In situ detection of nuclear atypia in Barrett's esophagus by using angle-resolved low-coherence interferometry

Background: Monitoring of patients with Barrett's esophagus (BE) for dysplasia, currently done by systematic biopsy, can be improved through increasing the proportion of at-risk tissue examined. Objective: Optical biopsy techniques, which do not remove the tissue but interrogate the tissue with light, offer a potential method to improve the monitoring of BE. Frequency-domain angle resolved low-coherence interferornetry (fa/LCI) is an optical spectroscopic technique applied through an endoscopic fiber bundle and measures the depth-resolved nuclear morphology of tissue, a key biomarker for identifying dysplasia. The aim of the study was to assess the diagnostic capability of fa/LCI for differentiating healthy and dysplastic tissue in patients with BE. Methods: Depth-resolved angular scattering data are acquired by using fa/LCI from tissue excised from 3 patients who had esophagogastrectomy. The data are processed to determine the average nuclear size and density as a function of depth beneath the tissue surface. These data are compared with the pathologic classification of the tissue. Main Outcome Measurements: Average of depth-resolved nuclear diameter and nuclear density measurements in tissue samples. Results: Upon comparison to pathologic diagnosis, the fa/LCI data results report the nuclear atypia characteristic of dysplasia in the epithelial tissue. Examination of the average nuclear morphology over the superficial 150 mu m results in complete separation between healthy columnar and BE dysplastic tissues. Limitations: Lack of in vivo data; lack of nondysplastic BE data because of limited sample size. Conclusions: In complicated tissue structures, such as BE, depth-resolved nuclear morphology measurements provided an excellent means to identify dysplasia. The preliminary results demonstrate the great potential for the in vivo application of fa/LCI as a targeting mechanism for physical biopsy in patients with BE.