Gastroenterology
Volume 140, Issue 1 , Pages 42-50, January 2011

Detection of Dysplasia in Barrett's Esophagus With In Vivo Depth-Resolved Nuclear Morphology Measurements

  • Neil G. Terry

      Affiliations

    • Department of Biomedical Engineering, Duke University, Durham, North Carolina
  • ,
  • Yizheng Zhu

      Affiliations

    • Department of Biomedical Engineering, Duke University, Durham, North Carolina
  • ,
  • Matthew T. Rinehart

      Affiliations

    • Department of Biomedical Engineering, Duke University, Durham, North Carolina
  • ,
  • William J. Brown

      Affiliations

    • Department of Biomedical Engineering, Duke University, Durham, North Carolina
    • Oncoscope, Inc, Durham, North Carolina
  • ,
  • Steven C. Gebhart

      Affiliations

    • Department of Biomedical Engineering, Duke University, Durham, North Carolina
    • Oncoscope, Inc, Durham, North Carolina
  • ,
  • Stephanie Bright

      Affiliations

    • Center for Esophageal Diseases and Swallowing, University of North Carolina, Chapel Hill, North Carolina
  • ,
  • Elizabeth Carretta

      Affiliations

    • Center for Esophageal Diseases and Swallowing, University of North Carolina, Chapel Hill, North Carolina
  • ,
  • Courtney G. Ziefle

      Affiliations

    • Center for Esophageal Diseases and Swallowing, University of North Carolina, Chapel Hill, North Carolina
  • ,
  • Masoud Panjehpour

      Affiliations

    • Thompson Cancer Survival Center, Knoxville, Tennessee
  • ,
  • Joseph Galanko

      Affiliations

    • Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
  • ,
  • Ryan D. Madanick

      Affiliations

    • Center for Esophageal Diseases and Swallowing, University of North Carolina, Chapel Hill, North Carolina
  • ,
  • Evan S. Dellon

      Affiliations

    • Center for Esophageal Diseases and Swallowing, University of North Carolina, Chapel Hill, North Carolina
  • ,
  • Dimitri Trembath

      Affiliations

    • Department of Pathology, University of North Carolina, Chapel Hill, North Carolina
  • ,
  • Ana Bennett

      Affiliations

    • Department of Pathology, Cleveland Clinic, Cleveland, Ohio
  • ,
  • John R. Goldblum

      Affiliations

    • Department of Pathology, Cleveland Clinic, Cleveland, Ohio
  • ,
  • Bergein F. Overholt

      Affiliations

    • Thompson Cancer Survival Center, Knoxville, Tennessee
  • ,
  • John T. Woosley

      Affiliations

    • Department of Pathology, University of North Carolina, Chapel Hill, North Carolina
  • ,
  • Nicholas J. Shaheen

      Affiliations

    • Center for Esophageal Diseases and Swallowing, University of North Carolina, Chapel Hill, North Carolina
  • ,
  • Adam Wax

      Affiliations

    • Department of Biomedical Engineering, Duke University, Durham, North Carolina
    • Corresponding Author InformationReprint requests Address requests for reprints to: Adam Wax, PhD, Box 90281, Durham, North Carolina 27708-0281. fax: (919) 684-4488

Received 26 February 2010; accepted 9 September 2010. published online 20 September 2010.

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.

Keywords: Barrett's Esophagus, Optical Techniques, Light Scattering

Abbreviations used in this paper: a/LCI, angle-resolved low coherence interferometry, AUC, area under the curve, BE, Barrett's esophagus, CI, confidence interval, HGD, high-grade dysplasia, LGD, low-grade dysplasia, ROC, receiver operating characteristic

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 Conflicts of interest The authors disclose the following: Dr Wax and Dr Brown have a financial interest in Oncoscope, Inc, the company that holds proprietary rights to the technology described in this study. Dr Gebhart and Mr Terry are consultants for Oncoscope, Inc. Dr Goldblum, Dr Overholt, and Dr Shaheen receive research support from Oncoscope, Inc. Dr Zhu, Mr Rinehart, Ms Bright, Ms Carretta, Ms Ziefle, Dr Panjehpour, Dr Galanko, Dr Madanick, Dr Dellon, Dr Trembath, Dr Bennett, and Dr Woosley disclose no conflicts.

 Funding Supported in part by the National Institutes of Health (National Cancer Institute R33-CA109907; DK 034987 and DK 056350), the National Science Foundation (BES 03-48204), a grant from the Coulter Foundation, and funding by Oncoscope, Inc, through a National Institutes of Health Small Business Innovative Research Phase II Grant.

PII: S0016-5085(10)01324-7

doi:10.1053/j.gastro.2010.09.008

Gastroenterology
Volume 140, Issue 1 , Pages 42-50, January 2011