The long range goal of this research was to develop autofluorescence technology and instrumentation for transition towards an in vivo endomicroscopy imaging system. This approach would provide resolution sufficient to image nuclei for real-time categorization of normal and abnormal tissue implicative of disease progression.;Esophageal adenocarcinoma was the chosen model to develop this diagnostic imaging system because the heterogeneous and multifocal nature of this disease makes early diagnosis extremely challenging during the window of time when the prognosis for survival is high. The asymptomatic character of this disease generally presents at a malignant stage when removal of the esophagus has become the standard treatment. The traditional gold standard of histologic diagnosis suffers from a slow turn-around-time from tissue removal to microscopic observation, compounded by error in random biopsy sampling and tissue-processing artifacts, in addition to significant variation in pathologist diagnosis. Optical biopsy has thus been developed to alleviate the problems associated with current standard video endoscopy and histopathology.;Following tremendous research in the realm of optical biopsy, some traction has been gained using confocal endomicroscopy. However, current confocal methods require contrast agents and optical sectioning in order to provide images at a cellular level. We have developed a minimally invasive imaging system using autofluorescence that highlights the short photon penetration depth of ultraviolet excitation. This approach provides cellular level resolution with a clinically relevant field of view without requiring contrast agents or optical sectioning. Optical histopathology has been demonstrated using unprocessed ex vivo human gastrointestinal tissues providing diagnostic assessment in real-time, a function imperative for improved patient care and quality of life. This robust bench-top prototype endomicroscopy system is capable of rapid throughput, high sensitivity and specificity, provides a user friendly interface, and preserves distinct advantages in cost based on instrumentation simplicity. These advantages poise this ultraviolet autofluorescence endomicroscopy system for break-through clinical implementation.
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