Abstract

We present a method for recovering the intrinsic fluorescence coefficient, defined as the product of the fluorophore absorption coefficient and the fluorescence energy yield, of an optically thick, homogeneous, turbid medium from a surface measurement of fluorescence and from knowledge of medium optical properties. The measured fluorescence signal is related to the intrinsic fluorescence coefficient by an optical property dependent path-length factor. A simple expression was developed for the path-length factor, which characterizes the penetration of excitation light and the escape of fluorescence from the medium. Experiments with fluorescent tissue phantoms demonstrated that intrinsic fluorescence line shape could be recovered and that fluorophore concentration could be estimated within ±15%, over a wide range of optical properties.

© 1996 Optical Society of America

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  1. R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
    [CrossRef] [PubMed]
  2. 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] [PubMed]
  3. M. Keijzer, R. Richards-Kortum, S. Jacques, M. Feld, “Fluorescence spectroscopy of turbid media: autofluorescence of the human aorta,” Appl. Opt. 28, 4286–42921989.
    [CrossRef] [PubMed]
  4. S. R. Brown, D. I. Vernon, “The quantitative determination of porphyrins in tissues and body fluids: applications in studies of photodynamic therapy,” in Photodynamic Therapy of Neoplastic Disease, D. Kessel, ed. (CRC, Ann Arbor, Mich., 1990) Vol. 1, pp. 109–128.
  5. G. H. M. Gijsbers, D. Breederveld, M. J. C. van Gemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–48 (1986).
  6. 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]
  7. R. Richards-Kortum, R. P. Rava, M. Fitzmaurice, L. L. Tong, N. B. Ratliff, J. R. Kramer, M. S. Feld, “A one-layer model of laser-induced fluorescence for diagnosis of disease in human tissue: applications to atherosclerosis,” IEEE Trans. Biomed. Eng. 36, 1222–1231 (1989).
    [CrossRef] [PubMed]
  8. W. R. Potter, T. S. Mang, “Photofrin II levels by in vivo fluorescence photometry,” in Porphyrin Localization and Treatment of Tumors, C. Gomer, D. Doiron, eds. (Liss, New York, 1984), pp. 177–186.
  9. A. E. Profio, S. Xie, K.-H. Shu, “Diagnosis of tumors by fluorescence: quantification of photosensitizer concentration,” in Photodynamic Therapy: Mechanisms II, T. J. Dougherty, ed., Proc. Soc. Photo-Opt. Instrum. Eng.1203, 12–18 (1990).
  10. J. Wu, M. S. Feld, R. P. Rava, “Analytic model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3585–3595 (1993).
    [CrossRef] [PubMed]
  11. 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]
  12. C. M. Gardner, S. L. Jacques, A. J. Welch, “Light transport in tissue: accurate expressions for one-dimensional fluence rate and escape function based upon Monte Carlo simulation,” Lasers Surg. Med. 18 (2), 129–138 (1996).
    [CrossRef] [PubMed]
  13. A. J. Durkin, S. Jaikumar, R. Richards-Kortum, “Optically dilute, absorbing, and turbid phantoms for fluorescence spectroscopy of homogeneous and inhomogeneous samples,” Appl. Spectrosc. 47, 2114–2121 (1993).
    [CrossRef]
  14. R. F. Kubin, A. N. Fletcher, “Fluorescence quantum yields of some rhodamine dyes,” J. Lumin. 27, 445–462 (1982).
    [CrossRef]
  15. B. C. Wilson, S. L. Jacques, “Optical reflectance and transmittance of tissues: principles and applications,” IEEE J. Quantum Electron. 26, 2186–2198 (1990).
    [CrossRef]
  16. S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12, 510–519 (1992).
    [CrossRef] [PubMed]
  17. C. F. Bohren, D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).
  18. W.-F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissue,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
    [CrossRef]
  19. S.A. Prahl, M. J. C. van Gemert, A. J. Welch, “Determining the optical properties of turbid media by using the adding–doubling method,” Appl. Opt. 32, 559–568 (1993).
    [CrossRef] [PubMed]
  20. J. Lakowicz, Principles of Fluorescence Spectroscopy (Plenum, New York, 1983).
    [CrossRef]
  21. N. Shaklai, J. Yguerabide, H. M. Ranney, “Interaction of hemoglobin with red blood cell membranes as shown by a fluorescent chromophore,” Biochemistry 16, 5585–5592 (1977).
    [CrossRef] [PubMed]
  22. T. J. Farrell, M. S. Patterson, B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
    [CrossRef] [PubMed]
  23. C. M. Gardner, “Modeling fluorescence escape from tissue phantoms,” Ph.D. dissertation (University of Texas at Austin, Austin, Tex., 1995).

1996

C. M. Gardner, S. L. Jacques, A. J. Welch, “Light transport in tissue: accurate expressions for one-dimensional fluence rate and escape function based upon Monte Carlo simulation,” Lasers Surg. Med. 18 (2), 129–138 (1996).
[CrossRef] [PubMed]

1994

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] [PubMed]

T. J. Farrell, M. S. Patterson, B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
[CrossRef] [PubMed]

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12, 510–519 (1992).
[CrossRef] [PubMed]

1990

W.-F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissue,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

B. C. Wilson, S. L. Jacques, “Optical reflectance and transmittance of tissues: principles and applications,” IEEE J. Quantum Electron. 26, 2186–2198 (1990).
[CrossRef]

1989

M. Keijzer, R. Richards-Kortum, S. Jacques, M. Feld, “Fluorescence spectroscopy of turbid media: autofluorescence of the human aorta,” Appl. Opt. 28, 4286–42921989.
[CrossRef] [PubMed]

R. Richards-Kortum, R. P. Rava, M. Fitzmaurice, L. L. Tong, N. B. Ratliff, J. R. Kramer, M. S. Feld, “A one-layer model of laser-induced fluorescence for diagnosis of disease in human tissue: applications to atherosclerosis,” IEEE Trans. Biomed. Eng. 36, 1222–1231 (1989).
[CrossRef] [PubMed]

R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

1986

G. H. M. Gijsbers, D. Breederveld, M. J. C. van Gemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–48 (1986).

1982

R. F. Kubin, A. N. Fletcher, “Fluorescence quantum yields of some rhodamine dyes,” J. Lumin. 27, 445–462 (1982).
[CrossRef]

1977

N. Shaklai, J. Yguerabide, H. M. Ranney, “Interaction of hemoglobin with red blood cell membranes as shown by a fluorescent chromophore,” Biochemistry 16, 5585–5592 (1977).
[CrossRef] [PubMed]

Bohren, C. F.

C. F. Bohren, D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).

Boon, T. A.

G. H. M. Gijsbers, D. Breederveld, M. J. C. van Gemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–48 (1986).

Breederveld, D.

G. H. M. Gijsbers, D. Breederveld, M. J. C. van Gemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–48 (1986).

Brown, S. R.

S. R. Brown, D. I. Vernon, “The quantitative determination of porphyrins in tissues and body fluids: applications in studies of photodynamic therapy,” in Photodynamic Therapy of Neoplastic Disease, D. Kessel, ed. (CRC, Ann Arbor, Mich., 1990) Vol. 1, pp. 109–128.

Cheong, W.-F.

W.-F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissue,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[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] [PubMed]

Cothren, R.

R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

Deutsch, T. F.

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] [PubMed]

Durkin, A. J.

Farrell, T. J.

T. J. Farrell, M. S. Patterson, B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
[CrossRef] [PubMed]

Feld, M.

Feld, M. S.

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

R. Richards-Kortum, R. P. Rava, M. Fitzmaurice, L. L. Tong, N. B. Ratliff, J. R. Kramer, M. S. Feld, “A one-layer model of laser-induced fluorescence for diagnosis of disease in human tissue: applications to atherosclerosis,” IEEE Trans. Biomed. Eng. 36, 1222–1231 (1989).
[CrossRef] [PubMed]

R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

Fitzmaurice, M.

R. Richards-Kortum, R. P. Rava, M. Fitzmaurice, L. L. Tong, N. B. Ratliff, J. R. Kramer, M. S. Feld, “A one-layer model of laser-induced fluorescence for diagnosis of disease in human tissue: applications to atherosclerosis,” IEEE Trans. Biomed. Eng. 36, 1222–1231 (1989).
[CrossRef] [PubMed]

Fletcher, A. N.

R. F. Kubin, A. N. Fletcher, “Fluorescence quantum yields of some rhodamine dyes,” J. Lumin. 27, 445–462 (1982).
[CrossRef]

Flock, S. T.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12, 510–519 (1992).
[CrossRef] [PubMed]

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] [PubMed]

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] [PubMed]

Gardner, C. M.

C. M. Gardner, S. L. Jacques, A. J. Welch, “Light transport in tissue: accurate expressions for one-dimensional fluence rate and escape function based upon Monte Carlo simulation,” Lasers Surg. Med. 18 (2), 129–138 (1996).
[CrossRef] [PubMed]

C. M. Gardner, “Modeling fluorescence escape from tissue phantoms,” Ph.D. dissertation (University of Texas at Austin, Austin, Tex., 1995).

Gijsbers, G. H. M.

G. H. M. Gijsbers, D. Breederveld, M. J. C. van Gemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–48 (1986).

Hayes, G.

R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

Huffman, D. R.

C. F. Bohren, D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).

Jacques, S.

Jacques, S. L.

C. M. Gardner, S. L. Jacques, A. J. Welch, “Light transport in tissue: accurate expressions for one-dimensional fluence rate and escape function based upon Monte Carlo simulation,” Lasers Surg. Med. 18 (2), 129–138 (1996).
[CrossRef] [PubMed]

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12, 510–519 (1992).
[CrossRef] [PubMed]

B. C. Wilson, S. L. Jacques, “Optical reflectance and transmittance of tissues: principles and applications,” IEEE J. Quantum Electron. 26, 2186–2198 (1990).
[CrossRef]

Jaikumar, S.

Keijzer, M.

Kittrell, C.

R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

Kolubayev, T.

R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

Kramer, J. R.

R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

R. Richards-Kortum, R. P. Rava, M. Fitzmaurice, L. L. Tong, N. B. Ratliff, J. R. Kramer, M. S. Feld, “A one-layer model of laser-induced fluorescence for diagnosis of disease in human tissue: applications to atherosclerosis,” IEEE Trans. Biomed. Eng. 36, 1222–1231 (1989).
[CrossRef] [PubMed]

Kubin, R. F.

R. F. Kubin, A. N. Fletcher, “Fluorescence quantum yields of some rhodamine dyes,” J. Lumin. 27, 445–462 (1982).
[CrossRef]

Lakowicz, J.

J. Lakowicz, Principles of Fluorescence Spectroscopy (Plenum, New York, 1983).
[CrossRef]

Langelaar, J.

G. H. M. Gijsbers, D. Breederveld, M. J. C. van Gemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–48 (1986).

Mang, T. S.

W. R. Potter, T. S. Mang, “Photofrin II levels by in vivo fluorescence photometry,” in Porphyrin Localization and Treatment of Tumors, C. Gomer, D. Doiron, eds. (Liss, New York, 1984), pp. 177–186.

Mehta, A.

R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

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] [PubMed]

Patterson, M. S.

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]

T. J. Farrell, M. S. Patterson, B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
[CrossRef] [PubMed]

Pogue, B. W.

Potter, W. R.

W. R. Potter, T. S. Mang, “Photofrin II levels by in vivo fluorescence photometry,” in Porphyrin Localization and Treatment of Tumors, C. Gomer, D. Doiron, eds. (Liss, New York, 1984), pp. 177–186.

Prahl, S. A.

W.-F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissue,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

Prahl, S.A.

Profio, A. E.

A. E. Profio, S. Xie, K.-H. Shu, “Diagnosis of tumors by fluorescence: quantification of photosensitizer concentration,” in Photodynamic Therapy: Mechanisms II, T. J. Dougherty, ed., Proc. Soc. Photo-Opt. Instrum. Eng.1203, 12–18 (1990).

Ramanujam, N.

Ranney, H. M.

N. Shaklai, J. Yguerabide, H. M. Ranney, “Interaction of hemoglobin with red blood cell membranes as shown by a fluorescent chromophore,” Biochemistry 16, 5585–5592 (1977).
[CrossRef] [PubMed]

Ratliff, N. B.

R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

R. Richards-Kortum, R. P. Rava, M. Fitzmaurice, L. L. Tong, N. B. Ratliff, J. R. Kramer, M. S. Feld, “A one-layer model of laser-induced fluorescence for diagnosis of disease in human tissue: applications to atherosclerosis,” IEEE Trans. Biomed. Eng. 36, 1222–1231 (1989).
[CrossRef] [PubMed]

Rava, R. P.

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

R. Richards-Kortum, R. P. Rava, M. Fitzmaurice, L. L. Tong, N. B. Ratliff, J. R. Kramer, M. S. Feld, “A one-layer model of laser-induced fluorescence for diagnosis of disease in human tissue: applications to atherosclerosis,” IEEE Trans. Biomed. Eng. 36, 1222–1231 (1989).
[CrossRef] [PubMed]

Rettschnick, R. P. H.

G. H. M. Gijsbers, D. Breederveld, M. J. C. van Gemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–48 (1986).

Richards-Kortum, R.

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 homogeneous and inhomogeneous samples,” Appl. Spectrosc. 47, 2114–2121 (1993).
[CrossRef]

R. Richards-Kortum, R. P. Rava, M. Fitzmaurice, L. L. Tong, N. B. Ratliff, J. R. Kramer, M. S. Feld, “A one-layer model of laser-induced fluorescence for diagnosis of disease in human tissue: applications to atherosclerosis,” IEEE Trans. Biomed. Eng. 36, 1222–1231 (1989).
[CrossRef] [PubMed]

R. Richards-Kortum, A. Mehta, G. Hayes, R. Cothren, T. Kolubayev, C. Kittrell, N. B. Ratliff, J. R. Kramer, M. S. Feld, “Spectral diagnosis of atherosclerosis using an optical fiber laser catheter,” Am. Heart J. 118, 381–391 (1989).
[CrossRef] [PubMed]

M. Keijzer, R. Richards-Kortum, S. Jacques, M. Feld, “Fluorescence spectroscopy of turbid media: autofluorescence of the human aorta,” Appl. Opt. 28, 4286–42921989.
[CrossRef] [PubMed]

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] [PubMed]

Schomacker, K. T.

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] [PubMed]

Shaklai, N.

N. Shaklai, J. Yguerabide, H. M. Ranney, “Interaction of hemoglobin with red blood cell membranes as shown by a fluorescent chromophore,” Biochemistry 16, 5585–5592 (1977).
[CrossRef] [PubMed]

Shu, K.-H.

A. E. Profio, S. Xie, K.-H. Shu, “Diagnosis of tumors by fluorescence: quantification of photosensitizer concentration,” in Photodynamic Therapy: Mechanisms II, T. J. Dougherty, ed., Proc. Soc. Photo-Opt. Instrum. Eng.1203, 12–18 (1990).

Star, W. M.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12, 510–519 (1992).
[CrossRef] [PubMed]

Tong, L. L.

R. Richards-Kortum, R. P. Rava, M. Fitzmaurice, L. L. Tong, N. B. Ratliff, J. R. Kramer, M. S. Feld, “A one-layer model of laser-induced fluorescence for diagnosis of disease in human tissue: applications to atherosclerosis,” IEEE Trans. Biomed. Eng. 36, 1222–1231 (1989).
[CrossRef] [PubMed]

van Gemert, M. J. C.

S.A. Prahl, M. J. C. van Gemert, A. J. Welch, “Determining the optical properties of turbid media by using the adding–doubling method,” Appl. Opt. 32, 559–568 (1993).
[CrossRef] [PubMed]

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12, 510–519 (1992).
[CrossRef] [PubMed]

G. H. M. Gijsbers, D. Breederveld, M. J. C. van Gemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–48 (1986).

Vernon, D. I.

S. R. Brown, D. I. Vernon, “The quantitative determination of porphyrins in tissues and body fluids: applications in studies of photodynamic therapy,” in Photodynamic Therapy of Neoplastic Disease, D. Kessel, ed. (CRC, Ann Arbor, Mich., 1990) Vol. 1, pp. 109–128.

Welch, A. J.

C. M. Gardner, S. L. Jacques, A. J. Welch, “Light transport in tissue: accurate expressions for one-dimensional fluence rate and escape function based upon Monte Carlo simulation,” Lasers Surg. Med. 18 (2), 129–138 (1996).
[CrossRef] [PubMed]

S.A. Prahl, M. J. C. van Gemert, A. J. Welch, “Determining the optical properties of turbid media by using the adding–doubling method,” Appl. Opt. 32, 559–568 (1993).
[CrossRef] [PubMed]

W.-F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissue,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

Wilson, B. C.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12, 510–519 (1992).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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Figures (7)

Fig. 1.
Fig. 1.

Theory of fluorescence escape. Excitation light is delivered normal to the surface and defines the cylindrical coordinate origin. Fluorescence is generated at (r′, z′, ϕ′) with strength βϕ. A fraction βϕG L escapes from the tissue surface at (r, θ, ϕ). Angle θ is defined with respect to the surface normal, and ϕ (not shown) is defined in the plane of the tissue surface by the line connecting the origin and the position of escape.

Fig. 2.
Fig. 2.

Distant detector measurement geometry. A detector at viewing angle θ intercepts light from the sample in solid angle ΔΩ. Note that the source and detector dimensions are much smaller than the source–detector separation.

Fig. 3.
Fig. 3.

Fluorescence and reflectance measurements. Light from an argon or tungsten white-light source was coupled into a 600-μm delivery fiber. Light from the delivery fiber was colli-mated and entered the tissue phantom sample at normal incidence in a 1-cm-diameter beam. A 600-μm collection fiber positioned 30 cm above the sample at a 10° angle from normal incidence detected a small portion of the total fluorescence escape power or diffuse reflectance power. OMA, optical multichannel analyzer.

Fig. 4.
Fig. 4.

Summary of measurements and calculations used to determine the intrinsic fluorescence coefficient for phantom 5: A, measurements of fluorescence and diffuse reflectance spectra; B, predetermined reduced scattering coefficient spectrum (0.48% microspheres by volume) and effective penetration depth spectrum calculated with Eq. (24); C, correction factor spectrum calculated with Eq. (12) and Table 1; D, intrinsic fluorescence coefficient spectra using Eq. (23), compared with the line shape of measured fluorescence.

Fig. 5.
Fig. 5.

Summary of intrinsic fluorescence recovery from the six tissue phantoms (see Table 2 for phantom compositions) and the two dilute R6G solutions: A, measured, uncorrected fluorescence spectra, F; B, corrected spectra, displayed as the intrinsic fluorescence coefficient, β.

Fig. 6.
Fig. 6.

Diffuse reflectance spectra of the six tissue phantoms. The excitation wavelength used in these experiments (514 nm) is marked by the vertical arrow. These spectra were used to correct fluorescence spectra from the phantoms using Eq. (23) and Table 1.

Fig. 7.
Fig. 7.

Intrinsic fluorescence line shapes. Intrinsic fluorescence spectra from Fig. 5B were normalized to their maximum values. The location of the 577-nm oxyhemoglobin absorption peak is denoted by the arrow.

Tables (4)

Tables Icon

Table 1. Empirical Expressions for How the Six Parameters of Eq. (13) Depend on Diffuse Reflectance (R d )

Tables Icon

Table 2. Tissue Phantom Composition

Tables Icon

Table 3. Sensitivity Analysis of the Calculated Intrinsic Fluorescence Coefficient, β, to Errors in Optical Parameters

Tables Icon

Table 4. Results of Least-Squares Estimation of Fluorophore Concentration a

Equations (32)

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β ( λ ex , λ em ) μ a , fl ( λ ex ) Φ λ ( λ em ) .
β ( λ ex , λ em ) = ln ( 10 ) fl ( λ ex ) C fl Φ λ ( λ em ) .
L ( r , λ ex , λ em ) = d 2 P ( r ; λ ex , λ em ) d A proj ( r ) ( r ) .
L ( r ; λ ex , λ em )        = volume β ( r    ; λ ex , λ em ) ϕ ( r    ; λ ex ) G L ( r , r    ; λ em ) d r ,
L ( r , θ , φ ; λ ex , λ em )         = 0 d z 0 2 π d φ 0 r d r [ β ( r , z , φ ; λ ex , λ em )            × ϕ ( r , z , φ ; λ ex ) G L ( r , θ , φ , r , z , φ ; λ em ) ] .
L ( r , θ , φ ; λ ex , λ em ) = 0 d z ( βϕ * * G L ) .
P ( λ ex , λ em ) = 0 2 π 0 π / 2                     × 0 d r [ r   cos  θ L ( r , θ , φ ; λ ex , λ em ) ] ,                  = 2 π 0 d z 0 π / 2 0 d r [ r   cos  θ ( βϕ * * G L ) ] .
P ( λ ex , λ em ) = β ( λ ex , λ em ) 0 d z [ ϕ p ( z ; λ ex ) G P ( z ; λ em ) ] ,
ϕ P ( z ; λ ex ) = C 1 ( λ ex ) exp [ k 1 ( λ ex ) z / δ ( λ ex ) ]                   C 2 ( λ ex ) exp [ k 2 ( λ ex ) z / δ ( λ ex ) ] ,
G P ( z ; λ em ) = C 3 ( λ em ) exp [ k 3 ( λ em ) z / δ ( λ em ) ] .
ϕ P ( z ; λ ex ) G P ( z ; λ em )                     = 2 π 0 π / 2 0 d r [ r   cos  θ ( ϕ * * G L ) ] .
P ( λ ex , λ em ) = β ( λ ex , λ em ) P 0 ( λ ex ) X 1 D ( λ ex , λ em ) ,
X 1 D ( λ ex , λ em ) = C 1 ( λ ex ) C 3 ( λ em ) k 1 ( λ ex ) / δ ( λ ex ) + k 3 ( λ em ) / δ ( λ em )                        C 2 ( λ ex ) C 3 ( λ em ) k 2 ( λ ex ) / δ ( λ ex ) + k 3 ( λ em ) / δ ( λ em ) .
δ = 1 { 3 μ a [ μ a + μ s ( 1 g ) ] } 1 / 2 ,
d 2 P det = L d A proj = L ( d A   cos  θ ) ,
d P det = Ω det ( L d A   cos  θ ) .
P det = A d A Ω det ( L   cos  θ ) .
P det = ( A eff d A L ) cos  θΔΩ , = I 0   cos  θΔΩ ,
0 2 π 0 π / 2 ( I 0   cos  θ  sin  θ ) = P .
I 0 = P π .
P det = P   cos  θ   ΔΩ π .
F ( λ ex , λ em ) = P det ( λ ex , λ em ) D ( λ em ) .
β ( λ ex , λ em ) = F ( λ ex , λ em ) P 0 ( λ ex ) X 1 D ( λ ex , λ em ) [ ( ΔΩ / π ) cosθ ] D ( λ em ) .
δ = N μ s ( 1 g ) [ 3 ( N + 1 ) ] 1 / 2 .
χ 2 = λ i = 530 650 [ β ( λ i ) C C dil β dil ( λ i ) ] 2 .
I ( θ t ; λ ex , λ em ) = β( λ ex λ em ) P 0 4 π × 1 exp [ ( μ a ( λ ex ) + μ a ( λ em ) / cos   θ i ) L ] μ ax + μ am / cos   θ i × ( 1 R 0 ) ( 1 R ) n t 2   cos   θ t n i 2   cos   θ i ,
R = R ( θ i , θ t ) = { R 0 = ( n i n t ) 2 ( n i + n t ) 2 θ i = 0 1 2 [ sin 2 ( θ i θ t ) sin 2 ( θ i + θ t ) + tan 2 ( θ i θ t ) tan 2 ( θ i + θ t ) ] 0 < θ i < θ c 1 θ i θ c ,
I dil ( θ t ; λ ex , λ em ) = β( λ ex , λ em ) P 0 4 π L ( 1 R 0 ) ( 1 R ) × n t 2   cos   θ t n i 2   cos  θ i .
F dil ( λ ex , λ em ) = I dil ( θ; λ ex , λ em ) ΔΩ D ( λ em ) = β( λ ex , λ em ) P 0 X dil ΔΩ π D ( λ em ) ,
X dil ( λ ex , λ em ) = L 4 ( 1 R 0 ) ( 1 R ) n t 2 cosθ n i 2 cos θ i ,
β dil ( λ ex , λ em ) = F dil ( λ ex , λ em ) P 0 ( λ ex ) X dil ( λ ex , λ em ) ( ΔΩ / π ) D ( λ em ) .
P 0 ( λ ex ) ΔΩ π D ( λ em ) = F std ( λ ex , λ em ) β std ( λ ex , λ em ) X std ( λ ex , λ em ) .

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