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Esophageal cancer is currently the fastest growing cancer in the United States. To help combat the recent rise in morbidity, our laboratory has developed a low-cost tethered capsule endoscope system (TCE) aimed at improving early detection of esophageal cancer. The TCE contains a resonant fiberoptic laser scanner (1.6 mm O.D.) which fits into 6.4-mm easy-to-swallow capsule at the distal tip. The tethered portion contains a single mode optical fiber multiplexed to three laser diodes at the proximal end. This design offers two main advantages over current endoscope technology. First, because of its small size, the TCE can be swallowed with minimal patient discomfort, thereby obviating sedation. Second, by imaging via directed laser light, the TCE is strategically positioned to employ several burgeoning laser-based diagnostic technologies, such as narrow-band, hyperspectral, and fluorescence imaging. It is believed that the combination of such imaging techniques with novel biomarkers of dysplasia will greatly assist in identifying precancerous conditions such as Barrett's esophagus (BE). As the probe is swallowed, the fiber scanner captures high resolution, wide-field color images of the gastroesophageal junction (500 lines at 0.05-mm resolution) currently at 15-Hz frame rate. Video images are recorded as the capsule is slowly retracted by its tether. Accompanying software generates panoramic images from the video output by mosaicing individual frames to aid in pattern recognition. This initial report describes the rationale for the unique TCE system design, results from preliminary testing in vitro and in vivo, and discussion on the merits of this new platform technology as a basis for developing a low-cost screening program for esophageal cancer.