| Biological tissues can be characterized by their optical properties which are in turn influenced by the structure and biochemical makeup of the tissue itself. It is well established that diseases such as cancer alter tissue structure and biochemistry and therefore change tissue optical properties. As a result, quantitative measurement of tissue optical properties by light scattering technologies has proven effective in the detection and diagnosis of disease. In particular, methods based on diffuse reflectance spectroscopy aided by well understood diffusion theory have found widespread application.;Tissue is structurally and functionally a multi-layered structure with diseases commencing in precise locations. The majority of cancers, known as carcinomas, first begin in the tissue epithelial layer which is less than a few hundred microns thick. A drawback of diffusion-based optical methods is that light will typically diffuse several millimeters below the tissue surface before being reflected back to the detector and therefore diffuse light cannot selectively interrogate the diagnostic epithelial layer. This problem has led to the development of depth-selective optical methods that more efficiently detect early carcinogenesis. One of these methods is termed polarization-gating. It is based on the principle that multiple scattering depolarizes the incident light. By analyzing light that maintains the incident polarization, multiple scattering from deeper tissue depths is suppressed and sensitivity to superficial depths is heightened.;This thesis is focused on the development of a fiber-optic polarization-gated spectroscopy probe capable of taking measurements in vivo and in real time. Monte Carlo simulations are used to develop models for the polarization-gated light penetration depth and path length which are crucial for understanding the sampling volume of polarization-gating spectroscopy and for extracting optical properties from polarization-gated signals. Simulations were also performed to directly relate the spectroscopic polarization-gated signals to sample optical properties In particular, this thesis demonstrates how polarization information can be utilized to measure the sample depolarization length scale, a parameter that cannot be measured by conventional scalar light scattering techniques. The simulation-based models were validated on tissue-simulating phantoms and applied in vivo to diagnose early dysplastic alterations in the esophagus, pancreas, and colon from animal and human subjects. |
