BACKGROUND:Optical coherence tomography (OCT) is a novel technique for noninvasive cross-sectional imaging with high spatial resolution (10 to 20 microm). OCT is similar to B-mode ultrasound except that it uses infrared light rather than ultrasound. We studied OCT imaging of the gastrointestinal (GI) tract in vitro to analyze the potential of this technique for endoscopic applications. METHODS:Human gastrointestinal tissues harvested from surgical resection and autopsy specimens were used. Specimens were imaged within 5 hours of resection or snap frozen in liquid nitrogen. After imaging, OCT scan locations were carefully marked using dye microinjections, fixed, and prepared for routine histologic processing. OCT images were then compared and correlated with the histologic sections. RESULTS:OCT images demonstrated clear delineation of the mucosa and submucosa in most specimens. Furthermore, microscopic structures such as crypts, blood vessels, or esophageal glands in the submucosa and lymphatic nodules were observed. CONCLUSIONS:The resolution of OCT images of GI wall is sufficient to delineate the microscopic structure of the mucosa and submucosa. Potentially, OCT would allow in vivo imaging at endoscopy of the microstructure of the mucosa and submucosa. This would be particularly useful in the detection and staging of small lesions such as early stage cancers.