Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements.

Fluorescence spectroscopy has shown promise for the detection of precancerous changes in vivo. The epithelial and stromal layers of tissue have very different optical properties; the albedo is relatively low in the epithelium and approaches one in the stroma. As precancer develops, the optical properties of the epithelium and stroma are altered in markedly different ways: epithelial scattering and fluorescence increase, and stromal scattering and fluorescence decrease. We present an analytical model of the fluorescence spectrum of a two-layer medium such as epithelial tissue. Our hypothesis is that accounting for the two different tissue layers will provide increased diagnostic information when used to analyze tissue fluorescence spectra measured in vivo. The Beer-Lambert law is used to describe light propagation in the epithelial layer, while light propagation in the highly scattering stromal layer is described with diffusion theory. Predictions of the analytical model are compared to results from Monte Carlo simulations of light propagation under a range of optical properties reported for normal and precancerous epithelial tissue. In all cases, the mean square error between the Monte Carlo simulations and the analytical model are within 15%. Finally, model predictions are compared to fluorescence spectra of normal and precancerous cervical tissue measured in vivo; the lineshape of fluorescence agrees well in both cases, and the decrease in fluorescence intensity from normal to precancerous tissue is correctly predicted to within 5%. Future work will explore the use of this model to extract information about changes in epithelial and stromal optical properties from clinical measurements and the diagnostic value of these parameters.

[1]  M. Schiffman,et al.  Interim guidelines for management of abnormal cervical cytology. The 1992 National Cancer Institute Workshop. , 1994, JAMA.

[2]  E. Trimble,et al.  Interim Guidelines for Management of Abnormal Cervical Cytology , 1994 .

[3]  Rebecca Richards-Kortum,et al.  Realistic three-dimensional epithelial tissue phantoms for biomedical optics. , 2002, Journal of biomedical optics.

[4]  R. Richards-Kortum,et al.  Cost‐Effectiveness Analysis of Diagnosis and Management of Cervical Squamous Intraepithelial Lesions , 1998, Obstetrics and gynecology.

[5]  Angela A. Eick,et al.  Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics. , 1998, Applied optics.

[6]  R H Smallwood,et al.  A study of the morphological parameters of cervical squamous epithelium. , 2003, Physiological measurement.

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

[8]  Michele Follen,et al.  Near real-time confocal microscopy of amelanotic tissue: detection of dysplasia in ex vivo cervical tissue. , 2002, Academic radiology.

[9]  R. Rava,et al.  Analytical model for extracting intrinsic fluorescence in turbid media. , 1993, Applied optics.

[10]  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.

[11]  H. Adami,et al.  International incidence rates of invasive cervical cancer after introduction of cytological screening , 1997, Cancer Causes & Control.

[12]  I. S. Saidi,et al.  Transcutaneous Optical Measurement of Hyperbilirubinemia in Neonates , 1992 .

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

[14]  R. Richards-Kortum,et al.  Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition. , 2003, Journal of biomedical optics.

[15]  Asima Pradhan,et al.  Determination of optical parameters of human breast tissue from spatially resolved fluorescence: a diffusion theory model. , 2002, Applied optics.

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

[17]  Craig Gardner,et al.  Propagation of fluorescent light , 1997, Lasers in surgery and medicine.

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

[19]  R. Lotan,et al.  Autofluorescence Microscopy of Fresh Cervical-Tissue Sections Reveals Alterations in Tissue Biochemistry with Dysplasia¶ , 2001, Photochemistry and photobiology.

[20]  B Palcic,et al.  Optical properties of normal and carcinomatous bronchial tissue. , 1994, Applied optics.

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

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

[23]  Rebecca Richards-Kortum,et al.  Fluorescence Spectroscopy of Turbid Media , 1995 .

[24]  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.

[25]  Akira Ishimaru,et al.  Wave propagation and scattering in random media , 1997 .

[26]  Ashleyj . Welch,et al.  Optical-Thermal Response of Laser-Irradiated Tissue , 1995 .

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

[28]  R. Richards-Kortum,et al.  Screening for squamous intraepithelial lesions with fluorescence spectroscopy. , 1999, Obstetrics and gynecology.

[29]  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.

[30]  M S Patterson,et al.  A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations. , 2001, Physics in medicine and biology.

[31]  Judith R. Mourant,et al.  Light scattering from cells: the contribution of the nucleus and the effects of proliferative status , 2000 .

[32]  B. Wilson,et al.  Monte Carlo modeling of light propagation in highly scattering tissues. I. Model predictions and comparison with diffusion theory , 1989, IEEE Transactions on Biomedical Engineering.

[33]  M. Patterson,et al.  Accuracy of the diffusion approximation in determining the optical properties of a two-layer turbid medium. , 1998, Applied optics.

[34]  Scott B. Cantor,et al.  COLPOSCOPY FOR THE DIAGNOSIS OF SQUAMOUS INTRAEPITHELIAL LESIONS: A META‐ANALYSIS , 1998, Obstetrics and gynecology.

[35]  Leopold G. Koss,et al.  The Papanicolaou test for cervical cancer detection. A triumph and a tragedy , 1989 .

[36]  A. Ishimaru Introduction to wave propagation and scattering in random media , 1985, IEEE Antennas and Propagation Society Newsletter.

[37]  Judith R. Mourant,et al.  Light scattering from cells: the contribution of the nucleus and the effects of proliferative status , 2000, BiOS.

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

[39]  J. Vesecky,et al.  Wave propagation and scattering. , 1989 .

[40]  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.

[41]  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.