Multispectral scanning during endoscopy guides biopsy of dysplasia in Barrett's esophagus

Abstract

Esophageal cancer is increasing in frequency in the United States faster than any other cancer. Barrett's esophagus, an otherwise benign complication of esophageal reflux, affects approximately three million Americans and precedes almost all cases of esophageal cancer. If detected as high-grade dysplasia (HGD), most esophageal cancers can be prevented. Standard-of-care screening for dysplasia uses visual endoscopy and a prescribed pattern of biopsy. This procedure, in which a tiny fraction of the affected tissue is selected for pathological examination, has a low probability of detection because dysplasia is highly focal and visually indistinguishable. We developed a system called endoscopic polarized scanning spectroscopy (EPSS), which performs rapid optical scanning and multispectral imaging of the entire esophageal surface and provides diagnoses in near real time. By detecting and mapping suspicious sites, guided biopsy of invisible, precancerous dysplasia becomes practicable. Here we report the development of EPSS and its application in several clinical cases, one of which merits special consideration.

Figure 1

Clinical EPSS instrument. The EPSS instrument is shown in the endoscopy suite before the clinical procedure, with the scanning probe inserted into the working channel of an endoscope. The insets show details of the scanning probe tip and the control box.

Figure 2

EPSS scanning esophageal epithelium during screening endoscopy. (a) Illustration depicting the probe tip extended from the endoscope working channel during the scan; arrows indicate linear and rotary motions of the probe tip before and during each scan, respectively. (b) Frame capture, obtained and shown via the EPSS user interface, of an image acquired by the endoscope video channel showing the actual EPSS probe tip during scanning of the esophageal epithelium of a patient with Barrett’s esophagus during a clinical procedure. The scanning illumination spot is seen on the esophagus wall at the upper right of the image. The EPSS probe tip diameter is 2.5 mm.

Figure 3

EPSS spectra acquired during routine screening endoscopy. (a) Parallel (solid red line) and perpendicular (dotted blue line) polarization spectra collected with the EPSS instrument from a single spatial location in a subject with Barrett’s esophagus. (b) Parallel polarization spectra from ten different locations in the same subject. AU, arbritary units.

Figure 4

Pseudo-color maps highlighting areas suspicious for dysplasia in five subjects. Maps produced from EPSS data are overlaid with circles indicating biopsy sites and confirmed pathology. The vertical axis indicates the angle of rotation (°) from the start of each rotary scan; the horizontal axis indicates the distance (cm) from upper incisors. Blue and green map areas and red and pink map areas represent epithelium unlikely for dysplasia and suspicious for dysplasia, respectively, as determined by EPSS. Red, pink and green circles indicate biopsy sites of HGD, LGD and nondysplastic Barrett’s esophagus, respectively, as determined by pathology. (a) EPSS maps, biopsy sites and pathology for subjects A–E. (b) Biopsies taken during the initial and follow-up endoscopy procedures for subject A, overlaid on the EPSS map acquired during the initial procedure. Three follow-up biopsies were guided by the EPSS map, and pathology was confirmed HGD for each (indicated at 360°).

Figure 5

HRE with NBI image of a location with invisible HGD. Video capture was acquired in subject A at one of the locations where invisible dysplasia was missed by visual examination by HRE with NBI, but located by EPSS, and later confirmed by pathology. The site is marked by an arrow. Note that the site is visually indistinguishable from the surrounding nondysplastic Barrett’s esophagus tissue.