Abstract

We report a probe-based portable and clinically compatible instrument for the spectral diagnosis of melanoma and nonmelanoma skin cancers. The instrument combines two modalities—diffuse reflectance and intrinsic fluorescence spectroscopy—to provide complementary information regarding tissue morphology, function, and biochemical composition. The instrument provides a good signal-to-noise ratio for the collected reflectance and laser-induced fluorescence spectra. Validation experiments on tissue phantoms over a physiologically relevant range of albedos (0.350.99) demonstrate an accuracy of close to 10% in determining scattering, absorption and fluorescence characteristics. We also demonstrate the ability of our instrument to collect in vivo diffuse reflectance and fluorescence measurements from clinically normal skin, dysplastic nevus, and malignant nonmelanoma skin cancer.

© 2010 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. American Cancer Society, “Cancer facts and figures 2009,” http://www.cancer.org/docroot/STT/content/STT_1x_Cancer_Facts__Figures_2009.asp?from=fast.
  2. M. Mogensen and G. Jemec, “Diagnosis of nonmelanoma skin cancer/keratinocyte carcinoma: a review of diagnostic accuracy of nonmelanoma skin cancer diagnostic tests and technologies,” Dermatol. Surg. 33, 1158-1174 (2007).
  3. G. Zonios, L. T. 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]
  4. R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
    [CrossRef]
  5. J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, and T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Surg. Med. 17, 350-357(1995).
    [CrossRef]
  6. J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, and I. J. Bigio, “Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms,” Appl. Opt. 36, 949-957 (1997).
    [CrossRef]
  7. 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]
  8. G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13, 014017 (2008).
  9. M. Panjehpour, B. F. Overholt, T. Vo-Dinh, R. C. Haggitt, D. H. Edwards, and F. P. Buckley III, “Endoscopic fluorescence detection of high-grade dysplasia in Barrett's esophagus,” Gastroenterology 111, 93-101 (1996).
    [CrossRef]
  10. N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 91, 10193-10197 (1994).
  11. M. Brewer, U. Utzinger, E. Silva, D. Gershenson, R. C. Bast Jr., M. Follen, and R. Richards-Kortum, “Fluorescence spectroscopy for in vivo characterization of ovarian tissue,” Lasers. Surg. Med. 29, 128-135 (2001).
  12. R. Richards-Kortum, R. Rava, R. Petras, M. Fitzmaurice, M. Sivak, and M. Feld, “Spectroscopic diagnosis of colonic dysplasia,” Photochem. Photobiol. 53, 777 (1991).
  13. J. M. Levitt, A. Baldwin, A. Papadakis, S. Puri, J. Xylas, K. Munger, and I. Georgakoudi, “Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells,” J. Biomed. Opt. 11, 064012 (2006).
  14. 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, 19494-19499 (2007).
  15. R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).
  16. L. Coghlan, U. Utzinger, R. Richards-Kortum, C. Brookner, A. Zuluaga, I. Gimenez-Conti, and M. Follen, “Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: spectroscopic changes precede morphologic changes,” Lasers. Surg. Med. 29, 1-10 (2001).
  17. Q. Zhang, M. G. Muller, J. Wu, and M. S. Feld, “Turbidity-free fluorescence spectroscopy of biological tissue,” Opt. Lett. 25, 1451-1453 (2000).
    [CrossRef]
  18. G. M. Palmer, and N. Ramanujam, “Monte-Carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt. 13, 024017 (2008).
  19. W. Cottrell, A. Oseroff, and T. Foster, “Portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease,” Rev. Sci. Instrum. 77, 064302 (2006).
    [CrossRef]
  20. C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach,” J. Biomed. Opt. 13, 034015 (2008).
  21. C. Zhu, T. M. Breslin, J. Harter, and N. Ramanujam, “Model based and empirical spectral analysis for the diagnosis of breast cancer,” Opt. Express 16, 14961-14978 (2008).
    [CrossRef]
  22. 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]
  23. 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).
  24. M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).
  25. Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).
  26. R. Zângaro, L. Silveira, R. Manoharan, G. Zonios, I. Itzkan, R. Dasari, J. Van Dam, and M. Feld, “Rapid multiexcitation fluorescence spectroscopy system for in vivo tissue diagnosis,” Appl. Opt. 35, 5211-5219 (1996).
    [CrossRef]
  27. 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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
    [CrossRef]
  28. M. Müller, A. Wax, I. Georgakoudi, R. Dasari, and M. Feld, “A reflectance spectrofluorimeter for real-time spectral diagnosis of disease,” Rev. Sci. Instrum. 73, 3933 (2002).
    [CrossRef]
  29. J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).
  30. S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).
  31. O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).
  32. A. Zuluaga, U. Utzinger, A. Durkin, H. Fuchs, A. Gillenwater, R. Jacob, B. Kemp, J. Fan, and R. Richards-Kortum, “Fluorescence excitation emission matrices of human tissue: a system for in vivo measurement and method of data analysis,” Appl. Spectrosc. 53, 302-311 (1999).
    [CrossRef]
  33. S. Chang, Y. Mirabal, E. 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).
  34. 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).
  35. J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).
  36. C. Redden Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. Macaulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt. 13, 064016 (2008).
  37. 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).
  38. D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
    [CrossRef]
  39. L. Coghlan, U. Utzinger, R. Drezek, D. Heintzelmann, A. Zuluaga, C. Brookner, R. Richards-Kortum, I. Gimenez-Conti, and M. Follen, “Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model,” Opt. Express 7, 436-446(2000).
    [CrossRef]
  40. N. Rajaram, T. H. Nguyen, and J. W. Tunnell, “Lookup table-based inverse model for determining optical properties of turbid media,” J. Biomed. Opt. 13, 050501 (2008).
  41. Z136 Committee, American National Standard for Safe Use of Lasers (ANSI Z136.1-2000) (ANSI, Laser Institute of America, 2000).
  42. T. J. Farrell, M. S. Patterson, and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879-888 (1992).
    [CrossRef]
  43. A. Kienle, and M. S. Patterson, “Improved solutions of the steady-state and the time-resolved diffusion equations for reflectance from a semi-infinite turbid medium,” J. Opt. Soc. Am. A 14, 246-254 (1997).
    [CrossRef]
  44. J. Wu, M. Feld, and R. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3585-3595 (1993).
    [CrossRef]
  45. V. P. Wallace, D. C. Crawford, P. S. Mortimer, R. J. Ott, and J. C. Bamber, “Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance,” Phys. Med. Biol. 45, 735-751 (2000).
    [CrossRef]
  46. B. W. Murphy, R. J. Webster, B. A. Turlach, C. J. Quirk, C. D. Clay, P. J. Heenan, and D. D. Sampson, “Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy,” J. Biomed. Opt. 10, 064020 (2005).
  47. A. Garcia-Uribe, N. Kehtarnavaz, G. Marquez, V. Prieto, M. Duvic, and L. V. Wang, “Skin cancer detection by spectroscopic oblique-incidence reflectometry: classification and physiological origins,” Appl. Opt. 43, 2643-2650 (2004).
    [CrossRef]
  48. M. Panjehpour, C. E. Julius, M. N. Phan, T. Vo-Dinh, and S. Overholt, “Laser-induced fluorescence spectroscopy for in vivo diagnosis of non-melanoma skin cancers,” Lasers Surg. Med. 31, 367-373 (2002).
    [CrossRef]
  49. H. Sterenborg, M. Motamedi, R. Wagner, M. Duvic, S. Thomsen, and S. Jacques, “In vivo fluorescence spectroscopy and imaging of human skin tumours,” Lasers Med. Sci. 9, 191-201 (1994).
  50. H. Zeng, C. MacAulay, B. Palcic, and D. I. McLean, “A computerized autofluorescence and diffuse reflectance spectroanalyser system for in vivo skin studies,” Phys. Med. Biol. 38, 231-240 (1993).
    [CrossRef]
  51. E. Borisova, P. Troyanova, P. Pavlova, and L. Avramov, “Diagnostics of pigmented skin tumors based on laser-induced autofluorescence and diffuse reflectance spectroscopy,” Quantum Electron. 38, 597-605 (2008).
    [CrossRef]
  52. S. Jacques, C. Alter, and S. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309-333 (1987).
  53. M. Van Gemert, S. Jacques, H. Sterenborg, and W. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146-1154(1989).
    [CrossRef]
  54. R. Reif, O. A'Amar, and I. Bigio, “Analytical model of light reflectance for extraction of the optical properties in small volumes of turbid media,” Appl. Opt. 46, 7317-7328(2007).
    [CrossRef]

2008 (9)

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13, 014017 (2008).

G. M. Palmer, and N. Ramanujam, “Monte-Carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt. 13, 024017 (2008).

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach,” J. Biomed. Opt. 13, 034015 (2008).

C. Zhu, T. M. Breslin, J. Harter, and N. Ramanujam, “Model based and empirical spectral analysis for the diagnosis of breast cancer,” Opt. Express 16, 14961-14978 (2008).
[CrossRef]

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

C. Redden Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. Macaulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt. 13, 064016 (2008).

N. Rajaram, T. H. Nguyen, and J. W. Tunnell, “Lookup table-based inverse model for determining optical properties of turbid media,” J. Biomed. Opt. 13, 050501 (2008).

E. Borisova, P. Troyanova, P. Pavlova, and L. Avramov, “Diagnostics of pigmented skin tumors based on laser-induced autofluorescence and diffuse reflectance spectroscopy,” Quantum Electron. 38, 597-605 (2008).
[CrossRef]

2007 (4)

R. Reif, O. A'Amar, and I. Bigio, “Analytical model of light reflectance for extraction of the optical properties in small volumes of turbid media,” Appl. Opt. 46, 7317-7328(2007).
[CrossRef]

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

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, 19494-19499 (2007).

M. Mogensen and G. Jemec, “Diagnosis of nonmelanoma skin cancer/keratinocyte carcinoma: a review of diagnostic accuracy of nonmelanoma skin cancer diagnostic tests and technologies,” Dermatol. Surg. 33, 1158-1174 (2007).

2006 (3)

W. Cottrell, A. Oseroff, and T. Foster, “Portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease,” Rev. Sci. Instrum. 77, 064302 (2006).
[CrossRef]

J. M. Levitt, A. Baldwin, A. Papadakis, S. Puri, J. Xylas, K. Munger, and I. Georgakoudi, “Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells,” J. Biomed. Opt. 11, 064012 (2006).

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

2005 (3)

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).

S. Chang, Y. Mirabal, E. 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).

B. W. Murphy, R. J. Webster, B. A. Turlach, C. J. Quirk, C. D. Clay, P. J. Heenan, and D. D. Sampson, “Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy,” J. Biomed. Opt. 10, 064020 (2005).

2004 (2)

2003 (3)

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

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]

2002 (4)

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).

M. Müller, A. Wax, I. Georgakoudi, R. Dasari, and M. Feld, “A reflectance spectrofluorimeter for real-time spectral diagnosis of disease,” Rev. Sci. Instrum. 73, 3933 (2002).
[CrossRef]

M. Panjehpour, C. E. Julius, M. N. Phan, T. Vo-Dinh, and S. Overholt, “Laser-induced fluorescence spectroscopy for in vivo diagnosis of non-melanoma skin cancers,” Lasers Surg. Med. 31, 367-373 (2002).
[CrossRef]

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).

2001 (4)

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).

L. Coghlan, U. Utzinger, R. Richards-Kortum, C. Brookner, A. Zuluaga, I. Gimenez-Conti, and M. Follen, “Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: spectroscopic changes precede morphologic changes,” Lasers. Surg. Med. 29, 1-10 (2001).

M. Brewer, U. Utzinger, E. Silva, D. Gershenson, R. C. Bast Jr., M. Follen, and R. Richards-Kortum, “Fluorescence spectroscopy for in vivo characterization of ovarian tissue,” Lasers. Surg. Med. 29, 128-135 (2001).

2000 (5)

Q. Zhang, M. G. Muller, J. Wu, and M. S. Feld, “Turbidity-free fluorescence spectroscopy of biological tissue,” Opt. Lett. 25, 1451-1453 (2000).
[CrossRef]

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

L. Coghlan, U. Utzinger, R. Drezek, D. Heintzelmann, A. Zuluaga, C. Brookner, R. Richards-Kortum, I. Gimenez-Conti, and M. Follen, “Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model,” Opt. Express 7, 436-446(2000).
[CrossRef]

Z136 Committee, American National Standard for Safe Use of Lasers (ANSI Z136.1-2000) (ANSI, Laser Institute of America, 2000).

V. P. Wallace, D. C. Crawford, P. S. Mortimer, R. J. Ott, and J. C. Bamber, “Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance,” Phys. Med. Biol. 45, 735-751 (2000).
[CrossRef]

1999 (2)

1997 (2)

1996 (2)

M. Panjehpour, B. F. Overholt, T. Vo-Dinh, R. C. Haggitt, D. H. Edwards, and F. P. Buckley III, “Endoscopic fluorescence detection of high-grade dysplasia in Barrett's esophagus,” Gastroenterology 111, 93-101 (1996).
[CrossRef]

R. Zângaro, L. Silveira, R. Manoharan, G. Zonios, I. Itzkan, R. Dasari, J. Van Dam, and M. Feld, “Rapid multiexcitation fluorescence spectroscopy system for in vivo tissue diagnosis,” Appl. Opt. 35, 5211-5219 (1996).
[CrossRef]

1995 (1)

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, and T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Surg. Med. 17, 350-357(1995).
[CrossRef]

1994 (2)

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 91, 10193-10197 (1994).

H. Sterenborg, M. Motamedi, R. Wagner, M. Duvic, S. Thomsen, and S. Jacques, “In vivo fluorescence spectroscopy and imaging of human skin tumours,” Lasers Med. Sci. 9, 191-201 (1994).

1993 (2)

H. Zeng, C. MacAulay, B. Palcic, and D. I. McLean, “A computerized autofluorescence and diffuse reflectance spectroanalyser system for in vivo skin studies,” Phys. Med. Biol. 38, 231-240 (1993).
[CrossRef]

J. Wu, M. Feld, and R. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3585-3595 (1993).
[CrossRef]

1992 (2)

T. J. Farrell, M. S. Patterson, and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879-888 (1992).
[CrossRef]

R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
[CrossRef]

1991 (1)

R. Richards-Kortum, R. Rava, R. Petras, M. Fitzmaurice, M. Sivak, and M. Feld, “Spectroscopic diagnosis of colonic dysplasia,” Photochem. Photobiol. 53, 777 (1991).

1989 (1)

M. Van Gemert, S. Jacques, H. Sterenborg, and W. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146-1154(1989).
[CrossRef]

1987 (1)

S. Jacques, C. Alter, and S. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309-333 (1987).

A'Amar, O.

Alter, C.

S. Jacques, C. Alter, and S. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309-333 (1987).

Amelink, A.

Angheloiu, G. O.

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

Atkinson, E.

S. Chang, Y. Mirabal, E. 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).

Atkinson, E. N.

C. Redden Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. Macaulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt. 13, 064016 (2008).

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

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).

Avramov, L.

E. Borisova, P. Troyanova, P. Pavlova, and L. Avramov, “Diagnostics of pigmented skin tumors based on laser-induced autofluorescence and diffuse reflectance spectroscopy,” Quantum Electron. 38, 597-605 (2008).
[CrossRef]

Awasthi, S.

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

Backman, V.

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

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).

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

G. Zonios, L. T. 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]

Badizadegan, K.

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

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).

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

Baldwin, A.

J. M. Levitt, A. Baldwin, A. Papadakis, S. Puri, J. Xylas, K. Munger, and I. Georgakoudi, “Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells,” J. Biomed. Opt. 11, 064012 (2006).

Bamber, J. C.

V. P. Wallace, D. C. Crawford, P. S. Mortimer, R. J. Ott, and J. C. Bamber, “Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance,” Phys. Med. Biol. 45, 735-751 (2000).
[CrossRef]

Bard, M. P.

Bassukas, I.

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13, 014017 (2008).

Bast, R. C.

M. Brewer, U. Utzinger, E. Silva, D. Gershenson, R. C. Bast Jr., M. Follen, and R. Richards-Kortum, “Fluorescence spectroscopy for in vivo characterization of ovarian tissue,” Lasers. Surg. Med. 29, 128-135 (2001).

Bechtel, K. L.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

Bigio, I.

Bigio, I. J.

J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, and I. J. Bigio, “Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms,” Appl. Opt. 36, 949-957 (1997).
[CrossRef]

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, and T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Surg. Med. 17, 350-357(1995).
[CrossRef]

Boiko, I.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).

Boone, C.

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

Borisova, E.

E. Borisova, P. Troyanova, P. Pavlova, and L. Avramov, “Diagnostics of pigmented skin tumors based on laser-induced autofluorescence and diffuse reflectance spectroscopy,” Quantum Electron. 38, 597-605 (2008).
[CrossRef]

Boyer, J.

J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, and I. J. Bigio, “Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms,” Appl. Opt. 36, 949-957 (1997).
[CrossRef]

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, and T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Surg. Med. 17, 350-357(1995).
[CrossRef]

Brambilla, M.

R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
[CrossRef]

Breslin, T. M.

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach,” J. Biomed. Opt. 13, 034015 (2008).

C. Zhu, T. M. Breslin, J. Harter, and N. Ramanujam, “Model based and empirical spectral analysis for the diagnosis of breast cancer,” Opt. Express 16, 14961-14978 (2008).
[CrossRef]

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).

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]

Brewer, M.

M. Brewer, U. Utzinger, E. Silva, D. Gershenson, R. C. Bast Jr., M. Follen, and R. Richards-Kortum, “Fluorescence spectroscopy for in vivo characterization of ovarian tissue,” Lasers. Surg. Med. 29, 128-135 (2001).

Brookner, C.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).

L. Coghlan, U. Utzinger, R. Richards-Kortum, C. Brookner, A. Zuluaga, I. Gimenez-Conti, and M. Follen, “Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: spectroscopic changes precede morphologic changes,” Lasers. Surg. Med. 29, 1-10 (2001).

L. Coghlan, U. Utzinger, R. Drezek, D. Heintzelmann, A. Zuluaga, C. Brookner, R. Richards-Kortum, I. Gimenez-Conti, and M. Follen, “Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model,” Opt. Express 7, 436-446(2000).
[CrossRef]

Buckley, F. P.

M. Panjehpour, B. F. Overholt, T. Vo-Dinh, R. C. Haggitt, D. H. Edwards, and F. P. Buckley III, “Endoscopic fluorescence detection of high-grade dysplasia in Barrett's esophagus,” Gastroenterology 111, 93-101 (1996).
[CrossRef]

Burgers, S. A.

Cascinelli, N.

R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
[CrossRef]

Chang, S.

S. Chang, Y. Mirabal, E. 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).

Chang, S. K.

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).

Clay, C. D.

B. W. Murphy, R. J. Webster, B. A. Turlach, C. J. Quirk, C. D. Clay, P. J. Heenan, and D. D. Sampson, “Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy,” J. Biomed. Opt. 10, 064020 (2005).

Clemente, C.

R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
[CrossRef]

Coghlan, L.

L. Coghlan, U. Utzinger, R. Richards-Kortum, C. Brookner, A. Zuluaga, I. Gimenez-Conti, and M. Follen, “Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: spectroscopic changes precede morphologic changes,” Lasers. Surg. Med. 29, 1-10 (2001).

L. Coghlan, U. Utzinger, R. Drezek, D. Heintzelmann, A. Zuluaga, C. Brookner, R. Richards-Kortum, I. Gimenez-Conti, and M. Follen, “Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model,” Opt. Express 7, 436-446(2000).
[CrossRef]

Committee, Z136

Z136 Committee, American National Standard for Safe Use of Lasers (ANSI Z136.1-2000) (ANSI, Laser Institute of America, 2000).

Conn, R. L.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, and T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Surg. Med. 17, 350-357(1995).
[CrossRef]

Cottrell, W.

W. Cottrell, A. Oseroff, and T. Foster, “Portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease,” Rev. Sci. Instrum. 77, 064302 (2006).
[CrossRef]

Cox, D.

S. Chang, Y. Mirabal, E. 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).

Cox, D. D.

C. Redden Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. Macaulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt. 13, 064016 (2008).

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

Crawford, D. C.

V. P. Wallace, D. C. Crawford, P. S. Mortimer, R. J. Ott, and J. C. Bamber, “Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance,” Phys. Med. Biol. 45, 735-751 (2000).
[CrossRef]

Crum, C. P.

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).

Dasari, R.

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

M. Müller, A. Wax, I. Georgakoudi, R. Dasari, and M. Feld, “A reflectance spectrofluorimeter for real-time spectral diagnosis of disease,” Rev. Sci. Instrum. 73, 3933 (2002).
[CrossRef]

R. Zângaro, L. Silveira, R. Manoharan, G. Zonios, I. Itzkan, R. Dasari, J. Van Dam, and M. Feld, “Rapid multiexcitation fluorescence spectroscopy system for in vivo tissue diagnosis,” Appl. Opt. 35, 5211-5219 (1996).
[CrossRef]

Dasari, R. R.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

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).

Desjardins, A. E.

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

Dimou, A.

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13, 014017 (2008).

Drezek, R.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).

L. Coghlan, U. Utzinger, R. Drezek, D. Heintzelmann, A. Zuluaga, C. Brookner, R. Richards-Kortum, I. Gimenez-Conti, and M. Follen, “Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model,” Opt. Express 7, 436-446(2000).
[CrossRef]

Durkin, A.

Duvic, M.

A. Garcia-Uribe, N. Kehtarnavaz, G. Marquez, V. Prieto, M. Duvic, and L. V. Wang, “Skin cancer detection by spectroscopic oblique-incidence reflectometry: classification and physiological origins,” Appl. Opt. 43, 2643-2650 (2004).
[CrossRef]

H. Sterenborg, M. Motamedi, R. Wagner, M. Duvic, S. Thomsen, and S. Jacques, “In vivo fluorescence spectroscopy and imaging of human skin tumours,” Lasers Med. Sci. 9, 191-201 (1994).

Edwards, D. H.

M. Panjehpour, B. F. Overholt, T. Vo-Dinh, R. C. Haggitt, D. H. Edwards, and F. P. Buckley III, “Endoscopic fluorescence detection of high-grade dysplasia in Barrett's esophagus,” Gastroenterology 111, 93-101 (1996).
[CrossRef]

Eickhoff, J.

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, 19494-19499 (2007).

Elackattu, A.

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

Eliceiri, K. W.

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, 19494-19499 (2007).

Fan, J.

Farrell, T. J.

T. J. Farrell, M. S. Patterson, and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879-888 (1992).
[CrossRef]

Feld, M.

M. Müller, A. Wax, I. Georgakoudi, R. Dasari, and M. Feld, “A reflectance spectrofluorimeter for real-time spectral diagnosis of disease,” Rev. Sci. Instrum. 73, 3933 (2002).
[CrossRef]

R. Zângaro, L. Silveira, R. Manoharan, G. Zonios, I. Itzkan, R. Dasari, J. Van Dam, and M. Feld, “Rapid multiexcitation fluorescence spectroscopy system for in vivo tissue diagnosis,” Appl. Opt. 35, 5211-5219 (1996).
[CrossRef]

J. Wu, M. Feld, and R. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3585-3595 (1993).
[CrossRef]

R. Richards-Kortum, R. Rava, R. Petras, M. Fitzmaurice, M. Sivak, and M. Feld, “Spectroscopic diagnosis of colonic dysplasia,” Photochem. Photobiol. 53, 777 (1991).

Feld, M. S.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

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).

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

Q. Zhang, M. G. Muller, J. Wu, and M. S. Feld, “Turbidity-free fluorescence spectroscopy of biological tissue,” Opt. Lett. 25, 1451-1453 (2000).
[CrossRef]

G. Zonios, L. T. 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]

Fitzmaurice, M.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

G. Zonios, L. T. 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]

R. Richards-Kortum, R. Rava, R. Petras, M. Fitzmaurice, M. Sivak, and M. Feld, “Spectroscopic diagnosis of colonic dysplasia,” Photochem. Photobiol. 53, 777 (1991).

Follen, M.

C. Redden Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. Macaulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt. 13, 064016 (2008).

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

S. Chang, Y. Mirabal, E. 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).

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).

M. Brewer, U. Utzinger, E. Silva, D. Gershenson, R. C. Bast Jr., M. Follen, and R. Richards-Kortum, “Fluorescence spectroscopy for in vivo characterization of ovarian tissue,” Lasers. Surg. Med. 29, 128-135 (2001).

L. Coghlan, U. Utzinger, R. Richards-Kortum, C. Brookner, A. Zuluaga, I. Gimenez-Conti, and M. Follen, “Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: spectroscopic changes precede morphologic changes,” Lasers. Surg. Med. 29, 1-10 (2001).

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).

L. Coghlan, U. Utzinger, R. Drezek, D. Heintzelmann, A. Zuluaga, C. Brookner, R. Richards-Kortum, I. Gimenez-Conti, and M. Follen, “Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model,” Opt. Express 7, 436-446(2000).
[CrossRef]

Foster, T.

W. Cottrell, A. Oseroff, and T. Foster, “Portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease,” Rev. Sci. Instrum. 77, 064302 (2006).
[CrossRef]

Freeberg, J. A.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

Fuchs, H.

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

A. Zuluaga, U. Utzinger, A. Durkin, H. Fuchs, A. Gillenwater, R. Jacob, B. Kemp, J. Fan, and R. Richards-Kortum, “Fluorescence excitation emission matrices of human tissue: a system for in vivo measurement and method of data analysis,” Appl. Spectrosc. 53, 302-311 (1999).
[CrossRef]

Fuentes, C.

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

Fuselier, T.

Galaris, D.

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13, 014017 (2008).

Galindo, L.

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

Gallagher, G.

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

Garcia-Uribe, A.

Gardecki, J. A.

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

Gendron-Fitzpatrick, A.

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, 19494-19499 (2007).

Georgakoudi, I.

J. M. Levitt, A. Baldwin, A. Papadakis, S. Puri, J. Xylas, K. Munger, and I. Georgakoudi, “Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells,” J. Biomed. Opt. 11, 064012 (2006).

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

M. Müller, A. Wax, I. Georgakoudi, R. Dasari, and M. Feld, “A reflectance spectrofluorimeter for real-time spectral diagnosis of disease,” Rev. Sci. Instrum. 73, 3933 (2002).
[CrossRef]

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).

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

Gershenson, D.

M. Brewer, U. Utzinger, E. Silva, D. Gershenson, R. C. Bast Jr., M. Follen, and R. Richards-Kortum, “Fluorescence spectroscopy for in vivo characterization of ovarian tissue,” Lasers. Surg. Med. 29, 128-135 (2001).

Gilchrist, K. W.

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]

Gillenwater, A.

Gillenwater, A. M.

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

Gimenez-Conti, I.

L. Coghlan, U. Utzinger, R. Richards-Kortum, C. Brookner, A. Zuluaga, I. Gimenez-Conti, and M. Follen, “Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: spectroscopic changes precede morphologic changes,” Lasers. Surg. Med. 29, 1-10 (2001).

L. Coghlan, U. Utzinger, R. Drezek, D. Heintzelmann, A. Zuluaga, C. Brookner, R. Richards-Kortum, I. Gimenez-Conti, and M. Follen, “Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model,” Opt. Express 7, 436-446(2000).
[CrossRef]

Gossage, K.

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

Haggitt, R. C.

M. Panjehpour, B. F. Overholt, T. Vo-Dinh, R. C. Haggitt, D. H. Edwards, and F. P. Buckley III, “Endoscopic fluorescence detection of high-grade dysplasia in Barrett's esophagus,” Gastroenterology 111, 93-101 (1996).
[CrossRef]

Haka, A. S.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

Harter, J.

C. Zhu, T. M. Breslin, J. Harter, and N. Ramanujam, “Model based and empirical spectral analysis for the diagnosis of breast cancer,” Opt. Express 16, 14961-14978 (2008).
[CrossRef]

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach,” J. Biomed. Opt. 13, 034015 (2008).

Heenan, P. J.

B. W. Murphy, R. J. Webster, B. A. Turlach, C. J. Quirk, C. D. Clay, P. J. Heenan, and D. D. Sampson, “Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy,” J. Biomed. Opt. 10, 064020 (2005).

Heintzelman, D. L.

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

Heintzelmann, D.

Itzkan, I.

Jacob, R.

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

A. Zuluaga, U. Utzinger, A. Durkin, H. Fuchs, A. Gillenwater, R. Jacob, B. Kemp, J. Fan, and R. Richards-Kortum, “Fluorescence excitation emission matrices of human tissue: a system for in vivo measurement and method of data analysis,” Appl. Spectrosc. 53, 302-311 (1999).
[CrossRef]

Jacobson, B. C.

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

Jacques, S.

H. Sterenborg, M. Motamedi, R. Wagner, M. Duvic, S. Thomsen, and S. Jacques, “In vivo fluorescence spectroscopy and imaging of human skin tumours,” Lasers Med. Sci. 9, 191-201 (1994).

M. Van Gemert, S. Jacques, H. Sterenborg, and W. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146-1154(1989).
[CrossRef]

S. Jacques, C. Alter, and S. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309-333 (1987).

Jemec, G.

M. Mogensen and G. Jemec, “Diagnosis of nonmelanoma skin cancer/keratinocyte carcinoma: a review of diagnostic accuracy of nonmelanoma skin cancer diagnostic tests and technologies,” Dermatol. Surg. 33, 1158-1174 (2007).

Johnson, T.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, and T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Surg. Med. 17, 350-357(1995).
[CrossRef]

Johnson, T. M.

Julius, C. E.

M. Panjehpour, C. E. Julius, M. N. Phan, T. Vo-Dinh, and S. Overholt, “Laser-induced fluorescence spectroscopy for in vivo diagnosis of non-melanoma skin cancers,” Lasers Surg. Med. 31, 367-373 (2002).
[CrossRef]

Kabani, S.

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

Kaxiras, E.

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13, 014017 (2008).

Kehtarnavaz, N.

Kemp, B.

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

A. Zuluaga, U. Utzinger, A. Durkin, H. Fuchs, A. Gillenwater, R. Jacob, B. Kemp, J. Fan, and R. Richards-Kortum, “Fluorescence excitation emission matrices of human tissue: a system for in vivo measurement and method of data analysis,” Appl. Spectrosc. 53, 302-311 (1999).
[CrossRef]

Kienle, A.

Kramer, J. R.

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

Laver, N.

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

Levitt, J. M.

J. M. Levitt, A. Baldwin, A. Papadakis, S. Puri, J. Xylas, K. Munger, and I. Georgakoudi, “Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells,” J. Biomed. Opt. 11, 064012 (2006).

Lotan, R.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).

Macaulay, C.

C. Redden Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. Macaulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt. 13, 064016 (2008).

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

H. Zeng, C. MacAulay, B. Palcic, and D. I. McLean, “A computerized autofluorescence and diffuse reflectance spectroanalyser system for in vivo skin studies,” Phys. Med. Biol. 38, 231-240 (1993).
[CrossRef]

Mahadevan, A.

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 91, 10193-10197 (1994).

Malpica, A.

S. Chang, Y. Mirabal, E. 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).

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).

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).

Manoharan, R.

Marchesini, R.

R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
[CrossRef]

Mardirossian, V.

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

Marquez, G.

Mascheroni, L.

R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
[CrossRef]

McGee, S.

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

McGee, S. A.

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

McKinnon, N.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

McLean, D. I.

H. Zeng, C. MacAulay, B. Palcic, and D. I. McLean, “A computerized autofluorescence and diffuse reflectance spectroanalyser system for in vivo skin studies,” Phys. Med. Biol. 38, 231-240 (1993).
[CrossRef]

Mirabal, Y.

S. Chang, Y. Mirabal, E. 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).

Mirabal, Y. N.

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).

Mirkovic, J.

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

Mitchell, M. F.

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 91, 10193-10197 (1994).

Mogensen, M.

M. Mogensen and G. Jemec, “Diagnosis of nonmelanoma skin cancer/keratinocyte carcinoma: a review of diagnostic accuracy of nonmelanoma skin cancer diagnostic tests and technologies,” Dermatol. Surg. 33, 1158-1174 (2007).

Mortimer, P. S.

V. P. Wallace, D. C. Crawford, P. S. Mortimer, R. J. Ott, and J. C. Bamber, “Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance,” Phys. Med. Biol. 45, 735-751 (2000).
[CrossRef]

Motamedi, M.

H. Sterenborg, M. Motamedi, R. Wagner, M. Duvic, S. Thomsen, and S. Jacques, “In vivo fluorescence spectroscopy and imaging of human skin tumours,” Lasers Med. Sci. 9, 191-201 (1994).

Motz, J. T.

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

Mourant, J. R.

J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, and I. J. Bigio, “Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms,” Appl. Opt. 36, 949-957 (1997).
[CrossRef]

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, and T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Surg. Med. 17, 350-357(1995).
[CrossRef]

Mueller, M. G.

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

Muller, M.

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

Muller, M. G.

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).

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

Q. Zhang, M. G. Muller, J. Wu, and M. S. Feld, “Turbidity-free fluorescence spectroscopy of biological tissue,” Opt. Lett. 25, 1451-1453 (2000).
[CrossRef]

Müller, M.

M. Müller, A. Wax, I. Georgakoudi, R. Dasari, and M. Feld, “A reflectance spectrofluorimeter for real-time spectral diagnosis of disease,” Rev. Sci. Instrum. 73, 3933 (2002).
[CrossRef]

Munger, K.

J. M. Levitt, A. Baldwin, A. Papadakis, S. Puri, J. Xylas, K. Munger, and I. Georgakoudi, “Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells,” J. Biomed. Opt. 11, 064012 (2006).

Murphy, B. W.

B. W. Murphy, R. J. Webster, B. A. Turlach, C. J. Quirk, C. D. Clay, P. J. Heenan, and D. D. Sampson, “Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy,” J. Biomed. Opt. 10, 064020 (2005).

Nazemi, J.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

Nguyen, F. T.

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

Nguyen, T. H.

N. Rajaram, T. H. Nguyen, and J. W. Tunnell, “Lookup table-based inverse model for determining optical properties of turbid media,” J. Biomed. Opt. 13, 050501 (2008).

Oseroff, A.

W. Cottrell, A. Oseroff, and T. Foster, “Portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease,” Rev. Sci. Instrum. 77, 064302 (2006).
[CrossRef]

Ott, R. J.

V. P. Wallace, D. C. Crawford, P. S. Mortimer, R. J. Ott, and J. C. Bamber, “Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance,” Phys. Med. Biol. 45, 735-751 (2000).
[CrossRef]

Overholt, B. F.

M. Panjehpour, B. F. Overholt, T. Vo-Dinh, R. C. Haggitt, D. H. Edwards, and F. P. Buckley III, “Endoscopic fluorescence detection of high-grade dysplasia in Barrett's esophagus,” Gastroenterology 111, 93-101 (1996).
[CrossRef]

Overholt, S.

M. Panjehpour, C. E. Julius, M. N. Phan, T. Vo-Dinh, and S. Overholt, “Laser-induced fluorescence spectroscopy for in vivo diagnosis of non-melanoma skin cancers,” Lasers Surg. Med. 31, 367-373 (2002).
[CrossRef]

Palcic, B.

H. Zeng, C. MacAulay, B. Palcic, and D. I. McLean, “A computerized autofluorescence and diffuse reflectance spectroanalyser system for in vivo skin studies,” Phys. Med. Biol. 38, 231-240 (1993).
[CrossRef]

Palmer, G. M.

G. M. Palmer, and N. Ramanujam, “Monte-Carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt. 13, 024017 (2008).

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach,” J. Biomed. Opt. 13, 034015 (2008).

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).

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]

Panjehpour, M.

M. Panjehpour, C. E. Julius, M. N. Phan, T. Vo-Dinh, and S. Overholt, “Laser-induced fluorescence spectroscopy for in vivo diagnosis of non-melanoma skin cancers,” Lasers Surg. Med. 31, 367-373 (2002).
[CrossRef]

M. Panjehpour, B. F. Overholt, T. Vo-Dinh, R. C. Haggitt, D. H. Edwards, and F. P. Buckley III, “Endoscopic fluorescence detection of high-grade dysplasia in Barrett's esophagus,” Gastroenterology 111, 93-101 (1996).
[CrossRef]

Papadakis, A.

J. M. Levitt, A. Baldwin, A. Papadakis, S. Puri, J. Xylas, K. Munger, and I. Georgakoudi, “Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells,” J. Biomed. Opt. 11, 064012 (2006).

Patterson, M. S.

A. Kienle, and M. S. Patterson, “Improved solutions of the steady-state and the time-resolved diffusion equations for reflectance from a semi-infinite turbid medium,” J. Opt. Soc. Am. A 14, 246-254 (1997).
[CrossRef]

T. J. Farrell, M. S. Patterson, and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879-888 (1992).
[CrossRef]

Pavlova, I.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).

Pavlova, P.

E. Borisova, P. Troyanova, P. Pavlova, and L. Avramov, “Diagnostics of pigmented skin tumors based on laser-induced autofluorescence and diffuse reflectance spectroscopy,” Quantum Electron. 38, 597-605 (2008).
[CrossRef]

Perelman, L. T.

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

G. Zonios, L. T. 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]

Petras, R.

R. Richards-Kortum, R. Rava, R. Petras, M. Fitzmaurice, M. Sivak, and M. Feld, “Spectroscopic diagnosis of colonic dysplasia,” Photochem. Photobiol. 53, 777 (1991).

Phan, M. N.

M. Panjehpour, C. E. Julius, M. N. Phan, T. Vo-Dinh, and S. Overholt, “Laser-induced fluorescence spectroscopy for in vivo diagnosis of non-melanoma skin cancers,” Lasers Surg. Med. 31, 367-373 (2002).
[CrossRef]

Pignoli, E.

R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
[CrossRef]

Pikkula, B.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

Pistey, R.

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

Prahl, S.

S. Jacques, C. Alter, and S. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309-333 (1987).

Price, R.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

Prieto, V.

Puri, S.

J. M. Levitt, A. Baldwin, A. Papadakis, S. Puri, J. Xylas, K. Munger, and I. Georgakoudi, “Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells,” J. Biomed. Opt. 11, 064012 (2006).

Quirk, C. J.

B. W. Murphy, R. J. Webster, B. A. Turlach, C. J. Quirk, C. D. Clay, P. J. Heenan, and D. D. Sampson, “Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy,” J. Biomed. Opt. 10, 064020 (2005).

Rajaram, N.

N. Rajaram, T. H. Nguyen, and J. W. Tunnell, “Lookup table-based inverse model for determining optical properties of turbid media,” J. Biomed. Opt. 13, 050501 (2008).

Ramanujam, N.

G. M. Palmer, and N. Ramanujam, “Monte-Carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt. 13, 024017 (2008).

C. Zhu, T. M. Breslin, J. Harter, and N. Ramanujam, “Model based and empirical spectral analysis for the diagnosis of breast cancer,” Opt. Express 16, 14961-14978 (2008).
[CrossRef]

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach,” J. Biomed. Opt. 13, 034015 (2008).

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, 19494-19499 (2007).

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).

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]

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 91, 10193-10197 (1994).

Rava, R.

J. Wu, M. Feld, and R. Rava, “Analytical model for extracting intrinsic fluorescence in turbid media,” Appl. Opt. 32, 3585-3595 (1993).
[CrossRef]

R. Richards-Kortum, R. Rava, R. Petras, M. Fitzmaurice, M. Sivak, and M. Feld, “Spectroscopic diagnosis of colonic dysplasia,” Photochem. Photobiol. 53, 777 (1991).

Redden Weber, C.

C. Redden Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. Macaulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt. 13, 064016 (2008).

Reif, R.

Richards-Kortum, R.

C. Redden Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. Macaulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt. 13, 064016 (2008).

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

S. Chang, Y. Mirabal, E. 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).

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).

M. Brewer, U. Utzinger, E. Silva, D. Gershenson, R. C. Bast Jr., M. Follen, and R. Richards-Kortum, “Fluorescence spectroscopy for in vivo characterization of ovarian tissue,” Lasers. Surg. Med. 29, 128-135 (2001).

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).

L. Coghlan, U. Utzinger, R. Richards-Kortum, C. Brookner, A. Zuluaga, I. Gimenez-Conti, and M. Follen, “Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: spectroscopic changes precede morphologic changes,” Lasers. Surg. Med. 29, 1-10 (2001).

L. Coghlan, U. Utzinger, R. Drezek, D. Heintzelmann, A. Zuluaga, C. Brookner, R. Richards-Kortum, I. Gimenez-Conti, and M. Follen, “Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model,” Opt. Express 7, 436-446(2000).
[CrossRef]

A. Zuluaga, U. Utzinger, A. Durkin, H. Fuchs, A. Gillenwater, R. Jacob, B. Kemp, J. Fan, and R. Richards-Kortum, “Fluorescence excitation emission matrices of human tissue: a system for in vivo measurement and method of data analysis,” Appl. Spectrosc. 53, 302-311 (1999).
[CrossRef]

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 91, 10193-10197 (1994).

R. Richards-Kortum, R. Rava, R. Petras, M. Fitzmaurice, M. Sivak, and M. Feld, “Spectroscopic diagnosis of colonic dysplasia,” Photochem. Photobiol. 53, 777 (1991).

Richards-Kortum, R. R.

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

Riching, K. M.

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, 19494-19499 (2007).

Sampson, D. D.

B. W. Murphy, R. J. Webster, B. A. Turlach, C. J. Quirk, C. D. Clay, P. J. Heenan, and D. D. Sampson, “Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy,” J. Biomed. Opt. 10, 064020 (2005).

Scepanovic, O. R.

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

Schwarz, R. A.

C. Redden Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. Macaulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt. 13, 064016 (2008).

Serachitopol, D. M.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

Sheets, E. E.

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).

Shenk, R.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

Shimada, T.

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, and T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Surg. Med. 17, 350-357(1995).
[CrossRef]

Silva, E.

M. Brewer, U. Utzinger, E. Silva, D. Gershenson, R. C. Bast Jr., M. Follen, and R. Richards-Kortum, “Fluorescence spectroscopy for in vivo characterization of ovarian tissue,” Lasers. Surg. Med. 29, 128-135 (2001).

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 91, 10193-10197 (1994).

Silveira, L.

Sivak, M.

R. Richards-Kortum, R. Rava, R. Petras, M. Fitzmaurice, M. Sivak, and M. Feld, “Spectroscopic diagnosis of colonic dysplasia,” Photochem. Photobiol. 53, 777 (1991).

Skala, M. C.

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, 19494-19499 (2007).

Star, W.

M. Van Gemert, S. Jacques, H. Sterenborg, and W. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146-1154(1989).
[CrossRef]

Sterenborg, H.

H. Sterenborg, M. Motamedi, R. Wagner, M. Duvic, S. Thomsen, and S. Jacques, “In vivo fluorescence spectroscopy and imaging of human skin tumours,” Lasers Med. Sci. 9, 191-201 (1994).

M. Van Gemert, S. Jacques, H. Sterenborg, and W. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146-1154(1989).
[CrossRef]

Sterenborg, H. J.

Sun, D.

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

Testori, A.

R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
[CrossRef]

Thomas, G. A.

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

Thomsen, S.

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 91, 10193-10197 (1994).

H. Sterenborg, M. Motamedi, R. Wagner, M. Duvic, S. Thomsen, and S. Jacques, “In vivo fluorescence spectroscopy and imaging of human skin tumours,” Lasers Med. Sci. 9, 191-201 (1994).

Troyanova, P.

E. Borisova, P. Troyanova, P. Pavlova, and L. Avramov, “Diagnostics of pigmented skin tumors based on laser-induced autofluorescence and diffuse reflectance spectroscopy,” Quantum Electron. 38, 597-605 (2008).
[CrossRef]

Tsolakidis, A.

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13, 014017 (2008).

Tunnell, J. W.

N. Rajaram, T. H. Nguyen, and J. W. Tunnell, “Lookup table-based inverse model for determining optical properties of turbid media,” J. Biomed. Opt. 13, 050501 (2008).

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

Turlach, B. A.

B. W. Murphy, R. J. Webster, B. A. Turlach, C. J. Quirk, C. D. Clay, P. J. Heenan, and D. D. Sampson, “Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy,” J. Biomed. Opt. 10, 064020 (2005).

Utzinger, U.

M. Brewer, U. Utzinger, E. Silva, D. Gershenson, R. C. Bast Jr., M. Follen, and R. Richards-Kortum, “Fluorescence spectroscopy for in vivo characterization of ovarian tissue,” Lasers. Surg. Med. 29, 128-135 (2001).

L. Coghlan, U. Utzinger, R. Richards-Kortum, C. Brookner, A. Zuluaga, I. Gimenez-Conti, and M. Follen, “Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: spectroscopic changes precede morphologic changes,” Lasers. Surg. Med. 29, 1-10 (2001).

L. Coghlan, U. Utzinger, R. Drezek, D. Heintzelmann, A. Zuluaga, C. Brookner, R. Richards-Kortum, I. Gimenez-Conti, and M. Follen, “Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model,” Opt. Express 7, 436-446(2000).
[CrossRef]

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

A. Zuluaga, U. Utzinger, A. Durkin, H. Fuchs, A. Gillenwater, R. Jacob, B. Kemp, J. Fan, and R. Richards-Kortum, “Fluorescence excitation emission matrices of human tissue: a system for in vivo measurement and method of data analysis,” Appl. Spectrosc. 53, 302-311 (1999).
[CrossRef]

Valdez, T.

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

Van Dam, J.

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

G. Zonios, L. T. 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]

R. Zângaro, L. Silveira, R. Manoharan, G. Zonios, I. Itzkan, R. Dasari, J. Van Dam, and M. Feld, “Rapid multiexcitation fluorescence spectroscopy system for in vivo tissue diagnosis,” Appl. Opt. 35, 5211-5219 (1996).
[CrossRef]

Van Gemert, M.

M. Van Gemert, S. Jacques, H. Sterenborg, and W. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146-1154(1989).
[CrossRef]

Venturoli, D.

R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
[CrossRef]

Vo-Dinh, T.

M. Panjehpour, C. E. Julius, M. N. Phan, T. Vo-Dinh, and S. Overholt, “Laser-induced fluorescence spectroscopy for in vivo diagnosis of non-melanoma skin cancers,” Lasers Surg. Med. 31, 367-373 (2002).
[CrossRef]

M. Panjehpour, B. F. Overholt, T. Vo-Dinh, R. C. Haggitt, D. H. Edwards, and F. P. Buckley III, “Endoscopic fluorescence detection of high-grade dysplasia in Barrett's esophagus,” Gastroenterology 111, 93-101 (1996).
[CrossRef]

Volynskaya, Z.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

Wagner, R.

H. Sterenborg, M. Motamedi, R. Wagner, M. Duvic, S. Thomsen, and S. Jacques, “In vivo fluorescence spectroscopy and imaging of human skin tumours,” Lasers Med. Sci. 9, 191-201 (1994).

Wallace, M. B.

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

Wallace, V. P.

V. P. Wallace, D. C. Crawford, P. S. Mortimer, R. J. Ott, and J. C. Bamber, “Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance,” Phys. Med. Biol. 45, 735-751 (2000).
[CrossRef]

Wang, L. V.

Wang, N.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

Wang, Z.

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

Warren, S.

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 91, 10193-10197 (1994).

Wax, A.

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

M. Müller, A. Wax, I. Georgakoudi, R. Dasari, and M. Feld, “A reflectance spectrofluorimeter for real-time spectral diagnosis of disease,” Rev. Sci. Instrum. 73, 3933 (2002).
[CrossRef]

Webster, R. J.

B. W. Murphy, R. J. Webster, B. A. Turlach, C. J. Quirk, C. D. Clay, P. J. Heenan, and D. D. Sampson, “Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy,” J. Biomed. Opt. 10, 064020 (2005).

White, J. G.

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, 19494-19499 (2007).

Wilson, B.

T. J. Farrell, M. S. Patterson, and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879-888 (1992).
[CrossRef]

Wu, J.

Xu, F.

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).

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]

Xylas, J.

J. M. Levitt, A. Baldwin, A. Papadakis, S. Puri, J. Xylas, K. Munger, and I. Georgakoudi, “Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells,” J. Biomed. Opt. 11, 064012 (2006).

Yu, C.

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

Zângaro, R.

Zeng, H.

H. Zeng, C. MacAulay, B. Palcic, and D. I. McLean, “A computerized autofluorescence and diffuse reflectance spectroanalyser system for in vivo skin studies,” Phys. Med. Biol. 38, 231-240 (1993).
[CrossRef]

Zhang, Q.

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

Q. Zhang, M. G. Muller, J. Wu, and M. S. Feld, “Turbidity-free fluorescence spectroscopy of biological tissue,” Opt. Lett. 25, 1451-1453 (2000).
[CrossRef]

Zhu, C.

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach,” J. Biomed. Opt. 13, 034015 (2008).

C. Zhu, T. M. Breslin, J. Harter, and N. Ramanujam, “Model based and empirical spectral analysis for the diagnosis of breast cancer,” Opt. Express 16, 14961-14978 (2008).
[CrossRef]

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).

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]

Zonios, G.

Zuluaga, A.

L. Coghlan, U. Utzinger, R. Richards-Kortum, C. Brookner, A. Zuluaga, I. Gimenez-Conti, and M. Follen, “Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: spectroscopic changes precede morphologic changes,” Lasers. Surg. Med. 29, 1-10 (2001).

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

L. Coghlan, U. Utzinger, R. Drezek, D. Heintzelmann, A. Zuluaga, C. Brookner, R. Richards-Kortum, I. Gimenez-Conti, and M. Follen, “Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model,” Opt. Express 7, 436-446(2000).
[CrossRef]

A. Zuluaga, U. Utzinger, A. Durkin, H. Fuchs, A. Gillenwater, R. Jacob, B. Kemp, J. Fan, and R. Richards-Kortum, “Fluorescence excitation emission matrices of human tissue: a system for in vivo measurement and method of data analysis,” Appl. Spectrosc. 53, 302-311 (1999).
[CrossRef]

Am. J. Obstet. Gynecol. (1)

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).

Appl. Opt. (6)

Appl. Spectrosc. (1)

Cancer Res. (1)

M. Muller, T. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. Boone, and R. Dasari, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer Res. 97, 1681-1692 (2003).

Dermatol. Surg. (1)

M. Mogensen and G. Jemec, “Diagnosis of nonmelanoma skin cancer/keratinocyte carcinoma: a review of diagnostic accuracy of nonmelanoma skin cancer diagnostic tests and technologies,” Dermatol. Surg. 33, 1158-1174 (2007).

Gastroenterology (2)

M. Panjehpour, B. F. Overholt, T. Vo-Dinh, R. C. Haggitt, D. H. Edwards, and F. P. Buckley III, “Endoscopic fluorescence detection of high-grade dysplasia in Barrett's esophagus,” Gastroenterology 111, 93-101 (1996).
[CrossRef]

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, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus,” Gastroenterology 120, 1620-1629 (2001).
[CrossRef]

IEEE Trans. Biomed. Eng. (2)

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]

M. Van Gemert, S. Jacques, H. Sterenborg, and W. Star, “Skin optics,” IEEE Trans. Biomed. Eng. 36, 1146-1154(1989).
[CrossRef]

J. Biomed. Opt. (14)

B. W. Murphy, R. J. Webster, B. A. Turlach, C. J. Quirk, C. D. Clay, P. J. Heenan, and D. D. Sampson, “Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy,” J. Biomed. Opt. 10, 064020 (2005).

S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, and K. Badizadegan, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13, 064034 (2008).

O. R. Scepanovic, M. Fitzmaurice, J. A. Gardecki, G. O. Angheloiu, S. Awasthi, J. T. Motz, J. R. Kramer, R. R. Dasari, and M. S. Feld, “Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy,” J. Biomed. Opt. 11, 021007 (2006).

N. Rajaram, T. H. Nguyen, and J. W. Tunnell, “Lookup table-based inverse model for determining optical properties of turbid media,” J. Biomed. Opt. 13, 050501 (2008).

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt. 13, 024012 (2008).

G. M. Palmer, and N. Ramanujam, “Monte-Carlo-based model for the extraction of intrinsic fluorescence from turbid media,” J. Biomed. Opt. 13, 024017 (2008).

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, “Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach,” J. Biomed. Opt. 13, 034015 (2008).

S. Chang, Y. Mirabal, E. 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).

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).

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, and B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12, 034015(2007).

C. Redden Weber, R. A. Schwarz, E. N. Atkinson, D. D. Cox, C. Macaulay, M. Follen, and R. Richards-Kortum, “Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer,” J. Biomed. Opt. 13, 064016 (2008).

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).

J. M. Levitt, A. Baldwin, A. Papadakis, S. Puri, J. Xylas, K. Munger, and I. Georgakoudi, “Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells,” J. Biomed. Opt. 11, 064012 (2006).

G. Zonios, A. Dimou, I. Bassukas, D. Galaris, A. Tsolakidis, and E. Kaxiras, “Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection,” J. Biomed. Opt. 13, 014017 (2008).

J. Opt. Soc. Am. A (1)

Lasers Life Sci. (1)

S. Jacques, C. Alter, and S. Prahl, “Angular dependence of HeNe laser light scattering by human dermis,” Lasers Life Sci. 1, 309-333 (1987).

Lasers Med. Sci. (1)

H. Sterenborg, M. Motamedi, R. Wagner, M. Duvic, S. Thomsen, and S. Jacques, “In vivo fluorescence spectroscopy and imaging of human skin tumours,” Lasers Med. Sci. 9, 191-201 (1994).

Lasers Surg. Med. (2)

M. Panjehpour, C. E. Julius, M. N. Phan, T. Vo-Dinh, and S. Overholt, “Laser-induced fluorescence spectroscopy for in vivo diagnosis of non-melanoma skin cancers,” Lasers Surg. Med. 31, 367-373 (2002).
[CrossRef]

J. R. Mourant, I. J. Bigio, J. Boyer, R. L. Conn, T. Johnson, and T. Shimada, “Spectroscopic diagnosis of bladder cancer with elastic light scattering,” Lasers Surg. Med. 17, 350-357(1995).
[CrossRef]

Lasers. Surg. Med. (2)

L. Coghlan, U. Utzinger, R. Richards-Kortum, C. Brookner, A. Zuluaga, I. Gimenez-Conti, and M. Follen, “Fluorescence spectroscopy of epithelial tissue throughout the dysplasia-carcinoma sequence in an animal model: spectroscopic changes precede morphologic changes,” Lasers. Surg. Med. 29, 1-10 (2001).

M. Brewer, U. Utzinger, E. Silva, D. Gershenson, R. C. Bast Jr., M. Follen, and R. Richards-Kortum, “Fluorescence spectroscopy for in vivo characterization of ovarian tissue,” Lasers. Surg. Med. 29, 128-135 (2001).

Med. Phys. (1)

T. J. Farrell, M. S. Patterson, and B. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879-888 (1992).
[CrossRef]

Opt. Express (2)

Opt. Lett. (2)

Photochem Photobiol (1)

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem Photobiol 73, 636-641 (2001).

Photochem. Photobiol. (3)

D. L. Heintzelman, U. Utzinger, H. Fuchs, A. Zuluaga, K. Gossage, A. M. Gillenwater, R. Jacob, B. Kemp, and R. R. Richards-Kortum, “Optimal excitation wavelengths for in vivo detection of oral neoplasia using fluorescence spectroscopy,” Photochem. Photobiol. 72, 103-113 (2000).
[CrossRef]

R. Marchesini, N. Cascinelli, M. Brambilla, C. Clemente, L. Mascheroni, E. Pignoli, A. Testori, and D. Venturoli, “In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma,” Photochem. Photobiol. 55, 515-522(1992).
[CrossRef]

R. Richards-Kortum, R. Rava, R. Petras, M. Fitzmaurice, M. Sivak, and M. Feld, “Spectroscopic diagnosis of colonic dysplasia,” Photochem. Photobiol. 53, 777 (1991).

Phys. Med. Biol. (2)

V. P. Wallace, D. C. Crawford, P. S. Mortimer, R. J. Ott, and J. C. Bamber, “Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance,” Phys. Med. Biol. 45, 735-751 (2000).
[CrossRef]

H. Zeng, C. MacAulay, B. Palcic, and D. I. McLean, “A computerized autofluorescence and diffuse reflectance spectroanalyser system for in vivo skin studies,” Phys. Med. Biol. 38, 231-240 (1993).
[CrossRef]

Proc. Natl. Acad. Sci. U.S.A. (2)

N. Ramanujam, M. F. Mitchell, A. Mahadevan, S. Warren, S. Thomsen, E. Silva, and R. Richards-Kortum, “In vivo diagnosis of cervical intraepithelial neoplasia using 337 nm excited laser-induced fluorescence,” Proc. Natl. Acad. Sci. U.S.A. 91, 10193-10197 (1994).

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, 19494-19499 (2007).

Quantum Electron. (1)

E. Borisova, P. Troyanova, P. Pavlova, and L. Avramov, “Diagnostics of pigmented skin tumors based on laser-induced autofluorescence and diffuse reflectance spectroscopy,” Quantum Electron. 38, 597-605 (2008).
[CrossRef]

Rev. Sci. Instrum. (2)

M. Müller, A. Wax, I. Georgakoudi, R. Dasari, and M. Feld, “A reflectance spectrofluorimeter for real-time spectral diagnosis of disease,” Rev. Sci. Instrum. 73, 3933 (2002).
[CrossRef]

W. Cottrell, A. Oseroff, and T. Foster, “Portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease,” Rev. Sci. Instrum. 77, 064302 (2006).
[CrossRef]

Technol. Cancer Res. Treat. (1)

J. W. Tunnell, A. E. Desjardins, L. Galindo, I. Georgakoudi, S. A. McGee, J. Mirkovic, M. G. Mueller, J. Nazemi, F. T. Nguyen, A. Wax, Q. Zhang, R. R. Dasari, and M. S. Feld, “Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia,” Technol. Cancer Res. Treat. 2, 505-514(2003).

Other (2)

American Cancer Society, “Cancer facts and figures 2009,” http://www.cancer.org/docroot/STT/content/STT_1x_Cancer_Facts__Figures_2009.asp?from=fast.

Z136 Committee, American National Standard for Safe Use of Lasers (ANSI Z136.1-2000) (ANSI, Laser Institute of America, 2000).

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (6)

Fig. 1
Fig. 1

Schematic representation of spectral diagnosis system.

Fig. 2
Fig. 2

(a), (b) Clinical instrument. (c) Fiber optic probe used with the clinical instrument.

Fig. 3
Fig. 3

(a) White light spectrum from the xenon flash lamp reflecting off a 20% reflectance standard. (b) Excitation pulses from the nitrogen laser at 337 nm and the dye laser at 445 nm . (c) Diffuse reflectance spectrum of a 1% intralipid solution. (d) Laser-induced fluorescence spectrum of a Rhodamine B solution ( 0.01 g / l ).

Fig. 4
Fig. 4

(a) Diffuse reflectance spectrum (solid curve) and the corresponding LUT fit (circles) from a tissue phantom [ μ s ( λ 0 ) = 2.46 mm 1 and [ Hb ] = 2 mg / ml ]. Scatter plot of the extracted versus expected values of (b)  μ a ( λ ) and (c)  μ s ( λ ) for all tissue phantoms. The solid line indicates perfect agreement.

Fig. 5
Fig. 5

(a) Data recorded from tissue phantoms with Stilbene 3 as fluorophore under test. The tissue phantoms contained a fixed scatterer concentration [ μ s ( λ 0 ) = 1 mm 1 ] and varying concentrations of hemoglobin [ 0 2 mg / ml ]. (b) Corresponding diffuse reflectance spectrum for each phantom. No measurement was possible for the intrinsic fluorescence phantom. (c) Intrinsic fluorescence spectra measured from a phantom (bold solid curve) and extracted by using the IFS model (dotted curve) compared with the laser-induced fluorescence spectrum (lighter solid curve).

Fig. 6
Fig. 6

In vivo measurements from normal skin (bold solid curve), dysplastic nevus (lighter solid curve) and malignant BCC (dashed curve) from three different patients. (a) Diffuse reflectance. The circles indicate the LUT model fit. (b) Intrinsic fluorescence spectra from 337 nm excitation. The circles indicate the fit to the linear combination model. (c) Intrinsic fluorescence spectra from 445 nm excitation.

Tables (1)

Tables Icon

Table 1 Light Source Specifications

Equations (4)

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

R diffuse ( λ ) = I sample ( λ ) I background ( λ ) [ I standard ( λ ) I background ( λ ) ] × 100 / R standard ,
R calibrated ( λ ) = R diffuse ( λ ) × R beads ( LUT ) ( λ ) R beads ( λ ) ,
F calib ( λ ) = [ f ( λ ) I bgd ( λ ) ] × I NIST ( λ ) I NIST SD ( λ ) × f rhod ( master ) ( λ max ) f rhod ( λ max ) .
IF 337 ( λ ) = [ NADH ] × IF NADH ( λ ) + [ collagen ] × IF collagen ( λ ) ,

Metrics