This project will develop a novel multi-spectral imaging (MSI) system using the synchronous luminescence (SL) concept to rapidly detect cancer in vivo. The proposal will address the problem of real-time in vivo identification and characterization of malignant and pre-malignant tissues in the upper gastrointestinal tract. While presence of Barrett's mucosa is simple to detect endoscopically, at the present time dysplasia and early cancer is found by extensive biopsies. The typical protocol is four quadrant biopsies at 2-cm intervals of the Barrett's mucosa. While this is the standard technique, it only provides 3-5 percent sampling of the mucosal surface where dysplasia and diffuse cancer may be found. The remaining 97-95 percent of the mucosa is not sampled. Laser-induced fluorescence (LIF) spectroscopy has already been used to detect cancer and high grade dysplasia in Barrett's esophagus. However, that system uses a contact technique which samples a 1 mm area of tissue at each measurement. While the contact LIF system is better than the pinch biopsy technique, a new system is needed to allow examination of the entire surface of the mucosa. To address this important need in imaging, a real-time synchronous imaging system will be developed, based on state-of-the-art acousto-optic tunable filter technology coupled to an endoscope. Novel MSI imaging technology will be developed to obtain spatially resolved images of the slight differences in SL properties of malignant versus non-malignant tumors. Synchronous luminescence analysis will greatly simplify the resulting fluorescence from the tissue. This in turn will provide a faster and more accurate in vivo analysis without biopsy. The unique imaging aspect of this MSI system will provide real-time spatial information, allowing for comprehensive diagnosis of large areas of interest. Following development of this technology, initial studies will be performed on two model systems, biopsied tissues as well as laboratory animals at Oak Ridge National Laboratory (ORNL) and the University of Tennessee. Once the system has been optimized, clinical in vivo studies will be performed on human subjects at the Thompson Cancer Survival Center (TCSC) in Knoxville, Tennessee. An interdisciplinary approach will be used to perform the proposed research to provide results in an efficient and cost effective manner. Project personnel include an interdisciplinary group of researchers, uniquely available at ORNL, with experience in a wide range of technical areas: molecular spectroscopy and advanced instrumentation, molecular biology, cellular biology. microelectroptics and molecular genetics and mouse studies. In addition, project personnel include a veterinarian at the University of Tennessee, and medical researchers with expertise in clinical studies at the TCSC.
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