Abstract

Samples of different animal tissues containing, at variable depth, a thin fluorescent sheet are irradiated with continuous violet or red light or with nonlinearly absorbed pulsed infrared light. The fluorescence intensity measured at the tissue surface as a function of the location of the fluorescent sheet exhibits, after a transition zone close to the tissue surface, an exponential decrease, the slope of which depends on the optical penetration depths of the exciting and the fluorescent light. From these results the total fluorescence output is determined for specific fluorophor distributions. It is seen that considerably deeper tissue layers are explored by use of excitation with red instead of violet light. Nonlinear excitation by infrared light can provide a further improvement, especially in liver tissue.

© 1999 Optical Society of America

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References

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  1. G. H. M. Gijsbers, D. Breederveld, M. J. C. vanGemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–47 (1986).
  2. S. G. Bown, “Photodynamic therapy to scientists and clinicians—one world or two?” J. Photochem. Photobiol. 6, 1–12 (1990).
    [CrossRef]
  3. J. Moan, H. Anholt, “Phthalocyanine fluorescence in tumors during PDT,” Photochem. Photobiol. 51, 379–381 (1990).
    [CrossRef] [PubMed]
  4. T. S. Mang, C. McGinnis, C. Liebow, U. O. Nseyo, D. H. Crean, T. J. Dougherty, “Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies,” Cancer 71, 269–276 (1993).
    [CrossRef] [PubMed]
  5. 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]
  6. R. Cubeddu, G. Canti, P. Taroni, G. Valentini, “Tumor visualization in a murine model by time-delayed fluorescence of sulphonated aluminium phthalocyanine,” Lasers Med. Sci. 12, 200–208 (1997).
    [CrossRef] [PubMed]
  7. M. J. H. Witjes, A. J. G. Mank, O. C. Speelman, “Distribution of aluminium phthalocyanine disulfonate in an oral squamous cell carcinoma model,” Photochem. Photobiol. 65, 685–693 (1997).
    [PubMed]
  8. R. S. Bodaness, D. S. King, “The two-photon induced fluorescence of the tumor localizing photosensitizer hematoporphyrin derivative via 1064-nm photons from a 20-ns Q-switched Nd-YAG laser,” Biochem. Biophys. Res. Commun. 126, 346–351 (1985).
    [CrossRef] [PubMed]
  9. P. Lenz, “In vivo excitation of photosensitizers by infrared light,” Photochem. Photobiol. 62, 333–338 (1995).
    [CrossRef] [PubMed]
  10. R. van Hillegersberg, J. W. Pickering, M. Aalders, J. F. Beek, “Optical properties of rat liver and tumor at 633 nm and 1064 nm: photofrin enhances scattering,” Lasers Surg. Med. 13, 31–39 (1993).
    [CrossRef] [PubMed]
  11. H. J. C. M. Sterenborg, M. J. C. van Gemert, W. Kamphorst, J. G. Wolbers, W. Holgervorst, “The spectral dependence of the optical properties of human brain,” Lasers Med. Sci. 4, 221–227 (1989).
    [CrossRef]

1997 (2)

R. Cubeddu, G. Canti, P. Taroni, G. Valentini, “Tumor visualization in a murine model by time-delayed fluorescence of sulphonated aluminium phthalocyanine,” Lasers Med. Sci. 12, 200–208 (1997).
[CrossRef] [PubMed]

M. J. H. Witjes, A. J. G. Mank, O. C. Speelman, “Distribution of aluminium phthalocyanine disulfonate in an oral squamous cell carcinoma model,” Photochem. Photobiol. 65, 685–693 (1997).
[PubMed]

1995 (1)

P. Lenz, “In vivo excitation of photosensitizers by infrared light,” Photochem. Photobiol. 62, 333–338 (1995).
[CrossRef] [PubMed]

1993 (3)

R. van Hillegersberg, J. W. Pickering, M. Aalders, J. F. Beek, “Optical properties of rat liver and tumor at 633 nm and 1064 nm: photofrin enhances scattering,” Lasers Surg. Med. 13, 31–39 (1993).
[CrossRef] [PubMed]

T. S. Mang, C. McGinnis, C. Liebow, U. O. Nseyo, D. H. Crean, T. J. Dougherty, “Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies,” Cancer 71, 269–276 (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]

1990 (2)

S. G. Bown, “Photodynamic therapy to scientists and clinicians—one world or two?” J. Photochem. Photobiol. 6, 1–12 (1990).
[CrossRef]

J. Moan, H. Anholt, “Phthalocyanine fluorescence in tumors during PDT,” Photochem. Photobiol. 51, 379–381 (1990).
[CrossRef] [PubMed]

1989 (1)

H. J. C. M. Sterenborg, M. J. C. van Gemert, W. Kamphorst, J. G. Wolbers, W. Holgervorst, “The spectral dependence of the optical properties of human brain,” Lasers Med. Sci. 4, 221–227 (1989).
[CrossRef]

1986 (1)

G. H. M. Gijsbers, D. Breederveld, M. J. C. vanGemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–47 (1986).

1985 (1)

R. S. Bodaness, D. S. King, “The two-photon induced fluorescence of the tumor localizing photosensitizer hematoporphyrin derivative via 1064-nm photons from a 20-ns Q-switched Nd-YAG laser,” Biochem. Biophys. Res. Commun. 126, 346–351 (1985).
[CrossRef] [PubMed]

Aalders, M.

R. van Hillegersberg, J. W. Pickering, M. Aalders, J. F. Beek, “Optical properties of rat liver and tumor at 633 nm and 1064 nm: photofrin enhances scattering,” Lasers Surg. Med. 13, 31–39 (1993).
[CrossRef] [PubMed]

Anholt, H.

J. Moan, H. Anholt, “Phthalocyanine fluorescence in tumors during PDT,” Photochem. Photobiol. 51, 379–381 (1990).
[CrossRef] [PubMed]

Beek, J. F.

R. van Hillegersberg, J. W. Pickering, M. Aalders, J. F. Beek, “Optical properties of rat liver and tumor at 633 nm and 1064 nm: photofrin enhances scattering,” Lasers Surg. Med. 13, 31–39 (1993).
[CrossRef] [PubMed]

Bodaness, R. S.

R. S. Bodaness, D. S. King, “The two-photon induced fluorescence of the tumor localizing photosensitizer hematoporphyrin derivative via 1064-nm photons from a 20-ns Q-switched Nd-YAG laser,” Biochem. Biophys. Res. Commun. 126, 346–351 (1985).
[CrossRef] [PubMed]

Boon, T. A.

G. H. M. Gijsbers, D. Breederveld, M. J. C. vanGemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–47 (1986).

Bown, S. G.

S. G. Bown, “Photodynamic therapy to scientists and clinicians—one world or two?” J. Photochem. Photobiol. 6, 1–12 (1990).
[CrossRef]

Breederveld, D.

G. H. M. Gijsbers, D. Breederveld, M. J. C. vanGemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–47 (1986).

Canti, G.

R. Cubeddu, G. Canti, P. Taroni, G. Valentini, “Tumor visualization in a murine model by time-delayed fluorescence of sulphonated aluminium phthalocyanine,” Lasers Med. Sci. 12, 200–208 (1997).
[CrossRef] [PubMed]

Crean, D. H.

T. S. Mang, C. McGinnis, C. Liebow, U. O. Nseyo, D. H. Crean, T. J. Dougherty, “Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies,” Cancer 71, 269–276 (1993).
[CrossRef] [PubMed]

Cubeddu, R.

R. Cubeddu, G. Canti, P. Taroni, G. Valentini, “Tumor visualization in a murine model by time-delayed fluorescence of sulphonated aluminium phthalocyanine,” Lasers Med. Sci. 12, 200–208 (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]

Dougherty, T. J.

T. S. Mang, C. McGinnis, C. Liebow, U. O. Nseyo, D. H. Crean, T. J. Dougherty, “Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies,” Cancer 71, 269–276 (1993).
[CrossRef] [PubMed]

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]

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]

Gijsbers, G. H. M.

G. H. M. Gijsbers, D. Breederveld, M. J. C. vanGemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–47 (1986).

Hasan, 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]

Holgervorst, W.

H. J. C. M. Sterenborg, M. J. C. van Gemert, W. Kamphorst, J. G. Wolbers, W. Holgervorst, “The spectral dependence of the optical properties of human brain,” Lasers Med. Sci. 4, 221–227 (1989).
[CrossRef]

Kamphorst, W.

H. J. C. M. Sterenborg, M. J. C. van Gemert, W. Kamphorst, J. G. Wolbers, W. Holgervorst, “The spectral dependence of the optical properties of human brain,” Lasers Med. Sci. 4, 221–227 (1989).
[CrossRef]

King, D. S.

R. S. Bodaness, D. S. King, “The two-photon induced fluorescence of the tumor localizing photosensitizer hematoporphyrin derivative via 1064-nm photons from a 20-ns Q-switched Nd-YAG laser,” Biochem. Biophys. Res. Commun. 126, 346–351 (1985).
[CrossRef] [PubMed]

Langelaar, J.

G. H. M. Gijsbers, D. Breederveld, M. J. C. vanGemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–47 (1986).

Lenz, P.

P. Lenz, “In vivo excitation of photosensitizers by infrared light,” Photochem. Photobiol. 62, 333–338 (1995).
[CrossRef] [PubMed]

Liebow, C.

T. S. Mang, C. McGinnis, C. Liebow, U. O. Nseyo, D. H. Crean, T. J. Dougherty, “Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies,” Cancer 71, 269–276 (1993).
[CrossRef] [PubMed]

Mang, T. S.

T. S. Mang, C. McGinnis, C. Liebow, U. O. Nseyo, D. H. Crean, T. J. Dougherty, “Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies,” Cancer 71, 269–276 (1993).
[CrossRef] [PubMed]

Mank, A. J. G.

M. J. H. Witjes, A. J. G. Mank, O. C. Speelman, “Distribution of aluminium phthalocyanine disulfonate in an oral squamous cell carcinoma model,” Photochem. Photobiol. 65, 685–693 (1997).
[PubMed]

McGinnis, C.

T. S. Mang, C. McGinnis, C. Liebow, U. O. Nseyo, D. H. Crean, T. J. Dougherty, “Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies,” Cancer 71, 269–276 (1993).
[CrossRef] [PubMed]

Moan, J.

J. Moan, H. Anholt, “Phthalocyanine fluorescence in tumors during PDT,” Photochem. Photobiol. 51, 379–381 (1990).
[CrossRef] [PubMed]

Nseyo, U. O.

T. S. Mang, C. McGinnis, C. Liebow, U. O. Nseyo, D. H. Crean, T. J. Dougherty, “Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies,” Cancer 71, 269–276 (1993).
[CrossRef] [PubMed]

Pickering, J. W.

R. van Hillegersberg, J. W. Pickering, M. Aalders, J. F. Beek, “Optical properties of rat liver and tumor at 633 nm and 1064 nm: photofrin enhances scattering,” Lasers Surg. Med. 13, 31–39 (1993).
[CrossRef] [PubMed]

Rettschnick, R. P. H.

G. H. M. Gijsbers, D. Breederveld, M. J. C. vanGemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–47 (1986).

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]

Speelman, O. C.

M. J. H. Witjes, A. J. G. Mank, O. C. Speelman, “Distribution of aluminium phthalocyanine disulfonate in an oral squamous cell carcinoma model,” Photochem. Photobiol. 65, 685–693 (1997).
[PubMed]

Sterenborg, H. J. C. M.

H. J. C. M. Sterenborg, M. J. C. van Gemert, W. Kamphorst, J. G. Wolbers, W. Holgervorst, “The spectral dependence of the optical properties of human brain,” Lasers Med. Sci. 4, 221–227 (1989).
[CrossRef]

Taroni, P.

R. Cubeddu, G. Canti, P. Taroni, G. Valentini, “Tumor visualization in a murine model by time-delayed fluorescence of sulphonated aluminium phthalocyanine,” Lasers Med. Sci. 12, 200–208 (1997).
[CrossRef] [PubMed]

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]

Valentini, G.

R. Cubeddu, G. Canti, P. Taroni, G. Valentini, “Tumor visualization in a murine model by time-delayed fluorescence of sulphonated aluminium phthalocyanine,” Lasers Med. Sci. 12, 200–208 (1997).
[CrossRef] [PubMed]

van Gemert, M. J. C.

H. J. C. M. Sterenborg, M. J. C. van Gemert, W. Kamphorst, J. G. Wolbers, W. Holgervorst, “The spectral dependence of the optical properties of human brain,” Lasers Med. Sci. 4, 221–227 (1989).
[CrossRef]

van Hillegersberg, R.

R. van Hillegersberg, J. W. Pickering, M. Aalders, J. F. Beek, “Optical properties of rat liver and tumor at 633 nm and 1064 nm: photofrin enhances scattering,” Lasers Surg. Med. 13, 31–39 (1993).
[CrossRef] [PubMed]

vanGemert, M. J. C.

G. H. M. Gijsbers, D. Breederveld, M. J. C. vanGemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–47 (1986).

Witjes, M. J. H.

M. J. H. Witjes, A. J. G. Mank, O. C. Speelman, “Distribution of aluminium phthalocyanine disulfonate in an oral squamous cell carcinoma model,” Photochem. Photobiol. 65, 685–693 (1997).
[PubMed]

Wolbers, J. G.

H. J. C. M. Sterenborg, M. J. C. van Gemert, W. Kamphorst, J. G. Wolbers, W. Holgervorst, “The spectral dependence of the optical properties of human brain,” Lasers Med. Sci. 4, 221–227 (1989).
[CrossRef]

Biochem. Biophys. Res. Commun. (1)

R. S. Bodaness, D. S. King, “The two-photon induced fluorescence of the tumor localizing photosensitizer hematoporphyrin derivative via 1064-nm photons from a 20-ns Q-switched Nd-YAG laser,” Biochem. Biophys. Res. Commun. 126, 346–351 (1985).
[CrossRef] [PubMed]

Cancer (1)

T. S. Mang, C. McGinnis, C. Liebow, U. O. Nseyo, D. H. Crean, T. J. Dougherty, “Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies,” Cancer 71, 269–276 (1993).
[CrossRef] [PubMed]

Cancer Res. (1)

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]

J. Photochem. Photobiol. (1)

S. G. Bown, “Photodynamic therapy to scientists and clinicians—one world or two?” J. Photochem. Photobiol. 6, 1–12 (1990).
[CrossRef]

Lasers Life Sci. (1)

G. H. M. Gijsbers, D. Breederveld, M. J. C. vanGemert, T. A. Boon, J. Langelaar, R. P. H. Rettschnick, “In vivo fluorescence excitation and emission spectra of hematoporphyrin derivative,” Lasers Life Sci. 1, 29–47 (1986).

Lasers Med. Sci. (2)

H. J. C. M. Sterenborg, M. J. C. van Gemert, W. Kamphorst, J. G. Wolbers, W. Holgervorst, “The spectral dependence of the optical properties of human brain,” Lasers Med. Sci. 4, 221–227 (1989).
[CrossRef]

R. Cubeddu, G. Canti, P. Taroni, G. Valentini, “Tumor visualization in a murine model by time-delayed fluorescence of sulphonated aluminium phthalocyanine,” Lasers Med. Sci. 12, 200–208 (1997).
[CrossRef] [PubMed]

Lasers Surg. Med. (1)

R. van Hillegersberg, J. W. Pickering, M. Aalders, J. F. Beek, “Optical properties of rat liver and tumor at 633 nm and 1064 nm: photofrin enhances scattering,” Lasers Surg. Med. 13, 31–39 (1993).
[CrossRef] [PubMed]

Photochem. Photobiol. (3)

M. J. H. Witjes, A. J. G. Mank, O. C. Speelman, “Distribution of aluminium phthalocyanine disulfonate in an oral squamous cell carcinoma model,” Photochem. Photobiol. 65, 685–693 (1997).
[PubMed]

J. Moan, H. Anholt, “Phthalocyanine fluorescence in tumors during PDT,” Photochem. Photobiol. 51, 379–381 (1990).
[CrossRef] [PubMed]

P. Lenz, “In vivo excitation of photosensitizers by infrared light,” Photochem. Photobiol. 62, 333–338 (1995).
[CrossRef] [PubMed]

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Figures (11)

Fig. 1
Fig. 1

Tissue samples containing, at a variable depth z, a thin sheet of phthalocyanine whose thickness is given by spacers (three are visible in the image).

Fig. 2
Fig. 2

Optical setup used for the fluorescence measurements. Beams of pulsed infrared or continuous visible excitation light are directed toward the sample by a prism. Fluorescent light is concentrated on a photomultiplier.

Fig. 3
Fig. 3

Section of the laser beam. The numbers shown in (c) are proportional to the local power densities.

Fig. 4
Fig. 4

Fluorescence intensity F collected at the tissue surface for turkey muscle as a function of the position z of the phthalocyanine sheet.

Fig. 5
Fig. 5

Fluorescence intensity F collected at the tissue surface for beef muscle as a function of the position z of the phthalocyanine sheet.

Fig. 6
Fig. 6

Fluorescence intensity F collected at the tissue surface for calf liver as a function of the position z of the phthalocyanine sheet.

Fig. 7
Fig. 7

Fluorescence intensity F collected at the tissue surface for calf brain (gray matter) as a function of the position z of the phthalocyanine sheet.

Fig. 8
Fig. 8

Fluorescence intensity F collected at the tissue surface for calf brain (white matter) as a function of the position z of the phthalocyanine sheet.

Fig. 9
Fig. 9

Relation of the slope of the exponential part of the fluorescence curves to the optical penetration depths of the exciting and fluorescent light. Ordinate: δf-1. Abscissa: δ610-1 + δ700-1 (black) and 2δ1064-1 (white). Units are inverse millimeters.

Fig. 10
Fig. 10

Relative change of the fluorescence signal intensity with the thickness of the surface layer that has the higher fluorophor concentration. Abscissa: thickness (in millimeters). Each third curve corresponds to a different excitation wavelength.

Fig. 11
Fig. 11

Relative change of the fluorescence signal intensity with the higher fluorophor concentration in a subsurface layer. Abscissa: depth of layer (in millimeters). Each third curve corresponds to a different excitation wavelength.

Tables (2)

Tables Icon

Table 1 Optical Penetration Depth (the Reciprocal of the Effective Attenuation Coefficient) of Tissues for Different Wavelengths

Tables Icon

Table 2 Thickness of the Tissue Layer That Accounts for 50% of the Measured Fluorescence for Different Wavelengths

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