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 highgrade 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.Previously we demonstrated that spectroscopic information in light scattered by nuclei could reveal precancer cellular changes 1 . The first application of light-scattering spectroscopy successfully detected dysplasia in Barrett's esophagus 1-5 using a fiber optic probe that illuminated 1 mm 2 of tissue. Searching the entire area of a diseased esophagus with a singlepoint probe is clinically impractical.Correspondence should be addressed to L.T.P. (ltperel@bidmc.harvard.edu). Note: Supplementary information is available on the Nature Medicine website. AUTHOR CONTRIBUTIONSL.Q., E.V., M.D.M., E.B.H., I.I. and L.T.P. developed and evaluated the method; S.I., L.Q. and E.V. contributed codes for instrument control; D.K.P., R.C., J.D.G., J.L., N.O., L.G., L.Q. and A.S. performed clinical procedures; L.Q., D.K.P., R.C., E.B.H., I.I. and L.T.P. contributed to the writing of the manuscript; E.B.H., I.I., D.K.P., R.C. and L.T.P. designed and planned the project. COMPETING FINANCIAL INTERESTSThe authors declare no competing financial interests.Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions/. Since then, several new approaches have been explored using high-resolution endoscopy (HRE) combined with narrow band imaging (NBI) 6 , autofluorescence imaging (AFI) 7 , trimodal imaging 8 , which is a combination of the previous three, and confocal laser endomicroscopy 9 . These techniques showed promise in increased detection of dysplasia in Barrett's esophagus, although none has as yet achieved clinical acceptance. NIH Public AccessA clinically useful technique in the detection of dysplasia in Barrett's esophagus must rapidly survey a comparatively large area while simultaneously detecting changes on a cellular scale. We felt we could achieve both goals by combining an endoscopically compatible scanning instrument with polarized light-scattering spectroscopy (PLSS) 5...

Light scattering spectroscopy identifies the malignant potential of pancreatic cysts during endoscopy

“…Following the same logic, our diagnostic criteria for cystic lesions classified Δ<0.1 as benign, 0.1<Δ<0.2 as low-grade dysplasia (LGD), and Δ>0.2 as high-grade dysplasia (HGD). The cut-offs Δ=0.1 and Δ=0.2 correspond to 25% and 50% enlarged nuclei according to our earlier work 13 . The use of the same diagnostic criteria as in the BE studies is rationalized by the fact that the two most common types of precancerous pancreatic cystic lesions, IPMN and MCN, are characterized by a similar type of lining as in the BE, columnar epithelium.…”

“…The LSS spectra from pancreatic resection samples were measured with the clinical LSS system and polarization gated probe, developed previously for Barrett’s esophagus (BE) studies 13 . The spectra were collected from multiple locations with the measured sites marked with India ink, and photographed to ensure proper co-registration with the subsequent histopathology examination.…”

“…The spectra were collected from multiple locations with the measured sites marked with India ink, and photographed to ensure proper co-registration with the subsequent histopathology examination. To differentiate various cystic neoplasm histopathologies we employed the diagnostic parameter Δ introduced in our BE studies 13 , with the only difference in that the root mean square normalized spectrum, employed in the diagnostic algorithm, was now calculated using all cystic lesion measurements. In our BE studies, if this diagnostic parameter was greater than 0.1 (10% of the mean squared spectrum summed over all spectral points), the site was considered to be dysplastic.…”

“…3d). This component carries diagnostic information and has been previously evaluated from the polarization gated data 13 .…”

The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

“…Another potential use of reflectance spectroscopy in EED could lie in determining some of the morphological changes relevant to the disease, such as the degree of cellular infiltration or the prevalence of breaks in the epithelial monolayer. Light scattering spectroscopy [84][85][86] and low-coherence enhanced backscattering spectroscopy 87 have both been used to assess aspects of cellular and tissue morphology (in vivo in the human oesophagus, colon and duodenum) and, as such, it might be pos sible to extend these techniques to EED. Fibre-optic fluorescence spectroscopy could also be used to monitor the leakage of intravenous fluorescent dye into the gut lumen in a similar manner to that described for fluorescence endomicroscopy.…”