Advanced imaging of the gastrointestinal tract

Posted by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital.

In recent years, there have been significant technical advances that have enabled the endoscopist to detect and resect a large number of lesions accurately with fewer biopsies. These exciting technologies have improved upon standard white light endoscopy (WLE) and include enhancements such as optical magnification and high definition cameras.

Endoscopy is the gold standard for evaluation and management of a multitude of gastrointestinal conditions, from premalignant lesions such as Barrett's esophagus and colon adenomas to inflammatory conditions such as colitis and Crohn's disease. In recent years, there have been significant technical advances that have enabled the endoscopist to detect and resect a large number of lesions accurately with fewer biopsies. These exciting technologies have improved upon standard white light endoscopy (WLE) and include innovations such as optical magnification and high definition (HD) cameras, drug-based staining endoscopy staining, electronic staining endoscopy, confocal laser endoscopy as well as emerging technologies such as endoscopy and molecular labeling. This review will describe the use of advanced endoscopic technologies.

Traditionally, white light endoscopy (WLE) has been used for direct visualization of the gastrointestinal mucosa. While WLE has the benefit of accurate color representation, it may not provide the most detailed images. In fact, the traditional endoscope is based on the standard definition (SD) television screens of years past. They are displayed in a 4:3 aspect ratio with approximately 640 pixels wide x 480 pixels high, creating an image of just under 400,000 pixels.
HD TVs have now become the norm and HD endoscopes are also becoming more common. Similar to the 720p HD television format, these endoscopes can be up to 720 pixels in height, producing an image consisting of nearly 1 million pixels. However, unlike the HD television format, which is displayed in a widescreen 16:9 aspect ratio, HD endoscopes are typically displayed in a 5:4 aspect ratio to better accommodate endoscopes. round. This HD endoscopic image enhances image clarity. A recent meta-analysis showed a benefit in detecting both colonic polyps and adenomas when comparing SD colonoscopy, with a treatment count of 25.
High-resolution endoscopes, typically The imager magnifies the image by about 30 to 35 times, but specialized optical zoom endoscopes can magnify the image up to 150 times. Two types of magnification include optical and digital, with optical magnification using a movable lens at the end of the endoscope, allowing for a closer image while maintaining high resolution. However, digital magnification only moves the image closer to the screen and is limited by fewer pixels in the same display area, thereby reducing image fidelity. Furthermore, digital magnification usually only allows 1.5 to 2x magnification, with a suitable video processor and equipment. So the best combination is an HD endoscope equipped with an optical zoom, known as a high-resolution endoscope (HRE) with magnification.
In a prospective randomized crossover study, HRE with magnification was found to be equally effective when compared with both dye-based endoscopic and indigo-carmine-stained endoscopy or Narrow band imaging (NBI) to detect high-grade dysplasia or Barrett's esophagus. Furthermore, HD colonoscopy was found to detect more adenomas per patient, more right-sided adenomas, and more flat adenomas when compared with SD white light colonoscopy in RCTs from 2011.

Dye-based endoscopy typically uses Lugol's solution (0.5%-3% potassium iodide and iodine in water), 0.5% methylene blue solution, or 0.1-0.4% indigo carmine solution. These dyes can be applied throughout the gastrointestinal mucosa to enhance endoscopic imaging. The resulting images can show mucosal topography and contours in more detail, especially for delicate lesions such as non-polypoid adenomas. Both Lugol solution and methylene blue are classified as absorbent stains, as they are actively absorbed by epithelial cells. For example, application of Lugol's solution will result in normal esophageal mucosa staining dark greenish brown for 5-8 minutes after application, while dysplastic and cancerous areas will not absorb the dye. Studies have shown that Lugol's solution improves visualization of squamous cell carcinoma in patients at increased risk, such as alcoholic patients and those with head and neck cancer.
Methylene blue is actively absorbed by intestinal rather than squamous epithelial cells and is therefore more suitable for enhanced detection of the hyperplastic columnar epithelium present in Barrett's esophagus. Canto et al. have shown that the use of this dye leads to a more targeted approach to Barrett's esophagus lesions and fewer biopsies than random sampling, as well as more samples. Biopsy contains more columnar epithelium. Furthermore, in a randomized controlled trial, Kiesslich et al found that surveillance gastroscopy performed in patients with ulcerative colitis (UC) using methylene blue dye resulted in the detection of significantly more intraepithelial neoplasia (32 versus 10 lesions) in 165 patients, with a sensitivity and specificity of 93% for differentiating between cancerous and noncancerous lesions.
Therefore, the American Gastroenterology Association (AGA) recommends surveillance gastroscopy with image-enhanced endoscopy (such as the use of contrast media) in patients with longstanding UC9. However, there is some concern regarding oxidative DNA damage with methylene blue and possible complications such as acute colitis and, therefore, this dye is not used as often as carmine eczema .
Indigo carmine is a non-absorbent dye mainly used for better demarcation of lesions, most useful for highlighting non-polypoid lesions. In fact, it is routinely used in Japan for better evaluation of gastric cancer after completion of standard white-light endoscopic examination. It is also very suitable for localizing colonic lesions, studies have shown that using indigo after mucosal resection to evaluate residual lesions has reduced local cancer recurrence from 8.7 % down to 0.5% (p < 0.01).

Virtual staining endoscopy can be thought of as a term for a set of newer, more recent technologies that can emphasize different wavelengths of light to improve imaging of abnormal gastrointestinal mucosa. NBI, flexible image color enhancement (FICE) technology, and i-scan will be discussed in this review. NBI technology uses two sets of physical filters placed in front of the endoscope light source at 415nm (corresponding to blue light) and 540nm (corresponding to blue light). The wavelength of blue light corresponds to the primary absorption peak of hemoglobin and the blue light corresponds to the secondary absorption peak of hemoglobin. This has the effect of emphasizing superficial and submucosal capillaries as well as irregular microstructural capillary patterns. This technology can be useful in characterizing neoplastic colon polyps, but is prone to error based on the endoscopist's experience with the technology. In addition, NBI technology can hardly be used regularly due to poor light intensity, especially in the stomach and colon.

FICE technology is software-based and does not require the use of physical filters like NBI. The technology uses spectral emission to build a single wavelength image, which is then randomly assigned to red, blue, or green channels to produce a virtually enhanced color image. The endoscopist can then select preset wavelengths for viewing (from 400 nm to 695 nm) or manually adjust the viewable wavelength in 5 nm increments. At any time, a push of a button can switch the view between standard FICE and WLE images. This technology, like NBI, can be combined with optical magnification to enhance mucosal imaging. Compared with the NBI, there are fewer studies evaluating the role of FICE. Although FICE is fairly accurate in characterizing colorectal polyps, FICE does not improve the detection of colon polyps when compared with standard WLE or chromoendoscopy with indigo carmine.

Finally, i-scan is another digital post-processing method that comes with three image enhancement modes, namely surface enhancement (SE), contrast enhancement (CE) and image enhancement. high tone (TE). Surface enhancement aids in edge recognition, contrast enhancement emphasizes sunken areas of vision, and tone enhancement corrects the red, green, and blue balance for the esophagus and stomach. and colon. SE and CE can be adjusted between low, medium and high, with multiple modes that can be applied with a simple push of a button (i.e. low SE and high CE). Similar to the NBI, the sensitivity and specificity of the i-scan to characterize colorectal polyps is high. However, a randomized trial of gastroscopy did not show any increase in adenoma output with i-scan when compared with HD colonoscopy. When compared with WLE images, i-scan images have no discernible difference in brightness or color, unlike NBI images. Thus, both FICE and i-scan appear to be reasonably accurate for characterizing colorectal lesions, but do not increase adenoma output. More studies are needed before they can be considered for routine clinical use.

Confocal laser endoscopy (CLE) is a promising new technology capable of providing real-time microscopic images during endoscopy. Digestive tissue is illuminated with a low-power laser, then fluorescent light reflected through the pinhole is detected. The term concentricity denotes that the illumination system and the collection system are in the same focal plane. The resulting images are sharp and have extremely high resolution because only light refocused through the pinhole is captured. Intravenous fluorcein (no nuclear staining) is commonly used for contrast, as topical acriflavin (nuclear staining) has been found to be a mutagenic and possibly carcinogenic dye in humans. Two types of CLE exist, probe-based (pCLE) and integrated endoscope (eCLE).
pCLE passes through the accessory channel of most endoscopes, eg gastroscopy,... and can therefore be used with bronchoscopes, cholangioscopes,... In addition, pCLE also has the advantage of being able to view video at 12 frames per second, and can visualize capillary flow. The disadvantages include a slightly lower resolution than eCLE and a slightly smaller field of view. The eCLE system captures images at 1.6 fps at 1024 × 512 pixels or 0.8 fps at 1024 × 1024 pixels, resulting in approximately 1000x magnification. We therefore recommend that CLE be used in a targeted manner for suspicious lesions. Furthermore, CLE can help the endoscopist target the most suspicious area for biopsy by screening multiple areas of metaplasia/dysplasia during the procedure. This technique has been applied in clinical practice in a study in which 42 patients returned to surveillance colonoscopy after previous polypectomy.
In this study, CLE was able to distinguish normal from regenerated and cancerous mucosa with 99.2% accuracy. This can help reduce the number of unnecessary biopsies (the biggest risk factor for major complications of endoscopy) as well as target actual cancerous lesions. In Barrett's esophagus, pCLE is also used to view the mucosa and prevent biopsies from appearing normal in vivo.

Unfortunately, there is a steep learning curve involved in using this technology and it adds a significant amount of time to the process. Its limited field of view also makes it unsuitable as a red flag technique and it should be combined with HD and virtual or dye-based staining endoscopy to identify suspect areas requiring endoscopic evaluation. . Therefore, although this technology appears to be safe and accurate in the hands of experts, additional studies are still needed to determine its full use for routine clinical practice. Another emerging endoscopic technique is nCLE. The principle of needle-based pulsed laser endoscopy (nCLE) is to image organs inside or next to the gastrointestinal tract by means of a small probe that is passed through an endoscopically guided endoscopic needle. . The basic principles of this technology, as well as the working principle of nCLE, are essentially similar to those of pCLE. The AQ-Flex 19 Confocal Miniprobe is compatible with 19G needle thread. It is expected to help differentiate different types of cystic lesions (mucosal and serous).

The cytoscope is capable of providing more magnified images than CLE, up to 1400x. The technology is currently available in probe-based and endoscope-based forms, but is still in the prototype development stage. In essence, it is a high-powered light microscope that projects very high-magnification images that require contact with the tissue surface. This requires pretreatment with a mucolytic agent such as N-acetyl-cysteine ​​as well as pre-staining with a compound such as methylene blue.
Molecular imaging takes biomarkers such as fluorescent dye-labeled monoclonal antibodies against carcinoembryonic antigen (CEA) to help detect cancers and adenomas. The antibody is physically applied through the colonoscope and specific filters capture fluorescence on the appropriate tissue. Many peptides are being tested, including those that target high-grade dysplasia in Barrett's esophagus as well as cathepsin B, which is modulated in colorectal cancer.

There is no doubt that endoscopic methods, such as gastroscopy, colonoscopy, etc. that are available today will continue to grow more sophisticated thanks to ever-advancing technological advances. Key in this evolution is the ability to exploit their increased sensitivity and individual benefits for patient improvement. As these technologies are further studied, some will be more effective than others, and those technologies must be fully developed, mature, and can be combined with other technologies (eg. such as staining endoscopy with CLE) to realize their potential. Throughout this process, costs will continue to fall, hopefully to the point where many of the technologies mentioned above become an available option for the outpatient endoscopist. The next few years could be exciting times in the field of advanced endoscopy.

References
Pushpak Taunk, et al., Advanced Imaging of the Gastrointestinal Lumen, frontiers in endoscopy, series
8, practicalgastro, january 2014 • volume XXXVIII, issue 1 Galloro, G. High technology imaging in digestive endoscopy. World J Gastrointest Endosc 2012; 4(2): 22-27. Subramanian V, Mannath J, Hawleg CJ, et al. High definition colonoscopy vs. standard video endoscopy for the detection of colonic polyps: a meta-analysis. Endoscopy 2011;43:499-505.