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