State of the art in advanced endoscopic imaging for the detection and evaluation of dysplasia and early cancer of the gastrointestinal tract

Abstract

Ideally, endoscopists should be able to detect, characterize, and confirm the nature of a lesion at the bedside, minimizing uncertainties and targeting biopsies and resections only where necessary. However, under conventional white-light inspection - at present, the sole established technique available to most of humanity - premalignant conditions and early cancers can frequently escape detection. In recent years, a range of innovative techniques have entered the endoscopic arena due to their ability to enhance the contrast of diseased tissue regions beyond what is inherently possible with standard white-light endoscopy equipment. The aim of this review is to provide an overview of the state-of-the-art advanced endoscopic imaging techniques available for clinical use that are impacting the way precancerous and neoplastic lesions of the gastrointestinal tract are currently detected and characterized at endoscopy. The basic instrumentation and the physics behind each method, followed by the most influential clinical experience, are described. High-definition endoscopy, with or without optical magnification, has contributed to higher detection rates compared with white-light endoscopy alone and has now replaced ordinary equipment in daily practice. Contrast-enhancement techniques, whether dye-based or computed, have been combined with white-light endoscopy to further improve its accuracy, but histology is still required to clarify the diagnosis. Optical microscopy techniques such as confocal laser endomicroscopy and endocytoscopy enable in vivo histology during endoscopy; however, although of invaluable assistance for tissue characterization, they have not yet made transition between research and clinical use. It is still unknown which approach or combination of techniques offers the best potential. The optimal method will entail the ability to survey wide areas of tissue in concert with the ability to obtain the degree of detailed information provided by microscopic techniques. In this respect, the challenging combination of autofluorescence imaging and confocal endomicroscopy seems promising, and further research is awaited.

Keywords: autofluorescence imaging; confocal laser endomicroscopy; fluorescence lifetime imaging; image-enhanced endoscopy; narrowband imaging.

Figure 1

Goal-oriented classification of image-enhancement, magnifying, and microscopic techniques currently available and approved for clinical use. Note: i-Scan is manufactured by Pentax. Abbreviations: AFI, autofluorescence imaging; CLE, confocal laser endomicroscopy; EC, endocytoscopy; FICE, Fuji intelligent chromoendoscopy; HDE, high-definition endoscopy; NBI, narrow-band imaging.

Figure 2

(A) Conventional endoscopic view of Barrett’s esophagus with concomitant esophagitis. (B) Positive staining of Barrett’s epithelium after absorption chromoendoscopy with methylene blue dye solution (1%, 10 mL). (C) Villous cerebroid pits with finger-like projections seen with magnification endoscopy (pattern 5 according to Endo’s classification). (D) Histological section of (C) showing intestinal metaplasia with glands of different size and shape and numerous goblet cells. Note: Images provided courtesy of Dr Sergio Coda and Professor Paolo Trentino, University of Rome “La Sapienza,” Italy.

Figure 3

Example images of areas of suspected early cancers of the gastric antrum (A and B) and cardia (C and D), imaged using standard WLE (A and C) and NBI (B and D) to demonstrate the contrast enhancement provided by NBI. Note: Images provided courtesy of Professor Paolo Trentino, University of Rome “La Sapienza,” Italy. Abbreviations: NBI, narrow-band imaging; WLE, white-light endoscopy.

Figure 4

Schematic diagram showing the difference between a standard RGB filter (A) and the NBI filter (B). Notes: Compared with the full range of white-light illumination, the filtered light penetrates the tissue less, highlighting the superficial details of the mucosa. Additionally, the filtered centered wavelengths fall within hemoglobin absorption bands (inset of B), and this leads to a higher contrast for vascular structures. The inset of B is reproduced from Zonios G, Perelman LT, Backman V, Manoharan R, Fitzmaurice M, Van Dam J, Feld MS. Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo. Appl Opt. 1999;38(31):6628–6637. Copyright © 1999 Optical Society of America. Abbreviations: CCD, charge-coupled device; NBI, narrow-band imaging; RGB, red, green, and blue.

Figure 5

Example images of a suspected early cancer of the gastric antrum, imaged using standard WLE (A) and AFI (B), to demonstrate the contrast enhancement provided by AFI (Olympus Corporation, Tokyo, Japan). Notes: Images provided courtesy of Dr Chizu Yokoi, National Center for Global Health and Medicine, Tokyo, Japan. Abbreviations: AFI, autofluorescence imaging; WLE, white-light endoscopy.

Figure 6

Schematic diagram of confocal microscopy principles. Notes: The blue rays (pre- and post-objective and excitation filter) indicate the laser illumination delivered to the tissue sample. The fluorescence emitted from a tissue layer in focus (orange rays) will pass through the pinhole and will be detected. The majority of the fluorescence emitted from tissue layers out of focus (red and green rays) will be rejected. Illumination and collection therefore occur in the same focal plane (ie, they are confocal). Figure adapted with permission from Kumar S. Development of Multidimensional Fluorescence Imaging Technology with a View towards the Imaging of Signalling at the Immunological Synapse [doctoral thesis]. London: Chemical Biology Centre, Department of Chemistry, Imperial College London; 2010. Abbreviation: PMT, photomultiplier tube.