Abstract

The fluorescence from a turbid medium such as biologic tissue contains information about scattering and absorption, as well as the intrinsic fluorescence, i.e., the fluorescence from an optically thin sample of pure fluorophores. The interplay of scattering and absorption can result in severe distortion of the intrinsic spectral features. These distortions can be removed by use of a photon-migration-based picture and information from simultaneously acquired fluorescence and reflectance spectra. We present experimental evidence demonstrating the validity of such an approach for extracting the intrinsic fluorescence for a wide range of scatterer and absorber concentrations in tissue models, ex vivo and in vivo tissues. We show that variations in line shape and intensity in intrinsic tissue fluorescence are significantly reduced compared with the corresponding measured fluorescence.

© 2001 Optical Society of America

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    [CrossRef] [PubMed]
  4. P. K. Gupta, S. K. Majumder, A. Uppal, “Breast cancer diagnosis using nitrogen laser excited autofluorescence spectroscopy,” Lasers Surg. Med. 21, 417–422 (1997).
    [CrossRef]
  5. C.-T. Chen, H. K. Chiang, S.-N. Chow, C.-Y. Wang, Y.-S. Lee, J.-C. Tsai, C.-P. Chiang, “Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis,” J. Oral Pathol. Med. 27, 470–474 (1998).
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    [CrossRef] [PubMed]
  27. N. N. Zhadin, R. R. Alfano, “Correction of the internal absorption effect in fluorescence emission and excitation spectra from absorbing and highly scattering media: theory and experiment,” J. Biomed. Opt. 3, 171–186 (1998).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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  32. In the current version we do not need to consider the effective albedo, aeff, introduced in Ref. 25, because the new form of the escape probability [Eq. 2(b)] takes into account differences in optical properties at the excitation and the emission wavelengths. Additionally, we find that the previously introduced effective anisotropy coefficient, geff, does not significantly affect the resulting intrinsic fluorescence spectrum.
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    [CrossRef] [PubMed]
  34. R. M. Cothren, G. B. Hayes, J. R. Kramer, B. A. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).
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  40. J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37, 3586–3593 (1998).
    [CrossRef]
  41. S. W. E. van de Poll, M. G. Müller, Q. Zhang, J. Myles, J. R. Kramer, M. S. Feld, “Combined fluorescence and reflectance spectroscopy of arterial wall improves the identification of atherosclerosis,” Circulation 100, 2349, Suppl. SNov.2 (1999).
  42. H. Zeng, C. MacAulay, D. I. McLean, B. Palcic, “Spectroscopic and microscopic characteristics of human skin autofluorescence emission,” Photochem. Photobiol. 61, 639–645 (1995).
    [CrossRef] [PubMed]
  43. G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
    [PubMed]

2000

1999

S. K. Majumder, P. K. Gupta, A. Uppal, “Autofluorescence spectroscopy of tissues from human oral cavity for discriminating malignant from normal,” Lasers Life Sci. 8, 211–227 (1999).

S. W. E. van de Poll, M. G. Müller, Q. Zhang, J. Myles, J. R. Kramer, M. S. Feld, “Combined fluorescence and reflectance spectroscopy of arterial wall improves the identification of atherosclerosis,” Circulation 100, 2349, Suppl. SNov.2 (1999).

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38, 6628–6637 (1999).
[CrossRef]

1998

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37, 3586–3593 (1998).
[CrossRef]

T. J. Farrell, R. P. Hawkes, M. S. Patterson, B. C. Wilson, “Modeling of photosensitizer fluorescence emission and photobleaching for photodynamic therapy dosimetry,” Appl. Opt. 37, 7168–7183 (1998).
[CrossRef]

N. N. Zhadin, R. R. Alfano, “Correction of the internal absorption effect in fluorescence emission and excitation spectra from absorbing and highly scattering media: theory and experiment,” J. Biomed. Opt. 3, 171–186 (1998).
[CrossRef] [PubMed]

C.-T. Chen, H. K. Chiang, S.-N. Chow, C.-Y. Wang, Y.-S. Lee, J.-C. Tsai, C.-P. Chiang, “Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis,” J. Oral Pathol. Med. 27, 470–474 (1998).
[CrossRef] [PubMed]

G. A. Wagnières, W. M. Star, B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–632 (1998).
[PubMed]

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

1997

A. J. L. Jongen, H. J. C. M. Sterenborg, “Mathematical description of photobleaching in vivo describing the influence of tissue optics on measured fluorescence signals,” Phys. Med. Biol. 42, 1701–1716 (1997).
[CrossRef] [PubMed]

P. K. Gupta, S. K. Majumder, A. Uppal, “Breast cancer diagnosis using nitrogen laser excited autofluorescence spectroscopy,” Lasers Surg. Med. 21, 417–422 (1997).
[CrossRef]

J. B. Fishkin, O. Coquoz, E. R. Anderson, M. Brenner, B. J. Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Opt. 36, 10–20 (1997).
[CrossRef] [PubMed]

1996

C. M. Gardner, S. L. Jacques, A. J. Welch, “Fluorescence spectroscopy of tissue: recovery of intrinsic fluorescence from measured fluorescence,” Appl. Opt. 35, 1780–1792 (1996).
[CrossRef] [PubMed]

R. A. Zangaro, L. Silveira, R. Manoharan, G. Zonios, I. Itzkan, R. R. Dasari, J. Van Dam, M. S. Feld, “Rapid multiexcitation fluorescence spectroscopy system for in vivo tissue diagnosis,” Appl. Opt. 35, 5211–5219 (1996).
[CrossRef] [PubMed]

M. Anidjar, O. Cussenot, S. Avrillier, D. Ettori, M. J. Villette, J. Fiet, P. Teillac, A. Le Duc, “Ultraviolet laser-induced autofluorescence distinction between malignant and normal urothelial cells and tissues,” J. Biomed. Opt. 1, 335–341 (1996).
[CrossRef] [PubMed]

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

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

1995

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer elastic light scattering,” Lasers Surg. Med. 17, 350–357 (1995).
[CrossRef]

H. Zeng, C. MacAulay, D. I. McLean, B. Palcic, “Spectroscopic and microscopic characteristics of human skin autofluorescence emission,” Photochem. Photobiol. 61, 639–645 (1995).
[CrossRef] [PubMed]

1994

A. J. Durkin, S. Jaikumar, N. Ramanujam, R. Richards-Kortum, “Relation between fluorescence-spectra of dilute and turbid samples,” Appl. Opt. 33, 414–423 (1994).
[CrossRef] [PubMed]

M. S. Patterson, B. W. Pogue, “Mathematical model for time-resolved and frequency-domain fluorescence spectroscopy in biological tissues,” Appl. Opt. 33, 1963–1974 (1994).
[CrossRef] [PubMed]

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. USA 91, 10193–10197 (1994).
[CrossRef]

1993

1992

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

1989

L. I. Laifer, K. M. O’Brien, M. L. Stetz, G. R. Gindi, T. J. Garrand, L. I. Deckelbaum, “Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence,” Circulation 80, 1893–1901 (1989).
[CrossRef] [PubMed]

M. Keijzer, R. R. Richards-Kortum, S. L. Jacques, M. S. Feld, “Fluorescence spectroscopy of turbid media—autofluorescence of the human aorta,” Appl. Opt. 28, 4286–4292 (1989).
[CrossRef] [PubMed]

1988

P. Lenz, “Endoscopic fluorescence detector,” Rev. Sci. Instrum. 59, 930–933 (1988).
[CrossRef]

1986

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. A. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

1984

G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
[PubMed]

A. E. Profio, D. R. Doiron, J. Sarnaik, “Fluorometer for endoscopic diagnosis of tumors,” Med. Phys. 11, 516–520 (1984).
[CrossRef] [PubMed]

1982

A. Mayevsky, B. Chance, “Intracellular oxidation-reduction state measured in situ by a multichannel fiber-optic surface fluorometer,” Science 217, 537–540 (1982).
[CrossRef] [PubMed]

1974

A. Mayevsky, B. Chance, “Repetitive patterns of metabolic changes during cortical spreading depression of the awake rat,” Brain Res. 65, 529–533 (1974).
[CrossRef] [PubMed]

1971

F. F. Jöbsis, M. O’Connor, A. Vitale, H. Vreman, “Intracellular redox changes in functioning cerebral cortex. I. Metabolic effects of epileptiform activity,” J. Neurophysiol. 34, 735–749 (1971).
[PubMed]

Akins, D. L.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Alfano, R. R.

N. N. Zhadin, R. R. Alfano, “Correction of the internal absorption effect in fluorescence emission and excitation spectra from absorbing and highly scattering media: theory and experiment,” J. Biomed. Opt. 3, 171–186 (1998).
[CrossRef] [PubMed]

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Anderson, E. R.

Anidjar, M.

M. Anidjar, O. Cussenot, S. Avrillier, D. Ettori, M. J. Villette, J. Fiet, P. Teillac, A. Le Duc, “Ultraviolet laser-induced autofluorescence distinction between malignant and normal urothelial cells and tissues,” J. Biomed. Opt. 1, 335–341 (1996).
[CrossRef] [PubMed]

Arendt, J. T.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

Avrillier, S.

M. Anidjar, O. Cussenot, S. Avrillier, D. Ettori, M. J. Villette, J. Fiet, P. Teillac, A. Le Duc, “Ultraviolet laser-induced autofluorescence distinction between malignant and normal urothelial cells and tissues,” J. Biomed. Opt. 1, 335–341 (1996).
[CrossRef] [PubMed]

Backman, V.

Baumgartner, R.

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

Berthier, J.-P.

G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
[PubMed]

Bigio, I. J.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer elastic light scattering,” Lasers Surg. Med. 17, 350–357 (1995).
[CrossRef]

Boyer, J.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer elastic light scattering,” Lasers Surg. Med. 17, 350–357 (1995).
[CrossRef]

Brackmann, U.

U. Brackmann, Lambdachrome Laser Dyes (Lambda Physik GmbH, Goettingen, Germany, 1997).

Brenner, M.

Bruining, H. A.

C. Ince, J. M. C. C. Coremans, H. A. Bruining, “In vivo NADH fluorescence,” in Oxygen Transport to Tissue XIV, W. Erdmann, D. F. Bruley, eds. (Plenum, New York, 1992).

Caron, A.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Celmer, E.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Chance, B.

A. Mayevsky, B. Chance, “Intracellular oxidation-reduction state measured in situ by a multichannel fiber-optic surface fluorometer,” Science 217, 537–540 (1982).
[CrossRef] [PubMed]

A. Mayevsky, B. Chance, “Repetitive patterns of metabolic changes during cortical spreading depression of the awake rat,” Brain Res. 65, 529–533 (1974).
[CrossRef] [PubMed]

Chen, C.-T.

C.-T. Chen, H. K. Chiang, S.-N. Chow, C.-Y. Wang, Y.-S. Lee, J.-C. Tsai, C.-P. Chiang, “Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis,” J. Oral Pathol. Med. 27, 470–474 (1998).
[CrossRef] [PubMed]

Chiang, C.-P.

C.-T. Chen, H. K. Chiang, S.-N. Chow, C.-Y. Wang, Y.-S. Lee, J.-C. Tsai, C.-P. Chiang, “Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis,” J. Oral Pathol. Med. 27, 470–474 (1998).
[CrossRef] [PubMed]

Chiang, H. K.

C.-T. Chen, H. K. Chiang, S.-N. Chow, C.-Y. Wang, Y.-S. Lee, J.-C. Tsai, C.-P. Chiang, “Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis,” J. Oral Pathol. Med. 27, 470–474 (1998).
[CrossRef] [PubMed]

Chow, S.-N.

C.-T. Chen, H. K. Chiang, S.-N. Chow, C.-Y. Wang, Y.-S. Lee, J.-C. Tsai, C.-P. Chiang, “Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis,” J. Oral Pathol. Med. 27, 470–474 (1998).
[CrossRef] [PubMed]

Cleary, J.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Compton, C. C.

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

Conn, R. L.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer elastic light scattering,” Lasers Surg. Med. 17, 350–357 (1995).
[CrossRef]

Coquoz, O.

Coremans, J. M. C. C.

C. Ince, J. M. C. C. Coremans, H. A. Bruining, “In vivo NADH fluorescence,” in Oxygen Transport to Tissue XIV, W. Erdmann, D. F. Bruley, eds. (Plenum, New York, 1992).

Cornillault, J.

G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
[PubMed]

Cothren, R. M.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. A. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Crawford, J. M.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

Cussenot, O.

M. Anidjar, O. Cussenot, S. Avrillier, D. Ettori, M. J. Villette, J. Fiet, P. Teillac, A. Le Duc, “Ultraviolet laser-induced autofluorescence distinction between malignant and normal urothelial cells and tissues,” J. Biomed. Opt. 1, 335–341 (1996).
[CrossRef] [PubMed]

Das, B. B.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Dasari, R. R.

Deckelbaum, L. I.

L. I. Laifer, K. M. O’Brien, M. L. Stetz, G. R. Gindi, T. J. Garrand, L. I. Deckelbaum, “Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence,” Circulation 80, 1893–1901 (1989).
[CrossRef] [PubMed]

Deutsch, T. F.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

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

Doiron, D. R.

A. E. Profio, D. R. Doiron, J. Sarnaik, “Fluorometer for endoscopic diagnosis of tumors,” Med. Phys. 11, 516–520 (1984).
[CrossRef] [PubMed]

Durkin, A. J.

Ehsan, A.

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

Eick, A. A.

Enquist, H.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

Ettori, D.

M. Anidjar, O. Cussenot, S. Avrillier, D. Ettori, M. J. Villette, J. Fiet, P. Teillac, A. Le Duc, “Ultraviolet laser-induced autofluorescence distinction between malignant and normal urothelial cells and tissues,” J. Biomed. Opt. 1, 335–341 (1996).
[CrossRef] [PubMed]

Farrell, T. J.

Feld, M. S.

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

S. W. E. van de Poll, M. G. Müller, Q. Zhang, J. Myles, J. R. Kramer, M. S. Feld, “Combined fluorescence and reflectance spectroscopy of arterial wall improves the identification of atherosclerosis,” Circulation 100, 2349, Suppl. SNov.2 (1999).

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38, 6628–6637 (1999).
[CrossRef]

R. A. Zangaro, L. Silveira, R. Manoharan, G. Zonios, I. Itzkan, R. R. Dasari, J. Van Dam, M. S. Feld, “Rapid multiexcitation fluorescence spectroscopy system for in vivo tissue diagnosis,” Appl. Opt. 35, 5211–5219 (1996).
[CrossRef] [PubMed]

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

J. Wu, M. S. Feld, R. P. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3585–3595 (1993).
[CrossRef] [PubMed]

M. Keijzer, R. R. Richards-Kortum, S. L. Jacques, M. S. Feld, “Fluorescence spectroscopy of turbid media—autofluorescence of the human aorta,” Appl. Opt. 28, 4286–4292 (1989).
[CrossRef] [PubMed]

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. A. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Fiet, J.

M. Anidjar, O. Cussenot, S. Avrillier, D. Ettori, M. J. Villette, J. Fiet, P. Teillac, A. Le Duc, “Ultraviolet laser-induced autofluorescence distinction between malignant and normal urothelial cells and tissues,” J. Biomed. Opt. 1, 335–341 (1996).
[CrossRef] [PubMed]

Fishkin, J. B.

Fitzmaurice, M.

Flotte, T. J.

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

Freyer, J. P.

Frisoli, J. K.

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

Gardner, C. M.

Garrand, T. J.

L. I. Laifer, K. M. O’Brien, M. L. Stetz, G. R. Gindi, T. J. Garrand, L. I. Deckelbaum, “Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence,” Circulation 80, 1893–1901 (1989).
[CrossRef] [PubMed]

Gindi, G. R.

L. I. Laifer, K. M. O’Brien, M. L. Stetz, G. R. Gindi, T. J. Garrand, L. I. Deckelbaum, “Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence,” Circulation 80, 1893–1901 (1989).
[CrossRef] [PubMed]

Glassman, W. L. S.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Godard, B.

G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
[PubMed]

Gupta, P. K.

S. K. Majumder, P. K. Gupta, A. Uppal, “Autofluorescence spectroscopy of tissues from human oral cavity for discriminating malignant from normal,” Lasers Life Sci. 8, 211–227 (1999).

P. K. Gupta, S. K. Majumder, A. Uppal, “Breast cancer diagnosis using nitrogen laser excited autofluorescence spectroscopy,” Lasers Surg. Med. 21, 417–422 (1997).
[CrossRef]

Hawkes, R. P.

Hayes, G. B.

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. A. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Hielscher, A. H.

Hofstetter, A.

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

Ince, C.

C. Ince, J. M. C. C. Coremans, H. A. Bruining, “In vivo NADH fluorescence,” in Oxygen Transport to Tissue XIV, W. Erdmann, D. F. Bruley, eds. (Plenum, New York, 1992).

Itzkan, I.

Jacques, S. L.

Jaikumar, S.

Jöbsis, F. F.

F. F. Jöbsis, M. O’Connor, A. Vitale, H. Vreman, “Intracellular redox changes in functioning cerebral cortex. I. Metabolic effects of epileptiform activity,” J. Neurophysiol. 34, 735–749 (1971).
[PubMed]

Johnson, T.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer elastic light scattering,” Lasers Surg. Med. 17, 350–357 (1995).
[CrossRef]

Johnson, T. M.

Jongen, A. J. L.

A. J. L. Jongen, H. J. C. M. Sterenborg, “Mathematical description of photobleaching in vivo describing the influence of tissue optics on measured fluorescence signals,” Phys. Med. Biol. 42, 1701–1716 (1997).
[CrossRef] [PubMed]

Keijzer, M.

Kittrell, C.

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. A. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Knuchel, R.

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

Koenig, F.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

Kollias, N.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

Kramer, J. R.

S. W. E. van de Poll, M. G. Müller, Q. Zhang, J. Myles, J. R. Kramer, M. S. Feld, “Combined fluorescence and reflectance spectroscopy of arterial wall improves the identification of atherosclerosis,” Circulation 100, 2349, Suppl. SNov.2 (1999).

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. A. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Kriegmair, M.

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

Laifer, L. I.

L. I. Laifer, K. M. O’Brien, M. L. Stetz, G. R. Gindi, T. J. Garrand, L. I. Deckelbaum, “Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence,” Circulation 80, 1893–1901 (1989).
[CrossRef] [PubMed]

Larne, R.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

Le Duc, A.

M. Anidjar, O. Cussenot, S. Avrillier, D. Ettori, M. J. Villette, J. Fiet, P. Teillac, A. Le Duc, “Ultraviolet laser-induced autofluorescence distinction between malignant and normal urothelial cells and tissues,” J. Biomed. Opt. 1, 335–341 (1996).
[CrossRef] [PubMed]

Lee, Y.-S.

C.-T. Chen, H. K. Chiang, S.-N. Chow, C.-Y. Wang, Y.-S. Lee, J.-C. Tsai, C.-P. Chiang, “Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis,” J. Oral Pathol. Med. 27, 470–474 (1998).
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Lenz, P.

P. Lenz, “Endoscopic fluorescence detector,” Rev. Sci. Instrum. 59, 930–933 (1988).
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Liu, C. H.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Lubicz, S. S.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Lumper, W.

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

MacAulay, C.

H. Zeng, C. MacAulay, D. I. McLean, B. Palcic, “Spectroscopic and microscopic characteristics of human skin autofluorescence emission,” Photochem. Photobiol. 61, 639–645 (1995).
[CrossRef] [PubMed]

Mahadevan, A.

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. USA 91, 10193–10197 (1994).
[CrossRef]

Majumder, S. K.

S. K. Majumder, P. K. Gupta, A. Uppal, “Autofluorescence spectroscopy of tissues from human oral cavity for discriminating malignant from normal,” Lasers Life Sci. 8, 211–227 (1999).

P. K. Gupta, S. K. Majumder, A. Uppal, “Breast cancer diagnosis using nitrogen laser excited autofluorescence spectroscopy,” Lasers Surg. Med. 21, 417–422 (1997).
[CrossRef]

Manoharan, R.

Mayevsky, A.

A. Mayevsky, B. Chance, “Intracellular oxidation-reduction state measured in situ by a multichannel fiber-optic surface fluorometer,” Science 217, 537–540 (1982).
[CrossRef] [PubMed]

A. Mayevsky, B. Chance, “Repetitive patterns of metabolic changes during cortical spreading depression of the awake rat,” Brain Res. 65, 529–533 (1974).
[CrossRef] [PubMed]

McGovern, F. J.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

McLean, D. I.

H. Zeng, C. MacAulay, D. I. McLean, B. Palcic, “Spectroscopic and microscopic characteristics of human skin autofluorescence emission,” Photochem. Photobiol. 61, 639–645 (1995).
[CrossRef] [PubMed]

Mitchell, M. F.

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. USA 91, 10193–10197 (1994).
[CrossRef]

Mourant, J. R.

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37, 3586–3593 (1998).
[CrossRef]

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer elastic light scattering,” Lasers Surg. Med. 17, 350–357 (1995).
[CrossRef]

Muffat-Joly, M.

G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
[PubMed]

Müller, M. G.

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

S. W. E. van de Poll, M. G. Müller, Q. Zhang, J. Myles, J. R. Kramer, M. S. Feld, “Combined fluorescence and reflectance spectroscopy of arterial wall improves the identification of atherosclerosis,” Circulation 100, 2349, Suppl. SNov.2 (1999).

Myles, J.

S. W. E. van de Poll, M. G. Müller, Q. Zhang, J. Myles, J. R. Kramer, M. S. Feld, “Combined fluorescence and reflectance spectroscopy of arterial wall improves the identification of atherosclerosis,” Circulation 100, 2349, Suppl. SNov.2 (1999).

Nishioka, N. S.

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

O’Brien, K. M.

L. I. Laifer, K. M. O’Brien, M. L. Stetz, G. R. Gindi, T. J. Garrand, L. I. Deckelbaum, “Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence,” Circulation 80, 1893–1901 (1989).
[CrossRef] [PubMed]

O’Connor, M.

F. F. Jöbsis, M. O’Connor, A. Vitale, H. Vreman, “Intracellular redox changes in functioning cerebral cortex. I. Metabolic effects of epileptiform activity,” J. Neurophysiol. 34, 735–749 (1971).
[PubMed]

Palcic, B.

H. Zeng, C. MacAulay, D. I. McLean, B. Palcic, “Spectroscopic and microscopic characteristics of human skin autofluorescence emission,” Photochem. Photobiol. 61, 639–645 (1995).
[CrossRef] [PubMed]

Patterson, M. S.

Perelman, L. T.

Pocidalo, J.-J.

G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
[PubMed]

Pogue, B. W.

Profio, A. E.

A. E. Profio, D. R. Doiron, J. Sarnaik, “Fluorometer for endoscopic diagnosis of tumors,” Med. Phys. 11, 516–520 (1984).
[CrossRef] [PubMed]

Prudente, R.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Ramanujam, N.

A. J. Durkin, S. Jaikumar, N. Ramanujam, R. Richards-Kortum, “Relation between fluorescence-spectra of dilute and turbid samples,” Appl. Opt. 33, 414–423 (1994).
[CrossRef] [PubMed]

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. USA 91, 10193–10197 (1994).
[CrossRef]

Rava, R. P.

Raynal, E.

G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
[PubMed]

Renault, G.

G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
[PubMed]

Richards-Kortum, R.

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

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. USA 91, 10193–10197 (1994).
[CrossRef]

A. J. Durkin, S. Jaikumar, N. Ramanujam, R. Richards-Kortum, “Relation between fluorescence-spectra of dilute and turbid samples,” Appl. Opt. 33, 414–423 (1994).
[CrossRef] [PubMed]

A. J. Durkin, S. Jaikumar, R. Richards-Kortum, “Optically dilute, absorbing and turbid phantoms for fluorescence spectroscopy of homogenous and inhomogenous samples,” Appl. Spectrosc. 47, 2114–2121 (1993).
[CrossRef]

Richards-Kortum, R. R.

Richter, J. M.

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

Rick, K.

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

Sacks, B. A.

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. A. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

Sarnaik, J.

A. E. Profio, D. R. Doiron, J. Sarnaik, “Fluorometer for endoscopic diagnosis of tumors,” Med. Phys. 11, 516–520 (1984).
[CrossRef] [PubMed]

Schomacker, K. T.

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

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

Sevick-Muraca, E.

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

Shen, D.

Shimada, T.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer elastic light scattering,” Lasers Surg. Med. 17, 350–357 (1995).
[CrossRef]

Silva, E.

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. USA 91, 10193–10197 (1994).
[CrossRef]

Silveira, L.

Sinet, M.

G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
[PubMed]

Star, W. M.

G. A. Wagnières, W. M. Star, B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–632 (1998).
[PubMed]

Steinbach, P.

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

Stepp, H.

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

Stepp, H. G.

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

Sterenborg, H. J. C. M.

A. J. L. Jongen, H. J. C. M. Sterenborg, “Mathematical description of photobleaching in vivo describing the influence of tissue optics on measured fluorescence signals,” Phys. Med. Biol. 42, 1701–1716 (1997).
[CrossRef] [PubMed]

Stetz, M. L.

L. I. Laifer, K. M. O’Brien, M. L. Stetz, G. R. Gindi, T. J. Garrand, L. I. Deckelbaum, “Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence,” Circulation 80, 1893–1901 (1989).
[CrossRef] [PubMed]

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C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

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M. Anidjar, O. Cussenot, S. Avrillier, D. Ettori, M. J. Villette, J. Fiet, P. Teillac, A. Le Duc, “Ultraviolet laser-induced autofluorescence distinction between malignant and normal urothelial cells and tissues,” J. Biomed. Opt. 1, 335–341 (1996).
[CrossRef] [PubMed]

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N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. USA 91, 10193–10197 (1994).
[CrossRef]

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C.-T. Chen, H. K. Chiang, S.-N. Chow, C.-Y. Wang, Y.-S. Lee, J.-C. Tsai, C.-P. Chiang, “Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis,” J. Oral Pathol. Med. 27, 470–474 (1998).
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S. K. Majumder, P. K. Gupta, A. Uppal, “Autofluorescence spectroscopy of tissues from human oral cavity for discriminating malignant from normal,” Lasers Life Sci. 8, 211–227 (1999).

P. K. Gupta, S. K. Majumder, A. Uppal, “Breast cancer diagnosis using nitrogen laser excited autofluorescence spectroscopy,” Lasers Surg. Med. 21, 417–422 (1997).
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O. W. van Assendelft, Spectrophotometry of Haemoglobin Derivatives (Thomas, Springfield, Ill., 1970).

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H. C. van de Hulst, Light Scattering by Small Particles (Dover, New York, 1957).

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S. W. E. van de Poll, M. G. Müller, Q. Zhang, J. Myles, J. R. Kramer, M. S. Feld, “Combined fluorescence and reflectance spectroscopy of arterial wall improves the identification of atherosclerosis,” Circulation 100, 2349, Suppl. SNov.2 (1999).

VanDam, J.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

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M. Anidjar, O. Cussenot, S. Avrillier, D. Ettori, M. J. Villette, J. Fiet, P. Teillac, A. Le Duc, “Ultraviolet laser-induced autofluorescence distinction between malignant and normal urothelial cells and tissues,” J. Biomed. Opt. 1, 335–341 (1996).
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F. F. Jöbsis, M. O’Connor, A. Vitale, H. Vreman, “Intracellular redox changes in functioning cerebral cortex. I. Metabolic effects of epileptiform activity,” J. Neurophysiol. 34, 735–749 (1971).
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G. A. Wagnières, W. M. Star, B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–632 (1998).
[PubMed]

Wang, C.-Y.

C.-T. Chen, H. K. Chiang, S.-N. Chow, C.-Y. Wang, Y.-S. Lee, J.-C. Tsai, C.-P. Chiang, “Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis,” J. Oral Pathol. Med. 27, 470–474 (1998).
[CrossRef] [PubMed]

Warren, S.

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. USA 91, 10193–10197 (1994).
[CrossRef]

Welch, A. J.

Wilson, B. C.

G. A. Wagnières, W. M. Star, B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–632 (1998).
[PubMed]

T. J. Farrell, R. P. Hawkes, M. S. Patterson, B. C. Wilson, “Modeling of photosensitizer fluorescence emission and photobleaching for photodynamic therapy dosimetry,” Appl. Opt. 37, 7168–7183 (1998).
[CrossRef]

Wu, J.

Yoo, K. M.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Zangaro, R. A.

Zeng, H.

H. Zeng, C. MacAulay, D. I. McLean, B. Palcic, “Spectroscopic and microscopic characteristics of human skin autofluorescence emission,” Photochem. Photobiol. 61, 639–645 (1995).
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N. N. Zhadin, R. R. Alfano, “Correction of the internal absorption effect in fluorescence emission and excitation spectra from absorbing and highly scattering media: theory and experiment,” J. Biomed. Opt. 3, 171–186 (1998).
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S. W. E. van de Poll, M. G. Müller, Q. Zhang, J. Myles, J. R. Kramer, M. S. Feld, “Combined fluorescence and reflectance spectroscopy of arterial wall improves the identification of atherosclerosis,” Circulation 100, 2349, Suppl. SNov.2 (1999).

Zhu, H. R.

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Zonios, G.

Zonios, G. I.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

G. I. Zonios, “Diffuse reflectance spectroscopy of human colon tissue,” Ph.D. dissertation (MIT, Cambridge, Mass., 1998).

Am. J. Physiol.

G. Renault, E. Raynal, M. Sinet, M. Muffat-Joly, J.-P. Berthier, J. Cornillault, B. Godard, J.-J. Pocidalo, “In situ double-beam NADH laser fluorimetry: a choice of a reference wavelength,” Am. J. Physiol. 246, H491–H499 (1984).
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Appl. Opt.

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J. Wu, M. S. Feld, R. P. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3585–3595 (1993).
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C. M. Gardner, S. L. Jacques, A. J. Welch, “Fluorescence spectroscopy of tissue: recovery of intrinsic fluorescence from measured fluorescence,” Appl. Opt. 35, 1780–1792 (1996).
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R. A. Zangaro, L. Silveira, R. Manoharan, G. Zonios, I. Itzkan, R. R. Dasari, J. Van Dam, M. S. Feld, “Rapid multiexcitation fluorescence spectroscopy system for in vivo tissue diagnosis,” Appl. Opt. 35, 5211–5219 (1996).
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J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37, 3586–3593 (1998).
[CrossRef]

T. J. Farrell, R. P. Hawkes, M. S. Patterson, B. C. Wilson, “Modeling of photosensitizer fluorescence emission and photobleaching for photodynamic therapy dosimetry,” Appl. Opt. 37, 7168–7183 (1998).
[CrossRef]

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38, 6628–6637 (1999).
[CrossRef]

Appl. Spectrosc.

Brain Res.

A. Mayevsky, B. Chance, “Repetitive patterns of metabolic changes during cortical spreading depression of the awake rat,” Brain Res. 65, 529–533 (1974).
[CrossRef] [PubMed]

Circulation

L. I. Laifer, K. M. O’Brien, M. L. Stetz, G. R. Gindi, T. J. Garrand, L. I. Deckelbaum, “Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence,” Circulation 80, 1893–1901 (1989).
[CrossRef] [PubMed]

S. W. E. van de Poll, M. G. Müller, Q. Zhang, J. Myles, J. R. Kramer, M. S. Feld, “Combined fluorescence and reflectance spectroscopy of arterial wall improves the identification of atherosclerosis,” Circulation 100, 2349, Suppl. SNov.2 (1999).

IEEE Trans. Biomed. Eng.

G. I. Zonios, R. M. Cothren, J. T. Arendt, J. Wu, J. VanDam, J. M. Crawford, R. Manoharan, M. S. Feld, “Morphological model of human colon tissue fluorescence,” IEEE Trans. Biomed. Eng. 43, 113–122 (1996).
[CrossRef] [PubMed]

J. Biomed. Opt.

M. Anidjar, O. Cussenot, S. Avrillier, D. Ettori, M. J. Villette, J. Fiet, P. Teillac, A. Le Duc, “Ultraviolet laser-induced autofluorescence distinction between malignant and normal urothelial cells and tissues,” J. Biomed. Opt. 1, 335–341 (1996).
[CrossRef] [PubMed]

N. N. Zhadin, R. R. Alfano, “Correction of the internal absorption effect in fluorescence emission and excitation spectra from absorbing and highly scattering media: theory and experiment,” J. Biomed. Opt. 3, 171–186 (1998).
[CrossRef] [PubMed]

J. Neurophysiol.

F. F. Jöbsis, M. O’Connor, A. Vitale, H. Vreman, “Intracellular redox changes in functioning cerebral cortex. I. Metabolic effects of epileptiform activity,” J. Neurophysiol. 34, 735–749 (1971).
[PubMed]

J. Oral Pathol. Med.

C.-T. Chen, H. K. Chiang, S.-N. Chow, C.-Y. Wang, Y.-S. Lee, J.-C. Tsai, C.-P. Chiang, “Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis,” J. Oral Pathol. Med. 27, 470–474 (1998).
[CrossRef] [PubMed]

J. Photochem. Photobiol. B

C. H. Liu, B. B. Das, W. L. S. Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. Celmer, A. Caron, R. R. Alfano, “Raman, fluorescence, and time-resolved light-scattering as optical diagnostic-techniques to separate diseased and normal biomedical media,” J. Photochem. Photobiol. B 16(2), 187–209(1992).
[CrossRef]

Lasers Life Sci.

R. M. Cothren, G. B. Hayes, J. R. Kramer, B. A. Sacks, C. Kittrell, M. S. Feld, “A multifiber catheter with an optical shield for laser angiosurgery,” Lasers Life Sci. 1, 1–12 (1986).

S. K. Majumder, P. K. Gupta, A. Uppal, “Autofluorescence spectroscopy of tissues from human oral cavity for discriminating malignant from normal,” Lasers Life Sci. 8, 211–227 (1999).

Lasers Surg. Med.

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

P. K. Gupta, S. K. Majumder, A. Uppal, “Breast cancer diagnosis using nitrogen laser excited autofluorescence spectroscopy,” Lasers Surg. Med. 21, 417–422 (1997).
[CrossRef]

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer elastic light scattering,” Lasers Surg. Med. 17, 350–357 (1995).
[CrossRef]

Med. Phys.

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[CrossRef] [PubMed]

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G. A. Wagnières, W. M. Star, B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–632 (1998).
[PubMed]

H. Zeng, C. MacAulay, D. I. McLean, B. Palcic, “Spectroscopic and microscopic characteristics of human skin autofluorescence emission,” Photochem. Photobiol. 61, 639–645 (1995).
[CrossRef] [PubMed]

Phys. Med. Biol.

A. J. L. Jongen, H. J. C. M. Sterenborg, “Mathematical description of photobleaching in vivo describing the influence of tissue optics on measured fluorescence signals,” Phys. Med. Biol. 42, 1701–1716 (1997).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. USA

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. USA 91, 10193–10197 (1994).
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[CrossRef] [PubMed]

Urologia Internationalis

M. Kriegmair, H. Stepp, P. Steinbach, W. Lumper, A. Ehsan, H. G. Stepp, K. Rick, R. Knuchel, R. Baumgartner, A. Hofstetter, “Fluorescence cystoscopy following intravesical instillation of 5-Aminolevulinic acid—a new procedure with high sensitivity for detection of hardly visible urothelial neoplasias,” Urologia Internationalis 55, 190–196 (1995).
[CrossRef]

Urology

F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998).
[CrossRef] [PubMed]

Other

C. Ince, J. M. C. C. Coremans, H. A. Bruining, “In vivo NADH fluorescence,” in Oxygen Transport to Tissue XIV, W. Erdmann, D. F. Bruley, eds. (Plenum, New York, 1992).

In the current version we do not need to consider the effective albedo, aeff, introduced in Ref. 25, because the new form of the escape probability [Eq. 2(b)] takes into account differences in optical properties at the excitation and the emission wavelengths. Additionally, we find that the previously introduced effective anisotropy coefficient, geff, does not significantly affect the resulting intrinsic fluorescence spectrum.

U. Brackmann, Lambdachrome Laser Dyes (Lambda Physik GmbH, Goettingen, Germany, 1997).

O. W. van Assendelft, Spectrophotometry of Haemoglobin Derivatives (Thomas, Springfield, Ill., 1970).

H. C. van de Hulst, Light Scattering by Small Particles (Dover, New York, 1957).

G. I. Zonios, “Diffuse reflectance spectroscopy of human colon tissue,” Ph.D. dissertation (MIT, Cambridge, Mass., 1998).

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Figures (12)

Fig. 1
Fig. 1

FastEEM instrument. Flash-lamp source is used for reflectance spectroscopy, (dye) laser source for fluorescence spectroscopy. The nitrogen laser pumps the dye cells to obtain ten dye laser wavelengths. A fiber-optic probe is used for light delivery and collection.

Fig. 2
Fig. 2

(a) Fluorescence emission spectra (337-nm excitation) and (b) corresponding reflectance spectra of physical tissue models. Curve i, for a dilute dye solution, gives the intrinsic fluorescence. In curves ii–viii the concentration of polystyrene beads is progressively increased. In volume percent, (i) 0, (ii) 0.016, (iii) 0.065, (iv) 0.325, (v) 0.65, (vi) 0.975, (vii) 1.3, (viii) 1.95. This provided values of μ s ′ ranging from 0 to 10 mm-1 at λ = 400 nm. Note that in these studies μ a = 0. Fluorescence intensity is in detector counts. The collected reflectance is in units of fraction of incident light.

Fig. 3
Fig. 3

(a) Fluorescence emission spectra of Fig. 2(a), normalized to their peak heights; (b) fluorescence ratio spectra, obtained from the curves of Fig. 2(a) by division by the intrinsic fluorescence, curve i. Note the small line-shape differences between the intrinsic fluorescence and the fluorescence with scatterers present.

Fig. 4
Fig. 4

Fluorescence ratio spectra: prediction [Eq. (4)], Monte Carlo simulation and experiment [curve v from Fig. 3(b)]. Error bars (5%) are due to fluctuations in Monte Carlo simulations because of finite numbers of photons.

Fig. 5
Fig. 5

Peak fluorescence intensity of physical tissue models as a function of polystyrene bead concentration. The peak values are taken from the spectra of Fig. 2(a). The error bars indicate the laser shot-to-shot excitation variations and accuracy of dye concentrations.

Fig. 6
Fig. 6

Effects of absorption and scattering on observed fluorescence. (a) Fluorescence spectrum of a dilute solution of dye (i) (intrinsic fluorescence) and physical tissue models with a fixed scatterer concentration and different concentrations of hemoglobin added: (ii) 0, (iii) 0.05, (iv) 0.125, (v) 0.25, (vi) 0.5, (vii) 0.75, (viii) 1, (ix) 1.5, (x) 2 g/l; (b) comparison of measured and extracted intrinsic fluorescence and observed fluorescence of a sample [Fig. 6(a), ix] with hemoglobin (1.5 g/l). All spectra are normalized. (c) Reflectance spectra of physical tissue models with various absorber concentrations. Note that the intensity decreases in (a) and (c) with increasing hemoglobin, especially at the major oxyhemoglobin absorption peak (415 nm). In all the above data, μ s ′ was held constant at approximately 2 mm-1.

Fig. 7
Fig. 7

Intrinsic fluorescence emission spectra, extracted from turbid physical tissue models Fig. 6(a), λ x = 337 nm: (a) normalized, (b) unnormalized. The measured intrinsic fluorescence is indicated. Note in (a) the excellent agreement of the corrected line shapes. The intensity differences in (b) are small, indicating good intensity corrections of data varying in intensity by an order of magnitude [compare Fig. 6(a)]. Analysis of the data gives l = 220 µm. See text for details.

Fig. 8
Fig. 8

EEMs of minced oral cavity tissue. (a) Minced tissue (∼2 g/l Hb concentration and 4-mm thickness). (b) Intrinsic fluorescence EEM of a thin section of minced tissue (∼10-µm thickness); absorption and scattering effects are negligible. (c) Extracted intrinsic fluorescence for minces with hemoglobin concentrations ranging from 0.7 to 4.7 g/l, λ x = 337 nm. (d) Extracted intrinsic fluorescence EEM of minced tissue. The similarity between (b) and (d) and the dissimilarity between (a) and (b,d) show the usefulness of the intrinsic fluorescence extraction method. Note that the hemoglobin dip in (a) has vanished. The 20-fold intensity difference between (b) and (d) corresponds well to the difference in the thickness of the thin section (∼10 µm) and the fluorescence collection depth (l = 220-µm probe parameter). The tenfold intensity difference between (a) and (d) is reasonable [compare Fig. 6(a)].

Fig. 9
Fig. 9

Fluorescence EEMs of bulk oral cavity tissue in vitro. (a) bulk tissue (∼5-mm thickness), (b) extracted intrinsic fluorescence. The similarity between (b) and Figs. 8(b) and 8(d) indicates that the influence of tissue layer structure on the intrinsic fluorescence is minor.

Fig. 10
Fig. 10

Comparison of intrinsic fluorescence of bulk oral cavity tissue and minced tissue in vivo and in vitro. (i) Minced tissue, extracted intrinsic fluorescence; (ii) minced tissue, thin sample; (iii) bulk tissue in vitro, extracted intrinsic fluorescence; (iv) bulk tissue in vivo, extracted intrinsic fluorescence; (v) measured mince fluorescence, (uncorrected). All spectra are normalized. The intrinsic fluorescence spectra essentially collapse to the same line shape. However, the mince fluorescence shows major differences, mostly owing to distortions from hemoglobin absorption.

Fig. 11
Fig. 11

In vivo fluorescence spectra of esophageal tissue from two patients. (a) Measured fluorescence, (b) intrinsic fluorescence. Note the variations in line shape and intensity in (a) and the similarity in spectra after extraction of the intrinsic fluorescence (b).

Fig. 12
Fig. 12

In vivo fluorescence spectra from buccal mucosa tissue. Comparison of intrinsic fluorescence from a normal tissue site (i) and a cancerous site (ii). The large peak shift can be attributed to stronger NADH fluorescence.

Equations (9)

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

Rλ=n=1 ρnwn,
FxmFλx, λm=n=1i=0n-1 ρniwni,
wn=an,
wni=axi+1fxmμsxl amn-i-1,
fxm=Ix/hνxμfxlϕxmhνm,
ρn=α exp-βn,
ρni=αxαm1/2 exp-βxi+1exp-βmn-i-1.
fxm=Fxm1μsxlR0xR0mxm1/2 RxR0xRmR0m+m.
fxm=Fxm1μsxlR0xR0mxm1/2 1+m.

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