Reflectance-based optical diagnosis of epithelial pre-cancer: modeling spectroscopic measurements, fiber-optic probe design considerations, and analysis of tissue micro-optical properties

Optical diagnostic techniques have the potential to improve early detection of pre-cancerous changes in tissues. These techniques can be implemented in real time without the need for biopsy removal, and are expected to have major impact in clinical practice. This dissertation describes a series of modeling studies aimed at establishing an improved understanding of reflectance properties of normal and pre-cancerous epithelial tissues, with the ultimate goal of revealing the potential of reflectance-based optical diagnosis of epithelial pre-cancer. The first part of the dissertation presents Monte Carlo modeling studies to provide a quantitative understanding of contrast observed in reflectance spectra of normal and pre-cancerous epithelial tissues. Simulation results provide important insights into the specific contributions of different epithelial and stromal optical parameters to the overall spectral response. Predictions from simulations agree well with in vivo measurements from cervical tissue, and can successfully describe differences in spatially resolved reflectance spectra of normal and precancerous tissue sites. Monte Carlo modeling is also used to evaluate different fiber-optic probe geometries with respect to sampling depth and to propose a probe design that can resolve spectral information from epithelium and stroma. The proposed design can reveal diagnostic features inherent in optical signatures unique to each of the two tissue layers. The research presented in the rest of the dissertation is targeted towards analyzing the micro-optical properties of epithelial tissues. The Finite-Difference Time-Domain (FDTD) method, a popular computational technique for solution of problems in electromagnetics, is used to model light scattering from epithelial cells and collagen fibers. FDTD simulation results indicate that morphological and structural changes associated with pre-cancer progression lead to significant alterations in light scattering properties of these microscopic tissue constituents. The modeling studies presented in this dissertation provide a framework to meaningfully interpret optical signals obtained from epithelial tissues and to optimize design of optical sensors for in vivo reflectance measurements. The results obtained throughout this research will aid in development and assessment of optical spectroscopic and imaging techniques for early, noninvasive diagnosis of epithelial pre-cancer.