Diagnosis of Dysplasia by Fluorescence Spectroscopy

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DESCRIPTION: (Applicant's Description) The goal of this research proposal is to provide salary support to facilitate the advancement and completion of an NCl-funded clinical research proposal. The Principal Investigator, a clinically active physician scientist, is a collaborator on NCI R01 CA 53717 "Real Time In Vivo Diagnosis of Dysplasia by Fluorescence." The goal of the R01 is, in part, to develop endoscope-compatible, fluorescence spectroscopy systems for the real time detection of precancerous (dysplastic) alterations in the luminal gastrointestinal tract. Both fiber optic-based contact probe techniques for localized detection and fluorescence spectral endoscope systems for wide area imaging of disease will be developed and applied clinically. Multi-wavelength excitation fluorescence and reflectance system will be used to characterize the optical/spectroscopic properties of relevant tissue types. The results of this study will be used to select optimal excitation wavelength(s) and design fiber probes with controllable sampling depth for targeting detection of superficial lesions. By combining this information with tissue optical parameters, models of colon and esophageal fluorescence measured at colonoscopy and gastroscopy respectively, will be developed. Inverse modeling will be developed for extracting histopathological information from the clinical spectra. The existing fluorescence imaging colonoscope will be modified for additional clinical studies, including application in patients with Barrett's esophagus. The techniques developed in this program will be clinically tested for rapid detection of colorectal dysplasia/carcinoma in chronic ulcerative colitis and dysplasia in Barrett's esophagus and as such are "translational" in nature. Based on extremely successful preliminary data, light (white light) scattering spectroscopy (LSS) will be used to determine the size and degree of "crowding" of nuclei of superficial mucosal cells in the columnar-lined (Barrett's) esophagus. LSS will be used to guide the endoscopic detection (and pathological grading) of mucosal dysplasia. The Principal Investigator is devoted to training clinical researchers and will continue the formalized instruction and mentoring of young clinicians so that they may successfully engage in meaningful clinical research. In this way, the Principal Investigator will help mentor the next generation of physician scientists.