Abstract

We have examined the light-scattering properties of inhomogeneous biological cells through a combination of theoretical simulations and goniometric measurements. A finite-difference time-domain (FDTD) technique was used to compute intensity as a function of scattering angle for cells containing multiple organelles and spatially varying index of refraction profiles. An automated goniometer was constructed to measure the scattering properties of dilute cell suspensions. Measurements compared favorably with FDTD predictions. FDTD and experimental results indicate that scattering properties are strongly influenced by cellular biochemical and morphological structure.

© 1999 Optical Society of America

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    [CrossRef] [PubMed]

1998 (6)

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

A. Nilsson, P. Alsholm, A. Karlsson, S. Andresson-Engels, “T-matrix computations of light scattering by red blood cells,” Appl. Opt. 37, 2735–2748 (1998).
[CrossRef]

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

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

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

C. Smithpeter, A. Dunn, R. Drezek, T. Collier, R. Richards-Kortum, “Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents, and limits of contrast,” J. Biomed. Opt. 3, 429–436 (1998).
[CrossRef] [PubMed]

1997 (1)

1996 (3)

A. Dunn, R. Richards-Kortum, “Three-dimensional computation of light scattering from cells,” IEEE J. Sel. Top. Quantum Electron. 2, 898–905 (1996).
[CrossRef]

H. Liu, B. Beauvoit, M. Kimura, B. Chance, “Dependence of tissue optical properties on solute-induced changes in refractive index and osmolarity,” J. Biomed. Opt. 1, 200–211 (1996).
[CrossRef] [PubMed]

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

1995 (2)

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

M. Rajadhyaksha, M. Grossman, D. Esterwitz, R. Webb, R. Anderson, “In-vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

1994 (2)

1993 (2)

G. Streekstra, A. Hoekstra, E. Nijhof, R. Heethaar, “Light scattering by red blood cells in ektacytometry: Fraunhofer versus anomalous diffraction,” Appl. Opt. 32, 2266–2272 (1993).
[CrossRef] [PubMed]

J. Izaat, M. Hee, D. Huang, A. Swanson, C. Lin, J. Schuman, C. Puliafito, J. Fujimoto, “Micron-resolution biomedical engineering with optical coherence tomography,” Opt. Photon. News 4, 14–19 (1993).
[CrossRef]

1992 (1)

C. Boone, G. Kelloff, V. Steele, “The natural history of intraepithelial neoplasia: relevance to the search for intermediate endpoint biomarkers,” J. Cell. Biochem. 16, 23–26 (1992).
[CrossRef]

1984 (2)

J. Valkenburg, C. Woldringh, “Phase separation between nucleoid and cytoplasm in E coli as defined by immersive refractometry,” J. Bacteriol. 160, 1151–1157 (1984).
[PubMed]

Z. Liao, H. Wong, B. Yang, Y. Yuan, “A transmitting boundary for transient wave analysis,” Sci. Sin. Ser A 27, 1063–1076 (1984).

1983 (1)

Y. Yarker, R. Aspden, D. Hukins, “Birefringence of articular cartilage and the distribution of collagen fibril orientations,” Connect. Tissue Res. 11, 207–213 (1983).
[CrossRef]

1974 (1)

A. Brunsting, P. Mullaney, “Differential light scattering from spherical mammalian cells,” Biophys. J. 14, 439–453 (1974).
[CrossRef] [PubMed]

1972 (1)

1957 (1)

Alsholm, P.

Anderson, E.

Anderson, M.

M. Anderson, J. Jordon, A. Morse, F. Sharp, A Text and Atlas of Integrated Colposcopy (Mosby, St. Louis, Mo., 1993).

Anderson, R.

M. Rajadhyaksha, M. Grossman, D. Esterwitz, R. Webb, R. Anderson, “In-vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

I. Vitkin, J. Woolsey, B. Wilson, R. Anderson, “Optical and thermal characterization of natural (sepia oficinalis) melanin,” Photochem. Photobio. 59, 455–462 (1994).
[CrossRef]

Andresson-Engels, S.

Aspden, R.

Y. Yarker, R. Aspden, D. Hukins, “Birefringence of articular cartilage and the distribution of collagen fibril orientations,” Connect. Tissue Res. 11, 207–213 (1983).
[CrossRef]

Backman, V.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Barer, R.

Beauvoit, B.

H. Liu, B. Beauvoit, M. Kimura, B. Chance, “Dependence of tissue optical properties on solute-induced changes in refractive index and osmolarity,” J. Biomed. Opt. 1, 200–211 (1996).
[CrossRef] [PubMed]

B. Beauvoit, T. Kitai, B. Chance, “Time-resolved spectroscopy of mitochondria, cells, and rat tissue under normal and pathological conditions,” in Photon Transport in Highly Scattering Tissue, S. Avrillier, B. Chance, G. J. Mueller, A. V. Priezzhev, V. V. Tuchin, eds., Proc. SPIE2326, 127–136 (1995).
[CrossRef]

Bigio, I.

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

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

Boone, C.

C. Boone, G. Kelloff, V. Steele, “The natural history of intraepithelial neoplasia: relevance to the search for intermediate endpoint biomarkers,” J. Cell. Biochem. 16, 23–26 (1992).
[CrossRef]

Boyer, J.

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

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

Brenner, M.

Brunsting, A.

A. Brunsting, P. Mullaney, “Differential light scattering from spherical mammalian cells,” Biophys. J. 14, 439–453 (1974).
[CrossRef] [PubMed]

A. Brunsting, P. Mullaney, “Light scattering from coated spheres: model for biological cells,” Appl. Opt. 11, 675–680 (1972).
[CrossRef] [PubMed]

Carneiro, J.

L. Junquerira, J. Carneiro, O. Kelly, Basic Histology (Appleton and Lange, New York, 1992).

Chance, B.

H. Liu, B. Beauvoit, M. Kimura, B. Chance, “Dependence of tissue optical properties on solute-induced changes in refractive index and osmolarity,” J. Biomed. Opt. 1, 200–211 (1996).
[CrossRef] [PubMed]

B. Beauvoit, T. Kitai, B. Chance, “Time-resolved spectroscopy of mitochondria, cells, and rat tissue under normal and pathological conditions,” in Photon Transport in Highly Scattering Tissue, S. Avrillier, B. Chance, G. J. Mueller, A. V. Priezzhev, V. V. Tuchin, eds., Proc. SPIE2326, 127–136 (1995).
[CrossRef]

Collier, T.

C. Smithpeter, A. Dunn, R. Drezek, T. Collier, R. Richards-Kortum, “Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents, and limits of contrast,” J. Biomed. Opt. 3, 429–436 (1998).
[CrossRef] [PubMed]

Conn, R.

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

Coquoz, O.

Crawford, J.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Drezek, R.

C. Smithpeter, A. Dunn, R. Drezek, T. Collier, R. Richards-Kortum, “Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents, and limits of contrast,” J. Biomed. Opt. 3, 429–436 (1998).
[CrossRef] [PubMed]

R. Drezek, “Finite difference time domain simulations and goniometric measurements of light scattering from cells,” M.S. thesis (University of Texas at Austin, Austin, Texas, 1998).

Dunn, A.

C. Smithpeter, A. Dunn, R. Drezek, T. Collier, R. Richards-Kortum, “Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents, and limits of contrast,” J. Biomed. Opt. 3, 429–436 (1998).
[CrossRef] [PubMed]

A. Dunn, R. Richards-Kortum, “Three-dimensional computation of light scattering from cells,” IEEE J. Sel. Top. Quantum Electron. 2, 898–905 (1996).
[CrossRef]

A. Dunn, “Light scattering properties of cells,” Ph.D. dissertation (University of Texas at Austin, Austin, Texas, 1997).

Eick, A.

Esterwitz, D.

M. Rajadhyaksha, M. Grossman, D. Esterwitz, R. Webb, R. Anderson, “In-vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

Fantini, S.

Feld, M.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Fishkin, J.

Franceschini, S.

Freyer, J.

Fujimoto, J.

J. Izaat, M. Hee, D. Huang, A. Swanson, C. Lin, J. Schuman, C. Puliafito, J. Fujimoto, “Micron-resolution biomedical engineering with optical coherence tomography,” Opt. Photon. News 4, 14–19 (1993).
[CrossRef]

Gratton, E.

Grossman, M.

M. Rajadhyaksha, M. Grossman, D. Esterwitz, R. Webb, R. Anderson, “In-vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

Hamano, T.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Hecht, E.

E. Hecht, Optics (Addison-Wesley, Reading, Mass., 1987).

Hee, M.

J. Izaat, M. Hee, D. Huang, A. Swanson, C. Lin, J. Schuman, C. Puliafito, J. Fujimoto, “Micron-resolution biomedical engineering with optical coherence tomography,” Opt. Photon. News 4, 14–19 (1993).
[CrossRef]

Heethaar, R.

Hielscher, A.

Hoekstra, A.

Huang, D.

J. Izaat, M. Hee, D. Huang, A. Swanson, C. Lin, J. Schuman, C. Puliafito, J. Fujimoto, “Micron-resolution biomedical engineering with optical coherence tomography,” Opt. Photon. News 4, 14–19 (1993).
[CrossRef]

Hukins, D.

Y. Yarker, R. Aspden, D. Hukins, “Birefringence of articular cartilage and the distribution of collagen fibril orientations,” Connect. Tissue Res. 11, 207–213 (1983).
[CrossRef]

Itzkan, I.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Izaat, J.

J. Izaat, M. Hee, D. Huang, A. Swanson, C. Lin, J. Schuman, C. Puliafito, J. Fujimoto, “Micron-resolution biomedical engineering with optical coherence tomography,” Opt. Photon. News 4, 14–19 (1993).
[CrossRef]

Johnson, T.

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

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

Jordon, J.

M. Anderson, J. Jordon, A. Morse, F. Sharp, A Text and Atlas of Integrated Colposcopy (Mosby, St. Louis, Mo., 1993).

Junquerira, L.

L. Junquerira, J. Carneiro, O. Kelly, Basic Histology (Appleton and Lange, New York, 1992).

Karlsson, A.

Kelloff, G.

C. Boone, G. Kelloff, V. Steele, “The natural history of intraepithelial neoplasia: relevance to the search for intermediate endpoint biomarkers,” J. Cell. Biochem. 16, 23–26 (1992).
[CrossRef]

Kelly, O.

L. Junquerira, J. Carneiro, O. Kelly, Basic Histology (Appleton and Lange, New York, 1992).

Kimura, M.

H. Liu, B. Beauvoit, M. Kimura, B. Chance, “Dependence of tissue optical properties on solute-induced changes in refractive index and osmolarity,” J. Biomed. Opt. 1, 200–211 (1996).
[CrossRef] [PubMed]

Kitai, T.

B. Beauvoit, T. Kitai, B. Chance, “Time-resolved spectroscopy of mitochondria, cells, and rat tissue under normal and pathological conditions,” in Photon Transport in Highly Scattering Tissue, S. Avrillier, B. Chance, G. J. Mueller, A. V. Priezzhev, V. V. Tuchin, eds., Proc. SPIE2326, 127–136 (1995).
[CrossRef]

Kumar, G.

Liao, Z.

Z. Liao, H. Wong, B. Yang, Y. Yuan, “A transmitting boundary for transient wave analysis,” Sci. Sin. Ser A 27, 1063–1076 (1984).

Lima, C.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Lin, C.

J. Izaat, M. Hee, D. Huang, A. Swanson, C. Lin, J. Schuman, C. Puliafito, J. Fujimoto, “Micron-resolution biomedical engineering with optical coherence tomography,” Opt. Photon. News 4, 14–19 (1993).
[CrossRef]

Liu, H.

H. Liu, B. Beauvoit, M. Kimura, B. Chance, “Dependence of tissue optical properties on solute-induced changes in refractive index and osmolarity,” J. Biomed. Opt. 1, 200–211 (1996).
[CrossRef] [PubMed]

Maier, J.

Manoharan, R.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Morse, A.

M. Anderson, J. Jordon, A. Morse, F. Sharp, A Text and Atlas of Integrated Colposcopy (Mosby, St. Louis, Mo., 1993).

Mourant, J.

Mullaney, P.

A. Brunsting, P. Mullaney, “Differential light scattering from spherical mammalian cells,” Biophys. J. 14, 439–453 (1974).
[CrossRef] [PubMed]

A. Brunsting, P. Mullaney, “Light scattering from coated spheres: model for biological cells,” Appl. Opt. 11, 675–680 (1972).
[CrossRef] [PubMed]

Ngo, D.

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

Nijhof, E.

Nilsson, A.

Nustrat, A.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Perelman, L.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Puliafito, C.

J. Izaat, M. Hee, D. Huang, A. Swanson, C. Lin, J. Schuman, C. Puliafito, J. Fujimoto, “Micron-resolution biomedical engineering with optical coherence tomography,” Opt. Photon. News 4, 14–19 (1993).
[CrossRef]

Rajadhyaksha, M.

M. Rajadhyaksha, M. Grossman, D. Esterwitz, R. Webb, R. Anderson, “In-vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

Richards-Kortum, R.

C. Smithpeter, A. Dunn, R. Drezek, T. Collier, R. Richards-Kortum, “Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents, and limits of contrast,” J. Biomed. Opt. 3, 429–436 (1998).
[CrossRef] [PubMed]

A. Dunn, R. Richards-Kortum, “Three-dimensional computation of light scattering from cells,” IEEE J. Sel. Top. Quantum Electron. 2, 898–905 (1996).
[CrossRef]

Schmitt, J.

Schuman, J.

J. Izaat, M. Hee, D. Huang, A. Swanson, C. Lin, J. Schuman, C. Puliafito, J. Fujimoto, “Micron-resolution biomedical engineering with optical coherence tomography,” Opt. Photon. News 4, 14–19 (1993).
[CrossRef]

Seiler, M.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Sharp, F.

M. Anderson, J. Jordon, A. Morse, F. Sharp, A Text and Atlas of Integrated Colposcopy (Mosby, St. Louis, Mo., 1993).

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Shields, S.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Shimada, T.

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

Smithpeter, C.

C. Smithpeter, A. Dunn, R. Drezek, T. Collier, R. Richards-Kortum, “Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents, and limits of contrast,” J. Biomed. Opt. 3, 429–436 (1998).
[CrossRef] [PubMed]

Steele, V.

C. Boone, G. Kelloff, V. Steele, “The natural history of intraepithelial neoplasia: relevance to the search for intermediate endpoint biomarkers,” J. Cell. Biochem. 16, 23–26 (1992).
[CrossRef]

Streekstra, G.

Swanson, A.

J. Izaat, M. Hee, D. Huang, A. Swanson, C. Lin, J. Schuman, C. Puliafito, J. Fujimoto, “Micron-resolution biomedical engineering with optical coherence tomography,” Opt. Photon. News 4, 14–19 (1993).
[CrossRef]

Tromberg, B.

Valkenburg, J.

J. Valkenburg, C. Woldringh, “Phase separation between nucleoid and cytoplasm in E coli as defined by immersive refractometry,” J. Bacteriol. 160, 1151–1157 (1984).
[PubMed]

Van Dam, J.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

van de Hulst, H. C.

H. C. van de Hulst, Light Scattering by Small Particles (Dover, New York, 1957).

Videen, G.

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

Vitkin, I.

I. Vitkin, J. Woolsey, B. Wilson, R. Anderson, “Optical and thermal characterization of natural (sepia oficinalis) melanin,” Photochem. Photobio. 59, 455–462 (1994).
[CrossRef]

Walker, S.

Wallace, M.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Webb, R.

M. Rajadhyaksha, M. Grossman, D. Esterwitz, R. Webb, R. Anderson, “In-vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

Wilson, B.

I. Vitkin, J. Woolsey, B. Wilson, R. Anderson, “Optical and thermal characterization of natural (sepia oficinalis) melanin,” Photochem. Photobio. 59, 455–462 (1994).
[CrossRef]

Woldringh, C.

J. Valkenburg, C. Woldringh, “Phase separation between nucleoid and cytoplasm in E coli as defined by immersive refractometry,” J. Bacteriol. 160, 1151–1157 (1984).
[PubMed]

Wong, H.

Z. Liao, H. Wong, B. Yang, Y. Yuan, “A transmitting boundary for transient wave analysis,” Sci. Sin. Ser A 27, 1063–1076 (1984).

Woolsey, J.

I. Vitkin, J. Woolsey, B. Wilson, R. Anderson, “Optical and thermal characterization of natural (sepia oficinalis) melanin,” Photochem. Photobio. 59, 455–462 (1994).
[CrossRef]

Yang, B.

Z. Liao, H. Wong, B. Yang, Y. Yuan, “A transmitting boundary for transient wave analysis,” Sci. Sin. Ser A 27, 1063–1076 (1984).

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Y. Yarker, R. Aspden, D. Hukins, “Birefringence of articular cartilage and the distribution of collagen fibril orientations,” Connect. Tissue Res. 11, 207–213 (1983).
[CrossRef]

Yuan, Y.

Z. Liao, H. Wong, B. Yang, Y. Yuan, “A transmitting boundary for transient wave analysis,” Sci. Sin. Ser A 27, 1063–1076 (1984).

Zonios, G.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Appl. Opt. (6)

Biophys. J. (1)

A. Brunsting, P. Mullaney, “Differential light scattering from spherical mammalian cells,” Biophys. J. 14, 439–453 (1974).
[CrossRef] [PubMed]

Connect. Tissue Res. (1)

Y. Yarker, R. Aspden, D. Hukins, “Birefringence of articular cartilage and the distribution of collagen fibril orientations,” Connect. Tissue Res. 11, 207–213 (1983).
[CrossRef]

IEEE J. Sel. Top. Quantum Electron. (1)

A. Dunn, R. Richards-Kortum, “Three-dimensional computation of light scattering from cells,” IEEE J. Sel. Top. Quantum Electron. 2, 898–905 (1996).
[CrossRef]

J. Bacteriol. (1)

J. Valkenburg, C. Woldringh, “Phase separation between nucleoid and cytoplasm in E coli as defined by immersive refractometry,” J. Bacteriol. 160, 1151–1157 (1984).
[PubMed]

J. Biomed. Opt. (3)

H. Liu, B. Beauvoit, M. Kimura, B. Chance, “Dependence of tissue optical properties on solute-induced changes in refractive index and osmolarity,” J. Biomed. Opt. 1, 200–211 (1996).
[CrossRef] [PubMed]

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

C. Smithpeter, A. Dunn, R. Drezek, T. Collier, R. Richards-Kortum, “Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents, and limits of contrast,” J. Biomed. Opt. 3, 429–436 (1998).
[CrossRef] [PubMed]

J. Cell. Biochem. (1)

C. Boone, G. Kelloff, V. Steele, “The natural history of intraepithelial neoplasia: relevance to the search for intermediate endpoint biomarkers,” J. Cell. Biochem. 16, 23–26 (1992).
[CrossRef]

J. Invest. Dermatol. (1)

M. Rajadhyaksha, M. Grossman, D. Esterwitz, R. Webb, R. Anderson, “In-vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol. 104, 946–952 (1995).
[CrossRef] [PubMed]

J. Opt. Soc. Am. (1)

Lasers Surg. Med. (1)

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

Opt. Lett. (2)

Opt. Photon. News (1)

J. Izaat, M. Hee, D. Huang, A. Swanson, C. Lin, J. Schuman, C. Puliafito, J. Fujimoto, “Micron-resolution biomedical engineering with optical coherence tomography,” Opt. Photon. News 4, 14–19 (1993).
[CrossRef]

Photochem. Photobio. (1)

I. Vitkin, J. Woolsey, B. Wilson, R. Anderson, “Optical and thermal characterization of natural (sepia oficinalis) melanin,” Photochem. Photobio. 59, 455–462 (1994).
[CrossRef]

Phys. Rev. Lett. (1)

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nustrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, M. 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]

Sci. Sin. Ser A (1)

Z. Liao, H. Wong, B. Yang, Y. Yuan, “A transmitting boundary for transient wave analysis,” Sci. Sin. Ser A 27, 1063–1076 (1984).

Other (7)

E. Hecht, Optics (Addison-Wesley, Reading, Mass., 1987).

B. Beauvoit, T. Kitai, B. Chance, “Time-resolved spectroscopy of mitochondria, cells, and rat tissue under normal and pathological conditions,” in Photon Transport in Highly Scattering Tissue, S. Avrillier, B. Chance, G. J. Mueller, A. V. Priezzhev, V. V. Tuchin, eds., Proc. SPIE2326, 127–136 (1995).
[CrossRef]

L. Junquerira, J. Carneiro, O. Kelly, Basic Histology (Appleton and Lange, New York, 1992).

H. C. van de Hulst, Light Scattering by Small Particles (Dover, New York, 1957).

M. Anderson, J. Jordon, A. Morse, F. Sharp, A Text and Atlas of Integrated Colposcopy (Mosby, St. Louis, Mo., 1993).

R. Drezek, “Finite difference time domain simulations and goniometric measurements of light scattering from cells,” M.S. thesis (University of Texas at Austin, Austin, Texas, 1998).

A. Dunn, “Light scattering properties of cells,” Ph.D. dissertation (University of Texas at Austin, Austin, Texas, 1997).

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Figures (15)

Fig. 1
Fig. 1

Schematic diagram of a goniometer built to measure light scattering as a function of angle.

Fig. 2
Fig. 2

Validation of the FDTD code. Comparison of FDTD results with Mie theory predictions for a 5-µm sphere (m = 1.04; λ = 900 nm).

Fig. 3
Fig. 3

Influence of nuclear structure on scattering pattern. Low-angle scatter is shown on a linear scale. There were no visible differences in scattering patterns at angles over 20°.

Fig. 4
Fig. 4

(a) Influence of N/C ratio on scattering cross section. (b) Influence of relative N/C refractive index on scattering cross section.

Fig. 5
Fig. 5

Influence of internal structure on scattering pattern. Three simulations are shown: a cell containing organelles of refractive index and size consistent with melanin (8.5% volume fraction), a cell containing organelles with index and size of mitochondria (8.5% volume fraction), and an amelanotic cell containing organelles with index and size of mitochondria but a smaller volume fraction (3%).

Fig. 6
Fig. 6

Comparison of scattering pattern from a cell with a specified internal structure (cytoplasm, nucleus, and organelles) with a cell with randomly assigned dielectric structure. Mean index of both cells is identical, n = 1.4.

Fig. 7
Fig. 7

Scattering pattern of two cells with randomly assigned dielectric structure. The spatial frequency of index fluctuations is higher in the top curve (labeled high frequency) than in the lower curve (labeled low frequency). Mean refractive index is the same for both cells.

Fig. 8
Fig. 8

(a) As a visible demonstration of reduction in scattering that is achievable by immersing cells in a solution of like index, two cuvettes are shown with equal concentrations of cells. In the cuvette on the left, cells are immersed in saline (n = 1.33); in the cuvette on the right, cells are immersed in a higher-index albumin solution (n = 1.37). Index matching reduces the scattering, and the text behind the cuvette is readable. (b) Influence of external medium on scattering pattern. The scattering patterns of the same cell immersed in media of varying index (n = 1.35, n = 1.37) are compared.

Fig. 9
Fig. 9

Scattering pattern of a collagen fiber. Curves shown are for three orientations of the collagen fiber with respect to an incoming plane wave along the +z axis. The collagen fibers were oriented along the x, y, and z axes, respectively.

Fig. 10
Fig. 10

Wavelength dependence of scattering pattern. The normalized scattering pattern of one cell is shown for three wavelengths (514 nm, 780 nm, 2 µm).

Fig. 11
Fig. 11

Scattering cross section versus wavelength for nucleus surrounded by cytoplasm. Three cases are shown. First, the van de Hulst approximation (anomalous diffraction approximation) is used to calculate scattering for a 5-µm nucleus (m = 1.04; n cytoplasm = 1.36). Second, the FDTD model is used to calculate scattering for a homogeneous 5-µm nucleus (m = 1.04; n cytoplasm = 1.36). Third, the FDTD model is used to calculate scattering for a heterogeneous 5-µm nucleus, with mean relative refractive index identical to the homogeneous case and spatial fluctuations ranging from 2 to 30 µm-1.

Fig. 12
Fig. 12

Validation of goniometer performance. Comparison of measured data and Mie theory predictions for 0.2-µm polystyrene spheres.

Fig. 13
Fig. 13

Comparison of measured and FDTD data for OVCA-420 cells. The FDTD data are the average over two orientations of the cell with respect to incident light.

Fig. 14
Fig. 14

Comparison of measured scattering pattern with Mie theory (10-µm sphere, m = 1.04, λ = 612 nm) and Henyey–Greenstein predictions. Asymmetry value of g = 0.97, calculated from measured data, was used in the Henyey–Greenstein model.

Fig. 15
Fig. 15

Measurements of a cervical cancer cell line before and after addition of 6% acetic acid (AA).

Tables (1)

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Table 1 Index of Refraction Values Obtained from the Literature

Equations (1)

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σsλ, l=12 πl21-sin2δ/λδ/λ+sinδ/λδ/λ2,

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