Detection and diagnosis of oral neoplasia with confocal microscopy and optical coherence microscopy

Oral cancer remains an important health issue in the world. In the United States, over 27,000 new cases and approximately 7,000 deaths attributable to oral cancer are expected in 2003. In some areas of the world, this malignancy is much more common; oral cancer is the most common cancer among men and the third most common cancer in women, in India [1]. Prognosis for patients with oral cancer remains low with five-year survival rates hovering in the fiftieth percentile [2]. High resolution, in vivo optical imaging may offer a clinically useful adjunct to standard histopathologic techniques. The work in this dissertation centered on optical imaging in the oral cavity to determine whether confocal microscopy and optical coherence microscopy could detect and diagnose oral neoplasia. A survey of features of normal epithelium and SCCs using a reflectance confocal microscope resolved nuclear density and morphology differences between neoplastic and non-neoplastic oral cavity specimens and features of noncancerous and cancerous oral tissue such as inflammation, fibrosis, muscle fibers and salivary glands. A detailed study of the differences between normal, preneoplastic, and neoplastic oral cavity tissue using images from a reflectance confocal microscope found that descriptive statistics characterizing nuclear morphology allowed slight differentiation between normal and dysplastic epithelium. Reviews of confocal images by trained pathologists and untrained engineers emphasized the need for situational awareness of the region of the epithelium occupied by the image plane. An optical coherence microscope with subcellular resolution and an estimated penetration depth (based on SNR) of 690 – 1,227 microns was built to support imaging deeply within oral mucosa. This increased penetration depth supported a study of epithelial scattering coefficients from reflected nuclear intensities which was successful in non-hyperkeratotic layers and showed differentiation between scattering properties of normal and dysplastic epithelium and SCCs. Overall, the research in this dissertation gives a thorough basis for optical imaging in the oral cavity. Images were acquired from five sites in the oral cavity and represented a wide variety of pathological conditions. Two approaches, morphologic statistical analysis and calculation of scattering coefficients, showed diagnostic contrast with the differentiation from the scattering coefficients being superior.