Detection of intestinal dysplasia using angle-resolved low coherence interferometry

Abstract

Angle-resolved low coherence interferometry (a/LCI) is an optical biopsy technique that allows for depth-resolved, label-free measurement of the average size and optical density of cell nuclei in epithelial tissue to assess the tissue health. a/LCI has previously been used clinically to identify the presence of dysplasia in Barrett's Esophagus patients undergoing routine surveillance. We present the results of a pilot, ex vivo study of tissues from 27 patients undergoing partial colonic resection surgery, conducted to evaluate the ability of a/LCI to identify dysplasia. Performance was determined by comparing the nuclear morphology measurements with pathological assessment of co-located physical biopsies. A statistically significant correlation between increased average nuclear size, reduced nuclear density, and the presence of dysplasia was noted at the basal layer of the epithelium, at a depth of 200 to 300 μm beneath the tissue surface. Using a decision line determined from a receiver operating characteristic, a/LCI was able to separate dysplastic from healthy tissues with a sensitivity of 92.9% (13/14), a specificity of 83.6% (56/67), and an overall accuracy of 85.2% (69/81). The study illustrates the extension of the a/LCI technique to the detection of intestinal dysplasia, and demonstrates the need for future in vivo studies.

Figure 1

a/LCI system diagram. (a) System illustration, (b) probe tip assembly illustration showing delivered (dark gray) and scattered (light gray) light, and (c) photograph of the endoscopic probe pictured next to a U.S. dime for scale. Illustration adapted from Zhu et al. (Ref. 22).

Figure 2

Typical a/LCI data. (a) Angle-resolved depth scan of light scattered from tissue. Lighter shades of gray indicate an increased amount of scattered light. (b) A-scan indicating depth increments used for processing. Fifty micrometer segments of the tissue used for processing are indicated. (c) Example angular scan pictured (solid line) with best-fit Mie theory solution (dashed line) and size indicated.

Figure 3

ROC curves corresponding to various discriminators for the third 100-μm segment of the epithelium. AUC (gray area) ratios are indicated. Circles indicate optimal value for each discriminant. (a) Nuclear diameter, AUC = 0.87; (b) nuclear density, AUC = 0.79; (c) nuclear diameter and nuclear density, AUC = 0.91.

Figure 4

Scatter plot showing nuclear size (micrometer) versus nuclear density for the epithelial depth segment 200 to 300 μm beneath the mucosal surface. Each point represents a single optical biopsy, and points are color-coded with respect to their pathological assessment. The dashed black line indicates the ideal decision line for these data for the prediction of dysplasia.