Abstract

Fluorescence spectroscopy provides potential contrast enhancement for near-infrared tissue imaging and physiologically correlated spectroscopy. We present a fluorescence photon migration model and test its quantitative predictive capabilities with a frequency-domain measurement that involves a homogeneous multiple-scattering tissue phantom (with optical properties similar to those of tissue in the near infrared) that contains a fluorophore (rhodamine B). After demonstrating the validity of the model, we explore its ability to recover the fluorophore’s spectral properties from within the multiple-scattering medium. The absolute quantum yield and the lifetime of the fluorophore are measured to within a few percent of the values measured independently in the absence of scattering. Both measurements are accomplished without the use of reference fluorophores. In addition, the model accurately predicts the fluorescence emission spectrum in the scattering medium. Implications of these absolute measurements of lifetime, quantum yield, concentration, and emission spectrum from within multiple-scattering media are discussed.

© 1997 Optical Society of America

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  1. Biomedical Optical Spectroscopy and Diagnostics, D. Benaron, E. Sevick-Muraca, eds., 1996 OSA Technical Digest (Optical Society of America, Washington D.C., 1996); Advances in Optical Imaging and Photon Migration, R. Alfano, J. Fujimoto, eds., 1996 OSA Technical Digest, (Optical Society of America, Washington D.C., 1996).
  2. R. A. De Blasi, S. Fantini, M. A. Franceschini, M. Ferrari, E. Gratton, “Cerebral and muscle oxygen saturation measurement by frequency-domain near infra-red spectrometer,” Med. Biol. Eng. Comput. 33, 228–230 (1995).
    [CrossRef] [PubMed]
  3. J. S. Maier, S. A. Walker, S. Fantini, M. A. Franceschini, E. Gratton, “Possible correlation between blood glucose concentration and the reduced scattering coefficient of tissues in the near infrared,” Opt. Lett. 19, 2062–2064 (1994).
    [CrossRef] [PubMed]
  4. M. Kohl, M. Cope, M. Essenpreis, D. Böcker, “Influence of glucose concentration on light scattering in tissue-simulating phantoms,” Opt. Lett. 19, 2170–2172 (1994).
    [CrossRef] [PubMed]
  5. B. C. Wilson, M. S. Patterson, “The physics of photodynamic therapy,” Phys. Med. Biol. 31, 327–360 (1986).
    [CrossRef] [PubMed]
  6. W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue,” Science 241, 1649–1651 (1988).
    [CrossRef] [PubMed]
  7. H. Szmacinski, J. R. Lakowicz, “Lifetime-based sensing,” in Probe Design and Chemical Sensing, J. R. Lakowicz, ed., Vol. 4 of Topics in Fluorescence Spectroscopy (Plenum, New York, 1994), pp. 295–334.
    [CrossRef]
  8. H. Szmacinski, J. R. Lakowicz, “Optical measurements of pH using fluorescence lifetimes and phase-modulation fluorometry,” Anal. Chem. 65, 1688–1674 (1993).
    [CrossRef]
  9. E. Allen, “Fluorescence white dyes: calculation of fluorescence from reflectivity values,” J. Opt. Soc. Am. 54, 506–515 (1964).
    [CrossRef]
  10. G. R. Seely, “Transport of fluorescence through highly scattering media: corrections to the determinations of quantum yields,” Biophys. J. 52, 311–316 (1987).
    [CrossRef] [PubMed]
  11. B. C. Wilson, M. S. Patterson, S. T. Flock, D. R. Wyman, “Tissue optical properties in relation to light propagation models and in vivo dosimetry,” in Photon Migration in Tissues, B. Chance, ed. (Plenum, New York, 1989), pp. 25–42.
  12. J. B. Fishkin, E. Gratton, “Propagation of photon-density waves in strongly scattering media containing an absorbing semi-infinite plane bounded by a straight edge,” J. Opt. Soc. Am. A 10, 127–140 (1993).
    [CrossRef] [PubMed]
  13. M. S. Patterson, B. Chance, B. C. Wilson, “Time-resolved reflectance and transmittance for the non-invasive measurement of tissue optical properties,” Appl.Opt. 28, 2331–2336 (1989).
  14. A. Ishimaru, Wave Propagation and Scattering in Random Media (Academic, New York, 1978).
  15. D. Oelkrug, “Fluorescence spectroscopy in turbid media and tissues,” in Probe Design and Chemical Sensing, J. R. Lakowicz, ed., Vol. 4 of Topics in Fluorescence Spectroscopy (Plenum, New York, 1994), pp. 223–253
    [CrossRef]
  16. 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, 1222–1232 (1989).
    [CrossRef] [PubMed]
  17. A. J. Durkin, S. Jaikumar, N. Ramanujam, R. Richards-Kortum, “Relation between fluorescence of dilute and turbid samples,” Appl. Opt. 33, 414–423 (1994).
    [CrossRef] [PubMed]
  18. 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]
  19. 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]
  20. X. D. Li, M. A. O’Leary, D. A. Boas, B. Chance, A. G. Yodh, “Fluorescent diffuse photon density waves in homogeneous and heterogeneous turbid media: analytic solutions and applications,” Appl. Opt. 35, 3746–3758 (1996).
    [CrossRef] [PubMed]
  21. J. J. Duderstadt, L. J. Hamilton, Nuclear Reactor Analysis (Wiley, New York, 1976), pp. 133–145.
  22. R. F. Bonner, R. Nossal, S. Havlin, G. H. Weiss, “Model for photon migration in turbid biological media,” J. Opt. Soc. Am. A 4, 423–432 (1987).
    [CrossRef] [PubMed]
  23. S. R. Arridge, M. Cope, D. T. Delpy, “Theoretical basis for the determination of optical path lengths in tissue: temporal and frequency analysis,” Phys. Med. Biol. 37, 1537–1560 (1992).
    [CrossRef]
  24. A. Yodh, B. Chance, “Imaging and spectroscopy using diffusing light,” Phys. Today 48(3), 34–40 (1995).
    [CrossRef]
  25. D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering and wavelength transduction of diffuse photon density waves,” Phys. Rev. E 47, 2999–3002 (1993).
    [CrossRef]
  26. B. Feddersen, D. W. Piston, E. Gratton, “Digital parallel acquisition in frequency-domain fluorometry,” Rev. Sci. Instrum. 60, 2929–2936 (1989).
    [CrossRef]
  27. F. López Arbeloa, T. López Arbeloa, M. J. Tapia Estévez, I. López Arbeloa, “Photophysics of rhodamines: molecular structure and solvent effects,” J. Phys. Chem. 95, 2203–2208 (1991).
  28. S. Fantini, M. A. Franceschini, J. B. Fishkin, B. Barbieri, E. Gratton, “Quantitative determination of the absorption spectra of chromophores in strongly scattering media: a light-emitting-diode based technique,” Appl. Opt. 33, 5204–5213 (1994).
    [CrossRef] [PubMed]
  29. R. A. Velapoldi, K. D. Mielenz, “A fluorescence standard reference material: quinine sulfate dihydrate,” (National Bureau of Standards, U.S. Government Printing Office, Washington, 1980).
  30. C. L. Hutchinson, J. R. Lakowicz, E. M. Sevick-Muraca, “Fluorescence lifetime-based sensing in tissues: a computational study,” Biophys. J. 68, 1574–1582 (1995).
    [CrossRef] [PubMed]
  31. C. L. Hutchinson, T. L. Troy, E. M. Sevick-Muraca, “Fluorescence-lifetime determination in tissues or other scattering media from measurement of excitation and emission kinetics,” Appl. Opt. 35, 2325–2332 (1996).
    [CrossRef] [PubMed]
  32. S. A. Ahmed, Z.-W. Zang, K. M. Yoo, M. A. Ali, R. R. Alfano, “Effect of multiple light scattering and self-absorption on the fluorescence and excitation spectra of dyes in random media,” Appl. Opt. 33, 2746–2750 (1994).
    [CrossRef] [PubMed]
  33. S. Fantini, M. A. Franceschini-Fantini, J. S. Maier, S. A. Walker, B. Barbieri, E. Gratton, “Frequency-domain multi-channel optical detector for non-invasive tissue spectroscopy and oximetry,” Opt. Eng. 34, 32–42 (1995).
    [CrossRef]
  34. J. N. Demas, G. A. Crosby, “The measurement of photoluminescence quantum yields: a review,” J. Phys. Chem. 75, 991–1024 (1971).
    [CrossRef]

1996 (2)

1995 (4)

S. Fantini, M. A. Franceschini-Fantini, J. S. Maier, S. A. Walker, B. Barbieri, E. Gratton, “Frequency-domain multi-channel optical detector for non-invasive tissue spectroscopy and oximetry,” Opt. Eng. 34, 32–42 (1995).
[CrossRef]

A. Yodh, B. Chance, “Imaging and spectroscopy using diffusing light,” Phys. Today 48(3), 34–40 (1995).
[CrossRef]

C. L. Hutchinson, J. R. Lakowicz, E. M. Sevick-Muraca, “Fluorescence lifetime-based sensing in tissues: a computational study,” Biophys. J. 68, 1574–1582 (1995).
[CrossRef] [PubMed]

R. A. De Blasi, S. Fantini, M. A. Franceschini, M. Ferrari, E. Gratton, “Cerebral and muscle oxygen saturation measurement by frequency-domain near infra-red spectrometer,” Med. Biol. Eng. Comput. 33, 228–230 (1995).
[CrossRef] [PubMed]

1994 (6)

1993 (4)

D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering and wavelength transduction of diffuse photon density waves,” Phys. Rev. E 47, 2999–3002 (1993).
[CrossRef]

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]

J. B. Fishkin, E. Gratton, “Propagation of photon-density waves in strongly scattering media containing an absorbing semi-infinite plane bounded by a straight edge,” J. Opt. Soc. Am. A 10, 127–140 (1993).
[CrossRef] [PubMed]

H. Szmacinski, J. R. Lakowicz, “Optical measurements of pH using fluorescence lifetimes and phase-modulation fluorometry,” Anal. Chem. 65, 1688–1674 (1993).
[CrossRef]

1992 (1)

S. R. Arridge, M. Cope, D. T. Delpy, “Theoretical basis for the determination of optical path lengths in tissue: temporal and frequency analysis,” Phys. Med. Biol. 37, 1537–1560 (1992).
[CrossRef]

1991 (1)

F. López Arbeloa, T. López Arbeloa, M. J. Tapia Estévez, I. López Arbeloa, “Photophysics of rhodamines: molecular structure and solvent effects,” J. Phys. Chem. 95, 2203–2208 (1991).

1989 (3)

B. Feddersen, D. W. Piston, E. Gratton, “Digital parallel acquisition in frequency-domain fluorometry,” Rev. Sci. Instrum. 60, 2929–2936 (1989).
[CrossRef]

M. S. Patterson, B. Chance, B. C. Wilson, “Time-resolved reflectance and transmittance for the non-invasive measurement of tissue optical properties,” Appl.Opt. 28, 2331–2336 (1989).

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, 1222–1232 (1989).
[CrossRef] [PubMed]

1988 (1)

W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue,” Science 241, 1649–1651 (1988).
[CrossRef] [PubMed]

1987 (2)

G. R. Seely, “Transport of fluorescence through highly scattering media: corrections to the determinations of quantum yields,” Biophys. J. 52, 311–316 (1987).
[CrossRef] [PubMed]

R. F. Bonner, R. Nossal, S. Havlin, G. H. Weiss, “Model for photon migration in turbid biological media,” J. Opt. Soc. Am. A 4, 423–432 (1987).
[CrossRef] [PubMed]

1986 (1)

B. C. Wilson, M. S. Patterson, “The physics of photodynamic therapy,” Phys. Med. Biol. 31, 327–360 (1986).
[CrossRef] [PubMed]

1971 (1)

J. N. Demas, G. A. Crosby, “The measurement of photoluminescence quantum yields: a review,” J. Phys. Chem. 75, 991–1024 (1971).
[CrossRef]

1964 (1)

Ahmed, S. A.

Alfano, R. R.

Ali, M. A.

Allen, E.

Arridge, S. R.

S. R. Arridge, M. Cope, D. T. Delpy, “Theoretical basis for the determination of optical path lengths in tissue: temporal and frequency analysis,” Phys. Med. Biol. 37, 1537–1560 (1992).
[CrossRef]

Barbieri, B.

S. Fantini, M. A. Franceschini-Fantini, J. S. Maier, S. A. Walker, B. Barbieri, E. Gratton, “Frequency-domain multi-channel optical detector for non-invasive tissue spectroscopy and oximetry,” Opt. Eng. 34, 32–42 (1995).
[CrossRef]

S. Fantini, M. A. Franceschini, J. B. Fishkin, B. Barbieri, E. Gratton, “Quantitative determination of the absorption spectra of chromophores in strongly scattering media: a light-emitting-diode based technique,” Appl. Opt. 33, 5204–5213 (1994).
[CrossRef] [PubMed]

Boas, D. A.

Böcker, D.

Bonner, R. F.

Chance, B.

X. D. Li, M. A. O’Leary, D. A. Boas, B. Chance, A. G. Yodh, “Fluorescent diffuse photon density waves in homogeneous and heterogeneous turbid media: analytic solutions and applications,” Appl. Opt. 35, 3746–3758 (1996).
[CrossRef] [PubMed]

A. Yodh, B. Chance, “Imaging and spectroscopy using diffusing light,” Phys. Today 48(3), 34–40 (1995).
[CrossRef]

D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering and wavelength transduction of diffuse photon density waves,” Phys. Rev. E 47, 2999–3002 (1993).
[CrossRef]

M. S. Patterson, B. Chance, B. C. Wilson, “Time-resolved reflectance and transmittance for the non-invasive measurement of tissue optical properties,” Appl.Opt. 28, 2331–2336 (1989).

Cope, M.

M. Kohl, M. Cope, M. Essenpreis, D. Böcker, “Influence of glucose concentration on light scattering in tissue-simulating phantoms,” Opt. Lett. 19, 2170–2172 (1994).
[CrossRef] [PubMed]

S. R. Arridge, M. Cope, D. T. Delpy, “Theoretical basis for the determination of optical path lengths in tissue: temporal and frequency analysis,” Phys. Med. Biol. 37, 1537–1560 (1992).
[CrossRef]

Crosby, G. A.

J. N. Demas, G. A. Crosby, “The measurement of photoluminescence quantum yields: a review,” J. Phys. Chem. 75, 991–1024 (1971).
[CrossRef]

De Blasi, R. A.

R. A. De Blasi, S. Fantini, M. A. Franceschini, M. Ferrari, E. Gratton, “Cerebral and muscle oxygen saturation measurement by frequency-domain near infra-red spectrometer,” Med. Biol. Eng. Comput. 33, 228–230 (1995).
[CrossRef] [PubMed]

Delpy, D. T.

S. R. Arridge, M. Cope, D. T. Delpy, “Theoretical basis for the determination of optical path lengths in tissue: temporal and frequency analysis,” Phys. Med. Biol. 37, 1537–1560 (1992).
[CrossRef]

Demas, J. N.

J. N. Demas, G. A. Crosby, “The measurement of photoluminescence quantum yields: a review,” J. Phys. Chem. 75, 991–1024 (1971).
[CrossRef]

Duderstadt, J. J.

J. J. Duderstadt, L. J. Hamilton, Nuclear Reactor Analysis (Wiley, New York, 1976), pp. 133–145.

Durkin, A. J.

Essenpreis, M.

Fantini, S.

R. A. De Blasi, S. Fantini, M. A. Franceschini, M. Ferrari, E. Gratton, “Cerebral and muscle oxygen saturation measurement by frequency-domain near infra-red spectrometer,” Med. Biol. Eng. Comput. 33, 228–230 (1995).
[CrossRef] [PubMed]

S. Fantini, M. A. Franceschini-Fantini, J. S. Maier, S. A. Walker, B. Barbieri, E. Gratton, “Frequency-domain multi-channel optical detector for non-invasive tissue spectroscopy and oximetry,” Opt. Eng. 34, 32–42 (1995).
[CrossRef]

J. S. Maier, S. A. Walker, S. Fantini, M. A. Franceschini, E. Gratton, “Possible correlation between blood glucose concentration and the reduced scattering coefficient of tissues in the near infrared,” Opt. Lett. 19, 2062–2064 (1994).
[CrossRef] [PubMed]

S. Fantini, M. A. Franceschini, J. B. Fishkin, B. Barbieri, E. Gratton, “Quantitative determination of the absorption spectra of chromophores in strongly scattering media: a light-emitting-diode based technique,” Appl. Opt. 33, 5204–5213 (1994).
[CrossRef] [PubMed]

Feddersen, B.

B. Feddersen, D. W. Piston, E. Gratton, “Digital parallel acquisition in frequency-domain fluorometry,” Rev. Sci. Instrum. 60, 2929–2936 (1989).
[CrossRef]

Feld, M. S.

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]

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, 1222–1232 (1989).
[CrossRef] [PubMed]

Ferrari, M.

R. A. De Blasi, S. Fantini, M. A. Franceschini, M. Ferrari, E. Gratton, “Cerebral and muscle oxygen saturation measurement by frequency-domain near infra-red spectrometer,” Med. Biol. Eng. Comput. 33, 228–230 (1995).
[CrossRef] [PubMed]

Fishkin, J. B.

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, 1222–1232 (1989).
[CrossRef] [PubMed]

Flock, S. T.

B. C. Wilson, M. S. Patterson, S. T. Flock, D. R. Wyman, “Tissue optical properties in relation to light propagation models and in vivo dosimetry,” in Photon Migration in Tissues, B. Chance, ed. (Plenum, New York, 1989), pp. 25–42.

Franceschini, M. A.

Franceschini-Fantini, M. A.

S. Fantini, M. A. Franceschini-Fantini, J. S. Maier, S. A. Walker, B. Barbieri, E. Gratton, “Frequency-domain multi-channel optical detector for non-invasive tissue spectroscopy and oximetry,” Opt. Eng. 34, 32–42 (1995).
[CrossRef]

Gratton, E.

S. Fantini, M. A. Franceschini-Fantini, J. S. Maier, S. A. Walker, B. Barbieri, E. Gratton, “Frequency-domain multi-channel optical detector for non-invasive tissue spectroscopy and oximetry,” Opt. Eng. 34, 32–42 (1995).
[CrossRef]

R. A. De Blasi, S. Fantini, M. A. Franceschini, M. Ferrari, E. Gratton, “Cerebral and muscle oxygen saturation measurement by frequency-domain near infra-red spectrometer,” Med. Biol. Eng. Comput. 33, 228–230 (1995).
[CrossRef] [PubMed]

J. S. Maier, S. A. Walker, S. Fantini, M. A. Franceschini, E. Gratton, “Possible correlation between blood glucose concentration and the reduced scattering coefficient of tissues in the near infrared,” Opt. Lett. 19, 2062–2064 (1994).
[CrossRef] [PubMed]

S. Fantini, M. A. Franceschini, J. B. Fishkin, B. Barbieri, E. Gratton, “Quantitative determination of the absorption spectra of chromophores in strongly scattering media: a light-emitting-diode based technique,” Appl. Opt. 33, 5204–5213 (1994).
[CrossRef] [PubMed]

J. B. Fishkin, E. Gratton, “Propagation of photon-density waves in strongly scattering media containing an absorbing semi-infinite plane bounded by a straight edge,” J. Opt. Soc. Am. A 10, 127–140 (1993).
[CrossRef] [PubMed]

B. Feddersen, D. W. Piston, E. Gratton, “Digital parallel acquisition in frequency-domain fluorometry,” Rev. Sci. Instrum. 60, 2929–2936 (1989).
[CrossRef]

Hamilton, L. J.

J. J. Duderstadt, L. J. Hamilton, Nuclear Reactor Analysis (Wiley, New York, 1976), pp. 133–145.

Havlin, S.

Hutchinson, C. L.

Ishimaru, A.

A. Ishimaru, Wave Propagation and Scattering in Random Media (Academic, New York, 1978).

Jaikumar, S.

Kohl, M.

Kramer, J. R.

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, 1222–1232 (1989).
[CrossRef] [PubMed]

Lakowicz, J. R.

C. L. Hutchinson, J. R. Lakowicz, E. M. Sevick-Muraca, “Fluorescence lifetime-based sensing in tissues: a computational study,” Biophys. J. 68, 1574–1582 (1995).
[CrossRef] [PubMed]

H. Szmacinski, J. R. Lakowicz, “Optical measurements of pH using fluorescence lifetimes and phase-modulation fluorometry,” Anal. Chem. 65, 1688–1674 (1993).
[CrossRef]

H. Szmacinski, J. R. Lakowicz, “Lifetime-based sensing,” in Probe Design and Chemical Sensing, J. R. Lakowicz, ed., Vol. 4 of Topics in Fluorescence Spectroscopy (Plenum, New York, 1994), pp. 295–334.
[CrossRef]

Li, X. D.

López Arbeloa, F.

F. López Arbeloa, T. López Arbeloa, M. J. Tapia Estévez, I. López Arbeloa, “Photophysics of rhodamines: molecular structure and solvent effects,” J. Phys. Chem. 95, 2203–2208 (1991).

López Arbeloa, I.

F. López Arbeloa, T. López Arbeloa, M. J. Tapia Estévez, I. López Arbeloa, “Photophysics of rhodamines: molecular structure and solvent effects,” J. Phys. Chem. 95, 2203–2208 (1991).

López Arbeloa, T.

F. López Arbeloa, T. López Arbeloa, M. J. Tapia Estévez, I. López Arbeloa, “Photophysics of rhodamines: molecular structure and solvent effects,” J. Phys. Chem. 95, 2203–2208 (1991).

Maier, J. S.

S. Fantini, M. A. Franceschini-Fantini, J. S. Maier, S. A. Walker, B. Barbieri, E. Gratton, “Frequency-domain multi-channel optical detector for non-invasive tissue spectroscopy and oximetry,” Opt. Eng. 34, 32–42 (1995).
[CrossRef]

J. S. Maier, S. A. Walker, S. Fantini, M. A. Franceschini, E. Gratton, “Possible correlation between blood glucose concentration and the reduced scattering coefficient of tissues in the near infrared,” Opt. Lett. 19, 2062–2064 (1994).
[CrossRef] [PubMed]

Mielenz, K. D.

R. A. Velapoldi, K. D. Mielenz, “A fluorescence standard reference material: quinine sulfate dihydrate,” (National Bureau of Standards, U.S. Government Printing Office, Washington, 1980).

Nossal, R.

O’Leary, M. A.

Oelkrug, D.

D. Oelkrug, “Fluorescence spectroscopy in turbid media and tissues,” in Probe Design and Chemical Sensing, J. R. Lakowicz, ed., Vol. 4 of Topics in Fluorescence Spectroscopy (Plenum, New York, 1994), pp. 223–253
[CrossRef]

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]

M. S. Patterson, B. Chance, B. C. Wilson, “Time-resolved reflectance and transmittance for the non-invasive measurement of tissue optical properties,” Appl.Opt. 28, 2331–2336 (1989).

B. C. Wilson, M. S. Patterson, “The physics of photodynamic therapy,” Phys. Med. Biol. 31, 327–360 (1986).
[CrossRef] [PubMed]

B. C. Wilson, M. S. Patterson, S. T. Flock, D. R. Wyman, “Tissue optical properties in relation to light propagation models and in vivo dosimetry,” in Photon Migration in Tissues, B. Chance, ed. (Plenum, New York, 1989), pp. 25–42.

Piston, D. W.

B. Feddersen, D. W. Piston, E. Gratton, “Digital parallel acquisition in frequency-domain fluorometry,” Rev. Sci. Instrum. 60, 2929–2936 (1989).
[CrossRef]

Pogue, B. W.

Ramanujam, N.

Ratliff, N. B.

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, 1222–1232 (1989).
[CrossRef] [PubMed]

Rava, R. P.

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]

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, 1222–1232 (1989).
[CrossRef] [PubMed]

Richards-Kortum, R.

A. J. Durkin, S. Jaikumar, N. Ramanujam, R. Richards-Kortum, “Relation between fluorescence of dilute and turbid samples,” Appl. Opt. 33, 414–423 (1994).
[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, 1222–1232 (1989).
[CrossRef] [PubMed]

Rumsey, W. L.

W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue,” Science 241, 1649–1651 (1988).
[CrossRef] [PubMed]

Seely, G. R.

G. R. Seely, “Transport of fluorescence through highly scattering media: corrections to the determinations of quantum yields,” Biophys. J. 52, 311–316 (1987).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

Szmacinski, H.

H. Szmacinski, J. R. Lakowicz, “Optical measurements of pH using fluorescence lifetimes and phase-modulation fluorometry,” Anal. Chem. 65, 1688–1674 (1993).
[CrossRef]

H. Szmacinski, J. R. Lakowicz, “Lifetime-based sensing,” in Probe Design and Chemical Sensing, J. R. Lakowicz, ed., Vol. 4 of Topics in Fluorescence Spectroscopy (Plenum, New York, 1994), pp. 295–334.
[CrossRef]

Tapia Estévez, M. J.

F. López Arbeloa, T. López Arbeloa, M. J. Tapia Estévez, I. López Arbeloa, “Photophysics of rhodamines: molecular structure and solvent effects,” J. Phys. Chem. 95, 2203–2208 (1991).

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, 1222–1232 (1989).
[CrossRef] [PubMed]

Troy, T. L.

Vanderkooi, J. M.

W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue,” Science 241, 1649–1651 (1988).
[CrossRef] [PubMed]

Velapoldi, R. A.

R. A. Velapoldi, K. D. Mielenz, “A fluorescence standard reference material: quinine sulfate dihydrate,” (National Bureau of Standards, U.S. Government Printing Office, Washington, 1980).

Walker, S. A.

S. Fantini, M. A. Franceschini-Fantini, J. S. Maier, S. A. Walker, B. Barbieri, E. Gratton, “Frequency-domain multi-channel optical detector for non-invasive tissue spectroscopy and oximetry,” Opt. Eng. 34, 32–42 (1995).
[CrossRef]

J. S. Maier, S. A. Walker, S. Fantini, M. A. Franceschini, E. Gratton, “Possible correlation between blood glucose concentration and the reduced scattering coefficient of tissues in the near infrared,” Opt. Lett. 19, 2062–2064 (1994).
[CrossRef] [PubMed]

Weiss, G. H.

Wilson, B. C.

M. S. Patterson, B. Chance, B. C. Wilson, “Time-resolved reflectance and transmittance for the non-invasive measurement of tissue optical properties,” Appl.Opt. 28, 2331–2336 (1989).

B. C. Wilson, M. S. Patterson, “The physics of photodynamic therapy,” Phys. Med. Biol. 31, 327–360 (1986).
[CrossRef] [PubMed]

B. C. Wilson, M. S. Patterson, S. T. Flock, D. R. Wyman, “Tissue optical properties in relation to light propagation models and in vivo dosimetry,” in Photon Migration in Tissues, B. Chance, ed. (Plenum, New York, 1989), pp. 25–42.

Wilson, D. F.

W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue,” Science 241, 1649–1651 (1988).
[CrossRef] [PubMed]

Wu, J.

Wyman, D. R.

B. C. Wilson, M. S. Patterson, S. T. Flock, D. R. Wyman, “Tissue optical properties in relation to light propagation models and in vivo dosimetry,” in Photon Migration in Tissues, B. Chance, ed. (Plenum, New York, 1989), pp. 25–42.

Yodh, A.

A. Yodh, B. Chance, “Imaging and spectroscopy using diffusing light,” Phys. Today 48(3), 34–40 (1995).
[CrossRef]

Yodh, A. G.

Yoo, K. M.

Zang, Z.-W.

Anal. Chem. (1)

H. Szmacinski, J. R. Lakowicz, “Optical measurements of pH using fluorescence lifetimes and phase-modulation fluorometry,” Anal. Chem. 65, 1688–1674 (1993).
[CrossRef]

Appl. Opt. (7)

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]

A. J. Durkin, S. Jaikumar, N. Ramanujam, R. Richards-Kortum, “Relation between fluorescence 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]

S. A. Ahmed, Z.-W. Zang, K. M. Yoo, M. A. Ali, R. R. Alfano, “Effect of multiple light scattering and self-absorption on the fluorescence and excitation spectra of dyes in random media,” Appl. Opt. 33, 2746–2750 (1994).
[CrossRef] [PubMed]

S. Fantini, M. A. Franceschini, J. B. Fishkin, B. Barbieri, E. Gratton, “Quantitative determination of the absorption spectra of chromophores in strongly scattering media: a light-emitting-diode based technique,” Appl. Opt. 33, 5204–5213 (1994).
[CrossRef] [PubMed]

C. L. Hutchinson, T. L. Troy, E. M. Sevick-Muraca, “Fluorescence-lifetime determination in tissues or other scattering media from measurement of excitation and emission kinetics,” Appl. Opt. 35, 2325–2332 (1996).
[CrossRef] [PubMed]

X. D. Li, M. A. O’Leary, D. A. Boas, B. Chance, A. G. Yodh, “Fluorescent diffuse photon density waves in homogeneous and heterogeneous turbid media: analytic solutions and applications,” Appl. Opt. 35, 3746–3758 (1996).
[CrossRef] [PubMed]

Appl.Opt. (1)

M. S. Patterson, B. Chance, B. C. Wilson, “Time-resolved reflectance and transmittance for the non-invasive measurement of tissue optical properties,” Appl.Opt. 28, 2331–2336 (1989).

Biophys. J. (2)

G. R. Seely, “Transport of fluorescence through highly scattering media: corrections to the determinations of quantum yields,” Biophys. J. 52, 311–316 (1987).
[CrossRef] [PubMed]

C. L. Hutchinson, J. R. Lakowicz, E. M. Sevick-Muraca, “Fluorescence lifetime-based sensing in tissues: a computational study,” Biophys. J. 68, 1574–1582 (1995).
[CrossRef] [PubMed]

IEEE Trans. Biomed. Eng. (1)

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, 1222–1232 (1989).
[CrossRef] [PubMed]

J. Opt. Soc. Am. (1)

J. Opt. Soc. Am. A (2)

J. Phys. Chem. (2)

F. López Arbeloa, T. López Arbeloa, M. J. Tapia Estévez, I. López Arbeloa, “Photophysics of rhodamines: molecular structure and solvent effects,” J. Phys. Chem. 95, 2203–2208 (1991).

J. N. Demas, G. A. Crosby, “The measurement of photoluminescence quantum yields: a review,” J. Phys. Chem. 75, 991–1024 (1971).
[CrossRef]

Med. Biol. Eng. Comput. (1)

R. A. De Blasi, S. Fantini, M. A. Franceschini, M. Ferrari, E. Gratton, “Cerebral and muscle oxygen saturation measurement by frequency-domain near infra-red spectrometer,” Med. Biol. Eng. Comput. 33, 228–230 (1995).
[CrossRef] [PubMed]

Opt. Eng. (1)

S. Fantini, M. A. Franceschini-Fantini, J. S. Maier, S. A. Walker, B. Barbieri, E. Gratton, “Frequency-domain multi-channel optical detector for non-invasive tissue spectroscopy and oximetry,” Opt. Eng. 34, 32–42 (1995).
[CrossRef]

Opt. Lett. (2)

Phys. Med. Biol. (2)

B. C. Wilson, M. S. Patterson, “The physics of photodynamic therapy,” Phys. Med. Biol. 31, 327–360 (1986).
[CrossRef] [PubMed]

S. R. Arridge, M. Cope, D. T. Delpy, “Theoretical basis for the determination of optical path lengths in tissue: temporal and frequency analysis,” Phys. Med. Biol. 37, 1537–1560 (1992).
[CrossRef]

Phys. Rev. E (1)

D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering and wavelength transduction of diffuse photon density waves,” Phys. Rev. E 47, 2999–3002 (1993).
[CrossRef]

Phys. Today (1)

A. Yodh, B. Chance, “Imaging and spectroscopy using diffusing light,” Phys. Today 48(3), 34–40 (1995).
[CrossRef]

Rev. Sci. Instrum. (1)

B. Feddersen, D. W. Piston, E. Gratton, “Digital parallel acquisition in frequency-domain fluorometry,” Rev. Sci. Instrum. 60, 2929–2936 (1989).
[CrossRef]

Science (1)

W. L. Rumsey, J. M. Vanderkooi, D. F. Wilson, “Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue,” Science 241, 1649–1651 (1988).
[CrossRef] [PubMed]

Other (7)

H. Szmacinski, J. R. Lakowicz, “Lifetime-based sensing,” in Probe Design and Chemical Sensing, J. R. Lakowicz, ed., Vol. 4 of Topics in Fluorescence Spectroscopy (Plenum, New York, 1994), pp. 295–334.
[CrossRef]

A. Ishimaru, Wave Propagation and Scattering in Random Media (Academic, New York, 1978).

D. Oelkrug, “Fluorescence spectroscopy in turbid media and tissues,” in Probe Design and Chemical Sensing, J. R. Lakowicz, ed., Vol. 4 of Topics in Fluorescence Spectroscopy (Plenum, New York, 1994), pp. 223–253
[CrossRef]

Biomedical Optical Spectroscopy and Diagnostics, D. Benaron, E. Sevick-Muraca, eds., 1996 OSA Technical Digest (Optical Society of America, Washington D.C., 1996); Advances in Optical Imaging and Photon Migration, R. Alfano, J. Fujimoto, eds., 1996 OSA Technical Digest, (Optical Society of America, Washington D.C., 1996).

B. C. Wilson, M. S. Patterson, S. T. Flock, D. R. Wyman, “Tissue optical properties in relation to light propagation models and in vivo dosimetry,” in Photon Migration in Tissues, B. Chance, ed. (Plenum, New York, 1989), pp. 25–42.

J. J. Duderstadt, L. J. Hamilton, Nuclear Reactor Analysis (Wiley, New York, 1976), pp. 133–145.

R. A. Velapoldi, K. D. Mielenz, “A fluorescence standard reference material: quinine sulfate dihydrate,” (National Bureau of Standards, U.S. Government Printing Office, Washington, 1980).

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Figures (6)

Fig. 1
Fig. 1

Experimental apparatus. The dashed lines represent the locked phases between components, and the labeled frequencies give the signal frequency at each step (Δf is the beat frequency of 400 Hz). A frequency-doubled Nd:YAG laser pulsed at 76.2 MHz delivered light to the phantom by a fiber-optic cable (during the characterization of the phantom, this beam pumped a rhodamine 6G dye laser instead). A bifurcated optical fiber split the light such that most of the light excited the phantom and some of it acted as a reference. A detector fiber gathered light from the medium, and a monochromator then selected a particular wavelength bandpass. After heterodyning, a computer digitized the signal and then performed a Fourier transform. The positioning device for the detector fiber is not drawn for the sake of clarity. PMT’s, photomultiplier tubes.

Fig. 2
Fig. 2

Absorption and reduced scattering spectra. In both panels, the ×’s are the optical coefficients of the phantom without rhodamine B, and the open squares represent the optical coefficients of the same phantom mixed with rhodamine B. Panel (a) is a plot of the absorption coefficient versus wavelength. The solid curve is a rhodamine B spectrum measured independently without any scattering; however, for purposes of comparison, the phantom absorption (without rhodamine) has been added to this nonscattering spectrum. Thus this curve represents the absorption spectrum that we should observe for the rhodamine B inside the phantom. We can cleanly extract the fluorophore’s absorption from the phantom. Panel (b) presents the reduced scattering coefficient versus wavelength. Rhodamine contributes little to the scattering. The precision uncertainty in the measurement of each coefficient is approximately 3%.

Fig. 3
Fig. 3

Fluorescence versus source–detector separation at 580 nm. In both plots, the filled squares are the measured values and the curves are the predictions of the theory. There are no fitting parameters of any kind in this plot; however, the predictions are based on independent measurements of the optical coefficients. Panel (a) is a plot of the dc fluorescence intensity as a function of distance. The four curves are four predictions of the dc fluorescence intensity for Λ values of 0.2, 0.3, 0.4, and 0.5. Note that these predictions are independent of τ. The average value of Λ needed to make the measurement at a given r coincide with its prediction is 0.34 ± 0.01 for all the sampled r’s, which agrees well with the published value of 0.31. Panel (b) is a plot of the phase of the fluorescence as a function of distance. The five curves are five predictions of the phase for τ values of 1.3, 1.4, 1.5, 1.6, and 1.7 ns. Note that these predictions are independent of Λ. The average value of τ needed to make the measurement at a given r coincide with its prediction for all the sampled r’s is 1.52 ± 0.02 ns, which agrees well with the independently measured value of 1.50 ± 0.01 ns. The experimental measurement errors are 0.1° for phase and less than 1% for dc counts.

Fig. 4
Fig. 4

dc fluorescence emission spectrum. The filled squares represent the measured dc fluorescence intensity at each wavelength for a fixed source–detector separation of 1 cm. The curve is again the prediction of Eq. (6) for each wavelength, also at a 1-cm source–detector separation. The agreement is excellent in the red part of the emission spectrum. There is less than a 10% discrepancy between the curves for the wavelengths ranging from 570 to 580 nm.

Fig. 5
Fig. 5

Theoretical dc sensitivity comparison. Values for the plots are found in Table 1. The modulation frequency was 76.2 MHz and the source–detector separation was r = 2 cm. The solid curve represents the fluorescence dc intensity calculated from the emission photon density [Eq. (6)], and the dashed curve represents the excitation dc intensity calculated from the excitation photon density [Eq. (2)]. The inset graph is the dc sensitivity, which is defined as the fractional change in counts with a 10-nM change in concentration (see the text for the definition). The fluorescence dc sensitivity SNR is superior to the excitation absorption dc sensitivity SNR for small fluorophore concentrations, but after ∼350 nM the fluorescence begins to saturate, and hence loses sensitivity. This crossing-over point of the sensitivities depends on the source–detector separation.

Fig. 6
Fig. 6

Theoretical phase-sensitivity comparison. The lower dashed curve represents the phase versus concentration as predicted by the excitation photon density [Eq. (2)], and the upper dashed curve represents the same thing, but predicted by the fluorescence photon density [Eq. (6)]. All variables are the same as those used in Fig. 5. Note that except for the lifetime effect, the curves are quite similar and are not useful for determining the fluorophore concentration. However, a phasor combination of both signals results in a vastly improved phase sensitivity with respect to fluorophore concentration. The amount of attenuation of the excitation relative to the emission is listed in the figure for optical densities of 0.3, 1, and 2.

Tables (1)

Tables Icon

Table 1 Medium Parameters for Theoretical Sensitivity Plotsa

Equations (8)

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Ur, tt-νD2Ur, t+νμaUr, t=qr, t,
Ur, ω=Pω4πνD1rexp-kωr,
k2ωμaD1-iωνμa.
0φmλdλ=1.
dqmr, t=νμafx0Uxr, t-texp-tτdtτ×Λφmλmdλm,
dqmr, ω=Λνμafx1+iωτ1+ω2τ2Uxr, ωφmλmdλm.
Umr, ω=ΛμafxΦmPω4πνDmDx1+iωτ1+ω2τ2×1rexp-kxωr-exp-kmωrkm2ω-kx2ω
Φmλm-Δλ2λm+Δλ2 φmλmγλmdλm.

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