Abstract

We demonstrate a new design for a fiber-optic bundle to measure fluorescence signals from tissue. In this design, the intensity of the signal is not significantly affected by the medium’s absorption and scattering coefficients and hence depends only on the fluorophore’s properties. Monte Carlo simulations of light scattering were used for designing and verifying the results obtained. The fiber-optic bundle was tested on tissue-simulating phantoms and compared with a standard nonimaging fiber-optic bundle. The new bundle was composed of 30 individual 100-μm fibers. Fibers on the end of the bundle that touch the tissue surface were separated from one another by approximately 1 mm. This design permits integration of the signal over several locations while maintaining localized sampling from regions smaller than the average mean free scattering path of the tissue. The bundle was tested by measurement of the fluorescence signals from tissue-simulating solutions containing fluorescent compounds. These studies demonstrate that the new bundle reduces the effect of the intrinsic absorption in the medium, permitting detection of fluorescence that is linearly proportional to the fluorophore concentration.

© 1998 Optical Society of America

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  1. M. Kriegmair, R. Baumgartner, R. Knuchel, H. Stepp, F. Hofstadter, A. Hofstetter, “Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence,” J. Urol. 155, 105–110 (1996).
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  4. R. Richards-Kortum, M. R. Mitchell, N. Ramanujam, A. Mahadevan, S. Thomsen, “In vivo fluorescence spectroscopy: potential for non-invasive, automated diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint biomarker,” J. Cell. Biochem. Suppl. 19, 111–119 (1994).
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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1997 (6)

D. Y. Paithankar, A. U. Chen, B. W. Pogue, M. S. Patterson, E. M. Sevick-Muraca, “Imaging of fluorescent yield and lifetime from multiply scattered light re-emitted from tissues and other random media,” Appl. Opt. 36, 2260–2272 (1997).
[CrossRef] [PubMed]

J. Chang, H. L. Graber, R. L. Barbour, “Luminescence optical tomography of dense scattering media,” J. Opt. Soc. Am. A 14, 288–299 (1997).
[CrossRef]

H. S. Zeng, C. MacAulay, D. I. McLean, “Reconstruction of in vivo skin autofluorescence spectrum from microscopic properties by Monte Carlo simulation,” J. Photochem Photobiol. B 38, 234–240 (1997).
[CrossRef] [PubMed]

R. J. Crilly, W. F. Cheong, B. C. Wilson, J. R. Spears, “Forward-adjoint fluorescence model: Monte Carlo integration and experimental validation,” Appl. Opt. 36, 6513–6519 (1997).
[CrossRef]

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

B. W. Pogue, T. Hasan, “Fluorophore quantitation in tissue-simulating media with confocal detection,” IEEE J. Quantum Electron. 2, 959–964 (1997).

1996 (2)

J. R. Mourant, J. Boyer, A. H. Hielscher, I. J. Bigio, “Influence of the scattering phase function on light transport measurements in turbid media performed with small source–detector separations,” Opt. Lett. 21, 546–548 (1996).
[CrossRef] [PubMed]

M. Kriegmair, R. Baumgartner, R. Knuchel, H. Stepp, F. Hofstadter, A. Hofstetter, “Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence,” J. Urol. 155, 105–110 (1996).
[CrossRef] [PubMed]

1995 (3)

M. Bellmunt, M. Portero, R. Pamplona, M. Muntaner, J. Prat, “Age-related fluorescence in rat lung collagen,” Lung 173, 177–185 (1995).
[CrossRef] [PubMed]

S. 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]

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]

1994 (4)

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]

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]

G. R. Martin, R. K. Jain, “Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy,” Cancer Res. 54, 5670–5674 (1994).
[PubMed]

R. Richards-Kortum, M. R. Mitchell, N. Ramanujam, A. Mahadevan, S. Thomsen, “In vivo fluorescence spectroscopy: potential for non-invasive, automated diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint biomarker,” J. Cell. Biochem. Suppl. 19, 111–119 (1994).

1993 (5)

M. Sinaasappel, H. J. C. M. Sterenborg, “Quantification of the hematoporphyrin derivative by fluorescence measurement using dual-wavelength excitation and dual-wavelength detection,” Appl. Opt. 32, 541–548 (1993).
[CrossRef] [PubMed]

J. K. Frisoli, E. G. Tudor, T. J. Flotte, T. Hasan, T. F. Deutsch, K. T. Schomacker, “Pharmacokinetics of a fluorescent drug using laser-induced fluorescence,” Cancer Res. 53, 5954–5961 (1993).
[PubMed]

S. Andersson-Engels, J. Ankerst, J. Johansson, K. Svanberg, S. Svanberg, “Laser-induced fluorescence in malignant and normal tissue of rats injected with BPD,” Photochem. Photobiol. 57, 978–983 (1993).
[CrossRef] [PubMed]

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

M. Panjehpour, R. E. Sneed, D. L. Frazier, M. A. Barnhill, S. F. O’Brien, W. Harb, B. F. Overholt, “Quantification of phthalocyanine concentration in rat tissue using laser-induced fluorescence spectroscopy,” Lasers Surg. Med. 13, 23–30 (1993).
[CrossRef] [PubMed]

1992 (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]

S. J. Madsen, M. S. Patterson, B. C. Wilson, “The use of India ink as an optical absorber in tissue-simulating phantoms,” Phys. Med. Biol. 37, 985–993 (1992).
[CrossRef] [PubMed]

1991 (2)

Andersson-Engels, S.

S. Andersson-Engels, J. Ankerst, J. Johansson, K. Svanberg, S. Svanberg, “Laser-induced fluorescence in malignant and normal tissue of rats injected with BPD,” Photochem. Photobiol. 57, 978–983 (1993).
[CrossRef] [PubMed]

Ankerst, J.

S. Andersson-Engels, J. Ankerst, J. Johansson, K. Svanberg, S. Svanberg, “Laser-induced fluorescence in malignant and normal tissue of rats injected with BPD,” Photochem. Photobiol. 57, 978–983 (1993).
[CrossRef] [PubMed]

Barbour, R. L.

Barnhill, M. A.

M. Panjehpour, R. E. Sneed, D. L. Frazier, M. A. Barnhill, S. F. O’Brien, W. Harb, B. F. Overholt, “Quantification of phthalocyanine concentration in rat tissue using laser-induced fluorescence spectroscopy,” Lasers Surg. Med. 13, 23–30 (1993).
[CrossRef] [PubMed]

Baumgartner, R.

M. Kriegmair, R. Baumgartner, R. Knuchel, H. Stepp, F. Hofstadter, A. Hofstetter, “Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence,” J. Urol. 155, 105–110 (1996).
[CrossRef] [PubMed]

Bellmunt, M.

M. Bellmunt, M. Portero, R. Pamplona, M. Muntaner, J. Prat, “Age-related fluorescence in rat lung collagen,” Lung 173, 177–185 (1995).
[CrossRef] [PubMed]

Bigio, I. J.

Boyer, J.

Braichotte, D.

D. Braichotte, J. F. Savary, P. Monnier, H. van den Bergh, “Enhanced photodynamic therapy and dosimetry by light-induced fluorescence,” in 5th International Photodynamic Association Biennial Meeting, D. A. Cortese, ed., Proc. SPIE2371, 120–124 (1995).
[CrossRef]

Chan, E.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Chang, J.

Chen, A. U.

Cheong, W. F.

R. J. Crilly, W. F. Cheong, B. C. Wilson, J. R. Spears, “Forward-adjoint fluorescence model: Monte Carlo integration and experimental validation,” Appl. Opt. 36, 6513–6519 (1997).
[CrossRef]

W. F. Cheong, “Summary of optical properties,” in Optical Thermal Response of Laser-Irradiated Tissue, A. J. Welch, M. J. C. van Gemert, eds. (Plenum, New York, 1995), pp. 275–303.

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]

Crilly, R. J.

Criswell, G.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Deutsch, T. F.

J. K. Frisoli, E. G. Tudor, T. J. Flotte, T. Hasan, T. F. Deutsch, K. T. Schomacker, “Pharmacokinetics of a fluorescent drug using laser-induced fluorescence,” Cancer Res. 53, 5954–5961 (1993).
[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] [PubMed]

Durkin, A. J.

Feld, M. S.

Flotte, T. J.

J. K. Frisoli, E. G. Tudor, T. J. Flotte, T. Hasan, T. F. Deutsch, K. T. Schomacker, “Pharmacokinetics of a fluorescent drug using laser-induced fluorescence,” Cancer Res. 53, 5954–5961 (1993).
[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] [PubMed]

Frazier, D. L.

M. Panjehpour, R. E. Sneed, D. L. Frazier, M. A. Barnhill, S. F. O’Brien, W. Harb, B. F. Overholt, “Quantification of phthalocyanine concentration in rat tissue using laser-induced fluorescence spectroscopy,” Lasers Surg. Med. 13, 23–30 (1993).
[CrossRef] [PubMed]

Frisoli, J. K.

J. K. Frisoli, E. G. Tudor, T. J. Flotte, T. Hasan, T. F. Deutsch, K. T. Schomacker, “Pharmacokinetics of a fluorescent drug using laser-induced fluorescence,” Cancer Res. 53, 5954–5961 (1993).
[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] [PubMed]

Gardner, C.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Gofstein, G.

S. L. Jacques, R. Joseph, G. Gofstein, “How photobleaching affects dosimetry and fluorescence monitoring of PDT in turbid media,” in Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy II, T. J. Dougherty, ed., Proc. SPIE1881, 168–179 (1993).
[CrossRef]

Graber, H. L.

Harb, W.

M. Panjehpour, R. E. Sneed, D. L. Frazier, M. A. Barnhill, S. F. O’Brien, W. Harb, B. F. Overholt, “Quantification of phthalocyanine concentration in rat tissue using laser-induced fluorescence spectroscopy,” Lasers Surg. Med. 13, 23–30 (1993).
[CrossRef] [PubMed]

Hasan, T.

B. W. Pogue, T. Hasan, “Fluorophore quantitation in tissue-simulating media with confocal detection,” IEEE J. Quantum Electron. 2, 959–964 (1997).

J. K. Frisoli, E. G. Tudor, T. J. Flotte, T. Hasan, T. F. Deutsch, K. T. Schomacker, “Pharmacokinetics of a fluorescent drug using laser-induced fluorescence,” Cancer Res. 53, 5954–5961 (1993).
[PubMed]

B. W. Pogue, T. Hasan, “Quantitative fluorescence measurements from tissue using confocal detection,” in Laser-Tissue Interaction VIII, S. L. Jacques, ed., Proc. SPIE2975, 202–207 (1997).
[CrossRef]

Hielscher, A. H.

Hofstadter, F.

M. Kriegmair, R. Baumgartner, R. Knuchel, H. Stepp, F. Hofstadter, A. Hofstetter, “Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence,” J. Urol. 155, 105–110 (1996).
[CrossRef] [PubMed]

Hofstetter, A.

M. Kriegmair, R. Baumgartner, R. Knuchel, H. Stepp, F. Hofstadter, A. Hofstetter, “Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence,” J. Urol. 155, 105–110 (1996).
[CrossRef] [PubMed]

Hung, J.

S. Lam, J. Hung, B. Palcic, “Mechanism of detection of early lung cancer by ratio fluorometry,” Lasers Life Sci. 3, 67–73 (1991).

Hutchinson, C. L.

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]

Jacques, S.

L. Wang, S. Jacques, Monte Carlo Modeling of Light Transport in Multi-Layered Tissues in Standard C (University of Texas, Houston, Tex., 1992–1993).

Jacques, S. L.

S. L. Jacques, R. Joseph, G. Gofstein, “How photobleaching affects dosimetry and fluorescence monitoring of PDT in turbid media,” in Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy II, T. J. Dougherty, ed., Proc. SPIE1881, 168–179 (1993).
[CrossRef]

Jaikumar, S.

Jain, R. K.

G. R. Martin, R. K. Jain, “Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy,” Cancer Res. 54, 5670–5674 (1994).
[PubMed]

Johansson, J.

S. Andersson-Engels, J. Ankerst, J. Johansson, K. Svanberg, S. Svanberg, “Laser-induced fluorescence in malignant and normal tissue of rats injected with BPD,” Photochem. Photobiol. 57, 978–983 (1993).
[CrossRef] [PubMed]

Joseph, R.

S. L. Jacques, R. Joseph, G. Gofstein, “How photobleaching affects dosimetry and fluorescence monitoring of PDT in turbid media,” in Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy II, T. J. Dougherty, ed., Proc. SPIE1881, 168–179 (1993).
[CrossRef]

Knuchel, R.

M. Kriegmair, R. Baumgartner, R. Knuchel, H. Stepp, F. Hofstadter, A. Hofstetter, “Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence,” J. Urol. 155, 105–110 (1996).
[CrossRef] [PubMed]

Kriegmair, M.

M. Kriegmair, R. Baumgartner, R. Knuchel, H. Stepp, F. Hofstadter, A. Hofstetter, “Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence,” J. Urol. 155, 105–110 (1996).
[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]

Lam, S.

S. Lam, J. Hung, B. Palcic, “Mechanism of detection of early lung cancer by ratio fluorometry,” Lasers Life Sci. 3, 67–73 (1991).

MacAulay, C.

H. S. Zeng, C. MacAulay, D. I. McLean, “Reconstruction of in vivo skin autofluorescence spectrum from microscopic properties by Monte Carlo simulation,” J. Photochem Photobiol. B 38, 234–240 (1997).
[CrossRef] [PubMed]

S. 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]

Madsen, S. J.

S. J. Madsen, M. S. Patterson, B. C. Wilson, “The use of India ink as an optical absorber in tissue-simulating phantoms,” Phys. Med. Biol. 37, 985–993 (1992).
[CrossRef] [PubMed]

Mahadevan, A.

R. Richards-Kortum, M. R. Mitchell, N. Ramanujam, A. Mahadevan, S. Thomsen, “In vivo fluorescence spectroscopy: potential for non-invasive, automated diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint biomarker,” J. Cell. Biochem. Suppl. 19, 111–119 (1994).

Martin, G. R.

G. R. Martin, R. K. Jain, “Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy,” Cancer Res. 54, 5670–5674 (1994).
[PubMed]

McLean, D. I.

H. S. Zeng, C. MacAulay, D. I. McLean, “Reconstruction of in vivo skin autofluorescence spectrum from microscopic properties by Monte Carlo simulation,” J. Photochem Photobiol. B 38, 234–240 (1997).
[CrossRef] [PubMed]

S. 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. R.

R. Richards-Kortum, M. R. Mitchell, N. Ramanujam, A. Mahadevan, S. Thomsen, “In vivo fluorescence spectroscopy: potential for non-invasive, automated diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint biomarker,” J. Cell. Biochem. Suppl. 19, 111–119 (1994).

Moes, C. J. M.

Monnier, P.

D. Braichotte, J. F. Savary, P. Monnier, H. van den Bergh, “Enhanced photodynamic therapy and dosimetry by light-induced fluorescence,” in 5th International Photodynamic Association Biennial Meeting, D. A. Cortese, ed., Proc. SPIE2371, 120–124 (1995).
[CrossRef]

Mourant, J. R.

Muntaner, M.

M. Bellmunt, M. Portero, R. Pamplona, M. Muntaner, J. Prat, “Age-related fluorescence in rat lung collagen,” Lung 173, 177–185 (1995).
[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]

O’Brien, S. F.

M. Panjehpour, R. E. Sneed, D. L. Frazier, M. A. Barnhill, S. F. O’Brien, W. Harb, B. F. Overholt, “Quantification of phthalocyanine concentration in rat tissue using laser-induced fluorescence spectroscopy,” Lasers Surg. Med. 13, 23–30 (1993).
[CrossRef] [PubMed]

Overholt, B. F.

M. Panjehpour, R. E. Sneed, D. L. Frazier, M. A. Barnhill, S. F. O’Brien, W. Harb, B. F. Overholt, “Quantification of phthalocyanine concentration in rat tissue using laser-induced fluorescence spectroscopy,” Lasers Surg. Med. 13, 23–30 (1993).
[CrossRef] [PubMed]

Paithankar, D. Y.

Palcic, B.

S. 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]

S. Lam, J. Hung, B. Palcic, “Mechanism of detection of early lung cancer by ratio fluorometry,” Lasers Life Sci. 3, 67–73 (1991).

Pamplona, R.

M. Bellmunt, M. Portero, R. Pamplona, M. Muntaner, J. Prat, “Age-related fluorescence in rat lung collagen,” Lung 173, 177–185 (1995).
[CrossRef] [PubMed]

Panjehpour, M.

M. Panjehpour, R. E. Sneed, D. L. Frazier, M. A. Barnhill, S. F. O’Brien, W. Harb, B. F. Overholt, “Quantification of phthalocyanine concentration in rat tissue using laser-induced fluorescence spectroscopy,” Lasers Surg. Med. 13, 23–30 (1993).
[CrossRef] [PubMed]

Patterson, M. S.

Pfefer, J.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Pogue, B. W.

B. W. Pogue, T. Hasan, “Fluorophore quantitation in tissue-simulating media with confocal detection,” IEEE J. Quantum Electron. 2, 959–964 (1997).

D. Y. Paithankar, A. U. Chen, B. W. Pogue, M. S. Patterson, E. M. Sevick-Muraca, “Imaging of fluorescent yield and lifetime from multiply scattered light re-emitted from tissues and other random media,” Appl. Opt. 36, 2260–2272 (1997).
[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]

B. W. Pogue, T. Hasan, “Quantitative fluorescence measurements from tissue using confocal detection,” in Laser-Tissue Interaction VIII, S. L. Jacques, ed., Proc. SPIE2975, 202–207 (1997).
[CrossRef]

Portero, M.

M. Bellmunt, M. Portero, R. Pamplona, M. Muntaner, J. Prat, “Age-related fluorescence in rat lung collagen,” Lung 173, 177–185 (1995).
[CrossRef] [PubMed]

Prahl, S. A.

Prat, J.

M. Bellmunt, M. Portero, R. Pamplona, M. Muntaner, J. Prat, “Age-related fluorescence in rat lung collagen,” Lung 173, 177–185 (1995).
[CrossRef] [PubMed]

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]

R. Richards-Kortum, M. R. Mitchell, N. Ramanujam, A. Mahadevan, S. Thomsen, “In vivo fluorescence spectroscopy: potential for non-invasive, automated diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint biomarker,” J. Cell. Biochem. Suppl. 19, 111–119 (1994).

Rava, R. P.

Richards-Kortum, R.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

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]

R. Richards-Kortum, M. R. Mitchell, N. Ramanujam, A. Mahadevan, S. Thomsen, “In vivo fluorescence spectroscopy: potential for non-invasive, automated diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint biomarker,” J. Cell. Biochem. Suppl. 19, 111–119 (1994).

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]

Savary, J. F.

D. Braichotte, J. F. Savary, P. Monnier, H. van den Bergh, “Enhanced photodynamic therapy and dosimetry by light-induced fluorescence,” in 5th International Photodynamic Association Biennial Meeting, D. A. Cortese, ed., Proc. SPIE2371, 120–124 (1995).
[CrossRef]

Schomacker, K. T.

J. K. Frisoli, E. G. Tudor, T. J. Flotte, T. Hasan, T. F. Deutsch, K. T. Schomacker, “Pharmacokinetics of a fluorescent drug using laser-induced fluorescence,” Cancer Res. 53, 5954–5961 (1993).
[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] [PubMed]

Sevick-Muraca, E. M.

Sinaasappel, M.

Sneed, R. E.

M. Panjehpour, R. E. Sneed, D. L. Frazier, M. A. Barnhill, S. F. O’Brien, W. Harb, B. F. Overholt, “Quantification of phthalocyanine concentration in rat tissue using laser-induced fluorescence spectroscopy,” Lasers Surg. Med. 13, 23–30 (1993).
[CrossRef] [PubMed]

Spears, J. R.

Stepp, H.

M. Kriegmair, R. Baumgartner, R. Knuchel, H. Stepp, F. Hofstadter, A. Hofstetter, “Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence,” J. Urol. 155, 105–110 (1996).
[CrossRef] [PubMed]

Sterenborg, H. J. C. M.

Svanberg, K.

S. Andersson-Engels, J. Ankerst, J. Johansson, K. Svanberg, S. Svanberg, “Laser-induced fluorescence in malignant and normal tissue of rats injected with BPD,” Photochem. Photobiol. 57, 978–983 (1993).
[CrossRef] [PubMed]

Svanberg, S.

S. Andersson-Engels, J. Ankerst, J. Johansson, K. Svanberg, S. Svanberg, “Laser-induced fluorescence in malignant and normal tissue of rats injected with BPD,” Photochem. Photobiol. 57, 978–983 (1993).
[CrossRef] [PubMed]

Thomsen, S.

R. Richards-Kortum, M. R. Mitchell, N. Ramanujam, A. Mahadevan, S. Thomsen, “In vivo fluorescence spectroscopy: potential for non-invasive, automated diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint biomarker,” J. Cell. Biochem. Suppl. 19, 111–119 (1994).

Tudor, E. G.

J. K. Frisoli, E. G. Tudor, T. J. Flotte, T. Hasan, T. F. Deutsch, K. T. Schomacker, “Pharmacokinetics of a fluorescent drug using laser-induced fluorescence,” Cancer Res. 53, 5954–5961 (1993).
[PubMed]

van den Bergh, H.

D. Braichotte, J. F. Savary, P. Monnier, H. van den Bergh, “Enhanced photodynamic therapy and dosimetry by light-induced fluorescence,” in 5th International Photodynamic Association Biennial Meeting, D. A. Cortese, ed., Proc. SPIE2371, 120–124 (1995).
[CrossRef]

van Gemert, M. J. C.

van Marle, J.

van Staveren, H. J.

Wang, L.

L. Wang, S. Jacques, Monte Carlo Modeling of Light Transport in Multi-Layered Tissues in Standard C (University of Texas, Houston, Tex., 1992–1993).

Warren, S.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Welch, A. J.

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[CrossRef] [PubMed]

Wilson, B. C.

R. J. Crilly, W. F. Cheong, B. C. Wilson, J. R. Spears, “Forward-adjoint fluorescence model: Monte Carlo integration and experimental validation,” Appl. Opt. 36, 6513–6519 (1997).
[CrossRef]

S. J. Madsen, M. S. Patterson, B. C. Wilson, “The use of India ink as an optical absorber in tissue-simulating phantoms,” Phys. Med. Biol. 37, 985–993 (1992).
[CrossRef] [PubMed]

Wu, J.

Zeng, H. S.

H. S. Zeng, C. MacAulay, D. I. McLean, “Reconstruction of in vivo skin autofluorescence spectrum from microscopic properties by Monte Carlo simulation,” J. Photochem Photobiol. B 38, 234–240 (1997).
[CrossRef] [PubMed]

Zeng, S.

S. 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]

Appl. Opt. (7)

Biophys. J. (1)

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]

Cancer Res. (2)

J. K. Frisoli, E. G. Tudor, T. J. Flotte, T. Hasan, T. F. Deutsch, K. T. Schomacker, “Pharmacokinetics of a fluorescent drug using laser-induced fluorescence,” Cancer Res. 53, 5954–5961 (1993).
[PubMed]

G. R. Martin, R. K. Jain, “Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy,” Cancer Res. 54, 5670–5674 (1994).
[PubMed]

IEEE J. Quantum Electron. (1)

B. W. Pogue, T. Hasan, “Fluorophore quantitation in tissue-simulating media with confocal detection,” IEEE J. Quantum Electron. 2, 959–964 (1997).

J. Cell. Biochem. Suppl. (1)

R. Richards-Kortum, M. R. Mitchell, N. Ramanujam, A. Mahadevan, S. Thomsen, “In vivo fluorescence spectroscopy: potential for non-invasive, automated diagnosis of cervical intraepithelial neoplasia and use as a surrogate endpoint biomarker,” J. Cell. Biochem. Suppl. 19, 111–119 (1994).

J. Opt. Soc. Am. A (1)

J. Photochem Photobiol. B (1)

H. S. Zeng, C. MacAulay, D. I. McLean, “Reconstruction of in vivo skin autofluorescence spectrum from microscopic properties by Monte Carlo simulation,” J. Photochem Photobiol. B 38, 234–240 (1997).
[CrossRef] [PubMed]

J. Urol. (1)

M. Kriegmair, R. Baumgartner, R. Knuchel, H. Stepp, F. Hofstadter, A. Hofstetter, “Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence,” J. Urol. 155, 105–110 (1996).
[CrossRef] [PubMed]

Lasers Life Sci. (1)

S. Lam, J. Hung, B. Palcic, “Mechanism of detection of early lung cancer by ratio fluorometry,” Lasers Life Sci. 3, 67–73 (1991).

Lasers Surg. Med. (3)

A. J. Welch, C. Gardner, R. Richards-Kortum, E. Chan, G. Criswell, J. Pfefer, S. Warren, “Propagation of fluorescent light,” Lasers Surg. Med. 21, 166–178 (1997).
[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] [PubMed]

M. Panjehpour, R. E. Sneed, D. L. Frazier, M. A. Barnhill, S. F. O’Brien, W. Harb, B. F. Overholt, “Quantification of phthalocyanine concentration in rat tissue using laser-induced fluorescence spectroscopy,” Lasers Surg. Med. 13, 23–30 (1993).
[CrossRef] [PubMed]

Lung (1)

M. Bellmunt, M. Portero, R. Pamplona, M. Muntaner, J. Prat, “Age-related fluorescence in rat lung collagen,” Lung 173, 177–185 (1995).
[CrossRef] [PubMed]

Opt. Lett. (1)

Photochem Photobiol (1)

S. 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]

Photochem. Photobiol. (1)

S. Andersson-Engels, J. Ankerst, J. Johansson, K. Svanberg, S. Svanberg, “Laser-induced fluorescence in malignant and normal tissue of rats injected with BPD,” Photochem. Photobiol. 57, 978–983 (1993).
[CrossRef] [PubMed]

Phys. Med. Biol. (1)

S. J. Madsen, M. S. Patterson, B. C. Wilson, “The use of India ink as an optical absorber in tissue-simulating phantoms,” Phys. Med. Biol. 37, 985–993 (1992).
[CrossRef] [PubMed]

Other (6)

W. F. Cheong, “Summary of optical properties,” in Optical Thermal Response of Laser-Irradiated Tissue, A. J. Welch, M. J. C. van Gemert, eds. (Plenum, New York, 1995), pp. 275–303.

B. W. Pogue, T. Hasan, “Quantitative fluorescence measurements from tissue using confocal detection,” in Laser-Tissue Interaction VIII, S. L. Jacques, ed., Proc. SPIE2975, 202–207 (1997).
[CrossRef]

L. Wang, S. Jacques, Monte Carlo Modeling of Light Transport in Multi-Layered Tissues in Standard C (University of Texas, Houston, Tex., 1992–1993).

M. Testorf, U. L. Osterberg, B. W. Pogue, K. D. Paulsen are preparing the following paper for publication: “Sampling of time and frequency domain signals in Monte Carlo simulations of photon migration.

S. L. Jacques, R. Joseph, G. Gofstein, “How photobleaching affects dosimetry and fluorescence monitoring of PDT in turbid media,” in Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy II, T. J. Dougherty, ed., Proc. SPIE1881, 168–179 (1993).
[CrossRef]

D. Braichotte, J. F. Savary, P. Monnier, H. van den Bergh, “Enhanced photodynamic therapy and dosimetry by light-induced fluorescence,” in 5th International Photodynamic Association Biennial Meeting, D. A. Cortese, ed., Proc. SPIE2371, 120–124 (1995).
[CrossRef]

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Figures (6)

Fig. 1
Fig. 1

Schematic diagram of the geometry for both Monte Carlo simulations and experimental measurements of fluorescence from tissue-simulating media. Both excitation (dark arrows) and fluorescence (light arrows) can be captured by the fiber optic when it is in contact with the medium. Fluorescent events (circles) occur when the photon is absorbed by the fluorophore.

Fig. 2
Fig. 2

Monte Carlo simulations of excitation fluence in the medium (top row) and in the fluorescence fluence that is captured by the fiber optic (bottom row). The left-most pair of images (top and bottom) shows the excitation and the captured fluorescence fluence for broadbeam illumination from the surface. The middle pair of images shows the same calculations for a 2-mm-diameter fiber optic, and the rightmost pair of images is for a 100-μm fiber optic. Scattering media properties were fixed at μ s ′ = 10.0 mm-1, μ a = 0.01 mm-1, and g = 0.90.

Fig. 3
Fig. 3

Theoretical calculations (Monte Carlo) of the average number of scattering events in the detected excitation signal and the detected fluorescence signal versus fiber-optic radius. Media optical properties were as in Fig. 2.

Fig. 4
Fig. 4

(a) Monte Carlo calculations of fluorescence detected from a fiber optic at the surface of a scattering medium, μ s = 10.0 mm-1, g = 0.90, with both a 1-mm simulated fiber and a 100-μm simulated fiber. A range of fluorophore absorption coefficients was used, with two different endogenous absorption values, μ a = 0.003 mm-1 and μ a = 0.03 mm-1. (b) Fluorescence measurements from two similar sets of tissue-simulating solutions containing serial dilutions of fluorophore, with one set containing no absorber (μ a = 0.0026 mm-1) and the other containing 1.5% ink (μ a = 0.073 mm-1). Measurements were taken both with a standard 1-mm fiber bundle and with the new fiber bundle with separated 100-μm fibers depicted in Fig. 5.

Fig. 5
Fig. 5

Schematic diagram of the apparatus, including an enlarged view of the end of the fiber-optic probe designed for these measurements. Light was delivered to the two photomultiplier tubes (PMT’s) via small fiber optics. The current from the photomultiplier tubes was measured with an oscilloscope terminated in 50 Ω. The intensity in millivolts for each measurement is plotted in Fig. 4(b) and 6. The fiber bundle used experimentally had 30 single fibers, rather than just the 12 shown here.

Fig. 6
Fig. 6

Fluorescence (at 650 nm) and scattered excitation light (at 488 and 514 nm) were detected from several solutions, all containing a constant 62 μM of fluorophore but with increasing concentration of Intralipid and hence increasing scattering coefficient. Here the ratio of fluorescence/scattered light is plotted. The background absorption coefficient was also constant at 0.01 mm-1.

Equations (7)

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

1 = 1 / μ s .
s i = - ln ε i / μ s ,
s w i = s w i - 1   exp - s μ a   s i ,
s Φ = I = 1 N s w i ,
P = exp - F u a s .
F w i = ϕ fl   s w i - 1   exp - F μ a s ,
F Φ = i = 1 N F w i .

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