Abstract

There has been significant interest in developing depth-selective optical interrogation of biological tissue in general and of superficial (e.g., mucosal) tissue in particular. We report an in vivo polarization-gating fiber-optic probe that obtains backscattering spectroscopic measurements from a range of near-surface depths (100200μm). The design and testing was performed with polarized light Monte Carlo simulations and in tissue model experiments. We used the probe to investigate mucosal changes in early carcinogenesis. Measurements performed in the colonic mucosa of 125 human subjects provide the first in vivo evidence that mucosal blood supply is increased early in carcinogenesis, not only in precancerous adenomatous lesions, but also in the histologically normal-appearing tissue surrounding these lesions. This effect was primarily limited to the mucosal microcirculation and was not present in the larger blood vessels located deeper in colonic tissue.

© 2008 Optical Society of America

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    [CrossRef]

2008 (2)

R. Reif, M. S. Amorosino, K. W. Calabro, O. A'Amar, S. K. Singh, and I. J. Bigioa, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt. 13, 010502 (2008).
[CrossRef]

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

2007 (2)

C. J. R. Sheppard, “Fractal model of light scattering in biological tissue and cells,” Opt. Lett. 32, 142-144 (2007).
[CrossRef]

H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

2006 (3)

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101, 343-350 (2006).
[CrossRef]

M. P. Siegel, Y. L. Kim, H. K. Roy, R. K. Wali, and V. Backman, “Assessment of blood supply in superficial tissue by polarization-gated elastic light-scattering spectroscopy,” Appl. Opt. 45, 335-342 (2006).
[CrossRef]

Y. L. Kim, V. M. Turzhitsky, Y. Liu, H. K. Roy, R. K. Wali, H. Subramanian, P. Pradhan, and V. Backman, “Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening,” J. Biomed. Opt. 11, 041125 (2006).

2005 (6)

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10, 044017 (2005).

Y. Liu, Y. L. Kim, X. Li, and V. Backman, “Investigation of depth selectivity of polarization gating for tissue characterization,” Opt. Express 13, 601-611 (2005).
[CrossRef]

J. C. Ramella-Roman, S. A. Prahl, and S. L. Jacques, “Three Monte Carlo programs of polarized light transport into scattering media: part II,” Opt. Express 13, 10392-10405 (2005).
[CrossRef]

J. C. Ramella-Roman, S. A. Prahl, and S. L. Jacques, “Three Monte Carlo programs of polarized light transport into scattering media: part I,” Opt. Express 13, 4420-4438 (2005).
[CrossRef]

H. J. Wei, D. Xing, G. Y. Wu, H. M. Gu, F. J. Lu, Y. Jin, and X. Y. Li, “Differences in optical properties between healthy and pathological human colon tissues using a Ti : sapphire laser: an in vitro study using the Monte Carlo inversion technique,” J. Biomed. Opt. 10, 044022 (2005).
[CrossRef]

2004 (6)

J. C. Finlay and T. H. Foster, “Effect of pigment packaging on diffuse reflectance spectroscopy of samples containing red blood cells,” Opt. Lett. 29, 965-967 (2004).
[CrossRef]

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

L. Nieman, A. Myakov, J. Aaron, and K. Sokolov, “Optical sectioning using a fiber probe with an angled illumination-collection geometry: evaluation in engineered tissue phantoms,” Appl. Opt. 43, 1308-1319 (2004).
[CrossRef]

M. C. Skala, G. M. Palmer, C. F. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial pre-cancers,” Lasers Surg. Med. 34, 25-38 (2004).
[CrossRef]

L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

A. Amelink, H. J. C. M. Sterenborg, M. P. L. Bard, and S. A. Burgers, “In vivo measurement of the local optical properties of tissue by use of differential path-length spectroscopy,” Opt. Lett. 29, 1087-1089 (2004).
[CrossRef]

2003 (3)

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and 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. Sel. Top. Quantum Electron. 9, 243-256 (2003).
[CrossRef]

B. J. M. Braakhuis, M. P. Tabor, J. A. Kummer, C. R. Leemans, and R. H. Brakenhoff, “A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications,” Cancer Res. 63, 1727-1730 (2003).

B. Shpitz, S. Gochberg, D. Neufeld, M. Grankin, G. Buklan, E. Klein, and J. Bernheim, “Angiogenic switch in earliest stages of human colonic tumorigenesis,” Anticancer Res. 23, 5153-5157 (2003).

1999 (1)

1998 (1)

1997 (1)

J. F. Beek, P. Blokland, P. Posthumus, M. Aalders, J. W. Pickering, H. J. C. M. Sterenborg, and 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]

1996 (1)

D. Hanahan and J. Folkman, “Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis,” Cell 86, 353-364 (1996).
[CrossRef]

Aalders, M.

J. F. Beek, P. Blokland, P. Posthumus, M. Aalders, J. W. Pickering, H. J. C. M. Sterenborg, and 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]

A'Amar, O.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A'Amar, S. K. Singh, and I. J. Bigioa, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt. 13, 010502 (2008).
[CrossRef]

Aaron, J.

Amelink, A.

Amorosino, M. S.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A'Amar, S. K. Singh, and I. J. Bigioa, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt. 13, 010502 (2008).
[CrossRef]

Backman, V.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

Y. L. Kim, V. M. Turzhitsky, Y. Liu, H. K. Roy, R. K. Wali, H. Subramanian, P. Pradhan, and V. Backman, “Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening,” J. Biomed. Opt. 11, 041125 (2006).

M. P. Siegel, Y. L. Kim, H. K. Roy, R. K. Wali, and V. Backman, “Assessment of blood supply in superficial tissue by polarization-gated elastic light-scattering spectroscopy,” Appl. Opt. 45, 335-342 (2006).
[CrossRef]

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

Y. Liu, Y. L. Kim, X. Li, and V. Backman, “Investigation of depth selectivity of polarization gating for tissue characterization,” Opt. Express 13, 601-611 (2005).
[CrossRef]

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and 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. Sel. Top. Quantum Electron. 9, 243-256 (2003).
[CrossRef]

Backman, V. M.

Baldwin, A.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Bard, M. P. L.

Beek, J. F.

J. F. Beek, P. Blokland, P. Posthumus, M. Aalders, J. W. Pickering, H. J. C. M. Sterenborg, and 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]

Bender, J. E.

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10, 044017 (2005).

Bennington, J. L.

L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

Bernheim, J.

B. Shpitz, S. Gochberg, D. Neufeld, M. Grankin, G. Buklan, E. Klein, and J. Bernheim, “Angiogenic switch in earliest stages of human colonic tumorigenesis,” Anticancer Res. 23, 5153-5157 (2003).

Bigioa, I. J.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A'Amar, S. K. Singh, and I. J. Bigioa, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt. 13, 010502 (2008).
[CrossRef]

Blokland, P.

J. F. Beek, P. Blokland, P. Posthumus, M. Aalders, J. W. Pickering, H. J. C. M. Sterenborg, and 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]

Bossuyt, P. M.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101, 343-350 (2006).
[CrossRef]

Braakhuis, B. J. M.

B. J. M. Braakhuis, M. P. Tabor, J. A. Kummer, C. R. Leemans, and R. H. Brakenhoff, “A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications,” Cancer Res. 63, 1727-1730 (2003).

Brakenhoff, R. H.

B. J. M. Braakhuis, M. P. Tabor, J. A. Kummer, C. R. Leemans, and R. H. Brakenhoff, “A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications,” Cancer Res. 63, 1727-1730 (2003).

Brotman, M.

L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

Buklan, G.

B. Shpitz, S. Gochberg, D. Neufeld, M. Grankin, G. Buklan, E. Klein, and J. Bernheim, “Angiogenic switch in earliest stages of human colonic tumorigenesis,” Anticancer Res. 23, 5153-5157 (2003).

Burgers, S. A.

Calabro, K. W.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A'Amar, S. K. Singh, and I. J. Bigioa, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt. 13, 010502 (2008).
[CrossRef]

Chang, S. Y.

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

Chen, K.

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and 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. Sel. Top. Quantum Electron. 9, 243-256 (2003).
[CrossRef]

Chen, L. C.

L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

Chiu, Y. S. Y.

L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

Dekker, E.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101, 343-350 (2006).
[CrossRef]

Drezek, R. A.

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10, 044017 (2005).

Eick, A. A.

Feld, M.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Feld, M. S.

Finlay, J. C.

Fitzmaurice, M.

Folkman, J.

D. Hanahan and J. Folkman, “Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis,” Cell 86, 353-364 (1996).
[CrossRef]

Foster, T. H.

Freyer, J. P.

Gendron-Fitzpatrick, A.

M. C. Skala, G. M. Palmer, C. F. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial pre-cancers,” Lasers Surg. Med. 34, 25-38 (2004).
[CrossRef]

Georgakoudi, I.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Gochberg, S.

B. Shpitz, S. Gochberg, D. Neufeld, M. Grankin, G. Buklan, E. Klein, and J. Bernheim, “Angiogenic switch in earliest stages of human colonic tumorigenesis,” Anticancer Res. 23, 5153-5157 (2003).

Goldberg, M. J.

H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and 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. Sel. Top. Quantum Electron. 9, 243-256 (2003).
[CrossRef]

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B. Shpitz, S. Gochberg, D. Neufeld, M. Grankin, G. Buklan, E. Klein, and J. Bernheim, “Angiogenic switch in earliest stages of human colonic tumorigenesis,” Anticancer Res. 23, 5153-5157 (2003).

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C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

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H. J. Wei, D. Xing, G. Y. Wu, H. M. Gu, F. J. Lu, Y. Jin, and X. Y. Li, “Differences in optical properties between healthy and pathological human colon tissues using a Ti : sapphire laser: an in vitro study using the Monte Carlo inversion technique,” J. Biomed. Opt. 10, 044022 (2005).
[CrossRef]

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D. Hanahan and J. Folkman, “Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis,” Cell 86, 353-364 (1996).
[CrossRef]

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L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

Hart, J.

H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

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Horwitz, J.

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

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C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

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Jin, Y.

H. J. Wei, D. Xing, G. Y. Wu, H. M. Gu, F. J. Lu, Y. Jin, and X. Y. Li, “Differences in optical properties between healthy and pathological human colon tissues using a Ti : sapphire laser: an in vitro study using the Monte Carlo inversion technique,” J. Biomed. Opt. 10, 044022 (2005).
[CrossRef]

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Kim, Y.

H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

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C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

M. P. Siegel, Y. L. Kim, H. K. Roy, R. K. Wali, and V. Backman, “Assessment of blood supply in superficial tissue by polarization-gated elastic light-scattering spectroscopy,” Appl. Opt. 45, 335-342 (2006).
[CrossRef]

Y. L. Kim, V. M. Turzhitsky, Y. Liu, H. K. Roy, R. K. Wali, H. Subramanian, P. Pradhan, and V. Backman, “Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening,” J. Biomed. Opt. 11, 041125 (2006).

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

Y. Liu, Y. L. Kim, X. Li, and V. Backman, “Investigation of depth selectivity of polarization gating for tissue characterization,” Opt. Express 13, 601-611 (2005).
[CrossRef]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and 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. Sel. Top. Quantum Electron. 9, 243-256 (2003).
[CrossRef]

Klein, E.

B. Shpitz, S. Gochberg, D. Neufeld, M. Grankin, G. Buklan, E. Klein, and J. Bernheim, “Angiogenic switch in earliest stages of human colonic tumorigenesis,” Anticancer Res. 23, 5153-5157 (2003).

Koetsier, J.

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

Koetsier, J. L.

H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

Kromin, A. K.

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and 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. Sel. Top. Quantum Electron. 9, 243-256 (2003).
[CrossRef]

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B. J. M. Braakhuis, M. P. Tabor, J. A. Kummer, C. R. Leemans, and R. H. Brakenhoff, “A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications,” Cancer Res. 63, 1727-1730 (2003).

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H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

Lee, N. M.

L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

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B. J. M. Braakhuis, M. P. Tabor, J. A. Kummer, C. R. Leemans, and R. H. Brakenhoff, “A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications,” Cancer Res. 63, 1727-1730 (2003).

Levitt, J. M.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Li, X.

Li, X. Y.

H. J. Wei, D. Xing, G. Y. Wu, H. M. Gu, F. J. Lu, Y. Jin, and X. Y. Li, “Differences in optical properties between healthy and pathological human colon tissues using a Ti : sapphire laser: an in vitro study using the Monte Carlo inversion technique,” J. Biomed. Opt. 10, 044022 (2005).
[CrossRef]

Liu, Q.

M. C. Skala, G. M. Palmer, C. F. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial pre-cancers,” Lasers Surg. Med. 34, 25-38 (2004).
[CrossRef]

Liu, Y.

H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

Y. L. Kim, V. M. Turzhitsky, Y. Liu, H. K. Roy, R. K. Wali, H. Subramanian, P. Pradhan, and V. Backman, “Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening,” J. Biomed. Opt. 11, 041125 (2006).

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

Y. Liu, Y. L. Kim, X. Li, and V. Backman, “Investigation of depth selectivity of polarization gating for tissue characterization,” Opt. Express 13, 601-611 (2005).
[CrossRef]

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and 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. Sel. Top. Quantum Electron. 9, 243-256 (2003).
[CrossRef]

Lu, F. J.

H. J. Wei, D. Xing, G. Y. Wu, H. M. Gu, F. J. Lu, Y. Jin, and X. Y. Li, “Differences in optical properties between healthy and pathological human colon tissues using a Ti : sapphire laser: an in vitro study using the Monte Carlo inversion technique,” J. Biomed. Opt. 10, 044022 (2005).
[CrossRef]

Manoharan, R.

Marshek-Stone, C. L.

M. C. Skala, G. M. Palmer, C. F. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial pre-cancers,” Lasers Surg. Med. 34, 25-38 (2004).
[CrossRef]

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L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

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L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

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L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
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L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
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Muenger, K.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

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C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
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Neufeld, D.

B. Shpitz, S. Gochberg, D. Neufeld, M. Grankin, G. Buklan, E. Klein, and J. Bernheim, “Angiogenic switch in earliest stages of human colonic tumorigenesis,” Anticancer Res. 23, 5153-5157 (2003).

Nieman, L.

Palmer, G. M.

M. C. Skala, G. M. Palmer, C. F. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial pre-cancers,” Lasers Surg. Med. 34, 25-38 (2004).
[CrossRef]

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Pfefer, J.

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10, 044017 (2005).

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J. F. Beek, P. Blokland, P. Posthumus, M. Aalders, J. W. Pickering, H. J. C. M. Sterenborg, and 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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J. F. Beek, P. Blokland, P. Posthumus, M. Aalders, J. W. Pickering, H. J. C. M. Sterenborg, and 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]

Pradhan, P.

Y. L. Kim, V. M. Turzhitsky, Y. Liu, H. K. Roy, R. K. Wali, H. Subramanian, P. Pradhan, and V. Backman, “Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening,” J. Biomed. Opt. 11, 041125 (2006).

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S. Prahl, “Tabulated molar extinction coefficient for hemoglobin in water” (Oregon Medical Laser Center, 1998), omlc.ogi.edu/spectra/hemoglobin/summary.html.

Prahl, S. A.

Ramanujam, N.

M. C. Skala, G. M. Palmer, C. F. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial pre-cancers,” Lasers Surg. Med. 34, 25-38 (2004).
[CrossRef]

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Reif, R.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A'Amar, S. K. Singh, and I. J. Bigioa, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt. 13, 010502 (2008).
[CrossRef]

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J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101, 343-350 (2006).
[CrossRef]

Roy, H. K.

H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

Y. L. Kim, V. M. Turzhitsky, Y. Liu, H. K. Roy, R. K. Wali, H. Subramanian, P. Pradhan, and V. Backman, “Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening,” J. Biomed. Opt. 11, 041125 (2006).

M. P. Siegel, Y. L. Kim, H. K. Roy, R. K. Wali, and V. Backman, “Assessment of blood supply in superficial tissue by polarization-gated elastic light-scattering spectroscopy,” Appl. Opt. 45, 335-342 (2006).
[CrossRef]

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and 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. Sel. Top. Quantum Electron. 9, 243-256 (2003).
[CrossRef]

Shen, D.

Sheppard, C. J. R.

Shpitz, B.

B. Shpitz, S. Gochberg, D. Neufeld, M. Grankin, G. Buklan, E. Klein, and J. Bernheim, “Angiogenic switch in earliest stages of human colonic tumorigenesis,” Anticancer Res. 23, 5153-5157 (2003).

Siegel, M. P.

Singh, S. K.

R. Reif, M. S. Amorosino, K. W. Calabro, O. A'Amar, S. K. Singh, and I. J. Bigioa, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt. 13, 010502 (2008).
[CrossRef]

Skala, M. C.

M. C. Skala, G. M. Palmer, C. F. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial pre-cancers,” Lasers Surg. Med. 34, 25-38 (2004).
[CrossRef]

Smith, A. P.

L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
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Sterenborg, H. J. C. M.

A. Amelink, H. J. C. M. Sterenborg, M. P. L. Bard, and S. A. Burgers, “In vivo measurement of the local optical properties of tissue by use of differential path-length spectroscopy,” Opt. Lett. 29, 1087-1089 (2004).
[CrossRef]

J. F. Beek, P. Blokland, P. Posthumus, M. Aalders, J. W. Pickering, H. J. C. M. Sterenborg, and 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]

Stoker, J.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101, 343-350 (2006).
[CrossRef]

Stucenski, L. A.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Subramanian, H.

Y. L. Kim, V. M. Turzhitsky, Y. Liu, H. K. Roy, R. K. Wali, H. Subramanian, P. Pradhan, and V. Backman, “Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening,” J. Biomed. Opt. 11, 041125 (2006).

Tabor, M. P.

B. J. M. Braakhuis, M. P. Tabor, J. A. Kummer, C. R. Leemans, and R. H. Brakenhoff, “A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications,” Cancer Res. 63, 1727-1730 (2003).

Tian, F.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
[CrossRef]

Turzhitsky, V.

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

Turzhitsky, V. M.

Y. L. Kim, V. M. Turzhitsky, Y. Liu, H. K. Roy, R. K. Wali, H. Subramanian, P. Pradhan, and V. Backman, “Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening,” J. Biomed. Opt. 11, 041125 (2006).

Utzinger, U.

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10, 044017 (2005).

van Dam, J.

van Deventer, S. J.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101, 343-350 (2006).
[CrossRef]

van Gemert, M. J. C.

J. F. Beek, P. Blokland, P. Posthumus, M. Aalders, J. W. Pickering, H. J. C. M. Sterenborg, and 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]

van Rijn, J. C.

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101, 343-350 (2006).
[CrossRef]

Vrotsos, K. M.

M. C. Skala, G. M. Palmer, C. F. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial pre-cancers,” Lasers Surg. Med. 34, 25-38 (2004).
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H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

Y. L. Kim, V. M. Turzhitsky, Y. Liu, H. K. Roy, R. K. Wali, H. Subramanian, P. Pradhan, and V. Backman, “Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening,” J. Biomed. Opt. 11, 041125 (2006).

M. P. Siegel, Y. L. Kim, H. K. Roy, R. K. Wali, and V. Backman, “Assessment of blood supply in superficial tissue by polarization-gated elastic light-scattering spectroscopy,” Appl. Opt. 45, 335-342 (2006).
[CrossRef]

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and 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. Sel. Top. Quantum Electron. 9, 243-256 (2003).
[CrossRef]

Wang, A. M. J.

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10, 044017 (2005).

Wei, H. J.

H. J. Wei, D. Xing, G. Y. Wu, H. M. Gu, F. J. Lu, Y. Jin, and X. Y. Li, “Differences in optical properties between healthy and pathological human colon tissues using a Ti : sapphire laser: an in vitro study using the Monte Carlo inversion technique,” J. Biomed. Opt. 10, 044022 (2005).
[CrossRef]

Wong, P.

L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

Wu, G. Y.

H. J. Wei, D. Xing, G. Y. Wu, H. M. Gu, F. J. Lu, Y. Jin, and X. Y. Li, “Differences in optical properties between healthy and pathological human colon tissues using a Ti : sapphire laser: an in vitro study using the Monte Carlo inversion technique,” J. Biomed. Opt. 10, 044022 (2005).
[CrossRef]

Xing, D.

H. J. Wei, D. Xing, G. Y. Wu, H. M. Gu, F. J. Lu, Y. Jin, and X. Y. Li, “Differences in optical properties between healthy and pathological human colon tissues using a Ti : sapphire laser: an in vitro study using the Monte Carlo inversion technique,” J. Biomed. Opt. 10, 044022 (2005).
[CrossRef]

Zhu, C. F.

M. C. Skala, G. M. Palmer, C. F. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial pre-cancers,” Lasers Surg. Med. 34, 25-38 (2004).
[CrossRef]

Zonios, G.

Am. J. Gastroenterol. (1)

J. C. van Rijn, J. B. Reitsma, J. Stoker, P. M. Bossuyt, S. J. van Deventer, and E. Dekker, “Polyp miss rate determined by tandem colonoscopy: a systematic review,” Am. J. Gastroenterol. 101, 343-350 (2006).
[CrossRef]

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B. Shpitz, S. Gochberg, D. Neufeld, M. Grankin, G. Buklan, E. Klein, and J. Bernheim, “Angiogenic switch in earliest stages of human colonic tumorigenesis,” Anticancer Res. 23, 5153-5157 (2003).

Appl. Opt. (4)

Cancer Res. (2)

B. J. M. Braakhuis, M. P. Tabor, J. A. Kummer, C. R. Leemans, and R. H. Brakenhoff, “A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications,” Cancer Res. 63, 1727-1730 (2003).

L. C. Chen, C. Y. Hao, Y. S. Y. Chiu, P. Wong, J. S. Melnick, M. Brotman, J. Moretto, F. Mendes, A. P. Smith, J. L. Bennington, D. Moore, and N. M. Lee, “Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients,” Cancer Res. 64, 3694-3700 (2004).
[CrossRef]

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D. Hanahan and J. Folkman, “Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis,” Cell 86, 353-364 (1996).
[CrossRef]

FEBS Lett. (1)

H. K. Roy, R. K. Wali, Y. Kim, Y. Liu, J. Hart, D. P. Kunte, J. L. Koetsier, M. J. Goldberg, and V. Backman, “Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis,” FEBS Lett. 581, 3857-3862 (2007).
[CrossRef]

Gastroenterology (1)

H. K. Roy, R. K. Wali, J. Koetsier, Y. Liu, Y. Kim, M. J. Goldberg, S. Y. Chang, J. Horwitz, V. Turzhitsky, and V. Backman, “Increased mucosal blood supply is an early preneoplastic marker in colon neoplasia,” Gastroenterology 126, A-38 (2004).
[CrossRef]

Gut (1)

R. K. Wali, H. K. Roy, Y. L. Kim, Y. Liu, J. L. Koetsier, D. P. Kunte, M. J. Goldberg, V. Turzhitsky, and V. Backman, “Increased microvascular blood content is an early event in colon carcinogenesis,” Gut 54, 654-660 (2005).
[CrossRef]

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

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, M. J. Goldberg, A. K. Kromin, K. Chen, and 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. Sel. Top. Quantum Electron. 9, 243-256 (2003).
[CrossRef]

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C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Muenger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer 122, 363-371 (2008).
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J. Biomed. Opt. (4)

H. J. Wei, D. Xing, G. Y. Wu, H. M. Gu, F. J. Lu, Y. Jin, and X. Y. Li, “Differences in optical properties between healthy and pathological human colon tissues using a Ti : sapphire laser: an in vitro study using the Monte Carlo inversion technique,” J. Biomed. Opt. 10, 044022 (2005).
[CrossRef]

Y. L. Kim, V. M. Turzhitsky, Y. Liu, H. K. Roy, R. K. Wali, H. Subramanian, P. Pradhan, and V. Backman, “Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening,” J. Biomed. Opt. 11, 041125 (2006).

R. Reif, M. S. Amorosino, K. W. Calabro, O. A'Amar, S. K. Singh, and I. J. Bigioa, “Analysis of changes in reflectance measurements on biological tissues subjected to different probe pressures,” J. Biomed. Opt. 13, 010502 (2008).
[CrossRef]

A. M. J. Wang, J. E. Bender, J. Pfefer, U. Utzinger, and R. A. Drezek, “Depth-sensitive reflectance measurements using obliquely oriented fiber probes,” J. Biomed. Opt. 10, 044017 (2005).

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M. C. Skala, G. M. Palmer, C. F. Zhu, Q. Liu, K. M. Vrotsos, C. L. Marshek-Stone, A. Gendron-Fitzpatrick, and N. Ramanujam, “Investigation of fiber-optic probe designs for optical spectroscopic diagnosis of epithelial pre-cancers,” Lasers Surg. Med. 34, 25-38 (2004).
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J. F. Beek, P. Blokland, P. Posthumus, M. Aalders, J. W. Pickering, H. J. C. M. Sterenborg, and 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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Figures (9)

Fig. 1
Fig. 1

Conceptualization of polarized light Monte Carlo numerical experiment. An infinitely narrow illumination fiber results in an illumination area with normal incidence onto the tissue surface. The collection area is identical to the illumination area and is controlled by the NA of the fibers and the focal length, f, of the lens.

Fig. 2
Fig. 2

Experimental setup. A fiber-optic probe is designed to collect backscattering angles of approximately 10 ° 20 ° with a 700 μm diameter illumination/collection area. (a) The probe consists of an input fiber, which is coupled to a xenon lamp, and two output fibers that are connected to an imaging spectrometer. (b) A magnified view of the probe tip, which comes in contact with the sample.

Fig. 3
Fig. 3

Schematic of the probe tip, showing the fibers, sheet polarizers, GRIN lens, and cover glass. The bottom left is a cross-section view showing the position of the orthogonally oriented polarizers with respect to the source fiber (S), copolarized collection fiber ( | | ), and cross-polarized collection channel (⊥). The bottom right shows the location and size of the illumination area, also corresponding to the location and size of the collection areas of the collecting fibers.

Fig. 4
Fig. 4

Experimental verification of penetration depth. (a) Representative data from a saturation curve experiment where the intensity is recorded as a function of the sample thickness, normalized by the maximum value (i.e., cumulative probability distribution). (b) Intensity distribution as a function of depth, calculated by taking the derivative of the intensity versus the sample thickness curve, normalized by the total area. (c) Average penetration depths for each of the polarization-gating signals taken from samples with a range of optical properties ( μ s = 35 111 cm 1 , μ a = 0 , g = 0.8 0.92 ).

Fig. 5
Fig. 5

Polarized light Monte Carlo results of penetration depth for each polarization signal (scaled by ls). (a) Average penetration depth for varying collection angles for each polarization-gating signal ( R / ls * = 0.5 ). (b) Average penetration depth for varying illumination/collection spot sizes for 9 + / 9 ° backscattering collection angle (medium μ s = 100 cm 1 , μ a = 0 , g = 0.87 ).

Fig. 6
Fig. 6

Calibration curves obtained for (a) delta-polarized, (b) copolarized, and (c) cross-polarized signals from the probe in phantoms with varying hemoglobin and scattering coefficient. The region within the horizontal and vertical dashed lines indicates concentrations that are typical for colon tissue (experimentally determined). The anisotropy factor was kept constant for these measurements ( g = 0.88 at λ = 540 nm ).

Fig. 7
Fig. 7

Example spectra obtained from polarization-gating probe in tissue. The model fit is shown as a solid line.

Fig. 8
Fig. 8

Probe measurements of Hb content from adenomatous lesions and uninvolved mucosa away from the lesion as compared to control patients with no dysplasia. There is a large difference between the Hb content of normal tissue from patients with no dysplasia (white bars) and adenomatous tissue (dark gray bars) for all three polarization-gating signals ( p < 0.01 ). There is also a significant difference between the Hb content from control patients and uninvolved mucosa measurements from colonic segments with adenomas. This difference in normal-appearing tissue progressively diminishes for probe signals with larger penetration depths (i.e., p = 0.03 for 95 μm depth, p = 0.24 for 185 μm depth).

Fig. 9
Fig. 9

Comparison of Hb content from patients with varying significance of precancerous lesions measured 10 30 cm away from the lesion. Patients with advanced adenomas have the highest increase in Hb content away from the lesion. This increase in Hb progressively diminishes for polarization signals with larger penetration depths.

Equations (10)

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I ( λ ) = i ( λ ) BG ( λ ) K · RF ( λ ) ,
I | | ( λ ) = i | | ( λ ) BG | | ( λ ) RF | | ( λ ) ,
Δ I ( λ ) = I | | ( λ ) I ( λ ) ,
I ( λ ) = I scattering ( λ ) · e α Hb O 2 · A Hb O 2 ( λ ) α Hb · A Hb ( λ ) ,
Q = ( 1 2 ( 2 μ a r ) 2 [ 1 ( 2 μ a r + 1 ) e 2 μ a r ] ) 3 ( 4 μ a r ) ,
I scattering ( λ ) λ 2 β 4 ,
I scattering ( λ ) = I ( λ ) · exp [ α Hb · A Hb ( λ ) · Q ( λ ) + α Hb O 2 · A Hb O 2 ( λ ) · Q ( λ ) ] λ 2 β 4 .
C ( T ) = 0 T I ( z ) d z .
d C d T = I ( z ) ,
AP = 0 2 cm z · I ( z ) · d z .

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