Abstract

We have used a multidimensional non-linear laser imaging approach to visualize ex-vivo samples of basal cell carcinoma (BCC). A combination of several non-linear laser imaging techniques involving fluorescence lifetime, multispectral two-photon and second-harmonic generation imaging has been used to image different skin layers. This approach has elucidated some morphological (supported by histopathological images), biochemical, and physiochemical differences of the healthy samples with respect to BCC ones. In particular, in comparison with normal skin, BCC showed a blue-shifted fluorescence emission, a higher fluorescence response at 800 nm excitation wavelength and a slightly longer mean fluorescence lifetime. Finally, the use of aminolevulinic acid as a contrast agent has been demonstrated to increase the constrast in tumor border detection. The results obtained provide further support for in-vivo non-invasive imaging of Basal Cell Carcinoma.

© 2007 Optical Society of America

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  1. W. Denk, J. H. Strickler and W. W. Webb, "Two-photon laser scanning fluorescence microscope," Science 248, 73-76 (1990).
    [CrossRef]
  2. W. R. Zipfel, R. M. Williams and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1369-1377 (2003).
    [CrossRef]
  3. 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. USA 99, 11014-11019 (2002).
  4. 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. USA 100, 7075-7080 (2003).
  5. B. R. Masters, P. T. C. So and E. Gratton, "Optical biopsy of in vivo human skin: multi-photon excitation microscopy," Lasers Med. Sci. 13, 196-203 (1998).
    [CrossRef]
  6. P. T. C. So, H. Kim and I. E. Kochevar, "Two-Photon deep tissue ex vivo imaging of mouse dermal and subcutaneous structures," Opt. Express 3, 339-351 (1998).
  7. J. C. Malone, A. F. Hood, T. Conley, J. Nürnberger, L. A. Baldridge, J. L. Clendenon, K. W. Dunn and C. L. Phillips, "Three-dimensional imaging of human skin and mucosa by two-photon laser scanning microscopy," J. Cutan. Pathol. 29, 453-458 (2002).
    [CrossRef]
  8. B. R. Masters and P. T. C. So, "Confocal microscopy and multi-photon excitation microscopy of human skin in vivo," Opt. Express 8, 2-9 (2001).
  9. K. König and I. Riemann, "High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution," J. Biomed. Opt. 8(3), 432-439 (2003).
  10. L. Moreaux, O. Sandre, S. Charpak, M. Blanchard-Desce and J. Mertz, "Coherent scattering in multi-harmonic light microscopy," Biophys. J. 80(3), 1568-1574 (2001).
  11. P. J. Campagnola and L. M. Loew, "Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms," Nat. Biotechnol. 21, 1356-1360 (2003).
    [CrossRef]
  12. P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone and W. A. Mohler, "Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 81, 493-508 (2002).
  13. S. Roth and I. Freund, "Second harmonic generation in collagen," J. Chem. Phys. 70, 1637-1643 (1979).
    [CrossRef]
  14. K. König, K. Schenke-Layland, I. Riemann and U. A. Stock, "Multiphoton autofluorescence imaging of intratissue elastic fibers," Biomaterials 26, 495-500 (2005).
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  15. 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).
  16. 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).
  17. T. Yasui, Y. Tohno and T. Araki, "Characterization of collagen orientation in human dermis by two-dimensional second-harmonic-generation polarimetry," J. Biomed. Opt. 9(2), 259-264 (2004).
    [CrossRef]
  18. 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).
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  19. 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]
  20. 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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  21. S. J. Lin, S. H. Jee, C. J. Kuo, R. J. Wu, W. C. Lin, J. S. Chen, Y. H. Liao, C. J. Hsu, T. F. Tsai, Y. F. Chen and C. Y. Dong, "Discrimination of basal cell carcinoma from normal dermal stroma by quantitative multiphoton imaging," Opt. Lett. 31, 2756-2758 (2006).
    [CrossRef]
  22. P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4(1), 38 (2006).
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  23. 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. 17, 2275-2277 (2005).
  24. M. J. Koehler, K. König, P. Elsner, R. Bückle and M. Kaatz, "In vivo assessment of human skin aging by multiphoton laser scanning tomography," Opt. Lett. 19, 2879-2881 (2006).
  25. P. J. Tadrous, "Methods for imaging the structure and function of living tissues and cells: 2. Fluorescence lifetime imaging," J. Pathol. 191, 229-234 (2000).
    [CrossRef]
  26. P. J. Tadrous, J. Siegel, P. M. W. French, S. Shousha, E. N. Lalani and G. W. H. Stamp, "Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer," J. Pathol. 199, 309-317 (2003).
    [CrossRef]
  27. Y. Chen and A. Periasamy, "Characterization of two-photon excitation fluorescence lifetime imaging microscopy for protein localization," Microsc. Res. Tech. 63(1), 72-80 (2004).
    [CrossRef]
  28. S. Y. Breusegem, M. Levi and N. P. Barry, "Fluorescence correlation spectroscopy and fluorescence lifetime imaging microscopy," Nephron. Exp. Nephrol. 103(2), e41-e49 (2006).
    [CrossRef]
  29. K. M. Hanson, M. J. Behne, N. P. Barry, T. M. Mauro, E. Gratton and R. M. Clegg, "Two-photon fluorescence lifetime imaging of the skin stratum corneum pH gradient," Biophys. J. 83, 1682-1690 (2002).
  30. A. M. Pena, M. Strupler, T. Boulesteix and M. C. Shanne-Klein, "Spectroscopic analysis of keratin endogenous signal for skin multiphoton microscopy," Opt. Express 13, 6268-6274 (2005).
    [CrossRef]
  31. L. H. Laiho, S. Pelet, T. M. Hancewicz, P. D. Kaplan and P. T. C. So, "Two-photon 3-D mapping of ex vivo human skin endogenous fluorescence species based on fluorescence emission spectra," J. Biomed. Opt. 10(2), 024016 (2005).
    [CrossRef]
  32. J. Chen, S. Zhuo, T. Luo, X. Jiang and J. Zhao, "Spectral characteristics of autofluorescence and second harmonic generation from ex vivo human skin induced by femtosecond laser and visible lasers," Scanning 28(6), 319-326 (2006).
  33. S. Gonzalez and Z. Tannous, "Real-time in vivo confocal reflectance microscopy of basal cell carcinoma," J. Am. Acad. Dermatol. 47, 869-874 (2002).
    [CrossRef]
  34. D. E. Marra, A. Torres, C. F: Schanbacher and S. Gonzalez, "Detection of residual basal cell carcinoma by in vivo confocal microscopy," Dermatol. Surg. 31, 538-541 (2005).
  35. M. B. Ericson, J. Uhre, C. Strandeberg, B. Stenquist, O. Larko, A. M. Wennberg and A. Rosen, "Bispectral fluorescence imaging combined with texture analysis and linear discrimination for correlation with histopathologic extent of basal cell carcinoma," J. Biomed. Opt. 10(3), 034009 (2005).
    [CrossRef]
  36. S. Andersson-Engels, G. Canti, R. Cubeddu, C. Eker, C. af Klinteberg, A. Pifferi, K. Svanberg, S. Svanberg, P. Taroni, G. Valentini and I. Wang, "Preliminary evaluation of two fluorescence imaging methods for the detection and the delineation of basal cell carcinomas of the skin," Lasers Surg. Med. 26(1), 76-82 (2000).
    [CrossRef]
  37. J. E. Blume and A. R. Oseroff, "Aminolevulinic acid photodynamic therapy for skin cancers," Dermatol. Clin. 25(1), 5-14 (2007).
  38. J. C. Kennedy, R. H. Pottier and D. C. Pross, "Photodynamic therapy with endogenous protoporphyrine IX: Basic principles and present clinical experience," J. Photochem. Photobiol. B 6, 143-148 (1990).
    [CrossRef]
  39. M. Kress, T. Meier, R. Steiner, F. Dolp, R. Erdmann, U. Ortmann and A. Rück, "Time-resolved microspectrofluorometry and fluorescence lifetime imaging of photosensitizers using picosecond pulsed diode lasers in laser scanning microscopes," J. Biomed. Opt. 8(1), 26-32 (2003).
    [CrossRef]
  40. J. R. Lackowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt and M. Johnson, "Fluorescence lifetime imaging," Ann. Biochem. 202: 316-330 (1992).
  41. M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12(2), 024014 (2007).
    [CrossRef]
  42. T. Mitschele, B. Diesel, M. Friedrich, V. Meineke, R. M. Maas, B. C. Gärtner, J. Kamradt, E. Meese, W. Tilgen and J. Reichrath, "Analysis of the vitamin D system in basal cell carcinomas (BCCs)," Lab. Invest. 84, 693-702 (2004).
    [CrossRef]
  43. D. D. Bikle, Y. Oda and Z. Xie, "Vitamin D and skin cancer: A problem in gene regulation," J. Steroid. Biochem. Mol. Biol. 97, 83-91 (2005).
    [CrossRef]

2007 (2)

J. E. Blume and A. R. Oseroff, "Aminolevulinic acid photodynamic therapy for skin cancers," Dermatol. Clin. 25(1), 5-14 (2007).

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12(2), 024014 (2007).
[CrossRef]

2006 (6)

S. J. Lin, S. H. Jee, C. J. Kuo, R. J. Wu, W. C. Lin, J. S. Chen, Y. H. Liao, C. J. Hsu, T. F. Tsai, Y. F. Chen and C. Y. Dong, "Discrimination of basal cell carcinoma from normal dermal stroma by quantitative multiphoton imaging," Opt. Lett. 31, 2756-2758 (2006).
[CrossRef]

J. Chen, S. Zhuo, T. Luo, X. Jiang and J. Zhao, "Spectral characteristics of autofluorescence and second harmonic generation from ex vivo human skin induced by femtosecond laser and visible lasers," Scanning 28(6), 319-326 (2006).

M. J. Koehler, K. König, P. Elsner, R. Bückle and M. Kaatz, "In vivo assessment of human skin aging by multiphoton laser scanning tomography," Opt. Lett. 19, 2879-2881 (2006).

S. Y. Breusegem, M. Levi and N. P. Barry, "Fluorescence correlation spectroscopy and fluorescence lifetime imaging microscopy," Nephron. Exp. Nephrol. 103(2), e41-e49 (2006).
[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]

P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4(1), 38 (2006).
[CrossRef]

2005 (9)

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. 17, 2275-2277 (2005).

K. König, K. Schenke-Layland, I. Riemann and U. A. Stock, "Multiphoton autofluorescence imaging of intratissue elastic fibers," Biomaterials 26, 495-500 (2005).
[CrossRef]

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).

L. H. Laiho, S. Pelet, T. M. Hancewicz, P. D. Kaplan and P. T. C. So, "Two-photon 3-D mapping of ex vivo human skin endogenous fluorescence species based on fluorescence emission spectra," J. Biomed. Opt. 10(2), 024016 (2005).
[CrossRef]

D. E. Marra, A. Torres, C. F: Schanbacher and S. Gonzalez, "Detection of residual basal cell carcinoma by in vivo confocal microscopy," Dermatol. Surg. 31, 538-541 (2005).

M. B. Ericson, J. Uhre, C. Strandeberg, B. Stenquist, O. Larko, A. M. Wennberg and A. Rosen, "Bispectral fluorescence imaging combined with texture analysis and linear discrimination for correlation with histopathologic extent of basal cell carcinoma," J. Biomed. Opt. 10(3), 034009 (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]

A. M. Pena, M. Strupler, T. Boulesteix and M. C. Shanne-Klein, "Spectroscopic analysis of keratin endogenous signal for skin multiphoton microscopy," Opt. Express 13, 6268-6274 (2005).
[CrossRef]

D. D. Bikle, Y. Oda and Z. Xie, "Vitamin D and skin cancer: A problem in gene regulation," J. Steroid. Biochem. Mol. Biol. 97, 83-91 (2005).
[CrossRef]

2004 (3)

T. Mitschele, B. Diesel, M. Friedrich, V. Meineke, R. M. Maas, B. C. Gärtner, J. Kamradt, E. Meese, W. Tilgen and J. Reichrath, "Analysis of the vitamin D system in basal cell carcinomas (BCCs)," Lab. Invest. 84, 693-702 (2004).
[CrossRef]

Y. Chen and A. Periasamy, "Characterization of two-photon excitation fluorescence lifetime imaging microscopy for protein localization," Microsc. Res. Tech. 63(1), 72-80 (2004).
[CrossRef]

T. Yasui, Y. Tohno and T. Araki, "Characterization of collagen orientation in human dermis by two-dimensional second-harmonic-generation polarimetry," J. Biomed. Opt. 9(2), 259-264 (2004).
[CrossRef]

2003 (7)

W. R. Zipfel, R. M. Williams and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1369-1377 (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. USA 100, 7075-7080 (2003).

K. König and I. Riemann, "High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution," J. Biomed. Opt. 8(3), 432-439 (2003).

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

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]

P. J. Tadrous, J. Siegel, P. M. W. French, S. Shousha, E. N. Lalani and G. W. H. Stamp, "Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer," J. Pathol. 199, 309-317 (2003).
[CrossRef]

M. Kress, T. Meier, R. Steiner, F. Dolp, R. Erdmann, U. Ortmann and A. Rück, "Time-resolved microspectrofluorometry and fluorescence lifetime imaging of photosensitizers using picosecond pulsed diode lasers in laser scanning microscopes," J. Biomed. Opt. 8(1), 26-32 (2003).
[CrossRef]

2002 (6)

S. Gonzalez and Z. Tannous, "Real-time in vivo confocal reflectance microscopy of basal cell carcinoma," J. Am. Acad. Dermatol. 47, 869-874 (2002).
[CrossRef]

K. M. Hanson, M. J. Behne, N. P. Barry, T. M. Mauro, E. Gratton and R. M. Clegg, "Two-photon fluorescence lifetime imaging of the skin stratum corneum pH gradient," Biophys. J. 83, 1682-1690 (2002).

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone and W. A. Mohler, "Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 81, 493-508 (2002).

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).

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. USA 99, 11014-11019 (2002).

J. C. Malone, A. F. Hood, T. Conley, J. Nürnberger, L. A. Baldridge, J. L. Clendenon, K. W. Dunn and C. L. Phillips, "Three-dimensional imaging of human skin and mucosa by two-photon laser scanning microscopy," J. Cutan. Pathol. 29, 453-458 (2002).
[CrossRef]

2001 (2)

L. Moreaux, O. Sandre, S. Charpak, M. Blanchard-Desce and J. Mertz, "Coherent scattering in multi-harmonic light microscopy," Biophys. J. 80(3), 1568-1574 (2001).

B. R. Masters and P. T. C. So, "Confocal microscopy and multi-photon excitation microscopy of human skin in vivo," Opt. Express 8, 2-9 (2001).

2000 (2)

P. J. Tadrous, "Methods for imaging the structure and function of living tissues and cells: 2. Fluorescence lifetime imaging," J. Pathol. 191, 229-234 (2000).
[CrossRef]

S. Andersson-Engels, G. Canti, R. Cubeddu, C. Eker, C. af Klinteberg, A. Pifferi, K. Svanberg, S. Svanberg, P. Taroni, G. Valentini and I. Wang, "Preliminary evaluation of two fluorescence imaging methods for the detection and the delineation of basal cell carcinomas of the skin," Lasers Surg. Med. 26(1), 76-82 (2000).
[CrossRef]

1998 (2)

B. R. Masters, P. T. C. So and E. Gratton, "Optical biopsy of in vivo human skin: multi-photon excitation microscopy," Lasers Med. Sci. 13, 196-203 (1998).
[CrossRef]

P. T. C. So, H. Kim and I. E. Kochevar, "Two-Photon deep tissue ex vivo imaging of mouse dermal and subcutaneous structures," Opt. Express 3, 339-351 (1998).

1992 (1)

J. R. Lackowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt and M. Johnson, "Fluorescence lifetime imaging," Ann. Biochem. 202: 316-330 (1992).

1990 (2)

J. C. Kennedy, R. H. Pottier and D. C. Pross, "Photodynamic therapy with endogenous protoporphyrine IX: Basic principles and present clinical experience," J. Photochem. Photobiol. B 6, 143-148 (1990).
[CrossRef]

W. Denk, J. H. Strickler and W. W. Webb, "Two-photon laser scanning fluorescence microscope," Science 248, 73-76 (1990).
[CrossRef]

1979 (1)

S. Roth and I. Freund, "Second harmonic generation in collagen," J. Chem. Phys. 70, 1637-1643 (1979).
[CrossRef]

Ann. Biochem. (1)

J. R. Lackowicz, H. Szmacinski, K. Nowaczyk, K. W. Berndt and M. Johnson, "Fluorescence lifetime imaging," Ann. Biochem. 202: 316-330 (1992).

Biomaterials (1)

K. König, K. Schenke-Layland, I. Riemann and U. A. Stock, "Multiphoton autofluorescence imaging of intratissue elastic fibers," Biomaterials 26, 495-500 (2005).
[CrossRef]

Biophys. J. (6)

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).

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).

L. Moreaux, O. Sandre, S. Charpak, M. Blanchard-Desce and J. Mertz, "Coherent scattering in multi-harmonic light microscopy," Biophys. J. 80(3), 1568-1574 (2001).

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone and W. A. Mohler, "Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 81, 493-508 (2002).

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]

K. M. Hanson, M. J. Behne, N. P. Barry, T. M. Mauro, E. Gratton and R. M. Clegg, "Two-photon fluorescence lifetime imaging of the skin stratum corneum pH gradient," Biophys. J. 83, 1682-1690 (2002).

BMC Med. (1)

P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4(1), 38 (2006).
[CrossRef]

Dermatol. Clin. (1)

J. E. Blume and A. R. Oseroff, "Aminolevulinic acid photodynamic therapy for skin cancers," Dermatol. Clin. 25(1), 5-14 (2007).

Dermatol. Surg. (1)

D. E. Marra, A. Torres, C. F: Schanbacher and S. Gonzalez, "Detection of residual basal cell carcinoma by in vivo confocal microscopy," Dermatol. Surg. 31, 538-541 (2005).

J. Am. Acad. Dermatol. (1)

S. Gonzalez and Z. Tannous, "Real-time in vivo confocal reflectance microscopy of basal cell carcinoma," J. Am. Acad. Dermatol. 47, 869-874 (2002).
[CrossRef]

J. Biomed. Opt. (6)

M. Kress, T. Meier, R. Steiner, F. Dolp, R. Erdmann, U. Ortmann and A. Rück, "Time-resolved microspectrofluorometry and fluorescence lifetime imaging of photosensitizers using picosecond pulsed diode lasers in laser scanning microscopes," J. Biomed. Opt. 8(1), 26-32 (2003).
[CrossRef]

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12(2), 024014 (2007).
[CrossRef]

M. B. Ericson, J. Uhre, C. Strandeberg, B. Stenquist, O. Larko, A. M. Wennberg and A. Rosen, "Bispectral fluorescence imaging combined with texture analysis and linear discrimination for correlation with histopathologic extent of basal cell carcinoma," J. Biomed. Opt. 10(3), 034009 (2005).
[CrossRef]

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