Abstract

A noninvasive optical diagnostic system for detection of cancerous and precancerous lesions of the cervix was evaluated in vivo. The optical system included a fiber-optic probe designed to measure polarized and unpolarized light transport properties of a small volume of tissue. An algorithm for diagnosing tissue based on the optical measurements was developed that used four optical properties, three of which were related to light scattering properties and the fourth of which was related to hemoglobin concentration. A sensitivity of 77% and specificities in the mid 60% range were obtained for separating high grade squamous intraepithelial lesions and cancer from other pathologies and normal tissue. The use of different cross-validation methods in algorithm development is analyzed, and the relative difficulties of diagnosing certain pathologies are assessed. Furthermore, the robustness of the optical system for use by different doctors and to changes in fiber-optic probe are also assessed, and potential improvements in the optical system are discussed.

© 2009 Optical Society of America

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  1. J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
    [CrossRef] [PubMed]
  2. J. T. Cox, M. Schiffman, and D. Solomon, “Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy,” Am. J. Obstet. Gynecol. 188, 1401-1412 (2003).
    [CrossRef]
  3. M. Spitzer, A. E. Cheryns, and V. L. Seltzer, “The use of large loop excision of the transformation zone in an inner-city population,” Obstet. Gynecol. 82, 731-735 (1993).
    [PubMed]
  4. L. A. Dainty, J. C. Elkas, G. S. Rose, and C. M. Zahn, “Controversial topics in abnormal cervical cytology: “see and treat”,” Clin. Obstet. Gynecol. 48, 193-201 (2005).
    [CrossRef] [PubMed]
  5. R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
  9. J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, “Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells,” Cancer Cytopath. 84, 366-374 (1998).
  10. J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical tissue diagnostics,” Appl. Opt. 37, 3586-3593 (1998).
    [CrossRef]
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    [CrossRef]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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  19. R. Drezek, M. Guillard, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt. 8, 7-16 (2003).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  21. I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
    [CrossRef] [PubMed]
  22. N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
    [CrossRef] [PubMed]
  23. R. J. Nordstrom, L. Burke, J. M. Niloff, and J. F. Myrtle, “Identification of cervical neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118-127 (2001).
    [CrossRef] [PubMed]
  24. W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
    [CrossRef] [PubMed]
  25. D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).
  26. R. D. Alvarez and T. C. Wright, “Effective cervical neoplasia detection with a novel optical detection system: A randomized trial,” Gynecol. Oncol. 104, 281-289 (2007).
    [CrossRef]
  27. R. D. Alvarez and T. C. Wright, “Increased detection of high-grade cervical intraepithelial neoplasia utilizing an optical detection system as an adjunct to colposcopy,” Gynecol. Oncol. 106, 23-28 (2007).
    [CrossRef] [PubMed]

2007 (5)

R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
[CrossRef] [PubMed]

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

R. D. Alvarez and T. C. Wright, “Effective cervical neoplasia detection with a novel optical detection system: A randomized trial,” Gynecol. Oncol. 104, 281-289 (2007).
[CrossRef]

R. D. Alvarez and T. C. Wright, “Increased detection of high-grade cervical intraepithelial neoplasia utilizing an optical detection system as an adjunct to colposcopy,” Gynecol. Oncol. 106, 23-28 (2007).
[CrossRef] [PubMed]

J. Ramachandran, T. M. Powers, S. Carpenter, A. Garcia-Lopez, J. P. Freyer, and J. R. Mourant “Light scattering and microarchitectural differences between tumorigenic and nontumorigenic cell models of tissue,” Opt. Express 15, 4039-4053 (2007).
[CrossRef] [PubMed]

2006 (1)

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

2005 (2)

L. A. Dainty, J. C. Elkas, G. S. Rose, and C. M. Zahn, “Controversial topics in abnormal cervical cytology: “see and treat”,” Clin. Obstet. Gynecol. 48, 193-201 (2005).
[CrossRef] [PubMed]

S. K. Chang, Y. N. Mirabal, E. N. Atkinson, D. Cox, A. Malpica, M. Follen, and R. Richards-Kortum, “Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.” J. Biomed. Opt. 10, 024031 (2005).
[CrossRef] [PubMed]

2004 (1)

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

2003 (2)

J. T. Cox, M. Schiffman, and D. Solomon, “Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy,” Am. J. Obstet. Gynecol. 188, 1401-1412 (2003).
[CrossRef]

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

2002 (3)

R. L. P. van Veen, W. Verkryusse, and H. J. M. C. Sterenborg, “Diffuse-reflectance spectroscopy from 500 to 1060 nm by correction for inhomogeneously distributed absorbers,” Opt. Lett. 27, 246-248 (2002).
[CrossRef]

I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
[CrossRef] [PubMed]

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, and R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587-594 (2002).
[CrossRef] [PubMed]

2001 (3)

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

R. J. Nordstrom, L. Burke, J. M. Niloff, and J. F. Myrtle, “Identification of cervical neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118-127 (2001).
[CrossRef] [PubMed]

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

2000 (1)

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt. 5, 131-137(2000).
[CrossRef] [PubMed]

1999 (1)

1998 (2)

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical tissue diagnostics,” Appl. Opt. 37, 3586-3593 (1998).
[CrossRef]

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, “Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells,” Cancer Cytopath. 84, 366-374 (1998).

1996 (1)

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

1995 (1)

R. Kohavi, “A study of cross-validation and bootstrap for accuracy estimation and model selection,” in Proceedings of the Fourteenth International Joint Conference on Artificial Intelligence (IJCAI) (IJCAI, 1995), Vol. 2, 1137-1143.

1993 (1)

M. Spitzer, A. E. Cheryns, and V. L. Seltzer, “The use of large loop excision of the transformation zone in an inner-city population,” Obstet. Gynecol. 82, 731-735 (1993).
[PubMed]

1992 (1)

L. Breiman and P. Spector, “Submodel selection and evaluation in regression--the X-random case,” Int. Statist. Rev. 60, 291-319 (1992).
[CrossRef]

1983 (1)

B. Efron, “Estimating the error rate of a prediction rule: improvement on cross-validation,” J. Am. Stat. Assoc. 78, 316-331 (1983).
[CrossRef]

Abbey, K.

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

Agrawal, A.

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

Alvarez, R. D.

R. D. Alvarez and T. C. Wright, “Increased detection of high-grade cervical intraepithelial neoplasia utilizing an optical detection system as an adjunct to colposcopy,” Gynecol. Oncol. 106, 23-28 (2007).
[CrossRef] [PubMed]

R. D. Alvarez and T. C. Wright, “Effective cervical neoplasia detection with a novel optical detection system: A randomized trial,” Gynecol. Oncol. 104, 281-289 (2007).
[CrossRef]

Atkinson, E. N.

S. K. Chang, Y. N. Mirabal, E. N. Atkinson, D. Cox, A. Malpica, M. Follen, and R. Richards-Kortum, “Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.” J. Biomed. Opt. 10, 024031 (2005).
[CrossRef] [PubMed]

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, and R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587-594 (2002).
[CrossRef] [PubMed]

Atkinson, N.

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

Avarez, R. D.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Backman, V.

I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
[CrossRef] [PubMed]

Badizadegan, K.

I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
[CrossRef] [PubMed]

Bambot, S.

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

Bocklage, T. J.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of HSIL and cancers in cervical tissue by in vivo light scattering,” J. Lower Genital Tract Disease , to be published.

Boiko, I.

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

Breiman, L.

L. Breiman and P. Spector, “Submodel selection and evaluation in regression--the X-random case,” Int. Statist. Rev. 60, 291-319 (1992).
[CrossRef]

Brocker, C.

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt. 5, 131-137(2000).
[CrossRef] [PubMed]

Bullock, K. L.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

Burke, L.

R. J. Nordstrom, L. Burke, J. M. Niloff, and J. F. Myrtle, “Identification of cervical neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118-127 (2001).
[CrossRef] [PubMed]

Burmke, L.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Canpolat, M.

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt. 5, 131-137(2000).
[CrossRef] [PubMed]

Carpenter, S.

Cestero, R. M.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Chang, S. K.

S. K. Chang, Y. N. Mirabal, E. N. Atkinson, D. Cox, A. Malpica, M. Follen, and R. Richards-Kortum, “Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.” J. Biomed. Opt. 10, 024031 (2005).
[CrossRef] [PubMed]

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, and R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587-594 (2002).
[CrossRef] [PubMed]

Cherian, J.

R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
[CrossRef] [PubMed]

Cheryns, A. E.

M. Spitzer, A. E. Cheryns, and V. L. Seltzer, “The use of large loop excision of the transformation zone in an inner-city population,” Obstet. Gynecol. 82, 731-735 (1993).
[PubMed]

Collier, T.

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

Cox, D.

S. K. Chang, Y. N. Mirabal, E. N. Atkinson, D. Cox, A. Malpica, M. Follen, and R. Richards-Kortum, “Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.” J. Biomed. Opt. 10, 024031 (2005).
[CrossRef] [PubMed]

Cox, J. T.

J. T. Cox, M. Schiffman, and D. Solomon, “Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy,” Am. J. Obstet. Gynecol. 188, 1401-1412 (2003).
[CrossRef]

Crum, C. P.

I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
[CrossRef] [PubMed]

Dainty, L. A.

L. A. Dainty, J. C. Elkas, G. S. Rose, and C. M. Zahn, “Controversial topics in abnormal cervical cytology: “see and treat”,” Clin. Obstet. Gynecol. 48, 193-201 (2005).
[CrossRef] [PubMed]

Dasari, R. R.

I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
[CrossRef] [PubMed]

Dickman, E. D.

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

Dippery, S.

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

Dorin, M. H.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of HSIL and cancers in cervical tissue by in vivo light scattering,” J. Lower Genital Tract Disease , to be published.

Drezek, R.

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

Efron, B.

B. Efron, “Estimating the error rate of a prediction rule: improvement on cross-validation,” J. Am. Stat. Assoc. 78, 316-331 (1983).
[CrossRef]

Eick, A. A.

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical tissue diagnostics,” Appl. Opt. 37, 3586-3593 (1998).
[CrossRef]

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, “Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells,” Cancer Cytopath. 84, 366-374 (1998).

Elkas, J. C.

L. A. Dainty, J. C. Elkas, G. S. Rose, and C. M. Zahn, “Controversial topics in abnormal cervical cytology: “see and treat”,” Clin. Obstet. Gynecol. 48, 193-201 (2005).
[CrossRef] [PubMed]

Esmy, P. O.

R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
[CrossRef] [PubMed]

Esponda-Ramos, O.

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt. 5, 131-137(2000).
[CrossRef] [PubMed]

Faupel, M. A.

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

Fayette, J. M.

R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
[CrossRef] [PubMed]

Feld, M. S.

I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
[CrossRef] [PubMed]

Ferris, D. G.

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

Flewelling, R. F.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Follen, M.

S. K. Chang, Y. N. Mirabal, E. N. Atkinson, D. Cox, A. Malpica, M. Follen, and R. Richards-Kortum, “Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.” J. Biomed. Opt. 10, 024031 (2005).
[CrossRef] [PubMed]

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

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, and R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587-594 (2002).
[CrossRef] [PubMed]

Frappart, L.

R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
[CrossRef] [PubMed]

Freyer, J. P.

J. Ramachandran, T. M. Powers, S. Carpenter, A. Garcia-Lopez, J. P. Freyer, and J. R. Mourant “Light scattering and microarchitectural differences between tumorigenic and nontumorigenic cell models of tissue,” Opt. Express 15, 4039-4053 (2007).
[CrossRef] [PubMed]

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

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt. 5, 131-137(2000).
[CrossRef] [PubMed]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical tissue diagnostics,” Appl. Opt. 37, 3586-3593 (1998).
[CrossRef]

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, “Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells,” Cancer Cytopath. 84, 366-374 (1998).

Gage, J. C.

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

Garcia, F. A.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Garcia-Lopez, A.

Gardner, S.

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

Georgakoudi, I.

I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
[CrossRef] [PubMed]

Gold, M. A.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Greene, H. M.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of HSIL and cancers in cervical tissue by in vivo light scattering,” J. Lower Genital Tract Disease , to be published.

Grogan, S.

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

Guido, R. S.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Guillard, M.

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

Hanson, V. W.

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

Harper, D.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Hielscher, A. H.

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, “Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells,” Cancer Cytopath. 84, 366-374 (1998).

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical tissue diagnostics,” Appl. Opt. 37, 3586-3593 (1998).
[CrossRef]

Holtzapple, N.

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

Huh, W. K.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Jansen, A. Mahadevan.

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

Jeronimo, J.

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

Johnson, T.

Johnson, T. M.

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

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt. 5, 131-137(2000).
[CrossRef] [PubMed]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical tissue diagnostics,” Appl. Opt. 37, 3586-3593 (1998).
[CrossRef]

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, “Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells,” Cancer Cytopath. 84, 366-374 (1998).

Kohavi, R.

R. Kohavi, “A study of cross-validation and bootstrap for accuracy estimation and model selection,” in Proceedings of the Fourteenth International Joint Conference on Artificial Intelligence (IJCAI) (IJCAI, 1995), Vol. 2, 1137-1143.

Kortum, R. Richards.

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

Kubota, J.

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

Lawhead, R. A.

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

Macaulay, C.

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

Malpica, A.

S. K. Chang, Y. N. Mirabal, E. N. Atkinson, D. Cox, A. Malpica, M. Follen, and R. Richards-Kortum, “Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.” J. Biomed. Opt. 10, 024031 (2005).
[CrossRef] [PubMed]

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

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, and R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587-594 (2002).
[CrossRef] [PubMed]

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

Marr-Lyon, L. R.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

Matanock, A.

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt. 5, 131-137(2000).
[CrossRef] [PubMed]

McIntyre-Seltman, K.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Miller, J. A.

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

Mirabal, Y. N.

S. K. Chang, Y. N. Mirabal, E. N. Atkinson, D. Cox, A. Malpica, M. Follen, and R. Richards-Kortum, “Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.” J. Biomed. Opt. 10, 024031 (2005).
[CrossRef] [PubMed]

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, and R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587-594 (2002).
[CrossRef] [PubMed]

Mitchell, M. F.

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

Mourant, J.

Mourant, J. R.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

J. Ramachandran, T. M. Powers, S. Carpenter, A. Garcia-Lopez, J. P. Freyer, and J. R. Mourant “Light scattering and microarchitectural differences between tumorigenic and nontumorigenic cell models of tissue,” Opt. Express 15, 4039-4053 (2007).
[CrossRef] [PubMed]

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

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt. 5, 131-137(2000).
[CrossRef] [PubMed]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical tissue diagnostics,” Appl. Opt. 37, 3586-3593 (1998).
[CrossRef]

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, “Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells,” Cancer Cytopath. 84, 366-374 (1998).

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of HSIL and cancers in cervical tissue by in vivo light scattering,” J. Lower Genital Tract Disease , to be published.

Mulller, M. G.

I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
[CrossRef] [PubMed]

Myrtle, J. F.

R. J. Nordstrom, L. Burke, J. M. Niloff, and J. F. Myrtle, “Identification of cervical neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118-127 (2001).
[CrossRef] [PubMed]

Niloff, J. M.

R. J. Nordstrom, L. Burke, J. M. Niloff, and J. F. Myrtle, “Identification of cervical neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118-127 (2001).
[CrossRef] [PubMed]

Nordstrom, R. J.

R. J. Nordstrom, L. Burke, J. M. Niloff, and J. F. Myrtle, “Identification of cervical neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118-127 (2001).
[CrossRef] [PubMed]

Powers, T. M.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

J. Ramachandran, T. M. Powers, S. Carpenter, A. Garcia-Lopez, J. P. Freyer, and J. R. Mourant “Light scattering and microarchitectural differences between tumorigenic and nontumorigenic cell models of tissue,” Opt. Express 15, 4039-4053 (2007).
[CrossRef] [PubMed]

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of HSIL and cancers in cervical tissue by in vivo light scattering,” J. Lower Genital Tract Disease , to be published.

Rajkumnar, R.

R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
[CrossRef] [PubMed]

Ramachandran, J.

Ramanujam, N.

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

Richards-Kortum, R.

S. K. Chang, Y. N. Mirabal, E. N. Atkinson, D. Cox, A. Malpica, M. Follen, and R. Richards-Kortum, “Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.” J. Biomed. Opt. 10, 024031 (2005).
[CrossRef] [PubMed]

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

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, and R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587-594 (2002).
[CrossRef] [PubMed]

Rose, G. S.

L. A. Dainty, J. C. Elkas, G. S. Rose, and C. M. Zahn, “Controversial topics in abnormal cervical cytology: “see and treat”,” Clin. Obstet. Gynecol. 48, 193-201 (2005).
[CrossRef] [PubMed]

Sankaranarayanan, R.

R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
[CrossRef] [PubMed]

Schiffman, M.

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

J. T. Cox, M. Schiffman, and D. Solomon, “Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy,” Am. J. Obstet. Gynecol. 188, 1401-1412 (2003).
[CrossRef]

Seltzer, V. L.

M. Spitzer, A. E. Cheryns, and V. L. Seltzer, “The use of large loop excision of the transformation zone in an inner-city population,” Obstet. Gynecol. 82, 731-735 (1993).
[PubMed]

Shanthakumary, S.

R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
[CrossRef] [PubMed]

Sheets, E. E.

I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
[CrossRef] [PubMed]

Shen, D.

Smith, H. O.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of HSIL and cancers in cervical tissue by in vivo light scattering,” J. Lower Genital Tract Disease , to be published.

Solomon, D.

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

J. T. Cox, M. Schiffman, and D. Solomon, “Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy,” Am. J. Obstet. Gynecol. 188, 1401-1412 (2003).
[CrossRef]

Spector, P.

L. Breiman and P. Spector, “Submodel selection and evaluation in regression--the X-random case,” Int. Statist. Rev. 60, 291-319 (1992).
[CrossRef]

Spitzer, M.

M. Spitzer, A. E. Cheryns, and V. L. Seltzer, “The use of large loop excision of the transformation zone in an inner-city population,” Obstet. Gynecol. 82, 731-735 (1993).
[PubMed]

Staerkel, G.

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

Sterenborg, H. J. M. C.

Stetter, K.

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt. 5, 131-137(2000).
[CrossRef] [PubMed]

Sum, S. T.

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

Thara, S.

R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
[CrossRef] [PubMed]

Thomsen, S. L.

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

van Veen, R. L. P.

Verkryusse, W.

Waxman, A. G.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of HSIL and cancers in cervical tissue by in vivo light scattering,” J. Lower Genital Tract Disease , to be published.

Wright, T.

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

Wright, T. C.

R. D. Alvarez and T. C. Wright, “Increased detection of high-grade cervical intraepithelial neoplasia utilizing an optical detection system as an adjunct to colposcopy,” Gynecol. Oncol. 106, 23-28 (2007).
[CrossRef] [PubMed]

R. D. Alvarez and T. C. Wright, “Effective cervical neoplasia detection with a novel optical detection system: A randomized trial,” Gynecol. Oncol. 104, 281-289 (2007).
[CrossRef]

Zahn, C. M.

L. A. Dainty, J. C. Elkas, G. S. Rose, and C. M. Zahn, “Controversial topics in abnormal cervical cytology: “see and treat”,” Clin. Obstet. Gynecol. 48, 193-201 (2005).
[CrossRef] [PubMed]

Zsemlye, M. M.

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of HSIL and cancers in cervical tissue by in vivo light scattering,” J. Lower Genital Tract Disease , to be published.

Am. J. Obstet. .Gynecol. (1)

I. Georgakoudi, E. E. Sheets, M. G. Mulller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and charaterization of cervical precancers in vivo,” Am. J. Obstet. .Gynecol. 186, 374-382 (2002).
[CrossRef] [PubMed]

Am. J. Obstet. Gynecol. (2)

W. K. Huh, R. M. Cestero, F. A. Garcia, M. A. Gold, R. S. Guido, K. McIntyre-Seltman, D. Harper, L. Burmke, S. T. Sum, R. F. Flewelling, and R. D. Avarez, “Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of 604 patient study,” Am. J. Obstet. Gynecol. 190, 1249-57(2004).
[CrossRef] [PubMed]

J. T. Cox, M. Schiffman, and D. Solomon, “Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy,” Am. J. Obstet. Gynecol. 188, 1401-1412 (2003).
[CrossRef]

Appl. Opt. (2)

Br. J. Cancer (1)

R. Sankaranarayanan, R. Rajkumnar, P. O. Esmy, J. M. Fayette, S. Shanthakumary, L. Frappart, S. Thara, and J. Cherian, “Effectiveness, safety and acceptability of 'see and treat' with cryotherapy by nurses in a cervical screening study in India,” Br. J. Cancer 96, 738-743(2007).
[CrossRef] [PubMed]

Cancer Cytopath. (1)

J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, “Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells,” Cancer Cytopath. 84, 366-374 (1998).

Clin. Obstet. Gynecol. (1)

L. A. Dainty, J. C. Elkas, G. S. Rose, and C. M. Zahn, “Controversial topics in abnormal cervical cytology: “see and treat”,” Clin. Obstet. Gynecol. 48, 193-201 (2005).
[CrossRef] [PubMed]

Gynecol. Oncol. (3)

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, K. L. Bullock, L. R. Marr-Lyon, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “In vivo light scattering measurements for detection of precancerous conditions of the cervix,” Gynecol. Oncol. 105, 439-445 (2007).
[CrossRef] [PubMed]

R. D. Alvarez and T. C. Wright, “Effective cervical neoplasia detection with a novel optical detection system: A randomized trial,” Gynecol. Oncol. 104, 281-289 (2007).
[CrossRef]

R. D. Alvarez and T. C. Wright, “Increased detection of high-grade cervical intraepithelial neoplasia utilizing an optical detection system as an adjunct to colposcopy,” Gynecol. Oncol. 106, 23-28 (2007).
[CrossRef] [PubMed]

Int. Statist. Rev. (1)

L. Breiman and P. Spector, “Submodel selection and evaluation in regression--the X-random case,” Int. Statist. Rev. 60, 291-319 (1992).
[CrossRef]

J. Am. Stat. Assoc. (1)

B. Efron, “Estimating the error rate of a prediction rule: improvement on cross-validation,” J. Am. Stat. Assoc. 78, 316-331 (1983).
[CrossRef]

J. Biomed. Opt. (4)

J. R. Mourant, M. Canpolat, C. Brocker, O. Esponda-Ramos, T. M. Johnson, A. Matanock, K. Stetter, and J. P. Freyer, “Light scattering from cells: the contribution of the nucleus and the effects of proliferative status,” J. Biomed. Opt. 5, 131-137(2000).
[CrossRef] [PubMed]

S. K. Chang, Y. N. Mirabal, E. N. Atkinson, D. Cox, A. Malpica, M. Follen, and R. Richards-Kortum, “Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.” J. Biomed. Opt. 10, 024031 (2005).
[CrossRef] [PubMed]

Y. N. Mirabal, S. K. Chang, E. N. Atkinson, A. Malpica, M. Follen, and R. Richards-Kortum, “Reflectance spectroscopy for in vivo detection of cervical precancer,” J. Biomed. Opt. 7, 587-594 (2002).
[CrossRef] [PubMed]

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

J. Lower Gen. Tract Disease (1)

D. G. Ferris, R. A. Lawhead, E. D. Dickman, N. Holtzapple, J. A. Miller, S. Grogan, S. Bambot, A. Agrawal, and M. A. Faupel, “Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia,” J. Lower Gen. Tract Disease 5, 65-72 (2001).

J. Lower Genital Tract Disease (1)

J. R. Mourant, T. J. Bocklage, T. M. Powers, H. M. Greene, M. H. Dorin, A. G. Waxman, M. M. Zsemlye, and H. O. Smith, “Detection of HSIL and cancers in cervical tissue by in vivo light scattering,” J. Lower Genital Tract Disease , to be published.

Lasers Surg. Med. (1)

R. J. Nordstrom, L. Burke, J. M. Niloff, and J. F. Myrtle, “Identification of cervical neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy,” Lasers Surg. Med. 29, 118-127 (2001).
[CrossRef] [PubMed]

Obstet. Gynecol. (2)

J. C. Gage, V. W. Hanson, K. Abbey, S. Dippery, S. Gardner, J. Kubota, M. Schiffman, D. Solomon, and J. Jeronimo, for the ASCUS LSIL Triage Study (ALTS) Group, “Number of cervical biopsies and sensitivity of colposcopy,” Obstet. Gynecol. 108, 264-272 (2006).
[CrossRef] [PubMed]

M. Spitzer, A. E. Cheryns, and V. L. Seltzer, “The use of large loop excision of the transformation zone in an inner-city population,” Obstet. Gynecol. 82, 731-735 (1993).
[PubMed]

Opt. Express (2)

Opt. Lett. (1)

Photochem. Photobiol. (1)

N. Ramanujam, M. F. Mitchell, A. Mahadevan. Jansen, S. L. Thomsen, G. Staerkel, A. Malpica, T. Wright, N. Atkinson, and R. Richards. Kortum, “Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths,” Photochem. Photobiol. 64, 720-735 (1996).
[CrossRef] [PubMed]

Other (1)

R. Kohavi, “A study of cross-validation and bootstrap for accuracy estimation and model selection,” in Proceedings of the Fourteenth International Joint Conference on Artificial Intelligence (IJCAI) (IJCAI, 1995), Vol. 2, 1137-1143.

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Figures (5)

Fig. 1
Fig. 1

(a) Schematic of the fiber-optic system. The tungsten lamp box contains two lamps each with its own computer-controlled shutter. One lamp illuminates an optical fiber, DP, while the other lamp illuminates an optical fiber, DU. These optical fibers can transport the light to the tissue via an optical probe that is in gentle contact with the tissue. Light that is collected from the tissue by several optical fibers is simultaneously dispersed using a spectrograph, and spectra for each of the fibers are measured using a TE-cooled CCD. (b) Schematic of the distal end of the probe. There is a polarizer at top left, covering delivery fiber DP and collection fibers 1 and 4, that polarizes the light horizontally. A polarizer at bottom left, covering only fiber 3, polarizes the light vertically. There is no polarizer over delivery fiber DU and collection fiber U.

Fig. 2
Fig. 2

Representative unpolarized spectrum and the fits to that spectrum. The thick black line from 850 to 1035 nm is a fit to the water absorption. The thick solid line from 690 to 790 nm is a fit to the slope, and the thin black line is a fit to Hb absorption.

Fig. 3
Fig. 3

Representative I1/I3 and I1/I4 spectra.

Fig. 4
Fig. 4

Probability distributions for the values of I1/I4 (a) and slope (b). The length of the x-axis is 1.4 times the range of measured values.

Fig. 5
Fig. 5

Receiver operating characteristic (ROC) curves. The dashed lines from (0,0) to (100,100) are to guide the eye.

Tables (5)

Tables Icon

Table 1 Pathology of the Measured Sites a

Tables Icon

Table 2 Ability to Detect HSIL and Cancer a

Tables Icon

Table 3 Comparison of the Ability to Detect HSIL and Cancer as Determined by Two Different Cross-Validation Methods a

Tables Icon

Table 4 In Vivo, Point Optical Studies of Cervical Pathologies a

Tables Icon

Table 5 In vivo, Optical Imaging Studies of Cervical Pathologies a

Equations (6)

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

I = ( c 0 λ c 1 ) e μ a l V ,
μ a l = C Hb ϵ Hb + C Hb O 2 ϵ Hb O 2 ,
V = 1 exp ( 2 μ a l R ) 2 R μ a l .
slope = Δ x Δ y 1 area Δ x Δ y 1 y Δ x = 1 y Δ y .
r 2 = i = 1 4 p i 2 4 p i 1 .
D i n = j = 1 4 d i j n r j ,

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