Abstract

We report on two-photon autofluorescence and second harmonic spectral imaging of live mouse tissues. The use of a high sensitivity detector and ultraviolet optics allowed us to record razor-sharp deep-tissue spectral images of weak autofluorescence and short-wavelength second harmonic generation by mouse skin. Real-color image representation combined with depth-resolved spectral analysis enabled us to identify tissue structures. The results show that linking nonlinear deep-tissue imaging microscopy with autofluorescence spectroscopy has the potential to provide important information for the diagnosis of skin tissues.

© 2006 Optical Society of America

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  6. Y. Guo, H. E. Savage, F. Liu, S. P. Schantz, P. P. Ho, and R. R. Alfano, "Subsurface tumor progression investigated by noninvasive optical second harmonic tomography," Proc. Natl. Acad. Sci. 96, 10854-10856 (1999).
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
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2005 (7)

D. ChorvatJr, J. Kirchnerova, M. Cagalinec, J. Smolka, A. Mateasik, and A. Chorvatova, "Spectral unmixing of flavin autofluorescence components in cardiac myocytes," Biophys. J. 105,073866 (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, (2005).
[CrossRef]

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65, 1180-1186 (2005).
[CrossRef]

D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, "Autofluorescence and diffuse reflectance spectroscopy for oral oncology," Lasers Surg. Med. 36, 356-364 (2005).
[CrossRef]

Y. C. Wu, P. Xi, J. N. Y. Qu, T. H. Cheung, and M. Y. Yu, "Depth-resolved fluorescence spectroscopy of normal and dysplastic cervical tissue," Opt. Express 13, 382-388 (2005).
[CrossRef]

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

Y. C. Wu, and J. N. Y. Qu, "Two-photon autofluorescence spectroscopy and second-harmonic generation of epithelial tissue," Opt. Lett. 30, 3045-3047 (2005).
[CrossRef]

2004 (5)

J. Sun, T. Shilagard, B. Bell, M. Motamedi, and G. Vargas, "In vivo multimodal nonlinear optical imaging of mucosal tissue," Opt. Express 12, 2478-2486 (2004).
[CrossRef]

J. V. Rocheleau, W. S. Head, and D. W. Piston, "Quantitative NAD (P)H/Flavoprotein autofluorescence imaging reveals metabolic mechanisms of Pancreatic Islet Pyruvate Response," J. Biol. Chem. 279, 31780-31787 (2004).
[CrossRef]

V. Ulrich, P. Fischer, I. Riemann, and K. Konigt, "Compact multiphoton/single photon laser scanning microscope for spectral imaging and fluorescence lifetime imaging," Scanning 26, 217-225 (2004).

R. C. Ecker, R. de Martin, G. E. Steiner, and J. A. Schmid, "Application of spectral imaging microscopy in cytomics and fluorescence resonance energy transfer (FRET) analysis," Cytometry. A 59, 172-181 (2004).

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

2003 (2)

W. R. Zipfel, R. M. Williams, R. Christie, A. Yu 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. 100, 7075-7080 (2003).
[CrossRef]

E. Brown, T. Mc Kee, E. di Tomaso, 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]

2002 (5)

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).

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. 99, 11014-11019 (2002).
[CrossRef]

T. Zimmermann, J. Rietdorf, A. Girod, V. Georget, and R. Pepperkok, "Spectral imaging and linear un-mixing enables improved FRET efficiency with a novel GFP2-YFP FRET pair," FEBS Lett. 531, 245-249 (2002).
[CrossRef]

T. Haraguchi, T. Shimi, T. Koujin, N. Hashiguchi, and Y. Hiraoka, "Spectral imaging fluorescence microscopy," Genes Cells 7, 881-887 (2002).
[CrossRef]

K. Sokolov, J. Galvan, A. Myakov, A. Lacy, R. Lotan, and R. Richards-Kortum, "Realistic three-dimensional epithelial tissue phantoms for biomedical optics," J. Biomed. Opt. 7, 148-156 (2002).
[CrossRef]

1999 (1)

Y. Guo, H. E. Savage, F. Liu, S. P. Schantz, P. P. Ho, and R. R. Alfano, "Subsurface tumor progression investigated by noninvasive optical second harmonic tomography," Proc. Natl. Acad. Sci. 96, 10854-10856 (1999).
[CrossRef]

1998 (2)

B. R. Masters, P. T. C. So, and E. Gratton, "Multiphoton excitation microscopy of in vivo human skin," Ann. N. Y. Acad. Sci. 838, 58-67 (1998).
[CrossRef]

B. Banerjee, B. Miedema, and H. R. Chandrasekhar, "Emission spectra of colonic tissue and endogenous fluorophores," Am. J. Med. Sci. 316, 220-226 (1998).
[CrossRef]

1997 (1)

B. R. Masters, P. T. C. So, and E. Gratton, "Multiphoton excitation fluorescence microscopy and spectroscopy of in vivo human skin," Biophys. J. 72, 2405-2412 (1997).

1995 (1)

D. W. Piston, B. R. Masters, and W. W. Webb, "Three-dimensionally resolved NAD(P)H cellular metabolic redox imaging of the in situ cornea with two-photon excitation laser scanning microscopy," J. Microsc. 178 (Pt 1), 20-27 (1995).

1994 (1)

H. J. C. M. Sterenborg, M. Motamedi, R. F. Wagner, M. Duvic, S. Thomsen, and S. L. Jacques, "In-Vivo fluorescence Spectroscopy and imaging of human skin tumors," Laser Med. Sci. 9, 191-201 (1994).
[CrossRef]

1993 (1)

A. Mahadevan, M. F. Mitchell, E. Silva, S. Thomsen, and R. R. Richards-Kortum, "Study of the fluorescence properties of normal and neoplastic human cervical tissue," Lasers Surg. Med. 13, 647-655 (1993).
[CrossRef]

1992 (1)

K. T. Schomacker, J. K. Frisoli, C. C. Compton, T. J. Flotte, J. M. Richter, N. S. Nishioka, and T. F. Deutsch, "Ultraviolet laser-induced fluorescence of colonic tissue: basic biology and diagnostic potential," Lasers Surg. Med. 12, 63-78 (1992).
[CrossRef]

1988 (1)

G. Weagle, P. E. Paterson, J. Kennedy, and R. Pottier, "The nature of the chromophore responsible for naturally occurring fluorescence in mouse skin," J. Photochem. Photobiol. B 2, 313-320 (1988).
[CrossRef]

1978 (1)

E. H. Epstein, Jr., and N. H. Munderloh, "Human skin collagen. Presence of type I and type III at all levels of the dermis," J. Biol. Chem. 253, 1336-1337 (1978).

Alfano, R. R.

Y. Guo, H. E. Savage, F. Liu, S. P. Schantz, P. P. Ho, and R. R. Alfano, "Subsurface tumor progression investigated by noninvasive optical second harmonic tomography," Proc. Natl. Acad. Sci. 96, 10854-10856 (1999).
[CrossRef]

Banerjee, B.

B. Banerjee, B. Miedema, and H. R. Chandrasekhar, "Emission spectra of colonic tissue and endogenous fluorophores," Am. J. Med. Sci. 316, 220-226 (1998).
[CrossRef]

Bell, B.

Boucher, Y.

E. Brown, T. Mc Kee, E. di Tomaso, 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]

Boulesteix, T.

Brown, E.

E. Brown, T. Mc Kee, E. di Tomaso, 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]

Cagalinec, M.

D. ChorvatJr, J. Kirchnerova, M. Cagalinec, J. Smolka, A. Mateasik, and A. Chorvatova, "Spectral unmixing of flavin autofluorescence components in cardiac myocytes," Biophys. J. 105,073866 (2005).

Campagnola, P. J.

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).

Chandrasekhar, H. R.

B. Banerjee, B. Miedema, and H. R. Chandrasekhar, "Emission spectra of colonic tissue and endogenous fluorophores," Am. J. Med. Sci. 316, 220-226 (1998).
[CrossRef]

Cheung, T. H.

Chorvat, D.

D. ChorvatJr, J. Kirchnerova, M. Cagalinec, J. Smolka, A. Mateasik, and A. Chorvatova, "Spectral unmixing of flavin autofluorescence components in cardiac myocytes," Biophys. J. 105,073866 (2005).

Chorvatova, A.

D. ChorvatJr, J. Kirchnerova, M. Cagalinec, J. Smolka, A. Mateasik, and A. Chorvatova, "Spectral unmixing of flavin autofluorescence components in cardiac myocytes," Biophys. J. 105,073866 (2005).

Christie, R.

W. R. Zipfel, R. M. Williams, R. Christie, A. Yu 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. 100, 7075-7080 (2003).
[CrossRef]

Compton, C. C.

K. T. Schomacker, J. K. Frisoli, C. C. Compton, T. J. Flotte, J. M. Richter, N. S. Nishioka, and T. F. Deutsch, "Ultraviolet laser-induced fluorescence of colonic tissue: basic biology and diagnostic potential," Lasers Surg. Med. 12, 63-78 (1992).
[CrossRef]

de Martin, R.

R. C. Ecker, R. de Martin, G. E. Steiner, and J. A. Schmid, "Application of spectral imaging microscopy in cytomics and fluorescence resonance energy transfer (FRET) analysis," Cytometry. A 59, 172-181 (2004).

de Veld, D. C.

D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, "Autofluorescence and diffuse reflectance spectroscopy for oral oncology," Lasers Surg. Med. 36, 356-364 (2005).
[CrossRef]

Deutsch, T. F.

K. T. Schomacker, J. K. Frisoli, C. C. Compton, T. J. Flotte, J. M. Richter, N. S. Nishioka, and T. F. Deutsch, "Ultraviolet laser-induced fluorescence of colonic tissue: basic biology and diagnostic potential," Lasers Surg. Med. 12, 63-78 (1992).
[CrossRef]

di Tomaso, E.

E. Brown, T. Mc Kee, E. di Tomaso, 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]

Duin, R. P.

D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, "Autofluorescence and diffuse reflectance spectroscopy for oral oncology," Lasers Surg. Med. 36, 356-364 (2005).
[CrossRef]

Dumas, D.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

Duvic, M.

H. J. C. M. Sterenborg, M. Motamedi, R. F. Wagner, M. Duvic, S. Thomsen, and S. L. Jacques, "In-Vivo fluorescence Spectroscopy and imaging of human skin tumors," Laser Med. Sci. 9, 191-201 (1994).
[CrossRef]

Ecker, R. C.

R. C. Ecker, R. de Martin, G. E. Steiner, and J. A. Schmid, "Application of spectral imaging microscopy in cytomics and fluorescence resonance energy transfer (FRET) analysis," Cytometry. A 59, 172-181 (2004).

Eickhoff, J. C.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65, 1180-1186 (2005).
[CrossRef]

Eliceiri, K. W.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65, 1180-1186 (2005).
[CrossRef]

Epstein, E. H.

E. H. Epstein, Jr., and N. H. Munderloh, "Human skin collagen. Presence of type I and type III at all levels of the dermis," J. Biol. Chem. 253, 1336-1337 (1978).

Fischer, P.

V. Ulrich, P. Fischer, I. Riemann, and K. Konigt, "Compact multiphoton/single photon laser scanning microscope for spectral imaging and fluorescence lifetime imaging," Scanning 26, 217-225 (2004).

Flotte, T. J.

K. T. Schomacker, J. K. Frisoli, C. C. Compton, T. J. Flotte, J. M. Richter, N. S. Nishioka, and T. F. Deutsch, "Ultraviolet laser-induced fluorescence of colonic tissue: basic biology and diagnostic potential," Lasers Surg. Med. 12, 63-78 (1992).
[CrossRef]

Frisoli, J. K.

K. T. Schomacker, J. K. Frisoli, C. C. Compton, T. J. Flotte, J. M. Richter, N. S. Nishioka, and T. F. Deutsch, "Ultraviolet laser-induced fluorescence of colonic tissue: basic biology and diagnostic potential," Lasers Surg. Med. 12, 63-78 (1992).
[CrossRef]

Frouin, F.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

Galvan, J.

K. Sokolov, J. Galvan, A. Myakov, A. Lacy, R. Lotan, and R. Richards-Kortum, "Realistic three-dimensional epithelial tissue phantoms for biomedical optics," J. Biomed. Opt. 7, 148-156 (2002).
[CrossRef]

Gambert, P.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

Gendron-Fitzpatrick, A.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65, 1180-1186 (2005).
[CrossRef]

Georget, V.

T. Zimmermann, J. Rietdorf, A. Girod, V. Georget, and R. Pepperkok, "Spectral imaging and linear un-mixing enables improved FRET efficiency with a novel GFP2-YFP FRET pair," FEBS Lett. 531, 245-249 (2002).
[CrossRef]

Girod, A.

T. Zimmermann, J. Rietdorf, A. Girod, V. Georget, and R. Pepperkok, "Spectral imaging and linear un-mixing enables improved FRET efficiency with a novel GFP2-YFP FRET pair," FEBS Lett. 531, 245-249 (2002).
[CrossRef]

Gratton, E.

B. R. Masters, P. T. C. So, and E. Gratton, "Multiphoton excitation microscopy of in vivo human skin," Ann. N. Y. Acad. Sci. 838, 58-67 (1998).
[CrossRef]

B. R. Masters, P. T. C. So, and E. Gratton, "Multiphoton excitation fluorescence microscopy and spectroscopy of in vivo human skin," Biophys. J. 72, 2405-2412 (1997).

Guo, Y.

Y. Guo, H. E. Savage, F. Liu, S. P. Schantz, P. P. Ho, and R. R. Alfano, "Subsurface tumor progression investigated by noninvasive optical second harmonic tomography," Proc. Natl. Acad. Sci. 96, 10854-10856 (1999).
[CrossRef]

Hancewicz, T. M.

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, (2005).
[CrossRef]

Haraguchi, T.

T. Haraguchi, T. Shimi, T. Koujin, N. Hashiguchi, and Y. Hiraoka, "Spectral imaging fluorescence microscopy," Genes Cells 7, 881-887 (2002).
[CrossRef]

Hashiguchi, N.

T. Haraguchi, T. Shimi, T. Koujin, N. Hashiguchi, and Y. Hiraoka, "Spectral imaging fluorescence microscopy," Genes Cells 7, 881-887 (2002).
[CrossRef]

Head, W. S.

J. V. Rocheleau, W. S. Head, and D. W. Piston, "Quantitative NAD (P)H/Flavoprotein autofluorescence imaging reveals metabolic mechanisms of Pancreatic Islet Pyruvate Response," J. Biol. Chem. 279, 31780-31787 (2004).
[CrossRef]

Hiraoka, Y.

T. Haraguchi, T. Shimi, T. Koujin, N. Hashiguchi, and Y. Hiraoka, "Spectral imaging fluorescence microscopy," Genes Cells 7, 881-887 (2002).
[CrossRef]

Ho, P. P.

Y. Guo, H. E. Savage, F. Liu, S. P. Schantz, P. P. Ho, and R. R. Alfano, "Subsurface tumor progression investigated by noninvasive optical second harmonic tomography," Proc. Natl. Acad. Sci. 96, 10854-10856 (1999).
[CrossRef]

Hoppe, P. E.

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).

Hyman, B. T.

W. R. Zipfel, R. M. Williams, R. Christie, A. Yu 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. 100, 7075-7080 (2003).
[CrossRef]

Jacques, S. L.

H. J. C. M. Sterenborg, M. Motamedi, R. F. Wagner, M. Duvic, S. Thomsen, and S. L. Jacques, "In-Vivo fluorescence Spectroscopy and imaging of human skin tumors," Laser Med. Sci. 9, 191-201 (1994).
[CrossRef]

Jain, R. K.

E. Brown, T. Mc Kee, E. di Tomaso, 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]

Kahn, E.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

Kaplan, P. D.

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, (2005).
[CrossRef]

Kennedy, J.

G. Weagle, P. E. Paterson, J. Kennedy, and R. Pottier, "The nature of the chromophore responsible for naturally occurring fluorescence in mouse skin," J. Photochem. Photobiol. B 2, 313-320 (1988).
[CrossRef]

Kirchnerova, J.

D. ChorvatJr, J. Kirchnerova, M. Cagalinec, J. Smolka, A. Mateasik, and A. Chorvatova, "Spectral unmixing of flavin autofluorescence components in cardiac myocytes," Biophys. J. 105,073866 (2005).

Konigt, K.

V. Ulrich, P. Fischer, I. Riemann, and K. Konigt, "Compact multiphoton/single photon laser scanning microscope for spectral imaging and fluorescence lifetime imaging," Scanning 26, 217-225 (2004).

Koujin, T.

T. Haraguchi, T. Shimi, T. Koujin, N. Hashiguchi, and Y. Hiraoka, "Spectral imaging fluorescence microscopy," Genes Cells 7, 881-887 (2002).
[CrossRef]

Lacy, A.

K. Sokolov, J. Galvan, A. Myakov, A. Lacy, R. Lotan, and R. Richards-Kortum, "Realistic three-dimensional epithelial tissue phantoms for biomedical optics," J. Biomed. Opt. 7, 148-156 (2002).
[CrossRef]

Laiho, L. H.

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, (2005).
[CrossRef]

Liu, F.

Y. Guo, H. E. Savage, F. Liu, S. P. Schantz, P. P. Ho, and R. R. Alfano, "Subsurface tumor progression investigated by noninvasive optical second harmonic tomography," Proc. Natl. Acad. Sci. 96, 10854-10856 (1999).
[CrossRef]

Lizard, G.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

Lotan, R.

K. Sokolov, J. Galvan, A. Myakov, A. Lacy, R. Lotan, and R. Richards-Kortum, "Realistic three-dimensional epithelial tissue phantoms for biomedical optics," J. Biomed. Opt. 7, 148-156 (2002).
[CrossRef]

Mahadevan, A.

A. Mahadevan, M. F. Mitchell, E. Silva, S. Thomsen, and R. R. Richards-Kortum, "Study of the fluorescence properties of normal and neoplastic human cervical tissue," Lasers Surg. Med. 13, 647-655 (1993).
[CrossRef]

Malone, C. J.

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).

Masters, B. R.

B. R. Masters, P. T. C. So, and E. Gratton, "Multiphoton excitation microscopy of in vivo human skin," Ann. N. Y. Acad. Sci. 838, 58-67 (1998).
[CrossRef]

B. R. Masters, P. T. C. So, and E. Gratton, "Multiphoton excitation fluorescence microscopy and spectroscopy of in vivo human skin," Biophys. J. 72, 2405-2412 (1997).

D. W. Piston, B. R. Masters, and W. W. Webb, "Three-dimensionally resolved NAD(P)H cellular metabolic redox imaging of the in situ cornea with two-photon excitation laser scanning microscopy," J. Microsc. 178 (Pt 1), 20-27 (1995).

Mateasik, A.

D. ChorvatJr, J. Kirchnerova, M. Cagalinec, J. Smolka, A. Mateasik, and A. Chorvatova, "Spectral unmixing of flavin autofluorescence components in cardiac myocytes," Biophys. J. 105,073866 (2005).

Mc Kee, T.

E. Brown, T. Mc Kee, E. di Tomaso, 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]

Miedema, B.

B. Banerjee, B. Miedema, and H. R. Chandrasekhar, "Emission spectra of colonic tissue and endogenous fluorophores," Am. J. Med. Sci. 316, 220-226 (1998).
[CrossRef]

Millard, A. C.

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).

Mitchell, M. F.

A. Mahadevan, M. F. Mitchell, E. Silva, S. Thomsen, and R. R. Richards-Kortum, "Study of the fluorescence properties of normal and neoplastic human cervical tissue," Lasers Surg. Med. 13, 647-655 (1993).
[CrossRef]

Mohler, W. A.

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).

Montange, T.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

Motamedi, M.

J. Sun, T. Shilagard, B. Bell, M. Motamedi, and G. Vargas, "In vivo multimodal nonlinear optical imaging of mucosal tissue," Opt. Express 12, 2478-2486 (2004).
[CrossRef]

H. J. C. M. Sterenborg, M. Motamedi, R. F. Wagner, M. Duvic, S. Thomsen, and S. L. Jacques, "In-Vivo fluorescence Spectroscopy and imaging of human skin tumors," Laser Med. Sci. 9, 191-201 (1994).
[CrossRef]

Munderloh, N. H.

E. H. Epstein, Jr., and N. H. Munderloh, "Human skin collagen. Presence of type I and type III at all levels of the dermis," J. Biol. Chem. 253, 1336-1337 (1978).

Myakov, A.

K. Sokolov, J. Galvan, A. Myakov, A. Lacy, R. Lotan, and R. Richards-Kortum, "Realistic three-dimensional epithelial tissue phantoms for biomedical optics," J. Biomed. Opt. 7, 148-156 (2002).
[CrossRef]

Nishioka, N. S.

K. T. Schomacker, J. K. Frisoli, C. C. Compton, T. J. Flotte, J. M. Richter, N. S. Nishioka, and T. F. Deutsch, "Ultraviolet laser-induced fluorescence of colonic tissue: basic biology and diagnostic potential," Lasers Surg. Med. 12, 63-78 (1992).
[CrossRef]

Paterson, P. E.

G. Weagle, P. E. Paterson, J. Kennedy, and R. Pottier, "The nature of the chromophore responsible for naturally occurring fluorescence in mouse skin," J. Photochem. Photobiol. B 2, 313-320 (1988).
[CrossRef]

Pelet, S.

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, (2005).
[CrossRef]

Pena, A. M.

Pepperkok, R.

T. Zimmermann, J. Rietdorf, A. Girod, V. Georget, and R. Pepperkok, "Spectral imaging and linear un-mixing enables improved FRET efficiency with a novel GFP2-YFP FRET pair," FEBS Lett. 531, 245-249 (2002).
[CrossRef]

Piston, D. W.

J. V. Rocheleau, W. S. Head, and D. W. Piston, "Quantitative NAD (P)H/Flavoprotein autofluorescence imaging reveals metabolic mechanisms of Pancreatic Islet Pyruvate Response," J. Biol. Chem. 279, 31780-31787 (2004).
[CrossRef]

D. W. Piston, B. R. Masters, and W. W. Webb, "Three-dimensionally resolved NAD(P)H cellular metabolic redox imaging of the in situ cornea with two-photon excitation laser scanning microscopy," J. Microsc. 178 (Pt 1), 20-27 (1995).

Pluen, A.

E. Brown, T. Mc Kee, E. di Tomaso, 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]

Pottier, R.

G. Weagle, P. E. Paterson, J. Kennedy, and R. Pottier, "The nature of the chromophore responsible for naturally occurring fluorescence in mouse skin," J. Photochem. Photobiol. B 2, 313-320 (1988).
[CrossRef]

Qu, J. N. Y.

Ramanujam, N.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65, 1180-1186 (2005).
[CrossRef]

Richards-Kortum, R.

K. Sokolov, J. Galvan, A. Myakov, A. Lacy, R. Lotan, and R. Richards-Kortum, "Realistic three-dimensional epithelial tissue phantoms for biomedical optics," J. Biomed. Opt. 7, 148-156 (2002).
[CrossRef]

Richards-Kortum, R. R.

A. Mahadevan, M. F. Mitchell, E. Silva, S. Thomsen, and R. R. Richards-Kortum, "Study of the fluorescence properties of normal and neoplastic human cervical tissue," Lasers Surg. Med. 13, 647-655 (1993).
[CrossRef]

Richter, J. M.

K. T. Schomacker, J. K. Frisoli, C. C. Compton, T. J. Flotte, J. M. Richter, N. S. Nishioka, and T. F. Deutsch, "Ultraviolet laser-induced fluorescence of colonic tissue: basic biology and diagnostic potential," Lasers Surg. Med. 12, 63-78 (1992).
[CrossRef]

Riedinger, J. M.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

Riemann, I.

V. Ulrich, P. Fischer, I. Riemann, and K. Konigt, "Compact multiphoton/single photon laser scanning microscope for spectral imaging and fluorescence lifetime imaging," Scanning 26, 217-225 (2004).

Rietdorf, J.

T. Zimmermann, J. Rietdorf, A. Girod, V. Georget, and R. Pepperkok, "Spectral imaging and linear un-mixing enables improved FRET efficiency with a novel GFP2-YFP FRET pair," FEBS Lett. 531, 245-249 (2002).
[CrossRef]

Robert, V.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

Rocheleau, J. V.

J. V. Rocheleau, W. S. Head, and D. W. Piston, "Quantitative NAD (P)H/Flavoprotein autofluorescence imaging reveals metabolic mechanisms of Pancreatic Islet Pyruvate Response," J. Biol. Chem. 279, 31780-31787 (2004).
[CrossRef]

Roodenburg, J. L.

D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, "Autofluorescence and diffuse reflectance spectroscopy for oral oncology," Lasers Surg. Med. 36, 356-364 (2005).
[CrossRef]

Savage, H. E.

Y. Guo, H. E. Savage, F. Liu, S. P. Schantz, P. P. Ho, and R. R. Alfano, "Subsurface tumor progression investigated by noninvasive optical second harmonic tomography," Proc. Natl. Acad. Sci. 96, 10854-10856 (1999).
[CrossRef]

Schanne-Klein, M. C.

Schantz, S. P.

Y. Guo, H. E. Savage, F. Liu, S. P. Schantz, P. P. Ho, and R. R. Alfano, "Subsurface tumor progression investigated by noninvasive optical second harmonic tomography," Proc. Natl. Acad. Sci. 96, 10854-10856 (1999).
[CrossRef]

Schmid, J. A.

R. C. Ecker, R. de Martin, G. E. Steiner, and J. A. Schmid, "Application of spectral imaging microscopy in cytomics and fluorescence resonance energy transfer (FRET) analysis," Cytometry. A 59, 172-181 (2004).

Schomacker, K. T.

K. T. Schomacker, J. K. Frisoli, C. C. Compton, T. J. Flotte, J. M. Richter, N. S. Nishioka, and T. F. Deutsch, "Ultraviolet laser-induced fluorescence of colonic tissue: basic biology and diagnostic potential," Lasers Surg. Med. 12, 63-78 (1992).
[CrossRef]

Seed, B.

E. Brown, T. Mc Kee, E. di Tomaso, 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]

Shilagard, T.

Shimi, T.

T. Haraguchi, T. Shimi, T. Koujin, N. Hashiguchi, and Y. Hiraoka, "Spectral imaging fluorescence microscopy," Genes Cells 7, 881-887 (2002).
[CrossRef]

Silva, E.

A. Mahadevan, M. F. Mitchell, E. Silva, S. Thomsen, and R. R. Richards-Kortum, "Study of the fluorescence properties of normal and neoplastic human cervical tissue," Lasers Surg. Med. 13, 647-655 (1993).
[CrossRef]

Skala, M. C.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65, 1180-1186 (2005).
[CrossRef]

Skurichina, M.

D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, "Autofluorescence and diffuse reflectance spectroscopy for oral oncology," Lasers Surg. Med. 36, 356-364 (2005).
[CrossRef]

Smolka, J.

D. ChorvatJr, J. Kirchnerova, M. Cagalinec, J. Smolka, A. Mateasik, and A. Chorvatova, "Spectral unmixing of flavin autofluorescence components in cardiac myocytes," Biophys. J. 105,073866 (2005).

So, P. T. C.

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, (2005).
[CrossRef]

B. R. Masters, P. T. C. So, and E. Gratton, "Multiphoton excitation microscopy of in vivo human skin," Ann. N. Y. Acad. Sci. 838, 58-67 (1998).
[CrossRef]

B. R. Masters, P. T. C. So, and E. Gratton, "Multiphoton excitation fluorescence microscopy and spectroscopy of in vivo human skin," Biophys. J. 72, 2405-2412 (1997).

Sokolov, K.

K. Sokolov, J. Galvan, A. Myakov, A. Lacy, R. Lotan, and R. Richards-Kortum, "Realistic three-dimensional epithelial tissue phantoms for biomedical optics," J. Biomed. Opt. 7, 148-156 (2002).
[CrossRef]

Squirrell, J. M.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65, 1180-1186 (2005).
[CrossRef]

Steiner, G. E.

R. C. Ecker, R. de Martin, G. E. Steiner, and J. A. Schmid, "Application of spectral imaging microscopy in cytomics and fluorescence resonance energy transfer (FRET) analysis," Cytometry. A 59, 172-181 (2004).

Sterenborg, H. J.

D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, "Autofluorescence and diffuse reflectance spectroscopy for oral oncology," Lasers Surg. Med. 36, 356-364 (2005).
[CrossRef]

Sterenborg, H. J. C. M.

H. J. C. M. Sterenborg, M. Motamedi, R. F. Wagner, M. Duvic, S. Thomsen, and S. L. Jacques, "In-Vivo fluorescence Spectroscopy and imaging of human skin tumors," Laser Med. Sci. 9, 191-201 (1994).
[CrossRef]

Stoltz, J. F.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

Strupler, M.

Sun, J.

Terasaki, M.

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).

Thomsen, S.

H. J. C. M. Sterenborg, M. Motamedi, R. F. Wagner, M. Duvic, S. Thomsen, and S. L. Jacques, "In-Vivo fluorescence Spectroscopy and imaging of human skin tumors," Laser Med. Sci. 9, 191-201 (1994).
[CrossRef]

A. Mahadevan, M. F. Mitchell, E. Silva, S. Thomsen, and R. R. Richards-Kortum, "Study of the fluorescence properties of normal and neoplastic human cervical tissue," Lasers Surg. Med. 13, 647-655 (1993).
[CrossRef]

Todd-Pokropek, A.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

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. 99, 11014-11019 (2002).
[CrossRef]

Ulrich, V.

V. Ulrich, P. Fischer, I. Riemann, and K. Konigt, "Compact multiphoton/single photon laser scanning microscope for spectral imaging and fluorescence lifetime imaging," Scanning 26, 217-225 (2004).

Vargas, G.

Vejux, A.

E. Kahn, A. Vejux, D. Dumas, T. Montange, F. Frouin, V. Robert, J. M. Riedinger, J. F. Stoltz, P. Gambert, A. Todd-Pokropek, and G. Lizard, "FRET multiphoton spectral imaging microscopy of 7-ketocholesterol and Nile Red in U937 monocytic cells loaded with 7-ketocholesterol," Anal. Quant. Cytol. Histol. 26, 304-313 (2004).

Vrotsos, K. M.

M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, "Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues," Cancer Res. 65, 1180-1186 (2005).
[CrossRef]

Wagner, R. F.

H. J. C. M. Sterenborg, M. Motamedi, R. F. Wagner, M. Duvic, S. Thomsen, and S. L. Jacques, "In-Vivo fluorescence Spectroscopy and imaging of human skin tumors," Laser Med. Sci. 9, 191-201 (1994).
[CrossRef]

Weagle, G.

G. Weagle, P. E. Paterson, J. Kennedy, and R. Pottier, "The nature of the chromophore responsible for naturally occurring fluorescence in mouse skin," J. Photochem. Photobiol. B 2, 313-320 (1988).
[CrossRef]

Webb, W. W.

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