OSA's Digital Library

Applied Optics

Applied Optics


  • Vol. 44, Iss. 11 — Apr. 10, 2005
  • pp: 2072–2081

Sources of scattering in cervical tissue: determination of the scattering coefficient by confocal microscopy

Tom Collier, Michele Follen, Anais Malpica, and Rebecca Richards-Kortum  »View Author Affiliations

Applied Optics, Vol. 44, Issue 11, pp. 2072-2081 (2005)

View Full Text Article

Enhanced HTML    Acrobat PDF (1770 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



Most models of light propagation through tissue assume that the scattering properties of various tissue layers are the same. We present evidence that the scattering coefficient of cervical epithelium varies by a factor of 3 within the epithelium owing to variations in nuclear density and to the presence of keratin. We estimated the scattering coefficient from regions of normal and precancerous cervical epithelium by fitting reflectance measurements from confocal images to an exponential function of depth based on Beer's law of attenuation. The results suggest that the normal cervix is characterized by highly variable scattering in the superficial epithelium, low scattering in the intermediate epithelium, and high scattering in the basal and stromal regions. In high-grade dysplasia, high scattering from high-density nuclei is observed throughout the entire epithelium.

© 2005 Optical Society of America

OCIS Codes
(170.1790) Medical optics and biotechnology : Confocal microscopy
(290.5820) Scattering : Scattering measurements

Original Manuscript: July 27, 2004
Revised Manuscript: December 6, 2004
Manuscript Accepted: December 14, 2004
Published: April 10, 2005

Tom Collier, Michele Follen, Anais Malpica, and Rebecca Richards-Kortum, "Sources of scattering in cervical tissue: determination of the scattering coefficient by confocal microscopy," Appl. Opt. 44, 2072-2081 (2005)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Surg. Med. 17, 350–357 (1995). [CrossRef] [PubMed]
  2. Z. Ge, K. T. Schomacker, N. S. Nishioka, “Identification of colonic dysplasia and neoplasia by diffuse reflectance spectroscopy and pattern recognition techniques,” Appl. Spectrosc. 52, 833–345 (1998). [CrossRef]
  3. F. Koenig, R. Larne, H. Enquist, F. J. McGovern, K. T. Schomacker, N. Kollias, T. F. Deutsch, “Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma,” Urology 51, 342–345 (1998). [CrossRef] [PubMed]
  4. M. S. Feld, “Spectral pathology using reflected light,” in Biomedical Optical Spectroscopy and Diagnostics/Therapeutic Laser Applications, E. M. Sevick-Muraca, J. A. Izatt, M. N. Ediger, eds., Vol. 22 of OSA Trends in Optics and Photonics Series (Optical Society of America, Washington, D.C., 1998).
  5. G. Zonios, L. T. Perelman, V. Backman, R. Manahoran, M. Fitzmaurice, J. Van Dam, M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo,” Appl. Opt. 38, 6628–6637 (1999). [CrossRef]
  6. I. J. Bigio, J. R. Mourant, “Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic scattering spectroscopy,” Phys. Med. Biol. 42, 803–814 (1997). [CrossRef] [PubMed]
  7. R. Glasgold, M. Glasgold, H. Savage, J. Pinto, R. Alfano, S. Schantz, “Tissue autofluorescence as an intermediate endpoint in NMBA-induced esophageal carcinogenesis,” Cancer Lett. 82, 33–41 (1994). [CrossRef] [PubMed]
  8. R. Alfano, A. Pradhan, G. Tang, S. Wahl, “Optical spectroscopic diagnosis of cancer and normal breast tissues,” J. Opt. Soc. Am. B 6, 1015–1023 (1989). [CrossRef]
  9. R. Richards-Kortum, E. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Annu. Rev. Phys. Chem. 47, 555–606 (1996). [CrossRef] [PubMed]
  10. I. Georgakoudi, B. C. Jacobson, J. Van Dam, V. Backman, M. B. Wallace, M. G. Muller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620–1629 (2001). [CrossRef] [PubMed]
  11. J. D. Pitts, R. D. Sloboda, K. H. Dragnev, E. Dmitrovsky, M. A. Mycek, “Autofluorescence characteristics of immortalized and carcinogen-transformed human bronchial epithelial cells,” J. Biomed. Opt. 6, 31–40 (2001). [CrossRef] [PubMed]
  12. F. Koenig, F. J. McGovern, A. F. Althausen, T. F. Deutsch, K. T. Schomacker, “Laser induced autofluorescence diagnosis of bladder cancer,” J. Urol. (Baltimore) 156, 1597–1601 (1996).
  13. Z. Haung, H. Zeng, I. Havzavi, D. McLean, H. Lui, “Rapid near-infrared Raman spectroscopy system for real-time in vivo skin measurements,” Opt. Lett. 26, 1782–1784 (2001). [CrossRef]
  14. A. Mahadevan-Jansen, R. Richards-Kortum, “Raman spectroscopy for the detection of cancers and precancers,” J. Biomed. Opt. 1, 31–70 (1996). [CrossRef] [PubMed]
  15. T. Collier, A. Lacy, A. Malpica, M. Follen, R. Richards-Kortum, “Near real time confocal microscopy of amelanotic tissue: detection of dysplasia in ex-vivo cervical tissue,” Acad. Radiol. 9, 504–512 (2002). [CrossRef] [PubMed]
  16. M. Rajadhyaksha, G. Menaker, T. Flotte, P. J. Dwyer, S. Gonzalez, “Confocal examination of nonmelanoma cancers in thick skin excisions to potentially guide mohs micrographic surgery without frozen histopathology,” J. Invest. Dermatol. 117, 1137–1143 (2001). [CrossRef] [PubMed]
  17. J. Busam, K. Hester, C. Charles, D. Sachs, C. Antonescu, S. Gonzalez, A. Halpern, “Detection of clinically amelanotic malignant melanoma and assessment of its margins by in vivo confocal scanning laser microscopy,” Acad. Dermatol. 137, 923–929 (2001).
  18. M. E. Brezinski, G. J. Tearney, B. E. Bouma, J. A. Izatt, M. R. Hee, E. A. Swanson, J. F. Southern, J. G. Fujimoto, “Optical coherence tomography for optical biopsy,” Circulation 93, 1206–1213 (1996). [CrossRef] [PubMed]
  19. F. I. Feldchtein, V. M. Gelikonov, G. V. Gelikonov, R. V. Kuranov, N. D. Gladkova, A. M. Sergeev, N. M. Shakhova, I. A. Kuznetzova, A. M. Denisenko, O. S. Streltzova, “Design and performance of an endoscopic OCT system for in vivo studies of human mucosa,” presented at the Conference on Lasers and Electro-Optics, San Francisco, Calif., 3–8 May 1998.
  20. R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, 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]
  21. K. Sokolov, R. Drezek, K. Gossage, R. Richards-Kortum, “Reflectance spectroscopy with polarized light: is it sensitive to cellular and nuclear morphology?” Opt. Express 5, 302–317 (1999), http://www.opticsexpress.org . [CrossRef] [PubMed]
  22. W. K. Hong, M. B. Sporn, “Recent advances in chemoprevention of cancer,” Science 278, 1073–1077 (1997). [CrossRef] [PubMed]
  23. I. Georgakoudi, E. E. Sheets, M. G. Muller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, 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]
  24. I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, 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]
  25. R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol. 73, 636–641 (2001). [CrossRef] [PubMed]
  26. R. J. Hunter, M. S. Patterson, T. J. Farrell, J. E. Hayward, “Hemoglobin oxygenation of a two-layer tissue-simulating phantom from time-resolved reflectance: effect of top layer thickness,” Phys. Med. Biol. 47, 193–208 (2002). [CrossRef] [PubMed]
  27. T. J. Pfefer, K. T. Schomacker, M. N. Ediger, N. S. Nishioka, “Multiple-fiber probe design for fluorescence spectroscopy in tissue,” Appl. Opt. 41, 4712–4721 (2002). [CrossRef] [PubMed]
  28. B. W. Pogue, G. Burke, “Fiber-optic bundle design for quantitative fluorescence measurements from tissue,” Appl. Opt. 31, 7429–7436 (1998). [CrossRef]
  29. L. Quan, N. Ramanujam, “Relationship between depth of a target in a turbid medium and fluorescence measured by a variable-aperture method,” Opt. Express 27, 104–106 (2002), http://www.opticsexpress.org .
  30. W. Cheong, S. Prahl, A. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990). [CrossRef]
  31. J. W. Pickering, S. A. Prahl, N. van Wierington, J. F. Beek, H. J. C. M. Sterenborg, M. J. C. van Gemert, “Doubleintegrating-sphere system for measuring the optical properties of tissue,” Appl. Opt. 33, 399–410 (1993). [CrossRef]
  32. S. A. Prahl, M. J. C. van Gemert, A. J. Welch, “Determining the optical properties of turbid media by using the adding-doubling method,” Appl. Opt. 32, 559–568 (1993). [CrossRef] [PubMed]
  33. T. Foster, E. Hull, “Optical tomography and spectroscopy of tissue: theory, instrumentation, model and human studies II,” in Proceedings of the Society of Photo-Optical Instrumentation Engineers (SPIE), B. Chance, R. R. Alfano, eds., Proc. SPIE2979, 355–364 (1997).
  34. S. Lin, L. Wang, S. Jacques, F. Tittel, “Measurement of tissue optical properties using oblique incidence optical fiber reflectometry,” Appl. Opt. 36, 136–143 (1997). [CrossRef] [PubMed]
  35. D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt. 8, 484–494 (2003). [CrossRef] [PubMed]
  36. R. Bays, G. Wagnieres, D. Robert, D. Braichotte, J. Savory, P. Monnier, H. van den Bergh, “Clinical determination of tissue optical properties by endoscopic spatially resolved reflectrometry,” Appl. Opt. 35, 1756–1766 (1996). [CrossRef] [PubMed]
  37. R. Hornung, T. H. Pham, K. A. Keefel, M. W. Berns, Y. Tadir, B. J. Tromberg, “Quantitative near-infrared spectroscopy of cervical dysplasia in vivo,” Hum. Reprod. 14, 2908–2916 (1999). [CrossRef] [PubMed]
  38. S. K. Sung, D. Arifler, R. Drezek, M. Follen, R. Richards-Kortum, “Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9, 511–522 (2004). [CrossRef]
  39. J. Qu, C. MacAuley, S. Lam, B. Palcic, “Optical properties of normal and carcinomatous bronchial tissue,” Appl. Opt. 33, 7397–7405 (1994). [CrossRef] [PubMed]
  40. C. Smithpeter, A. Dunn, A. Welch, R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” Appl. Opt. 37, 2749–2754 (1998). [CrossRef]
  41. M. Kempe, W. Rudolph, E. Welsch, “Comparative study of confocal and heterodyne microscopy for imaging through scattering media,” J. Opt. Soc. Am. 13, 46–52 (1996). [CrossRef]
  42. J. Schmitt, A. Knuttel, M. Yadlowsky, “Confocal microscopy in turbid media,” J. Opt. Soc. Am. 11, 2226–2235 (1994). [CrossRef]
  43. T. Collier, D. Arifler, A. Malpica, M. Follen, R. Richards-Kortum, “Determination of the epithelial tissue scattering coefficient using confocal microscopy,” Sel. Top. Quantum Electron. 9, 307–313 (2003). [CrossRef]
  44. J. Key, E. R. Davies, R. C. Jackson, P. N. Wells, “Optical attenuation characteristics of breast tissues at visible and near-infrared wavelengths,” Phys. Med. Biol. 36, 579–590 (1991). [CrossRef] [PubMed]
  45. C. R. Simpson, M. Kohl, M. Essenpreis, M. Cope, “Nearinfrared optical properties of ex vivo human skin and subcutaneous tissues measured using the Monte Carlo inversion technique,” Phys. Med. Biol. 43, 2465–2478 (1998). [CrossRef] [PubMed]
  46. B. Luck, A. Bovic, R. Richards-Kortum, “Segmenting cervical epithelial nuclei from confocal images using Gaussian Markov random fields,” in Proceedings of the IEEE International Conference on Image Processing (Institute of Electrical and Electronics Engineers, New York, 2003), Vol. 2, pp. 14–17.
  47. V. G. Peters, D. R. Wyman, M. S. Patterson, G. L. Frank, “Optical properties of normal and diseased human breast tissues in the visible and near infrared,” Phys. Med. Biol. 35, 1317–1334 (1990). [CrossRef] [PubMed]
  48. T. L. Troy, S. N. Thennadil, “Optical properties of human skin in the near infrared wavelength range of 1000 to 2200 nm,” J. Biomed. Opt. 6, 167–176 (2001). [CrossRef] [PubMed]
  49. J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, I. J. Bigio, “Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms,” Appl. Opt. 36, 949–957 (1997). [CrossRef] [PubMed]
  50. A. Zoumi, A. Yeh, B. J. Tromberg, “Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence,” Proc. Natl. Acad. Sci. USA 99, 11014–11019 (2002).

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited