The national cancer-screening program in South Korea has prioritized gastroenterologists' mission to diagnose and treat early gastrointestinal cancers. Early detection of such cancers is emphasized because those previously treated surgically can currently be cured endoscopically. Some gastroenterologists can make exact diagnoses regardless of the type of endoscopy used, but certain conditions are generally required for an optimal diagnosis. First, clinically important lesions must be readily detectable. Second, the borders and morphology of lesions must be readily characterized. Third, lesions must be exactly diagnosed. Precancers and early cancers are often subtle and can pose a challenge to gastroenterologists attempting to visualize them using standard white light endoscopy. The use of dye solutions aids the diagnosis of early gastrointestinal cancers; however, constant use of dye solutions is cumbersome, and the solution often hinders observation by pooling in lesion depressions or ulcerations. To overcome this weakness, newer endoscopes have been developed that allow for "image-enhanced endoscopy" using optical and/or electronic methods, such as narrow-band imaging (NBI), autofluorescence imaging (AFI), i-scans, flexible spectral imaging color enhancement (FICE), and confocal laser endomicroscopy (CLE). A discussion of image-enhanced endoscopy follows.

AFI is based on the detection of natural tissue fluorescence emitted by endogenous molecules (fluorophores), such as collagen, nicotinamide, adenine dinucleotide, flavin, and porphyrins. After excitation by a short-wavelength light source, these fluorophores emit light of longer wavelengths (fluorescence). These metabolites may be responsible for the observed differences in the autofluorescence spectra of normal and diseased tissues. In AFI images, normal tissue and vessels appear green and bright green, respectively. However, normal fundic mucosa and early gastric cancers appear as well-defined pink lesions. The differential light attenuation of dysplasia/cancer is likely due to: 1) an increased nuclear/cytoplasmic ratio, 2) decreased collagen, and 3) an increased hemoglobin concentration due to an increased mucosal blood supply. AFI may be useful for defining the location and border of gastric lesions because of the autofluorescence of abnormal tissue. Some previous studies have suggested that AFI is useful in predicting the depth of invasion, but others have reported that depressive early gastric cancers may appear green in color (Fig. 8).23-27

Kara et al.28 reported that AFI detected more dysplastic and neoplastic changes in Barrett's esophagus than did conventional endoscopy with four-quadrant biopsies. Ohkawa et al.29 documented that AFI provided a sensitivity of 96.4% and specificity of 49.1% because some benign lesions produced fluorescence similar to that of malignant tumors. Therefore, AFI was recently assessed as part of trimodal imaging with white light endoscopy and ME-NBI. One study in the UK demonstrated that AFI did not show better sensitivity or specificity and exhibited worse accuracy and interobserver agreement than NBI in the diagnosis of colon polyps <10 mm in size.30 In conclusion, AFI might be useful as a complementary modality in the detection of gastric lesions.

I-scan technology is the newly developed image-enhanced endoscopic technology from PENTAX (Tokyo, Japan). It consists of three types of algorithms: surface enhancement (SE), contrast enhancement (CE), and tone enhancement (TE). SE enhances light/dark contrast by obtaining luminance intensity data for each pixel and applying an algorithm that allows for the detailed observation of mucosal surface structure. SE allows for more extensive observation of minute glandular structures, which facilitates the evaluation of changes on the basis of structural differences. The SE component of the i-scan system is comparable with the SE function of Olympus and has a chromoendoscopic effect similar to that of acetic acid solution.

CE digitally adds blue color in relatively dark areas by obtaining luminance intensity data for each pixel and applying an algorithm that allows for detailed observation of subtle irregularities around the surface. With TE, the RGB components of an ordinary endoscopic image are disintegrated into each component, and each component thus isolated is converted independently along the tone curve, followed by a re-synthesis of the three components to yield a reconstructed image. NBI is an optical-filter technology that uses two narrow-band filters to provide tissue illumination in the blue and green light spectra, whereas TE is a digital filter that modifies normal images through software functions.

At present, six types of TE are available: TE-p, TE-v, TE-b, TE-e, TE-g, and TE-c. TE-p, which enhances the dark R component, allows the ready identification of mucosal surface lesions and pit patterns. TE-v, which suppresses the R component in a manner similar to NBI filtration, allows the ready identification of vascular form. TE-b is similar to TE-p in the enhancement of dark-red color, but is designed for the observation of Barrett's esophagus. With TE-e (for esophagus), the J-type tone curve, which suppresses the maximum output, is adopted for the R component to elevate G/B contrast and make structural changes clearer. With TE-g (for stomach), the J-type tone curve, which suppresses the maximum output, is adopted for the R component to elevate G/B contrast, and the S-type tone curve is adopted for the G and B components to elevate color contrast. In this way, TE-g yields images that allow the ready identification of a lesion because it can increase the contrast for even minor differences in color tone (Fig. 9). TE-c, the J-type tone curve, is adopted for the R component, but the output is higher than that with TE-g, which results in a slightly reddish image. The EPK-i system is expected to play a role similar to that of other image-enhanced endoscopic techniques, although few detailed reports have assessed the application of this system to the evaluation of gastrointestinal cancers.31,32 In one study from Germany,33,34 the authors inspected the last 30 cm of the colon in a screening population with high-definition (HD)+ resolution alone, in combination with i-scan, and subsequently with chromoendoscopy. In 69 patients, i-scan augmented the identification of lesions from 176 to 335; chromoendoscopy brought this number to 646. Most (74%) lesions recognized only using i-scan or chromoendoscopy were flat (type IIb). The amount of neoplasia did not differ significantly, but all could be correctly predicted using i-scan or chromoendoscopy. Furthermore, the authors performed screening colonoscopies in 200 patients with HD+ colonoscopy in conjunction with i-scan SE or standard video colonoscopy. HD+ colonoscopy with i-scan functionality detected significantly more patients with colorectal neoplasia (38%) compared with standard-resolution endoscopy (13%).

Significantly more neoplastic (adenomatous and cancerous) lesions and more flat adenomas could be detected using HD endoscopy with SE. Final histology could be predicted with high accuracy within the HD+ group.

We performed HD+ white-light gastroscopy in conjunction with i-scan TE-g and TE-c or chromoendoscopy using 1.5% acetic acid and indigo carmine in 76 patients with early gastric cancer to clearly define the border before endoscopic submucosal dissection. HD+ gastroscopy in conjunction with i-scan TE-c defined the border more clearly compared with TE-g, and did not differ from the definitions achieved with chromoendoscopy using 1.5% acetic acid and indigo carmine. Therefore, we expect that image-enhanced endoscopy alone without classic chromoendoscopy might outline the safe borders of early gastric cancers before endoscopic treatment.35

Optimal band imaging (OBI), the generic term for FICE, enhances the visualization of mucosal structure and microcirculation by the selection of spectral transmittance with a dedicated wavelength. In contrast to NBI, in which the bandwidth of the spectral transmittance is narrowed by optical filters, the OBI system is based on a new computed spectral-estimation technique. In NBI, the observer must change optical filters to observe wavelengths other than the established wavelength; in OBI, however, the observer can select an optimal set of wavelengths by simply switching a key. Thus, an optimal wavelength can be used to evaluate the esophagus, stomach, and colon. In OBI, endoscopists can select 60 spectral images per 5 nm at visible wavelengths between 400 and 695 nm, and set up five gradations of spectral image intensities. Because OBI was created by the selection of three of 300 series of spectral image intensities (60×5 steps), 27 millions of OBI images (300³) were obtained in one type of conventional endoscopic image. In the present study, the demarcation of depressed-type early gastric cancer was identified in 26 of 27 cases (96%), and elevated-type early gastric cancer was identified in all 81 cases without magnification, which allowed for planning of endoscopic submucosal dissection (ESD). In 61 patients undergoing upper endoscopy for a clinical history of malabsorption or serologic suspicion of celiac disease, which is rare in Korea, the sensitivity, specificity, and positive and negative predictive values of OBI-based duodenoscopy were 100% in the evaluation of villous patterns.36,37

CLE is the latest endoscopic imaging technique. CLE images were collected using an argon beam with a scanning depth of 0 (epithelium) to 250 µm (lamina propria) and analyzed using the reflected light. CLE is also called "virtual biopsy" because a 1,000× magnified image is obtained, similar to the microscopic observation of tissues. Contrast medium is necessary to obtain CLE images; fluorescein, which spreads in cell tissues (except the cell nucleus) through capillary vessels, is commonly used and can allow for the observation of tissue structure. Thus, benign and malignant neoplasias can be distinguished by identification of the change in mucosal structure (Figs. 10, 11). Two models currently employ CLE systems. One is a PENTAX system, in which a confocal laser microscope is integrated into the distal tip of a conventional video endoscope. The advantages of this system include the production of high-quality images, better penetration capacity, and the ability to be used as an instrumental channel. However, it has disadvantages, such as a large endoscope diameter and limitation of banding of the distal tip of the scope. The other system is a probe-type CLE (Cellvizio) developed by Mauna Kea Technologies (Paris, France). Unlike the all-in-one CLE, this system can be used in endoscopic retrograde cholangiopancreatography; moreover, it does not require the preparation of additional endoscopic equipment. However, it has a lower resolution and lower penetration ratio compared with those of the PENTAX CLE. Many studies of the differentiation of gastrointestinal cancer and the diagnosis of coexisting malignancies of inflammatory bowel disease using CLE have been published, and the study territory has been extended to the field of pulmonology, which uses bronchoscopy.38-41 In our study group, we compared the results of endoscopic biopsies before ESD and those of biopsies using CLE with the post-ESD histopathological findings of 35 cases (11 adenomas, 24 adenocarcinomas). The overall accuracy of CLE diagnosis of gastric adenomas and adenocarcinomas was significantly higher than that of endoscopic biopsy (94.2% vs. 85.7%). The overall accuracy of CLE diagnosis of differentiated and undifferentiated adenocarcinomas was also higher than that of endoscopic biopsy. In another study involving approximately 1,786 cases of early gastrointestinal cancer, images obtained by CLE showed a high sensitivity (88.1%) and specificity (98.6%). In the differentiation of early cancer and dysplasia, the sensitivity, specificity, and accuracy of real-time CLE diagnosis (88.9%, 99.3%, and 98.8%, respectively) were superior to those of standard videoendoscopy (72.2%, 95.1%, and 94.1%, respectively).42 If the issues regarding diagnostic accordance between observers and health insurance payments are resolved, CLE will be spotlighted in the near future because it will expand the diagnostic territory and shorten treatment courses.

The early detection and treatment of gastrointestinal cancer and premalignant lesions is very important for the efficacy of treatment and the maintenance of a high quality of life; which is why gastrointestinal endoscopists have tremendous responsibilities. Optical imaging technology is advancing due to the development of endoscopic technology; the diagnostic accuracy and image reconstruction capabilities of this technology are similar to those of pathological imaging. If we give attention to various endoscopic features and are well informed of their advantages and disadvantages, optical imaging technology will become helpful for the diagnosis and treatment of gastrointestinal abnormalities.