA 98, 1230-1234 (2001).
[CrossRef] [PubMed]

Denk, W.

F. Helmchen and W. Denk, "New developments in multiphoton microscopy", Curr. Opin. Neurobiol. 12, 593-601 (2002).
[CrossRef] [PubMed]

K. Svoboda, W. Denk, D. Kleinfeld and D. W. Tank, "In vivo dendritic calcium dynamics in neocortical pyramidal neurons," Nature 385, 161-165 (1997).
[CrossRef] [PubMed]

Djaker, N.

Eisenberg, H.

Y. Barad, H. Eisenberg, M. Horowitz and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," Appl. Phys. Lett. 70, 922-924 (1997).
[CrossRef]

Elmore, S.

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. Nat. Acad. Sci. USA 102, 16807-12 (2005).
[CrossRef] [PubMed]

Fabre, A.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Fachima, R.

D. Oron, D. Yelin, E. Tal, S. Raz, R. Fachima and Y. Silberberg, "Depth-resolved structural imaging by third-harmonic generation microscopy," J. Struct. Biol. 147, 3-11 (2004).
[CrossRef] [PubMed]

Farge, E.

W. Supatto, D. Débarre, B. Moulia, E. Brouzés, J.-L. Martin, E. Farge and E. Beaurepaire, "In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses," Proc. Nat. Acad. Sci. USA 102, 1047-1052 (2005).
[CrossRef] [PubMed]

D. Débarre, W. Supatto, E. Farge, B. Moulia, M.-C. Schanne-Klein and E. Beaurepaire, "Velocimetric third-harmonic generation microscopy: micrometer-scale quantification of morphogenetic movements in unstained embryos," Opt. Lett. 29, 2881-2883 (2004).
[CrossRef]

Fetler, L.

S. Hugues, L. Fetler, L. Bonifaz, J. Helft, F. Amblard and S. Amigorena, "Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity," Nat. Immunol. 5, 1235-42 (2004).
[CrossRef] [PubMed]

Frohlich, V. C.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

Gachet, D.

Greenhalgh, C.

Helft, J.

S. Hugues, L. Fetler, L. Bonifaz, J. Helft, F. Amblard and S. Amigorena, "Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity," Nat. Immunol. 5, 1235-42 (2004).
[CrossRef] [PubMed]

Helmchen, F.

F. Helmchen and W. Denk, "New developments in multiphoton microscopy", Curr. Opin. Neurobiol. 12, 593-601 (2002).
[CrossRef] [PubMed]

Horowitz, M.

Y. Barad, H. Eisenberg, M. Horowitz and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," Appl. Phys. Lett. 70, 922-924 (1997).
[CrossRef]

Huang, H.-Y.

Hugues, S.

S. Hugues, L. Fetler, L. Bonifaz, J. Helft, F. Amblard and S. Amigorena, "Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity," Nat. Immunol. 5, 1235-42 (2004).
[CrossRef] [PubMed]

Huttelmaier, S.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

Jacques, S. L.

S. A. Prahl, M. Keijzer, S. L. Jacques and A. J. Welch, "A Monte Carlo model of light propagation in tissue," SPIE Institute Series 5, 102-111 (1989).

Keijzer, M.

S. A. Prahl, M. Keijzer, S. L. Jacques and A. J. Welch, "A Monte Carlo model of light propagation in tissue," SPIE Institute Series 5, 102-111 (1989).

Kleinfeld, D.

Lacomb, R.

Lee, W.-J.

Lenne, P.-F.

Liao, Y.-H.

Lin, B.-L.

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. Nat. Acad. Sci. USA 102, 16807-12 (2005).
[CrossRef] [PubMed]

Lippitz, M.

M. LippitzM. A. van Dijk.and M. Orrit, "Third-harmonic generation from single gold nanoparticules," Nano Lett. 5, 799-802 (2005).
[CrossRef] [PubMed]

Liu, H.-L.

Martin, J.-L.

W. Supatto, D. Débarre, B. Moulia, E. Brouzés, J.-L. Martin, E. Farge and E. Beaurepaire, "In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses," Proc. Nat. Acad. Sci. USA 102, 1047-1052 (2005).
[CrossRef] [PubMed]

Mertz, J.

E. Beaurepaire and J. Mertz, "Epifluorescence collection in two-photon microscopy," Appl. Opt. 41, 5376-5382 (2002).
[CrossRef] [PubMed]

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz and S. Charpak, "Two-photon microscopy in brain tissue: parameters influencing the imaging depth," J. Neurosci. Methods 111, 29-37 (2001).
[CrossRef] [PubMed]

S. Charpak, J. Mertz, E. Beaurepaire, L. Moreaux and K. Delaney, "Odor-evoked calcium signals in dendrites of rat mitral cells," Proc. Nat. Acad. Sci. USA 98, 1230-1234 (2001).
[CrossRef] [PubMed]

J. Mertz and L. Moreaux, "Second-harmonic generation by focused excitation of inhomogeneously distributed scatterers," Opt. Commun. 196, 325-330 (2001).
[CrossRef]

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

Millard, A. C.

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]

Mock, J. J.

J. J. Mock, M. Barbic, D. R. Smith, D. A. Schultz and S. Schultz, "Shape effects in plasmon resonance of individual silver nanoparticles," J. Chem. Phys. 116, 6755-6759 (2002).
[CrossRef]

Mohler, W. A.

Moreaux, L.

J. Mertz and L. Moreaux, "Second-harmonic generation by focused excitation of inhomogeneously distributed scatterers," Opt. Commun. 196, 325-330 (2001).
[CrossRef]

S. Charpak, J. Mertz, E. Beaurepaire, L. Moreaux and K. Delaney, "Odor-evoked calcium signals in dendrites of rat mitral cells," Proc. Nat. Acad. Sci. USA 98, 1230-1234 (2001).
[CrossRef] [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]

Moulia, B.

W. Supatto, D. Débarre, B. Moulia, E. Brouzés, J.-L. Martin, E. Farge and E. Beaurepaire, "In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses," Proc. Nat. Acad. Sci. USA 102, 1047-1052 (2005).
[CrossRef] [PubMed]

D. Débarre, W. Supatto, E. Farge, B. Moulia, M.-C. Schanne-Klein and E. Beaurepaire, "Velocimetric third-harmonic generation microscopy: micrometer-scale quantification of morphogenetic movements in unstained embryos," Opt. Lett. 29, 2881-2883 (2004).
[CrossRef]

Müller, M.

M. Müller, J. Squier, K. R. Wilson and G. J. Brakenhoff, "3D-microscopy of transparent objects using third-harmonic generation," J. Microsc. 191, 266-274 (1998).
[CrossRef] [PubMed]

Nadiarnykh, O.

Oheim, M.

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz and S. Charpak, "Two-photon microscopy in brain tissue: parameters influencing the imaging depth," J. Neurosci. Methods 111, 29-37 (2001).
[CrossRef] [PubMed]

Oleynikov, Y.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

Oron, D.

D. Oron, D. Yelin, E. Tal, S. Raz, R. Fachima and Y. Silberberg, "Depth-resolved structural imaging by third-harmonic generation microscopy," J. Struct. Biol. 147, 3-11 (2004).
[CrossRef] [PubMed]

Orrit, M.

M. LippitzM. A. van Dijk.and M. Orrit, "Third-harmonic generation from single gold nanoparticules," Nano Lett. 5, 799-802 (2005).
[CrossRef] [PubMed]

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]

Pena, A.-M.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Popruzhenko, S. V.

S. V. Popruzhenko, D. F. Zaretsky and W. Becker, "Third-harmonic generation by small clusters in a dielectric medium," J. Phys. B. 39, 4933-4943 (2006).
[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. Nat. Acad. Sci. USA 102, 16807-12 (2005).
[CrossRef] [PubMed]

Prahl, S. A.

S. A. Prahl, M. Keijzer, S. L. Jacques and A. J. Welch, "A Monte Carlo model of light propagation in tissue," SPIE Institute Series 5, 102-111 (1989).

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. Nat. Acad. Sci. USA 102, 16807-12 (2005).
[CrossRef] [PubMed]

Raz, S.

D. Oron, D. Yelin, E. Tal, S. Raz, R. Fachima and Y. Silberberg, "Depth-resolved structural imaging by third-harmonic generation microscopy," J. Struct. Biol. 147, 3-11 (2004).
[CrossRef] [PubMed]

Richards, B.

B. Richards and E. Wolf, "Electromagnetic diffraction in optical systems II. Structure of the image field in an aplanetic system," Proc. Royal Soc. London Ser. A 253, 358-379 (1959).
[CrossRef]

Rigneault, H.

Sandeau, N.

Sandre, O.

Schaffer, C. B.

Schanne-Klein, M.-C.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

D. Débarre, W. Supatto, E. Farge, B. Moulia, M.-C. Schanne-Klein and E. Beaurepaire, "Velocimetric third-harmonic generation microscopy: micrometer-scale quantification of morphogenetic movements in unstained embryos," Opt. Lett. 29, 2881-2883 (2004).
[CrossRef]

Schultz, D. A.

J. J. Mock, M. Barbic, D. R. Smith, D. A. Schultz and S. Schultz, "Shape effects in plasmon resonance of individual silver nanoparticles," J. Chem. Phys. 116, 6755-6759 (2002).
[CrossRef]

Schultz, S.

J. J. Mock, M. Barbic, D. R. Smith, D. A. Schultz and S. Schultz, "Shape effects in plasmon resonance of individual silver nanoparticles," J. Chem. Phys. 116, 6755-6759 (2002).
[CrossRef]

Segall, J. E.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

Sejnowski, T. J.

Shieh, D.-B.

Silberberg, Y.

D. Oron, D. Yelin, E. Tal, S. Raz, R. Fachima and Y. Silberberg, "Depth-resolved structural imaging by third-harmonic generation microscopy," J. Struct. Biol. 147, 3-11 (2004).
[CrossRef] [PubMed]

D. Yelin and Y. Silberberg, "Laser scanning third-harmonic generation microscopy in biology," Opt. Express 5, 169-175 (1999).
[CrossRef] [PubMed]

Y. Barad, H. Eisenberg, M. Horowitz and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," Appl. Phys. Lett. 70, 922-924 (1997).
[CrossRef]

Singer, R. H.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

Smith, D. R.

J. J. Mock, M. Barbic, D. R. Smith, D. A. Schultz and S. Schultz, "Shape effects in plasmon resonance of individual silver nanoparticles," J. Chem. Phys. 116, 6755-6759 (2002).
[CrossRef]

Squier, J.

M. Müller, J. Squier, K. R. Wilson and G. J. Brakenhoff, "3D-microscopy of transparent objects using third-harmonic generation," J. Microsc. 191, 266-274 (1998).
[CrossRef] [PubMed]

Squier, J. A.

Squirrell, J. M.

J. M. Squirrell, D. L. Wokosin, J. G. White and B. D. Bavister, "Long-term two photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef] [PubMed]

Sun, C.-K.

Supatto, W.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

D. Débarre, W. Supatto and E. Beaurepaire, "Structure sensitivity in third-harmonic generation microscopy," Opt. Lett. 30, 2134-2136 (2005).
[CrossRef] [PubMed]

W. Supatto, D. Débarre, B. Moulia, E. Brouzés, J.-L. Martin, E. Farge and E. Beaurepaire, "In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses," Proc. Nat. Acad. Sci. USA 102, 1047-1052 (2005).
[CrossRef] [PubMed]

D. Débarre, W. Supatto, E. Farge, B. Moulia, M.-C. Schanne-Klein and E. Beaurepaire, "Velocimetric third-harmonic generation microscopy: micrometer-scale quantification of morphogenetic movements in unstained embryos," Opt. Lett. 29, 2881-2883 (2004).
[CrossRef]

Svoboda, K.

K. Svoboda, W. Denk, D. Kleinfeld and D. W. Tank, "In vivo dendritic calcium dynamics in neocortical pyramidal neurons," Nature 385, 161-165 (1997).
[CrossRef] [PubMed]

Tai, S.-P.

Tal, E.

D. Oron, D. Yelin, E. Tal, S. Raz, R. Fachima and Y. Silberberg, "Depth-resolved structural imaging by third-harmonic generation microscopy," J. Struct. Biol. 147, 3-11 (2004).
[CrossRef] [PubMed]

Tank, D. W.

K. Svoboda, W. Denk, D. Kleinfeld and D. W. Tank, "In vivo dendritic calcium dynamics in neocortical pyramidal neurons," Nature 385, 161-165 (1997).
[CrossRef] [PubMed]

Tordjmann, T.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Tsai, P. S.

Tsai, T.-H.

van Dijk, M. A.

M. LippitzM. A. van Dijk.and M. Orrit, "Third-harmonic generation from single gold nanoparticules," Nano Lett. 5, 799-802 (2005).
[CrossRef] [PubMed]

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, 1328-1347 (2002).
[CrossRef]

Vucinic, D.

Wang, W.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

Webb, W. W.

R. M. Williams, W. R. Zipfel and W. W. Webb, "Interpreting second-harmonic images of collagen I fibrils," Biophys. J. 88, 1377-1386 (2005).
[CrossRef]

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

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]

Welch, A. J.

S. A. Prahl, M. Keijzer, S. L. Jacques and A. J. Welch, "A Monte Carlo model of light propagation in tissue," SPIE Institute Series 5, 102-111 (1989).

White, J. G.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

J. M. Squirrell, D. L. Wokosin, J. G. White and B. D. Bavister, "Long-term two photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef] [PubMed]

Williams, R. M.

R. M. Williams, W. R. Zipfel and W. W. Webb, "Interpreting second-harmonic images of collagen I fibrils," Biophys. J. 88, 1377-1386 (2005).
[CrossRef]

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

Wilson, K. R.

M. Müller, J. Squier, K. R. Wilson and G. J. Brakenhoff, "3D-microscopy of transparent objects using third-harmonic generation," J. Microsc. 191, 266-274 (1998).
[CrossRef] [PubMed]

Wokosin, D. L.

J. M. Squirrell, D. L. Wokosin, J. G. White and B. D. Bavister, "Long-term two photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef] [PubMed]

Wolf, E.

B. Richards and E. Wolf, "Electromagnetic diffraction in optical systems II. Structure of the image field in an aplanetic system," Proc. Royal Soc. London Ser. A 253, 358-379 (1959).
[CrossRef]

Wu, P.-C.

Wyckoff, J. B.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

Xie, X. S.

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. Nat. Acad. Sci. USA 102, 16807-12 (2005).
[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, 1328-1347 (2002).
[CrossRef]

J.-X. Cheng and X. S. Xie, "Green's function formulation for third harmonic generation microscopy," J. Opt. Soc. Am. B 19, 1604-1610 (2002).
[CrossRef]

Yelin, D.

D. Oron, D. Yelin, E. Tal, S. Raz, R. Fachima and Y. Silberberg, "Depth-resolved structural imaging by third-harmonic generation microscopy," J. Struct. Biol. 147, 3-11 (2004).
[CrossRef] [PubMed]

D. Yelin and Y. Silberberg, "Laser scanning third-harmonic generation microscopy in biology," Opt. Express 5, 169-175 (1999).
[CrossRef] [PubMed]

Yu, C.-H.

Zaretsky, D. F.

S. V. Popruzhenko, D. F. Zaretsky and W. Becker, "Third-harmonic generation by small clusters in a dielectric medium," J. Phys. B. 39, 4933-4943 (2006).
[CrossRef]

Zavadil, J.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[PubMed]

Zhang, K. Y. J.

Zipfel, W. R.

R. M. Williams, W. R. Zipfel and W. W. Webb, "Interpreting second-harmonic images of collagen I fibrils," Biophys. J. 88, 1377-1386 (2005).
[CrossRef]

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

Appl. Opt.

Appl. Phys. Lett.

Y. Barad, H. Eisenberg, M. Horowitz and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," Appl. Phys. Lett. 70, 922-924 (1997).
[CrossRef]

Biophys. J.

R. M. Williams, W. R. Zipfel and W. W. Webb, "Interpreting second-harmonic images of collagen I fibrils," Biophys. J. 88, 1377-1386 (2005).
[CrossRef]

Cancer Res.

W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, J. E. Segall and J. S. Condeelis, "Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling," Cancer Res. 62, 6278-88 (2002).
[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]

Curr. Opin. Neurobiol.

F. Helmchen and W. Denk, "New developments in multiphoton microscopy", Curr. Opin. Neurobiol. 12, 593-601 (2002).
[CrossRef] [PubMed]

J. Chem. Phys.

J. J. Mock, M. Barbic, D. R. Smith, D. A. Schultz and S. Schultz, "Shape effects in plasmon resonance of individual silver nanoparticles," J. Chem. Phys. 116, 6755-6759 (2002).
[CrossRef]

J. Microsc.

M. Müller, J. Squier, K. R. Wilson and G. J. Brakenhoff, "3D-microscopy of transparent objects using third-harmonic generation," J. Microsc. 191, 266-274 (1998).
[CrossRef] [PubMed]

J. Neurosci. Methods

M. Oheim, E. Beaurepaire, E. Chaigneau, J. Mertz and S. Charpak, "Two-photon microscopy in brain tissue: parameters influencing the imaging depth," J. Neurosci. Methods 111, 29-37 (2001).
[CrossRef] [PubMed]

J. Opt. Soc. Am. B

J. Phys. B.

S. V. Popruzhenko, D. F. Zaretsky and W. Becker, "Third-harmonic generation by small clusters in a dielectric medium," J. Phys. B. 39, 4933-4943 (2006).
[CrossRef]

J. Struct. Biol.

D. Oron, D. Yelin, E. Tal, S. Raz, R. Fachima and Y. Silberberg, "Depth-resolved structural imaging by third-harmonic generation microscopy," J. Struct. Biol. 147, 3-11 (2004).
[CrossRef] [PubMed]

Nano Lett.

M. LippitzM. A. van Dijk.and M. Orrit, "Third-harmonic generation from single gold nanoparticules," Nano Lett. 5, 799-802 (2005).
[CrossRef] [PubMed]

Nat. Biotechnol.

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

J. M. Squirrell, D. L. Wokosin, J. G. White and B. D. Bavister, "Long-term two photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef] [PubMed]

Nat. Immunol.

S. Hugues, L. Fetler, L. Bonifaz, J. Helft, F. Amblard and S. Amigorena, "Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity," Nat. Immunol. 5, 1235-42 (2004).
[CrossRef] [PubMed]

Nat. Methods

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Nature

K. Svoboda, W. Denk, D. Kleinfeld and D. W. Tank, "In vivo dendritic calcium dynamics in neocortical pyramidal neurons," Nature 385, 161-165 (1997).
[CrossRef] [PubMed]

Opt. Commun.

J. Mertz and L. Moreaux, "Second-harmonic generation by focused excitation of inhomogeneously distributed scatterers," Opt. Commun. 196, 325-330 (2001).
[CrossRef]

Opt. Express

Opt. Lett.

Proc. Nat. Acad. Sci. USA

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. Nat. Acad. Sci. USA 102, 16807-12 (2005).
[CrossRef] [PubMed]

S. Charpak, J. Mertz, E. Beaurepaire, L. Moreaux and K. Delaney, "Odor-evoked calcium signals in dendrites of rat mitral cells," Proc. Nat. Acad. Sci. USA 98, 1230-1234 (2001).
[CrossRef] [PubMed]

W. Supatto, D. Débarre, B. Moulia, E. Brouzés, J.-L. Martin, E. Farge and E. Beaurepaire, "In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses," Proc. Nat. Acad. Sci. USA 102, 1047-1052 (2005).
[CrossRef] [PubMed]

Proc. Royal Soc. London Ser. A

B. Richards and E. Wolf, "Electromagnetic diffraction in optical systems II. Structure of the image field in an aplanetic system," Proc. Royal Soc. London Ser. A 253, 358-379 (1959).
[CrossRef]

SPIE Institute Series

S. A. Prahl, M. Keijzer, S. L. Jacques and A. J. Welch, "A Monte Carlo model of light propagation in tissue," SPIE Institute Series 5, 102-111 (1989).

Other

C. G. Bohren and D. R. Huffman, Absorption and scattering of light by small particles, (Wiley, New York, 1983).

M. H. Niemz, Laser-tissue interactions - Fundamentals and Applications - Third ed., (Springer, 2004).

R. W. Boyd, Nonlinear Optics, 2nd ed., (Academic Press, 2003).

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Figures (8)

Fig. 1.
Fig. 1.

(A) Geometry and notations (see text). (B) Wave vector mismatch in the forward and backward direction. A slab-like sample is shown for illustrative purpose (see discussion).

Fig. 2.
Fig. 2.

Spatial frequency spectrum for an interface (A) perpendicular and (B) parallel to the excitation beam. In both cases, the large backward wave vector mismatch is not efficiently compensated by the sample structure.

Fig. 3.
Fig. 3.

TH emission patterns for a sphere and a thin slab at the focus of a Gaussian beam. (A) Normalized radiation patterns as a function of slab thickness (top) and sphere diameter (bottom). (B1) Slab: Forward (green triangles, right) and backward (red circles, left) emitted power as a function of thickness (NA=0.9). (B2) Sphere: forward (green triangles, right) and backward (red circles, left) emitted power as a function of diameter (NA=0.9). (C) Sphere: ratio of forward/backward emitted power as a function of diameter and excitation N A (semilog plot).

Fig. 4.
Fig. 4.

Forward and backward emitted TH powers from an axially periodic (sine-like) object in a focused Gaussian beam, as a function of the spatial period δe. (A) Forward and backward emission for several NAs. (B) Radiation patterns for periodicities δe=2μm and δe=152nm (NA=0.9).

Fig. 5.
Fig. 5.

Visibility of dielectric and metallic particles in THG microscopy. (A) Sixth-power dependence of the trans-THG signal on dielectric bead size. Squares: signal obtained from the center of individual polystyrene beads embedded in agarose and centered at the beam focus. Plain lines: sixth-power fits. Dotted line: numerical calculation for NA=0.9 and linear indexes of polystyrene (1.57 at 1180 nm and 1.61 at 393 nm). (B) Top: trans- and epi-detected THG images of a transparent gel containing 330-nm polystyrene beads and 150-nm gold particles. Gold particles are visible in the epi image, whereas polystyrene spheres are not. Bottom: profile through the broken lines indicated in the images. Scale bar is 3 μm. Excitation wavelength is 1180 nm.

Fig. 6.
Fig. 6.

Incidence of absorption and scattering on epidetection of backscattered harmonic light and multiphoton-excited fluorescence from a turbid medium. (A1) Detection of backscattered forward-emitted light (THG). (A2) Detection of light from an isotropic source (2PEF). (B) Epidetected fraction of THG and 2PEF as a function of tissue albedo (g=0.92, ls=25μm, NA=0.95, field of view=1000μm, working distance=2mm, sample thickness=2500μm).

Fig. 7.
Fig. 7.

Incidence of the microscope angular acceptance (field of view) on epidetection of THG and 2PEF from a turbid medium. (A) Measured epidetected fraction as a function of slab thickness (symbols and dotted lines), and corresponding Monte Carlo simulations (plain lines) for two different objectives (60×, 0.9NA and 20×, 0.95NA). Simulations assume that ls (400) =25μm and that the angular field of view is clipped to 0.13 rad (half-angle) by the collection optics. (B) Measured epidetected THG and 2PEF signal at the center of the field, as a function of the angular acceptance of the collection optics.

Fig. 8.
Fig. 8.

Trans- and epi-detection of endogenous THG and multiphoton-excited fluorescence from a washed fresh lung tissue sample. Epi-THG imaging is possible only in thick areas, as opposed to epi-fluorescence. Epi/Trans image pairs were acquired simultaneously. THG and fluorescence images were recorded at different locations. Acquisition time, 10 μs/pixel. Scale bar, 50 μm.

Tables (1)

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Table 1. Forward/Backward THG power ratio generated at an interface as a function of excitation NA.

Equations (1)

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E ( THG ) ( R ) V dV ( I ̂ + k 3 2 ) exp ( ik 3 R r ) 4 π R r P ( 3 ω ) ( r )

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