Abstract

Second Harmonic Generation (SHG) microscopy probes the organization of tissue or material structure through morphological and polarization analyses. In terms of diagnostic or analytical potential, it is important to understand the coherent and incoherent aspects of the emission in highly scattering environments. It is also of fundamental importance whether the SHG polarization signatures are retained in such turbid media. We examine these issues for purified cellulose specimens, which, in analogy to structural proteins, comprise highly birefringent and chiral fibrillar structures. In these matrices we observe predominantly coherent forward directed emission as well as backwards contrast consisting of direct, coherent emission and an incoherent component arising from multiply scattered forward directed SHG. These processes display a pronounced depth dependence evidenced by changes in morphology as well in the measured forward-backwards ratio (F/B). Specifically, from regions near the surface the backwards channel displays small fibrils not present in the forward emission. In addition, at depths beyond one mean free path, the fibril morphologies become highly similar, suggesting the observed backwards contrast is also comprised of a component that arises from multiple scattering of the initially forward directed wave. The depth dependence of the forward to backward ratio is consistent with Monte Carlo simulations of photon diffusion based on the measured scattering coefficient μs of 75 cm-1 and anisotropy factor, g=0.94 at the SHG wavelength. Consistent with the experimental observations, these simulations indicate that the backwards channel becomes increasingly incoherent with increasing depth into the specimen. We also demonstrate that the polarization dependence of the SHG can be measured through 500 µm of thickness. Similarly, the SHG signal anisotropy is largely preserved through this depth with only a slight depolarization being observed.

© 2007 Optical Society of America

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  1. P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).
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    [CrossRef]
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  5. W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U S A 100, 7075-7080 (2003).
    [CrossRef]
  6. S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
    [CrossRef]
  7. E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
    [CrossRef]
  8. 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]
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  12. C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, 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. U S A 102, 16807-16812 (2005).
    [CrossRef]
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    [CrossRef]
  16. R. M. J. Brown, A. C. Millard, and P. J. Campagnola, "Macromolecular structure of cellulose studied by second-harmonic generation imaging microscopy," Opt. Lett. 28, 2207-2209 (2003).
  17. G. Helenius, H. Backdahl, A. Bodin, U. Nannmark, P. Gatenholm, and B. Risberg, "In vivo biocompatibility of bacterial cellulose," J. Biomed. Mater. Res. A 76(2), 431-438 (2006).
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  20. R. Marchesini, A. Bertoni, S. Andreola, E. Melloni, and A. E. Sichirollo, "Extinction and absorption coefficients and scattering phase functions of human tissues in vitro," Appl. Opt. 28, 2318-2324 (1989).
  21. S.-P. Tai, T.-H. Tsai, W.-J. Lee, D.-B. Shieh, Y.-H. Liao, H.-Y. Huang, K. 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]

2006 (2)

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys. J. 90, 693-703 (2006).

G. Helenius, H. Backdahl, A. Bodin, U. Nannmark, P. Gatenholm, and B. Risberg, "In vivo biocompatibility of bacterial cellulose," J. Biomed. Mater. Res. A 76(2), 431-438 (2006).

2005 (4)

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

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, 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. U S A 102, 16807-16812 (2005).
[CrossRef]

M. Han, G. Giese, and J. F. Bille, "Second harmonic generation imaging of collagen fibrils in cornea and sclera," Opt. Express 13, 5791-5797 (2005).
[CrossRef]

S.-P. Tai, T.-H. Tsai, W.-J. Lee, D.-B. Shieh, Y.-H. Liao, H.-Y. Huang, K. 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]

2004 (1)

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef]

2003 (3)

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U S A 100, 7075-7080 (2003).
[CrossRef]

R. M. J. Brown, A. C. Millard, and P. J. Campagnola, "Macromolecular structure of cellulose studied by second-harmonic generation imaging microscopy," Opt. Lett. 28, 2207-2209 (2003).

2002 (2)

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).

A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U S A 99, 11014-11019 (2002).
[CrossRef]

2001 (2)

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]

V. Ottani, M. Raspanti, and A. Ruggeri, "Collagen structure and functional implications," Micron 32, 251-260 (2001).
[CrossRef]

1998 (1)

K. Beck and B. Brodsky, "Supercoiled Protein Motifs: The collagen triple-helix and the alpha-helical coiled coil," J. Struct. Biol. 122, 17-29 (1998).
[CrossRef]

1996 (1)

1995 (1)

L. Wang, S. L. Jacques, and L. Zheng, "MCML--Monte Carlo modeling of light transport in multi-layered tissues," Comput. Methods Programs Biomed. 47, 131-146 (1995).
[CrossRef]

1989 (1)

1984 (1)

T. Itoh and J. R.M. Brown, "The assembly of cellulose microfibrils in Valonia macrophysa," Planta 160, 372-381 (1984).
[CrossRef]

1983 (1)

1973 (1)

Andreola, S.

Backdahl, H.

G. Helenius, H. Backdahl, A. Bodin, U. Nannmark, P. Gatenholm, and B. Risberg, "In vivo biocompatibility of bacterial cellulose," J. Biomed. Mater. Res. A 76(2), 431-438 (2006).

Beck, K.

K. Beck and B. Brodsky, "Supercoiled Protein Motifs: The collagen triple-helix and the alpha-helical coiled coil," J. Struct. Biol. 122, 17-29 (1998).
[CrossRef]

Bertoni, A.

Bille, J. F.

Bodin, A.

G. Helenius, H. Backdahl, A. Bodin, U. Nannmark, P. Gatenholm, and B. Risberg, "In vivo biocompatibility of bacterial cellulose," J. Biomed. Mater. Res. A 76(2), 431-438 (2006).

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]

Bosch, J. J. T.

Boucher, Y.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef]

Brodsky, B.

K. Beck and B. Brodsky, "Supercoiled Protein Motifs: The collagen triple-helix and the alpha-helical coiled coil," J. Struct. Biol. 122, 17-29 (1998).
[CrossRef]

Brown, E.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef]

Brown, J. R.M.

T. Itoh and J. R.M. Brown, "The assembly of cellulose microfibrils in Valonia macrophysa," Planta 160, 372-381 (1984).
[CrossRef]

Brown, R. M. J.

Campagnola, P. J.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys. J. 90, 693-703 (2006).

R. M. J. Brown, A. C. Millard, and P. J. Campagnola, "Macromolecular structure of cellulose studied by second-harmonic generation imaging microscopy," Opt. Lett. 28, 2207-2209 (2003).

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).

Chen, S.-Y.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef]

Chen, Y.-C.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef]

Cheng, J.-X.

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]

Chern, G.-W.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef]

Christie, R.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U S A 100, 7075-7080 (2003).
[CrossRef]

Chu, S.-W.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef]

Cote, D.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, 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. U S A 102, 16807-16812 (2005).
[CrossRef]

diTomaso, E.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef]

Evans, C. L.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, 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. U S A 102, 16807-16812 (2005).
[CrossRef]

Ferwerda, H. A.

Gatenholm, P.

G. Helenius, H. Backdahl, A. Bodin, U. Nannmark, P. Gatenholm, and B. Risberg, "In vivo biocompatibility of bacterial cellulose," J. Biomed. Mater. Res. A 76(2), 431-438 (2006).

Giese, G.

Groenhuis, R. A. J.

Han, M.

Helenius, G.

G. Helenius, H. Backdahl, A. Bodin, U. Nannmark, P. Gatenholm, and B. Risberg, "In vivo biocompatibility of bacterial cellulose," J. Biomed. Mater. Res. A 76(2), 431-438 (2006).

Hoppe, P. E.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).

Huang, H.-Y.

Hyman, B. T.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U S A 100, 7075-7080 (2003).
[CrossRef]

Itoh, T.

T. Itoh and J. R.M. Brown, "The assembly of cellulose microfibrils in Valonia macrophysa," Planta 160, 372-381 (1984).
[CrossRef]

Jacques, S. L.

L. Wang, S. L. Jacques, and L. Zheng, "MCML--Monte Carlo modeling of light transport in multi-layered tissues," Comput. Methods Programs Biomed. 47, 131-146 (1995).
[CrossRef]

Jain, R. K.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef]

Lee, W.-J.

Li, H.

Liao, Y.-H.

Lin, B.-L.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef]

Lin, C. P.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, 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. U S A 102, 16807-16812 (2005).
[CrossRef]

Liu, H.-L.

Malone, C. J.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).

Marchesini, R.

McKee, T.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef]

Melloni, E.

Millard, A. C.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys. J. 90, 693-703 (2006).

R. M. J. Brown, A. C. Millard, and P. J. Campagnola, "Macromolecular structure of cellulose studied by second-harmonic generation imaging microscopy," Opt. Lett. 28, 2207-2209 (2003).

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).

Mohler, W. A.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys. J. 90, 693-703 (2006).

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).

Nannmark, U.

G. Helenius, H. Backdahl, A. Bodin, U. Nannmark, P. Gatenholm, and B. Risberg, "In vivo biocompatibility of bacterial cellulose," J. Biomed. Mater. Res. A 76(2), 431-438 (2006).

Nikitin, A. Y.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U S A 100, 7075-7080 (2003).
[CrossRef]

Ottani, V.

V. Ottani, M. Raspanti, and A. Ruggeri, "Collagen structure and functional implications," Micron 32, 251-260 (2001).
[CrossRef]

Plotnikov, S. V.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys. J. 90, 693-703 (2006).

Pluen, A.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef]

Potma, E. O.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, 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. U S A 102, 16807-16812 (2005).
[CrossRef]

Puoris'haag, M.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, 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. U S A 102, 16807-16812 (2005).
[CrossRef]

Raspanti, M.

V. Ottani, M. Raspanti, and A. Ruggeri, "Collagen structure and functional implications," Micron 32, 251-260 (2001).
[CrossRef]

Reichman, J.

Risberg, B.

G. Helenius, H. Backdahl, A. Bodin, U. Nannmark, P. Gatenholm, and B. Risberg, "In vivo biocompatibility of bacterial cellulose," J. Biomed. Mater. Res. A 76(2), 431-438 (2006).

Ruggeri, A.

V. Ottani, M. Raspanti, and A. Ruggeri, "Collagen structure and functional implications," Micron 32, 251-260 (2001).
[CrossRef]

Seed, B.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef]

Shieh, D.-B.

Sichirollo, A. E.

Sun, C.-K.

S.-P. Tai, T.-H. Tsai, W.-J. Lee, D.-B. Shieh, Y.-H. Liao, H.-Y. Huang, K. 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]

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef]

Tai, S.-P.

Terasaki, M.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).

Tromberg, B. J.

A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U S A 99, 11014-11019 (2002).
[CrossRef]

Tsai, T.-H.

S.-P. Tai, T.-H. Tsai, W.-J. Lee, D.-B. Shieh, Y.-H. Liao, H.-Y. Huang, K. 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).
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S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
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Volkmer, A.

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).
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Wang, L.

L. Wang, S. L. Jacques, and L. Zheng, "MCML--Monte Carlo modeling of light transport in multi-layered tissues," Comput. Methods Programs Biomed. 47, 131-146 (1995).
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Webb, W. W.

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

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U S A 100, 7075-7080 (2003).
[CrossRef]

Williams, R. M.

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

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U S A 100, 7075-7080 (2003).
[CrossRef]

Xie, S.

Xie, X. S.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, 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. U S A 102, 16807-16812 (2005).
[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]

Yeh, A.

A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U S A 99, 11014-11019 (2002).
[CrossRef]

Zhang, K.

Zheng, L.

L. Wang, S. L. Jacques, and L. Zheng, "MCML--Monte Carlo modeling of light transport in multi-layered tissues," Comput. Methods Programs Biomed. 47, 131-146 (1995).
[CrossRef]

Zipfel, W. R.

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

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U S A 100, 7075-7080 (2003).
[CrossRef]

Zoumi, A.

A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U S A 99, 11014-11019 (2002).
[CrossRef]

Appl. Opt. (4)

Biophys. J. (4)

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).

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

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys. J. 90, 693-703 (2006).

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef]

Comput. Methods Programs Biomed. (1)

L. Wang, S. L. Jacques, and L. Zheng, "MCML--Monte Carlo modeling of light transport in multi-layered tissues," Comput. Methods Programs Biomed. 47, 131-146 (1995).
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J. Biomed. Mater. Res. A (1)

G. Helenius, H. Backdahl, A. Bodin, U. Nannmark, P. Gatenholm, and B. Risberg, "In vivo biocompatibility of bacterial cellulose," J. Biomed. Mater. Res. A 76(2), 431-438 (2006).

J. Phys. Chem. B (1)

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]

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K. Beck and B. Brodsky, "Supercoiled Protein Motifs: The collagen triple-helix and the alpha-helical coiled coil," J. Struct. Biol. 122, 17-29 (1998).
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Micron (1)

V. Ottani, M. Raspanti, and A. Ruggeri, "Collagen structure and functional implications," Micron 32, 251-260 (2001).
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Nat. Med. (1)

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
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Opt. Express (2)

Opt. Lett. (1)

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T. Itoh and J. R.M. Brown, "The assembly of cellulose microfibrils in Valonia macrophysa," Planta 160, 372-381 (1984).
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Proc. Natl. Acad. Sci. U S A (3)

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Cote, 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. U S A 102, 16807-16812 (2005).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U S A 100, 7075-7080 (2003).
[CrossRef]

A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U S A 99, 11014-11019 (2002).
[CrossRef]

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