Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.

Optical technologies, such as reflectance and fluorescence spectroscopy, have shown the potential to provide improved point-of-care detection methods for cervical neoplasia that are sensitive, specific, and cost-effective. Our specific goals are to analyze the diagnostic potential of reflectance and fluorescence spectra, alone and in combination, to discriminate normal and precancerous cervical tissue in vivo and to identify which classification features contain significant diagnostic information. Reflectance spectra are measured at four source-detector separations and fluorescence emission spectra are measured at 16 excitation wavelengths, from 324 sites in 161 patients. These 20 spectral features are permuted in all possible combinations of one, two, and three; and classification algorithms are developed to evaluate the diagnostic performance of each combination. Algorithms based on fluorescence spectra alone yield better diagnostic performance than those based on reflectance spectra alone. The combination of fluorescence and reflectance do not significantly improve diagnostic performance compared to fluorescence alone, except in the case of discriminating high-grade precancers from columnar normal tissue. In general, fluorescence emission spectra at 330- to 360-nm and 460- to 470-nm excitation provide the best diagnostic performance for separating all pairs of tissue categories.

[1]  Gregg Staerkel,et al.  Cervical Precancer Detection Using a Multivariate Statistical Algorithm Based on Laser‐Induced Fluorescence Spectra at Multiple Excitation Wavelengths , 1996, Photochemistry and photobiology.

[2]  M. Goldstein,et al.  Multivariate Analysis: Methods and Applications , 1984 .

[3]  Rick E. Sneed,et al.  In vivo cancer diagnosis of the esophagus using differential normalized fluorescence (DNF) indices , 1995, Lasers in surgery and medicine.

[4]  R. Richards-Kortum,et al.  Microanatomical and Biochemical Origins of Normal and Precancerous Cervical Autofluorescence Using Laser-scanning Fluorescence Confocal Microscopy¶ , 2003, Photochemistry and photobiology.

[5]  R. Robert.  LIGHT SHEDS LIGHT ON CANCER - DISTINGUISHING MALIGNANT TUMORS FROM BENIGN TISSUES AND TUMORS , 2007 .

[6]  D. Choy,et al.  Fluorescence spectra from cancerous and normal human breast and lung tissues , 1987, Annual Meeting Optical Society of America.

[7]  L Irwig,et al.  Meta-analysis of Pap test accuracy. , 1995, American journal of epidemiology.

[8]  M. Nichols,et al.  Design and testing of a white-light, steady-state diffuse reflectance spectrometer for determination of optical properties of highly scattering systems. , 1997, Applied optics.

[9]  Rebecca R. Richards-Kortum,et al.  Optimal excitation wavelengths for discrimination of cervical neoplasia , 2002, IEEE Transactions on Biomedical Engineering.

[10]  H. Fox,et al.  "CERVICAL INTRAEPITHELIAL NEOPLASIA" , 1982, The Lancet.

[11]  A H Hielscher,et al.  Influence of the scattering phase function on light transport measurements in turbid media performed with small source-detector separations. , 1996, Optics letters.

[12]  L Burke,et al.  Identification of cervical intraepithelial neoplasia (CIN) using UV‐excited fluorescence and diffuse‐reflectance tissue spectroscopy , 2001, Lasers in surgery and medicine.

[13]  Michele Follen,et al.  Reflectance spectroscopy for in vivo detection of cervical precancer. , 2002, Journal of biomedical optics.

[14]  R. Richards-Kortum,et al.  Microanatomical and Biochemical Origins of Normal and Precancerous Cervical Autofluorescence Using Laser‐scanning Fluorescence Confocal Microscopy ¶ , 2003 .

[15]  S L Jacques,et al.  Measurement of tissue optical properties by the use of oblique-incidence optical fiber reflectometry. , 1997, Applied optics.

[16]  R R Alfano,et al.  Light sheds light on cancer--distinguishing malignant tumors from benign tissues and tumors. , 1991, Bulletin of the New York Academy of Medicine.

[17]  Robert R. Alfano,et al.  Ultraviolet excited fluorescence spectra from non-malignant and malignant tissues of the gynecological tract , 1992 .

[18]  A. Ferenczy.  Cervical Intraepithelial Neoplasia , 1982 .

[19]  Andres F. Zuluaga,et al.  Fluorescence Excitation Emission Matrices of Human Tissue: A System for in vivo Measurement and Method of Data Analysis , 1999 .

[20]  V. Skladnev,et al.  An electronic approach to the detection of pre-cancer and cancer of the uterine cervix: a preliminary evaluation of Polarprobe , 1993, International Journal of Gynecologic Cancer.

[21]  Rebecca Richards-Kortum,et al.  Determination of epithelial tissue scattering coefficient using confocal microscopy , 2003 .

[22]  J. Ferlay,et al.  Estimates of the worldwide mortality from 25 cancers in 1990 , 1999, International journal of cancer.

[23]  E.V. Trujillo,et al.  Performance estimation of diagnostic tests for cervical precancer based on fluorescence spectroscopy: effects of tissue type, sample size, population, and signal-to-noise ratio , 1999, IEEE Transactions on Biomedical Engineering.

[24]  J. Ferlay,et al.  Erratum: Estimates of the worldwide mortality from 25 cancers in 1990. Int. J. Cancer, 83, 18–29 (1999). , 1999, International journal of cancer.

[25]  I J Bigio,et al.  Spectroscopic diagnosis of bladder cancer with elastic light scattering , 1995, Lasers in surgery and medicine.

[26]  R M Cothren,et al.  Detection of dysplasia at colonoscopy using laser-induced fluorescence: a blinded study. , 1996, Gastrointestinal endoscopy.

[27]  H. Moch,et al.  Angiogenesis in cervical neoplasia: microvessel quantitation in precancerous lesions and invasive carcinomas with clinicopathological correlations. , 1997, Gynecologic oncology.

[28]  R. Richards-Kortum,et al.  Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture. , 2003, Journal of biomedical optics.

[29]  G. Zonios,et al.  Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo. , 1999, Applied optics.

[30]  Irene Georgakoudi,et al.  Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo. , 2002, American journal of obstetrics and gynecology.