Optical molecular imaging in the gastrointestinal tract

Abstract

Recent developments in optical molecular imaging allow for real-time identification of morphologic and biochemical changes in tissue associated with gastrointestinal neoplasia. This review summarizes widefield and high-resolution imaging modalities in preclinical and clinical evaluation for the detection of colorectal cancer and esophageal cancer. Widefield techniques discussed include high-definition white light endoscopy, narrow band imaging, autofluoresence imaging, and chromoendoscopy; high-resolution techniques discussed include probe-based confocal laser endomicroscopy, high-resolution microendoscopy, and optical coherence tomography. New approaches to enhance image contrast using vital dyes and molecular-specific targeted contrast agents are evaluated.

Figure 1

Top row: widefield images acquired from endoscopically normal esophagus with (A), HD-WLE, (B) AFI, and (C) standard WLE. Middle row: widefield images acquired from an, early carcinoma with (D) HD-WLE and (E) WLE; the carcinoma is located at the 12 o’clock, position. Bottom row: (F) and (G) show an AFI positive lesion (arrow) containing high-grade, intra-epithelial neoplasia that was not seen during HD-WLE. (H) NBI showed irregular mucosal, and vascular patterns and abnormal blood vessels suspicious for dysplasia. (Curvers W, van, Vilsteren FG, Baak LC, et al. Endoscopic trimodal imaging versus standard video endoscopy for, detection of early Barrett’s neoplasia: a multicenter randomized, crossover study in general, practice. Gastrointest Endosc 2011;73:195-203; with permission)

Figure 2

Endoscopic identification of the squamous islands in short-segment Barrett’s, esophagus with three different modalities: white light endoscopy (a), narrow band imaging, endoscopy (b), and iodine chromoendoscopy (c). (Ishimura N, Amano Y, Uno G, et al., Endoscopic characteristics of short-segment Barrett’s esophagus, focusing on squamous islands, and mucosal folds. J Gastroenterol Hepatol 2012;27:82-7; with permission)

Figure 3

pCLE imaging of normal squamous epithelium in the esophagus (A), BE without, dyslplasia (B), high-grade dysplasia (C), and carcinoma (D). (Shahid MW and Wallace MB., Endoscopic Imaging for the Detection of Esophageal Dysplasia and Carcinoma. Gastrointest, Endosc Clin N Am 2010;20:11-24; with permission)

Figure 4

Whole-organ imaging ex vivo.(a) White-light (left), fluorescence at 490–560 nm prior to the application of WGA (middle), fluorescence at 490–560 nm after application of WGA and Alexa Fluor 488 (right). Areas of low WGA binding appear in purple and high binding in green. The dashed white line is to facilitate orientation between images. (b) Grid showing pathological map of the resected specimen. The black dashed line in b represents the longitudinal axis shown in a. (c) The same specimen opened longitudinally with grid overlay from b. (d) Esophagus specimen imaged using an IVIS 200 camera which quantified fluorescence by color coded map. 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). (e) Histology from various grid locations. (Bird-Lieberman EL, Neves AA, Lao-Sirieix P, et al. Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus. Nat Med 2012;18:315-21; with permission)

Figure 5

In vivo confocal fluorescence images of the border between colonic adenoma and, normal mucosa, showing peptide binding to dysplastic epithelial cells. The endoscopic view (A),, border (B), dysplastic crypt (C) and adjacent mucosa (D) are shown with scale bars of 20µm., (Hsiung PL, Hardy J, Friedland S, et al. Detection of colonic dysplasia in vivo using a targeted, heptapeptide and confocal microendoscopy. Nat Med 2008;14:454-8; with permission)

Figure 6

Co-registered OCT/FMI imaging of intestinal polyps incubated with UEA-1 conjugated liposomes ex vivo(A) OCT en face surface image. Tissue surface height is color-coded (ranging from 1 – 2.5 mm). Four polyps are clearly visible as elevated tissue surface height. (B–I) Cross-sectional OCT images corresponding to the horizontal lines 1-4 in A. Polyps (P) are visible as, protruded masses in B, D, and H. Normal mucosa is shown in F. The scale bars in B–H are, physical distance and a refractive index of 1.4 for tissue was used for calculating the physical, distance. Corresponding histology (C, E, G, I) confirm the OCT images. (J) Tissue scattering, coefficient (µ_s) image ranges from 100–200 cm⁻¹. Polyps show higher extinction coefficients. (K), Fluorescence image using the UEA-1 conjugated contrast agents. Fluorescence intensities are, higher around polyp areas than the surrounding mucosa. (L) Fused scattering coefficient and, fluorescence image with a scale bar of 1 mm. (Yuan S, Roney CA, Wierwille J, et al., Combining Optical Coherence Tomography with Fluorescence Molecular Imaging: Towards, Simultaneous Morphology and Molecular Imaging. Phys Med Biol 2010;55:191–206; with, permission.)