Abstract

The goal of this study was to evaluate the capabilities of a calibrated autofluorescence imaging method for detecting neoplastic lesions. An imaging system that records autofluorescence images calibrated by the cross-polarized reflection images from excitation was instrumented for the evaluation. Cervical tissue was selected as the living tissue model. Sixteen human subjects were examined in vivo with the imaging system before routine examination procedures. It was found that calibrated autofluorescence signals from neoplastic lesions were generally lower than signals from normal cervical tissue. Neoplastic lesions can be differentiated from surrounding normal tissue based on the contrast in the calibrated autofluorescence. The effects of the optical properties of tissue on the calibrated fluorescence imaging were investigated.

© 2003 Optical Society of America

Full Article  |  PDF Article
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  1. R. Richards-Kortum and E. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Ann. Rev. Phy. Chem. 47, 555–606 (1996).
    [Crossref]
  2. G. A. Wagnieres, W. M. Star, and B.C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–32 (1998).
    [PubMed]
  3. N. Ramanujam, “Fluorescence spectroscopy of neoplastic and non-neoplastic tissues,” Neoplasia 2, 89–117 (2000).
    [Crossref] [PubMed]
  4. R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
    [Crossref] [PubMed]
  5. J. Qu, C. MacAulay, S. Lam, and B. Palcic, “Laser-induced fluorescence spectroscopy at endoscopy: tissue optics, Monte Carlo modeling, and in vivo measurements,” Opt. Eng. 34, 3334–3343 (1995).
    [Crossref]
  6. M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. J. Wagnieres, “In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers,” J. Biomed. Opt. 6, 41–51 (2001).
    [Crossref] [PubMed]
  7. N. Ramanujam, M.F. Mitchell, A. Mahadevan, S. Thomsen, E. Silva, and R. Richards-Kortum, “Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial neoplasia (CIN),” Gynecol. Oncol. 52, 31–38 (1994).
    [Crossref] [PubMed]
  8. R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,” J. Biomed. Opt. 6, 385–396 (2001).
    [Crossref] [PubMed]
  9. I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
    [PubMed]
  10. K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
    [Crossref] [PubMed]
  11. M. Kobayashi, K. Shibuya, H. Hoshino, and T. Fujisawa, “Spectroscopic analysis of the autofluorescence from human bronchus using an ultraviolet laser diode,” J. Biomed. Opt. 7, 603–608 (2002).
    [Crossref] [PubMed]
  12. J. Y. Qu, Z. J. Huang, and J. W. Hua, “Excitation and collection geometry insensitive fluorescence imaging of tissue-simulating turbid media,” Appl. Opt. 39, 3344–3356 (2000).
    [Crossref]
  13. J. Y. Qu, J. W. Hua, and Z. J. Huang, “Correction of Geometrical Effects on Fluorescence Imaging of Tissue,” Opt. Commun. 176, 319–326 (2000).
    [Crossref]
  14. J. Y. Qu and J. W. Hua, “Calibrated fluorescence imaging of tissue in vivo,” Appl. Phys. Lett. 78, 4040–4042(2001).
    [Crossref]
  15. S. Jutamulia and T. Asakura, “Reduction of coherent noise using various artificial incoherent soures,” Optik 70, 52–57 (1985).
  16. A. Agrawal, C. Brookner, M. F. Mitchell, and R. Richards-Kortum, “Fluorescence spectroscopy of the cervix: Influence of acetic acid, cervical mucus, and vaginal medications,” Laser Surg. Med. 25, 237–249(1999)
    [Crossref]
  17. Q. G. Zhang, M. G. Muller, J. Wu, and M. S. Feld, “Turbidity-free fluorescence spectroscopy of biological tissue,” Opt. Lett. 25, 1451–1453 (2000).
    [Crossref]
  18. M. G. Muller, I. Georgakoudi, Q. G. Zhang, J. Wu, and Feld MS, Intrinsic fluorescence spectroscopy in turbid media: disentangling effects of scattering and absorption,” Appl. Opt. 40, 4633–4646 (2001).
    [Crossref]
  19. S. P. Lin, L. H. Wang, S. L. Jacques, and F. K. Tittel, “Measurement of tissue optical properties by the use of oblique-incidence optical fiber reflectometry,” Appl. Opt. 36, 136–143 (1997).
    [Crossref] [PubMed]
  20. L. V. Wang and S. L. Jacques, “Source of error in calculation of optical diffuse reflectance from turbid media using diffusion theory,” Comput. Meth. Prog. Bio. 61, 163–170 (2000).
    [Crossref]

2002 (2)

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

M. Kobayashi, K. Shibuya, H. Hoshino, and T. Fujisawa, “Spectroscopic analysis of the autofluorescence from human bronchus using an ultraviolet laser diode,” J. Biomed. Opt. 7, 603–608 (2002).
[Crossref] [PubMed]

2001 (4)

J. Y. Qu and J. W. Hua, “Calibrated fluorescence imaging of tissue in vivo,” Appl. Phys. Lett. 78, 4040–4042(2001).
[Crossref]

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. J. Wagnieres, “In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers,” J. Biomed. Opt. 6, 41–51 (2001).
[Crossref] [PubMed]

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,” J. Biomed. Opt. 6, 385–396 (2001).
[Crossref] [PubMed]

M. G. Muller, I. Georgakoudi, Q. G. Zhang, J. Wu, and Feld MS, Intrinsic fluorescence spectroscopy in turbid media: disentangling effects of scattering and absorption,” Appl. Opt. 40, 4633–4646 (2001).
[Crossref]

2000 (5)

L. V. Wang and S. L. Jacques, “Source of error in calculation of optical diffuse reflectance from turbid media using diffusion theory,” Comput. Meth. Prog. Bio. 61, 163–170 (2000).
[Crossref]

N. Ramanujam, “Fluorescence spectroscopy of neoplastic and non-neoplastic tissues,” Neoplasia 2, 89–117 (2000).
[Crossref] [PubMed]

Q. G. Zhang, M. G. Muller, J. Wu, and M. S. Feld, “Turbidity-free fluorescence spectroscopy of biological tissue,” Opt. Lett. 25, 1451–1453 (2000).
[Crossref]

J. Y. Qu, Z. J. Huang, and J. W. Hua, “Excitation and collection geometry insensitive fluorescence imaging of tissue-simulating turbid media,” Appl. Opt. 39, 3344–3356 (2000).
[Crossref]

J. Y. Qu, J. W. Hua, and Z. J. Huang, “Correction of Geometrical Effects on Fluorescence Imaging of Tissue,” Opt. Commun. 176, 319–326 (2000).
[Crossref]

1999 (2)

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

A. Agrawal, C. Brookner, M. F. Mitchell, and R. Richards-Kortum, “Fluorescence spectroscopy of the cervix: Influence of acetic acid, cervical mucus, and vaginal medications,” Laser Surg. Med. 25, 237–249(1999)
[Crossref]

1998 (1)

G. A. Wagnieres, W. M. Star, and B.C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–32 (1998).
[PubMed]

1997 (1)

1996 (1)

R. Richards-Kortum and E. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Ann. Rev. Phy. Chem. 47, 555–606 (1996).
[Crossref]

1995 (1)

J. Qu, C. MacAulay, S. Lam, and B. Palcic, “Laser-induced fluorescence spectroscopy at endoscopy: tissue optics, Monte Carlo modeling, and in vivo measurements,” Opt. Eng. 34, 3334–3343 (1995).
[Crossref]

1994 (1)

N. Ramanujam, M.F. Mitchell, A. Mahadevan, S. Thomsen, E. Silva, and R. Richards-Kortum, “Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial neoplasia (CIN),” Gynecol. Oncol. 52, 31–38 (1994).
[Crossref] [PubMed]

1990 (1)

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

1985 (1)

S. Jutamulia and T. Asakura, “Reduction of coherent noise using various artificial incoherent soures,” Optik 70, 52–57 (1985).

Agrawal, A.

A. Agrawal, C. Brookner, M. F. Mitchell, and R. Richards-Kortum, “Fluorescence spectroscopy of the cervix: Influence of acetic acid, cervical mucus, and vaginal medications,” Laser Surg. Med. 25, 237–249(1999)
[Crossref]

Asakura, T.

S. Jutamulia and T. Asakura, “Reduction of coherent noise using various artificial incoherent soures,” Optik 70, 52–57 (1985).

Badizadegan, K.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

Blackman, R.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Boiko, I.

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,” J. Biomed. Opt. 6, 385–396 (2001).
[Crossref] [PubMed]

Boku, N.

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

Boone, C. W.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

Boyce, G.A.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Brookner, C.

A. Agrawal, C. Brookner, M. F. Mitchell, and R. Richards-Kortum, “Fluorescence spectroscopy of the cervix: Influence of acetic acid, cervical mucus, and vaginal medications,” Laser Surg. Med. 25, 237–249(1999)
[Crossref]

Carr-Locke, D. L.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

Cothren, R.M.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Crum, C. P.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

Dasari, R. R.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

Doxtader, M.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Drezek, R.

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,” J. Biomed. Opt. 6, 385–396 (2001).
[Crossref] [PubMed]

Feld, M. S.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

Q. G. Zhang, M. G. Muller, J. Wu, and M. S. Feld, “Turbidity-free fluorescence spectroscopy of biological tissue,” Opt. Lett. 25, 1451–1453 (2000).
[Crossref]

Feld, M.S.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Fitzmaurice, M.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Follen, M.

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,” J. Biomed. Opt. 6, 385–396 (2001).
[Crossref] [PubMed]

Fujii, T.

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

Fujisawa, T.

M. Kobayashi, K. Shibuya, H. Hoshino, and T. Fujisawa, “Spectroscopic analysis of the autofluorescence from human bronchus using an ultraviolet laser diode,” J. Biomed. Opt. 7, 603–608 (2002).
[Crossref] [PubMed]

Georgakoudi, I.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

M. G. Muller, I. Georgakoudi, Q. G. Zhang, J. Wu, and Feld MS, Intrinsic fluorescence spectroscopy in turbid media: disentangling effects of scattering and absorption,” Appl. Opt. 40, 4633–4646 (2001).
[Crossref]

Goujon, D.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. J. Wagnieres, “In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers,” J. Biomed. Opt. 6, 41–51 (2001).
[Crossref] [PubMed]

Grosjean, P.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. J. Wagnieres, “In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers,” J. Biomed. Opt. 6, 41–51 (2001).
[Crossref] [PubMed]

Hayes, G.B.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Hoshino, H.

M. Kobayashi, K. Shibuya, H. Hoshino, and T. Fujisawa, “Spectroscopic analysis of the autofluorescence from human bronchus using an ultraviolet laser diode,” J. Biomed. Opt. 7, 603–608 (2002).
[Crossref] [PubMed]

Hua, J. W.

J. Y. Qu and J. W. Hua, “Calibrated fluorescence imaging of tissue in vivo,” Appl. Phys. Lett. 78, 4040–4042(2001).
[Crossref]

J. Y. Qu, Z. J. Huang, and J. W. Hua, “Excitation and collection geometry insensitive fluorescence imaging of tissue-simulating turbid media,” Appl. Opt. 39, 3344–3356 (2000).
[Crossref]

J. Y. Qu, J. W. Hua, and Z. J. Huang, “Correction of Geometrical Effects on Fluorescence Imaging of Tissue,” Opt. Commun. 176, 319–326 (2000).
[Crossref]

Huang, Z. J.

J. Y. Qu, J. W. Hua, and Z. J. Huang, “Correction of Geometrical Effects on Fluorescence Imaging of Tissue,” Opt. Commun. 176, 319–326 (2000).
[Crossref]

J. Y. Qu, Z. J. Huang, and J. W. Hua, “Excitation and collection geometry insensitive fluorescence imaging of tissue-simulating turbid media,” Appl. Opt. 39, 3344–3356 (2000).
[Crossref]

Ivanc, T.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Izuishi, K.

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

Jacobson, B. C.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

Jacques, S. L.

L. V. Wang and S. L. Jacques, “Source of error in calculation of optical diffuse reflectance from turbid media using diffusion theory,” Comput. Meth. Prog. Bio. 61, 163–170 (2000).
[Crossref]

S. P. Lin, L. H. Wang, S. L. Jacques, and F. K. Tittel, “Measurement of tissue optical properties by the use of oblique-incidence optical fiber reflectometry,” Appl. Opt. 36, 136–143 (1997).
[Crossref] [PubMed]

Jutamulia, S.

S. Jutamulia and T. Asakura, “Reduction of coherent noise using various artificial incoherent soures,” Optik 70, 52–57 (1985).

Kinoshita, T.

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

Kobayashi, M.

M. Kobayashi, K. Shibuya, H. Hoshino, and T. Fujisawa, “Spectroscopic analysis of the autofluorescence from human bronchus using an ultraviolet laser diode,” J. Biomed. Opt. 7, 603–608 (2002).
[Crossref] [PubMed]

Lam, S.

J. Qu, C. MacAulay, S. Lam, and B. Palcic, “Laser-induced fluorescence spectroscopy at endoscopy: tissue optics, Monte Carlo modeling, and in vivo measurements,” Opt. Eng. 34, 3334–3343 (1995).
[Crossref]

Lin, S. P.

MacAulay, C.

J. Qu, C. MacAulay, S. Lam, and B. Palcic, “Laser-induced fluorescence spectroscopy at endoscopy: tissue optics, Monte Carlo modeling, and in vivo measurements,” Opt. Eng. 34, 3334–3343 (1995).
[Crossref]

Mahadevan, A.

N. Ramanujam, M.F. Mitchell, A. Mahadevan, S. Thomsen, E. Silva, and R. Richards-Kortum, “Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial neoplasia (CIN),” Gynecol. Oncol. 52, 31–38 (1994).
[Crossref] [PubMed]

Malpica, A.

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,” J. Biomed. Opt. 6, 385–396 (2001).
[Crossref] [PubMed]

Mitchell, M. F.

A. Agrawal, C. Brookner, M. F. Mitchell, and R. Richards-Kortum, “Fluorescence spectroscopy of the cervix: Influence of acetic acid, cervical mucus, and vaginal medications,” Laser Surg. Med. 25, 237–249(1999)
[Crossref]

Mitchell, M.F.

N. Ramanujam, M.F. Mitchell, A. Mahadevan, S. Thomsen, E. Silva, and R. Richards-Kortum, “Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial neoplasia (CIN),” Gynecol. Oncol. 52, 31–38 (1994).
[Crossref] [PubMed]

Monnier, P.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. J. Wagnieres, “In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers,” J. Biomed. Opt. 6, 41–51 (2001).
[Crossref] [PubMed]

MS, Feld

Muller, M. G.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

M. G. Muller, I. Georgakoudi, Q. G. Zhang, J. Wu, and Feld MS, Intrinsic fluorescence spectroscopy in turbid media: disentangling effects of scattering and absorption,” Appl. Opt. 40, 4633–4646 (2001).
[Crossref]

Q. G. Zhang, M. G. Muller, J. Wu, and M. S. Feld, “Turbidity-free fluorescence spectroscopy of biological tissue,” Opt. Lett. 25, 1451–1453 (2000).
[Crossref]

Ohnishi, T.

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

Ohtsu, A.

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

Palcic, B.

J. Qu, C. MacAulay, S. Lam, and B. Palcic, “Laser-induced fluorescence spectroscopy at endoscopy: tissue optics, Monte Carlo modeling, and in vivo measurements,” Opt. Eng. 34, 3334–3343 (1995).
[Crossref]

Petras, R.E.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Qu, J.

J. Qu, C. MacAulay, S. Lam, and B. Palcic, “Laser-induced fluorescence spectroscopy at endoscopy: tissue optics, Monte Carlo modeling, and in vivo measurements,” Opt. Eng. 34, 3334–3343 (1995).
[Crossref]

Qu, J. Y.

J. Y. Qu and J. W. Hua, “Calibrated fluorescence imaging of tissue in vivo,” Appl. Phys. Lett. 78, 4040–4042(2001).
[Crossref]

J. Y. Qu, J. W. Hua, and Z. J. Huang, “Correction of Geometrical Effects on Fluorescence Imaging of Tissue,” Opt. Commun. 176, 319–326 (2000).
[Crossref]

J. Y. Qu, Z. J. Huang, and J. W. Hua, “Excitation and collection geometry insensitive fluorescence imaging of tissue-simulating turbid media,” Appl. Opt. 39, 3344–3356 (2000).
[Crossref]

Ramanujam, N.

N. Ramanujam, “Fluorescence spectroscopy of neoplastic and non-neoplastic tissues,” Neoplasia 2, 89–117 (2000).
[Crossref] [PubMed]

N. Ramanujam, M.F. Mitchell, A. Mahadevan, S. Thomsen, E. Silva, and R. Richards-Kortum, “Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial neoplasia (CIN),” Gynecol. Oncol. 52, 31–38 (1994).
[Crossref] [PubMed]

Rava, R.P.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Richards-Kortum, R.

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,” J. Biomed. Opt. 6, 385–396 (2001).
[Crossref] [PubMed]

A. Agrawal, C. Brookner, M. F. Mitchell, and R. Richards-Kortum, “Fluorescence spectroscopy of the cervix: Influence of acetic acid, cervical mucus, and vaginal medications,” Laser Surg. Med. 25, 237–249(1999)
[Crossref]

R. Richards-Kortum and E. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Ann. Rev. Phy. Chem. 47, 555–606 (1996).
[Crossref]

N. Ramanujam, M.F. Mitchell, A. Mahadevan, S. Thomsen, E. Silva, and R. Richards-Kortum, “Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial neoplasia (CIN),” Gynecol. Oncol. 52, 31–38 (1994).
[Crossref] [PubMed]

Richards-Kortum, R.R.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Ryu, M.

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

Sevick-Muraca, E.

R. Richards-Kortum and E. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Ann. Rev. Phy. Chem. 47, 555–606 (1996).
[Crossref]

Sheets, E. E.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

Shibuya, K.

M. Kobayashi, K. Shibuya, H. Hoshino, and T. Fujisawa, “Spectroscopic analysis of the autofluorescence from human bronchus using an ultraviolet laser diode,” J. Biomed. Opt. 7, 603–608 (2002).
[Crossref] [PubMed]

Silva, E.

N. Ramanujam, M.F. Mitchell, A. Mahadevan, S. Thomsen, E. Silva, and R. Richards-Kortum, “Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial neoplasia (CIN),” Gynecol. Oncol. 52, 31–38 (1994).
[Crossref] [PubMed]

Sivak, M.V.

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Sokolov, K.

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,” J. Biomed. Opt. 6, 385–396 (2001).
[Crossref] [PubMed]

Star, W. M.

G. A. Wagnieres, W. M. Star, and B.C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–32 (1998).
[PubMed]

Tajiri, H.

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

Thomsen, S.

N. Ramanujam, M.F. Mitchell, A. Mahadevan, S. Thomsen, E. Silva, and R. Richards-Kortum, “Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial neoplasia (CIN),” Gynecol. Oncol. 52, 31–38 (1994).
[Crossref] [PubMed]

Tittel, F. K.

Utzinger, U.

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,” J. Biomed. Opt. 6, 385–396 (2001).
[Crossref] [PubMed]

Van Dam, J.

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

van den Bergh, H.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. J. Wagnieres, “In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers,” J. Biomed. Opt. 6, 41–51 (2001).
[Crossref] [PubMed]

Wagnieres, G. A.

G. A. Wagnieres, W. M. Star, and B.C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–32 (1998).
[PubMed]

Wagnieres, G. J.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. J. Wagnieres, “In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers,” J. Biomed. Opt. 6, 41–51 (2001).
[Crossref] [PubMed]

Wang, L. H.

Wang, L. V.

L. V. Wang and S. L. Jacques, “Source of error in calculation of optical diffuse reflectance from turbid media using diffusion theory,” Comput. Meth. Prog. Bio. 61, 163–170 (2000).
[Crossref]

Wilson, B.C.

G. A. Wagnieres, W. M. Star, and B.C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–32 (1998).
[PubMed]

Wu, J.

Yoshida, S.

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

Zellweger, M.

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. J. Wagnieres, “In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers,” J. Biomed. Opt. 6, 41–51 (2001).
[Crossref] [PubMed]

Zhang, Q. G.

Ann. Rev. Phy. Chem. (1)

R. Richards-Kortum and E. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Ann. Rev. Phy. Chem. 47, 555–606 (1996).
[Crossref]

Appl. Opt. (3)

Appl. Phys. Lett. (1)

J. Y. Qu and J. W. Hua, “Calibrated fluorescence imaging of tissue in vivo,” Appl. Phys. Lett. 78, 4040–4042(2001).
[Crossref]

Cancer Res. (1)

I. Georgakoudi, B. C. Jacobson, M. G. Muller, E. E. Sheets, K. Badizadegan, D. L. Carr-Locke, C. P. Crum, C. W. Boone, R. R. Dasari, J. Van Dam, and M. S. Feld, “NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes,” Cancer Res. 62, 682–687 (2002).
[PubMed]

Comput. Meth. Prog. Bio. (1)

L. V. Wang and S. L. Jacques, “Source of error in calculation of optical diffuse reflectance from turbid media using diffusion theory,” Comput. Meth. Prog. Bio. 61, 163–170 (2000).
[Crossref]

Endoscopy (1)

K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, and S. Yoshida, “The histological basis of detection of adenoma and cancer in the colon by autofluorescence endoscopic imaging,” Endoscopy 31, 511–516 (1999).
[Crossref] [PubMed]

Gastrointest. Endosc. (1)

R.M. Cothren, R.R. Richards-Kortum, M.V. Sivak, M. Fitzmaurice, R.P. Rava, G.A. Boyce, G.B. Hayes, M. Doxtader, R. Blackman, T. Ivanc, M.S. Feld, and R.E. Petras, “Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy,” Gastrointest. Endosc. 36, 105–111 (1990).
[Crossref] [PubMed]

Gynecol. Oncol. (1)

N. Ramanujam, M.F. Mitchell, A. Mahadevan, S. Thomsen, E. Silva, and R. Richards-Kortum, “Fluorescence spectroscopy: a diagnostic tool for cervical intraepithelial neoplasia (CIN),” Gynecol. Oncol. 52, 31–38 (1994).
[Crossref] [PubMed]

J. Biomed. Opt. (3)

R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: Modeling, measurements, and implications,” J. Biomed. Opt. 6, 385–396 (2001).
[Crossref] [PubMed]

M. Zellweger, P. Grosjean, D. Goujon, P. Monnier, H. van den Bergh, and G. J. Wagnieres, “In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers,” J. Biomed. Opt. 6, 41–51 (2001).
[Crossref] [PubMed]

M. Kobayashi, K. Shibuya, H. Hoshino, and T. Fujisawa, “Spectroscopic analysis of the autofluorescence from human bronchus using an ultraviolet laser diode,” J. Biomed. Opt. 7, 603–608 (2002).
[Crossref] [PubMed]

Laser Surg. Med. (1)

A. Agrawal, C. Brookner, M. F. Mitchell, and R. Richards-Kortum, “Fluorescence spectroscopy of the cervix: Influence of acetic acid, cervical mucus, and vaginal medications,” Laser Surg. Med. 25, 237–249(1999)
[Crossref]

Neoplasia (1)

N. Ramanujam, “Fluorescence spectroscopy of neoplastic and non-neoplastic tissues,” Neoplasia 2, 89–117 (2000).
[Crossref] [PubMed]

Opt. Commun. (1)

J. Y. Qu, J. W. Hua, and Z. J. Huang, “Correction of Geometrical Effects on Fluorescence Imaging of Tissue,” Opt. Commun. 176, 319–326 (2000).
[Crossref]

Opt. Eng. (1)

J. Qu, C. MacAulay, S. Lam, and B. Palcic, “Laser-induced fluorescence spectroscopy at endoscopy: tissue optics, Monte Carlo modeling, and in vivo measurements,” Opt. Eng. 34, 3334–3343 (1995).
[Crossref]

Opt. Lett. (1)

Optik (1)

S. Jutamulia and T. Asakura, “Reduction of coherent noise using various artificial incoherent soures,” Optik 70, 52–57 (1985).

Photochem. Photobiol. (1)

G. A. Wagnieres, W. M. Star, and B.C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–32 (1998).
[PubMed]

Supplementary Material (1)

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Figures (4)

Fig. 1.
Fig. 1.

(a) A schematic of the F/R colposcopic imaging system. P1 and P2 are the polarizers with their polarization orientations perpendicular to each other. F is the filter to remove the residual reflection of the excitation light. (b) Picture of actual imaging head.

Fig. 2.
Fig. 2.

Typical results obtained from a subject with low-grade SILs and high-grade SILs. (a)raw fluorescence image; (b) cross-polarized reflection image; (c) F/R ratio image.

Fig. 3.
Fig. 3.

F/R ratio image superimposed with real-time reflection image for guided biopsy. (a) (1.6 MB) Video clip of guided biopsy; (b) F/R ratio image.

Fig. 4.
Fig. 4.

Bar chart illustration of the mean values of the F/R ratio for the examined cervical tissues from 16 subjects.

Equations (3)

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

f ( λ em ) = μ s ex l · R 0 ( λ ex ) ( R 0 ( λ ex ) R 0 ( λ em ) ε ( λ ex ) ε ( λ em ) ) 1 2 ( R ( λ em ) R 0 ( λ em ) + ε ( λ em ) ) · F ( λ em ) R ( λ ex )
f μ s ε l ( R R 0 + ε ) · F R
f ( λ em ) μ s ex l ( ε ( λ ex ) ε ( λ em ) ) 1 2 R 0 ( λ ex ) ( R 0 ( λ ex ) R 0 ( λ em ) ) 1 2 ( 1 + ε ( λ em ) ) · F ( λ em ) R ( λ ex )

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