Background:Barrett's esophagus develops through dysplasia into adenocarcinoma. Surveillance for dysplasia using conventional white light endoscopy requires histological examination of multiple random biopsies, and has a poor diagnostic yield. Recently, fluorescence endoscopy has become available to detect abnormal areas for targeting biopsy. Elastic scattering spectroscopy (ESS) is another novel technique for minimally invasive optical diagnosis of tissue pathology, which is being developed by our groups. It takes a point measurement, which is sensitive to the size and structure of cellular and sub-cellular components. It is therefore complementary to fluorescence endoscopy and can potentially be used for realtime in vivo `optical biopsy' measurements. We present our preliminary data using this technology to diagnose dysplasia or cancer within Barrett's esophagus. Patients & Methods:Elastic scattering spectra (optical biopsy) and matched esophageal biopsies were taken from 41 sites in 27 patients with Barrett's metaplasia. A pulse of white light from a xenon arc lamp was passed down a probe the size of normal biopsy forceps that contained two parallel and adjacent fibers, one to deliver the light to the tissue and the other to detect scattered light. The probe tip was placed in gentle contact with the tissue surface for the sites being interrogated. Histologically, biopsies were defined as normal, dysplastic or carcinoma. Optical biopsies took less than 1 second to perform. Data were normalized to the region 650-700 nm and analysis of spectra was carried out between 330 and 650 nm using two mathematical pattern-recognition methods: artificial neural networks and hierarchical cluster analysis. Results:Histological findings were correlated with appropriate spectra. For each analysis some of the data sets (spectra and corresponding histology) were used for training the pattern recognition methods and others were reserved for testing. Preliminary analysis of these data gives a sensitivity for detecting an abnormality (cancer or dysplasia) of 90-95% with a specificity of 85-90% and a correct tissue diagnosis (neoplastic or normal) in about 90% of sites. Conclusions:Preliminary results using ESS show that this technique has potential as a real time diagnostic test for in vivo diagnosis of dysplasia or cancer within Barrett's mucosa. The technique is complementary to fluorescence endoscopy and is more robust than fluorescence spectroscopy as it utilizes white light to generate a strong spectroscopic signal rather than a blue light to generate a weak fluorescent one and can be used during routine white light endoscopy.