Fujifilm endoscopes

Reducing patient discomfort and enhancing imaging precision. Industry-leading Fujifilm innovations include the transnasal endoscope and double-balloon endoscope. More »

Fujinon EVE 590 series

With the pioneering 4400 endoscopy system, Fujinon is already meeting tomorrow’s standards in endoscopy today. More »

Fujifilm endoscopes 600 series

The leading-edge high resolution endoscopes, equipped with over megapixel customised CMOS image sensor, realize advanced observation and diagnosis. More »

Transnasal Endoscopy

In order to counter increasing cost pressure in modern endoscopy, Fujifilm has developed a complete product range for transnasal endoscopy (TNE). More »

 

Endoscopic Robotic Drones for Gut Cancer Detection

Detecting cancer 1 pixel at a time
Gastrointestinal cancers are silent killers: they develop slowly and do not produce symptoms until is too late. Worldwide every year, 2.8 million people are diagnosed with gastrointestinal cancers (including esophagus, stomach, colon and rectum). And every year, these cancers together kill 1.8 million. The earlier we detect these cancers, the better are the chances of survival. Colonoscopy is the best current available tool to early detect and treat these pre-cancer lesions before they become cancer. However, we still missing 22% of the pre-cancer lesions. This means 22% of the patients that went through a colonoscopy are still at risk of developing cancer because we didn’t catch pre-cancer lesions on time. We propose a robotic drone that scans the gut from the inside, pinpointing where the pre-cancer and cancer lesions are, so the endoscopist can treat them in only one procedure. This drone works as an accessory for current conventional endoscopes used worldwide

Huge Problem

We are not catching enough pre-cancer lesions in the gut.

Radical Solution

Endoscopic drones that scan the entire gut and provide a map to the endoscopist, highlighting were the pre-cancer lesions are.

Technology Breakthrough

An endoscopic robotic drone that slides along any conventional endoscope and scans the gut using multiple cheap optical sensors.

Full Endoscopic Spinal Surgery Techniques: Advancements, Indications, and Outcomes

Abstract

Advancements in both surgical instrumentation and full endoscopic spine techniques have resulted in positive clinical outcomes in the treatment of cervical, thoracic, and lumbar spine pathologies. Endoscopic techniques impart minimal approach related disruption of non-pathologic spinal anatomy and function while concurrently maximizing functional visualization and correction of pathological tissues. An advanced understanding of the applicable functional neuroanatomy, in particular the neuroforamen, is essential for successful outcomes. Additionally, an understanding of the varying types of disc prolapse pathology in relation to the neuroforamen will result in more optimal surgical outcomes. Indications for lumbar endoscopic spine surgery include disc herniations, spinal stenosis, infections, medial branch rhizotomy, and interbody fusion. Limitations are based on both non spine and spine related findings. A high riding iliac wing, a more posteriorly located retroperitoneal cavity, an overly distal or proximally migrated herniated disc are all relative contra-indications to lumbar endoscopic spinal surgery techniques.

Modifications in scope size and visual field of view angulation have enabled both anterior and posterior cervical decompression. Endoscopic burrs, electrocautery, and focused laser technology allow for the least invasive spinal surgical techniques in all age groups and across varying body habitus. Complications include among others, dural tears, dysesthsia, nerve injury, and infection.

keywords:
Endoscopic Spine Surgery, History, Lumbar, Techniques
Volume 9 Article 17
doi:
10.14444/2017

Utilization of LEDs in a Communication Protocol for Endoscopic Submarine Capsules

ABSTRACT.

The traditional method of screening for diseases within the gastrointestinal tract using flexible endoscopy is effective but poorly perceived among most patients due to the invasive intubation required. Wireless capsule endoscopy, which utilizes a passive pill-sized camera device, presents a diagnostic alternative to flexible endoscopy, but limited functionality prevents its widespread use. This work evaluates the potential advantages, such as increased efficiency and improved visualization, gained by multiple capsules working together as a swarm in the gastric region during endoscopy of a liquid-distended stomach.  A communication protocol was developed that utilizes 3-channel color sensors and light emitting diodes (LEDs) of different wavelengths within the visible spectrum. The protocol was tested using endoscopic submarine capsules emitting a distinctive wavelength from their respective LEDs. Each capsule responds specifically to the wavelength of another capsule in the swarm through its color sensor. This allows the capsules to autonomously assemble in a follow-the-leader type fashion. Test results show that the color sensors are able to detect the difference between different wavelengths, and that it is possible to program the color sensor to recognize each wavelength at a specified distance. This work represents the first step in enabling collaboration among multiple endoscopic capsules, which can lead to improved efficiency and diagnostic capabilities for wireless capsule endoscopy.

INTRODUCTION.

In 2012, gastric cancer was the fifth most common cancer [1] and the third leading cause of cancer mortality [2]. In the United States, the National Cancer Institute reported a 5-year survival rate of only 28.3% for people diagnosed with the cancer between the years 2004 and 2010 [3], mostly due to late detection.  Gastric cancer is among the many stomach diseases that can be treated if diagnosed early. Therefore, early detection through effective screening protocols can be lifesaving. The traditional screening method of the gastrointestinal (GI) tract is flexible endoscopy.

Flexible endoscopy utilizes a maneuverable insertion tube that is attached at the end to a camera, which is wirelessly connected to an external monitor [4]. While flexible endoscopy is a generally accepted procedure and its diagnostic accuracy is high (82% of Invendoscope (Invendo Medical GmbH, Kissing, Germany) patients are comfortable without sedation [4]), the process is known to be uncomfortably invasive and not patient-friendly [4].  Patient compliance for doctor-recommended endoscopies is low, with only 62.9% of Americans undergoing regular colonoscopy, the most common endoscopic procedure [4]. Recent years have brought the development of wireless capsule endoscopy (WCE), a diagnostic alternative to flexible endoscopy [4]. In WCE, the traditional endoscope is replaced with a wirelessly monitored pill-sized camera that is swallowed by the patient and moves passively and comfortably through the GI tract [4]. WCE eludes the intubation, sedation, and pain that are often associated with flexible endoscopy. The FDA has approved a few of the capsule endoscopes, including the 11 mm x 32 mm PillCam (Given Imaging, Yoqneam, Israel), which is capable of movement through the small bowel, esophagus, and colon [5]. The PillCam procedure takes between twenty-four to seventy-two hours as the capsule naturally travels through the digestive system [5]. However, patients are able to go about their day as normal, only returning to the doctor for data collection afterwards [5]. The widespread use of WCE is restricted by its currently limited functionality. Limitations include procedural costs, which currently surpass flexible endoscopy costs [4], and capsule retention within the gastrointestinal tract [5]. The capsules, including the PillCam, are also limited by their single capability as a passive camera that cannot be controlled by doctors [4-5].

One potential type of WCE, the endoscopic submarine capsule, has the capability to maneuver using controlled motorized propellers [6], a modification from the current passive capsules that move freely without controlled motion. The varied dimensions of the stomach are not suitable for current WCE technology, which rely on being able to independently glide along the tunnel-like forms of organs such as the colon [7]. In addition, the stomach measures at a minimum of 50 mL in volume during the relaxed state, but is able to expand up to 1400 mL [7]. The capsule endoscope is thus limited in efficacy due to the disproportional ratio of sizes. Several studies [6-8] have published material on the design of endoscopic submarine capsules specifically for the stomach. These studies address the functionality of motorized propellers, including concerns over efficient power supply systems and weight distribution. Efficiency is a concern of WCE, and all three related studies offer solutions for maximum propeller efficiency with regards to the other components within the capsules. However, the noted limitations of the work include high material cost and inconvenient capsule sizes. The presented work aims to evaluate the potential advantages gained by multiple capsules working together as a swarm in the gastric region during endoscopy of a liquid-distended stomach. It is hypothesized that a swarm of wireless capsule endoscopes will increase precision and efficiency of endoscopy in the stomach due to enhanced visual coverage of any given gastric volume.

In this work, a protocol that utilizes light emitting diodes (LEDs) and 3-channel color sensors was developed for communication among a swarm.   The LEDs were of different wavelengths within the visible spectrum, representing the colors blue, green, and amber. Each capsule emits one of the three distinctive wavelengths and has a color sensor programmed to detect the emitted wavelength of another capsule. Thus, each capsule shares a unique link to another capsule, which allows the swarm to arrange itself into a follow-the-leader type pattern. The overall product is a chain of communicating submarine capsules. The communication protocol represents the first step in enabling collaboration among multiple endoscopic capsules. This could lead to improved efficiency and diagnostic capabilities for wireless capsule endoscopy. The goal is to turn WCE into an effective, patient-friendly approach to screening for malignant diseases within the gastrointestinal tract.

MATERIALS AND METHODS.

Capsule Configuration

The capsule shell that encloses all of the required components was designed on Creo Parametric 2.0 (PTC, Needham, MA) and printed using VeroWhite material on the Objet Alaris30 3D printer (Stratasys, Eden Prairie, MN). The shell was 42.65 mm long with a diameter of 14.90 mm. The TAOS TCS3200 color sensors and the light emitting diodes (in blue, green, and amber) were components utilized specifically for the communication protocol. Note that each capsule prototype contained only one LED. Other hardware components that were present in the prototype for functionality were microcontrollers, inertial measurement units, Renata lithium coin cell batteries, motor drivers, motors, and 3-blade propellers. Table S1 (located in Supporting Information) lists the dimensions of all the components. The components were arranged so that the color sensor and LED were opposed from each other and faced outwards from the capsule. Each capsule contained four motors and propellers. The research focused exclusively on the relationship between the color sensor and LEDs; motor qualifications were based off previous studies [8]. The three different colors of LED were chosen for their distanced wavelengths.

Sensitivity Trials

The TAOS TCS3200 color sensor (ams, Unterpremstaetten, Austria) contains an 8 x 8 array of photodiodes, equally split among blue, green, red, and clear filters. The sensor calculates light intensity and returns outputs in the form of RGB values. A series of tests were conducted to test the sensitivity and functionality of the color sensor in a water environment at various distances from the LED as a simulation of the endoscopy of a liquid-distended stomach. Light that is submerged underwater produces different properties than light that travels in the air [9]. Due to this, a second set of trials was conducted in an air environment for comparison purposes. To simulate the characteristics of a stomach, all trials were conducted within the darkness of an enclosed box. Each of the three LEDs was tested in both conditions (air and water) at distance intervals of 5, 10, 20, and 30 mm away from a color sensor.

The tests were conducted before the color sensor and LEDs were positioned into their respective capsules. Both components rested at 90° angles in separate props placed in one clear container, as shown in Figure 1. The distances were adjusted based on a ruler attached to the bottom of the container. The container was filled with either air or water for the trial environment. Each trial consisted of three seconds of darkness (serving as the control), ten seconds of light from the LED, and three more seconds of darkness. The RGB value outputs from the color sensor were graphed using Matlab (Mathworks, Natick, MA) and visually analyzed. The graphs displayed a light intensity range of 4 units to 800 units, where 4 units represented the absence of light intensity (darkness) and 800 units represented the highest intensity of light.

hoang_figure01_large

Figure 1 shows the testing apparatus that was used to assess the color sensor.

Locomotion Programming

The capsule’s four motors moved independently of each other and individuals were activated only when required. For example, the capsule turned left when only the two rightmost motors were moving.  This reduced the amount of power the capsule were required to run on. Each wavelength, in both environments, was characterized by a different range of RGB values, as detected by the color sensor. Furthermore, the RGB values were unique among the three distances of each wavelength, as calculated in Matlab. This allowed the each capsule to be programmed to travel around at random until it detected its leading capsule at 20 mm away. This distance was chosen because the RGB values of each LED at this point maintain uniqueness without compromising capsule intervals (being too close or too far away for proposed camera efficiency). Matlab was also used to clear the outliers from the RGB value ranges for improved wavelength detection precision.

RESULTS.

Capsule Configuration

Components of the capsule were chosen based on the smallest size available in the market. They were arranged in the following order within the capsule shell: color sensor, microcontroller, inertial measurement unit (IMU), battery, motor driver, motors, LED, propellers. Figure 2 displays the creation of the capsule prototype.

hoang_figure02_large

Figure 2 shows the configuration of the capsule protocol. (2A) Design of the capsule shell as created on Creo Parametric 2.0. (2B)Structural view of the physical capsule prototype.

The battery contained 3 V. The amount of voltage used by the motorized propellers was dependent on the number of motors running at the moment. The LEDs had a light intensity of 1300 mcd (blue), 900 mcd (green), and 2500 mcd (amber). At the LEDs’ maximum forward voltages, their light intensities passed the maximum detection level for the color sensor; all RGB values reached 800 units. Therefore, each LED was set to maintain a detectable, but still distinctive level of light intensity at specific voltages: 2.6 V (blue), 2.7 V (green) and 1.8 V (amber).

Sensitivity Trials

While trials in air maintained concise ranges of RGB values, trials in water displayed expansive ranges of RGB values, as visually shown in Figure 3. In this figure, each individual graph is displayed as light intensity (in RGB values) over time. The flux, or oscillation, in RGB values of the water trials was expected, due to the tendency of light particles to scatter in water [9]. Despite the differences in value outputs, the color sensor displayed the same pattern in color dominance for each wavelength in both environments. Dominance is defined by the color that emitted the highest light intensity, closest to the maximum value of 800. For example, Figure 3 shows that the color sensor detected the amber LED to be dominant in red light, with blue and then green light following. The green LED emitted green light the strongest, followed by blue and then red light. The blue LED emitted mostly blue light, followed closely by green light, and a low level of red light. Therefore, the data supported the color sensor’s ability to detect the differences between colors in both air and water environments.

Figure 3 also shows that at 5 mm away from the LEDs, the color sensor yielded RGB values close to the maximum light intensity it could detect. When the distance was increased up to 30 mm, the RGB values were defined at lower and more distinct units. As the distance between the color sensor and the LED increased, the light intensity began declining for all RGB values regardless of the LED being emitted. This observation suggested the color sensor’s ability to indirectly distinguish distance. The data supported the programming of the capsule to maneuver itself at a specific distance away from another capsule since the yielded RGB values were dependent on distance.

hoang_figure03_largehoang_figure03_key

Figure 3 displays the color sensor response graphs of the three LEDs for visual comparison between wavelengths, as well as distances and testing environment. Each individual graph is displayed as light intensity over time. The graphs show that the set of RGB values differs for each unique condition of light, which allows capsules to be controlled at specified distances away from each other.

Locomotion Programming

At 20 mm of distance between the color sensor and LED, each diode was characterized by specific RGB values, as shown in Table 1. This table numerically shows the ranges of RGB values for each LED at the set conditions. These values excluded outliers. The values from the water trials were used to program the capsules of a swarm to detect each other.

hoang_table01

Table 1 displays the RGB value parameters set for the color sensors.

 

DISCUSSION.

Gastric cancer is among many gastrointestinal tract diseases that have preventable deaths if diagnosed early. Advancement in endoscopic technology signifies the potential that robots have in the medical field. The collaboration of multiple endoscopic submarine capsules represents the next step in providing both a patient-friendly and an efficient method of screening within the gastrointestinal tract.

The current endoscopic capsules, as approved by the FDA, are limited by their single function as a camera and independent, passive travel through the gastrointestinal tract [4]. An abundance of research currently seeks to identify the most efficient method of technician-controlled movement as well as other capabilities for the endoscope, including drug delivery [11-12]. The presented research aimed to develop an efficient protocol that would allow multiple capsules amongst a swarm to communicate. The capsules were designed as submarine capsules with motorized propellers that could maneuver through a liquid-distended stomach, similar to those in [6-7]. While comparative data describing the protocol’s productivity has not yet been analyzed, test results have supported the swarm’s capability to communicate under water. Each capsule’s color sensor was able to identify different wavelengths based on their RGB values, which were unique based on color and distance. The color sensor returned RGB values as outputs, which were used by the microcontroller to direct the capsule’s movement until the sensor located the LED that the capsule was programmed to follow.

The overall dimensions of the capsule were 42.65 mm by a diameter of 14.90 mm, an inconvenient size for swallowing. The size was limited by market-available components, most of which were not available in smaller proportions. Further research is recommended for the reduction of the capsule size, in respect to neutral buoyancy. An ideal dimension is 32 mm by a diameter of 11 mm, the current size of the PillCam [5]. Another suggestion for future study is the addition of more capsules in the swarm and the study of how order can be maintained until the capsules have assembled into a chain. The color sensor should also be tested under other distance increments for an increased dataset on its capability for underwater communication. In addition, comparative data between a swarm and a single capsule is recommended for analysis on the swarm’s efficiency.

In summary, the work presented a novel idea for a protocol that allows a swarm of three submarine capsules to communicate using LEDs and corresponding color sensors. The color sensors were able to output RGB values at different conditions of light. Furthermore, each condition had a unique set of RGB values associated with it, thus supporting the feasibility of an LED-orientated communication protocol. The preliminary data is limited, but represents a novel idea for swarm efficiency in capsule endoscopy.

ACKNOWLEDGMENTS.

The authors would like to thank Charreau Bell, Ekawahyu Susilo, Robert Caprara, and Dr. Pietro Valdastri of the Vanderbilt STORM Laboratory and Dr. Mary Loveless of the School for Math and Science at Vanderbilt for their mentorship, support, and assistance throughout the project. This material is based upon work supported by the National Science Foundation under grant number CNS-1239355. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

SUPPORTING INFORMATION.

Supplemental Methods

Table S1 lists the components that appear in the capsule prototype. Note that each prototype contained only one LED. (Ø = diameter)

hoang_supplementarytable01

Olympus Revises Duodenoscope Reprocessing Instructions

Olympus released its revised manual for reprocessing the TJF-Q180V duodenoscope, the model recently linked to several patient-to-patient infections of Carbapenem-resistantEnterobacteriaceae (CRE) bacteria associated with ERCP procedures. Information on cleaning, disinfection and sterilization of the TJF-Q180V from the Olympus website states:

“Olympus recommends you pay careful attention to the Supplemental Instructions to the TJF-Q180V Reprocessing Manual, including precleaning and alcohol flushing steps, when using automated endoscope reprocessors (AERs). Please note the setting of the elevator to the intermediate position (half up/half down) when placed in an AER. Olympus has provided major AER manufacturers with these Supplemental Instructions, and asks that you please contact the manufacturer of your AER for instructions and information relating to use of their equipment.”

Olympus has also posted an instructional video on how to reprocess its ultrasound endoscopes, which have also been linked to patient-to-patient infections following endoscopic ultrasound procedures.

Advances in the Endoscopic Assessment of Inflammatory Bowel Diseases: Cooperation between Endoscopic and Pathologic Evaluations

Endoscopic assessment has a crucial role in the management of inflammatory bowel disease (IBD). It is particularly useful for the assessment of IBD disease extension, severity, and neoplasia surveillance. Recent advances in endoscopic imaging techniques have been revolutionized over the past decades, progressing from conventional white light endoscopy to novel endoscopic techniques using molecular probes or electronic filter technologies. These new technologies allow for visualization of the mucosa in detail and monitor for inflammation/dysplasia at the cellular or sub-cellular level. These techniques may enable us to alter the IBD surveillance paradigm from four quadrant random biopsy to targeted biopsy and diagnosis. High definition endoscopy and dye-based chromoendoscopy can improve the detection rate of dysplasia and evaluate inflammatory changes with better visualization. Dye-less chromoendoscopy, including narrow band imaging, iScan, and autofluorescence imaging can also enhance surveillance in comparison to white light endoscopy with optical or electronic filter technologies. Moreover, confocal laser endomicroscopy or endocytoscopy have can achieve real-time histology evaluation in vivo and have greater accuracy in comparison with histology. These new technologies could be combined with standard endoscopy or further histologic confirmation in patients with IBD. This review offers an evidence-based overview of new endoscopic techniques in patients with IBD.

Keywords: Inflammatory bowel diseases, High definition endoscopy, Chromoendoscopy, Narrow band imaging, Microscopy, confocal, iScan, Autofluorescence imaging, Endocytoscopy

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic, relapsing inflammatory disease in the gastrointestinal tract. The cause of IBD is unknown. It has been suggested that genetic, environmental, and immunologic factors are involved in the pathogenesis of IBD, but the precise etiologic mechanisms remain unclear.

Diagnostic and therapeutic approaches for IBD have evolved over the past decades, but precise diagnosis and assessment of disease status is still an important matter of concern for physicians and IBD specialists. Precise diagnosis and assessment of patients with IBD is particularly difficult because medical therapies, surgical approaches, and long-term prognosis differ by IBD subtypes, even if patients have similar signs and symptoms.

The most valuable tool for primary diagnosis of IBD is endoscopic assessment with tissue sampling [1,2]. It can be used to observe inflammatory changes in the intestinal mucosa, evaluate the extent of disease. It also plays a role in assessing treatment efficacy in terms of mucosal healing and the risk of postsurgical recurrence. Importantly, colonoscopy with random biopsy is essential to endoscopic diagnosis, management, and treatment of IBD. The relationship between longstanding IBD and increased colorectal cancer (CRC) risk has been well established [3]. CRC is regarded as the primary cause of death in up to 15% of IBD patients. The overall rate of CRC in UC patients is 3.7% with cumulative probabilities of 18% by 30 years, according to a metaanalysis of 116 studies on the subject [4]. There is also a 2–3 fold increased risk of CRC in CD than in patients without IBD 18.3 years after initial CD diagnosis [5]. Recent studies suggest a decreased risk of CRC in IBD patients as highly developed endoscopic surveillance techniques have been adopted. According to a one time-trend study, the relative risk of CRC decreased from 1.34 in 1979–1988 to 0.57 in 1999–2008 [6]. In this sense, proper cancer surveillance with conventional and novel endoscopic techniques has major clinical implications for patients with IBD [7].

Generally, the standard recommendations for random biopsy in surveillance colonoscopy for IBD patients include four quadrant biopsies taken every 10 cm. These biopsies generally begin 8 to 10 years after diagnosis. Extra biopsies can be obtained from strictured, raised, or color changed areas in the colorectum [8-13]. However, these biopsies can be time consuming and laborious. Recent endoscopic techniques are evolving with the aim of visualizing detailed surface architecture of the mucosa, vascular patterns, and even the cellular and subcellular structures in real time. Precise observation and targeted biopsy are possible with the progress of technologies such as high definition endoscopy, narrow band imaging, chromoendoscopy, confocal endomicroscopy, etc. The present review focuses on novel endoscopic technologies and diagnostic strategies for inflammation and dysplasia in IBD patients.

Go to:

RECENT DEVELOPMENT OF TECHNIQUES FOR ENDOSCOPY IN INFLAMMATORY BOWEL DISEASE

Endoscopic techniques have led to improved observation of mucosal details, which may lead to reduced random biopsies since biopsies will be able to be targeted for histological evaluation. These techniques include image enhancement with modifying conventional endoscopy and improvement in mucosal imaging with magnification or several optical techniques (Table 1).

Table 1.

Table 1.
Categories of endoscopic techniques used in inflammatory bowel disease

Each of these techniques is at a different stage of development and use in clinical medicine. Some of the equipment, such as probe-based or scope-based confocal laser techniques or endocytoscopy, are available only in specialized academic centers, whereas high definition endoscopy has become the standard and is widely used in clinical practice. In addition, specialized training and adequate clinical experience are necessary to adequately perform these novel endoscopies. In the case of image-enhanced endoscopy, it is important to prepare the patient with bowel cleansing in order to ensure the efficacy and safety of the procedure prior to use. This technique should be used to visualize a specific area in detail rather than for observation of the entire colon. Each of the advanced endoscopies has their own advantages and limitations. These techniques are far from being used as the gold standard in IBD, and some studies have been controversial. Thus, it requires more experience before implementing them in clinical practice and cautious use for patients on clinical use.

High definition endoscopy

High definition or high resolution endoscopy presents signal images with 850,000 to 1 million pixels, while standard definition signals offer 100,000 to 400,000 pixels on an SD format [14,15]. High resolution endoscopy results in visualization of subtle mucosal details and improves the sensitivity and specificity of dysplastic lesion detection. Furthermore, it facilitates endoscopic resection by delineating borders of neoplastic lesions in IBD patients.

The majority of published data comes from non-IBD patients and found high definition endoscopy to be superior compared with conventional endoscopy. A retrospective study with 160 colonoscopies including long-standing (>7 years) colonic IBD patients demonstrated 2.21 greater likelihood (95% confidence interval [CI], 1.09 to 4.45) adjusted prevalence ratio of detecting any dysplastic lesions and 2.99 (95% CI, 1.16 to 7.79) of detecting dysplastic lesions on targeted biopsy with high definition colonoscopy compared to conventional endoscopy [16]. There was also a 3-fold higher neoplasia detection rate with high definition endoscopy when compared with standard definition endoscopy in IBD patients.

Chromoendoscopy

Chromoendoscopy is considered a cost-effective technique intended to enhance visualization of mucosal detail, submucosal vascular patterns, and lesion characterization. In particular, chromoendoscopy can facilitate the identification of flat lesions harboring intraepithelial neoplasia. With this, it can guide biopsies and reduces the number of biopsies. It is divided into dye-based and dye-less imaging techniques.

Dye-based chromoendoscopy has been used for over a decade and increases the rate of dysplastic lesion detection, especially in patients with long-standing IBD (Fig. 1A). In addition, Dye-based chromoendoscopy allows for improved assessment of disease severity and extent. Absorptive agents (e.g., Lugol solution, methylene blue, toludine blue, and cresyl violet), contrast agents (e.g., indigo carmine and acetic acid), agents for tattooing (e.g., India ink, Indocyanine green, and methylene blue), and reactive staining agents (e.g., congo red and phenol red) can be used in dye-based chromoendoscopy [17,18]. Several studies have shown the superiority of chromoendoscopy compared to conventional white light endoscopy. Dye-based chromoendoscopy has a moderate to high sensitivity for diagnosis, improved dysplasia detection, and prediction of mucosal change using magnification techniques (Fig. 1B). Two meta-analyses also demonstrated the superiority of targeted biopsy with dye-based chromoendoscopy in diagnosing and assessing mucosal ulcerations and dysplasia [19,20] while reducing the number of biopsies. Most recently, Soetikno et al. [20] included 665 patients from 6 studies and confirmed that the rate of detection of any dysplasia was approximately 9 times higher with dye-based chromoendoscopy with targeted biopsy than using white light endoscopy, with an 8.9 pooled odds ratio (95% CI, 3.4 to 23.0). When comparing the difference in the mean procedure time, dye-based chromoendoscopy is 10.9 minutes shorter than white light endoscopy, including the time spent on random biopsies.

Fig. 1.

Fig. 1.
Chromoendoscopy using indigocarmine (A) and combined with magnification technique (B) for colonic dysplasia in ulcerative colitis (Courtesy of Dr. Jeong-Sik Byeon at Asan Medical Center).

Dye-less chromoendoscopy is a novel imaging technology that allows for a detailed examination of both the mucosal surface and the mucosal vascular pattern by pushing a button on the handle of the endoscope, thereby enabling high-contrast imaging of the mucosal surface in real time without the use of special equipment. These dye-less chromoendoscopy techniques are divided into two types. One is an optical filter system including narrow band imaging (NBI) from Olympus, Tokyo, Japan and Compound Band Imaging from Aohua, Shanghai, China, and the other is digital chromoendoscopy with a post-processing system including i-Scan from Pentax, Tokyo, Japan and FICE (Fuji intelligent color enhancement from Fujinon, Tokyo, Japan) [21,22].

Optical chromoendoscopy techniques are based on optical lenses integrated within the light source of the endoscope, usually in front of the excitation white light source, to narrow the bandwidth in the blue and green regions of the spectrum [23,24]. In contrast, digital chromoendoscopy uses digital postprocessing of endoscopic images made in real-time by the video processor [25]. Recent studies indicate that dye-less chromoendoscopy, including optical and digital ones, are useful and practical for the differentiation of adenoma versus hyperplastic colon polyps and have good histological correlations [26-28].

Narrow band imaging

NBI is the most recognized among the virtual chromoendoscopy. This in vivo method uses optical filters in front of the light source to narrow the wavelength of the projected light to a 30 nm wide blue (415 nm) and green (540 nm) spectra, which enables visualization of micro-vessel morphological changes in superficial neoplastic lesions. NBI enhances the visibility of the small irregularities that accompany non-neoplastic inflammatory changes using the same logic as dye-based chromoendoscopy (Fig. 2).

Fig. 2.

Fig. 2.
Observation findings of colonic dysplasia using white light endoscopy (A), narrow band imaging technique (B), and autofluorescence imaging technique (C) in ulcerative colitis (Courtesy of Dr. Jeong-Sik Byeon at Asan Medical Center).

However, the role of NBI in detecting dysplasia in IBD remains somewhat uncertain due to conflicting results in the literature. A paper by East et al. [29] was the first to describe the use of NBI to distinguish dysplastic from nondysplastic mucosa in patients with longstanding. Subsequent to this case report, several randomized controlled studies have been published. Dekker et al. [30] demonstrated that NBI does not improve the detection rate of neoplasia in UC compared with high-definition white light endoscopy with a randomized crossover study of 42 patients. Of 11 patients with neoplastic lesions, four were detected with both modalities, four with NBI alone, and three with standard white light colonoscopy alone.

Two additional randomized trials comparing NBI to white light endoscopy also found no significant difference in the detection of neoplastic lesions. Random background biopsies were also ineffective in detecting dysplasia. According to Ignjatovic et al. [31], dysplasia detection was 9% in each arm and the yield of dysplasia detection from random nontargeted biopsies was 0.04%. Van den Broek et al. [32] found 13 of 16 neoplastic lesions (81%) using high definition-NBI compared with 11 of 16 neoplastic lesions (69%) using high definition -white light endoscopy. A study using a new-generation NBI system compared with dye based chromoendoscopy for the early detection of colitis-associated dysplasia and cancer in patients with longstanding colonic IBD demonstrated that NBI is less time-consuming (26.87±9.89 minutes vs 15.74±5.62 minutes, p<.01), but has no advantages over conventional endoscopy for the detection of intraepithelial neoplasia [33]. However, NBI has some advantages over dye-based chromoendoscopy, as it does not require additional dye agents and is easier to use in practice. These findings have led to controversy regarding the real role of NBI in dysplasia detection in IBD patients.

i-Scan

Currently, two virtual chromoendoscopy techniques are available, including FICE and i-Scan is a new endoscopic system using post processing light filter technology based on software algorithms with real time image mapping. It enhances different elements of the mucosa by three different image processes such as surface enhancement, tone enhancement, and contrast enhancement. Activation between different modes is done by pushing a button on the handle of the endoscope [34,35]. To date, most randomized trials have not shown that NBI or FICE can improve the detection of colorectal neoplasia when comparing colonoscopy with and without filter enhancement.

A randomized controlled study was conducted on 78 IBD patients in Germany to identify whether i-Scan has the potential to enhance assessment of disease severity and extent in mild or inactive IBD patients. The average duration of the examination for high definition—white light endoscopy and i-Scan groups was 18 and 20.5 minutes, respectively, but these differences were not statistically significant. When comparing the endoscopic prediction of inflammatory extent and activity with the histological results, there was overall agreement of 48.71% and 53.85% in the high definition—white light endoscopy group and 92.31% and 89.74% in the i-Scan group (p<.001 and p=.066) [36].

Patients with intestinal food allergy present with lymphoid hyperplasia, slight mucosal edema, and blurred mucosal vascular pattern in the colon. Based on this, an observational study reported on the potential of i-Scan for prediction of mucosal changes with suspected food allergy. Positive and negative predictive values for i-Scan to predict food allergy were 92% and 80%, respectively. Moreover, i-Scan predicted food allergy with a sensitivity, specificity, and accuracy of 85%, 89%, and 86%, respectively [37].

Confocal laser endomicroscopy

Observation and characterization of the colonic mucosal surface and abnormalities of blood vessel architecture are crucial in predicting histology, and this can be performed more efficiently with chromoendoscopy. However, histologic confirmation is needed to determine whether the presence of mucosal abnormalities is a result of IBD or not. This can be accomplished by confocal endomicroscopy in vivo, which may provide images similar to histologic findings in real time (Fig. 3). Endomicroscopy is regarded as optical biopsy that can achieve an image of the cellular structure of the mucosa with 1,500 fold magnification [38]. Currently, two endomicroscopy systems are available including an integrated endoscopy system (iCLE, Pentax) and a probe-based system (pCLE, Cellvizio, Mauna Kea Technologies, Paris, France). In vivo CLE uses an excitation wavelength of 488 nm with a single line laser; the laser power output is up to 1 mW at the tissue surface. Images are collected at a scan rate of 0.8 frames per second at a resolution of 1,024×1,024 pixels or 1.6 frames per second with 1,024×512 pixels [39]. It can capture the z axis which enables interrogation of the epithelium and lamina propria 0–250 mm below the surface layer [40]. The pCLEsystem uses a fixed laser power and a fixed image plane depth. The purpose of the system is to observe mucosal microarchitecture with an increased field of view (4×2 mm) through postpocessing with Cellvio Viewer (Fig. 4A). It enables virtual staining of mucosal structures to further enhance tissue contrast. The probe requires an accessory channel of 2.8 mm and has a resolution of 1 μm with a field of view of 240 μm and a fixed image plane depth varying between 55–65 μm (Fig. 4B).

Fig. 3.

Fig. 3.
Confocal laser endomicroscopic findings for normal mucosa (A) and mucosa in active ulcerative colitis (B). In ulcerative colitis, lamina propria widening, inflammatory infiltrates, goblet cell depletion, and crypt distortion are observed.
Fig. 4.

Fig. 4.
Cellvizio system for probe based confocal laser endomicroscopy (A) and a probe (B).

Crypt architecture, microvascular alterations, fluorescein leakage, and cellular infiltrates within the lamina propria are important observational markers in CLE evaluation [12,41-44]. CLE can aid in demonstrating mucosal healing in terms of deep remission beyond the absence of mucosal ulceration.

Watanabe et al. [45] investigated the features of CLE in the inflamed and noninflamed rectal mucosa of 17 UC patients and compared these results to standard histology. In this study, the crypts of colonic mucosa in active UC were large, variously shaped and irregular in arrangement. Numerous inflammatory cells and capillaries were visible in the lamina propria with CLE. Li et al. [42] also assessed crypt architecture, fluorescein leakage, and microvascular alterations in 73 consecutive UC patients and showed a correlation with histological results (p<.001). On post-CLE objective assessment, subjective architectural classifications were supported by the number of crypts per image (p<.001), but not fluorescein leakage results by gray scale (p=.194). Most recently, CLE also proved a sensitive tool in predicting UC relapse. In this study, 17 of 20 patients (85%) with histologically confirmed normal or chronic inflammation were diagnosed as having nonactive inflammation by real-time CLE. Twenty two of 23 patients (96%) with histologically confirmed acute inflammation were diagnosed as having active inflammation by CLE. The results of CLE were highly consistent with those of conventional histology (kappa value=0.812). Eleven percent of patients in the nonactive inflammation group relapsed, while 64% of patients in the active inflammation group relapsed. The relapse rate of patients with active inflammation was significantly higher than of those with nonactive inflammation (p<.001).

Neumann et al. [46] proposed the Crohn’s Disease Endomicroscopic Activity Score for assessing CD activity in vivo from comparison data between CD patients and a normal control group with standard white-light endoscopy followed by CLE. Active CD patients showed a higher proportion of increased colonic crypt tortuosity, enlarged crypt lumens, microerosions, augmented vascularization, and increased cellular infiltrates within the lamina propria. In the case of quiescent CD patients, there was a significant increase in crypt and goblet cell number compared with controls.

Autofluorescence imaging

Autofluorescence imaging (AFI) is a technique using the natural principle that cells contain molecules that become fluorescent when excited by UV/Vis radiation of a certain wavelength. Among the endogenous fluorophores, collagen and elastin have a relatively high quantum yield, so the extracellular matrix usually contributes to the autofluorescence emission more than cellular components. Autofluorescence imaging videoendoscopy produces real-time pseudo-color images based on tissue autofluorescence emitted by excitation of endogenous tissue fluorophores.

It is well known that cell and tissue state change resulting from modifications of the amount and distribution of endogenous fluorophores and the chemical-physical properties of their microenvironment during physiological and/or pathological processes. Therefore, AFI can be utilized in order to obtain information about the morphological and physiological state of cells and tissues (Fig. 2).

AFI has been used to highlight various lesions, such as neoplastic tissue, minimal changes in reflux esophagitis, the extent of chronic atrophic fundal gastritis, and Barrett’s esophagus [47-50]. AFI improves detection rates of neoplasia in patients with IBD and decreases the number of random biopsies needed. In a randomized, comparative study with 50 UC patients, neoplasia miss-rates for AFI and white light endoscopy were 0% and 50%, respectively (p=.036) [51]. AFI had 100% of sensitivity since all neoplasia was colored purple on AFI, while NBI had a 75% of sensitivity according to the Kudo classification.

AFI also has the ability to detect inflammatory lesions, including microscopic activity, in the colonic mucosa. Osada et al. [52] evaluated 572 images from 42 UC patients including white light endoscopy and AFI to validate the clinical relevance of AFI endoscopy for the assessment of the severity of inflammation. The green color component of AFI corresponded more closely with mucosal inflammation sites (r=–0.62, p<.01) than the red (r=0.52, p<.01) or blue (r=0.56, p<.01) color components. There were significant differences in green color components between limited (0.399±0.042) and extensive (0.375±0.044) (p=.014) polymorphonuclear cell infiltration within MES-0. It was observed that the green color component of AFI decreased as the severity of the mucosal inflammation increased.

Endocytoscopy

Endocytoscopy (Olympus, Tokyo, Japan) is a new technique, enabling observation of the gastrointestinal mucosa at the cellular level. Microscopic imaging for the gut mucosal layer can be observed at a magnification up to 1,400-fold with a contact light microscope [53]. It requires preparation of the mucosal layer with absorptive contrast agents like methylene blue or toluidine blue. Thus, endoscopists can distinguish architectural details such as epithelial structure, cellular features, and vascular patterns in terms of size, leakage, and tortuosity [54-56].

Some studies suggest that endocytoscopy has a potential role in in vivo evaluation. A study in patients who have colorectal aberrant crypt foci demonstrated that endocystoscopy was able to detect tissue abnormalities in the normal mucosa surrounding CRC and to identify neoplasia in aberrant crypt foci with 91.4% sensitivity [56]. A pilot study with IBD patients showed that endocytoscopy could reliably distinguish single inflammatory cells with high sensitivities and specificities (neutrophilic [60% and 95%], basophilic [74.43% and 94.44%], eosinophilic granulocytes [75% and 90.48%], and lymphocytes [88.89% and 93.33%]). It also showed that the concordance between endocytoscopy and histopathology for grading intestinal disease activity in IBD was 100% [54]. This new imaging technique introduces possibilities for the development ofin vivo research while allowing surface magnification at cellular and subcellular resolution, but little data is currently available on endocytoscopy.

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CONCLUSION

Diagnostic techniques in the field of IBD including endoscopy, molecular pathology, genetics, epigenetics, metabolomics, and proteomics have emerged over the past few decades. An improvement in endoscopic techniques has enabled precise diagnosis and identification of dysplasia with advanced image processing software and optical filter technology. The two major advances provide better recognition of abnormalities enabling a refined classification and characterize the extent and depth of the inflammation or mucosal healing, facilitating targeted biopsy. Real-time microscopy during the ongoing endoscopy at a subcellular resolution is noninvasive and timesaving. These features provide high diagnostic accuracy for the detection of disease activity, location, severity, and complications and can provide valuable guidance for choosing medical and surgical treatments (Table 2).

Table 2.

Table 2.
Potential clinical use of image-enhanced endoscopy in inflammatory bowel disease

Despite the promising data, the generalizability of the procedure should be confirmed with more well designed clinical investigations. Moreover, the utility of these techniques are dependent on the skill of the observers, so it is practically impossible to avoid “intra-observer variation” and “inter-observer variation.”

The new endoscopic imaging modalities used in clinical practice still warrant further investigation. In addition, even if endoscopy in IBD patients is clear, final diagnosis of intraepithelial neoplasia and disease activity still remains on histopathology. It will be important to identify the challenges associated with implementing these advanced endoscopy techniques in clinical practice.

How is EUS performed?

Upon arrival at the endoscopy center, the nurse or the doctor will discuss the procedure and answer any questions. You will then be asked to sign a consent form indicating you were informed about the procedure, its alternatives, and its risks. You will undress and put on a hospital gown. An IV will be placed in a vein and kept open with a slow drip of IV fluid. This IV will be used to administer the sedatives or other required medication. Anesthesia is rarely used. You will then be taken into the procedure room and, after the administration of the sedation, the EUS will be carried out. Small electrode patches will be placed on your skin for the monitoring of your blood pressure, pulse, and blood oxygen.

Once sleepy, the special endoscope will be inserted and the procedure started. Due to the sedation, you will only feel minimal discomfort, if any, during the entire procedure. The physician will observe the inside of your intestinal tract on a TV monitor and the ultrasound image on another monitor. The entire procedure generally takes 30 to 90 minutes depending on the complexity and whether fine needle aspiration (FNA) is performed.

After the procedure, you will be sleepy for up to one hour and be unable to drink or walk. Once you are fully awake, the doctor will discuss with you and, if desired the person with you, the findings of the procedure. Barring any rare complications, when you are fully awake, your companion will be able to take you home where you should rest for the remainder of the day. Light meals and fluids are allowed. You may feel bloated from the carbon dioxide that may have been used to distend your abdomen, but this feeling will only be temporary. Should your throat be mildly sore, for a day or two, salt-water gargles will provide relieve. You should call your doctor if concerned about your progress or having severe pain, vomiting, passage or vomiting of blood, chills or fever. If EUS was particularly difficult or complicated you may be kept in the hospital overnight. The endoscopist will discuss this with you, when you wake up.

When is EUS useful?

The uses for EUS are still being developed and, presently, it is being utilized in some of the following situations:

  • Staging of cancers of the esophagus, stomach, pancreas and rectum.
  • Staging of lung cancer.
  • Evaluating chronic pancreatitis and other masses or cysts of the pancreas.
  • Studying bile duct abnormalities including stones in the bile duct or gallbladder, or bile duct, gallbladder, or liver tumors.
  • Studying the muscles of the lower rectum and anal canal in evaluating reasons for fecal incontinence.
  • Studying ‘submucosal lesions’ such as nodules or ‘bumps’ that may be hiding in the intestinal wall covered by normal appearing lining of the intestinal tract.

Staging of cancer is becoming an important use of EUS. The prognosis of a cancer victim is related to the stage of the cancer at the time of cancer detection. For example, early stage colon cancer refers to cancer confined to the inner surface of the colon before it is spread to adjacent tissues or distant organs. Therefore early stage colon cancer can be completely resected with good chances for cure. However, if cancer is detected at later stages, the cancer tissues have already penetrated the colon wall and invaded neighboring organs and lymph nodes, or have spread to distant organs such as liver and lungs. Complete surgical excision becomes highly unlikely. EUS can provide information regarding the depth of penetration of the cancer and spread of cancer to adjacent tissues and lymph nodes, information useful for staging. 

What is Endoscopic Ultrasound (EUS)?

Endoscopic Ultrasound (EUS) combines endoscopy and ultrasound in order to obtain images and information about the digestive tract and the surrounding tissue and organs. Endoscopy refers to the procedure of inserting a long flexible tube via the mouth or the rectum to visualize the digestive tract (for further information, please visit the Colonoscopy and Flexible Sigmoidoscopy articles), whereas ultrasound uses high-frequency sound waves to produce images of the organs and structures inside the body such as ovaries, uterus, liver, gallbladder, pancreas, or aorta.

Traditional ultrasound sends sound waves to the organ(s) and back with a transducer placed on the skin overlying the organ(s) of interest. Images obtained by traditional ultrasound are not always of high quality. In EUS a small ultrasound transducer is installed on the tip of the endoscope. By inserting the endoscope into the upper or the lower digestive tract one can obtain high quality ultrasound images of the organs inside the body.

Placing the transducer on the tip of an endoscope allows the transducer to get close to the organs inside the body. Because of the proximity of the EUS transducer to the organ(s) of interest, the images obtained are frequently more accurate and more detailed than the ones obtained by traditional ultrasound. The EUS also can obtain information about the layers of the intestinal wall as well as adjacent areas such as lymph nodes and the blood vessels.

Other uses of EUS include studying the flow of blood inside blood vessels using Doppler ultrasound, and to obtain tissue samples by passing a special needle, under ultrasound guidance, into enlarged lymph nodes or suspicious tumors. The tissue or cells obtained by the needle can be examined by a pathologist under a microscope. The process of obtaining tissue with a thin needle is called fine needle aspiration (FNA). 

What are the risks of EUS ?

Like other endoscopy procedures, EUS is safe and well tolerated. No procedure is without risk, but complications with EUS are quite rare. Complication rate for EUS without the fine needle aspiration is about one in two thousand. This is similar to the complication rate of other endoscopy procedures. Sometimes, patients can develop reactions such as hives, skin rashor nausea to the medications used during EUS. A lump may appear in the area of the vein where the IV was placed. This usually resolves over time. Should it persist, you should contact your physician. The main complication of serious note is perforation (making a hole in the intestinal wall) that may require surgical repair. This is quite rare and all precautions are taken to avoid it.

When FNA is performed complications occur more often but are still uncommon (0.5-1.0%). Passing a needle through the gut wall may cause minor bleeding. If unusual bleeding occurs, the patient may be hospitalized briefly for observation, but blood transfusions are rarely needed. Infection is another rare complication of FNA. Infection can occur during aspiration of fluid from cysts and antibiotics may be given before the procedure. If the FNA is performed on the pancreas, pancreatitis (inflammation of the pancreas) can rarely occur. Pancreatitis calls for hospitalization, observation, rest, IV fluid, and medication for abdominal pain. It usually resolves spontaneously in a few days.

Increasing Demand for HD Flexible Endoscopes Spurring Growth in the Global Flexible Endoscopes Market

Reportstack has announced a new market research report on the global flexible endoscopes market 2015-2019, which is expected to grow at a CAGR of 5.99% during the forecast period of 2014-2019.

Market growth of flexible endoscopes is predominantly facilitated by the increasing population of elderly individuals, high incidence of chronic diseases, and increased public awareness of endoscopic procedures. These flexible endoscopes are widely used in healthcare settings for diagnostic and therapeutic purposes. Also, recent advances and innovations in the field of endoscopy technology positively affect the growth of this market.

“Manufacturers are now offering a wide range of HD flexible endoscopes that provide high-quality images when used with compatible processors for better diagnosis of diseased organs or areas,”.