Abstract

We demonstrate the feasibility of measuring the particle size distribution (PSD) of internal cell structures in vitro. We use polarized light spectroscopy to probe the internal morphology of mammalian breast cancer (MCF7) and cervical cancer (Siha) cells. We find that graphing the least-squared error versus the scatterer size provides insight into cell scattering. A nonlinear optimization scheme is used to determine the PSD iteratively. The results suggest that 2-μm particles (possibly the mitochondria) contribute most to the scattering. Other subcellular structures, such as the nucleoli and the nucleus, may also contribute significantly. We reconstruct the PSD of the mitochondria, as verified by optical microscopy. We also demonstrate the angle dependence of the PSD.

© 2004 Optical Society of America

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    [Crossref]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref]
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    [Crossref] [PubMed]
  12. M. Bartlett, H. Jiang, “Measurement of particle size distribution in multilayered skin phantoms using polarized light spectroscopy,” Phys. Rev. E 65, 031906-1–031908 (2002).
    [Crossref]
  13. V. Sankaran, J. T. Walsh, D. J. Maitland, “Polarized light propagation through tissue phantoms containing densely packed scatterers,” Opt. Lett. 25, 239–241 (2000).
    [Crossref]
  14. K. M. Yoo, R. R. Alfano, “Time resolved depolarization of multiple backscattered light from random media,” Phys. Lett. A 142, 531–536 (1989).
    [Crossref]
  15. R. C. N. Studinski, I. A. Vitkin, “Methodology for examining polarized light interactions with tissues and tissue like media in the exact back scattering direction,” J. Biomed. Opt. 5, 330–337 (2000).
    [Crossref] [PubMed]
  16. A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. R. Kortum, K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance,” J. Biomed. Opt. 7, 388–397 (2002).
    [Crossref] [PubMed]
  17. R. Drezek, A. Dunn, R. R. Kortum, “Light scattering from cells: finite-difference time-domain simulations and goniometric measurements,” Appl. Opt. 38, 3651–3661 (1999).
    [Crossref]
  18. C. F. Bohren, D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, New York, 1983).
  19. J. Darnell, H. Lodish, D. Baltimore, Molecular Cell Biology, 2nd ed. (Scientific American Books, New York, 1990), Chap. 4, P. 144.
  20. E. Kashuba, K. Mattsson, G. Klein, L. Szekely, “pI4ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes,” Mol. Cancer 2(18), 1–9 (2003).

2003 (2)

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, R. R. Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

E. Kashuba, K. Mattsson, G. Klein, L. Szekely, “pI4ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes,” Mol. Cancer 2(18), 1–9 (2003).

2002 (3)

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. R. Kortum, K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance,” J. Biomed. Opt. 7, 388–397 (2002).
[Crossref] [PubMed]

M. Bartlett, H. Jiang, “Measurement of particle size distribution in multilayered skin phantoms using polarized light spectroscopy,” Phys. Rev. E 65, 031906-1–031908 (2002).
[Crossref]

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7, 378–387 (2002).
[Crossref] [PubMed]

2001 (3)

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, M. S. Feld, “Imaging human epithelial properties with polarized light scattering spectroscopy,” Nat. Med. 7, 1245–1248 (2001).
[Crossref] [PubMed]

J. R. Mourant, T. M. Johnson, J. P. Freyer, “Characterizing mammalian cells and cell phantoms by polarized backscattering fiber-optic measurements,” Appl. Opt. 40, 5114–5123 (2001).
[Crossref]

2000 (2)

R. C. N. Studinski, I. A. Vitkin, “Methodology for examining polarized light interactions with tissues and tissue like media in the exact back scattering direction,” J. Biomed. Opt. 5, 330–337 (2000).
[Crossref] [PubMed]

V. Sankaran, J. T. Walsh, D. J. Maitland, “Polarized light propagation through tissue phantoms containing densely packed scatterers,” Opt. Lett. 25, 239–241 (2000).
[Crossref]

1999 (4)

1989 (2)

M. J. C. Van Gemert, S. L. Jacques, H. J. Sterenborg, W. M. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146–1154 (1989).
[Crossref] [PubMed]

K. M. Yoo, R. R. Alfano, “Time resolved depolarization of multiple backscattered light from random media,” Phys. Lett. A 142, 531–536 (1989).
[Crossref]

Aida, T.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7, 378–387 (2002).
[Crossref] [PubMed]

Alfano, R. R.

K. M. Yoo, R. R. Alfano, “Time resolved depolarization of multiple backscattered light from random media,” Phys. Lett. A 142, 531–536 (1989).
[Crossref]

Backman, V.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, M. S. Feld, “Imaging human epithelial properties with polarized light scattering spectroscopy,” Nat. Med. 7, 1245–1248 (2001).
[Crossref] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[Crossref]

Badizadegan, K.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, M. S. Feld, “Imaging human epithelial properties with polarized light scattering spectroscopy,” Nat. Med. 7, 1245–1248 (2001).
[Crossref] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[Crossref]

Baltimore, D.

J. Darnell, H. Lodish, D. Baltimore, Molecular Cell Biology, 2nd ed. (Scientific American Books, New York, 1990), Chap. 4, P. 144.

Bartlett, M.

M. Bartlett, H. Jiang, “Measurement of particle size distribution in multilayered skin phantoms using polarized light spectroscopy,” Phys. Rev. E 65, 031906-1–031908 (2002).
[Crossref]

Bohren, C. F.

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

Boiko, I.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, R. R. Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

Boone, C. W.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

Carpenter, S.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7, 378–387 (2002).
[Crossref] [PubMed]

Collier, T.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, R. R. Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

Darnell, J.

J. Darnell, H. Lodish, D. Baltimore, Molecular Cell Biology, 2nd ed. (Scientific American Books, New York, 1990), Chap. 4, P. 144.

Dasari, R. R.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, M. S. Feld, “Imaging human epithelial properties with polarized light scattering spectroscopy,” Nat. Med. 7, 1245–1248 (2001).
[Crossref] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[Crossref]

Drezek, R.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, R. R. Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

R. Drezek, A. Dunn, R. R. Kortum, “Light scattering from cells: finite-difference time-domain simulations and goniometric measurements,” Appl. Opt. 38, 3651–3661 (1999).
[Crossref]

Dunn, A.

Feld, M. S.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, M. S. Feld, “Imaging human epithelial properties with polarized light scattering spectroscopy,” Nat. Med. 7, 1245–1248 (2001).
[Crossref] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[Crossref]

Follen, M.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, R. R. Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

Freyer, J. P.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7, 378–387 (2002).
[Crossref] [PubMed]

J. R. Mourant, T. M. Johnson, J. P. Freyer, “Characterizing mammalian cells and cell phantoms by polarized backscattering fiber-optic measurements,” Appl. Opt. 40, 5114–5123 (2001).
[Crossref]

Georgakoudi, I.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, M. S. Feld, “Imaging human epithelial properties with polarized light scattering spectroscopy,” Nat. Med. 7, 1245–1248 (2001).
[Crossref] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

Gopal, V.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

Guerra, A.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7, 378–387 (2002).
[Crossref] [PubMed]

Guillaud, M.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, R. R. Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

Gurjar, R.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[Crossref]

Gurjar, R. S.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, M. S. Feld, “Imaging human epithelial properties with polarized light scattering spectroscopy,” Nat. Med. 7, 1245–1248 (2001).
[Crossref] [PubMed]

Huffman, D. R.

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

Itzkan, I.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, M. S. Feld, “Imaging human epithelial properties with polarized light scattering spectroscopy,” Nat. Med. 7, 1245–1248 (2001).
[Crossref] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[Crossref]

Jacques, S. L.

M. J. C. Van Gemert, S. L. Jacques, H. J. Sterenborg, W. M. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146–1154 (1989).
[Crossref] [PubMed]

Jiang, H.

M. Bartlett, H. Jiang, “Measurement of particle size distribution in multilayered skin phantoms using polarized light spectroscopy,” Phys. Rev. E 65, 031906-1–031908 (2002).
[Crossref]

Johnson, T. M.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7, 378–387 (2002).
[Crossref] [PubMed]

J. R. Mourant, T. M. Johnson, J. P. Freyer, “Characterizing mammalian cells and cell phantoms by polarized backscattering fiber-optic measurements,” Appl. Opt. 40, 5114–5123 (2001).
[Crossref]

T. M. Johnson, J. R. Mourant, “Polarized wavelength-dependent measurements of turbid media,” Opt. Express 4, 200–216 (1999).
[Crossref] [PubMed]

Kalashnikov, M.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

Kashuba, E.

E. Kashuba, K. Mattsson, G. Klein, L. Szekely, “pI4ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes,” Mol. Cancer 2(18), 1–9 (2003).

Klein, G.

E. Kashuba, K. Mattsson, G. Klein, L. Szekely, “pI4ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes,” Mol. Cancer 2(18), 1–9 (2003).

Kortum, R. R.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, R. R. Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. R. Kortum, K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance,” J. Biomed. Opt. 7, 388–397 (2002).
[Crossref] [PubMed]

R. Drezek, A. Dunn, R. R. Kortum, “Light scattering from cells: finite-difference time-domain simulations and goniometric measurements,” Appl. Opt. 38, 3651–3661 (1999).
[Crossref]

Lide, D. R.

D. R. Lide, CRC Handbook of Chemistry and Physics, 83rd ed. (CRC Press LLC, New York, 2002).

Lodish, H.

J. Darnell, H. Lodish, D. Baltimore, Molecular Cell Biology, 2nd ed. (Scientific American Books, New York, 1990), Chap. 4, P. 144.

Macaulay, C.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, R. R. Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

Maitland, D. J.

Malpica, A.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, R. R. Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

Mattsson, K.

E. Kashuba, K. Mattsson, G. Klein, L. Szekely, “pI4ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes,” Mol. Cancer 2(18), 1–9 (2003).

Mourant, J. R.

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7, 378–387 (2002).
[Crossref] [PubMed]

J. R. Mourant, T. M. Johnson, J. P. Freyer, “Characterizing mammalian cells and cell phantoms by polarized backscattering fiber-optic measurements,” Appl. Opt. 40, 5114–5123 (2001).
[Crossref]

T. M. Johnson, J. R. Mourant, “Polarized wavelength-dependent measurements of turbid media,” Opt. Express 4, 200–216 (1999).
[Crossref] [PubMed]

Mueller, M.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

Myakov, A.

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. R. Kortum, K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance,” J. Biomed. Opt. 7, 388–397 (2002).
[Crossref] [PubMed]

Nieman, L.

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. R. Kortum, K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance,” J. Biomed. Opt. 7, 388–397 (2002).
[Crossref] [PubMed]

Perelman, L. T.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, M. S. Feld, “Imaging human epithelial properties with polarized light scattering spectroscopy,” Nat. Med. 7, 1245–1248 (2001).
[Crossref] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[Crossref]

Sankaran, V.

Schonenberger, K.

Sokolov, K.

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. R. Kortum, K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance,” J. Biomed. Opt. 7, 388–397 (2002).
[Crossref] [PubMed]

Star, W. M.

M. J. C. Van Gemert, S. L. Jacques, H. J. Sterenborg, W. M. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146–1154 (1989).
[Crossref] [PubMed]

Sterenborg, H. J.

M. J. C. Van Gemert, S. L. Jacques, H. J. Sterenborg, W. M. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146–1154 (1989).
[Crossref] [PubMed]

Studinski, R. C. N.

R. C. N. Studinski, I. A. Vitkin, “Methodology for examining polarized light interactions with tissues and tissue like media in the exact back scattering direction,” J. Biomed. Opt. 5, 330–337 (2000).
[Crossref] [PubMed]

Szekely, L.

E. Kashuba, K. Mattsson, G. Klein, L. Szekely, “pI4ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes,” Mol. Cancer 2(18), 1–9 (2003).

Utzinger, U.

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. R. Kortum, K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance,” J. Biomed. Opt. 7, 388–397 (2002).
[Crossref] [PubMed]

Van Gemert, M. J. C.

M. J. C. Van Gemert, S. L. Jacques, H. J. Sterenborg, W. M. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146–1154 (1989).
[Crossref] [PubMed]

Vitkin, I. A.

R. C. N. Studinski, I. A. Vitkin, “Methodology for examining polarized light interactions with tissues and tissue like media in the exact back scattering direction,” J. Biomed. Opt. 5, 330–337 (2000).
[Crossref] [PubMed]

Walsh, J. T.

Wax, A.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

Wicky, L.

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. R. Kortum, K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance,” J. Biomed. Opt. 7, 388–397 (2002).
[Crossref] [PubMed]

Yoo, K. M.

K. M. Yoo, R. R. Alfano, “Time resolved depolarization of multiple backscattered light from random media,” Phys. Lett. A 142, 531–536 (1989).
[Crossref]

Appl. Opt. (3)

IEEE J. Sel. Top. Quantum Electron. (2)

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” IEEE J. Sel. Top. Quantum Electron. 5, 1019–1026 (1999).
[Crossref]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Georgakoudi, M. Mueller, C. W. Boone, R. R. Dasari, M. S. Feld, “Measuring cellular structure at submicrometer scale with light scattering spectroscopy,” IEEE J. Sel. Top. Quantum Electron. 7, 887–893 (2001).
[Crossref]

IEEE Trans. Biomed. Eng. (1)

M. J. C. Van Gemert, S. L. Jacques, H. J. Sterenborg, W. M. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146–1154 (1989).
[Crossref] [PubMed]

J. Biomed. Opt. (4)

R. C. N. Studinski, I. A. Vitkin, “Methodology for examining polarized light interactions with tissues and tissue like media in the exact back scattering direction,” J. Biomed. Opt. 5, 330–337 (2000).
[Crossref] [PubMed]

A. Myakov, L. Nieman, L. Wicky, U. Utzinger, R. R. Kortum, K. Sokolov, “Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance,” J. Biomed. Opt. 7, 388–397 (2002).
[Crossref] [PubMed]

J. R. Mourant, T. M. Johnson, S. Carpenter, A. Guerra, T. Aida, J. P. Freyer, “Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures,” J. Biomed. Opt. 7, 378–387 (2002).
[Crossref] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, R. R. Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7–16 (2003).
[Crossref] [PubMed]

Mol. Cancer (1)

E. Kashuba, K. Mattsson, G. Klein, L. Szekely, “pI4ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes,” Mol. Cancer 2(18), 1–9 (2003).

Nat. Med. (1)

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, M. S. Feld, “Imaging human epithelial properties with polarized light scattering spectroscopy,” Nat. Med. 7, 1245–1248 (2001).
[Crossref] [PubMed]

Opt. Express (1)

Opt. Lett. (1)

Phys. Lett. A (1)

K. M. Yoo, R. R. Alfano, “Time resolved depolarization of multiple backscattered light from random media,” Phys. Lett. A 142, 531–536 (1989).
[Crossref]

Phys. Rev. E (1)

M. Bartlett, H. Jiang, “Measurement of particle size distribution in multilayered skin phantoms using polarized light spectroscopy,” Phys. Rev. E 65, 031906-1–031908 (2002).
[Crossref]

Other (4)

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

J. Darnell, H. Lodish, D. Baltimore, Molecular Cell Biology, 2nd ed. (Scientific American Books, New York, 1990), Chap. 4, P. 144.

D. R. Lide, CRC Handbook of Chemistry and Physics, 83rd ed. (CRC Press LLC, New York, 2002).

American Cancer Society , Cancer Facts and Figures (American Cancer Society, Atlanta, Ga., 2003).

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Figures (10)

Fig. 1
Fig. 1

(a) Schematic of the experimental setup. Following the path of light, the system consists of a 100-W tungsten-halogen light, 200-μm fiber-optic cable, 14-mm focal-length lens, linear polarizer, multilayered sample, linear analyzer, 14-mm collection lens, 200-μm optic fiber, CCD and spectrometer, and computer interface. (b) Solid arrows represent the light single scattered from the top layer, which maintains its incident polarization. Dotted arrows represent multiply scattered light, which penetrates deeper and looses its polarization through scattering.

Fig. 2
Fig. 2

Intensity-versus-wavelength curves for (a) the 2.065-μm- and (b) the 9.10-μm-diameter polystyrene spheres. The measured intensity is the solid curve, and the fitted data is the dotted curve. Both spectra were measured at a Δθ of 40°. Plots (c) and (d) show the PSDs for 2- and 9-μm particles, respectively. The solid curves represent the PSDs provided by the factory or measured under a microscope. The dotted curves represent the reconstructed PSDs. Both measured peak sizes are within 3% of the factory and microscope particle sizes.

Fig. 3
Fig. 3

Optical microscope image of (a) Siha cells and (b) MCF7 cells at 60× magnification. The cells have been dyed with Acridine Orange to make the nucleus fluoresce. The solid arrows point at the nucleus, which appears lighter than the background. The dotted arrows point to the dark spots believed to be nucleoli.

Fig. 4
Fig. 4

Optical microscope image of (a) Siha cells and (b) MCF7 cells at 100× magnification. The cells have been dyed with Rhodamine 123 to make the mitochondria fluoresce. Image (b) shows bright spots of mitochondria within the cells. The figures have been enhanced with Photoshop to make the mitochondria easily visible in black and white.

Fig. 5
Fig. 5

Least square error versus particle diameter for a mixture of 2.065 and 9.10-μm latex spheres. The figures were calculated by optimizing the amplitude and SD for each increment of the particle size. Each plot represents the intensity spectrum at a different incident angle Δθ: (a) 40°, (b) 60°, (c) 80°, and (d) 110°. These angles were modified by Snell’s law to 23.9°, 44.2°, 57.3°, and 69.9°, respectively.

Fig. 6
Fig. 6

Intensity-versus-wavelength curves for the 2.065- and 9.1-μm-diameter particles. The solid curves represent the measured data, the dashed curves represent the fit with initial guess near the 2-μm size, and the dotted curves represent the fit with an initial guess near the 9-μm size. Each figure represents the intensity spectrum at a different incident angle Δθ: (a) 40°, (b) 60°, (c) 80°, and (d) 110°. These angles were modified by Snell’s law to 23.9°, 44.2°, 57.3°, and 69.9°, respectively.

Fig. 7
Fig. 7

Cell data representing the least square error versus the particle size: (a) measured from Siha cells at a Δθ of 40°, modified by Snell’s law to 29.1; (b) measured from MCF7 cells at a Δθ of 45°, modified by Snell’s law to 32.4°. Notice that there are three local minima at 2, 4, and 9 μm. We believe that these may be due to the mitochondria, nucleoli, and nucleus, respectively.

Fig. 8
Fig. 8

Normalized intensity versus wavelength for (a) Siha and (b) MCF7 cells. The solid curve is the measured intensity, and the dotted curve is the optimized fit with the 2-μm size as the initial guess. (c) and (d) represent the relative number of scatterers on the y axis and the particle size on the x axis, respectively. The Δθ for each measurement was 40°, modified by Snell’s law to 29.1°.

Fig. 9
Fig. 9

Normalized intensity versus wavelength for (a) Siha and (b) MCF7 cells. The solid curve is the measured intensity, and the dotted curve is the optimized fit with the 9-μm size as the initial guess. (c) and (d) represent the relative number of scatterers on the y axis and the particle size on the x axis, respectively. The Δθ for each measurement was 40°, modified by Snell’s law to 29.1°.

Fig. 10
Fig. 10

Average particle size versus Δθ between the incident and collector fibers for (a) Siha and (b) MCF7 cells. The initial guess for each of these optimized values was 2.4 μm. Note an increase in the average particle size with increasing Δθ.

Tables (2)

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Table 1 Optical Microscope Results for Siha and MCF7 Cellsa

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Table 2 Average Results for the Least-Squared Error and the Five Optimized Parameters for Siha and MCF7 Cellsa

Equations (6)

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

Im-Im=I topm+I bottomm-I bottomm=I topm.
I topcλ, θ=|S1λ, θ|2kr2,
Icλ, θ, x=N xixfθiθf |S1λ, θ, x|2f×x, a, b, csin θdθdx,
Csca=πk20π|S1θ|2+|S2θ|2sin θdθ,
χ=1nwImλ-Icλ2nw-11/2,
limΔnm,p0ΔS1nm,pΔnm,p,

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