Early detection of curable precancerous lesions in the oral cavity using polarized reflectance spectroscopy

In 2004, the American Cancer Society estimates that more than 1,500 deaths a day associated with cancer will occur. For all cancers, the five-year survival rate is greater if diagnosis is made at an early stage of cancer development. The focus of this dissertation is on the development of a highly selective and sensitive non-invasive optical device for the early detection of epithelial precancers, which has enormous potential to reduce patient morbidity and mortality. Specifically, this dissertation will concentrate on the assessment of the polarized reflectance spectroscopy (PRS) to detect and diagnose early curable precancerous lesions within the oral cavity. PRS is a variation of elastic scattering spectroscopy which is sensitive to important morphological indicators of early precancer, such as scatterer size and refractive index. In this dissertation I will present a fiber optic probe that combines polarized illumination and detection with an angled distal probe geometry to detect the size dependent scattering within the epithelial layer of tissue, where most cancer originate. This technique allows a simple Mie theory based model to be used to extract the nuclear sizes. Tissue phantoms that mimic the two-layered scattering structure of mucosal tissue were used to test the feasibility of PRS to extract scatter sizes. Results of these studies showed excellent agreement between spectroscopically derived scatter sizes and direct microscopy measurements. In vivo measurements within the oral cavity of normal volunteers also yielded nuclear sizes that corresponded very well to published values. The PRS device was found to be capable of discriminating normal oral mucosa tissue from severe dysplasia in a collaborative pilot clinical trial of 21 patients, at the UT MD Anderson Cancer Center. Nuclear morphology extracted from the polarized spectroscopy measurements compared very well to quantitative histopathology. Overall this dissertation gives a thorough basis for a larger statistically significant clinical trial to be performed to determine the sensitivity and specificity of polarized reflectance spectroscopy as a screening and diagnostic instrument in the oral cavity. The work in this dissertation lays the foundation for future exploration of the optical scattering properties polarized light within tissue for clinical applications.