Abstract

Although the phenomenon of coherent backscattering (CBS) in nonbiological media has generated substantial research interest, observing CBS in biological tissue has been extremely difficult. Here we show that the combination of low-spatial-coherence, broadband illumination, and low-temporal-coherence, spectrally resolved detection significantly facilitates CBS observation in biological tissue and other random media with long-transport mean-free path lengths, which have been previously beyond the reach of conventional CBS investigations. Furthermore, we demonstrate that depth-selective, speckle-free, low-coherent backscattering spectroscopy has the potential to diagnose the earliest, previously undetectable, precancerous alterations in the colon by means of probing short light paths.

© 2005 Optical Society of America

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2004 (4)

R. Sapienza, S. Mujumdar, C. Cheung, A. G. Yodh, D. Wiersma, “Anisotropic weak localization of light,” Phys. Rev. Lett. 92, 033903 (2004).
[CrossRef] [PubMed]

T. M. Breslin, F. S. Xu, G. M. Palmer, C. F. Zhu, K. W. Gilchrist, N. Ramanujam, “Autofluorescence and diffuse reflectance properties of malignant and benign breast tissues,” Ann. Surgical Oncol. 11, 65–70 (2004).
[CrossRef]

H. K. Roy, Y. Liu, R. K. Wali, Y. L. Kim, A. K. Kromin, M. J. Goldberg, V. Backman, “Four-dimensional elastic light-scattering fingerprints as preneoplastic markers in the rat model of colon carcinogenesis,” Gastroenterology 126, 1071–1081 (2004).
[CrossRef] [PubMed]

Y. L. Kim, Y. Liu, V. M. Turzhitsky, H. K. Roy, R. K. Wali, V. Backman, “Coherent backscattering spectroscopy,” Opt. Lett. 29, 1906–1908 (2004).
[CrossRef] [PubMed]

2003 (3)

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Select. Topics Quantum Electron. 9, 267–276 (2003).
[CrossRef]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Select. Topics Quantum Electron. 9, 243–256 (2003).
[CrossRef]

A. Wax, C. H. Yang, M. G. Muller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63, 3556–3559 (2003).
[PubMed]

2002 (2)

A. Wax, C. H. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82, 2256–2264 (2002).

S. L. Jacques, J. C. Ramella-Roman, K. Lee, “Imaging skin pathology with polarized light,” J. Biomed. Opt. 7, 329–340 (2002).
[CrossRef] [PubMed]

2001 (4)

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Muller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120, 1620–1629 (2001).
[CrossRef] [PubMed]

N. Shah, A. Cerussi, C. Eker, J. Espinoza, J. Butler, J. Fishkin, R. Hornung, B. Tromberg, “Noninvasive functional optical spectroscopy of human breast tissue,” Proc. Natl. Acad. Sci. (USA) 98, 4420–4425 (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,” Nature Med. 7, 1245–1248 (2001).
[CrossRef] [PubMed]

S. K. Gayen, M. Alrubaiee, H. E. Savage, S. P. Schantz, R. R. Alfano, “Parotid gland tissues investigated by picosecond time-gated and optical spectroscopic imaging techniques,” IEEE J. Select. Topics Quantum Electron. 7, 906–911 (2001).
[CrossRef]

2000 (5)

M. Kobaek-Larsen, I. Thorup, A. Diederichsen, C. Fenger, M. R. Hoitinga, “Review of colorectal cancer and its metastases in rodent models: comparative aspects with those in humans,” Comparative Med. 50, 16–26 (2000).

L. Roncucci, M. Pedroni, F. Vaccina, P. Benatti, L. Marzona, A. De Pol, “Aberrant crypt foci in colorectal carcinogenesis. Cell and crypt dynamics,” Cell Proliferation 33, 1–18 (2000).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406, 35–36 (2000).
[CrossRef] [PubMed]

A. Wax, S. Bali, J. E. Thomas, “Time-resolved phase-space distributions for light backscattered from it disordered medium,” Phys. Rev. Lett. 85, 66–69 (2000).
[CrossRef] [PubMed]

S. G. Demos, H. B. Radousky, R. R. Alfano, “Deep subsurface imaging in tissues using spectral and polarization filtering,” Opt. Express 7, 23–28 (2000).
[CrossRef] [PubMed]

1999 (2)

K. Sokolov, R. D. Drezek, K. Gossage, R. R. Richards-Kortum, “Reflectance spectroscopy with polarized light: is it sensitive to cellular and nuclear morphology?,” Opt. Express 5, 302–317 (1999).
[CrossRef] [PubMed]

G. Labeyrie, F. de Tomasi, J. C. Bernard, C. A. Muller, C. Miniatura, R. Kaiser, “Coherent backscattering of light by cold atoms,” Phys. Rev. Lett. 83, 5266–5269 (1999).
[CrossRef]

1998 (3)

A. Banerjee, P. Quirke, “Experimental models of colorectal cancer,” Diseases Colon Rectum 41, 490–505 (1998).
[CrossRef]

L. T. 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. M. Crawford, M. S. 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]

J. N. Winn, L. T. Perelman, K. Chen, J. Wu, R. R. Dasari, M. S. Feld, “Distribution of the paths of early-arriving photons traversing a turbid medium,” Appl. Opt. 37, 8085–8091 (1998).
[CrossRef]

1997 (3)

1996 (3)

1995 (2)

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 Surgery Med. 17, 350–357 (1995).
[CrossRef]

D. S. Wiersma, M. P. van Albada, A. Lagendijk, “Coherent backscattering of light from amplifying random media,” Phys. Rev. Lett. 75, 1739–1742 (1995).
[CrossRef] [PubMed]

1994 (1)

M. Ospeck, S. Fraden, “Influence of reflecting boundaries and finite interfacial thickness on the coherent backscattering cone,” Phys. Rev. E 49, 4578–4589 (1994).
[CrossRef]

1993 (2)

M. I. Mishchenko, J. M. Dlugach, “Coherent backscatter and the opposition effect for E-type asteroids,” Planet. Space Sci. 41, 173–181 (1993).
[CrossRef]

G. Yoon, D. N. G. Roy, R. C. Straight, “Coherent backscattering in biological media: measurement and estimation of optical properties,” Appl. Opt. 32, 580–585 (1993).
[CrossRef] [PubMed]

1992 (2)

P. M. Saulnier, G. H. Watson, “Role of surface reflectivity in coherent backscattering measurements,” Opt. Lett. 17, 946–948 (1992).
[CrossRef] [PubMed]

A. Dogariu, J. Uozumi, T. Asakura, “Enhancement of the backscattered intensity from fractal aggregates,” Waves Random Media 2, 259–263 (1992).
[CrossRef]

1991 (1)

M. Tomita, H. Ikari, “Influence of finite coherence length of incoming light on enhanced backscattering,” Phys. Rev. B 43, 3716–3719 (1991).
[CrossRef]

1990 (2)

1989 (1)

K. M. Yoo, Y. Takiguchi, R. R. Alfano, “Weak localization of photons: contributions from the different scattering path-lengths,” IEEE Photonics Technol. Lett. 58, 94–96 (1989).
[CrossRef]

1988 (3)

R. Vreeker, M. P. van Albada, R. Sprik, A. Lagendijk, “Femtosecond time-resolved measurements of weak localization of light,” Phys. Lett. A 132, 51–54 (1988).
[CrossRef]

M. B. van der Mark, M. P. van Albada, A. Lagendijk, “Light scattering in strongly scattering media: multiple scattering and weak localization,” Phys. Rev. B 37, 3575–3592 (1988).
[CrossRef]

P. E. Wolf, G. Maret, E. Akkermans, R. Maynard, “Optical coherent backscattering by random media: an experimental study,” J. Phys. 49, 63–75 (1988).
[CrossRef]

1987 (1)

S. Etemad, R. Thompson, M. J. Andrejco, “Weak localization of photons: termination of coherent random walks by absorption and confined geometry,” Phys. Rev. Lett. 59, 1420–1423 (1987).
[CrossRef] [PubMed]

1986 (1)

S. Etemad, R. Thompson, M. J. Andrejco, “Weak localization of photons: universal fluctuations and ensemble averaging,” Phys. Rev. Lett. 57, 575–578 (1986).
[CrossRef] [PubMed]

1984 (1)

Akkermans, E.

P. E. Wolf, G. Maret, E. Akkermans, R. Maynard, “Optical coherent backscattering by random media: an experimental study,” J. Phys. 49, 63–75 (1988).
[CrossRef]

Alders, M.

J. F. Beek, P. Blokland, P. Posthumus, M. Alders, J. W. Pickering, H. Sterenborg, M. J. C. van Gemert, “In vitro double-integrating-sphere optical properties of tissues between 630 and 1064 nm,” Phys. Med. Biol. 42, 2255–2261 (1997).
[CrossRef] [PubMed]

Alfano, R. R.

Alrubaiee, M.

S. K. Gayen, M. Alrubaiee, H. E. Savage, S. P. Schantz, R. R. Alfano, “Parotid gland tissues investigated by picosecond time-gated and optical spectroscopic imaging techniques,” IEEE J. Select. Topics Quantum Electron. 7, 906–911 (2001).
[CrossRef]

Andrejco, M. J.

S. Etemad, R. Thompson, M. J. Andrejco, “Weak localization of photons: termination of coherent random walks by absorption and confined geometry,” Phys. Rev. Lett. 59, 1420–1423 (1987).
[CrossRef] [PubMed]

S. Etemad, R. Thompson, M. J. Andrejco, “Weak localization of photons: universal fluctuations and ensemble averaging,” Phys. Rev. Lett. 57, 575–578 (1986).
[CrossRef] [PubMed]

Arendt, J. T.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406, 35–36 (2000).
[CrossRef] [PubMed]

Asakura, T.

T. Okamoto, T. Asakura, “Enhanced backscattering of partially coherent light,” Opt. Lett. 21, 369–371 (1996).
[CrossRef] [PubMed]

A. Dogariu, J. Uozumi, T. Asakura, “Enhancement of the backscattered intensity from fractal aggregates,” Waves Random Media 2, 259–263 (1992).
[CrossRef]

Backman, V.

Y. L. Kim, Y. Liu, V. M. Turzhitsky, H. K. Roy, R. K. Wali, V. Backman, “Coherent backscattering spectroscopy,” Opt. Lett. 29, 1906–1908 (2004).
[CrossRef] [PubMed]

H. K. Roy, Y. Liu, R. K. Wali, Y. L. Kim, A. K. Kromin, M. J. Goldberg, V. Backman, “Four-dimensional elastic light-scattering fingerprints as preneoplastic markers in the rat model of colon carcinogenesis,” Gastroenterology 126, 1071–1081 (2004).
[CrossRef] [PubMed]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Select. Topics Quantum Electron. 9, 243–256 (2003).
[CrossRef]

A. Wax, C. H. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82, 2256–2264 (2002).

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,” Nature Med. 7, 1245–1248 (2001).
[CrossRef] [PubMed]

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Muller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120, 1620–1629 (2001).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406, 35–36 (2000).
[CrossRef] [PubMed]

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N. Shah, A. Cerussi, C. Eker, J. Espinoza, J. Butler, J. Fishkin, R. Hornung, B. Tromberg, “Noninvasive functional optical spectroscopy of human breast tissue,” Proc. Natl. Acad. Sci. (USA) 98, 4420–4425 (2001).
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L. T. 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. M. Crawford, M. S. 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, 1995).

van der Mark, M. B.

M. B. van der Mark, M. P. van Albada, A. Lagendijk, “Light scattering in strongly scattering media: multiple scattering and weak localization,” Phys. Rev. B 37, 3575–3592 (1988).
[CrossRef]

van Gemert, M. J. C.

J. F. Beek, P. Blokland, P. Posthumus, M. Alders, J. W. Pickering, H. Sterenborg, M. J. C. van Gemert, “In vitro double-integrating-sphere optical properties of tissues between 630 and 1064 nm,” Phys. Med. Biol. 42, 2255–2261 (1997).
[CrossRef] [PubMed]

Vitkin, E.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Select. Topics Quantum Electron. 9, 267–276 (2003).
[CrossRef]

Vogelstein, B.

K. W. Kinzler, B. Vogelstein, “Colorectal tumors,” in The Genetic Basis of Human Cancer,B. Vogelstein, K. W. Kinzler, eds. (McGraw-Hill, New York, 1998), pp. 565–587.

Vreeker, R.

R. Vreeker, M. P. van Albada, R. Sprik, A. Lagendijk, “Femtosecond time-resolved measurements of weak localization of light,” Phys. Lett. A 132, 51–54 (1988).
[CrossRef]

Wali, R. K.

H. K. Roy, Y. Liu, R. K. Wali, Y. L. Kim, A. K. Kromin, M. J. Goldberg, V. Backman, “Four-dimensional elastic light-scattering fingerprints as preneoplastic markers in the rat model of colon carcinogenesis,” Gastroenterology 126, 1071–1081 (2004).
[CrossRef] [PubMed]

Y. L. Kim, Y. Liu, V. M. Turzhitsky, H. K. Roy, R. K. Wali, V. Backman, “Coherent backscattering spectroscopy,” Opt. Lett. 29, 1906–1908 (2004).
[CrossRef] [PubMed]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Select. Topics Quantum Electron. 9, 243–256 (2003).
[CrossRef]

Wallace, M.

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

Wallace, M. B.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Muller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120, 1620–1629 (2001).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406, 35–36 (2000).
[CrossRef] [PubMed]

Watson, G. H.

Wax, A.

A. Wax, C. H. Yang, M. G. Muller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63, 3556–3559 (2003).
[PubMed]

A. Wax, C. H. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82, 2256–2264 (2002).

A. Wax, S. Bali, J. E. Thomas, “Time-resolved phase-space distributions for light backscattered from it disordered medium,” Phys. Rev. Lett. 85, 66–69 (2000).
[CrossRef] [PubMed]

Wiersma, D.

R. Sapienza, S. Mujumdar, C. Cheung, A. G. Yodh, D. Wiersma, “Anisotropic weak localization of light,” Phys. Rev. Lett. 92, 033903 (2004).
[CrossRef] [PubMed]

Wiersma, D. S.

D. S. Wiersma, M. P. van Albada, A. Lagendijk, “Coherent backscattering of light from amplifying random media,” Phys. Rev. Lett. 75, 1739–1742 (1995).
[CrossRef] [PubMed]

Winn, J. N.

Wolf, E.

M. Born, E. Wolf, Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light, 7th ed. (Cambridge University, Cambridge, UK, 1999), pp. 572–580.

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P. E. Wolf, G. Maret, E. Akkermans, R. Maynard, “Optical coherent backscattering by random media: an experimental study,” J. Phys. 49, 63–75 (1988).
[CrossRef]

Wu, J.

Xu, F. S.

T. M. Breslin, F. S. Xu, G. M. Palmer, C. F. Zhu, K. W. Gilchrist, N. Ramanujam, “Autofluorescence and diffuse reflectance properties of malignant and benign breast tissues,” Ann. Surgical Oncol. 11, 65–70 (2004).
[CrossRef]

Yang, C. H.

A. Wax, C. H. Yang, M. G. Muller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63, 3556–3559 (2003).
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A. Wax, C. H. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82, 2256–2264 (2002).

Yodh, A. G.

R. Sapienza, S. Mujumdar, C. Cheung, A. G. Yodh, D. Wiersma, “Anisotropic weak localization of light,” Phys. Rev. Lett. 92, 033903 (2004).
[CrossRef] [PubMed]

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Yoon, G.

Zaman, M. M.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Select. Topics Quantum Electron. 9, 267–276 (2003).
[CrossRef]

Zhang, Q.

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Muller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120, 1620–1629 (2001).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406, 35–36 (2000).
[CrossRef] [PubMed]

Zhu, C. F.

T. M. Breslin, F. S. Xu, G. M. Palmer, C. F. Zhu, K. W. Gilchrist, N. Ramanujam, “Autofluorescence and diffuse reflectance properties of malignant and benign breast tissues,” Ann. Surgical Oncol. 11, 65–70 (2004).
[CrossRef]

Zonios, G.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, M. S. Feld, “Detection of preinvasive cancer cells,” Nature 406, 35–36 (2000).
[CrossRef] [PubMed]

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

Ann. Surgical Oncol. (1)

T. M. Breslin, F. S. Xu, G. M. Palmer, C. F. Zhu, K. W. Gilchrist, N. Ramanujam, “Autofluorescence and diffuse reflectance properties of malignant and benign breast tissues,” Ann. Surgical Oncol. 11, 65–70 (2004).
[CrossRef]

Appl. Opt. (5)

Biophys. J. (1)

A. Wax, C. H. Yang, V. Backman, K. Badizadegan, C. W. Boone, R. R. Dasari, M. S. Feld, “Cellular organization and substructure measured using angle-resolved low-coherence interferometry,” Biophys. J. 82, 2256–2264 (2002).

Cancer Res. (1)

A. Wax, C. H. Yang, M. G. Muller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63, 3556–3559 (2003).
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H. K. Roy, Y. Liu, R. K. Wali, Y. L. Kim, A. K. Kromin, M. J. Goldberg, V. Backman, “Four-dimensional elastic light-scattering fingerprints as preneoplastic markers in the rat model of colon carcinogenesis,” Gastroenterology 126, 1071–1081 (2004).
[CrossRef] [PubMed]

I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Muller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology 120, 1620–1629 (2001).
[CrossRef] [PubMed]

IEEE J. Select. Topics Quantum Electron. (3)

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, L. T. Perelman, “Noninvasive sizing of subcellular organelles with light scattering spectroscopy,” IEEE J. Select. Topics Quantum Electron. 9, 267–276 (2003).
[CrossRef]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, V. Backman, “Simultaneous measurement of angular and spectral properties of light scattering for characterization of tissue microarchitecture and its alteration in early precancer,” IEEE J. Select. Topics Quantum Electron. 9, 243–256 (2003).
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S. K. Gayen, M. Alrubaiee, H. E. Savage, S. P. Schantz, R. R. Alfano, “Parotid gland tissues investigated by picosecond time-gated and optical spectroscopic imaging techniques,” IEEE J. Select. Topics Quantum Electron. 7, 906–911 (2001).
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P. E. Wolf, G. Maret, E. Akkermans, R. Maynard, “Optical coherent backscattering by random media: an experimental study,” J. Phys. 49, 63–75 (1988).
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Nature (1)

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[CrossRef] [PubMed]

Nature 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,” Nature Med. 7, 1245–1248 (2001).
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Opt. Express (2)

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R. Vreeker, M. P. van Albada, R. Sprik, A. Lagendijk, “Femtosecond time-resolved measurements of weak localization of light,” Phys. Lett. A 132, 51–54 (1988).
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J. F. Beek, P. Blokland, P. Posthumus, M. Alders, J. W. Pickering, H. Sterenborg, M. J. C. van Gemert, “In vitro double-integrating-sphere optical properties of tissues between 630 and 1064 nm,” Phys. Med. Biol. 42, 2255–2261 (1997).
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[CrossRef]

A. Wax, S. Bali, J. E. Thomas, “Time-resolved phase-space distributions for light backscattered from it disordered medium,” Phys. Rev. Lett. 85, 66–69 (2000).
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H. C. van de Hulst, Light Scattering by Small Particles (Dover, New York, 1995).

M. Born, E. Wolf, Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light, 7th ed. (Cambridge University, Cambridge, UK, 1999), pp. 572–580.

K. W. Kinzler, B. Vogelstein, “Colorectal tumors,” in The Genetic Basis of Human Cancer,B. Vogelstein, K. W. Kinzler, eds. (McGraw-Hill, New York, 1998), pp. 565–587.

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Figures (7)

Fig. 1
Fig. 1

Low-coherent backscattering (LCBS) spectroscopy instrument: (a) C, condenser; L, lenses; A, apertures; P, polarizers; M, mirror; B, beam splitter; SS, sample stage; SP, spectrograph. (b) Unfolded view without the polarizer P2 and the beam splitter B. The entrance slit is in the focal plane of the lens L3. All scattered rays with an identical scattering 3 angle are focused into a point on the entrance slit. The spectrograph disperses this light in the direction perpendicular to the slit according to its wavelengths. Thus the CCD records a matrix of scattered intensities as a function of wavelength and scattering angle I(λ, θ).

Fig. 2
Fig. 2

CBS intensity obtained from a rat colon tissue under low-spatial-coherence illumination (Lcs = 140 μm) as a function of wavelength. Low-coherent backscattering (LCBS) exhibits unique features not present in conventional CBS recorded using coherent light sources. LCBS intensity is speckle-free and dramatically broader (FWHM ~0.3°) than a conventional CBS peak [FWHM ~ 0.001°; see Eq. (1)].

Fig. 3
Fig. 3

(a) Angular profile of the CBS peaks from a sample of white paint (ls* = 4 μm) under low-spatial-coherence illumination (Xe lamp, λ = 632 nm, Lcs = 160 μm) (squares) and coherent illumination (He–Ne laser, Lcs ~ 1 mm) (crosses). Solid black curve: prediction of the conventional diffusion-approximation-based CBS theory.3 The CBS peaks were normalized by the incoherent baseline intensity measured at large backscattering angles (θ > 4°). (b) Inverse CBS peak width w−1 as a function of ls* under low-spatial-coherence illumination (Xe lamp at λ = 632 nm, Lcs = 160 μm) for the aqueous suspensions of polystyrene microspheres. Microspheres of three different diameters, 0.24 μm, 0.30 μm, and 0.89 μm, with the anisotropy factors g = 0.52, 0.69, and 0.92, respectively, were used.

Fig. 4
Fig. 4

(a) Schematic of a two-layered phantom. The phantom consists of a superficial layer of thickness Ts and a base layer of thickness TB(TBls*). The base layer is an optically thick turbid medium consisting of polystyrene microspheres and red blood cells. The superficial layer consists of microspheres but does not contain red blood cells or any other absorbers. (b) Representative CBS intensity at scattering angle θ = 0° recorded from one of typical two-layered tissue phantoms for different physical thicknesses of the superficial layer (ls = 50 μm, ls* = 479 μm, Lcs = 160 μm). The CBS intensity recorded from the base layer without a superficial layer (Ts = 0) shows the characteristic Hb absorption bands at ~ 550 nm. As the thickness of the superficial layer increases (Ts = 35 and 44 μm), the Hb absorption bands vanishes, indicating that the majority of photons contributing to CBS are localized within the superficial layer.

Fig. 5
Fig. 5

(a) Typical CBS intensity obtained from one of typical two-layered physical tissue models (superficial layer: ls = 50 μm, ls* = 126 μm) under low-spatial-coherence illumination (Lcs = 160 μm) as a function of wavelength. The optical thickness of the superficial layer τ = 0.7 and the geometrical thickness Ts = 35 μm. Only the base layer contains absorbers (i.e., RBCs). (b) CBS intensity spectra at different scattering angles θ = 0.0°, 0.26°, and 1.76° in the backward direction. Only the CBS intensity spectrum recorded from the top of the CBS peak (θ = 0°) shows Hb absorption.

Fig. 6
Fig. 6

LCBS spectroscopy of rat colon tissues for detection of early precancer. The CBS intensity spectra were measured from the colonic tissues of the control and AOM-treated rats. The diffuse reflectance spectrum (the inset figure) was measured from the same tissue site on the colon of an AOM-treated rat. The diffuse intensity spectrum shows strong Hb absorption bands that obscure the endogenous spectral signatures of the epithelial layers. For comparison, the LCBS intensity spectrum does not suffer from this problem because CBS-photons are localized within superficial tissue. Moreover, the CBS intensity spectra obtained from control and precancerous tissues are clearly different.

Fig. 7
Fig. 7

Changes in the CBS spectral slope obtained from precancerous colonic tissue 2, 4, and 6 weeks after the initiation of colon carcinogenesis compared with the control values (saline-treated rats). The change in the CBS spectral slope follows the temporal progression of carcinogenesis (analysis of variance P value of 3 × 10−24).

Tables (1)

Tables Icon

Table 1 Optical Properties of the Superficial Layers in the Two-Layered Tissue Models

Equations (3)

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

w λ / ( 3 π l s * ) ,
I CBS ( q ) = P ( r ) exp ( i q · r ) d 2 r ,
I CBS ( q ) 0 r P ( r ) exp ( i q r ) d r ,

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