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dc.contributor.advisor Ramanujam, Nirmala
dc.contributor.advisor White, John G.
dc.contributor.advisor Dewhirst, Mark W.
dc.contributor.advisor Vo-Dinh, Tuan
dc.contributor.advisor Fridovich, Irwin
dc.contributor.advisor Wax, Adam P.
dc.contributor.author Skala, Melissa Caroline
dc.date 2007
dc.date.accessioned 2007-05-03T18:53:35Z
dc.date.available 2007-05-03T18:53:35Z
dc.date.issued 2007-05-03T18:53:35Z
dc.identifier.uri http://hdl.handle.net/10161/182
dc.description Dissertation
dc.description.abstract Cancer morbidity and mortality is greatly reduced when the disease is diagnosed and treated early in its development. Tissue biopsies are the gold standard for cancer diagnosis, and an accurate diagnosis requires a biopsy from the malignant portion of an organ. Light, guided through a fiber optic probe, could be used to inspect regions of interest and provide real-time feedback to determine the optimal tissue site for biopsy. This approach could increase the diagnostic accuracy of current biopsy procedures. The studies in this thesis have characterized changes in tissue optical signals with carcinogenesis, increasing our understanding of the sensitivity of optical techniques for cancer detection. All in vivo studies were conducted on the dimethylbenz[alpha]anthracene treated hamster cheek pouch model of epithelial carcinogenesis. Multiphoton microscopy studies in the near infrared wavelength region quantified changes in tissue morphology and fluorescence with carcinogenesis in vivo. Statistically significant morphological changes with precancer included increased epithelial thickness, loss of stratification in the epithelium, and increased nuclear diameter. Fluorescence changes included a statistically significant decrease in the epithelial fluorescence intensity per voxel at 780 nm excitation, a decrease in the fluorescence lifetime of protein-bound nicotinamide adenine dinucleotide (NADH, an electron donor in oxidative phosphorylation), and an increase in the fluorescence lifetime of protein-bound flavin adenine dinucleotide (FAD, an electron acceptor in oxidative phosphorylation) with precancer. The redox ratio (fluorescence intensity of FAD/NADH, a measure of the cellular oxidation-reduction state) did not significantly change with precancer. Cell culture experiments (MCF10A cells) indicated that the decrease in protein-bound NADH with precancer could be due to increased levels of glycolysis. Point measurements of diffuse reflectance and fluorescence spectra in the ultraviolet to visible wavelength range indicated that the most diagnostic optical signals originate from sub-surface tissue layers. Optical properties extracted from these spectroscopy measurements showed a significant decrease in the hemoglobin saturation, absorption coefficient, reduced scattering coefficient and fluorescence intensity (at 400 nm excitation) in neoplastic compared to normal tissues. The results from these studies indicate that multiphoton microscopy and optical spectroscopy can non-invasively provide information on tissue structure and function in vivo that is related to tissue pathology. en
dc.format.extent 11486322 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US en
dc.subject metabolism en
dc.subject animals en
dc.subject carcinoma en
dc.subject oral cancer en
dc.subject stratified squamous epithelium en
dc.subject fluorescence microscopy en
dc.title Multiphoton microscopy, fluorescence lifetime imaging and optical spectroscopy for the diagnosis of neoplasia en
dc.type Dissertation en
dc.department Biomedical Engineering

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