Angle-resolved low-coherence interferometry: an optical biopsy technique for clinical detection of dysplasia in Barrett's esophagus.

Angle-resolved low-coherence interferometry (a/LCI) is an optical biopsy technique that measures scattered light from tissue to determine nuclear size with submicron-level accuracy. The a/LCI probe can be deployed through the accessory channel of a standard endoscope and provides feedback to physicians to guide physical biopsies. The technique has been validated in animal and ex vivo human studies, and has been used to detect dysplasia in Barrett's esophagus patients in vivo. In a recent clinical study of 46 Barrett's esophagus patients, a/LCI was able to detect dysplasia with 100% sensitivity and 84% specificity. This report reviews the technique and discusses its potential clinical utility.

Development of angle-resolved low coherence interferometry for clinical detection of dysplasia.

This review covers the development of angle-resolved low coherence interferometry (a/LCI) from initial development through clinical application. In the first applications, the approach used a time-domain interferometry scheme and was validated using animal models of carcinogenesis to assess the feasibility of detecting dysplasia in situ. Further development of the approach led to Fourier-domain interferometry schemes with higher throughput and endoscope-compatible probes to enable clinical application. These later implementations have been applied to clinical studies of dysplasia in Barrett's esophagus tissues, a metaplastic tissue type that is associated with an increased risk of esophageal adenocarcinoma. As an alternative to systematic biopsy, the a/LCI approach offers high sensitivity and specificity for detecting dysplasia in these tissues while avoiding the need for tissue removal or exogenous contrast agents. Here, the various implementations of a/LCI are discussed and the results of the preliminary animal experiments and ex vivo human tissue studies are reviewed. A review of a recent in vivo clinical study is also presented.

Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology.

We present a novel Fourier-domain angle-resolved low-coherence interferometry (a /LCI) fiber probe designed for in vivo clinical application in gastrointestinal endoscopy. The a/LCI technique measures the depth-resolved angular scattering distribution to determine the size distribution and optical density of cell nuclei for assessing the health of epithelial tissues. Clinical application is enabled by an endoscopic fiber-optic probe that employs a 2.3-m-long coherent fiber bundle and is compatible with the standard 2.8-mm-diam biopsy channel of a gastroscope. The probe allows for real-time data acquisition by collecting the scattering from multiple angles in parallel, enabled by the Fourier domain approach. The performance of the probe is characterized through measurement of critical parameters. The depth-resolved sizing capability of the system is demonstrated using single- and double-layer microsphere phantoms with subwavelength sizing precision and accuracy achieved. Initial results from a clinical feasibility test are also presented to show in vivo application in the human esophagus.

Detection of dysplasia in Barrett's esophagus with in vivo depth-resolved nuclear morphology measurements.

BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) show increased risk of developing esophageal adenocarcinoma and are routinely examined using upper endoscopy with biopsy to detect neoplastic changes. Angle-resolved low coherence interferometry (a/LCI) uses in vivo depth-resolved nuclear morphology measurements to detect dysplasia. We assessed the clinical utility of a/LCI in the endoscopic surveillance of patients with BE. METHODS: Consecutive patients undergoing routine surveillance upper endoscopy for BE were recruited at 2 endoscopy centers. A novel, endoscope-compatible a/LCI system measured the mean diameter and refractive index of cell nuclei in esophageal epithelium at 172 biopsy sites in 46 patients. At each site, an a/LCI measurement was correlated with a concurrent endoscopic biopsy specimen. Each biopsy specimen was assessed histologically and classified as normal, nondysplastic BE, indeterminate for dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). The a/LCI data from multiple depths were analyzed to evaluate its ability to differentiate dysplastic from nondysplastic tissue. RESULTS: Pathology characterized 5 of the scanned sites as HGD, 8 as LGD, 75 as nondysplastic BE, 70 as normal tissue types, and 14 as indeterminate for dysplasia. The a/LCI nuclear size measurements separated dysplastic from nondysplastic tissue at a statistically significant (P < .001) level for the tissue segment 200 to 300 µm beneath the surface with an accuracy of 86% (147/172). A receiver operator characteristic analysis indicated an area under the curve of 0.91, and an optimized decision point gave 100% (13/13) sensitivity and 84% (134/159) specificity. CONCLUSIONS: These preliminary data suggest a/LCI is accurate in detecting dysplasia in vivo in patients with BE.

Scanning fiber angle-resolved low coherence interferometry.

We present a fiber-optic probe for Fourier-domain angle-resolved low coherence interferometry for the determination of depth-resolved scatterer size. The probe employs a scanning single-mode fiber to collect the angular scattering distribution of the sample, which is analyzed using the Mie theory to obtain the average size of the scatterers. Depth sectioning is achieved with low coherence Mach-Zehnder interferometry. In the sample arm of the interferometer, a fixed fiber illuminates the sample through an imaging lens and a collection fiber samples the backscattered angular distribution by scanning across the Fourier plane image of the sample. We characterize the optical performance of the probe and demonstrate the ability to execute depth-resolved sizing with subwavelength accuracy by using a double-layer phantom containing two sizes of polystyrene microspheres.