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Optics Express

Optics Express

  • Editor: C. Martijn de Sterke
  • Vol. 15, Iss. 12 — Jun. 11, 2007
  • pp: 7863–7875

Comparison of a physical model and principal component analysis for the diagnosis of epithelial neoplasias in vivo using diffuse reflectance spectroscopy

Melissa C. Skala, Gregory M. Palmer, Kristin M. Vrotsos, Annette Gendron-Fitzpatrick, and Nirmala Ramanujam  »View Author Affiliations

Optics Express, Vol. 15, Issue 12, pp. 7863-7875 (2007)

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We explored the use of diffuse reflectance spectroscopy in the ultraviolet-visible (UV-VIS) spectrum for the diagnosis of epithelial pre-cancers and cancers in vivo. A physical model (Monte Carlo inverse model) and an empirical model (principal component analysis, (PCA)) based approach were compared for extracting diagnostic features from diffuse reflectance spectra measured in vivo from the dimethylbenz[α]anthracene-treated hamster cheek pouch model of oral carcinogenesis. These diagnostic features were input into a support vector machine algorithm to classify each tissue sample as normal (n=10) or neoplastic (dysplasia to carcinoma, n=10) and cross-validated using a leave one out method. There was a statistically significant decrease in the absorption and reduced scattering coefficient at 460 nm in neoplastic compared to normal tissues, and these two features provided 90% classification accuracy. The first two principal components extracted from PCA provided a classification accuracy of 95%. The first principal component was highly correlated with the wavelength-averaged reduced scattering coefficient. Although both methods show similar classification accuracy, the physical model provides insight into the physiological and structural features that discriminate between normal and neoplastic tissues and does not require a priori, a representative set of spectral data from which to derive the principal components.

© 2007 Optical Society of America

OCIS Codes
(160.4760) Materials : Optical properties
(170.1470) Medical optics and biotechnology : Blood or tissue constituent monitoring
(170.4580) Medical optics and biotechnology : Optical diagnostics for medicine
(170.6510) Medical optics and biotechnology : Spectroscopy, tissue diagnostics

ToC Category:
Medical Optics and Biotechnology

Original Manuscript: March 26, 2007
Revised Manuscript: May 29, 2007
Manuscript Accepted: June 5, 2007
Published: June 8, 2007

Virtual Issues
Vol. 2, Iss. 7 Virtual Journal for Biomedical Optics

Melissa C. Skala, Gregory M. Palmer, Kristin M. Vrotsos, Annette Gendron-Fitzpatrick, and Nirmala Ramanujam, "Comparison of a physical model and principal component analysis for the diagnosis of epithelial neoplasias in vivo using diffuse reflectance spectroscopy," Opt. Express 15, 7863-7875 (2007)

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  1. "Cancer Facts and Figures," (American Cancer Society, 2006).
  2. R. J. Nordstrom, L. Burke, J. M. Niloff, and J. F. Myrtle, "Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy," Lasers Surg. Med. 29, 118-127 (2001). [CrossRef] [PubMed]
  3. I. Georgakoudi, E. E. Sheets, M. G. Muller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, "Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo," Am. J. Obstet. Gynecol. 186, 374-382 (2002). [CrossRef] [PubMed]
  4. M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, "Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma," Cancer 97, 1681-1692 (2003). [CrossRef] [PubMed]
  5. D. J. Parekh, W. C. Lin, and S. D. Herrell, "Optical spectroscopy characteristics can differentiate benign and malignant renal tissues: a potentially useful modality," J. Urol. 174, 1754-1758 (2005). [CrossRef] [PubMed]
  6. N. Subhash, J. R. Mallia, S. S. Thomas, A. Mathews, P. Sebastian, and J. Madhavan, "Oral cancer detection using diffuse reflectance spectral ratio R540/R575 of oxygenated hemoglobin bands," J. Biomed. Opt. 11, 014018 (2006). [CrossRef] [PubMed]
  7. D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, and J. L. Roodenburg, "Autofluorescence and diffuse reflectance spectroscopy for oral oncology," Lasers Surg. Med. 36, 356-364 (2005). [CrossRef] [PubMed]
  8. G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Comparison of multiexcitation fluorescence and diffuse reflectance spectroscopy for the diagnosis of breast cancer (March 2003)," IEEE Trans. Biomed. Eng. 50, 1233-1242 (2003). [CrossRef] [PubMed]
  9. Y. S. Fawzy, M. Petek, M. Tercelj, and H. Zeng, "In vivo assessment and evaluation of lung tissue morphologic and physiological changes from non-contact endoscopic reflectance spectroscopy for improving lung cancer detection," J. Biomed. Opt. 11, 044003 (2006). [CrossRef] [PubMed]
  10. A. Amelink, H. J. Sterenborg, M. P. 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] [PubMed]
  11. P. Thueler, I. Charvet, F. Bevilacqua, M. St Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, "In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties," J. Biomed. Opt. 8, 495-503 (2003). [CrossRef] [PubMed]
  12. G. Zonios, L. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, "Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo," Appl. Opt. 38, 6628-6637 (1999). [CrossRef]
  13. J. C. Finlay and T. H. Foster, "Hemoglobin oxygen saturations in phantoms and in vivo from measurements of steady-state diffuse reflectance at a single, short source-detector separation," Med. Phys. 31, 1949-1959 (2004). [CrossRef] [PubMed]
  14. T. J. Pfefer, L. S. Matchette, C. L. Bennett, J. A. Gall, J. N. Wilke, A. J. Durkin, and M. N. Ediger, "Reflectance-based determination of optical properties in highly attenuating tissue," J. Biomed. Opt. 8, 206-215 (2003). [CrossRef] [PubMed]
  15. N. Ghosh, S. K. Mohanty, S. K. Majumder, and P. K. Gupta, "Measurement of optical transport properties of normal and malignant human breast tissue," Appl. Opt. 40, 176-184 (2001). [CrossRef]
  16. G. M. Palmer and N. Ramanujam, "Monte Carlo-based inverse model for calculating tissue optical properties. Part I: Theory and validation on synthetic phantoms," Appl. Opt. 45, 1062-1071 (2006). [CrossRef] [PubMed]
  17. C. T. Chen, H. K. Chiang, S. N. Chow, C. Y. Wang, Y. S. Lee, J. C. Tsai, and C. P. Chiang, "Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis," J. Oral Pathol. Med. 27, 470-474 (1998). [CrossRef] [PubMed]
  18. S. Andrejevic, J. F. Savary, C. Fontolliet, P. Monnier, and H. van Den Bergh, "7,12-dimethylbenz[a]anthracene-induced 'early' squamous cell carcinoma in the Golden Syrian hamster: evaluation of an animal model and comparison with 'early' forms of human squamous cell carcinoma in the upper aero-digestive tract," Int. J. Exp. Pathol. 77, 7-14 (1996). [CrossRef] [PubMed]
  19. F. H. White, K. Gohari, and C. J. Smith, "Histological and ultrastructural morphology of 7,12 dimethylbenz(alpha)-anthracene carcinogenesis in hamster cheek pouch epithelium," Diagn. Histopathol. 4, 307-333 (1981). [PubMed]
  20. M. C. Skala, G. M. Palmer, C. 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] [PubMed]
  21. M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007). [CrossRef] [PubMed]
  22. 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, 1180-1186 (2005). [CrossRef] [PubMed]
  23. C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, "Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer," J. Biomed. Opt. 10, 024032 (2005). [CrossRef] [PubMed]
  24. C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "Diagnosis of breast cancer using diffuse reflectance spectroscopy: Comparison of a Monte Carlo versus partial least squares analysis based feature extraction technique," Lasers Surg. Med. 38, 714-724 (2006). [CrossRef] [PubMed]
  25. D. G. MacDonald, and S. M. Saka, Structural Indicators of the High Risk Lesion (Cambridge Univ. Press, Cambridge, 1991).
  26. M. L. Ellsworth, R. N. Pittman, and C. G. Ellis, "Measurement of hemoglobin oxygen saturation in capillaries," Am. J. Physiol. 252, H1031-1040 (1987). [PubMed]
  27. S. R. Millon, K. M. Roldan-Perez, K. M. Riching, G. M. Palmer, and N. Ramanujam, "Effect of optical clearing agents on the in vivo optical properties of squamous epithelial tissue," Lasers Surg. Med. 38, 920-927 (2006). [CrossRef] [PubMed]
  28. J. Mourant, J. Freyer, A. Hielscher, A. Eick, D. Shen, and T. Johnson, "Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics," Appl. Opt. 37, 3586-3593 (1998). [CrossRef]
  29. G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Monte Carlo-based inverse model for calculating tissue optical properties. Part II: Application to breast cancer diagnosis," Appl. Opt. 45, 1072-1078 (2006). [CrossRef] [PubMed]
  30. W. R. Dillon and M. Goldstein, Multivariate analysis: methods and applications (Wiley, New York, 1984).
  31. J. Devore, Probability and Statistics for Engineering and the Sciences (Duxbury, Pacific Grove, 2000).
  32. N. Cristianini and J. Shawe-Taylor, An introduction to support vector machines: and other Kernel-based learning methods (Cambridge University Press, Cambridge, 2000).
  33. J. Hjorth, Computer intensive statistical methods: Validation, model selection, and bootstrap (Chapman & Hall, London, New York, 1994).
  34. R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, "Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications," J. Biomed. Opt. 6, 385-396 (2001). [CrossRef] [PubMed]
  35. U. Sunar, H. Quon, T. Durduran, J. Zhang, J. Du, C. Zhou, G. Yu, R. Choe, A. Kilger, R. Lustig, L. Loevner, S. Nioka, B. Chance, and A. G. Yodh, "Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study," J. Biomed. Opt. 11, 064021 (2006). [CrossRef]
  36. R. Hornung, T. H. Pham, K. A. Keefe, M. W. Berns, Y. Tadir, and B. J. Tromberg, "Quantitative near-infrared spectroscopy of cervical dysplasia in vivo," Hum. Reprod. 14, 2908-2916 (1999). [CrossRef] [PubMed]
  37. C. J. Gulledge and M. W. Dewhirst, "Tumor oxygenation: a matter of supply and demand," Anticancer Res. 16, 741-749 (1996). [PubMed]
  38. C. Baudelet and B. Gallez, "Effect of anesthesia on the signal intensity in tumors using BOLD-MRI: comparison with flow measurements by Laser Doppler flowmetry and oxygen measurements by luminescence-based probes," Magn. Reson. Imaging 22, 905-912 (2004). [CrossRef] [PubMed]
  39. F. Steinberg, H. J. Rohrborn, T. Otto, K. M. Scheufler, and C. Streffer, "NIR reflection measurements of hemoglobin and cytochrome aa3 in healthy tissue and tumors. Correlations to oxygen consumption: preclinical and clinical data," Adv. Exp. Med. Biol. 428, 69-77 (1997). [CrossRef] [PubMed]
  40. T. Collier, M. Follen, A. Malpica, and R. Richards-Kortum, "Sources of scattering in cervical tissue: determination of the scattering coefficient by confocal microscopy," Appl. Opt. 44, 2072-2081 (2005). [CrossRef] [PubMed]
  41. I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, "Microanatomical and biochemical origins of normal and precancerous cervical autofluorescence using laser-scanning fluorescence confocal microscopy," Photochem. Photobiol. 77, 550-555 (2003). [CrossRef] [PubMed]
  42. I. Saidi, S. Jacques, and F. Tittel, "Mie and Rayleigh modeling of visible-light scattering in neonatal skin," Appl. Opt. 34, 7410-7418 (1995). [CrossRef] [PubMed]

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