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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 2, Iss. 3 — Mar. 1, 2011
  • pp: 615–619

Label-free monitoring of colonic cancer progression using multiphoton microscopy

Shuangmu Zhuo, Jun Yan, Gang Chen, Jianxin Chen, Yuchun Liu, Jianping Lu, Xiaoqin Zhu, Xingshan Jiang, and Shusen Xie  »View Author Affiliations

Biomedical Optics Express, Vol. 2, Issue 3, pp. 615-619 (2011)

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Abstract: Real-time histology or virtual biopsy for the diagnosis of colonic cancer is of great medical significance. In this work, we show that label-free multiphoton imaging is feasible and effective in monitoring colonic cancer progression by providing cellular and subcellular details in fresh, unfixed, unstained colonic specimens. Our results also demonstrate the capability of using tissue quantitative analysis of the redox ratio for quantifying colonic cancer progression. These results suggest that multiphoton microscopy has potential to become an in situ histological tool, which is free from the labeling requirement of conventional methods, for the early diagnosis and detection of malignant lesions in the colon.


OCIS Codes
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.6510) Medical optics and biotechnology : Spectroscopy, tissue diagnostics
(180.4315) Microscopy : Nonlinear microscopy

ToC Category:
Optics in Cancer Research

Original Manuscript: November 30, 2010
Revised Manuscript: February 7, 2011
Manuscript Accepted: February 15, 2011
Published: February 16, 2011

Shuangmu Zhuo, Jun Yan, Gang Chen, Jianxin Chen, Yuchun Liu, Jianping Lu, Xiaoqin Zhu, Xingshan Jiang, and Shusen Xie, "Label-free monitoring of colonic cancer progression using multiphoton microscopy," Biomed. Opt. Express 2, 615-619 (2011)

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  1. A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, and M. J. Thun, “Cancer statistics, 2009,” CA Cancer J. Clin. 59(4), 225–249 (2009). [CrossRef] [PubMed]
  2. M. Goetz and R. Kiesslich, “Advances of endomicroscopy for gastrointestinal physiology and diseases,” Am. J. Physiol. Gastrointest. Liver Physiol. 298(6), G797–G806 (2010). [CrossRef] [PubMed]
  3. R. Kiesslich, J. Burg, M. Vieth, J. Gnaendiger, M. Enders, P. Delaney, A. Polglase, W. McLaren, D. Janell, S. Thomas, B. Nafe, P. R. Galle, and M. F. Neurath, “Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo,” Gastroenterology 127(3), 706–713 (2004). [CrossRef] [PubMed]
  4. W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7075–7080 (2003). [CrossRef] [PubMed]
  5. M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A. 104(49), 19494–19499 (2007). [CrossRef] [PubMed]
  6. P. T. C. So, C. Y. Dong, B. R. Masters, and K. M. Berland, “Two-photon excitation fluorescence microscopy,” Annu. Rev. Biomed. Eng. 2(1), 399–429 (2000). [CrossRef] [PubMed]
  7. S. M. Zhuo, L. Q. Zheng, J. X. Chen, S. S. Xie, X. Q. Zhu, and X. S. Jiang, “Depth-cumulated epithelial redox ratio and stromal collagen quantity as quantitative intrinsic indicators for differentiating normal, inflammatory, and dysplastic epithelial tissues,” Appl. Phys. Lett. 97(17), 173701 (2010). [CrossRef]
  8. P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol. 21(11), 1356–1360 (2003). [CrossRef] [PubMed]
  9. V. A. Hovhannisyan, P.-J. Su, S.-J. Lin, and C. Y. Dong, “Quantifying thermodynamics of collagen thermal denaturation by second harmonic generation imaging,” Appl. Phys. Lett. 94(23), 233902 (2009). [CrossRef]
  10. S. M. Zhuo, J. X. Chen, G. Z. Wu, S. S. Xie, L. Q. Zheng, X. S. Jiang, and X. Q. Zhu, “Quantitatively linking collagen alteration and epithelial tumor progression by second harmonic generation microscopy,” Appl. Phys. Lett. 96(21), 213704 (2010). [CrossRef]
  11. R. Cicchi, A. Crisci, A. Cosci, G. Nesi, D. Kapsokalyvas, S. Giancane, M. Carini, and F. S. Pavone, “Time- and Spectral-resolved two-photon imaging of healthy bladder mucosa and carcinoma in situ,” Opt. Express 18(4), 3840–3849 (2010). [CrossRef] [PubMed]
  12. K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, “Clinical two-photon microendoscopy,” Microsc. Res. Tech. 70(5), 398–402 (2007). [CrossRef] [PubMed]
  13. M. Gu, H. C. Bao, and J. L. Li, “Cancer-cell microsurgery using nonlinear optical endomicroscopy,” J. Biomed. Opt. 15(5), 050502 (2010). [CrossRef] [PubMed]
  14. J. R. Jass, V. L. Whitehall, J. Young, and B. A. Leggett, “Emerging concepts in colorectal neoplasia,” Gastroenterology 123(3), 862–876 (2002). [CrossRef] [PubMed]
  15. A. Leslie, F. A. Carey, N. R. Pratt, and R. J. Steele, “The colorectal adenoma-carcinoma sequence,” Br. J. Surg. 89(7), 845–860 (2002). [CrossRef] [PubMed]
  16. S. Zhuo, J. Chen, T. Luo, D. Zou, and J. Zhao, “Multimode nonlinear optical imaging of the dermis in ex vivo human skin based on the combination of multichannel mode and Lambda mode,” Opt. Express 14(17), 7810–7820 (2006). [CrossRef] [PubMed]
  17. S. M. Zhuo, J. X. Chen, S. S. Xie, Z. B. Hong, and X. S. Jiang, “Extracting diagnostic stromal organization features based on intrinsic two-photon excited fluorescence and second-harmonic generation signals,” J. Biomed. Opt. 14(2), 020503 (2009). [CrossRef] [PubMed]
  18. S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J. 82(5), 2811–2825 (2002). [CrossRef] [PubMed]
  19. C. Y. Dong, P. T. C. So, C. Buehler, and E. Gratton, “Spatial resolution in pump-probe microscopy,” Optik (Stuttg.) 106, 7–14 (1997).
  20. J. N. Rogart, J. Nagata, C. S. Loeser, R. D. Roorda, H. Aslanian, M. E. Robert, W. R. Zipfel, and M. H. Nathanson, “Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo,” Clin. Gastroenterol. Hepatol. 6(1), 95–101 (2008). [CrossRef] [PubMed]
  21. M. C. Skala, J. M. Squirrell, K. M. Vrotsos, J. C. Eickhoff, A. Gendron-Fitzpatrick, K. W. Eliceiri, and N. Ramanujam, “Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues,” Cancer Res. 65(4), 1180–1186 (2005). [CrossRef] [PubMed]

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