Detection and Diagnosis of Oral Neoplasia with Confocal Microscopy and Optical Coherence

摘要

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. Prognosis for patients with oral cancer remains low with 5-year survival rates hovering in the 50th percentile. High resolution, in vivo optical imaging may offer a clinically useful adjunct to standard histopathologic diagnosis. 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 SSCs 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 that was successful in non-hyperkeratotic layers and showed differentiation between scattering properties of normal and dysplastic epithelium and SCCs.