Abstract

Polarization-resolved, second harmonic generation (P-SHG) microscopy at single pixel resolution is utilized for medical diagnosis of pathological skin dermis. In analyzing the large area, pixel by pixel, second-order susceptibility of normal and pathological skin dermis, we found that P-SHG can be used to distinguish normal and dermal pathological conditions of keloid, morphea, and dermal elastolysis. Specifically, we found that the second order susceptibility tensor ratio of d33/d31 for normal skins is 1.27±0.20, while the corresponding values for keloid, morphea, and dermal elastolysis are respectively 1.67±0.29, 1.79±0.30, and 1.75±0.31. We also found that the histograms of the d33/d31 ratio for the pathological skins contain two peak values and are 1.5 times wider than that of the normal case, suggesting that the pathological dermal collagen fibers tend to be more structurally heterogeneous. Our work demonstrates that pixel-resolved, second-order susceptibility microscopy is effective for detecting heterogeneity in spatial distribution of collagen fibers and maybe used for future clinical diagnosis and in vivo studies of collagen pathological conditions.

© 2009 Optical Society of America

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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
  4. B. Berman, and M. R. Duncan, "Pentoxifylline Inhibits the Proliferation of Human Fibroblasts Derived from Keloid, Scleroderma and Morphea Skin and Their Production of Collagen, Glycosaminoglycans and Fibronectin," British J. Dermatology 123, 339-346 (1990).
    [CrossRef]
  5. K. G. Lewis, L. Bercovitch, S. W. Dill, and L. Robinson-Bostom, "Acquired disorders of elastic tissue: Part II. Decreased elastic tissue," J. Am. Acad. Dermatology 51, 165-185 (2004).
    [CrossRef]
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    [CrossRef]
  7. X. Han, R. M. Burke, M. L. Zettel, P. Tang, and E. B. Brown, "Second harmonic properties of tumor collagen: determining the structural relationship between reactive stroma and healthy stroma," Opt. Express 16, 1846-1859 (2008).
    [CrossRef] [PubMed]
  8. H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
    [CrossRef]
  9. W. L. Chen, Y. Sun, W. Lo, H. Y. Tan, and C. Y. Dong, "Combination of multiphoton and reflective confocal imaging of cornea," Microsc. Res. and Tech. 71, 83-85 (2008).
    [CrossRef]
  10. P. Stoller, B. M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J. of Biomed. Opt. 7, 205-214 (2002).
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    [CrossRef]
  13. S. W. Chu, S. Y. Chen, G. W. Chern, T. H. Tsai, Y. C. Chen, B. L. Lin, and C. K. Sun, "Studies of x((2))/x((3)) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
    [CrossRef] [PubMed]
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    [CrossRef]
  17. W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
    [CrossRef]
  18. C. K. Chou, W. L. Chen, P. T. Fwu, S. J. Lin, H. S. Lee, and C. Y. Dong, "Polarization ellipticity compensation in polarization second-harmonic generation microscopy without specimen rotation," J. Biomed. Opt. 13, 014005 (2008).
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  19. Q2. B. Richards, and E. Wolf, "Electromagnetic Diffraction in Optical Systems.2. Structure of the Image Field in an Aplanatic System," Proc. Roy. Soc. London Ser. A-Math.Phys. Scie. 253, 358-379 (1959).
    [CrossRef]
  20. S. W. Chu, S. P. Tai, T. M. Liu, C. K. Sun, and C. H. Lin, "Selective imaging in second-harmonic-generation microscopy with anisotropic radiation," J. Biomed. Opt. 14, 010504 (2009).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  23. E. H. Epstein, "[Alpha1(Iii)]3 Human Skin Collagen - Release by Pepsin Digestion and Preponderance in Fetal Life," J. Biol. Chem. 249, 3225-3231 (1974).
    [PubMed]
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    [CrossRef] [PubMed]
  25. C. Odin, T. Guilbert, A. Alkilani, O. P. Boryskina, V. Fleury, and Y. Le Grand, "Collagen and myosin characterization by orientation field second harmonic microscopy," Opt. Express 16, 16151-16165 (2008).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  28. B. M. Kim, J. Eichler, K. M. Reiser, A. M. Rubenchik, and L. B. Da Silva, "Collagen structure and nonlinear susceptibility: Effects of heat, glycation, and enzymatic cleavage on second harmonic signal intensity," Lasers Surg. Med. 27, 329-335 (2000).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  31. R. W. Boyd, Nonlinear Optics (Academic Press, San Diego, CA., 1992), Chap. 1.

2009 (2)

S. W. Chu, S. P. Tai, T. M. Liu, C. K. Sun, and C. H. Lin, "Selective imaging in second-harmonic-generation microscopy with anisotropic radiation," J. Biomed. Opt. 14, 010504 (2009).
[CrossRef] [PubMed]

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

2008 (7)

C. K. Chou, W. L. Chen, P. T. Fwu, S. J. Lin, H. S. Lee, and C. Y. Dong, "Polarization ellipticity compensation in polarization second-harmonic generation microscopy without specimen rotation," J. Biomed. Opt. 13, 014005 (2008).
[CrossRef] [PubMed]

X. Han, R. M. Burke, M. L. Zettel, P. Tang, and E. B. Brown, "Second harmonic properties of tumor collagen: determining the structural relationship between reactive stroma and healthy stroma," Opt. Express 16, 1846-1859 (2008).
[CrossRef] [PubMed]

C. Odin, T. Guilbert, A. Alkilani, O. P. Boryskina, V. Fleury, and Y. Le Grand, "Collagen and myosin characterization by orientation field second harmonic microscopy," Opt. Express 16, 16151-16165 (2008).
[CrossRef] [PubMed]

J. C. Mansfield, C. P. Winlove, J. Moger, and S. J. Matcher, "Collagen fiber arrangement in normal and diseased cartilage studied by polarization sensitive nonlinear microscopy," J. Biomed. Opt. 13, 044020 (2008).
[CrossRef] [PubMed]

C. Odin, Y. Le Grand, A. Renault, L. Gailhouste, and G. Baffet, "Orientation fields of nonlinear biological fibrils by second harmonic generation microscopy," J. Microscopy-Oxford 229, 32-38 (2008).
[CrossRef]

V. Da Costa, R. Wei, R. Lim, C-H. Sun, J. J. Brown, B. J-F. Wong, "Nondestructive imaging of live human keloid and facial tissue using multiphoton microscopy," Arc. Facial Plastic Surg. 10, 38-43 (2008).
[CrossRef]

W. L. Chen, Y. Sun, W. Lo, H. Y. Tan, and C. Y. Dong, "Combination of multiphoton and reflective confocal imaging of cornea," Microsc. Res. and Tech. 71, 83-85 (2008).
[CrossRef]

2007 (2)

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

F. Tiaho, G. Recher, and D. Rouede, "Estimation of helical angles of myosin and collagen by second harmonic generation imaging microscopy," Opt. Express 15, 12286-12295 (2007).
[CrossRef] [PubMed]

2006 (5)

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, "Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging," Biophys. J. 91, 2620-2625 (2006).
[CrossRef] [PubMed]

M. J. Koehler, K. Konig, P. Elsner, R. Buckle, and M. Kaatz, "In vivo assessment of human skin aging by multiphoton laser scanning tomography," Opt. Lett. 31, 2879-2881 (2006).
[CrossRef] [PubMed]

A. Al-Attar, S. Mess, J. M. Thomassen, C. L. Kauffman, and S. P. Davison, "Keloid pathogenesis and treatment," Plastic Reconstruct. Surg. 117, 286-300 (2006).
[CrossRef]

A. E. Slemp, and R. E. Kirschner, "Keloids and scars: a review of keloids and scars, their pathogenesis, risk factors, and management," Curr. Opin. Ped. 18, 396-402 (2006).
[CrossRef]

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).
[CrossRef]

2005 (3)

2004 (3)

S. W. Chu, S. Y. Chen, G. W. Chern, T. H. Tsai, Y. C. Chen, B. L. Lin, and C. K. Sun, "Studies of x((2))/x((3)) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

K. G. Lewis, L. Bercovitch, S. W. Dill, and L. Robinson-Bostom, "Acquired disorders of elastic tissue: Part II. Decreased elastic tissue," J. Am. Acad. Dermatology 51, 165-185 (2004).
[CrossRef]

K. G. Lewis, S. W. Dill, C. S. Wilkel, and L. Robinson-Bostom, "Mid-dermal elastolysis preceded by acute neutrophilic dermatosis," J. Cutaneous Pathology 31, 72-76 (2004).
[CrossRef]

2002 (2)

P. Stoller, B. M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J. of Biomed. Opt. 7, 205-214 (2002).
[CrossRef]

P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
[CrossRef] [PubMed]

2000 (1)

B. M. Kim, J. Eichler, K. M. Reiser, A. M. Rubenchik, and L. B. Da Silva, "Collagen structure and nonlinear susceptibility: Effects of heat, glycation, and enzymatic cleavage on second harmonic signal intensity," Lasers Surg. Med. 27, 329-335 (2000).
[CrossRef] [PubMed]

1998 (1)

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

1990 (1)

B. Berman, and M. R. Duncan, "Pentoxifylline Inhibits the Proliferation of Human Fibroblasts Derived from Keloid, Scleroderma and Morphea Skin and Their Production of Collagen, Glycosaminoglycans and Fibronectin," British J. Dermatology 123, 339-346 (1990).
[CrossRef]

1977 (1)

W. N. Meigel, S. Gay, and L. Weber, "Dermal Architecture and Collagen Type Distribution," Arch. Dermatol. Res. 259, 1-10 (1977).
[CrossRef] [PubMed]

1974 (1)

E. H. Epstein, "[Alpha1(Iii)]3 Human Skin Collagen - Release by Pepsin Digestion and Preponderance in Fetal Life," J. Biol. Chem. 249, 3225-3231 (1974).
[PubMed]

1959 (1)

Q2. B. Richards, and E. Wolf, "Electromagnetic Diffraction in Optical Systems.2. Structure of the Image Field in an Aplanatic System," Proc. Roy. Soc. London Ser. A-Math.Phys. Scie. 253, 358-379 (1959).
[CrossRef]

Al-Attar, A.

A. Al-Attar, S. Mess, J. M. Thomassen, C. L. Kauffman, and S. P. Davison, "Keloid pathogenesis and treatment," Plastic Reconstruct. Surg. 117, 286-300 (2006).
[CrossRef]

Alkilani, A.

Baffet, G.

C. Odin, Y. Le Grand, A. Renault, L. Gailhouste, and G. Baffet, "Orientation fields of nonlinear biological fibrils by second harmonic generation microscopy," J. Microscopy-Oxford 229, 32-38 (2008).
[CrossRef]

Beck, K.

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

Bercovitch, L.

K. G. Lewis, L. Bercovitch, S. W. Dill, and L. Robinson-Bostom, "Acquired disorders of elastic tissue: Part II. Decreased elastic tissue," J. Am. Acad. Dermatology 51, 165-185 (2004).
[CrossRef]

Berman, B.

B. Berman, and M. R. Duncan, "Pentoxifylline Inhibits the Proliferation of Human Fibroblasts Derived from Keloid, Scleroderma and Morphea Skin and Their Production of Collagen, Glycosaminoglycans and Fibronectin," British J. Dermatology 123, 339-346 (1990).
[CrossRef]

Boryskina, O. P.

Boyd, R. W.

R. W. Boyd, Nonlinear Optics (Academic Press, San Diego, CA., 1992), Chap. 1.

Brodsky, B.

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

Brown, E. B.

Brown, J. J.

V. Da Costa, R. Wei, R. Lim, C-H. Sun, J. J. Brown, B. J-F. Wong, "Nondestructive imaging of live human keloid and facial tissue using multiphoton microscopy," Arc. Facial Plastic Surg. 10, 38-43 (2008).
[CrossRef]

Buckle, R.

Burke, R. M.

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).
[CrossRef]

Celliers, P. M.

P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
[CrossRef] [PubMed]

Chen, J. S.

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 x((2))/x((3)) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Chen, W. L.

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

W. L. Chen, Y. Sun, W. Lo, H. Y. Tan, and C. Y. Dong, "Combination of multiphoton and reflective confocal imaging of cornea," Microsc. Res. and Tech. 71, 83-85 (2008).
[CrossRef]

C. K. Chou, W. L. Chen, P. T. Fwu, S. J. Lin, H. S. Lee, and C. Y. Dong, "Polarization ellipticity compensation in polarization second-harmonic generation microscopy without specimen rotation," J. Biomed. Opt. 13, 014005 (2008).
[CrossRef] [PubMed]

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, "Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging," Biophys. J. 91, 2620-2625 (2006).
[CrossRef] [PubMed]

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 x((2))/x((3)) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Chen, Y. F.

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, "Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging," Biophys. J. 91, 2620-2625 (2006).
[CrossRef] [PubMed]

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 x((2))/x((3)) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Chou, C. K.

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

C. K. Chou, W. L. Chen, P. T. Fwu, S. J. Lin, H. S. Lee, and C. Y. Dong, "Polarization ellipticity compensation in polarization second-harmonic generation microscopy without specimen rotation," J. Biomed. Opt. 13, 014005 (2008).
[CrossRef] [PubMed]

Chu, S. W.

S. W. Chu, S. P. Tai, T. M. Liu, C. K. Sun, and C. H. Lin, "Selective imaging in second-harmonic-generation microscopy with anisotropic radiation," J. Biomed. Opt. 14, 010504 (2009).
[CrossRef] [PubMed]

S. W. Chu, S. Y. Chen, G. W. Chern, T. H. Tsai, Y. C. Chen, B. L. Lin, and C. K. Sun, "Studies of x((2))/x((3)) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Da Costa, V.

V. Da Costa, R. Wei, R. Lim, C-H. Sun, J. J. Brown, B. J-F. Wong, "Nondestructive imaging of live human keloid and facial tissue using multiphoton microscopy," Arc. Facial Plastic Surg. 10, 38-43 (2008).
[CrossRef]

Da Silva, L. B.

P. Stoller, B. M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J. of Biomed. Opt. 7, 205-214 (2002).
[CrossRef]

B. M. Kim, J. Eichler, K. M. Reiser, A. M. Rubenchik, and L. B. Da Silva, "Collagen structure and nonlinear susceptibility: Effects of heat, glycation, and enzymatic cleavage on second harmonic signal intensity," Lasers Surg. Med. 27, 329-335 (2000).
[CrossRef] [PubMed]

Davison, S. P.

A. Al-Attar, S. Mess, J. M. Thomassen, C. L. Kauffman, and S. P. Davison, "Keloid pathogenesis and treatment," Plastic Reconstruct. Surg. 117, 286-300 (2006).
[CrossRef]

Dill, S. W.

K. G. Lewis, L. Bercovitch, S. W. Dill, and L. Robinson-Bostom, "Acquired disorders of elastic tissue: Part II. Decreased elastic tissue," J. Am. Acad. Dermatology 51, 165-185 (2004).
[CrossRef]

K. G. Lewis, S. W. Dill, C. S. Wilkel, and L. Robinson-Bostom, "Mid-dermal elastolysis preceded by acute neutrophilic dermatosis," J. Cutaneous Pathology 31, 72-76 (2004).
[CrossRef]

Dong, C. Y.

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

W. L. Chen, Y. Sun, W. Lo, H. Y. Tan, and C. Y. Dong, "Combination of multiphoton and reflective confocal imaging of cornea," Microsc. Res. and Tech. 71, 83-85 (2008).
[CrossRef]

C. K. Chou, W. L. Chen, P. T. Fwu, S. J. Lin, H. S. Lee, and C. Y. Dong, "Polarization ellipticity compensation in polarization second-harmonic generation microscopy without specimen rotation," J. Biomed. Opt. 13, 014005 (2008).
[CrossRef] [PubMed]

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, "Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging," Biophys. J. 91, 2620-2625 (2006).
[CrossRef] [PubMed]

S. J. Lin, R. J. Wu, H. Y. Tan, W. Lo, W. C. Lin, T. H. Young, C. J. Hsu, J. S. Chen, S. H. Jee, and C. Y. Dong, "Evaluating cutaneous photoaging by use of multiphoton fluorescence and second-harmonic generation microscopy," Opt. Lett. 30, 2275-2277 (2005).
[CrossRef] [PubMed]

S. J. Lin, C. Y. Hsiao, Y. Sun, W. Lo, W. C. Lin, G. J. Jan, S. H. Jee, and C. Y. Dong, "Monitoring the thermally induced structural transitions of collagen by use of second-harmonic generation microscopy," Opt. Lett. 30, 622-624 (2005).
[CrossRef] [PubMed]

Duncan, M. R.

B. Berman, and M. R. Duncan, "Pentoxifylline Inhibits the Proliferation of Human Fibroblasts Derived from Keloid, Scleroderma and Morphea Skin and Their Production of Collagen, Glycosaminoglycans and Fibronectin," British J. Dermatology 123, 339-346 (1990).
[CrossRef]

Eichler, J.

B. M. Kim, J. Eichler, K. M. Reiser, A. M. Rubenchik, and L. B. Da Silva, "Collagen structure and nonlinear susceptibility: Effects of heat, glycation, and enzymatic cleavage on second harmonic signal intensity," Lasers Surg. Med. 27, 329-335 (2000).
[CrossRef] [PubMed]

Elsner, P.

Epstein, E. H.

E. H. Epstein, "[Alpha1(Iii)]3 Human Skin Collagen - Release by Pepsin Digestion and Preponderance in Fetal Life," J. Biol. Chem. 249, 3225-3231 (1974).
[PubMed]

Fleury, V.

Fwu, P. T.

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

C. K. Chou, W. L. Chen, P. T. Fwu, S. J. Lin, H. S. Lee, and C. Y. Dong, "Polarization ellipticity compensation in polarization second-harmonic generation microscopy without specimen rotation," J. Biomed. Opt. 13, 014005 (2008).
[CrossRef] [PubMed]

Gailhouste, L.

C. Odin, Y. Le Grand, A. Renault, L. Gailhouste, and G. Baffet, "Orientation fields of nonlinear biological fibrils by second harmonic generation microscopy," J. Microscopy-Oxford 229, 32-38 (2008).
[CrossRef]

Gay, S.

W. N. Meigel, S. Gay, and L. Weber, "Dermal Architecture and Collagen Type Distribution," Arch. Dermatol. Res. 259, 1-10 (1977).
[CrossRef] [PubMed]

Guilbert, T.

Han, X.

Hsiao, C. H.

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

Hsiao, C. Y.

Hsu, C. J.

Huang, S. C. M.

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

Jan, G. J.

Jee, S. H.

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, "Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging," Biophys. J. 91, 2620-2625 (2006).
[CrossRef] [PubMed]

S. J. Lin, C. Y. Hsiao, Y. Sun, W. Lo, W. C. Lin, G. J. Jan, S. H. Jee, and C. Y. Dong, "Monitoring the thermally induced structural transitions of collagen by use of second-harmonic generation microscopy," Opt. Lett. 30, 622-624 (2005).
[CrossRef] [PubMed]

S. J. Lin, R. J. Wu, H. Y. Tan, W. Lo, W. C. Lin, T. H. Young, C. J. Hsu, J. S. Chen, S. H. Jee, and C. Y. Dong, "Evaluating cutaneous photoaging by use of multiphoton fluorescence and second-harmonic generation microscopy," Opt. Lett. 30, 2275-2277 (2005).
[CrossRef] [PubMed]

Kaatz, M.

Kauffman, C. L.

A. Al-Attar, S. Mess, J. M. Thomassen, C. L. Kauffman, and S. P. Davison, "Keloid pathogenesis and treatment," Plastic Reconstruct. Surg. 117, 286-300 (2006).
[CrossRef]

Kim, B. M.

P. Stoller, B. M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J. of Biomed. Opt. 7, 205-214 (2002).
[CrossRef]

B. M. Kim, J. Eichler, K. M. Reiser, A. M. Rubenchik, and L. B. Da Silva, "Collagen structure and nonlinear susceptibility: Effects of heat, glycation, and enzymatic cleavage on second harmonic signal intensity," Lasers Surg. Med. 27, 329-335 (2000).
[CrossRef] [PubMed]

Kim, D.

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

Kirschner, R. E.

A. E. Slemp, and R. E. Kirschner, "Keloids and scars: a review of keloids and scars, their pathogenesis, risk factors, and management," Curr. Opin. Ped. 18, 396-402 (2006).
[CrossRef]

Koehler, M. J.

Konig, K.

Le Grand, Y.

C. Odin, T. Guilbert, A. Alkilani, O. P. Boryskina, V. Fleury, and Y. Le Grand, "Collagen and myosin characterization by orientation field second harmonic microscopy," Opt. Express 16, 16151-16165 (2008).
[CrossRef] [PubMed]

C. Odin, Y. Le Grand, A. Renault, L. Gailhouste, and G. Baffet, "Orientation fields of nonlinear biological fibrils by second harmonic generation microscopy," J. Microscopy-Oxford 229, 32-38 (2008).
[CrossRef]

Lee, H. S.

C. K. Chou, W. L. Chen, P. T. Fwu, S. J. Lin, H. S. Lee, and C. Y. Dong, "Polarization ellipticity compensation in polarization second-harmonic generation microscopy without specimen rotation," J. Biomed. Opt. 13, 014005 (2008).
[CrossRef] [PubMed]

Lewis, K. G.

K. G. Lewis, L. Bercovitch, S. W. Dill, and L. Robinson-Bostom, "Acquired disorders of elastic tissue: Part II. Decreased elastic tissue," J. Am. Acad. Dermatology 51, 165-185 (2004).
[CrossRef]

K. G. Lewis, S. W. Dill, C. S. Wilkel, and L. Robinson-Bostom, "Mid-dermal elastolysis preceded by acute neutrophilic dermatosis," J. Cutaneous Pathology 31, 72-76 (2004).
[CrossRef]

Li, T. H.

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

Lim, R.

V. Da Costa, R. Wei, R. Lim, C-H. Sun, J. J. Brown, B. J-F. Wong, "Nondestructive imaging of live human keloid and facial tissue using multiphoton microscopy," Arc. Facial Plastic Surg. 10, 38-43 (2008).
[CrossRef]

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 x((2))/x((3)) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Lin, C. H.

S. W. Chu, S. P. Tai, T. M. Liu, C. K. Sun, and C. H. Lin, "Selective imaging in second-harmonic-generation microscopy with anisotropic radiation," J. Biomed. Opt. 14, 010504 (2009).
[CrossRef] [PubMed]

Lin, H. C.

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

Lin, L. C.

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, "Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging," Biophys. J. 91, 2620-2625 (2006).
[CrossRef] [PubMed]

Lin, S. J.

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

C. K. Chou, W. L. Chen, P. T. Fwu, S. J. Lin, H. S. Lee, and C. Y. Dong, "Polarization ellipticity compensation in polarization second-harmonic generation microscopy without specimen rotation," J. Biomed. Opt. 13, 014005 (2008).
[CrossRef] [PubMed]

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, "Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging," Biophys. J. 91, 2620-2625 (2006).
[CrossRef] [PubMed]

S. J. Lin, R. J. Wu, H. Y. Tan, W. Lo, W. C. Lin, T. H. Young, C. J. Hsu, J. S. Chen, S. H. Jee, and C. Y. Dong, "Evaluating cutaneous photoaging by use of multiphoton fluorescence and second-harmonic generation microscopy," Opt. Lett. 30, 2275-2277 (2005).
[CrossRef] [PubMed]

S. J. Lin, C. Y. Hsiao, Y. Sun, W. Lo, W. C. Lin, G. J. Jan, S. H. Jee, and C. Y. Dong, "Monitoring the thermally induced structural transitions of collagen by use of second-harmonic generation microscopy," Opt. Lett. 30, 622-624 (2005).
[CrossRef] [PubMed]

Lin, W. C.

Liu, T. M.

S. W. Chu, S. P. Tai, T. M. Liu, C. K. Sun, and C. H. Lin, "Selective imaging in second-harmonic-generation microscopy with anisotropic radiation," J. Biomed. Opt. 14, 010504 (2009).
[CrossRef] [PubMed]

Lo, W.

W. L. Chen, Y. Sun, W. Lo, H. Y. Tan, and C. Y. Dong, "Combination of multiphoton and reflective confocal imaging of cornea," Microsc. Res. and Tech. 71, 83-85 (2008).
[CrossRef]

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

S. J. Lin, R. J. Wu, H. Y. Tan, W. Lo, W. C. Lin, T. H. Young, C. J. Hsu, J. S. Chen, S. H. Jee, and C. Y. Dong, "Evaluating cutaneous photoaging by use of multiphoton fluorescence and second-harmonic generation microscopy," Opt. Lett. 30, 2275-2277 (2005).
[CrossRef] [PubMed]

S. J. Lin, C. Y. Hsiao, Y. Sun, W. Lo, W. C. Lin, G. J. Jan, S. H. Jee, and C. Y. Dong, "Monitoring the thermally induced structural transitions of collagen by use of second-harmonic generation microscopy," Opt. Lett. 30, 622-624 (2005).
[CrossRef] [PubMed]

Ma, D. H. K.

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

Mansfield, J. C.

J. C. Mansfield, C. P. Winlove, J. Moger, and S. J. Matcher, "Collagen fiber arrangement in normal and diseased cartilage studied by polarization sensitive nonlinear microscopy," J. Biomed. Opt. 13, 044020 (2008).
[CrossRef] [PubMed]

Matcher, S. J.

J. C. Mansfield, C. P. Winlove, J. Moger, and S. J. Matcher, "Collagen fiber arrangement in normal and diseased cartilage studied by polarization sensitive nonlinear microscopy," J. Biomed. Opt. 13, 044020 (2008).
[CrossRef] [PubMed]

Meigel, W. N.

W. N. Meigel, S. Gay, and L. Weber, "Dermal Architecture and Collagen Type Distribution," Arch. Dermatol. Res. 259, 1-10 (1977).
[CrossRef] [PubMed]

Mess, S.

A. Al-Attar, S. Mess, J. M. Thomassen, C. L. Kauffman, and S. P. Davison, "Keloid pathogenesis and treatment," Plastic Reconstruct. Surg. 117, 286-300 (2006).
[CrossRef]

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).
[CrossRef]

Moger, J.

J. C. Mansfield, C. P. Winlove, J. Moger, and S. J. Matcher, "Collagen fiber arrangement in normal and diseased cartilage studied by polarization sensitive nonlinear microscopy," J. Biomed. Opt. 13, 044020 (2008).
[CrossRef] [PubMed]

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).
[CrossRef]

Odin, C.

C. Odin, T. Guilbert, A. Alkilani, O. P. Boryskina, V. Fleury, and Y. Le Grand, "Collagen and myosin characterization by orientation field second harmonic microscopy," Opt. Express 16, 16151-16165 (2008).
[CrossRef] [PubMed]

C. Odin, Y. Le Grand, A. Renault, L. Gailhouste, and G. Baffet, "Orientation fields of nonlinear biological fibrils by second harmonic generation microscopy," J. Microscopy-Oxford 229, 32-38 (2008).
[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).
[CrossRef]

Recher, G.

Reiser, K. M.

P. Stoller, B. M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J. of Biomed. Opt. 7, 205-214 (2002).
[CrossRef]

P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
[CrossRef] [PubMed]

B. M. Kim, J. Eichler, K. M. Reiser, A. M. Rubenchik, and L. B. Da Silva, "Collagen structure and nonlinear susceptibility: Effects of heat, glycation, and enzymatic cleavage on second harmonic signal intensity," Lasers Surg. Med. 27, 329-335 (2000).
[CrossRef] [PubMed]

Renault, A.

C. Odin, Y. Le Grand, A. Renault, L. Gailhouste, and G. Baffet, "Orientation fields of nonlinear biological fibrils by second harmonic generation microscopy," J. Microscopy-Oxford 229, 32-38 (2008).
[CrossRef]

Richards, B.

Q2. B. Richards, and E. Wolf, "Electromagnetic Diffraction in Optical Systems.2. Structure of the Image Field in an Aplanatic System," Proc. Roy. Soc. London Ser. A-Math.Phys. Scie. 253, 358-379 (1959).
[CrossRef]

Robinson-Bostom, L.

K. G. Lewis, L. Bercovitch, S. W. Dill, and L. Robinson-Bostom, "Acquired disorders of elastic tissue: Part II. Decreased elastic tissue," J. Am. Acad. Dermatology 51, 165-185 (2004).
[CrossRef]

K. G. Lewis, S. W. Dill, C. S. Wilkel, and L. Robinson-Bostom, "Mid-dermal elastolysis preceded by acute neutrophilic dermatosis," J. Cutaneous Pathology 31, 72-76 (2004).
[CrossRef]

Rouede, D.

Rubenchik, A. M.

P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
[CrossRef] [PubMed]

P. Stoller, B. M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J. of Biomed. Opt. 7, 205-214 (2002).
[CrossRef]

B. M. Kim, J. Eichler, K. M. Reiser, A. M. Rubenchik, and L. B. Da Silva, "Collagen structure and nonlinear susceptibility: Effects of heat, glycation, and enzymatic cleavage on second harmonic signal intensity," Lasers Surg. Med. 27, 329-335 (2000).
[CrossRef] [PubMed]

Slemp, A. E.

A. E. Slemp, and R. E. Kirschner, "Keloids and scars: a review of keloids and scars, their pathogenesis, risk factors, and management," Curr. Opin. Ped. 18, 396-402 (2006).
[CrossRef]

So, P. T. C.

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, "Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging," Biophys. J. 91, 2620-2625 (2006).
[CrossRef] [PubMed]

Stoller, P.

P. Stoller, B. M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J. of Biomed. Opt. 7, 205-214 (2002).
[CrossRef]

P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
[CrossRef] [PubMed]

Su, P. J.

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

Sun, C. K.

S. W. Chu, S. P. Tai, T. M. Liu, C. K. Sun, and C. H. Lin, "Selective imaging in second-harmonic-generation microscopy with anisotropic radiation," J. Biomed. Opt. 14, 010504 (2009).
[CrossRef] [PubMed]

S. W. Chu, S. Y. Chen, G. W. Chern, T. H. Tsai, Y. C. Chen, B. L. Lin, and C. K. Sun, "Studies of x((2))/x((3)) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Sun, C-H.

V. Da Costa, R. Wei, R. Lim, C-H. Sun, J. J. Brown, B. J-F. Wong, "Nondestructive imaging of live human keloid and facial tissue using multiphoton microscopy," Arc. Facial Plastic Surg. 10, 38-43 (2008).
[CrossRef]

Sun, Y.

W. L. Chen, Y. Sun, W. Lo, H. Y. Tan, and C. Y. Dong, "Combination of multiphoton and reflective confocal imaging of cornea," Microsc. Res. and Tech. 71, 83-85 (2008).
[CrossRef]

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, "Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging," Biophys. J. 91, 2620-2625 (2006).
[CrossRef] [PubMed]

S. J. Lin, C. Y. Hsiao, Y. Sun, W. Lo, W. C. Lin, G. J. Jan, S. H. Jee, and C. Y. Dong, "Monitoring the thermally induced structural transitions of collagen by use of second-harmonic generation microscopy," Opt. Lett. 30, 622-624 (2005).
[CrossRef] [PubMed]

Tai, S. P.

S. W. Chu, S. P. Tai, T. M. Liu, C. K. Sun, and C. H. Lin, "Selective imaging in second-harmonic-generation microscopy with anisotropic radiation," J. Biomed. Opt. 14, 010504 (2009).
[CrossRef] [PubMed]

Tan, H. Y.

W. L. Chen, Y. Sun, W. Lo, H. Y. Tan, and C. Y. Dong, "Combination of multiphoton and reflective confocal imaging of cornea," Microsc. Res. and Tech. 71, 83-85 (2008).
[CrossRef]

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

S. J. Lin, R. J. Wu, H. Y. Tan, W. Lo, W. C. Lin, T. H. Young, C. J. Hsu, J. S. Chen, S. H. Jee, and C. Y. Dong, "Evaluating cutaneous photoaging by use of multiphoton fluorescence and second-harmonic generation microscopy," Opt. Lett. 30, 2275-2277 (2005).
[CrossRef] [PubMed]

Tang, P.

Teng, S. W.

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

Thomassen, J. M.

A. Al-Attar, S. Mess, J. M. Thomassen, C. L. Kauffman, and S. P. Davison, "Keloid pathogenesis and treatment," Plastic Reconstruct. Surg. 117, 286-300 (2006).
[CrossRef]

Tiaho, F.

Tsai, T. H.

S. W. Chu, S. Y. Chen, G. W. Chern, T. H. Tsai, Y. C. Chen, B. L. Lin, and C. K. Sun, "Studies of x((2))/x((3)) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

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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).
[CrossRef]

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W. N. Meigel, S. Gay, and L. Weber, "Dermal Architecture and Collagen Type Distribution," Arch. Dermatol. Res. 259, 1-10 (1977).
[CrossRef] [PubMed]

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V. Da Costa, R. Wei, R. Lim, C-H. Sun, J. J. Brown, B. J-F. Wong, "Nondestructive imaging of live human keloid and facial tissue using multiphoton microscopy," Arc. Facial Plastic Surg. 10, 38-43 (2008).
[CrossRef]

Wilkel, C. S.

K. G. Lewis, S. W. Dill, C. S. Wilkel, and L. Robinson-Bostom, "Mid-dermal elastolysis preceded by acute neutrophilic dermatosis," J. Cutaneous Pathology 31, 72-76 (2004).
[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).
[CrossRef]

Winlove, C. P.

J. C. Mansfield, C. P. Winlove, J. Moger, and S. J. Matcher, "Collagen fiber arrangement in normal and diseased cartilage studied by polarization sensitive nonlinear microscopy," J. Biomed. Opt. 13, 044020 (2008).
[CrossRef] [PubMed]

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Q2. B. Richards, and E. Wolf, "Electromagnetic Diffraction in Optical Systems.2. Structure of the Image Field in an Aplanatic System," Proc. Roy. Soc. London Ser. A-Math.Phys. Scie. 253, 358-379 (1959).
[CrossRef]

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V. Da Costa, R. Wei, R. Lim, C-H. Sun, J. J. Brown, B. J-F. Wong, "Nondestructive imaging of live human keloid and facial tissue using multiphoton microscopy," Arc. Facial Plastic Surg. 10, 38-43 (2008).
[CrossRef]

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H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

S. J. Lin, R. J. Wu, H. Y. Tan, W. Lo, W. C. Lin, T. H. Young, C. J. Hsu, J. S. Chen, S. H. Jee, and C. Y. Dong, "Evaluating cutaneous photoaging by use of multiphoton fluorescence and second-harmonic generation microscopy," Opt. Lett. 30, 2275-2277 (2005).
[CrossRef] [PubMed]

Young, T. H.

Zettel, M. L.

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).
[CrossRef]

Appl. Phy. Lett. (1)

W. L. Chen, T. H. Li, P. J. Su, C. K. Chou, P. T. Fwu, S. J. Lin, D. Kim, P. T. C. So, and C. Y. Dong, "Second harmonic generation chi tensor microscopy for tissue imaging," Appl. Phy. Lett. 94, 183902 (2009).
[CrossRef]

Arc. Facial Plastic Surg. (1)

V. Da Costa, R. Wei, R. Lim, C-H. Sun, J. J. Brown, B. J-F. Wong, "Nondestructive imaging of live human keloid and facial tissue using multiphoton microscopy," Arc. Facial Plastic Surg. 10, 38-43 (2008).
[CrossRef]

Arch. Dermatol. Res. (1)

W. N. Meigel, S. Gay, and L. Weber, "Dermal Architecture and Collagen Type Distribution," Arch. Dermatol. Res. 259, 1-10 (1977).
[CrossRef] [PubMed]

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P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
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Y. Sun, W. L. Chen, S. J. Lin, S. H. Jee, Y. F. Chen, L. C. Lin, P. T. C. So, and C. Y. Dong, "Investigating mechanisms of collagen thermal denaturation by high resolution second-harmonic generation imaging," Biophys. J. 91, 2620-2625 (2006).
[CrossRef] [PubMed]

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).
[CrossRef]

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).
[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 x((2))/x((3)) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

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B. Berman, and M. R. Duncan, "Pentoxifylline Inhibits the Proliferation of Human Fibroblasts Derived from Keloid, Scleroderma and Morphea Skin and Their Production of Collagen, Glycosaminoglycans and Fibronectin," British J. Dermatology 123, 339-346 (1990).
[CrossRef]

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A. E. Slemp, and R. E. Kirschner, "Keloids and scars: a review of keloids and scars, their pathogenesis, risk factors, and management," Curr. Opin. Ped. 18, 396-402 (2006).
[CrossRef]

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K. G. Lewis, L. Bercovitch, S. W. Dill, and L. Robinson-Bostom, "Acquired disorders of elastic tissue: Part II. Decreased elastic tissue," J. Am. Acad. Dermatology 51, 165-185 (2004).
[CrossRef]

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[PubMed]

J. Biomed. Opt. (3)

C. K. Chou, W. L. Chen, P. T. Fwu, S. J. Lin, H. S. Lee, and C. Y. Dong, "Polarization ellipticity compensation in polarization second-harmonic generation microscopy without specimen rotation," J. Biomed. Opt. 13, 014005 (2008).
[CrossRef] [PubMed]

S. W. Chu, S. P. Tai, T. M. Liu, C. K. Sun, and C. H. Lin, "Selective imaging in second-harmonic-generation microscopy with anisotropic radiation," J. Biomed. Opt. 14, 010504 (2009).
[CrossRef] [PubMed]

J. C. Mansfield, C. P. Winlove, J. Moger, and S. J. Matcher, "Collagen fiber arrangement in normal and diseased cartilage studied by polarization sensitive nonlinear microscopy," J. Biomed. Opt. 13, 044020 (2008).
[CrossRef] [PubMed]

J. Cutaneous Pathology (1)

K. G. Lewis, S. W. Dill, C. S. Wilkel, and L. Robinson-Bostom, "Mid-dermal elastolysis preceded by acute neutrophilic dermatosis," J. Cutaneous Pathology 31, 72-76 (2004).
[CrossRef]

J. Microscopy-Oxford (1)

C. Odin, Y. Le Grand, A. Renault, L. Gailhouste, and G. Baffet, "Orientation fields of nonlinear biological fibrils by second harmonic generation microscopy," J. Microscopy-Oxford 229, 32-38 (2008).
[CrossRef]

J. of Biomed. Opt. (2)

H. Y. Tan, Y. Sun, W. Lo, S. W. Teng, R. J. Wu, S. H. Jee, W. C. Lin, C. H. Hsiao, H. C. Lin, Y. F. Chen, D. H. K. Ma, S. C. M. Huang, S. J. Lin, and C. Y. Dong, "Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis," J. of Biomed. Opt. 12, 024013 (2007).
[CrossRef]

P. Stoller, B. M. Kim, A. M. Rubenchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J. of Biomed. Opt. 7, 205-214 (2002).
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B. M. Kim, J. Eichler, K. M. Reiser, A. M. Rubenchik, and L. B. Da Silva, "Collagen structure and nonlinear susceptibility: Effects of heat, glycation, and enzymatic cleavage on second harmonic signal intensity," Lasers Surg. Med. 27, 329-335 (2000).
[CrossRef] [PubMed]

Microsc. Res. and Tech. (1)

W. L. Chen, Y. Sun, W. Lo, H. Y. Tan, and C. Y. Dong, "Combination of multiphoton and reflective confocal imaging of cornea," Microsc. Res. and Tech. 71, 83-85 (2008).
[CrossRef]

Opt. Express (3)

Opt. Lett. (3)

Phys. Scie. (1)

Q2. B. Richards, and E. Wolf, "Electromagnetic Diffraction in Optical Systems.2. Structure of the Image Field in an Aplanatic System," Proc. Roy. Soc. London Ser. A-Math.Phys. Scie. 253, 358-379 (1959).
[CrossRef]

Plastic Reconstruct. Surg. (1)

A. Al-Attar, S. Mess, J. M. Thomassen, C. L. Kauffman, and S. P. Davison, "Keloid pathogenesis and treatment," Plastic Reconstruct. Surg. 117, 286-300 (2006).
[CrossRef]

Other (1)

R. W. Boyd, Nonlinear Optics (Academic Press, San Diego, CA., 1992), Chap. 1.

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Figures (6)

Fig. 1.
Fig. 1.

Graphical illustration showing the polarization direction of the laser relative to the orientation of the fiber. The laser is incident along the +y direction. θL is the angle of the excitation polarization and θF is the angle of fiber orientation measured with respect to the z-axis. The angle between excitation polarization and fiber orientation is ϕ=θL -θF .

Fig. 2.
Fig. 2.

Schematic diagram of the P-SHG microscope. Half and quarter wave plates were used to compensate the depolarization caused by the main dichroic mirror.

Fig. 3.
Fig. 3.

Single-pixel resolved, P-SHG image analysis in normal skin dermis. (a). SHG intensity image. (b). Plot of SHG intensity versus the relative angle between laser and fiber for the selected pixel (red square) in A. The fitting parameters determined with Eq. (3) are d33/d31 =1.41±0.05, d15/d31 =0.78±0.09. (c) Image and (d) histogram of d33/d31 for the normal dermis image shown in (a). Inhomogeneous distribution of d33/d31 is revealed in (c) and (d). Pk and Sd stand for the peak value and standard deviation of the histogram. Scale bar is 50µm.

Fig. 4.
Fig. 4.

Spatially resolved d33/d31 maps for normal and pathological dermis are shown. (a)~(d): normal, E~H: keloid, I~L: morphea, and M~Q: dermal elastolysis. The false color palette mapping the corresponding d33/d31 values is displayed on the upper right corner. Each image size is 206×206 µm2.

Fig. 5.
Fig. 5.

Histograms of (a) d33/d31 and (b) d15/d31 for normal, keloid, morphea, and dermal elastolysis skin dermis are shown with the peak value (Pk) and the standard deviation (Sd) of each distribution. Histograms of d33/d31 and d15/d31 for normal and pathological skin dermis range respectively from 0.64 to 2.25 and 0.1 to 1.5. Note that the d33/d31 distributions for the pathological samples all have wider spread than that of the normal samples. Such dependence was not observed in the d15/d31 results.

Fig. 6.
Fig. 6.

(a). Peak values and (b) the standard deviation of the distribution of d33/d31 for each sample. The letter denotes the sample type and the number corresponds to the specimen number. N: normal dermis, K: keloid, M: morphea,, and D: dermal elastolysis.

Tables (1)

Tables Icon

Table 1. Numerical summary of second-order susceptibility analysis for normal and pathological dermis

Equations (3)

Equations on this page are rendered with MathJax. Learn more.

P=χ(1) E +χ(2) E E +χ(3)E E E + ...,
{Px=(d15sin2φ)E2Pz=(d31sin2φ+d33cos2φ)E2
I Px2 +Pz2 {(d15d31sin2ϕ)2+(sin2ϕ+d33d31cos2ϕ)2} E4

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