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Chronic oral epithelial tissue inflammation is considered a potential diagnostic precursor to oral cancer. A key step in the inflammation response of epithelial tissue is the generation of cyclooxygenase (Cox), which has been associated with immunosuppression and carcinogenesis. New chemoprevention drugs that inhibit Cox-2 production and lead to decreases in PGE2 levels are now available, but evaluating the effectiveness of these chemoprevention drugs requires quantitative measures of epithelial inflammation. These are traditionally obtained from the histology of punch biopsies, which cause patient discomfort and morbidity, thereby limiting the options for repeat measurements to monitor patient progress. In principle, by using the visible light spectrum, information on numerous aspects of a tissue milieu and its biochemistry can be ascertained by non-invasive means. However, for such subsurface spectroscopy, special techniques are needed to remove the effects of scattering, which otherwise would confound the spectral analysis of relevant analytes.
We have designed an optical reflectance spectroscopy (ORS) device for measuring the thickness of the epithelial layer, and have developed an assessment technique based on oblique angle reflectance spectroscopy that allows us to assess the scattering and absorption properties of the epithelium and stroma. Our ORS device is being tested in a randomized, double blind, placebo controlled, phase IIB trial of Ketorolac mouth rinse on oropharyngeal leukoplakia, currently being conducted by NCI, NIDCD, and NIDCR. In the trial, the reduction of inflammation in the epithelial layer over a three-month period is measured using invasive punch biopsies and immunohistochemistry, combined with non-invasive OCT, and ORS. We have found encouraging qualitative agreements between histological and optical data collected from both normal and patient subjects. Based on the information obtained thus far, we are designing an optical probe with finer resolution and more channels of acquired data (eight vs. the current four). We plan to collect data from several more patients with this device, and will make repeat measurements on the same patients to allow us to look for indications of the effectiveness of treatment.
Oblique Angle Spectroscopy (Design and Patented by SBSP): Monitoring the Effectiveness of Chemopreventative (Cox 2 inhibitors) Drugs in Leukoplakia Patients
Hattery, D., B. Hattery, V. Chernomordik, P. Smith, M. Loew, J. Mulshine, and A. Gandjbakhche. Differential oblique angle spectroscopy of the oral epithelium. J. Biomed. Opt. 9(5) (2004).
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