Abstract

We describe azimuthal light scattering spectroscopy (ϕLSS), a novel technique for assessing epithelial-cell nuclear morphology. The difference between the spectra measured at azimuthal angles ϕ=0° and ϕ=90° preferentially isolates the single backscattering contribution due to large (10μm) structures such as epithelial cell nuclei by discriminating against scattering from smaller organelles and diffusive background. We demonstrate the feasibility of using ϕLSS for cancer detection by showing that spectra from cancerous colon tissue exhibit significantly greater azimuthal asymmetry than spectra from normal colonic tissues.

© 2006 Optical Society of America

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  1. H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
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    [CrossRef] [PubMed]
  4. J. D. Wilson and T. H. Foster, Opt. Lett. 30, 2442 (2005).
    [CrossRef] [PubMed]
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    [CrossRef]
  6. V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. Dasari, L. Perelman, and M. Feld, IEEE J. Sel. Top. Quantum Electron. 5, 1019 (1999).
    [CrossRef]
  7. K. Sokolov, R. Drezek, K. Gossage, and R. Richards-Kortum, Opt. Express 5, 302 (1999).
    [CrossRef] [PubMed]
  8. J. Mourant, J. Freyer, A. Hielscher, A. Eick, D. Shen, and T. Johnson, Appl. Opt. 37, 3586 (1998).
    [CrossRef]
  9. H. C. van de Hulst, Light Scattering by Small Particles (Dover, New York, 1981).

2005 (2)

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, Biophys. J. 88, 2929 (2005).
[CrossRef] [PubMed]

J. D. Wilson and T. H. Foster, Opt. Lett. 30, 2442 (2005).
[CrossRef] [PubMed]

2004 (1)

2003 (1)

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

1999 (2)

K. Sokolov, R. Drezek, K. Gossage, and R. Richards-Kortum, Opt. Express 5, 302 (1999).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. Dasari, L. Perelman, and M. Feld, IEEE J. Sel. Top. Quantum Electron. 5, 1019 (1999).
[CrossRef]

1998 (2)

J. Mourant, J. Freyer, A. Hielscher, A. Eick, D. Shen, and T. Johnson, Appl. Opt. 37, 3586 (1998).
[CrossRef]

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Backman, V.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. Dasari, L. Perelman, and M. Feld, IEEE J. Sel. Top. Quantum Electron. 5, 1019 (1999).
[CrossRef]

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Badizadegan, K.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. Dasari, L. Perelman, and M. Feld, IEEE J. Sel. Top. Quantum Electron. 5, 1019 (1999).
[CrossRef]

Bartlett, M.

Bigelow, C. E.

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, Biophys. J. 88, 2929 (2005).
[CrossRef] [PubMed]

Bigio, I. J.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Calkins, D. J.

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, Biophys. J. 88, 2929 (2005).
[CrossRef] [PubMed]

Cipolloni, P. B.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Crawford, J.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Dasari, R.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. Dasari, L. Perelman, and M. Feld, IEEE J. Sel. Top. Quantum Electron. 5, 1019 (1999).
[CrossRef]

Drezek, R.

Eick, A.

Fang, H.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Feld, M.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. Dasari, L. Perelman, and M. Feld, IEEE J. Sel. Top. Quantum Electron. 5, 1019 (1999).
[CrossRef]

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Foster, T. H.

J. D. Wilson and T. H. Foster, Opt. Lett. 30, 2442 (2005).
[CrossRef] [PubMed]

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, Biophys. J. 88, 2929 (2005).
[CrossRef] [PubMed]

Freedman, S. D.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Freyer, J.

Gossage, K.

Gurjar, R.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. Dasari, L. Perelman, and M. Feld, IEEE J. Sel. Top. Quantum Electron. 5, 1019 (1999).
[CrossRef]

Hamano, T.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Hanlon, E. B.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Hielscher, A.

Huang, G.

Itzkan, I.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. Dasari, L. Perelman, and M. Feld, IEEE J. Sel. Top. Quantum Electron. 5, 1019 (1999).
[CrossRef]

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Jiang, H.

Johnson, T.

Kimerer, L. M.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Larcom, L.

Lima, C.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Manoharan, R.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Mourant, J.

Nusrat, A.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Ollera, M.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Perelman, L.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. Dasari, L. Perelman, and M. Feld, IEEE J. Sel. Top. Quantum Electron. 5, 1019 (1999).
[CrossRef]

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Perelman, L. T.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Richards-Kortum, R.

Seiler, M.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Shen, D.

Shields, S.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Sokolov, K.

Van Dam, J.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

van de Hulst, H. C.

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

Vitkin, E.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Wallace, M.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Wilson, J. D.

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, Biophys. J. 88, 2929 (2005).
[CrossRef] [PubMed]

J. D. Wilson and T. H. Foster, Opt. Lett. 30, 2442 (2005).
[CrossRef] [PubMed]

Zaman, M. M.

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Zonios, G.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Appl. Opt. (2)

Biophys. J. (1)

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, Biophys. J. 88, 2929 (2005).
[CrossRef] [PubMed]

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

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. Dasari, L. Perelman, and M. Feld, IEEE J. Sel. Top. Quantum Electron. 5, 1019 (1999).
[CrossRef]

H. Fang, M. Ollera, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, IEEE J. Sel. Top. Quantum Electron. 9, 267 (2003).
[CrossRef]

Opt. Express (1)

Opt. Lett. (1)

Phys. Rev. Lett. (1)

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. Crawford, and M. Feld, Phys. Rev. Lett. 80, 627 (1998).
[CrossRef]

Other (1)

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

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Figures (4)

Fig. 1
Fig. 1

Scattering intensity angular maps (radial direction, θ, angular direction, ϕ) for θ = 180 ° (center of plot) to 172 ° and ϕ = 0 ° to 360°, computed from Mie theory with m = 1.059 and λ = 450 nm .

Fig. 2
Fig. 2

ϕ LSS experimental system. BS, beam splitter; M, mirror. Other abbreviations defined in text.

Fig. 3
Fig. 3

(a) Reflectance R ϕ = 0 ° ( λ ) and (b) intensity I Δ ϕ ( λ ) for phantoms with varying numbers of 1 μ m spheres measured at θ = 177.5 ° . The legend shows the ratio between number of 1 μ m spheres and 10 μ m spheres. The optical density of 10 μ m spheres is approximately 0.2. The insets of (a) and (b) show I ϕ = 0 ° ( λ ) and I Δ ϕ ( λ ) measured from 10 μ m spheres alone (no small spheres, no diffuse background) and corresponding fits based on Mie theory.

Fig. 4
Fig. 4

(a) I Δ ϕ ( λ ) measured at θ 0 = 177.5 ° from two colon tissue samples. (b) Histograms of d LSS and d M (defined in text). (c) Histograms of d LSS and L M (defined in text). The y axes indicate the number of occurrences. For morphometry results, the measured d M and L M from all samples are binned in 0.5 μ m units. For ϕ LSS results, the 12 extracted d LSS are binned in 0.5 μ m units.

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