Abstract

During precancer development in epithelium, neoplastic cells remodel the underlying stroma, for example, the basement membrane, capillaries, fibroblasts, and extracellular matrix. The purpose of this study is to investigate the relationship between the nonlinear optical signals from the collagen matrix in stroma and the progression of early epithelial carcinogenesis. Two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) signals were measured from the stroma of hamster oral cheek pouch in vivo. We found that three features, including the intensity ratio of TPEF over SHG, the spatial frequency distribution, and the texture feature of SHG images, provide the quantitative identification of epithelial precancer at different pathologic stages. We demonstrated that the combination of all three features by using a support vector machine algorithm can significantly improve the accuracy in the detection of epithelial precancer.

© 2011 Optical Society of America

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  1. J. A. Joyce and J. W. Pollard, Nat. Rev. Cancer 9, 239 (2009).
    [CrossRef] [PubMed]
  2. M. Egeblad and Z. Werb, Nat. Rev. Cancer 2, 161 (2002).
    [CrossRef] [PubMed]
  3. S. Lin, S. Jee, C. Kuo, R. Wu, W. Lin, J. Chen, Y. Liao, C. Hsu, T. Tsai, Y. Chen, and C. Dong, Opt. Lett. 31, 2756 (2006).
    [CrossRef] [PubMed]
  4. M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
    [CrossRef] [PubMed]
  5. O. Nadiarnykh, R. B. LaComb, M. A. Brewer, and P. J. Campagnola, BMC Cancer 10, 94 (2010).
    [CrossRef] [PubMed]
  6. N. D. Kirkpatrick, M. A. Brewer, and U. Utzinger, Cancer Epidemiol Biomark. Prev. 16, 2048 (2007).
    [CrossRef]
  7. R. M. Williams, A. Flesken-Nikitin, L. H. Ellenson, D. C. Connolly, T. C. Hamilton, A. Y. Nikitin, and W. R. Zipfel, Translational Oncology 3, 181 (2010).
    [PubMed]
  8. W. Zheng, Y. Wu, D. Li, and J. Y. Qu, J. Biomed. Opt. 13, 054010 (2008).
    [CrossRef] [PubMed]
  9. S. Andrejevic, J. Savary, C. Fontolliet, P. Monnier, and H. Van Den Bergh, Int. J. Exp. Pathol. 77, 7 (1996).
    [CrossRef] [PubMed]
  10. R. M. Haralick, Proc. IEEE 67, 786 (1979).
    [CrossRef]
  11. C. Cortes and V. Vapnik, Mach. Learn. 20, 273 (1995).
    [CrossRef]
  12. C. Chang and C. Lin, “LIBSVM: a library for support vector machines,” http://www.csie.ntu.edu.tw/~cjlin/libsvm.
  13. L. Breiman and P. Spector, Int. Stat. Rev. 60, 291 (1992).
    [CrossRef]

2011

M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
[CrossRef] [PubMed]

2010

O. Nadiarnykh, R. B. LaComb, M. A. Brewer, and P. J. Campagnola, BMC Cancer 10, 94 (2010).
[CrossRef] [PubMed]

R. M. Williams, A. Flesken-Nikitin, L. H. Ellenson, D. C. Connolly, T. C. Hamilton, A. Y. Nikitin, and W. R. Zipfel, Translational Oncology 3, 181 (2010).
[PubMed]

2009

J. A. Joyce and J. W. Pollard, Nat. Rev. Cancer 9, 239 (2009).
[CrossRef] [PubMed]

2008

W. Zheng, Y. Wu, D. Li, and J. Y. Qu, J. Biomed. Opt. 13, 054010 (2008).
[CrossRef] [PubMed]

2007

N. D. Kirkpatrick, M. A. Brewer, and U. Utzinger, Cancer Epidemiol Biomark. Prev. 16, 2048 (2007).
[CrossRef]

2006

2002

M. Egeblad and Z. Werb, Nat. Rev. Cancer 2, 161 (2002).
[CrossRef] [PubMed]

1996

S. Andrejevic, J. Savary, C. Fontolliet, P. Monnier, and H. Van Den Bergh, Int. J. Exp. Pathol. 77, 7 (1996).
[CrossRef] [PubMed]

1995

C. Cortes and V. Vapnik, Mach. Learn. 20, 273 (1995).
[CrossRef]

1992

L. Breiman and P. Spector, Int. Stat. Rev. 60, 291 (1992).
[CrossRef]

1979

R. M. Haralick, Proc. IEEE 67, 786 (1979).
[CrossRef]

Andrejevic, S.

S. Andrejevic, J. Savary, C. Fontolliet, P. Monnier, and H. Van Den Bergh, Int. J. Exp. Pathol. 77, 7 (1996).
[CrossRef] [PubMed]

Breiman, L.

L. Breiman and P. Spector, Int. Stat. Rev. 60, 291 (1992).
[CrossRef]

Brewer, M. A.

O. Nadiarnykh, R. B. LaComb, M. A. Brewer, and P. J. Campagnola, BMC Cancer 10, 94 (2010).
[CrossRef] [PubMed]

N. D. Kirkpatrick, M. A. Brewer, and U. Utzinger, Cancer Epidemiol Biomark. Prev. 16, 2048 (2007).
[CrossRef]

Campagnola, P. J.

O. Nadiarnykh, R. B. LaComb, M. A. Brewer, and P. J. Campagnola, BMC Cancer 10, 94 (2010).
[CrossRef] [PubMed]

Chang, C.

C. Chang and C. Lin, “LIBSVM: a library for support vector machines,” http://www.csie.ntu.edu.tw/~cjlin/libsvm.

Chen, J.

Chen, Y.

Conklin, M. W.

M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
[CrossRef] [PubMed]

Connolly, D. C.

R. M. Williams, A. Flesken-Nikitin, L. H. Ellenson, D. C. Connolly, T. C. Hamilton, A. Y. Nikitin, and W. R. Zipfel, Translational Oncology 3, 181 (2010).
[PubMed]

Cortes, C.

C. Cortes and V. Vapnik, Mach. Learn. 20, 273 (1995).
[CrossRef]

Dong, C.

Egeblad, M.

M. Egeblad and Z. Werb, Nat. Rev. Cancer 2, 161 (2002).
[CrossRef] [PubMed]

Eickhoff, J. C.

M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
[CrossRef] [PubMed]

Eliceiri, K. W.

M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
[CrossRef] [PubMed]

Ellenson, L. H.

R. M. Williams, A. Flesken-Nikitin, L. H. Ellenson, D. C. Connolly, T. C. Hamilton, A. Y. Nikitin, and W. R. Zipfel, Translational Oncology 3, 181 (2010).
[PubMed]

Flesken-Nikitin, A.

R. M. Williams, A. Flesken-Nikitin, L. H. Ellenson, D. C. Connolly, T. C. Hamilton, A. Y. Nikitin, and W. R. Zipfel, Translational Oncology 3, 181 (2010).
[PubMed]

Fontolliet, C.

S. Andrejevic, J. Savary, C. Fontolliet, P. Monnier, and H. Van Den Bergh, Int. J. Exp. Pathol. 77, 7 (1996).
[CrossRef] [PubMed]

Friedl, A.

M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
[CrossRef] [PubMed]

Hamilton, T. C.

R. M. Williams, A. Flesken-Nikitin, L. H. Ellenson, D. C. Connolly, T. C. Hamilton, A. Y. Nikitin, and W. R. Zipfel, Translational Oncology 3, 181 (2010).
[PubMed]

Haralick, R. M.

R. M. Haralick, Proc. IEEE 67, 786 (1979).
[CrossRef]

Hsu, C.

Jee, S.

Joyce, J. A.

J. A. Joyce and J. W. Pollard, Nat. Rev. Cancer 9, 239 (2009).
[CrossRef] [PubMed]

Keely, P. J.

M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
[CrossRef] [PubMed]

Kirkpatrick, N. D.

N. D. Kirkpatrick, M. A. Brewer, and U. Utzinger, Cancer Epidemiol Biomark. Prev. 16, 2048 (2007).
[CrossRef]

Kuo, C.

LaComb, R. B.

O. Nadiarnykh, R. B. LaComb, M. A. Brewer, and P. J. Campagnola, BMC Cancer 10, 94 (2010).
[CrossRef] [PubMed]

Li, D.

W. Zheng, Y. Wu, D. Li, and J. Y. Qu, J. Biomed. Opt. 13, 054010 (2008).
[CrossRef] [PubMed]

Liao, Y.

Lin, C.

C. Chang and C. Lin, “LIBSVM: a library for support vector machines,” http://www.csie.ntu.edu.tw/~cjlin/libsvm.

Lin, S.

Lin, W.

Monnier, P.

S. Andrejevic, J. Savary, C. Fontolliet, P. Monnier, and H. Van Den Bergh, Int. J. Exp. Pathol. 77, 7 (1996).
[CrossRef] [PubMed]

Nadiarnykh, O.

O. Nadiarnykh, R. B. LaComb, M. A. Brewer, and P. J. Campagnola, BMC Cancer 10, 94 (2010).
[CrossRef] [PubMed]

Nikitin, A. Y.

R. M. Williams, A. Flesken-Nikitin, L. H. Ellenson, D. C. Connolly, T. C. Hamilton, A. Y. Nikitin, and W. R. Zipfel, Translational Oncology 3, 181 (2010).
[PubMed]

Pehlke, C. A.

M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
[CrossRef] [PubMed]

Pollard, J. W.

J. A. Joyce and J. W. Pollard, Nat. Rev. Cancer 9, 239 (2009).
[CrossRef] [PubMed]

Provenzano, P. P.

M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
[CrossRef] [PubMed]

Qu, J. Y.

W. Zheng, Y. Wu, D. Li, and J. Y. Qu, J. Biomed. Opt. 13, 054010 (2008).
[CrossRef] [PubMed]

Riching, K. M.

M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
[CrossRef] [PubMed]

Savary, J.

S. Andrejevic, J. Savary, C. Fontolliet, P. Monnier, and H. Van Den Bergh, Int. J. Exp. Pathol. 77, 7 (1996).
[CrossRef] [PubMed]

Spector, P.

L. Breiman and P. Spector, Int. Stat. Rev. 60, 291 (1992).
[CrossRef]

Tsai, T.

Utzinger, U.

N. D. Kirkpatrick, M. A. Brewer, and U. Utzinger, Cancer Epidemiol Biomark. Prev. 16, 2048 (2007).
[CrossRef]

Van Den Bergh, H.

S. Andrejevic, J. Savary, C. Fontolliet, P. Monnier, and H. Van Den Bergh, Int. J. Exp. Pathol. 77, 7 (1996).
[CrossRef] [PubMed]

Vapnik, V.

C. Cortes and V. Vapnik, Mach. Learn. 20, 273 (1995).
[CrossRef]

Werb, Z.

M. Egeblad and Z. Werb, Nat. Rev. Cancer 2, 161 (2002).
[CrossRef] [PubMed]

Williams, R. M.

R. M. Williams, A. Flesken-Nikitin, L. H. Ellenson, D. C. Connolly, T. C. Hamilton, A. Y. Nikitin, and W. R. Zipfel, Translational Oncology 3, 181 (2010).
[PubMed]

Wu, R.

Wu, Y.

W. Zheng, Y. Wu, D. Li, and J. Y. Qu, J. Biomed. Opt. 13, 054010 (2008).
[CrossRef] [PubMed]

Zheng, W.

W. Zheng, Y. Wu, D. Li, and J. Y. Qu, J. Biomed. Opt. 13, 054010 (2008).
[CrossRef] [PubMed]

Zipfel, W. R.

R. M. Williams, A. Flesken-Nikitin, L. H. Ellenson, D. C. Connolly, T. C. Hamilton, A. Y. Nikitin, and W. R. Zipfel, Translational Oncology 3, 181 (2010).
[PubMed]

Am. J. Pathol.

M. W. Conklin, J. C. Eickhoff, K. M. Riching, C. A. Pehlke, K. W. Eliceiri, P. P. Provenzano, A. Friedl, and P. J. Keely, Am. J. Pathol. 178, 1221 (2011).
[CrossRef] [PubMed]

BMC Cancer

O. Nadiarnykh, R. B. LaComb, M. A. Brewer, and P. J. Campagnola, BMC Cancer 10, 94 (2010).
[CrossRef] [PubMed]

Cancer Epidemiol Biomark. Prev.

N. D. Kirkpatrick, M. A. Brewer, and U. Utzinger, Cancer Epidemiol Biomark. Prev. 16, 2048 (2007).
[CrossRef]

Int. J. Exp. Pathol.

S. Andrejevic, J. Savary, C. Fontolliet, P. Monnier, and H. Van Den Bergh, Int. J. Exp. Pathol. 77, 7 (1996).
[CrossRef] [PubMed]

Int. Stat. Rev.

L. Breiman and P. Spector, Int. Stat. Rev. 60, 291 (1992).
[CrossRef]

J. Biomed. Opt.

W. Zheng, Y. Wu, D. Li, and J. Y. Qu, J. Biomed. Opt. 13, 054010 (2008).
[CrossRef] [PubMed]

Mach. Learn.

C. Cortes and V. Vapnik, Mach. Learn. 20, 273 (1995).
[CrossRef]

Nat. Rev. Cancer

J. A. Joyce and J. W. Pollard, Nat. Rev. Cancer 9, 239 (2009).
[CrossRef] [PubMed]

M. Egeblad and Z. Werb, Nat. Rev. Cancer 2, 161 (2002).
[CrossRef] [PubMed]

Opt. Lett.

Proc. IEEE

R. M. Haralick, Proc. IEEE 67, 786 (1979).
[CrossRef]

Translational Oncology

R. M. Williams, A. Flesken-Nikitin, L. H. Ellenson, D. C. Connolly, T. C. Hamilton, A. Y. Nikitin, and W. R. Zipfel, Translational Oncology 3, 181 (2010).
[PubMed]

Other

C. Chang and C. Lin, “LIBSVM: a library for support vector machines,” http://www.csie.ntu.edu.tw/~cjlin/libsvm.

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Figures (3)

Fig. 1
Fig. 1

Nonlinear optical signals from collagen matrix. (a)–(c): Nonlinear optical images of normal collagen matrix based on (a) SHG signal, (b) TPEF signal, and (c) merged signal. A stromal cell (white arrowhead) is presented in TPEF image. (d) TPEF and SHG spectra of collagen matrix. (e) Statistical result of the ratio of TPEF over SHG. The line within each notch box represents the median, and the lower and upper boundaries of the box indicate first and third quartiles (25% and 75%), respectively. Error bars (whiskers) represent the standard deviation (SD). The square represents the mean, and the upper and lower asterisks indicate the maximum and the minimum, respectively. (f)–(h): Representative SHG images from (f) low-grade, (g) mid-grade, and (h) high-grade precancers. Sampling area of each image is 100 μm × 100 μm .

Fig. 2
Fig. 2

Quantitative assessment of collagen morphological alternations during carcinoma progression. (a) Statistical result of GLCM correlation measured from different groups of epithelial tissues. The GLCM texture analyzer module (v0.4) in ImageJ software (NIH) was used and the pixel distance was set as 1. (b) Statistical result of the content of lower spatial frequency ( < 10 μm 1 , excluding the DC component) in image. The legend is the same as Fig. 1e.

Fig. 3
Fig. 3

ROC curves of SVM algorithm for (a) screening purpose and (b) diagnostic purpose.

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