Abstract

A newly designed instrument, the static light-scattering (SLS) microscope, which combines light microscopy with SLS, enables us to characterize local light-scattering patterns of thin tissue sections. Each measurement is performed with an illumination beam of 70-μm diameter. On these length scales, tissue is not homogeneous. Both structural ordering and small heterogeneities contribute to the scattering signal. Raw SLS data consist of a two-dimensional intensity distribution map I(θ, φ), showing the dependence of the scattered intensity I on the scattering angle θ and the azimuthal angle φ. In contrast to the majority of experiments and to simulations that consider only the scattering angle, we additionally perform an analysis of the azimuthal dependence I(φ). We estimate different contributions to the azimuthal scattering variation and show that a significant fraction of the azimuthal amplitude is the result of tissue structure. As a demonstration of the importance of the structure-dependent part of the azimuthal signal, we show that this function of the scattered light alone can be used to classify tissue types with surprisingly high specificity and sensitivity.

© 2003 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppard, C. Pitris, J. F. Southern, J. G. Fujimoto, “In vivo endoscopic biopsy with optical coherence tomography,” Science 276, 2037–2039 (1997).
    [CrossRef]
  2. A. M. Siegel, J. J. A. Marotas, D. A. Boas, “Design and evaluation of a continuous-wave diffuse optical tomography system,” Opt. Express 4, 287–298 (1999), http://www.opticsexpress.org .
    [CrossRef]
  3. S. J. Matcher, “Nonuniqueness in optical tomography: relevance of the P1 approximation,” Opt. Lett. 24, 1729–1731 (1999).
    [CrossRef]
  4. J. M. Schmitt, G. Kumar, “Optical scattering properties of soft tissue: a discrete particle model,” Appl. Opt. 37, 2788–2797 (1998).
    [CrossRef]
  5. G. Videen, D. Ngo, “Light scattering multipole solution for a cell,” J. Biomed. Opt. 3, 212–220 (1998).
    [CrossRef] [PubMed]
  6. B. Chance, N. G. Wang, M. Maris, S. Nioka, S. Sevick, “Quantification of tissue optical characteristics and hemoglobin desaturation by time- and frequency-resolved multi-wavelength spectrophotometry,” Adv. Exp. Med. Biol. 317, 297–304 (1992).
    [CrossRef]
  7. J. B. Fishkin, O. Coquoz, E. R. Anderson, M. Brenner, B. J. Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Optics 36, 10–20 (1997).
    [CrossRef]
  8. W.-F. Cheung, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
    [CrossRef]
  9. F. Bevilacqua, P. Marquet, C. Depreursinge, E. B. De Haller, “Determination of reduced scattering and absorption coefficients by a single charge-coupled device array. II. Measurements on biological tissue,” Opt. Eng. 34, 2064–2069 (1995).
    [CrossRef]
  10. A. H. Hielscher, R. E. Alcouffe, R. L. Barbour, “Comparison of finite-difference transport and diffusion calculations for photon migration in homogenous and heterogenous tissues,” Phys. Med. Biol. 43, 1285–1302 (1998).
    [CrossRef] [PubMed]
  11. D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solutions and applications,” Proc. Natl. Acad. Sci. USA 91, 4887–4891 (1994).
    [CrossRef]
  12. F. Bevilacqua, C. Depreursinge, “Monte Carlo study of diffuse reflectance at source-detector separations close to one transport mean free path,” J. Opt. Soc. Am. A 16, 2935–2945 (1999).
    [CrossRef]
  13. V. V. Tuchin, “Light scattering studies of tissues,” Phys. Usp. 40, 494–515 (1997).
    [CrossRef]
  14. S. J. Matcher, M. Cope, D. T. Delpy, “In vivo measurements of the wavelength dependence of tissue-scattering coefficients between 760 and 900 nm,” Appl. Opt. 36, 386–396 (1997).
    [CrossRef] [PubMed]
  15. S. P. Treweek, J. C. Barbenel, “Direct measurement of the optical properties of breast skin,” Med. Biol. Eng. Comp. 34, 285–289 (1995).
    [CrossRef]
  16. D. J. Smithies, P. H. Butler, “Modelling the distribution of laser in port wine stains with the Monte Carlo method,” Phys. Med. Biol. 40, 701–731 (1995).
    [CrossRef] [PubMed]
  17. E. Luther, L. A. Kamentsky, “Resolution of mitotic cells using laser scanning cytometry,” Cytometry 23, 272–278 (1996).
    [CrossRef] [PubMed]
  18. J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnosis,” Appl. Opt. 37, 3586–3593 (1998).
    [CrossRef]
  19. F. Bevilacqua, P. Marquet, O. Coquoz, C. Depreursinge, “Role of tissue structure in photon migration through breast tissues,” Appl. Opt. 36, 44–51 (1997).
    [CrossRef] [PubMed]
  20. S. L. Jacques, C. A. Alter, S. A. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309–333 (1987).
  21. J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnostic of bladder cancer by elastic light scattering,” Laser Surg. Med. 17, 350–357 (1995).
    [CrossRef]
  22. L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. VanDam, J. M. Crawford, M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for nuclear size distribution,” Phys. Rev. Lett. 80, 627–630 (1998).
    [CrossRef]
  23. A. H. Hielscher, J. R. Mourant, I. J. Bigio, “Influence of particle size and concentration on the diffuse backscattering of polarized light from tissue phantoms and biological cell suspensions,” Appl. Opt. 36, 125–135 (1997).
    [CrossRef] [PubMed]
  24. A. H. Hielscher, A. E. Eick, J. R. Mourant, D. Shen, J. P. Freyer, I. J. Bigio, “Diffuse backscattering Mueller matrices of highly scattering media,” Opt. Express 1, 441–453 (1998), http://www.opticsexpress.org .
    [CrossRef]
  25. M. T. Valentine, A. K. Popp, P. D. Kaplan, D. A. Weitz, “Microscope-based static light scattering apparatus,” Opt. Lett. 26, 890–892 (2001).
    [CrossRef]
  26. A. K. Popp, M. T. Valentine, P. D. Kaplan, D. A. Weitz, “Light scattering microscope to investigate heterogeneities of tissues,” in Optical Biopsy III, R. R. Alfano, ed., Proc. SPIE3917, 22–33 (2000).
    [CrossRef]
  27. P. D. Kaplan, V. Trappe, D. A. Weitz, “Light scattering microscope,” Appl. Opt. 38, 4151–4157 (1999).
    [CrossRef]
  28. L. G. Henyey, J. L. Greenstein, “Diffuse radiation in the galaxy,” Astrophys. J. 93, 70–83 (1941).
    [CrossRef]
  29. S. T. Flock, B. C. Wilson, M. S. Patterson, “Total attenuation coefficients and scattering phase functions of tissues and phantom materials at 633 nm,” Med. Phys. 14, 835–841 (1987).
    [CrossRef] [PubMed]
  30. R. Marchesini, A. Bertoni, S. Andreola, E. Melloin, A. E. Sichirollo, “Extinction and absorption coefficients and scattering phase functions of human tissues in vitro,” Appl. Opt. 28, 2318–2324 (1989).
    [CrossRef] [PubMed]
  31. P. Dimon, S. K. Sinha, D. A. Weitz, C. R. Safinya, G. S. Smith, W. A. Varady, H. M. Lindsay, “Structure of aggregated gold colloids,” Phys. Rev. Lett. 57, 595–598 (1986).
    [CrossRef] [PubMed]
  32. T. Nicolai, D. Durand, J.-C. Gimel, “Scattering properties and modelling of aggregating and gelling systems,” in Lightscattering: Principles and Development, W. Brown, ed. (Oxford University Press, New York, 1996).
  33. M. Takeda, T. Norisuye, M. Shibayama, “Critical dynamics of cross-linked polymer chains near the gelation threshold,” Macromol. 33, 2909–2915 (2000).
    [CrossRef]
  34. J. Teixeira, “Experimental methods for studying fractal aggregates,” in On Growth and Form, H. E. Stanley, N. Ostrowski, eds. (Martinus Nijhoff, Dordrecht, The Netherlands, 1986), pp. 145–162.
  35. B. Mandelbrot, The Fractal Geometry of Nature (Freeman, New York, 1982).
  36. J. M. Schmitt, G. Kumar, “Turbulent nature of refractive-index variations in biological tissue,” Opt. Lett. 21, 1310–1312 (1996).
    [CrossRef] [PubMed]
  37. R. K. K. Wang, “Modelling optical properties of soft tissue by fractal distribution of scatterers,” J. Mod. Opt. 47, 103–120 (2000).
  38. H. C. van de Hulst, Lightscattering by Small Particles (Dover, New York, 1981).
  39. W. S. Bickel, W. M. Bailey, “Stokes vectors, Mueller matrices and polarized light,” Am. J. Phys. 53, 468–478 (1985).
    [CrossRef]
  40. H. Liu, D. A Boas, Y. Zhang, A. G. Yodh, B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
    [CrossRef] [PubMed]
  41. N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
    [CrossRef]
  42. N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
    [CrossRef] [PubMed]

2001 (1)

2000 (2)

M. Takeda, T. Norisuye, M. Shibayama, “Critical dynamics of cross-linked polymer chains near the gelation threshold,” Macromol. 33, 2909–2915 (2000).
[CrossRef]

R. K. K. Wang, “Modelling optical properties of soft tissue by fractal distribution of scatterers,” J. Mod. Opt. 47, 103–120 (2000).

1999 (4)

1998 (6)

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

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnosis,” Appl. Opt. 37, 3586–3593 (1998).
[CrossRef]

A. H. Hielscher, A. E. Eick, J. R. Mourant, D. Shen, J. P. Freyer, I. J. Bigio, “Diffuse backscattering Mueller matrices of highly scattering media,” Opt. Express 1, 441–453 (1998), http://www.opticsexpress.org .
[CrossRef]

G. Videen, D. Ngo, “Light scattering multipole solution for a cell,” J. Biomed. Opt. 3, 212–220 (1998).
[CrossRef] [PubMed]

A. H. Hielscher, R. E. Alcouffe, R. L. Barbour, “Comparison of finite-difference transport and diffusion calculations for photon migration in homogenous and heterogenous tissues,” Phys. Med. Biol. 43, 1285–1302 (1998).
[CrossRef] [PubMed]

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

1997 (6)

V. V. Tuchin, “Light scattering studies of tissues,” Phys. Usp. 40, 494–515 (1997).
[CrossRef]

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppard, C. Pitris, J. F. Southern, J. G. Fujimoto, “In vivo endoscopic biopsy with optical coherence tomography,” Science 276, 2037–2039 (1997).
[CrossRef]

J. B. Fishkin, O. Coquoz, E. R. Anderson, M. Brenner, B. J. Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Optics 36, 10–20 (1997).
[CrossRef]

S. J. Matcher, M. Cope, D. T. Delpy, “In vivo measurements of the wavelength dependence of tissue-scattering coefficients between 760 and 900 nm,” Appl. Opt. 36, 386–396 (1997).
[CrossRef] [PubMed]

F. Bevilacqua, P. Marquet, O. Coquoz, C. Depreursinge, “Role of tissue structure in photon migration through breast tissues,” Appl. Opt. 36, 44–51 (1997).
[CrossRef] [PubMed]

A. H. Hielscher, J. R. Mourant, I. J. Bigio, “Influence of particle size and concentration on the diffuse backscattering of polarized light from tissue phantoms and biological cell suspensions,” Appl. Opt. 36, 125–135 (1997).
[CrossRef] [PubMed]

1996 (4)

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

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

E. Luther, L. A. Kamentsky, “Resolution of mitotic cells using laser scanning cytometry,” Cytometry 23, 272–278 (1996).
[CrossRef] [PubMed]

1995 (5)

F. Bevilacqua, P. Marquet, C. Depreursinge, E. B. De Haller, “Determination of reduced scattering and absorption coefficients by a single charge-coupled device array. II. Measurements on biological tissue,” Opt. Eng. 34, 2064–2069 (1995).
[CrossRef]

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnostic of bladder cancer by elastic light scattering,” Laser Surg. Med. 17, 350–357 (1995).
[CrossRef]

S. P. Treweek, J. C. Barbenel, “Direct measurement of the optical properties of breast skin,” Med. Biol. Eng. Comp. 34, 285–289 (1995).
[CrossRef]

D. J. Smithies, P. H. Butler, “Modelling the distribution of laser in port wine stains with the Monte Carlo method,” Phys. Med. Biol. 40, 701–731 (1995).
[CrossRef] [PubMed]

H. Liu, D. A Boas, Y. Zhang, A. G. Yodh, B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

1994 (1)

D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solutions and applications,” Proc. Natl. Acad. Sci. USA 91, 4887–4891 (1994).
[CrossRef]

1992 (1)

B. Chance, N. G. Wang, M. Maris, S. Nioka, S. Sevick, “Quantification of tissue optical characteristics and hemoglobin desaturation by time- and frequency-resolved multi-wavelength spectrophotometry,” Adv. Exp. Med. Biol. 317, 297–304 (1992).
[CrossRef]

1990 (1)

W.-F. Cheung, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

1989 (1)

1987 (2)

S. L. Jacques, C. A. Alter, S. A. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309–333 (1987).

S. T. Flock, B. C. Wilson, M. S. Patterson, “Total attenuation coefficients and scattering phase functions of tissues and phantom materials at 633 nm,” Med. Phys. 14, 835–841 (1987).
[CrossRef] [PubMed]

1986 (1)

P. Dimon, S. K. Sinha, D. A. Weitz, C. R. Safinya, G. S. Smith, W. A. Varady, H. M. Lindsay, “Structure of aggregated gold colloids,” Phys. Rev. Lett. 57, 595–598 (1986).
[CrossRef] [PubMed]

1985 (1)

W. S. Bickel, W. M. Bailey, “Stokes vectors, Mueller matrices and polarized light,” Am. J. Phys. 53, 468–478 (1985).
[CrossRef]

1941 (1)

L. G. Henyey, J. L. Greenstein, “Diffuse radiation in the galaxy,” Astrophys. J. 93, 70–83 (1941).
[CrossRef]

Alcouffe, R. E.

A. H. Hielscher, R. E. Alcouffe, R. L. Barbour, “Comparison of finite-difference transport and diffusion calculations for photon migration in homogenous and heterogenous tissues,” Phys. Med. Biol. 43, 1285–1302 (1998).
[CrossRef] [PubMed]

Alter, C. A.

S. L. Jacques, C. A. Alter, S. A. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309–333 (1987).

Anderson, E. R.

J. B. Fishkin, O. Coquoz, E. R. Anderson, M. Brenner, B. J. Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Optics 36, 10–20 (1997).
[CrossRef]

Andreola, S.

Atkinson, N.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

Backman, V.

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

Bailey, W. M.

W. S. Bickel, W. M. Bailey, “Stokes vectors, Mueller matrices and polarized light,” Am. J. Phys. 53, 468–478 (1985).
[CrossRef]

Barbenel, J. C.

S. P. Treweek, J. C. Barbenel, “Direct measurement of the optical properties of breast skin,” Med. Biol. Eng. Comp. 34, 285–289 (1995).
[CrossRef]

Barbour, R. L.

A. H. Hielscher, R. E. Alcouffe, R. L. Barbour, “Comparison of finite-difference transport and diffusion calculations for photon migration in homogenous and heterogenous tissues,” Phys. Med. Biol. 43, 1285–1302 (1998).
[CrossRef] [PubMed]

Bertoni, A.

Bevilacqua, F.

Bickel, W. S.

W. S. Bickel, W. M. Bailey, “Stokes vectors, Mueller matrices and polarized light,” Am. J. Phys. 53, 468–478 (1985).
[CrossRef]

Bigio, I. J.

Boas, D. A

H. Liu, D. A Boas, Y. Zhang, A. G. Yodh, B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

Boas, D. A.

A. M. Siegel, J. J. A. Marotas, D. A. Boas, “Design and evaluation of a continuous-wave diffuse optical tomography system,” Opt. Express 4, 287–298 (1999), http://www.opticsexpress.org .
[CrossRef]

D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solutions and applications,” Proc. Natl. Acad. Sci. USA 91, 4887–4891 (1994).
[CrossRef]

Boppard, S. A.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppard, C. Pitris, J. F. Southern, J. G. Fujimoto, “In vivo endoscopic biopsy with optical coherence tomography,” Science 276, 2037–2039 (1997).
[CrossRef]

Bouma, B. E.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppard, C. Pitris, J. F. Southern, J. G. Fujimoto, “In vivo endoscopic biopsy with optical coherence tomography,” Science 276, 2037–2039 (1997).
[CrossRef]

Boyer, J.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnostic of bladder cancer by elastic light scattering,” Laser Surg. Med. 17, 350–357 (1995).
[CrossRef]

Brenner, M.

J. B. Fishkin, O. Coquoz, E. R. Anderson, M. Brenner, B. J. Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Optics 36, 10–20 (1997).
[CrossRef]

Brezinski, M. E.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppard, C. Pitris, J. F. Southern, J. G. Fujimoto, “In vivo endoscopic biopsy with optical coherence tomography,” Science 276, 2037–2039 (1997).
[CrossRef]

Butler, P. H.

D. J. Smithies, P. H. Butler, “Modelling the distribution of laser in port wine stains with the Monte Carlo method,” Phys. Med. Biol. 40, 701–731 (1995).
[CrossRef] [PubMed]

Chance, B.

H. Liu, D. A Boas, Y. Zhang, A. G. Yodh, B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solutions and applications,” Proc. Natl. Acad. Sci. USA 91, 4887–4891 (1994).
[CrossRef]

B. Chance, N. G. Wang, M. Maris, S. Nioka, S. Sevick, “Quantification of tissue optical characteristics and hemoglobin desaturation by time- and frequency-resolved multi-wavelength spectrophotometry,” Adv. Exp. Med. Biol. 317, 297–304 (1992).
[CrossRef]

Cheung, W.-F.

W.-F. Cheung, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

Conn, R. L.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnostic of bladder cancer by elastic light scattering,” Laser Surg. Med. 17, 350–357 (1995).
[CrossRef]

Cope, M.

Coquoz, O.

F. Bevilacqua, P. Marquet, O. Coquoz, C. Depreursinge, “Role of tissue structure in photon migration through breast tissues,” Appl. Opt. 36, 44–51 (1997).
[CrossRef] [PubMed]

J. B. Fishkin, O. Coquoz, E. R. Anderson, M. Brenner, B. J. Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Optics 36, 10–20 (1997).
[CrossRef]

Crawford, J. M.

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

De Haller, E. B.

F. Bevilacqua, P. Marquet, C. Depreursinge, E. B. De Haller, “Determination of reduced scattering and absorption coefficients by a single charge-coupled device array. II. Measurements on biological tissue,” Opt. Eng. 34, 2064–2069 (1995).
[CrossRef]

Delpy, D. T.

Depreursinge, C.

Dimon, P.

P. Dimon, S. K. Sinha, D. A. Weitz, C. R. Safinya, G. S. Smith, W. A. Varady, H. M. Lindsay, “Structure of aggregated gold colloids,” Phys. Rev. Lett. 57, 595–598 (1986).
[CrossRef] [PubMed]

Durand, D.

T. Nicolai, D. Durand, J.-C. Gimel, “Scattering properties and modelling of aggregating and gelling systems,” in Lightscattering: Principles and Development, W. Brown, ed. (Oxford University Press, New York, 1996).

Eick, A. A.

Eick, A. E.

Feld, M. S.

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

Fishkin, J. B.

J. B. Fishkin, O. Coquoz, E. R. Anderson, M. Brenner, B. J. Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Optics 36, 10–20 (1997).
[CrossRef]

Flock, S. T.

S. T. Flock, B. C. Wilson, M. S. Patterson, “Total attenuation coefficients and scattering phase functions of tissues and phantom materials at 633 nm,” Med. Phys. 14, 835–841 (1987).
[CrossRef] [PubMed]

Follen Mitchell, M.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

Freyer, J. P.

Fujimoto, J. G.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppard, C. Pitris, J. F. Southern, J. G. Fujimoto, “In vivo endoscopic biopsy with optical coherence tomography,” Science 276, 2037–2039 (1997).
[CrossRef]

Gimel, J.-C.

T. Nicolai, D. Durand, J.-C. Gimel, “Scattering properties and modelling of aggregating and gelling systems,” in Lightscattering: Principles and Development, W. Brown, ed. (Oxford University Press, New York, 1996).

Greenstein, J. L.

L. G. Henyey, J. L. Greenstein, “Diffuse radiation in the galaxy,” Astrophys. J. 93, 70–83 (1941).
[CrossRef]

Hamano, T.

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

Henyey, L. G.

L. G. Henyey, J. L. Greenstein, “Diffuse radiation in the galaxy,” Astrophys. J. 93, 70–83 (1941).
[CrossRef]

Hielscher, A. H.

Itzkan, I.

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

Jacques, S. L.

S. L. Jacques, C. A. Alter, S. A. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309–333 (1987).

Johnson, T.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnostic of bladder cancer by elastic light scattering,” Laser Surg. Med. 17, 350–357 (1995).
[CrossRef]

Johnson, T. M.

Kamentsky, L. A.

E. Luther, L. A. Kamentsky, “Resolution of mitotic cells using laser scanning cytometry,” Cytometry 23, 272–278 (1996).
[CrossRef] [PubMed]

Kaplan, P. D.

M. T. Valentine, A. K. Popp, P. D. Kaplan, D. A. Weitz, “Microscope-based static light scattering apparatus,” Opt. Lett. 26, 890–892 (2001).
[CrossRef]

P. D. Kaplan, V. Trappe, D. A. Weitz, “Light scattering microscope,” Appl. Opt. 38, 4151–4157 (1999).
[CrossRef]

A. K. Popp, M. T. Valentine, P. D. Kaplan, D. A. Weitz, “Light scattering microscope to investigate heterogeneities of tissues,” in Optical Biopsy III, R. R. Alfano, ed., Proc. SPIE3917, 22–33 (2000).
[CrossRef]

Kumar, G.

Lima, C.

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

Lindsay, H. M.

P. Dimon, S. K. Sinha, D. A. Weitz, C. R. Safinya, G. S. Smith, W. A. Varady, H. M. Lindsay, “Structure of aggregated gold colloids,” Phys. Rev. Lett. 57, 595–598 (1986).
[CrossRef] [PubMed]

Liu, H.

H. Liu, D. A Boas, Y. Zhang, A. G. Yodh, B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

Luther, E.

E. Luther, L. A. Kamentsky, “Resolution of mitotic cells using laser scanning cytometry,” Cytometry 23, 272–278 (1996).
[CrossRef] [PubMed]

Mahadevan, A.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

Mahadevan-Janson, A.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

Malpica, A.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

Mandelbrot, B.

B. Mandelbrot, The Fractal Geometry of Nature (Freeman, New York, 1982).

Manoharan, R.

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

Marchesini, R.

Maris, M.

B. Chance, N. G. Wang, M. Maris, S. Nioka, S. Sevick, “Quantification of tissue optical characteristics and hemoglobin desaturation by time- and frequency-resolved multi-wavelength spectrophotometry,” Adv. Exp. Med. Biol. 317, 297–304 (1992).
[CrossRef]

Marotas, J. J. A.

Marquet, P.

F. Bevilacqua, P. Marquet, O. Coquoz, C. Depreursinge, “Role of tissue structure in photon migration through breast tissues,” Appl. Opt. 36, 44–51 (1997).
[CrossRef] [PubMed]

F. Bevilacqua, P. Marquet, C. Depreursinge, E. B. De Haller, “Determination of reduced scattering and absorption coefficients by a single charge-coupled device array. II. Measurements on biological tissue,” Opt. Eng. 34, 2064–2069 (1995).
[CrossRef]

Matcher, S. J.

Melloin, E.

Mourant, J. R.

Ngo, D.

G. Videen, D. Ngo, “Light scattering multipole solution for a cell,” J. Biomed. Opt. 3, 212–220 (1998).
[CrossRef] [PubMed]

Nicolai, T.

T. Nicolai, D. Durand, J.-C. Gimel, “Scattering properties and modelling of aggregating and gelling systems,” in Lightscattering: Principles and Development, W. Brown, ed. (Oxford University Press, New York, 1996).

Nioka, S.

B. Chance, N. G. Wang, M. Maris, S. Nioka, S. Sevick, “Quantification of tissue optical characteristics and hemoglobin desaturation by time- and frequency-resolved multi-wavelength spectrophotometry,” Adv. Exp. Med. Biol. 317, 297–304 (1992).
[CrossRef]

Norisuye, T.

M. Takeda, T. Norisuye, M. Shibayama, “Critical dynamics of cross-linked polymer chains near the gelation threshold,” Macromol. 33, 2909–2915 (2000).
[CrossRef]

Nusrat, A.

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

O’Leary, M. A.

D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solutions and applications,” Proc. Natl. Acad. Sci. USA 91, 4887–4891 (1994).
[CrossRef]

Patterson, M. S.

S. T. Flock, B. C. Wilson, M. S. Patterson, “Total attenuation coefficients and scattering phase functions of tissues and phantom materials at 633 nm,” Med. Phys. 14, 835–841 (1987).
[CrossRef] [PubMed]

Perelman, L. T.

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

Pitris, C.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppard, C. Pitris, J. F. Southern, J. G. Fujimoto, “In vivo endoscopic biopsy with optical coherence tomography,” Science 276, 2037–2039 (1997).
[CrossRef]

Popp, A. K.

M. T. Valentine, A. K. Popp, P. D. Kaplan, D. A. Weitz, “Microscope-based static light scattering apparatus,” Opt. Lett. 26, 890–892 (2001).
[CrossRef]

A. K. Popp, M. T. Valentine, P. D. Kaplan, D. A. Weitz, “Light scattering microscope to investigate heterogeneities of tissues,” in Optical Biopsy III, R. R. Alfano, ed., Proc. SPIE3917, 22–33 (2000).
[CrossRef]

Prahl, S. A.

W.-F. Cheung, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

S. L. Jacques, C. A. Alter, S. A. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309–333 (1987).

Ramanujam, N.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

Richards-Kortum, R.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

Safinya, C. R.

P. Dimon, S. K. Sinha, D. A. Weitz, C. R. Safinya, G. S. Smith, W. A. Varady, H. M. Lindsay, “Structure of aggregated gold colloids,” Phys. Rev. Lett. 57, 595–598 (1986).
[CrossRef] [PubMed]

Schmitt, J. M.

Seiler, M.

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

Sevick, S.

B. Chance, N. G. Wang, M. Maris, S. Nioka, S. Sevick, “Quantification of tissue optical characteristics and hemoglobin desaturation by time- and frequency-resolved multi-wavelength spectrophotometry,” Adv. Exp. Med. Biol. 317, 297–304 (1992).
[CrossRef]

Shen, D.

Shibayama, M.

M. Takeda, T. Norisuye, M. Shibayama, “Critical dynamics of cross-linked polymer chains near the gelation threshold,” Macromol. 33, 2909–2915 (2000).
[CrossRef]

Shields, S.

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

Shimada, T.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnostic of bladder cancer by elastic light scattering,” Laser Surg. Med. 17, 350–357 (1995).
[CrossRef]

Sichirollo, A. E.

Siegel, A. M.

Sinha, S. K.

P. Dimon, S. K. Sinha, D. A. Weitz, C. R. Safinya, G. S. Smith, W. A. Varady, H. M. Lindsay, “Structure of aggregated gold colloids,” Phys. Rev. Lett. 57, 595–598 (1986).
[CrossRef] [PubMed]

Smith, G. S.

P. Dimon, S. K. Sinha, D. A. Weitz, C. R. Safinya, G. S. Smith, W. A. Varady, H. M. Lindsay, “Structure of aggregated gold colloids,” Phys. Rev. Lett. 57, 595–598 (1986).
[CrossRef] [PubMed]

Smithies, D. J.

D. J. Smithies, P. H. Butler, “Modelling the distribution of laser in port wine stains with the Monte Carlo method,” Phys. Med. Biol. 40, 701–731 (1995).
[CrossRef] [PubMed]

Southern, J. F.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppard, C. Pitris, J. F. Southern, J. G. Fujimoto, “In vivo endoscopic biopsy with optical coherence tomography,” Science 276, 2037–2039 (1997).
[CrossRef]

Staerkel, G.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

Takeda, M.

M. Takeda, T. Norisuye, M. Shibayama, “Critical dynamics of cross-linked polymer chains near the gelation threshold,” Macromol. 33, 2909–2915 (2000).
[CrossRef]

Tearney, G. J.

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppard, C. Pitris, J. F. Southern, J. G. Fujimoto, “In vivo endoscopic biopsy with optical coherence tomography,” Science 276, 2037–2039 (1997).
[CrossRef]

Teixeira, J.

J. Teixeira, “Experimental methods for studying fractal aggregates,” in On Growth and Form, H. E. Stanley, N. Ostrowski, eds. (Martinus Nijhoff, Dordrecht, The Netherlands, 1986), pp. 145–162.

Thomsen, S.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

Thomsen, S. L.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

Trappe, V.

Treweek, S. P.

S. P. Treweek, J. C. Barbenel, “Direct measurement of the optical properties of breast skin,” Med. Biol. Eng. Comp. 34, 285–289 (1995).
[CrossRef]

Tromberg, B. J.

J. B. Fishkin, O. Coquoz, E. R. Anderson, M. Brenner, B. J. Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Optics 36, 10–20 (1997).
[CrossRef]

Tuchin, V. V.

V. V. Tuchin, “Light scattering studies of tissues,” Phys. Usp. 40, 494–515 (1997).
[CrossRef]

Valentine, M. T.

M. T. Valentine, A. K. Popp, P. D. Kaplan, D. A. Weitz, “Microscope-based static light scattering apparatus,” Opt. Lett. 26, 890–892 (2001).
[CrossRef]

A. K. Popp, M. T. Valentine, P. D. Kaplan, D. A. Weitz, “Light scattering microscope to investigate heterogeneities of tissues,” in Optical Biopsy III, R. R. Alfano, ed., Proc. SPIE3917, 22–33 (2000).
[CrossRef]

van de Hulst, H. C.

H. C. van de Hulst, Lightscattering by Small Particles (Dover, New York, 1981).

VanDam, J.

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

Varady, W. A.

P. Dimon, S. K. Sinha, D. A. Weitz, C. R. Safinya, G. S. Smith, W. A. Varady, H. M. Lindsay, “Structure of aggregated gold colloids,” Phys. Rev. Lett. 57, 595–598 (1986).
[CrossRef] [PubMed]

Videen, G.

G. Videen, D. Ngo, “Light scattering multipole solution for a cell,” J. Biomed. Opt. 3, 212–220 (1998).
[CrossRef] [PubMed]

Wallace, M.

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

Wang, N. G.

B. Chance, N. G. Wang, M. Maris, S. Nioka, S. Sevick, “Quantification of tissue optical characteristics and hemoglobin desaturation by time- and frequency-resolved multi-wavelength spectrophotometry,” Adv. Exp. Med. Biol. 317, 297–304 (1992).
[CrossRef]

Wang, R. K. K.

R. K. K. Wang, “Modelling optical properties of soft tissue by fractal distribution of scatterers,” J. Mod. Opt. 47, 103–120 (2000).

Weitz, D. A.

M. T. Valentine, A. K. Popp, P. D. Kaplan, D. A. Weitz, “Microscope-based static light scattering apparatus,” Opt. Lett. 26, 890–892 (2001).
[CrossRef]

P. D. Kaplan, V. Trappe, D. A. Weitz, “Light scattering microscope,” Appl. Opt. 38, 4151–4157 (1999).
[CrossRef]

P. Dimon, S. K. Sinha, D. A. Weitz, C. R. Safinya, G. S. Smith, W. A. Varady, H. M. Lindsay, “Structure of aggregated gold colloids,” Phys. Rev. Lett. 57, 595–598 (1986).
[CrossRef] [PubMed]

A. K. Popp, M. T. Valentine, P. D. Kaplan, D. A. Weitz, “Light scattering microscope to investigate heterogeneities of tissues,” in Optical Biopsy III, R. R. Alfano, ed., Proc. SPIE3917, 22–33 (2000).
[CrossRef]

Welch, A. J.

W.-F. Cheung, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

Wilson, B. C.

S. T. Flock, B. C. Wilson, M. S. Patterson, “Total attenuation coefficients and scattering phase functions of tissues and phantom materials at 633 nm,” Med. Phys. 14, 835–841 (1987).
[CrossRef] [PubMed]

Wright, T.

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

Yodh, A. G.

H. Liu, D. A Boas, Y. Zhang, A. G. Yodh, B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solutions and applications,” Proc. Natl. Acad. Sci. USA 91, 4887–4891 (1994).
[CrossRef]

Zhang, Y.

H. Liu, D. A Boas, Y. Zhang, A. G. Yodh, B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

Zonios, G.

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

Adv. Exp. Med. Biol. (1)

B. Chance, N. G. Wang, M. Maris, S. Nioka, S. Sevick, “Quantification of tissue optical characteristics and hemoglobin desaturation by time- and frequency-resolved multi-wavelength spectrophotometry,” Adv. Exp. Med. Biol. 317, 297–304 (1992).
[CrossRef]

Am. J. Phys. (1)

W. S. Bickel, W. M. Bailey, “Stokes vectors, Mueller matrices and polarized light,” Am. J. Phys. 53, 468–478 (1985).
[CrossRef]

Appl. Opt. (7)

Appl. Optics (1)

J. B. Fishkin, O. Coquoz, E. R. Anderson, M. Brenner, B. J. Tromberg, “Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject,” Appl. Optics 36, 10–20 (1997).
[CrossRef]

Astrophys. J. (1)

L. G. Henyey, J. L. Greenstein, “Diffuse radiation in the galaxy,” Astrophys. J. 93, 70–83 (1941).
[CrossRef]

Cytometry (1)

E. Luther, L. A. Kamentsky, “Resolution of mitotic cells using laser scanning cytometry,” Cytometry 23, 272–278 (1996).
[CrossRef] [PubMed]

IEEE J. Quantum Electron. (1)

W.-F. Cheung, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990).
[CrossRef]

J. Biomed. Opt. (1)

G. Videen, D. Ngo, “Light scattering multipole solution for a cell,” J. Biomed. Opt. 3, 212–220 (1998).
[CrossRef] [PubMed]

J. Mod. Opt. (1)

R. K. K. Wang, “Modelling optical properties of soft tissue by fractal distribution of scatterers,” J. Mod. Opt. 47, 103–120 (2000).

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

Laser Surg. Med. (1)

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnostic of bladder cancer by elastic light scattering,” Laser Surg. Med. 17, 350–357 (1995).
[CrossRef]

Lasers Life Sci. (1)

S. L. Jacques, C. A. Alter, S. A. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309–333 (1987).

Lasers Surg. Med. (1)

N. Ramanujam, M. Follen Mitchell, A. Mahadevan, S. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo,” Lasers Surg. Med. 19, 46–62 (1996).
[CrossRef] [PubMed]

Macromol. (1)

M. Takeda, T. Norisuye, M. Shibayama, “Critical dynamics of cross-linked polymer chains near the gelation threshold,” Macromol. 33, 2909–2915 (2000).
[CrossRef]

Med. Biol. Eng. Comp. (1)

S. P. Treweek, J. C. Barbenel, “Direct measurement of the optical properties of breast skin,” Med. Biol. Eng. Comp. 34, 285–289 (1995).
[CrossRef]

Med. Phys. (1)

S. T. Flock, B. C. Wilson, M. S. Patterson, “Total attenuation coefficients and scattering phase functions of tissues and phantom materials at 633 nm,” Med. Phys. 14, 835–841 (1987).
[CrossRef] [PubMed]

Opt. Eng. (1)

F. Bevilacqua, P. Marquet, C. Depreursinge, E. B. De Haller, “Determination of reduced scattering and absorption coefficients by a single charge-coupled device array. II. Measurements on biological tissue,” Opt. Eng. 34, 2064–2069 (1995).
[CrossRef]

Opt. Express (2)

Opt. Lett. (3)

Photchem. Photobiol. (1)

N. Ramanujam, M. Follen Mitchell, A. Mahadevan-Janson, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, R. Richards-Kortum, “Cervical cancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple wave lengths,” Photchem. Photobiol. 64, 720–735 (1996).
[CrossRef]

Phys. Med. Biol. (3)

H. Liu, D. A Boas, Y. Zhang, A. G. Yodh, B. Chance, “Determination of optical properties and blood oxygenation in tissue using continuous NIR light,” Phys. Med. Biol. 40, 1983–1993 (1995).
[CrossRef] [PubMed]

A. H. Hielscher, R. E. Alcouffe, R. L. Barbour, “Comparison of finite-difference transport and diffusion calculations for photon migration in homogenous and heterogenous tissues,” Phys. Med. Biol. 43, 1285–1302 (1998).
[CrossRef] [PubMed]

D. J. Smithies, P. H. Butler, “Modelling the distribution of laser in port wine stains with the Monte Carlo method,” Phys. Med. Biol. 40, 701–731 (1995).
[CrossRef] [PubMed]

Phys. Rev. Lett. (2)

P. Dimon, S. K. Sinha, D. A. Weitz, C. R. Safinya, G. S. Smith, W. A. Varady, H. M. Lindsay, “Structure of aggregated gold colloids,” Phys. Rev. Lett. 57, 595–598 (1986).
[CrossRef] [PubMed]

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

Phys. Usp. (1)

V. V. Tuchin, “Light scattering studies of tissues,” Phys. Usp. 40, 494–515 (1997).
[CrossRef]

Proc. Natl. Acad. Sci. USA (1)

D. A. Boas, M. A. O’Leary, B. Chance, A. G. Yodh, “Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solutions and applications,” Proc. Natl. Acad. Sci. USA 91, 4887–4891 (1994).
[CrossRef]

Science (1)

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppard, C. Pitris, J. F. Southern, J. G. Fujimoto, “In vivo endoscopic biopsy with optical coherence tomography,” Science 276, 2037–2039 (1997).
[CrossRef]

Other (5)

A. K. Popp, M. T. Valentine, P. D. Kaplan, D. A. Weitz, “Light scattering microscope to investigate heterogeneities of tissues,” in Optical Biopsy III, R. R. Alfano, ed., Proc. SPIE3917, 22–33 (2000).
[CrossRef]

T. Nicolai, D. Durand, J.-C. Gimel, “Scattering properties and modelling of aggregating and gelling systems,” in Lightscattering: Principles and Development, W. Brown, ed. (Oxford University Press, New York, 1996).

J. Teixeira, “Experimental methods for studying fractal aggregates,” in On Growth and Form, H. E. Stanley, N. Ostrowski, eds. (Martinus Nijhoff, Dordrecht, The Netherlands, 1986), pp. 145–162.

B. Mandelbrot, The Fractal Geometry of Nature (Freeman, New York, 1982).

H. C. van de Hulst, Lightscattering by Small Particles (Dover, New York, 1981).

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (9)

Fig. 1
Fig. 1

Real-space images (left) and scattering patterns (right) from different tissues. The real-space images show a field of view of 60-μm width, displaying the surface onto which the incident laser beam is directed. The scattering patterns are intensity distributions and show bright spots for high scattered intensity. In (a) Rana Sartorius muscle fibers are oriented parallel to the surface of the coverslip (“striated muscle ‖”). Influence of orientation of the fibers on image and scattering patterns can be observed by a comparison with (b), a striated muscle sample mostly cross-sectionally oriented to the surface of the coverslip (“striated muscle ⊥”). (c) and (d) Real-space images and scattering patterns from lung smooth muscle and skin (stratum corneum), respectively. In skin, the amount of light scattered on the left-hand side of the beam block is much higher than the intensity on the other side, another manifestation of anisotropy. The smooth muscle scatters light more isotropically.

Fig. 2
Fig. 2

Schematic of the SLS microscope. A laser beam from an Ar+-ion laser (Coherent Innova 304, 514.5 nm), attenuated to typically 50 μW, is coupled into the illumination path of a commercially available inverted microscope (Leica DM-IRBE). A photodiode monitors the incoming beam intensity, which allows us to correct for differences in input intensity. The laser beam is collimated at the sample plane to a beam diameter of 70 μm. The conventional objective lens of the microscope (plan-apochromatic, 100× magnification) collects both forward-scattered and transmitted light. Pixelized scattered-light intensity distributions are measured at a 16-bit cooled CCD detector (Princeton Instruments, Model CCD-512SF, 512 × 512 array of 24-μm-sized square pixels) located on an extension of the microscope. The scattering patterns on the detector are enlarged images of the back focal plane of the objective (BFPO), with the transmitted beam blocked. In addition, the same regions of our samples are imaged by means of conventional bright-field microscopy by diverting a portion of the illuminating light to the side camera port equipped with a video camera.

Fig. 3
Fig. 3

Henyey-Greenstein fits of the form factors 〈I(θ)〉φ for the interval 0.995 ≥ cos θ ≥ 0.9, with the method of Jacques et al.20 The systematic deviations from the small-angle Henyey-Greenstein parameters at larger angles are matched by previous studies. These data show the compatibility of averages of our measurements to bulk measurements that inherently average over a large illumination area.

Fig. 4
Fig. 4

Slice-averaged form factors of different tissue types show a power-law decay I(q) ∼ q -z . The decay law for skin (z = 3.6) is substantially different than for the other tissue types (z ≈ 2.5).

Fig. 5
Fig. 5

Radial intensity distribution I(φ) of a single measurement for each investigated tissue type. The skin sample, as well as the parallel oriented muscle sample, shows a large amount of scattering dependent on the azimuthal angle. Samples showing unordered structures have by far less anisotropic scattering.

Fig. 6
Fig. 6

Composition of azimuthal light scattering of the investigated tissues. Skin (stratum corneum) shows the highest asymmetric scattering component of all investigated tissues; striated muscle and lung, the lowest. Up to 50% of the scattered light is scattered asymmetrically. The rest is symmetric or static scattering owing to a random distribution of scatterers (“random”). All investigated tissues suggest that amounts of more than 30% of the scattering are not due to a homogenous distribution of particles. Parallel-aligned striated muscle has the highest rotation-variant symmetric scattering amplitude; skin (stratum corneum), the lowest.

Fig. 7
Fig. 7

Distribution of random anisotropic scattering for the two tissue types separable best according to the scattering component that is due to random scatterer distribution. The probability of obtaining a certain “random” scattering fraction is shown versus the fraction itself.

Fig. 8
Fig. 8

Eigenvalues of the PCA (right-hand axis) represent the variation of scores of the PCA analysis, performed for all tissues together. They show the pronounced importance of the first four components and can be scaled as percentage of variation (left-hand axis). The figure shows that more than 90% of the variation of the data is represented by the first four principal components.

Fig. 9
Fig. 9

Scatter plot of PC1 versus PC2: This plot shows the comparably strong variation in principal components of the ordered structures. Much smaller variation is observed for principal components of cross-sectionally oriented striated muscle and of lung smooth muscle, which have no directional order.

Tables (2)

Tables Icon

Table 1 Average Tissue-Scattering Propertiesa

Tables Icon

Table 2 Results of the Cluster Analysisa

Equations (4)

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

θ=arcsinnGnS Cδx.
Iθ=I01-gHG21+gHG2-2gHG cos θ3/2.
Iφ=m=- cm exp-imφ.
=m2k |cm|m=-,  |cm|, k0.

Metrics