Abstract

We have studied the optical properties of mammalian cell suspensions to provide a mechanistic basis for interpreting the optical properties of tissues in vivo. Measurements of the wavelength dependence of the reduced scattering coefficient and measurements of the phase function demonstrated that there is a distribution of scatterer sizes. The volumes of the scatterers are equivalent to those of spheres with diameters in the range between ∼0.4 and 2.0 μm. Measurements of isolated organelles indicate that mitochondria and other similarly sized organelles are responsible for scattering at large angles, whereas nuclei are responsible for small-angle scattering. Therefore optical diagnostics are expected to be sensitive to organelle morphology but not directly to the size and shape of the cells.

© 1998 Optical Society of America

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

1998

K. E. A. LaRue, E. M. Bradbury, J. P. Freyer, “Differential regulation of cyclin-dependent kinase inhibitors in monolayers and spheroid cultures of tumorigenic and nontumorigenic fibroblasts,” Cancer Res. 58, 1305–1314 (1998).
[PubMed]

A. M. K. Nilsson, C. Sturesson, D. L. Liu, S. Andersson-Engels, “Changes in spectral shape of tissue optical properties in conjunction with laser-induced thermotherapy,” Appl. Opt. 37, 1256–1267 (1998).
[CrossRef]

1997

1996

J. R. Mourant, I. J. Bigio, J. Boyer, T. Johnson, J. Lacey, “Detection of gastrointestinal cancer by elastic-scattering spectroscopy,” J. Biomed. Opt. 1, 192–199 (1996).
[CrossRef] [PubMed]

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

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

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, G. Muller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef] [PubMed]

A. M. James, Y.-H. Wei, C.-Y. Pang, M. P. Murphy, “Altered mitochondrial-function in fibroblasts containing Melas or Merrf mitochondrial-DNA mutations,” Biochem J. 318, 401–407 (1996).

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

1995

L. A. Kunz-Schughart, A. Simm, W. Mueller-Klieser, “Oncogene-associated transformation of rodent fibroblasts is accompanied by large morphological and metabolic changes,” Oncol. Rep. 2, 651–661 (1995).

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

B. Beauvoit, S. M. Evans, Y. W. Jenkins, E. Miller, B. Chance, “Correlation between the light scattering and the mitochondrial content of normal and tissues and transplantable rodent tumors,” Anal. Biochem. 226, 167–174 (1995).
[CrossRef] [PubMed]

1994

B. Beauvoit, T. Kitai, B. Chance, “Contribution of the mitochondrial compartment to the optical properties of rat liver: a theoretical and practical approach,” Biophys. J. 67, 2501–2510 (1994).
[CrossRef] [PubMed]

R. C. Haskell, L. O. Svaasand, T.-T. Tsay, “Boundary conditions for the diffusion equation in radiative transfer,” J. Opt. Soc. Am. A 11, 2727–2741 (1994).
[CrossRef]

1993

B. Beauvoit, H. Liu, K. Kang, P. D. Kaplan, M. Miwa, B. Chance, “Characterization of absorption and scattering properties of various yeast strains by time-resolved spectroscopy,” Cell Biophys. 23, 91–109 (1993).

1992

T. J. Farrell, M. S. Patterson, M. S. Patterson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
[CrossRef] [PubMed]

R. Graaff, J. G. Aarnoose, J. R. Zijp, P. M. A. Sloot, F. F. M. de Mul, J. Greve, M. H. Koelink, “Reduced light-scattering properties for mixtures of spherical particles: a simple approximation derived from Mie calculations,” Appl. Opt. 31, 1370–1376 (1992).
[CrossRef] [PubMed]

1987

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

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

1977

A. Bloin, R. P. Bolender, E. R. Weibel, “Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study,” J. Cell Biol. 72, 441–455 (1977).
[CrossRef]

Aarnoose, J. G.

Alberts, A.

A. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, J. D. Watson, Molecular Biology of the Cell (Garland, New York, 1994), pp. 18–19.

Alter, C. A.

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

Anderson, E. R.

Andersson-Engels, S.

Avrillier, S.

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

Baltimore, D.

H. Lodish, D. Baltimore, A. Berk, S. L. Zipurssky, P. Matsudaira, J. Darnell, Molecular Cell Biology (Freeman, New York, 1995), Chap. 5.

Beauvoit, B.

B. Beauvoit, S. M. Evans, Y. W. Jenkins, E. Miller, B. Chance, “Correlation between the light scattering and the mitochondrial content of normal and tissues and transplantable rodent tumors,” Anal. Biochem. 226, 167–174 (1995).
[CrossRef] [PubMed]

B. Beauvoit, T. Kitai, B. Chance, “Contribution of the mitochondrial compartment to the optical properties of rat liver: a theoretical and practical approach,” Biophys. J. 67, 2501–2510 (1994).
[CrossRef] [PubMed]

B. Beauvoit, H. Liu, K. Kang, P. D. Kaplan, M. Miwa, B. Chance, “Characterization of absorption and scattering properties of various yeast strains by time-resolved spectroscopy,” Cell Biophys. 23, 91–109 (1993).

Berk, A.

H. Lodish, D. Baltimore, A. Berk, S. L. Zipurssky, P. Matsudaira, J. Darnell, Molecular Cell Biology (Freeman, New York, 1995), Chap. 5.

Beuthan, J.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, G. Muller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef] [PubMed]

Bigio, I. J.

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

J. R. Mourant, I. J. Bigio, J. Boyer, T. Johnson, J. Lacey, “Detection of gastrointestinal cancer by elastic-scattering spectroscopy,” J. Biomed. Opt. 1, 192–199 (1996).
[CrossRef] [PubMed]

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

Bloin, A.

A. Bloin, R. P. Bolender, E. R. Weibel, “Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study,” J. Cell Biol. 72, 441–455 (1977).
[CrossRef]

Bohren, C. F.

C. F. Bohren, D. R. Hoffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).

Bolender, R. P.

A. Bloin, R. P. Bolender, E. R. Weibel, “Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study,” J. Cell Biol. 72, 441–455 (1977).
[CrossRef]

Boppart, S. E.

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

Bouma, B. E.

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

Boyer, J.

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

J. R. Mourant, I. J. Bigio, J. Boyer, T. Johnson, J. Lacey, “Detection of gastrointestinal cancer by elastic-scattering spectroscopy,” J. Biomed. Opt. 1, 192–199 (1996).
[CrossRef] [PubMed]

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

Bradbury, E. M.

K. E. A. LaRue, E. M. Bradbury, J. P. Freyer, “Differential regulation of cyclin-dependent kinase inhibitors in monolayers and spheroid cultures of tumorigenic and nontumorigenic fibroblasts,” Cancer Res. 58, 1305–1314 (1998).
[PubMed]

Bray, D.

A. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, J. D. Watson, Molecular Biology of the Cell (Garland, New York, 1994), pp. 18–19.

Brenner, M.

Brezinski, M. E.

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

Carneiro, J.

L. C. Junquerira, J. Carneiro, R. O. Kelley, Basic Histology (Appleton & Lange, Norwalk, Conn., 1992), pp. 66, 391.

Chance, B.

B. Beauvoit, S. M. Evans, Y. W. Jenkins, E. Miller, B. Chance, “Correlation between the light scattering and the mitochondrial content of normal and tissues and transplantable rodent tumors,” Anal. Biochem. 226, 167–174 (1995).
[CrossRef] [PubMed]

B. Beauvoit, T. Kitai, B. Chance, “Contribution of the mitochondrial compartment to the optical properties of rat liver: a theoretical and practical approach,” Biophys. J. 67, 2501–2510 (1994).
[CrossRef] [PubMed]

B. Beauvoit, H. Liu, K. Kang, P. D. Kaplan, M. Miwa, B. Chance, “Characterization of absorption and scattering properties of various yeast strains by time-resolved spectroscopy,” Cell Biophys. 23, 91–109 (1993).

Conn, R. L.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. 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.

Darnell, J.

H. Lodish, D. Baltimore, A. Berk, S. L. Zipurssky, P. Matsudaira, J. Darnell, Molecular Cell Biology (Freeman, New York, 1995), Chap. 5.

de Mul, F. F. M.

Delpy, D. T.

P. van der Zee, M. Essenpreis, D. T. Delpy, “Optical properties of brain tissue,” in Photon Migration and Imaging in Random Media and Tissues, B. Chance, R. R. Alfano, A. Katzir, eds., Proc. SPIE1888, 454–465 (1993).
[CrossRef]

Dunn, A.

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

Essenpreis, M.

P. van der Zee, M. Essenpreis, D. T. Delpy, “Optical properties of brain tissue,” in Photon Migration and Imaging in Random Media and Tissues, B. Chance, R. R. Alfano, A. Katzir, eds., Proc. SPIE1888, 454–465 (1993).
[CrossRef]

Evans, S. M.

B. Beauvoit, S. M. Evans, Y. W. Jenkins, E. Miller, B. Chance, “Correlation between the light scattering and the mitochondrial content of normal and tissues and transplantable rodent tumors,” Anal. Biochem. 226, 167–174 (1995).
[CrossRef] [PubMed]

Farrell, T. J.

T. J. Farrell, M. S. Patterson, M. S. Patterson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
[CrossRef] [PubMed]

Fishkin, J. B.

Flock, S. T.

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

Freyer, J. P.

K. E. A. LaRue, E. M. Bradbury, J. P. Freyer, “Differential regulation of cyclin-dependent kinase inhibitors in monolayers and spheroid cultures of tumorigenic and nontumorigenic fibroblasts,” Cancer Res. 58, 1305–1314 (1998).
[PubMed]

Fujimoto, J. G.

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

Fuselier, T.

Gelebart, B.

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

Graaff, R.

Greve, J.

Haskell, R. C.

Helfmann, J.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, G. Muller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef] [PubMed]

Herrig, M.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, G. Muller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef] [PubMed]

Hoffman, D. R.

C. F. Bohren, D. R. Hoffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).

Jacques, S. L.

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

James, A. M.

A. M. James, Y.-H. Wei, C.-Y. Pang, M. P. Murphy, “Altered mitochondrial-function in fibroblasts containing Melas or Merrf mitochondrial-DNA mutations,” Biochem J. 318, 401–407 (1996).

Jenkins, F. A.

F. A. Jenkins, H. E. White, Fundamentals of Optics, 4th ed. (McGraw-Hill, New York, 1976), pp. 30–31.

Jenkins, Y. W.

B. Beauvoit, S. M. Evans, Y. W. Jenkins, E. Miller, B. Chance, “Correlation between the light scattering and the mitochondrial content of normal and tissues and transplantable rodent tumors,” Anal. Biochem. 226, 167–174 (1995).
[CrossRef] [PubMed]

Johnson, T.

J. R. Mourant, I. J. Bigio, J. Boyer, T. Johnson, J. Lacey, “Detection of gastrointestinal cancer by elastic-scattering spectroscopy,” J. Biomed. Opt. 1, 192–199 (1996).
[CrossRef] [PubMed]

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

Johnson, T. M.

Junquerira, L. C.

L. C. Junquerira, J. Carneiro, R. O. Kelley, Basic Histology (Appleton & Lange, Norwalk, Conn., 1992), pp. 66, 391.

Kang, K.

B. Beauvoit, H. Liu, K. Kang, P. D. Kaplan, M. Miwa, B. Chance, “Characterization of absorption and scattering properties of various yeast strains by time-resolved spectroscopy,” Cell Biophys. 23, 91–109 (1993).

Kaplan, P. D.

B. Beauvoit, H. Liu, K. Kang, P. D. Kaplan, M. Miwa, B. Chance, “Characterization of absorption and scattering properties of various yeast strains by time-resolved spectroscopy,” Cell Biophys. 23, 91–109 (1993).

Kelley, R. O.

L. C. Junquerira, J. Carneiro, R. O. Kelley, Basic Histology (Appleton & Lange, Norwalk, Conn., 1992), pp. 66, 391.

Kitai, T.

B. Beauvoit, T. Kitai, B. Chance, “Contribution of the mitochondrial compartment to the optical properties of rat liver: a theoretical and practical approach,” Biophys. J. 67, 2501–2510 (1994).
[CrossRef] [PubMed]

Knuttel, A.

Koelink, M. H.

Kumar, G.

Kunz-Schughart, L. A.

L. A. Kunz-Schughart, A. Simm, W. Mueller-Klieser, “Oncogene-associated transformation of rodent fibroblasts is accompanied by large morphological and metabolic changes,” Oncol. Rep. 2, 651–661 (1995).

Lacey, J.

J. R. Mourant, I. J. Bigio, J. Boyer, T. Johnson, J. Lacey, “Detection of gastrointestinal cancer by elastic-scattering spectroscopy,” J. Biomed. Opt. 1, 192–199 (1996).
[CrossRef] [PubMed]

LaRue, K. E. A.

K. E. A. LaRue, E. M. Bradbury, J. P. Freyer, “Differential regulation of cyclin-dependent kinase inhibitors in monolayers and spheroid cultures of tumorigenic and nontumorigenic fibroblasts,” Cancer Res. 58, 1305–1314 (1998).
[PubMed]

Lewis, J.

A. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, J. D. Watson, Molecular Biology of the Cell (Garland, New York, 1994), pp. 18–19.

Liu, D. L.

Liu, H.

B. Beauvoit, H. Liu, K. Kang, P. D. Kaplan, M. Miwa, B. Chance, “Characterization of absorption and scattering properties of various yeast strains by time-resolved spectroscopy,” Cell Biophys. 23, 91–109 (1993).

Lodish, H.

H. Lodish, D. Baltimore, A. Berk, S. L. Zipurssky, P. Matsudaira, J. Darnell, Molecular Cell Biology (Freeman, New York, 1995), Chap. 5.

Matsudaira, P.

H. Lodish, D. Baltimore, A. Berk, S. L. Zipurssky, P. Matsudaira, J. Darnell, Molecular Cell Biology (Freeman, New York, 1995), Chap. 5.

Miller, E.

B. Beauvoit, S. M. Evans, Y. W. Jenkins, E. Miller, B. Chance, “Correlation between the light scattering and the mitochondrial content of normal and tissues and transplantable rodent tumors,” Anal. Biochem. 226, 167–174 (1995).
[CrossRef] [PubMed]

Minet, O.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, G. Muller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef] [PubMed]

Miwa, M.

B. Beauvoit, H. Liu, K. Kang, P. D. Kaplan, M. Miwa, B. Chance, “Characterization of absorption and scattering properties of various yeast strains by time-resolved spectroscopy,” Cell Biophys. 23, 91–109 (1993).

Mourant, J. R.

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

J. R. Mourant, I. J. Bigio, J. Boyer, T. Johnson, J. Lacey, “Detection of gastrointestinal cancer by elastic-scattering spectroscopy,” J. Biomed. Opt. 1, 192–199 (1996).
[CrossRef] [PubMed]

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

Mueller-Klieser, W.

L. A. Kunz-Schughart, A. Simm, W. Mueller-Klieser, “Oncogene-associated transformation of rodent fibroblasts is accompanied by large morphological and metabolic changes,” Oncol. Rep. 2, 651–661 (1995).

Muller, G.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, G. Muller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef] [PubMed]

Murphy, M. P.

A. M. James, Y.-H. Wei, C.-Y. Pang, M. P. Murphy, “Altered mitochondrial-function in fibroblasts containing Melas or Merrf mitochondrial-DNA mutations,” Biochem J. 318, 401–407 (1996).

Nilsson, A. M. K.

Palade, G. E.

G. E. Palade, “An electron microscope study of the mitochondrial structure,” in Mitochondria, E. Sato, ed., Vol. 10 of Selected Papers in Biochemistry (University Park Press, Baltimore, Md., 1972), pp. 35–58.

Pang, C.-Y.

A. M. James, Y.-H. Wei, C.-Y. Pang, M. P. Murphy, “Altered mitochondrial-function in fibroblasts containing Melas or Merrf mitochondrial-DNA mutations,” Biochem J. 318, 401–407 (1996).

Patterson, M. S.

T. J. Farrell, M. S. Patterson, M. S. Patterson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
[CrossRef] [PubMed]

T. J. Farrell, M. S. Patterson, M. S. Patterson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
[CrossRef] [PubMed]

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

Pitris, C.

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

Prahl, S. A.

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

Raff, M.

A. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, J. D. Watson, Molecular Biology of the Cell (Garland, New York, 1994), pp. 18–19.

Richards-Kortum, R.

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

Roberts, K.

A. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, J. D. Watson, Molecular Biology of the Cell (Garland, New York, 1994), pp. 18–19.

Schmitt, J. M.

Shimada, T.

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

Simm, A.

L. A. Kunz-Schughart, A. Simm, W. Mueller-Klieser, “Oncogene-associated transformation of rodent fibroblasts is accompanied by large morphological and metabolic changes,” Oncol. Rep. 2, 651–661 (1995).

Sloot, P. M. A.

Southern, J. F.

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

Sturesson, C.

Svaasand, L. O.

Tearney, G. J.

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

Tinet, E.

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

Tromberg, B. J.

Tsay, T.-T.

Tualle, J. M.

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

van der Zee, P.

P. van der Zee, M. Essenpreis, D. T. Delpy, “Optical properties of brain tissue,” in Photon Migration and Imaging in Random Media and Tissues, B. Chance, R. R. Alfano, A. Katzir, eds., Proc. SPIE1888, 454–465 (1993).
[CrossRef]

Watson, J. D.

A. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, J. D. Watson, Molecular Biology of the Cell (Garland, New York, 1994), pp. 18–19.

Watson, J. V.

J. V. Watson, Introduction to Flow Cytometry (Cambridge U. Press, Cambridge, 1991), Chap. 10.
[CrossRef]

Wei, Y.-H.

A. M. James, Y.-H. Wei, C.-Y. Pang, M. P. Murphy, “Altered mitochondrial-function in fibroblasts containing Melas or Merrf mitochondrial-DNA mutations,” Biochem J. 318, 401–407 (1996).

Weibel, E. R.

A. Bloin, R. P. Bolender, E. R. Weibel, “Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study,” J. Cell Biol. 72, 441–455 (1977).
[CrossRef]

White, H. E.

F. A. Jenkins, H. E. White, Fundamentals of Optics, 4th ed. (McGraw-Hill, New York, 1976), pp. 30–31.

Wilson, B. C.

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

Zijp, J. R.

Zipurssky, S. L.

H. Lodish, D. Baltimore, A. Berk, S. L. Zipurssky, P. Matsudaira, J. Darnell, Molecular Cell Biology (Freeman, New York, 1995), Chap. 5.

Anal. Biochem.

B. Beauvoit, S. M. Evans, Y. W. Jenkins, E. Miller, B. Chance, “Correlation between the light scattering and the mitochondrial content of normal and tissues and transplantable rodent tumors,” Anal. Biochem. 226, 167–174 (1995).
[CrossRef] [PubMed]

Appl. Opt.

Biochem J.

A. M. James, Y.-H. Wei, C.-Y. Pang, M. P. Murphy, “Altered mitochondrial-function in fibroblasts containing Melas or Merrf mitochondrial-DNA mutations,” Biochem J. 318, 401–407 (1996).

Biophys. J.

B. Beauvoit, T. Kitai, B. Chance, “Contribution of the mitochondrial compartment to the optical properties of rat liver: a theoretical and practical approach,” Biophys. J. 67, 2501–2510 (1994).
[CrossRef] [PubMed]

Cancer Res.

K. E. A. LaRue, E. M. Bradbury, J. P. Freyer, “Differential regulation of cyclin-dependent kinase inhibitors in monolayers and spheroid cultures of tumorigenic and nontumorigenic fibroblasts,” Cancer Res. 58, 1305–1314 (1998).
[PubMed]

Cell Biophys.

B. Beauvoit, H. Liu, K. Kang, P. D. Kaplan, M. Miwa, B. Chance, “Characterization of absorption and scattering properties of various yeast strains by time-resolved spectroscopy,” Cell Biophys. 23, 91–109 (1993).

IEEE J. Sel. Topics Quantum Electron.

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

J. Biomed. Opt.

J. R. Mourant, I. J. Bigio, J. Boyer, T. Johnson, J. Lacey, “Detection of gastrointestinal cancer by elastic-scattering spectroscopy,” J. Biomed. Opt. 1, 192–199 (1996).
[CrossRef] [PubMed]

J. Cell Biol.

A. Bloin, R. P. Bolender, E. R. Weibel, “Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study,” J. Cell Biol. 72, 441–455 (1977).
[CrossRef]

J. Opt. Soc. Am. A

Lasers Life Sci.

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

Lasers Surg. Med.

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

Med. Phys.

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

T. J. Farrell, M. S. Patterson, M. S. Patterson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992).
[CrossRef] [PubMed]

Oncol. Rep.

L. A. Kunz-Schughart, A. Simm, W. Mueller-Klieser, “Oncogene-associated transformation of rodent fibroblasts is accompanied by large morphological and metabolic changes,” Oncol. Rep. 2, 651–661 (1995).

Opt. Lett.

Phys. Med. Biol.

J. Beuthan, O. Minet, J. Helfmann, M. Herrig, G. Muller, “The spatial variation of the refractive index in biological cells,” Phys. Med. Biol. 41, 369–382 (1996).
[CrossRef] [PubMed]

Pure Appl. Opt.

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

Science

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

Other

A. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, J. D. Watson, Molecular Biology of the Cell (Garland, New York, 1994), pp. 18–19.

G. E. Palade, “An electron microscope study of the mitochondrial structure,” in Mitochondria, E. Sato, ed., Vol. 10 of Selected Papers in Biochemistry (University Park Press, Baltimore, Md., 1972), pp. 35–58.

C. F. Bohren, D. R. Hoffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).

H. Lodish, D. Baltimore, A. Berk, S. L. Zipurssky, P. Matsudaira, J. Darnell, Molecular Cell Biology (Freeman, New York, 1995), Chap. 5.

F. A. Jenkins, H. E. White, Fundamentals of Optics, 4th ed. (McGraw-Hill, New York, 1976), pp. 30–31.

J. V. Watson, Introduction to Flow Cytometry (Cambridge U. Press, Cambridge, 1991), Chap. 10.
[CrossRef]

L. C. Junquerira, J. Carneiro, R. O. Kelley, Basic Histology (Appleton & Lange, Norwalk, Conn., 1992), pp. 66, 391.

P. van der Zee, M. Essenpreis, D. T. Delpy, “Optical properties of brain tissue,” in Photon Migration and Imaging in Random Media and Tissues, B. Chance, R. R. Alfano, A. Katzir, eds., Proc. SPIE1888, 454–465 (1993).
[CrossRef]

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Figures (11)

Fig. 1
Fig. 1

Schematic of the experimental system used to measure elastic scatter as a function of both source–detector separation and wavelength. White light incident through the delivery fiber is scattered by the biological cell suspension. Some of this light is then detected by a collection fiber a distance d from the delivery fiber and dispersed onto a CCD array. The delivery fiber is 600 μm in diameter, and the collection fiber is 200 μm in diameter. Both fibers were set into pieces of black plastic in contact with the surface to match the boundary conditions near the fibers. The sample cell holding the cell suspension had a depth of 3 cm, a length of 3 cm, and a width of 1.9 cm.

Fig. 2
Fig. 2

Comparison of measurements and theory for μ s ′(λ) for 0.895-μm-diameter polystyrene spheres.

Fig. 3
Fig. 3

Schematic of the goniometer system used for measuring P(θ). A He–Ne laser is incident upon a cylindrical sample cell containing a suspension of biological cells. The scattered light is measured as a function of angle by a photomultiplier tube, which is rotated around the sample cell. The thick black line represents a thin tube that is black on the inside and is critical for angular resolution and elimination of stray light. The intensity as a function of wavelength must be multiplied by the geometrical factor, cos θ, to account for the change in acceptance angle as the detector is rotated around the sample.

Fig. 4
Fig. 4

Comparison of a measurement of P(θ) and a theoretical calculation of P(θ) for 0.895-μm-diameter polystyrene spheres. Both the measurements and the theoretical values are for unpolarized 632.8-nm incident light and unpolarized detection.

Fig. 5
Fig. 5

Values of g for spheres calculated by Mie theory at 633 nm. Circles, sphere index of 1.4; crosses, sphere index of 1.41. In both cases the medium index was assumed to be 1.35.

Fig. 6
Fig. 6

Effect of the standard deviation on the value of g at λ = 633 nm for distributions of scatterer sizes. The distributions of scatterers were Gaussian with mean radii as shown. The standard deviation is stated on the x axis. (The Gaussian distributions of sphere sizes were truncated where the amplitude was 0.05 of the peak.) The refractive indices of the scatterer and the media were 1.4 and 1.35, respectively.

Fig. 7
Fig. 7

Relationship between the radius of a scattering particle and the wavelength dependence of μ s ′(λ). The reduced scattering coefficient, μ s ′(λ), for narrow distributions of spheres sizes was fitted to -x . (The standard deviation was 0.005, except for the spheres with a radius of 0.01 μm, for which the standard deviation was 0.001.) The power-law dependence of μ s ′(λ) on wavelength, x, is plotted along the y axis. Circles, scatter index of 1.4; squares, scatter index of 1.45. In both cases the background medium had an index of 1.35.

Fig. 8
Fig. 8

Effect of the standard deviation on the power-law dependence of μ s ′(λ) on wavelength for distributions of scatterer sizes. The distributions of were Gaussian with mean radii as shown. The standard deviation is given on the x axis. (The Gaussian distributions of sphere sizes were truncated where the amplitude was 0.05 of the peak.) The refractive indices of the scatterer and the media were 1.4 and 1.35, respectively.

Fig. 9
Fig. 9

Example of measurement of μ s ′(λ) for MR1 cells. The fits are to the function -x . One fit included points in the vicinity of 562 nm; the other did not.

Fig. 10
Fig. 10

Results of measuring the phase function of M1 cells at 633 nm. The values at 0° and above 171° were extrapolated as described in the text. A Henyey–Greenstein function with the same value of g as the phase function of the M1 cells is shown for comparison.

Fig. 11
Fig. 11

Measured angular scattering distributions, P(θ), for cells, nuclei, and mitochondria. Values below 9° and above 168° were extrapolated as described in the text. All curves are normalized such that ∫ P(θ)dΩ = 1.

Equations (6)

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

μ s λ = i = 1 N   μ s , i λ ,
P θ ,   λ = i = 1 N   P i θ ,   λ μ s , i λ i = 1 N   μ s , i λ ,
g λ =   P θ ,   λ cos   θ d Ω ,
μ s = μ s λ 1 - g λ .
I d = μ t exp - μ eff r 1 r 1 - exp - μ eff r 2 r 2 + 1 μ t 1 r 1   + μ eff exp - μ eff r 1 r 1 2 + 1 μ t + 2 z b 1 r 2 + μ eff exp ( - μ eff r 2 r 2 2 ,
r 1 = 1 / μ t 2 + d 2 1 / 2 , r 2 = 1 μ t + 2 z b 2 + d 2 1 / 2 , μ eff = μ a / D , μ t = μ s + μ a , D = 1 3 μ s + μ a ,     z b = 2 AD .

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