Abstract

We present two forward-adjoint models for recovering intrinsic fluorescence spectra and hemoglobin oxygen saturation of turbid samples. The first fits measured diffuse reflectance spectra to obtain the absorption and scattering spectra of the medium, and these are then used to correct distortions imposed on the fluorescence spectrum by absorption and scattering. The second fits only the measured fluorescence spectrum to determine simultaneously the amplitudes of absorption and fluorescence basis spectra and scattering parameters. Both methods are validated with Monte Carlo simulations and experimentally in scattering phantoms containing nicotinamide adenine dinucleotide and human erythrocytes. Preliminary measurements from murine tumors in vivo are presented.

© 2005 Optical Society of America

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    [CrossRef] [PubMed]
  5. R. Bissonnette, H. Zeng, D. I. McLean, W. E. Schreiber, D. L. Roscoe, H. Lui, “Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX,” J. Invest. Dermatol. 111, 586–591 (1998).
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  17. S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
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  22. E. L. Hull, T. H. Foster, “Steady-state reflectance spectroscopy in the P3 approximation,” J. Opt. Soc. Am. A 18, 584–599 (2001).
    [CrossRef]
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  25. E. L. Hull, M. G. Nichols, T. H. Foster, “Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes,” Phys. Med. Biol. 43, 3381–3404 (1998).
    [CrossRef] [PubMed]
  26. J. C. Finlay, T. H. Foster, “Hemoglobin oxygen saturations in phantoms and in vivo from measurements of steady state diffuse reflectance at a single, short source-detector separation,” Med. Phys. 31, 1949–1959 (2004).
    [CrossRef] [PubMed]
  27. J. Lee, B. M. Fenton, C. J. Koch, J. G. Frelinger, E. M. Lord, “Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment,” Cancer Res. 58, 1478–1485 (1998).
    [PubMed]
  28. J. C. Finlay, T. H. Foster, “Effect of pigment packaging on diffuse reflectance spectroscopy of samples containing red blood cells,” Opt. Lett. 29, 965–967 (2004).
    [CrossRef] [PubMed]
  29. W. H. Press, S. A. Teukolsky, W. T. Vetterling, B. P. Flannery, Numerical Recipes in C: The Art of Scientific Computing,2nd ed. (Cambridge University Press, New York, 1992).
  30. H. J. van Staveren, C. J. M. Moes, J. van Marle, S. A. Prahl, M. J. C. van Gemert, “Light scattering in Intralipid-10 in the wavelength range of 400–1100 nm,” Appl. Opt. 30, 4507–4515 (1991).
    [CrossRef] [PubMed]
  31. 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]
  32. G. A. Wagnières, W. Star, B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol. 68, 603–632 (1998).
    [CrossRef] [PubMed]
  33. A. V. Hill, “The possible effects of the aggregation of the molecules of hemoglobin on its dissociation curves,” J. Physiol. (Proc.) 40, iv–vii (1910).
  34. A. Zwart, G. Kwant, B. Oeseburg, W. G. Zijlstra, “Human whole blood oxygen affinity: Effect of temperature,” J. Appl. Physiol. 57, 429–434 (1984).
  35. I. S. Saidi, S. L. Jacques, F. K. Tittle, “Mie and Rayleigh modeling of visible-light scattering in neonatal skin,” Appl. Opt. 34, 7410–7418 (1995).
    [CrossRef] [PubMed]

2004

J. C. Finlay, T. H. Foster, “Hemoglobin oxygen saturations in phantoms and in vivo from measurements of steady state diffuse reflectance at a single, short source-detector separation,” Med. Phys. 31, 1949–1959 (2004).
[CrossRef] [PubMed]

J. C. Finlay, T. H. Foster, “Effect of pigment packaging on diffuse reflectance spectroscopy of samples containing red blood cells,” Opt. Lett. 29, 965–967 (2004).
[CrossRef] [PubMed]

2001

E. L. Hull, T. H. Foster, “Steady-state reflectance spectroscopy in the P3 approximation,” J. Opt. Soc. Am. A 18, 584–599 (2001).
[CrossRef]

R. Bissonnette, H. Zeng, D. I. McLean, M. Korbelik, H. Lui, “Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells,” Photochem. Photobiol. 74, 339–345 (2001).
[CrossRef] [PubMed]

B. W. Pogue, J. D. Pitts, M. A. Mycek, R. D. Sloboda, C. M. Wilmot, J. F. Brandsema, J. A. O’Hara, “In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy,” Photochem. Photobiol. 74, 817–824 (2001).
[CrossRef]

J. C. Finlay, D. L. Conover, E. L. Hull, T. H. Foster, “Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo,” Photochem. Photobiol. 73, 54–63 (2001).
[CrossRef] [PubMed]

R. W. Weersink, M. S. Patterson, K. Diamond, S. Silver, N. Padgett, “Noninvasive measurement of fluorophore concentration in turbid media with a simple fluorescence/reflectance ratio technique,” Appl. Opt. 40, 6389–6395 (2001).
[CrossRef]

M. G. Muller, I. Georgakoudi, Q. Zhang, J. Wu, M. S. Feld, “Intrinsic fluorescence spectroscopy in turbid media: disentangling effects of scattering and absorption,” Appl. Opt. 40, 4633–4646 (2001).
[CrossRef]

2000

R. E. N. Shehada, V. Z. Marmarelis, H. N. Mansour, W. S. Grundfest, “Laser induced fluorescence attenuation spectroscopy: detection of hypoxia,” IEEE Trans. Biomed. Eng. 47, 301–312 (2000).
[CrossRef] [PubMed]

1999

M. Inaguma, K. Hashimoto, “Porphyrin-like fluorescence in oral cancer,” Cancer 86, 2201–2211 (1999).
[CrossRef] [PubMed]

1998

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

R. Bissonnette, H. Zeng, D. I. McLean, W. E. Schreiber, D. L. Roscoe, H. Lui, “Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX,” J. Invest. Dermatol. 111, 586–591 (1998).
[CrossRef] [PubMed]

L. van der Laan, A. Coremans, C. Inde, H. A. Bruining, “NADH videofluorimetry to monitor the energy state of skeletal muscle in vivo,” J. Surg. Res. 74, 155–160 (1998).
[CrossRef] [PubMed]

J. Lee, B. M. Fenton, C. J. Koch, J. G. Frelinger, E. M. Lord, “Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment,” Cancer Res. 58, 1478–1485 (1998).
[PubMed]

E. L. Hull, M. G. Nichols, T. H. Foster, “Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes,” Phys. Med. Biol. 43, 3381–3404 (1998).
[CrossRef] [PubMed]

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

1997

1996

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

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

A. Kienle, M. S. Patterson, “Determination of the optical properties of turbid media from a single Monte Carlo simulation,” Phys. Med. Biol. 41, 2221–2227 (1996).
[CrossRef] [PubMed]

1995

I. S. Saidi, S. L. Jacques, F. K. Tittle, “Mie and Rayleigh modeling of visible-light scattering in neonatal skin,” Appl. Opt. 34, 7410–7418 (1995).
[CrossRef] [PubMed]

P. G. Cordeiro, R. E. Kirschner, Q.-Y. Hu, J. J. C. Chiao, H. Savage, R. R. Alfano, L. A. Hoffman, D. A. Hidalgo, “Ultraviolet excitation fluorescence spectroscopy: a noninvasive method for the measurement of redox changes in ischemic myocutaneous flaps,” Plast. Reconstr. Surg. 96, 673–680 (1995).
[CrossRef] [PubMed]

1994

1993

J. Wu, M. S. Feld, R. P. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3583–3595 (1993).
[CrossRef]

1992

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

1991

M. L. Williams, “Generalized contribution response theory,” Nucl. Sci. Eng. 108, 355–383 (1991).

H. J. van Staveren, C. J. M. Moes, J. van Marle, S. A. Prahl, M. J. C. van Gemert, “Light scattering in Intralipid-10 in the wavelength range of 400–1100 nm,” Appl. Opt. 30, 4507–4515 (1991).
[CrossRef] [PubMed]

S. Andersson-Engels, J. Johansson, K. Svanberg, “Fluorescence imaging and point measurements of tissue: applications to the demarcation of malignant tumors and athersclerotic lesions from normal tissue,” Photochem. Photobiol. 53, 807–814 (1991).
[PubMed]

1984

A. Zwart, G. Kwant, B. Oeseburg, W. G. Zijlstra, “Human whole blood oxygen affinity: Effect of temperature,” J. Appl. Physiol. 57, 429–434 (1984).

1972

D. J. Pappajohn, R. Pennys, B. Chance, “NADH spectrofluorometry of rat skin,” J. Appl. Physiol. 33, 684–687 (1972).
[PubMed]

1961

C. W. Maynard, “An application of the reciprocity theorem to the acceleration of Monte Carlo calculations,” Nucl. Sci. Eng. 10, 97–101 (1961).

1910

A. V. Hill, “The possible effects of the aggregation of the molecules of hemoglobin on its dissociation curves,” J. Physiol. (Proc.) 40, iv–vii (1910).

Alfano, R. R.

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

P. G. Cordeiro, R. E. Kirschner, Q.-Y. Hu, J. J. C. Chiao, H. Savage, R. R. Alfano, L. A. Hoffman, D. A. Hidalgo, “Ultraviolet excitation fluorescence spectroscopy: a noninvasive method for the measurement of redox changes in ischemic myocutaneous flaps,” Plast. Reconstr. Surg. 96, 673–680 (1995).
[CrossRef] [PubMed]

Andersson-Engels, S.

S. Andersson-Engels, J. Johansson, K. Svanberg, “Fluorescence imaging and point measurements of tissue: applications to the demarcation of malignant tumors and athersclerotic lesions from normal tissue,” Photochem. Photobiol. 53, 807–814 (1991).
[PubMed]

Bissonnette, R.

R. Bissonnette, H. Zeng, D. I. McLean, M. Korbelik, H. Lui, “Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells,” Photochem. Photobiol. 74, 339–345 (2001).
[CrossRef] [PubMed]

R. Bissonnette, H. Zeng, D. I. McLean, W. E. Schreiber, D. L. Roscoe, H. Lui, “Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX,” J. Invest. Dermatol. 111, 586–591 (1998).
[CrossRef] [PubMed]

Brandsema, J. F.

B. W. Pogue, J. D. Pitts, M. A. Mycek, R. D. Sloboda, C. M. Wilmot, J. F. Brandsema, J. A. O’Hara, “In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy,” Photochem. Photobiol. 74, 817–824 (2001).
[CrossRef]

Bruining, H. A.

L. van der Laan, A. Coremans, C. Inde, H. A. Bruining, “NADH videofluorimetry to monitor the energy state of skeletal muscle in vivo,” J. Surg. Res. 74, 155–160 (1998).
[CrossRef] [PubMed]

Chance, B.

D. J. Pappajohn, R. Pennys, B. Chance, “NADH spectrofluorometry of rat skin,” J. Appl. Physiol. 33, 684–687 (1972).
[PubMed]

Cheong, W.-F.

Chiao, J. J. C.

P. G. Cordeiro, R. E. Kirschner, Q.-Y. Hu, J. J. C. Chiao, H. Savage, R. R. Alfano, L. A. Hoffman, D. A. Hidalgo, “Ultraviolet excitation fluorescence spectroscopy: a noninvasive method for the measurement of redox changes in ischemic myocutaneous flaps,” Plast. Reconstr. Surg. 96, 673–680 (1995).
[CrossRef] [PubMed]

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]

Conover, D. L.

J. C. Finlay, D. L. Conover, E. L. Hull, T. H. Foster, “Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo,” Photochem. Photobiol. 73, 54–63 (2001).
[CrossRef] [PubMed]

Cordeiro, P. G.

P. G. Cordeiro, R. E. Kirschner, Q.-Y. Hu, J. J. C. Chiao, H. Savage, R. R. Alfano, L. A. Hoffman, D. A. Hidalgo, “Ultraviolet excitation fluorescence spectroscopy: a noninvasive method for the measurement of redox changes in ischemic myocutaneous flaps,” Plast. Reconstr. Surg. 96, 673–680 (1995).
[CrossRef] [PubMed]

Coremans, A.

L. van der Laan, A. Coremans, C. Inde, H. A. Bruining, “NADH videofluorimetry to monitor the energy state of skeletal muscle in vivo,” J. Surg. Res. 74, 155–160 (1998).
[CrossRef] [PubMed]

Crilly, R. J.

Deutsch, T. F.

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

Diamond, K.

Duffy, J. T.

S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
[CrossRef]

Durkin, A. J.

Feld, M. S.

Fenton, B. M.

J. Lee, B. M. Fenton, C. J. Koch, J. G. Frelinger, E. M. Lord, “Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment,” Cancer Res. 58, 1478–1485 (1998).
[PubMed]

Finlay, J. C.

J. C. Finlay, T. H. Foster, “Hemoglobin oxygen saturations in phantoms and in vivo from measurements of steady state diffuse reflectance at a single, short source-detector separation,” Med. Phys. 31, 1949–1959 (2004).
[CrossRef] [PubMed]

J. C. Finlay, T. H. Foster, “Effect of pigment packaging on diffuse reflectance spectroscopy of samples containing red blood cells,” Opt. Lett. 29, 965–967 (2004).
[CrossRef] [PubMed]

J. C. Finlay, D. L. Conover, E. L. Hull, T. H. Foster, “Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo,” Photochem. Photobiol. 73, 54–63 (2001).
[CrossRef] [PubMed]

Flannery, B. P.

W. H. Press, S. A. Teukolsky, W. T. Vetterling, B. P. Flannery, Numerical Recipes in C: The Art of Scientific Computing,2nd ed. (Cambridge University Press, New York, 1992).

Flotte, T. J.

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

Foster, T. H.

J. C. Finlay, T. H. Foster, “Effect of pigment packaging on diffuse reflectance spectroscopy of samples containing red blood cells,” Opt. Lett. 29, 965–967 (2004).
[CrossRef] [PubMed]

J. C. Finlay, T. H. Foster, “Hemoglobin oxygen saturations in phantoms and in vivo from measurements of steady state diffuse reflectance at a single, short source-detector separation,” Med. Phys. 31, 1949–1959 (2004).
[CrossRef] [PubMed]

E. L. Hull, T. H. Foster, “Steady-state reflectance spectroscopy in the P3 approximation,” J. Opt. Soc. Am. A 18, 584–599 (2001).
[CrossRef]

J. C. Finlay, D. L. Conover, E. L. Hull, T. H. Foster, “Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo,” Photochem. Photobiol. 73, 54–63 (2001).
[CrossRef] [PubMed]

E. L. Hull, M. G. Nichols, T. H. Foster, “Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes,” Phys. Med. Biol. 43, 3381–3404 (1998).
[CrossRef] [PubMed]

Frelinger, J. G.

J. Lee, B. M. Fenton, C. J. Koch, J. G. Frelinger, E. M. Lord, “Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment,” Cancer Res. 58, 1478–1485 (1998).
[PubMed]

Frisoli, J. K.

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

Gardner, C. M.

Georgakoudi, I.

Grundfest, W. S.

R. E. N. Shehada, V. Z. Marmarelis, H. N. Mansour, W. S. Grundfest, “Laser induced fluorescence attenuation spectroscopy: detection of hypoxia,” IEEE Trans. Biomed. Eng. 47, 301–312 (2000).
[CrossRef] [PubMed]

S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
[CrossRef]

Hashimoto, K.

M. Inaguma, K. Hashimoto, “Porphyrin-like fluorescence in oral cancer,” Cancer 86, 2201–2211 (1999).
[CrossRef] [PubMed]

Hidalgo, D. A.

P. G. Cordeiro, R. E. Kirschner, Q.-Y. Hu, J. J. C. Chiao, H. Savage, R. R. Alfano, L. A. Hoffman, D. A. Hidalgo, “Ultraviolet excitation fluorescence spectroscopy: a noninvasive method for the measurement of redox changes in ischemic myocutaneous flaps,” Plast. Reconstr. Surg. 96, 673–680 (1995).
[CrossRef] [PubMed]

Hill, A. V.

A. V. Hill, “The possible effects of the aggregation of the molecules of hemoglobin on its dissociation curves,” J. Physiol. (Proc.) 40, iv–vii (1910).

Hoffman, L. A.

P. G. Cordeiro, R. E. Kirschner, Q.-Y. Hu, J. J. C. Chiao, H. Savage, R. R. Alfano, L. A. Hoffman, D. A. Hidalgo, “Ultraviolet excitation fluorescence spectroscopy: a noninvasive method for the measurement of redox changes in ischemic myocutaneous flaps,” Plast. Reconstr. Surg. 96, 673–680 (1995).
[CrossRef] [PubMed]

Hu, Q.-Y.

P. G. Cordeiro, R. E. Kirschner, Q.-Y. Hu, J. J. C. Chiao, H. Savage, R. R. Alfano, L. A. Hoffman, D. A. Hidalgo, “Ultraviolet excitation fluorescence spectroscopy: a noninvasive method for the measurement of redox changes in ischemic myocutaneous flaps,” Plast. Reconstr. Surg. 96, 673–680 (1995).
[CrossRef] [PubMed]

Hull, E. L.

J. C. Finlay, D. L. Conover, E. L. Hull, T. H. Foster, “Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo,” Photochem. Photobiol. 73, 54–63 (2001).
[CrossRef] [PubMed]

E. L. Hull, T. H. Foster, “Steady-state reflectance spectroscopy in the P3 approximation,” J. Opt. Soc. Am. A 18, 584–599 (2001).
[CrossRef]

E. L. Hull, M. G. Nichols, T. H. Foster, “Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes,” Phys. Med. Biol. 43, 3381–3404 (1998).
[CrossRef] [PubMed]

Inaguma, M.

M. Inaguma, K. Hashimoto, “Porphyrin-like fluorescence in oral cancer,” Cancer 86, 2201–2211 (1999).
[CrossRef] [PubMed]

Inde, C.

L. van der Laan, A. Coremans, C. Inde, H. A. Bruining, “NADH videofluorimetry to monitor the energy state of skeletal muscle in vivo,” J. Surg. Res. 74, 155–160 (1998).
[CrossRef] [PubMed]

Jacques, S. L.

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

I. S. Saidi, S. L. Jacques, F. K. Tittle, “Mie and Rayleigh modeling of visible-light scattering in neonatal skin,” Appl. Opt. 34, 7410–7418 (1995).
[CrossRef] [PubMed]

S. A. Prahl, M. Keijzer, S. L. Jacques, A. J. Welch, “A Monte Carlo model of light propagation in tissue,” in Dosimetry of Laser Radiation in Medicine and Biology, G. Mueller, D. Sliney, eds., Vol. IS5 of SPIE Institute Series (SPIE Press, Bellingham, Wash., 1989), pp. 102–111.

Jaikumar, S.

Johansson, J.

S. Andersson-Engels, J. Johansson, K. Svanberg, “Fluorescence imaging and point measurements of tissue: applications to the demarcation of malignant tumors and athersclerotic lesions from normal tissue,” Photochem. Photobiol. 53, 807–814 (1991).
[PubMed]

Keijzer, M.

S. A. Prahl, M. Keijzer, S. L. Jacques, A. J. Welch, “A Monte Carlo model of light propagation in tissue,” in Dosimetry of Laser Radiation in Medicine and Biology, G. Mueller, D. Sliney, eds., Vol. IS5 of SPIE Institute Series (SPIE Press, Bellingham, Wash., 1989), pp. 102–111.

Kienle, A.

A. Kienle, M. S. Patterson, “Determination of the optical properties of turbid media from a single Monte Carlo simulation,” Phys. Med. Biol. 41, 2221–2227 (1996).
[CrossRef] [PubMed]

Kirschner, R. E.

P. G. Cordeiro, R. E. Kirschner, Q.-Y. Hu, J. J. C. Chiao, H. Savage, R. R. Alfano, L. A. Hoffman, D. A. Hidalgo, “Ultraviolet excitation fluorescence spectroscopy: a noninvasive method for the measurement of redox changes in ischemic myocutaneous flaps,” Plast. Reconstr. Surg. 96, 673–680 (1995).
[CrossRef] [PubMed]

Koch, C. J.

J. Lee, B. M. Fenton, C. J. Koch, J. G. Frelinger, E. M. Lord, “Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment,” Cancer Res. 58, 1478–1485 (1998).
[PubMed]

Korbelik, M.

R. Bissonnette, H. Zeng, D. I. McLean, M. Korbelik, H. Lui, “Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells,” Photochem. Photobiol. 74, 339–345 (2001).
[CrossRef] [PubMed]

Kwant, G.

A. Zwart, G. Kwant, B. Oeseburg, W. G. Zijlstra, “Human whole blood oxygen affinity: Effect of temperature,” J. Appl. Physiol. 57, 429–434 (1984).

Lee, J.

J. Lee, B. M. Fenton, C. J. Koch, J. G. Frelinger, E. M. Lord, “Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment,” Cancer Res. 58, 1478–1485 (1998).
[PubMed]

Lord, E. M.

J. Lee, B. M. Fenton, C. J. Koch, J. G. Frelinger, E. M. Lord, “Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment,” Cancer Res. 58, 1478–1485 (1998).
[PubMed]

Lui, H.

R. Bissonnette, H. Zeng, D. I. McLean, M. Korbelik, H. Lui, “Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells,” Photochem. Photobiol. 74, 339–345 (2001).
[CrossRef] [PubMed]

R. Bissonnette, H. Zeng, D. I. McLean, W. E. Schreiber, D. L. Roscoe, H. Lui, “Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX,” J. Invest. Dermatol. 111, 586–591 (1998).
[CrossRef] [PubMed]

Mansour, H. N.

R. E. N. Shehada, V. Z. Marmarelis, H. N. Mansour, W. S. Grundfest, “Laser induced fluorescence attenuation spectroscopy: detection of hypoxia,” IEEE Trans. Biomed. Eng. 47, 301–312 (2000).
[CrossRef] [PubMed]

Marmarelis, V. Z.

R. E. N. Shehada, V. Z. Marmarelis, H. N. Mansour, W. S. Grundfest, “Laser induced fluorescence attenuation spectroscopy: detection of hypoxia,” IEEE Trans. Biomed. Eng. 47, 301–312 (2000).
[CrossRef] [PubMed]

Maynard, C. W.

C. W. Maynard, “An application of the reciprocity theorem to the acceleration of Monte Carlo calculations,” Nucl. Sci. Eng. 10, 97–101 (1961).

McLean, D. I.

R. Bissonnette, H. Zeng, D. I. McLean, M. Korbelik, H. Lui, “Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells,” Photochem. Photobiol. 74, 339–345 (2001).
[CrossRef] [PubMed]

R. Bissonnette, H. Zeng, D. I. McLean, W. E. Schreiber, D. L. Roscoe, H. Lui, “Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX,” J. Invest. Dermatol. 111, 586–591 (1998).
[CrossRef] [PubMed]

Moes, C. J. M.

Muller, M. G.

Mycek, M. A.

B. W. Pogue, J. D. Pitts, M. A. Mycek, R. D. Sloboda, C. M. Wilmot, J. F. Brandsema, J. A. O’Hara, “In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy,” Photochem. Photobiol. 74, 817–824 (2001).
[CrossRef]

Nichols, M. G.

E. L. Hull, M. G. Nichols, T. H. Foster, “Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes,” Phys. Med. Biol. 43, 3381–3404 (1998).
[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’Hara, J. A.

B. W. Pogue, J. D. Pitts, M. A. Mycek, R. D. Sloboda, C. M. Wilmot, J. F. Brandsema, J. A. O’Hara, “In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy,” Photochem. Photobiol. 74, 817–824 (2001).
[CrossRef]

Oeseburg, B.

A. Zwart, G. Kwant, B. Oeseburg, W. G. Zijlstra, “Human whole blood oxygen affinity: Effect of temperature,” J. Appl. Physiol. 57, 429–434 (1984).

Padgett, N.

Papaioannou, T.

S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
[CrossRef]

Papazoglou, T. G.

S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
[CrossRef]

Pappajohn, D. J.

D. J. Pappajohn, R. Pennys, B. Chance, “NADH spectrofluorometry of rat skin,” J. Appl. Physiol. 33, 684–687 (1972).
[PubMed]

Patterson, M. S.

Pennys, R.

D. J. Pappajohn, R. Pennys, B. Chance, “NADH spectrofluorometry of rat skin,” J. Appl. Physiol. 33, 684–687 (1972).
[PubMed]

Pergadia, V. R.

S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
[CrossRef]

Pitts, J. D.

B. W. Pogue, J. D. Pitts, M. A. Mycek, R. D. Sloboda, C. M. Wilmot, J. F. Brandsema, J. A. O’Hara, “In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy,” Photochem. Photobiol. 74, 817–824 (2001).
[CrossRef]

Pogue, B. W.

B. W. Pogue, J. D. Pitts, M. A. Mycek, R. D. Sloboda, C. M. Wilmot, J. F. Brandsema, J. A. O’Hara, “In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy,” Photochem. Photobiol. 74, 817–824 (2001).
[CrossRef]

Prahl, S. A.

H. J. van Staveren, C. J. M. Moes, J. van Marle, S. A. Prahl, M. J. C. van Gemert, “Light scattering in Intralipid-10 in the wavelength range of 400–1100 nm,” Appl. Opt. 30, 4507–4515 (1991).
[CrossRef] [PubMed]

S. A. Prahl, M. Keijzer, S. L. Jacques, A. J. Welch, “A Monte Carlo model of light propagation in tissue,” in Dosimetry of Laser Radiation in Medicine and Biology, G. Mueller, D. Sliney, eds., Vol. IS5 of SPIE Institute Series (SPIE Press, Bellingham, Wash., 1989), pp. 102–111.

Press, W. H.

W. H. Press, S. A. Teukolsky, W. T. Vetterling, B. P. Flannery, Numerical Recipes in C: The Art of Scientific Computing,2nd ed. (Cambridge University Press, New York, 1992).

Ramanujam, N.

Rava, R. P.

J. Wu, M. S. Feld, R. P. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3583–3595 (1993).
[CrossRef]

Richards-Kortum, R.

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

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]

Roscoe, D. L.

R. Bissonnette, H. Zeng, D. I. McLean, W. E. Schreiber, D. L. Roscoe, H. Lui, “Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX,” J. Invest. Dermatol. 111, 586–591 (1998).
[CrossRef] [PubMed]

Saidi, I. S.

Savage, H.

P. G. Cordeiro, R. E. Kirschner, Q.-Y. Hu, J. J. C. Chiao, H. Savage, R. R. Alfano, L. A. Hoffman, D. A. Hidalgo, “Ultraviolet excitation fluorescence spectroscopy: a noninvasive method for the measurement of redox changes in ischemic myocutaneous flaps,” Plast. Reconstr. Surg. 96, 673–680 (1995).
[CrossRef] [PubMed]

Schomacker, K. T.

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

Schreiber, W. E.

R. Bissonnette, H. Zeng, D. I. McLean, W. E. Schreiber, D. L. Roscoe, H. Lui, “Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX,” J. Invest. Dermatol. 111, 586–591 (1998).
[CrossRef] [PubMed]

Sevick-Muraca, E.

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

Shehada, R. E. N.

R. E. N. Shehada, V. Z. Marmarelis, H. N. Mansour, W. S. Grundfest, “Laser induced fluorescence attenuation spectroscopy: detection of hypoxia,” IEEE Trans. Biomed. Eng. 47, 301–312 (2000).
[CrossRef] [PubMed]

Silver, S.

Sloboda, R. D.

B. W. Pogue, J. D. Pitts, M. A. Mycek, R. D. Sloboda, C. M. Wilmot, J. F. Brandsema, J. A. O’Hara, “In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy,” Photochem. Photobiol. 74, 817–824 (2001).
[CrossRef]

Snyder, W. J.

S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
[CrossRef]

Spears, J. R.

Star, W.

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

Stavridi, M.

S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
[CrossRef]

Svanberg, K.

S. Andersson-Engels, J. Johansson, K. Svanberg, “Fluorescence imaging and point measurements of tissue: applications to the demarcation of malignant tumors and athersclerotic lesions from normal tissue,” Photochem. Photobiol. 53, 807–814 (1991).
[PubMed]

Teukolsky, S. A.

W. H. Press, S. A. Teukolsky, W. T. Vetterling, B. P. Flannery, Numerical Recipes in C: The Art of Scientific Computing,2nd ed. (Cambridge University Press, New York, 1992).

Thomas, R.

S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
[CrossRef]

Tittle, F. K.

van der Laan, L.

L. van der Laan, A. Coremans, C. Inde, H. A. Bruining, “NADH videofluorimetry to monitor the energy state of skeletal muscle in vivo,” J. Surg. Res. 74, 155–160 (1998).
[CrossRef] [PubMed]

van Gemert, M. J. C.

van Marle, J.

van Staveren, H. J.

Vari, S. G.

S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
[CrossRef]

Vetterling, W. T.

W. H. Press, S. A. Teukolsky, W. T. Vetterling, B. P. Flannery, Numerical Recipes in C: The Art of Scientific Computing,2nd ed. (Cambridge University Press, New York, 1992).

Wagnières, G. A.

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

Weersink, R. W.

Weiss, A. B.

S. G. Vari, T. G. Papazoglou, V. R. Pergadia, M. Stavridi, W. J. Snyder, T. Papaioannou, J. T. Duffy, A. B. Weiss, R. Thomas, W. S. Grundfest, “Blood perfusion and pH monitoring in organs by laser induced fluorescence spectroscopy,” in Optical Biopsy, R. Cubeddu, S. Svanberg, H. van den Bergh, eds., Proc. SPIE2081, 117–128 (1993).
[CrossRef]

Welch, A. J.

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

S. A. Prahl, M. Keijzer, S. L. Jacques, A. J. Welch, “A Monte Carlo model of light propagation in tissue,” in Dosimetry of Laser Radiation in Medicine and Biology, G. Mueller, D. Sliney, eds., Vol. IS5 of SPIE Institute Series (SPIE Press, Bellingham, Wash., 1989), pp. 102–111.

Williams, M. L.

M. L. Williams, “Generalized contribution response theory,” Nucl. Sci. Eng. 108, 355–383 (1991).

Wilmot, C. M.

B. W. Pogue, J. D. Pitts, M. A. Mycek, R. D. Sloboda, C. M. Wilmot, J. F. Brandsema, J. A. O’Hara, “In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy,” Photochem. Photobiol. 74, 817–824 (2001).
[CrossRef]

Wilson, B. C.

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

Wu, J.

Zeng, H.

R. Bissonnette, H. Zeng, D. I. McLean, M. Korbelik, H. Lui, “Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells,” Photochem. Photobiol. 74, 339–345 (2001).
[CrossRef] [PubMed]

R. Bissonnette, H. Zeng, D. I. McLean, W. E. Schreiber, D. L. Roscoe, H. Lui, “Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX,” J. Invest. Dermatol. 111, 586–591 (1998).
[CrossRef] [PubMed]

Zhadin, N. N.

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

Zhang, Q.

Zijlstra, W. G.

A. Zwart, G. Kwant, B. Oeseburg, W. G. Zijlstra, “Human whole blood oxygen affinity: Effect of temperature,” J. Appl. Physiol. 57, 429–434 (1984).

Zwart, A.

A. Zwart, G. Kwant, B. Oeseburg, W. G. Zijlstra, “Human whole blood oxygen affinity: Effect of temperature,” J. Appl. Physiol. 57, 429–434 (1984).

Annu. Rev. Phys. Chem.

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

Appl. Opt.

R. W. Weersink, M. S. Patterson, K. Diamond, S. Silver, N. Padgett, “Noninvasive measurement of fluorophore concentration in turbid media with a simple fluorescence/reflectance ratio technique,” Appl. Opt. 40, 6389–6395 (2001).
[CrossRef]

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

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]

J. Wu, M. S. Feld, R. P. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3583–3595 (1993).
[CrossRef]

M. G. Muller, I. Georgakoudi, Q. Zhang, J. Wu, M. S. Feld, “Intrinsic fluorescence spectroscopy in turbid media: disentangling effects of scattering and absorption,” Appl. Opt. 40, 4633–4646 (2001).
[CrossRef]

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]

H. J. van Staveren, C. J. M. Moes, J. van Marle, S. A. Prahl, M. J. C. van Gemert, “Light scattering in Intralipid-10 in the wavelength range of 400–1100 nm,” Appl. Opt. 30, 4507–4515 (1991).
[CrossRef] [PubMed]

I. S. Saidi, S. L. Jacques, F. K. Tittle, “Mie and Rayleigh modeling of visible-light scattering in neonatal skin,” Appl. Opt. 34, 7410–7418 (1995).
[CrossRef] [PubMed]

Cancer

M. Inaguma, K. Hashimoto, “Porphyrin-like fluorescence in oral cancer,” Cancer 86, 2201–2211 (1999).
[CrossRef] [PubMed]

Cancer Res.

J. Lee, B. M. Fenton, C. J. Koch, J. G. Frelinger, E. M. Lord, “Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment,” Cancer Res. 58, 1478–1485 (1998).
[PubMed]

IEEE Trans. Biomed. Eng.

R. E. N. Shehada, V. Z. Marmarelis, H. N. Mansour, W. S. Grundfest, “Laser induced fluorescence attenuation spectroscopy: detection of hypoxia,” IEEE Trans. Biomed. Eng. 47, 301–312 (2000).
[CrossRef] [PubMed]

J. Appl. Physiol.

A. Zwart, G. Kwant, B. Oeseburg, W. G. Zijlstra, “Human whole blood oxygen affinity: Effect of temperature,” J. Appl. Physiol. 57, 429–434 (1984).

D. J. Pappajohn, R. Pennys, B. Chance, “NADH spectrofluorometry of rat skin,” J. Appl. Physiol. 33, 684–687 (1972).
[PubMed]

J. Biomed. Opt.

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

J. Invest. Dermatol.

R. Bissonnette, H. Zeng, D. I. McLean, W. E. Schreiber, D. L. Roscoe, H. Lui, “Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX,” J. Invest. Dermatol. 111, 586–591 (1998).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A

J. Physiol. (Proc.)

A. V. Hill, “The possible effects of the aggregation of the molecules of hemoglobin on its dissociation curves,” J. Physiol. (Proc.) 40, iv–vii (1910).

J. Surg. Res.

L. van der Laan, A. Coremans, C. Inde, H. A. Bruining, “NADH videofluorimetry to monitor the energy state of skeletal muscle in vivo,” J. Surg. Res. 74, 155–160 (1998).
[CrossRef] [PubMed]

Lasers Surg. Med.

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

Med. Phys.

J. C. Finlay, T. H. Foster, “Hemoglobin oxygen saturations in phantoms and in vivo from measurements of steady state diffuse reflectance at a single, short source-detector separation,” Med. Phys. 31, 1949–1959 (2004).
[CrossRef] [PubMed]

Nucl. Sci. Eng.

C. W. Maynard, “An application of the reciprocity theorem to the acceleration of Monte Carlo calculations,” Nucl. Sci. Eng. 10, 97–101 (1961).

M. L. Williams, “Generalized contribution response theory,” Nucl. Sci. Eng. 108, 355–383 (1991).

Opt. Lett.

Photochem. Photobiol.

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

B. W. Pogue, J. D. Pitts, M. A. Mycek, R. D. Sloboda, C. M. Wilmot, J. F. Brandsema, J. A. O’Hara, “In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy,” Photochem. Photobiol. 74, 817–824 (2001).
[CrossRef]

J. C. Finlay, D. L. Conover, E. L. Hull, T. H. Foster, “Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo,” Photochem. Photobiol. 73, 54–63 (2001).
[CrossRef] [PubMed]

S. Andersson-Engels, J. Johansson, K. Svanberg, “Fluorescence imaging and point measurements of tissue: applications to the demarcation of malignant tumors and athersclerotic lesions from normal tissue,” Photochem. Photobiol. 53, 807–814 (1991).
[PubMed]

R. Bissonnette, H. Zeng, D. I. McLean, M. Korbelik, H. Lui, “Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells,” Photochem. Photobiol. 74, 339–345 (2001).
[CrossRef] [PubMed]

Phys. Med. Biol.

A. Kienle, M. S. Patterson, “Determination of the optical properties of turbid media from a single Monte Carlo simulation,” Phys. Med. Biol. 41, 2221–2227 (1996).
[CrossRef] [PubMed]

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Figures (10)

Fig. 1
Fig. 1

Schematic of the distances in millimeters between detection fibers (D) and the fluorescence excitation source fiber (F). The source fiber used for diffuse reflectance measurements (R) is also shown.

Fig. 2
Fig. 2

Simulated fluorescence spectra detected at source–detector separations of (a) 0.55 mm and (b) 1.05 mm in turbid media containing various concentrations of hemoglobin, as indicated in the legend. The spectra shown were calculated by use of a scaled Monte Carlo method, as described in the text. Calculations were performed for tissue with a μs′, of 1 mm−1 at 630 nm, a scattering exponent of 1.5, and an SO2 of 0.75. The corresponding spectra corrected for the effects of absorption and scattering with a forward-adjoint P3 algorithm informed by the optical properties obtained by fitting reflectance spectra are shown in panels (c) and (d). The solid curve in each panel depicts the intrinsic fluorescence emission spectrum.

Fig. 3
Fig. 3

Typical normalized fluorescence spectra acquired from an erythrocyte phantom containing NADH at oxygen tensions of (a) 149 Torr and (b) 0 Torr with detection fibers 0.53 and 1.06 mm from the source fiber. Each spectrum is the average of several spectra obtained at the same oxygen tension. Error bars are omitted for clarity. The corresponding spectra corrected for the effects of absorption and scattering with the scaled Monte Carlo forward-adjoint algorithm informed by optical properties obtained by reflectance fitting, are shown in panels (c) and (d), respectively. For clarity, only every fifth point is shown. The solid curves indicate the normalized intrinsic fluorescence of the phantom.

Fig. 4
Fig. 4

Simulated fluorescence spectra distorted by propagation through (a) 0.55 mm and (b) 1.05 mm of turbid media (symbols) and best fits with the forward-adjoint P3 model (lines). Calculations were performed for samples with a μs′ of 1 mm−1 at 605 nm, a scattering exponent of 1.5, and an SO2 of 0.75. The value of [Hb]t for each curve is listed in the legend. The solid curves indicate the best fit to each curve by use of the forward-adjoint P3 expression. The corresponding corrected spectra are shown in panels (c) and (d). The heavy solid curve in each plot indicates the intrinsic fluorescence emission spectrum used to generate the data set.

Fig. 5
Fig. 5

Fluorescence amplitudes of the NADH and background components recovered from fits to the simulated data sets with source–detector separations of (a) 0.55 mm and (b) 1.05 mm. At each [Hb]t, the results of five fits at different values of SO2 are plotted. Error bars indicate the uncertainties in the fitted values. Best-fit values of (c) SO2 and (d) [Hb]t extracted from the same synthetic fluorescence data set by the forward-adjoint P3 fitting routine, plotted as functions of the true values.

Fig. 6
Fig. 6

Typical normalized fluorescence spectra acquired from an erythrocyte phantom at oxygen tensions of (a) 149 Torr and (b) 0 Torr with detection fibers 0.53 and 1.06 mm from the source fiber. The solid curves represent the best fit to each spectrum with the scaled Monte Carlo forward-adjoint algorithm. The corresponding spectra after correction for the effects of absorption and scattering and normalized to 1.0 at the peak are shown in panels (c) and (d), respectively. The solid curve corresponds to the phantom’s intrinsic fluorescence emission spectrum.

Fig. 7
Fig. 7

Typical erythrocyte phantom fluorescence spectrum (symbols) corrected for the effects of absorption and scattering, along with the contributions of spectral components assigned by the forward-adjoint fitting algorithm (dashed curves) and their sum (solid curve).

Fig. 8
Fig. 8

Best-fit values of the fluorescence amplitudes of NADH and Liposyn as functions of phantom oxygen concentration. Fits are shown for source–detector separations of (a) 0.53 mm and (b) 1.06 mm.

Fig. 9
Fig. 9

Fitted concentrations of oxyhemoglobin and deoxyhemoglobin based on fluorescence spectra acquired from an erythrocyte phantom with detection fibers (a) 0.53 mm and (b) 1.06 mm from the source fiber. The corresponding values of SO2 (symbols) and fits of the Hill equation (—) are shown in panels (c) and (d), respectively. Dashed curves (– – –) indicate the Hill curves derived from fits to reflectance spectra acquired by each fiber.

Fig. 10
Fig. 10

Fluorescence emission spectra obtained in vivo at source–detector separations of (a) 0.53 mm and (b) 1.06 mm on the surface of an EMT6 tumor in an anesthetized mouse. Spectra were taken while the animal breathed room air, carbogen, and nitrogen. The corresponding intrinsic fluorescence emission spectra extracted with optical properties determined by fluorescence fitting are shown in panels (c) and (d). The solid curves indicate the sum of fluorescence basis spectra determined by the fit.

Tables (1)

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Table 1 Hill Parameters Extracted from Erythrocyte Phantom Fluorescence

Equations (12)

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F det = ( λ x / λ m ) μ a f ϕ f V Φ x ( r ) Φ ˜ m ( r ) d 3 r ,
Φ ( r ) = B - exp ( - v - r ) v - r + B + exp ( - v + r ) v + r ,
v ± = [ β ± ( β 2 - Γ ) 1 / 2 18 ] 1 / 2 ,
β = 27 μ a μ t ( 1 ) + 28 μ a μ t ( 3 ) + 35 μ t ( 2 ) μ t ( 3 ) ,
Γ = 3780 μ a μ t ( 1 ) μ t ( 2 ) μ t ( 3 ) ,
B ± = ( v ± ) 5 [ 3 μ a μ t ( 1 ) - ( v ) 2 ] 12 π μ a 2 μ t ( 1 ) [ ( v ± ) 2 - ( v ) 2 ] ,
F det = 4 π F 0 i = ( + , - ) j = ( + , - ) B i B j v x i v m j [ ( v x i ) 2 - ( v m j ) 2 ] r s d × [ exp ( - v m j r s d ) - exp ( - v x i r s d ) ] ,
Φ m ( ρ ,     z ) = l = 0 c 3 Φ MC ( c ρ ,     c z ,     c l ) × exp ( - [ μ a - c μ a MC ] l ) d l ,
F det = F 0 l x l m V c x 3 c m 3 Φ MC ( c x ρ ,     c x z ,     c x l x ) exp - [ ( μ a x - c x μ aMC ) l x ] Φ MC ( c m ρ ,     c m z ,     c m l m ) exp - [ ( μ a m - c m μ aMC ) l m ] d 3 r d l x d l m ,
F detMC ( l x ,     l m ) = F 0 v c x 3 c m 3 Φ MC ( c x ρ ,     c x z ,     c x l x ) × Φ MC ( c m ρ ,     c m z ,     c m l m ) d 3 r .
μ s ( λ ) = a 3 ( λ / λ 0 ) a 4 .
F 0 ( λ ) = C n [ F 1 ( λ ) + a 5 F 2 ( λ ) + a 6 F 3 ( λ ) + ] ,

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