Clin Endosc.  2013 Nov;46(6):603-610.

Endoscopic Molecular Imaging: Status and Future Perspective

• Muguruma N
• Miyamoto H
• Okahisa T
• Takayama T

Abstract

During the last decade, researchers have made great progress in the development of new image processing technologies for gastrointestinal endoscopy. However, diagnosis using conventional endoscopy with white light optical imaging is essentially limited, and ultimately, we still rely on the histopathological diagnosis from biopsy specimens. Molecular imaging represents the most novel imaging methods in medicine, and the future of endoscopic diagnosis is likely to be impacted by a combination of biomarkers and technology. Endoscopic molecular imaging can be defined as the visualization of molecular characteristics with endoscopy. These innovations will allow us not only to locate a tumor or dysplastic lesion but also to visualize its molecular characteristics and the activity of specific molecules and biological processes that affect tumor behavior and/or its response to therapy. In the near future, these promising technologies will play a central role in endoluminal oncology.

Keyword

Gastrointestinal neoplasms; Technology; Molecular imaging

MeSH Terms

Biological Processes
Biopsy
Diagnosis
Endoscopy
Endoscopy, Gastrointestinal
Gastrointestinal Neoplasms
Methods
Molecular Imaging*
Optical Imaging
Biomarkers

Figure

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  Fig. 1 Endoscopic imaging classification proposed by Tajiri and Niwa (modified by the authors). FICE, flexible spectral imaging color enhancement; NBI, narrow band imaging; AFI, autofluorescence imaging.

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  Fig. 2 Strategy based on the imaging classification in endoluminal oncology. ESD, endoscopic submucosal dissection; EMR, endoscopic mucosal resection; OCT, optical coherence tomography; EUS, endoscopic ultrasound.

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  Fig. 3 Comparison of different molecular probe classes. Adapted from Goetz et al. Gastroenterology 2010;138:828-833, with permission from Elsevier.32 ab, antibody.

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  Fig. 4 In vivo confocal fluorescence images of the border between a colonic adenoma and normal mucosa showing peptide binding to dysplastic colonocytes. (A) Endoscopic view. (B) Border. (C) Dysplastic crypt. (D) Adjacest mucosa. Scale bars, 20 µm.

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  Fig.5 Molecular imaging of an esophagectomy specimen with a 6-cm segment of Barrett esophagus containing macroscopically invisible residual high grade dysplasia (HGD) and focal intramucosal carcinoma. (A) Images taken with an endoscope. White-light image (left), imaging fluorescence at 490 to 560 nm before white germ agglutinin. Application (middle) and imaging fluorescence at 490 to 560 nm after wheat germ agglutinin (WGA) and Alexa Fluor 488 application (right). The areas of low WGA binding appear in purple. (B) The dashed white line is placed longitudinally along the posterior wall of the esophagus to facilitate orientation between the different images, and the numbers 7, 8, and 9 refer to the y coordinates on the reference grid in. White-light imaging of the lower esophagus revealed no macroscopic abnormalities such as ulcers or nodules, and before WGA application, we detected no appreciable differences in mucosal autofluorescence; however, after incubation with WGA, differences in lectin binding were evident. High binding is represented by a green signal and low binding is represented by a purple signal on the pseudocolor image. Grid showing the pathological diagnostic map (color-coded, with darker colors representing a worsening grade of dysplasia) of each block made from the resection specimen. This same grid can be compared with the endoscopic and in vivo imaging system (IVIS) fluorescence images in (A), on the right, and in (D). The dashed line represents the longitudinal axis along the posterior wall of the esophagus. (C) The same specimen after being opened longitudinally along the anterior border of the esophagus is shown with the overlying grid from (B). (D) The WGA fluorescence signal from the esophageal specimen taken with the IVIS 200 camera. The pink arrow marks an area of artifact from the exposed submucosal tissue, and the blue arrow indicates the site of a previous endoscopic mucosal resection (outlined with a dashed gray box). The specimen was cut into 11 transverse sections (rows labeled 1 to 11), and the pathologist divided each of these further into 8 areas (columns labeled A-H) to allow mapping. (E) Examples of the histological appearance (×40) at various coordinates from the grid. From left to right, the images show nondysplastic Barrett esophagus, low grade dysplasia (LGD), and two examples of HGD. The corresponding grid reference is given at the bottom of each image. Adapted from Bird-Lieberman et al. Nat Med 2012;18:315-321, with permission from Nature Publishing Group.40

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  Fig. 6 Imaging applications in the drug discovery and development process. Adapted from Rudin et al. Nat Rev Drug Discov 2003;2:123-131, with permission from Nature Publishing Group.31

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