Imaging of the gastrointestinal (GI) tract largely relies on the inspection of the wall lining using optical endoscopy procedures or virtual endoscopic methods based on image analysis of radiologic approaches such as computed tomography. Other endoscopic methods of imaging have been also considered, including ultrasonography and optical tissue-sectioning microscopy methods. Whole-body methods are useful in obtaining a volumetric impression of the GI tract and investigate for disease spread, but they cannot match optical endoscopy resolution and sensitivity.1 Current application of virtual computed tomography endoscopy using barium administration remains important in the investigation of the GI tract. Magnetic resonance imaging is also employed, although less frequently, owing to using nonionizing radiation and providing good soft tissue contrast that can be further enhanced by the use of gadolinium. Nuclear imaging methods are useful in cancer staging applications and treatment monitoring, but their role in the primary diagnosis of GI tract disease has not been well defined as of yet. Used more extensively compared with radiology methods, endoscopic optical imaging remains a major diagnostic method in GI tract diseases. Wide-field white-light endoscopy allows the observation of anatomic features and discolorations indicative of disease and is utilized to guide tissue biopsies. Despite its wide clinical acceptance, the method is limited by human vision, namely, the lack of sensitivity to subsurface activity or to particular physiologic or molecular disease features. In response, several methods have been investigated to alleviate those issues.2 Using adapted hite-light endoscopy to detect fluorescence, autofluoescence imaging has been employed to investigate disase related intrinsic tissue fluorochromes modificaion. Similarly, narrow-band imaging uses the spectral roperties of hemoglobin present in the mucosal paterns and vessels to highlight angiogenesis as a bioarker for early neoplastic changes. Autofluorescence maging and narrow-band imaging are applied under esearch protocols but have not yet been diagnostically onfirmed for large-scale clinical adoption. Consequently, attention has turned to the endocopic application of tissue sectioning microscopy ethods. Confocal endomicroscopy can achieve peneration depths of 200 m and 1,000 magnification, attaining submicrometer resolution, whereby 2-photon microscopy endoscopes can penetrate deeper ( 600 m) albeit sacrificing some of the resolution achieved y confocal. Endoscopic tissue-sectioning microscopy is enerally limited by small fields of view ( 500 500 m), but can reveal tissue morphology at the detail evel of histopathology; offering valuable information n vivo. A current limitation is the ability to interrogate nly small parts of the GI wall lining by bringing small ber bundles in contact with tissue. Methods that can visualize deeper in the tract wall ave also been investigated. High-frequency ultrasonic ndoscopic imaging can penetrate for several millimeers to centimeters in tissue; however, the contrast chieved is generally poor and interpretation of data emains difficult. The optical equivalent of ultrasonogaphy, that is, the optical coherence tomography, allows or higher resolution compared with ultrasound and chieves a penetration depth of a few millimeters. By roviding good anatomic contrast, optical coherence omography is also investigated as an alternative to issue sectioning microscopy methods and ultrasonogaphy. A common challenge is the limitation of diagnostic otential when intrinsic tissue contrast or nonspecific ptical agents are visualized. However, similar to progess in other imaging applications, endoscopic imaging an significantly benefit from the administration of
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