Research Papers

Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia

[+] Author Affiliations
Sung K. Chang

Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114

Nena Marin

The University of Texas at Austin, Department of Biomedical Engineering, Austin, Texas 78712

Michele Follen

The University of Texas M.D. Anderson Cancer Center, Department of Gynecologic Oncology, Houston, Texas 77030

Rebecca Richards-Kortum

Rice University, Department of Bioengineering, Houston, Texas 77251

J. Biomed. Opt. 11(2), 024008 (March 27, 2006). doi:10.1117/1.2187979
History: Received July 26, 2005; Revised November 11, 2005; Accepted November 14, 2005; Published March 27, 2006
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We present a mathematical model to calculate the relative concentration of light scatterers, light absorbers, and fluorophores in the epithelium and stroma. This mathematical description is iteratively fit to the fluorescence spectra measured in vivo, yielding relative concentrations of each molecule. The mathematical model is applied to a total of 493 fluorescence measurements of normal and dysplastic cervical tissue acquired in vivo from 292 patients. The estimated parameters are compared with histopathologic diagnosis to evaluate their diagnostic potential. The mathematical model is validated using fluorescence spectra simulated with known sets of optical parameters. Subsequent application of the mathematical model to in vivo fluorescence measurements from cervical tissue yields fits that accurately describe measured data. The optical parameters estimated from 493 fluorescence measurements show an increase in epithelial flavin adenine dinucleotide (FAD) fluorescence, a decrease in epithelial keratin fluorescence, an increase in epithelial light scattering, a decrease in stromal collagen fluorescence, and an increase in stromal hemoglobin light absorption in dysplastic tissue compared to normal tissue. These changes likely reflect an increase in the metabolic activity and loss of differentiation of epithelial dysplastic cells, and stromal angiogenesis associated with dysplasia. The model presented here provides a tool to analyze clinical fluorescence spectra yielding quantitative information about molecular changes related to dysplastic transformation.

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© 2006 Society of Photo-Optical Instrumentation Engineers

Citation

Sung K. Chang ; Nena Marin ; Michele Follen and Rebecca Richards-Kortum
"Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia", J. Biomed. Opt. 11(2), 024008 (March 27, 2006). ; http://dx.doi.org/10.1117/1.2187979


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