Abstract

We have investigated the possibility of determining changes in the volume fraction of microstructure scatterers in the superficial tissue layers by using diffuse reflectance spectroscopy. To that extent we have built a two-layer optical phantom by using microparticles with various sizes in order to simulate the scattering properties of tissue microstructures. Reflectance spectral measurements were performed on a number of optical phantoms having different volume fractions of various microparticle sizes. An analytical model was developed using light-transport theory and fractal modeling approaches and was then fitted to the measured reflectance to calculate the volume fractions of the microparticles in phantoms. The results showed that we could measure changes in both the total volume fraction of the microparticles and in the overall size distribution of the microparticles with good accuracy (>80%). These results suggest the potential of using this method for measuring the volume fraction changes of tissue microstructure scatterers and applications in the detection of cancerous related morphological and structural changes.

© 2006 Optical Society of America

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2004

2001

D. E. Hyde, T. J. Farrell, M. S. Patterson, and B. C. Wilson, "A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations," Phys. Med. Biol. 46, 369-383 (2001).
[CrossRef] [PubMed]

M. Bartlett and H. Jiang, "Measurement of particle size-distribution in concentrated, rapidly flowing potassium chloride (KCl) suspensions using continuous-wave photon migration techniques," AIChE J. 47, 60-65 (2001).
[CrossRef]

2000

1999

1998

J. M. Schmitt and G. Kumar, "Optical scattering properties of soft tissue: a discrete particle model," Appl. Opt. 37, 2788-2797 (1998).
[CrossRef]

V. Venugopalan, J. S. You, and B. J. Tromberg, "Radiative transport in the diffusion approximation: an extension for highly absorbing media and small source-detector separation," Phys. Rev. E 58, 2395-2407 (1998).
[CrossRef]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Jonson, "Mechanism of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics," Appl. Opt. 37, 3586-3593 (1998)
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer 84, 366-374 (1998).
[CrossRef]

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer Cytopathol. 84, 336-374 (1998).

H. Jiang, G. Marquez, and L. Wang, "Particle sizing in concentrated suspensions using steady-state, continuous-wave photon migration techniques," Opt. Lett. 23, 394-396 (1998).
[CrossRef]

1997

J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, and I. J. Bigio, "Predictions and measurements of scattering and absorption over broad wavelength range in the tissue phantoms," Appl. Opt. 36, 949-957 (1997).
[CrossRef] [PubMed]

M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

1996

B. Gelebart, E. Tinet, J. M. Tualle, and S. Avrillier, "Phase function simulation in tissue phantoms: a fractal approach," Pure Appl. Opt. 5, 377-388 (1996).
[CrossRef]

J. M. Schmitt and G. Kumar, "Turbulent nature of refractive-index variations in biological tissue," Opt. Lett. 21, 1310-1312 (1996).
[CrossRef] [PubMed]

1995

L.-H. Wang, S. L. Jacques, and L.-Q. Zheng, "MCML--Monte Carlo modeling of—hoton transport in multi-layered tissues" Comput. Methods Programs Biomed. 47, 131-146 (1995).
[CrossRef] [PubMed]

1994

1983

E. Marx and G. W. Mulholland, "Size and refractive index determination of single polystyrene spheres," J. Res. Natl. Bur. Stand. 88, 321-338 (1983).

Avrillier, S.

B. Gelebart, E. Tinet, J. M. Tualle, and S. Avrillier, "Phase function simulation in tissue phantoms: a fractal approach," Pure Appl. Opt. 5, 377-388 (1996).
[CrossRef]

Backman, V.

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, "Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo," Appl. Opt. 38, 6628-6637 (1999).
[CrossRef]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurements of epithelial cellular structures in situ," IEEE Trans. Biomed. Eng. 5, 1019-1026 (1999).

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

Badizadegan, K.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurements of epithelial cellular structures in situ," IEEE Trans. Biomed. Eng. 5, 1019-1026 (1999).

Bartlett, M.

M. Bartlett and H. Jiang, "Measurement of particle size-distribution in concentrated, rapidly flowing potassium chloride (KCl) suspensions using continuous-wave photon migration techniques," AIChE J. 47, 60-65 (2001).
[CrossRef]

Bigio, I. J.

Bohren, C. F.

C. F. Bohren and D. R. Huffman, Absorption and scattering of light by small particles (Wiley, 1983).

Boone, C. W.

M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

Boyer, J.

Crawford, J. M.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Dasari, R. R.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurements of epithelial cellular structures in situ," IEEE Trans. Biomed. Eng. 5, 1019-1026 (1999).

M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

Derman, C.

C. Derman, L. J. Gleser, and I. Olkin, A Guide to Probability Theory and Application (Holt, Rinehart & Winston, 1973), Chap. 8, p. 378.

Drezek, R.

Eick, A. A.

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Jonson, "Mechanism of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics," Appl. Opt. 37, 3586-3593 (1998)
[CrossRef]

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer 84, 366-374 (1998).
[CrossRef]

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer Cytopathol. 84, 336-374 (1998).

Farrell, T. J.

D. E. Hyde, T. J. Farrell, M. S. Patterson, and B. C. Wilson, "A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations," Phys. Med. Biol. 46, 369-383 (2001).
[CrossRef] [PubMed]

Feld, M. S.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurements of epithelial cellular structures in situ," IEEE Trans. Biomed. Eng. 5, 1019-1026 (1999).

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, "Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo," Appl. Opt. 38, 6628-6637 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

Feng, T. C.

Fitzmaurice, M.

Flannery, B. P.

W. H. Press, S. A. Teukolsky, W. T. Vetterling, and B. P. Flannery, Numerical Recipes in C, 2nd ed. (Cambridge U. Press, 1992).

Freyer, J. P.

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer Cytopathol. 84, 336-374 (1998).

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer 84, 366-374 (1998).
[CrossRef]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Jonson, "Mechanism of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics," Appl. Opt. 37, 3586-3593 (1998)
[CrossRef]

Fuentes, C.

M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

Fuselier, T.

Gelebart, B.

B. Gelebart, E. Tinet, J. M. Tualle, and S. Avrillier, "Phase function simulation in tissue phantoms: a fractal approach," Pure Appl. Opt. 5, 377-388 (1996).
[CrossRef]

Georgakoudi, I.

M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

Gleser, L. J.

C. Derman, L. J. Gleser, and I. Olkin, A Guide to Probability Theory and Application (Holt, Rinehart & Winston, 1973), Chap. 8, p. 378.

Gossage, K.

Gurjar, R.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurements of epithelial cellular structures in situ," IEEE Trans. Biomed. Eng. 5, 1019-1026 (1999).

Hamano, T.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Haskell, R. C.

Hielscher, A. H.

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer Cytopathol. 84, 336-374 (1998).

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer 84, 366-374 (1998).
[CrossRef]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Jonson, "Mechanism of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics," Appl. Opt. 37, 3586-3593 (1998)
[CrossRef]

Huffman, D. R.

C. F. Bohren and D. R. Huffman, Absorption and scattering of light by small particles (Wiley, 1983).

Hyde, D. E.

D. E. Hyde, T. J. Farrell, M. S. Patterson, and B. C. Wilson, "A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations," Phys. Med. Biol. 46, 369-383 (2001).
[CrossRef] [PubMed]

Itzkan, I.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurements of epithelial cellular structures in situ," IEEE Trans. Biomed. Eng. 5, 1019-1026 (1999).

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Jacques, S. L.

L.-H. Wang, S. L. Jacques, and L.-Q. Zheng, "MCML--Monte Carlo modeling of—hoton transport in multi-layered tissues" Comput. Methods Programs Biomed. 47, 131-146 (1995).
[CrossRef] [PubMed]

Jiang, H.

M. Bartlett and H. Jiang, "Measurement of particle size-distribution in concentrated, rapidly flowing potassium chloride (KCl) suspensions using continuous-wave photon migration techniques," AIChE J. 47, 60-65 (2001).
[CrossRef]

H. Jiang, G. Marquez, and L. Wang, "Particle sizing in concentrated suspensions using steady-state, continuous-wave photon migration techniques," Opt. Lett. 23, 394-396 (1998).
[CrossRef]

Johnson, T. M.

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer Cytopathol. 84, 336-374 (1998).

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer 84, 366-374 (1998).
[CrossRef]

J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, and I. J. Bigio, "Predictions and measurements of scattering and absorption over broad wavelength range in the tissue phantoms," Appl. Opt. 36, 949-957 (1997).
[CrossRef] [PubMed]

Jonson, T. M.

Kabani, S.

M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

Kumar, G.

Lam, S.

Laver, N.

M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

Lima, C.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

MacAulay, C.

Manoharan, R.

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, "Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo," Appl. Opt. 38, 6628-6637 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Marquez, G.

Marx, E.

E. Marx and G. W. Mulholland, "Size and refractive index determination of single polystyrene spheres," J. Res. Natl. Bur. Stand. 88, 321-338 (1983).

McAdams, M. S.

McWilliams, A.

Mourant, J. R.

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer Cytopathol. 84, 336-374 (1998).

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer 84, 366-374 (1998).
[CrossRef]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Jonson, "Mechanism of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics," Appl. Opt. 37, 3586-3593 (1998)
[CrossRef]

J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, and I. J. Bigio, "Predictions and measurements of scattering and absorption over broad wavelength range in the tissue phantoms," Appl. Opt. 36, 949-957 (1997).
[CrossRef] [PubMed]

Mulholland, G. W.

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M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

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L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
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D. E. Hyde, T. J. Farrell, M. S. Patterson, and B. C. Wilson, "A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations," Phys. Med. Biol. 46, 369-383 (2001).
[CrossRef] [PubMed]

Perelman, L. T.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurements of epithelial cellular structures in situ," IEEE Trans. Biomed. Eng. 5, 1019-1026 (1999).

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, "Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo," Appl. Opt. 38, 6628-6637 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
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L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

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M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
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Shields, S.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
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W. M. Star, in Optical-Thermal Response of Laser-Irradiated Tissue, A.J.Welch and M.J. C.van Gemert eds. (Plenum, 1995), pp. 131-206.

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[CrossRef]

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B. Gelebart, E. Tinet, J. M. Tualle, and S. Avrillier, "Phase function simulation in tissue phantoms: a fractal approach," Pure Appl. Opt. 5, 377-388 (1996).
[CrossRef]

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M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

Van Dam, J.

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, "Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo," Appl. Opt. 38, 6628-6637 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

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V. Venugopalan, J. S. You, and B. J. Tromberg, "Radiative transport in the diffusion approximation: an extension for highly absorbing media and small source-detector separation," Phys. Rev. E 58, 2395-2407 (1998).
[CrossRef]

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L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

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[CrossRef] [PubMed]

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M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

Wilson, B. C.

D. E. Hyde, T. J. Farrell, M. S. Patterson, and B. C. Wilson, "A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations," Phys. Med. Biol. 46, 369-383 (2001).
[CrossRef] [PubMed]

You, J. S.

V. Venugopalan, J. S. You, and B. J. Tromberg, "Radiative transport in the diffusion approximation: an extension for highly absorbing media and small source-detector separation," Phys. Rev. E 58, 2395-2407 (1998).
[CrossRef]

Zeng, H.

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L.-H. Wang, S. L. Jacques, and L.-Q. Zheng, "MCML--Monte Carlo modeling of—hoton transport in multi-layered tissues" Comput. Methods Programs Biomed. 47, 131-146 (1995).
[CrossRef] [PubMed]

Zonios, G.

G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, "Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo," Appl. Opt. 38, 6628-6637 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
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Appl. Opt.

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M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (1997).
[CrossRef]

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J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, "Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells," Cancer Cytopathol. 84, 336-374 (1998).

Comput. Methods Programs Biomed.

L.-H. Wang, S. L. Jacques, and L.-Q. Zheng, "MCML--Monte Carlo modeling of—hoton transport in multi-layered tissues" Comput. Methods Programs Biomed. 47, 131-146 (1995).
[CrossRef] [PubMed]

IEEE Trans. Biomed. Eng.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurements of epithelial cellular structures in situ," IEEE Trans. Biomed. Eng. 5, 1019-1026 (1999).

J. Opt. Soc. Am. A

J. Res. Natl. Bur. Stand.

E. Marx and G. W. Mulholland, "Size and refractive index determination of single polystyrene spheres," J. Res. Natl. Bur. Stand. 88, 321-338 (1983).

Opt. Express

Opt. Lett.

Phys. Med. Biol.

D. E. Hyde, T. J. Farrell, M. S. Patterson, and B. C. Wilson, "A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations," Phys. Med. Biol. 46, 369-383 (2001).
[CrossRef] [PubMed]

Phys. Rev. E

V. Venugopalan, J. S. You, and B. J. Tromberg, "Radiative transport in the diffusion approximation: an extension for highly absorbing media and small source-detector separation," Phys. Rev. E 58, 2395-2407 (1998).
[CrossRef]

Phys. Rev. Lett.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Sciler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Pure Appl. Opt.

B. Gelebart, E. Tinet, J. M. Tualle, and S. Avrillier, "Phase function simulation in tissue phantoms: a fractal approach," Pure Appl. Opt. 5, 377-388 (1996).
[CrossRef]

Other

W. H. Press, S. A. Teukolsky, W. T. Vetterling, and B. P. Flannery, Numerical Recipes in C, 2nd ed. (Cambridge U. Press, 1992).

W. M. Star, in Optical-Thermal Response of Laser-Irradiated Tissue, A.J.Welch and M.J. C.van Gemert eds. (Plenum, 1995), pp. 131-206.

C. F. Bohren and D. R. Huffman, Absorption and scattering of light by small particles (Wiley, 1983).

C. Derman, L. J. Gleser, and I. Olkin, A Guide to Probability Theory and Application (Holt, Rinehart & Winston, 1973), Chap. 8, p. 378.

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Figures (8)

Fig. 1
Fig. 1

(a) Schematic diagram of the system setup used to measure the reflectance spectra from the two-layer phantoms. (b) Equivalent measurement geometry of the system.

Fig. 2
Fig. 2

Accuracy of the estimated parameters obtained for reflectance spectra generated using different PSD functions (group 1, exponential; group 2, Gaussian; group 3, log normal). The distribution function used in the inversion procedure during the fitting was (a) Weibull-distribution function and (b) the same distribution functions as used in generating the simulated reflectance spectra for each group.

Fig. 3
Fig. 3

Effect of refractive index uncertainty on the fitting accuracy [Average Err% = 1∕3 Err%(γ + μ + σ)].

Fig. 4
Fig. 4

(a) Effect of the superficial layer thickness on the accuracy of the volume fraction (squares) and on the mean diameter (triangles), with the standard deviation known a priori (open symbols) and with the standard deviation not known a priori (filled symbols). The scattering properties of the top and the bottom layers used during this run were (top μ = 1.2, σ = 1.0, γ = 0.024; μ s (λ=550 nm) = 1.05 mm−1) and (bottom: μ = 2.5, σ = 1.6, γ = 0.075; μ s (λ=550 nm) = 1.98 nm−1) respectively. (b) The superficial layer thickness that corresponds to 20% average error in the derived parameters versus different top layer scattering and background optical properties with albedo of 0.98 (solid squares) and 0.6 (open circles). No prior information about the standard deviation was available before the fitting.

Fig. 5
Fig. 5

Effect of bottom layer optical properties on the mean (open triangle) and standard deviation (open square): (a) absorption coefficient, (b) scattering coefficient, and on the total volume fraction (solid square): (c) absorption coefficient, (d) scattering coefficient. The scattering properties of the top layer were μ = 1.2, σ = 1.0, γ = 0.05; μs (λ=550 nm) = 1.49 mm−1 and l = 0.5 mm.

Fig. 6
Fig. 6

(a) Reflectance spectra measured from four different phantoms and (b) the fitted spectra for phantoms PH3 and PH4. For clarity, graphs for PH1 and PH2 are not shown in (b), but the agreement between measured spectra and fitting curves is similar.

Fig. 7
Fig. 7

Comparison of derived PSDs with the real PSD for phantom PH1.

Fig. 8
Fig. 8

Comparison of derived PSDs with the real PSD for phantom PH2.

Tables (4)

Tables Icon

Table 1 Scatterers' Properties and Thickness of the Top Layers for the Four Phantoms

Tables Icon

Table 2 Top Layer a and Bottom Layer Optical Properties for the Four Phantoms

Tables Icon

Table 3 Errors of the Derived Particle Parameters When No Prior Information was Used

Tables Icon

Table 4 Errors of the Derived Particle Parameters When Prior Information About the Particle-Size Distribution and σ Was Used in the Fitting

Equations (23)

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ϕ ( r , z ) 3 μ a μ tr ϕ ( r , z ) = 3 μ s * μ tr S ( r , z ) + 3 g * μ s * S ( r , z ) ,
μ s ( λ ) = 0 [ Q ( x , n , λ ) ] γ f ( x ) υ ( x )  d x ,
g ( λ ) = 0 [ g ( x , n , λ ) Q ( x , n , λ ) ] γ f ( x ) υ ( x )  d x 0 [ Q ( x , n , λ ) ] γ f ( x ) υ ( x )  d x ,
f ( x ) = a b [ ( x a ) b ] c - 1 exp [ ( x a ) b ] c ,
R d = R d ( γ , a , b , c , μ a , λ ) .
μ = b + a Γ ( 1 c + 1 ) , σ = a Γ ( 2 c + 1 ) Γ ( 1 c + 1 ) 2 ,
f ( x ) = 1 b exp [ ( x a ) b ] ,     with   μ = b + a ,     σ = b ,
f ( x ) = 1 b 2 π exp [ ( x a ) 2 2 b 2 ] ,     with   μ = a , σ = b ,
f ( x ) = 1 x c b 2 π exp [ ( ln x ) 2 2 b 2 ] ,     with   μ = exp ( 0.5 b 2 ) ,
σ = exp ( b 2 ) [ exp ( b 2 ) ] 1     for c = 1 ,
μ a ( λ ) = ρ [ α μ HbO 2 + ( 1 α ) μ Hb ] ,
2 ϕ ( r , z ) 3 μ a μ tr ϕ ( r , z ) = 3 μ s * μ tr S ( r , z ) + 3 g * μ s * S ( r , z ) .
S 1 ( r ) = I 0 exp ( μ t 1 * z )   for   0 < z < 1 , S 2 ( r ) = I 0 exp ( μ t 1 * l ) exp [ μ t 2 * ( z l ) ]   for   z > l ,
2 ϕ ( z ) κ d 2 ϕ ( r ) = β S ( z ) ,
ϕ | z = l + = ϕ | z = l and j | z = l + = j | z = l .
j | z = 0 + = Ω ϕ | z = 0   with   Ω = ( 1 R e f f ) ( 2 + 2 R e f f ) 1 ,
ϕ 1 ( z ) = A 1 exp ( μ t 1 * z ) + B 1 exp ( κ d 1 z ) + B 2 exp ( κ d 1 z ) for  0 < z l ,
ϕ 2 ( z ) = A 2 exp [ μ t 2 * ( z - l ) ] + B 3 exp ( κ d 2 z ) for  z > l ,
A 1 = I 0 β 1 μ s 1 * κ d 1 2 ( κ d 1 2 μ t 1 * 2 ) ,
A 2 = I 0 β 1 μ s 2 * κ d 2 2 ( κ d 2 2 μ t 2 * ) exp ( μ t 1 * l ) .
R d = β 1 ϕ ( z ) | z = 0 .
R d = β 1 ( μ t 1 * A 1 + κ d 1 B 1 - κ d 1 B 2 ) .
R d = R d ( γ , a , b , c , μ a , λ ) .

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