Esophageal-guided biopsy with volumetric laser endomicroscopy and laser cautery marking: a pilot clinical study

Abstract

Background: Biopsy surveillance protocols for the assessment of Barrett's esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites.

Objective: The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo.

Design: A pilot feasibility study.

Setting: Massachusetts General Hospital.

Patients: A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barrett's esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants.

Intervention: Volumetric laser endomicroscopy.

Main outcome measurements: Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks.

Results: There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%-83%), for VLE intent-to-biopsy images 93% (95% CI, 78%-99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations.

Limitations: This is a single-center feasibility study with a limited number of patients.

Conclusion: Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. (

Clinical trial registration number: NCT01439633.).

Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Figures

Figure 1

Schematic of the VLE–guided biopsy system and balloon-centering catheter. The interchangeable balloon catheter is inserted into the esophagus at the gastroesophageal junction and inflated. The balloon catheter is connected to the imaging system via an optical rotary junction. The rotary junction spins a driveshaft that encloses an optical fiber. The optical fiber is terminated by focusing optics at the distal end that spin with the driveshaft. The driveshaft is pulled back while spinning to effectuate a helical OCT scan of the esophagus. A foot pedal is used to initiate laser marking. The entire procedure is monitored by real-time visualization of the displayed, cross-sectional OCT image. VLE, volumetric laser endomicroscopy; OCT, optical coherence tomography.

Figure 2

A, Flow chart of the VLE-guided biopsy procedure. B, Video endoscopy image of the balloon inflated within the esophagus. C, Pre-marking image showing squamous mucosa circumferentially. The center of the intent-to-biopsy site is delineated by a red diamond and arrow. D, Post-marking image in the study aspect ratio demonstrates regions of high optical coherence tomography signal flanking the target region (blue arrows). E, Video endoscopy shows 2 white laser cautery marks (cyan arrows). F, Squamous epithelium is evident in the histology of the biopsy acquired between the marks. VLE, volumetric laser endomicroscopy.

Figure 3

VLE-guided biopsy of squamous mucosa in vivo. A, Pre-marking image in the study aspect ratio demonstrates that the entire esophageal wall circumference has a layered appearance consistent with squamous mucosa. An intent-to-biopsy site is selected (red box and arrow). B, The post-marking image in the study aspect ratio shows areas of high OCT signal in the squamous epithelium, surrounding the target site. C, Video endoscopy shows the laser cautery marks as focal, bright regions (black arrows) on the esophageal luminal surface. D, Histology from a biopsy excised at the marks shows squamous mucosa. Black tick marks in A and B, 350 µm in depth. Magenta scale bars in A and B, 5 mm along the circumference. Scale bar in D, 500 µm. VLE, volumetric laser endomicroscopy; OCT, optical coherence tomography.

Figure 4

VLE–guided biopsy of columnar-lined esophageal mucosa in vivo. A, This pre-marking image displayed in the study aspect ratio has an optical coherence tomography (OCT) appearance that is consistent with columnar mucosa. An intent-to-biopsy site is selected (red box and arrow). B, The post-marking image displayed in the study aspect ratio shows areas of high OCT signal in the mucosa, flanking the intent-to-biopsy site. C, Video endoscopy shows the laser cautery marks as focal, bright regions (black arrows) on the esophageal wall. D, Histology from a biopsy specimen excised at the marks shows columnar mucosa with intestinal metaplasia. Black tick marks in A and B, 350 µm in depth. Magenta scale bars in A and B, 5 mm along the circumference. Scale bar in D, 500 µm. VLE, volumetric laser endomicroscopy; OCT, optical coherence tomography.

Figure 5

VLE–guided biopsy of columnar-lined esophageal and squamous mucosa in vivo. A, An area containing OCT features of columnar-lined esophagus (c) is identified as an intent-to-biopsy region (center of target region delineated by red diamond and arrow). This area is bordered on the left by tissue with OCT features of an island squamous mucosa (s). B, After the marking laser is activated, the superficially cauterized mucosa can be seen as darkened regions in this post-marking VLE image displayed in the study aspect ratio (blue arrows). C, Videoendoscopy performed after the balloon-centering catheter was withdrawn shows the 2 laser cautery marks (black arrows) within slightly reddened mucosa (yellow arrow), adjacent to a squamous island (s). D, Histology from the biopsy obtained at the marks shows columnar-lined esophagus with a small portion of adjacent squamous mucosa. Black tick marks in A and B, 350 µm in depth. Magenta scale bars in A and B, 3 mm along the circumference. Scale bar in D, 500 µm. VLE, volumetric laser endomicroscopy; OCT, optical coherence tomography.

Figure 6

Volumetric laser endomicroscopy (VLE)–guided biopsy of where the pre-marking and post-marking diagnoses in the study aspect ratio did not correspond to the majority histopathologic diagnosis. A, An area containing optical coherence tomography (OCT) features of columnar-lined esophagus (c) is identified as an intent-to-biopsy region (center of target region delineated by red diamond and arrow). B, After the marking laser is activated, the superficially cauterized mucosa can be seen as darkened regions in this post-marking VLE image (blue arrows). The region between the marks also was diagnosed as columnar-lined esophagus by the blinded OCT reviewer when it was assessed in the study aspect ratio as displayed. C, Videoendoscopy performed after the balloon-centering catheter was withdrawn shows the 2 laser cautery marks (black arrows) that are apparently on squamous mucosa. D, Histology from the biopsy specimen obtained at the marks shows a predominance of squamous epithelium with a small portion of columnar epithelium with intestinal metaplasia. E, The post-marking image displayed at the correct full aspect ratio and filtered to remove the radial striping artifact seen in B. This image demonstrates that the area between the marks has a layered appearance that is consistent with squamous mucosa (s). The rightmost mark borders tissue with OCT features of columnar mucosa (C). F, An expanded view of the histology in D shows squamous mucosa with a fragment of columnar-lined esophagus with intestinal metaplasia. Black tick marks in A and B, 350 µm in depth. Magenta scale bars in A and B, 3 mm along the circumference. Scale bar in D, 500 µm. Tick marks in E, 1 mm.