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171Diagnostic Procedures
5.7.2.6.1 Colonoscopy
Lower GI endoscopy is mainly confined to the large bowel. However, experienced endoscopists are able to intubate the last loops of the ileum. Screening of cancer or preforms (polyps) is the most common cause. Inflammatory bowel disease and bleeding are additional indications.
Colonoscopy is technically considerably more demanding than upper
GI endoscopy (
Fig. 5.47).
Prior to colonoscopy, the patient has to undergo full bowel prepara­tion, which means that stool has to be removed completely. The list of bowel preparation regimens is long, encompassing strong laxatives, polyethylene-glycol balanced electrolyte solutions and others. A complete washout of the colon has to be achieved to facilitate a comprehensive exploration. For the patient, this is the most unpleasant par t of the proce­dure, but still unavoidable
5.7.2.6.2 Enteroscopy, Deep Endoscopy
[156].
The small intestine was, for many decades, something like a “white spot” on the map of flexible endoscopy, since it could be reached through nei­ther the mouth nor the anus.
The length and the mobility of the jejunum and the ileum did not allow to introduce the endoscope by “push and retract” methods like in gastroscopy and colonoscopy. The mobile segments are just stretched if the endoscopist tries to push the endoscope forward. Hence, an active forward moving element is required. Since it did not exist for a long time, the assessment of small intestine disorders remained the domain of the radiologists (see
Section 5.1.4: Real-Time Radiography).
With the advent of capsule endoscopy in the beginning of the new millennium, the diagnostic gap concerning the small intestine could be closed, at least to a limited degree.
However, locomotion of the capsule is passive only. The localization of a lesion is less than precise and it does not offer any therapeutic option (see
Section 5.7.8: Wireless Capsule Endoscopy).
Since a couple of years, even the small intestine is now endoscopically accessible via the mouth using the so-called “balloon” technique (so-called “device-assisted enteroscopes”)
[157].
The tip of the specially designed, long endoscope is advanced by pull­ing it stepwise forward according to the inchworm principle (see Chapter
10.1.3.2: Systems With Elements of Autonomous Locomotion).
Figure 5.47 A voyage through the colon. The insert in the left lower corner repre­sents the actual configuration of the colonoscope: (A) The entrance of the colorec­tum: the rectal ampulla. (B) The curved sigma between rectum and descending
(Continued)
Diagnostic Procedures
173
Either one or two balloons are used. Fig. 5.48 illustrates the use of a single-balloon system.
The most common indication for enteroscopy of the small bowel is obscure gastrointestinal bleeding with a high rate of identification and treatment of bleeding spots. Other indications are the staging of Crohn’s disease, evaluation of findings on capsule endoscopy, and investigation of small bowel tumors
[158,159].
Enteroscopy, with its rather short history, has still a slightly higher complication rate than the upper GI endoscopy or colonoscopy. Hopefully, further technical improvements will make it even safer and easier to perform.
Figure 5.48 Balloon enteroscopy: Plain abdominal X-ray. The endoscope can be easily recognized. Courtesy: Prof. S. v. Delius, Klinikum rechts der Isar.
colon. (C) The ascending colon. (D) Left (splenic) flexure which is often difficult to
L
pass. (E) As soon as the left flexure is overcome, the transverse colon with the char­acteristic triangular diameter of the transverse colon becomes visible. (F) In the mid­dle of the transverse colon. (G) The tip of the colonoscope close to the right (hepatic) flexure. (H) A few centimeters further on, a glimpse into the ascending colon is offered (right upper corner). (I) After passing the right flexure, a full view of the ascending colon. (J) In the middle of the ascending colon. Deep down, the end of the colon (cecum) can already be recognized. (K) Bauhin s valve: The entrance into the terminal ileum can be observed at the upper left corner. (L) A closer look on the end of the colon (cecum). Note the entrance of the appendix (center). All
from MITI.
174
Biomedical Engineering in Gastrointestinal Surgery

5.7.3 Autofluorescence Imaging Endoscopy

Fluorescence imaging is mainly used in microscopy. With endogenously or exogenously induced fluorescence, it is possible to visualize and quantify fluorescent markers distributed in tissue and to identify pathological lesions. Autofluorescence imaging (AFI) is based on the detection of natural tissue fluorescence emitted by fluorescent molecules (see Fluorescence Imaging). The overall fluorescence emission differs among various tissue types due to corresponding differences in fluorophore con­centration, metabolic state, and/or spatial distribution
In endoscopy, the principle of autofluorescence is mainly used in gastro­intestinal diagnostic workup to detect diseases such as Barrett’s esophagus, gastric cancer, and polyps. It also finds application during bronchoscopy.
In autofluorescence endoscopy, the tissue is excited by a short­wavelength light source that emits ultraviolet, blue, or green light. After the excitation, the fluorophores emit light of longer wavelengths. Autofluorescence endoscopy is based on the acquisition exclusively of this light, which is emitted by fluorescing molecules. Therefore, a CCD with a barrier filter is incorporated to exclude the excitation light and capture only the weak reflected autofluorescence.
There are autofluorescence imaging systems that postprocess the images and enhance them in real-time with pseudocolors. In this case, the image is composed of three parts: the total autofluorescence, exclu­sively the green reflectance, and exclusively the red reflectance light.
With AFI, it is possible to visualize and quantify fluorescent molecules distributed in tissue and to identify malignant tissue more easily because early cancer sites are better visualized (
Fig. 5.49). Tissues may contain
several fluorophores such as NADH, elastin, collagen, and flavin.
Section 5.6.3: Optical
[160].
Figure 5.49 Comparison of white-light (left) and autofluorescence endoscopy (right) in depiction of cancerous tissue. From Aihara H, Tajiri H, Suzuki T. Application of auto-
fluorescence endoscopy for colorectal cancer screening: rationale and an update. Gastroenterol Res Pract 2012;2012:971383.
Table 5.17 Key facts on AFI endoscopy Typical applications Strengths and
weaknesses
Recent developments
175Diagnostic Procedures
Research potential and future trends
Pulmonology Gastroenterology
High contrast
without color markers
High false
positive detection rate
Improvement
of image quality
Trimodal
imaging
Smaller devices
FLIM Identification of
distinct molecules and their concentration
Autofluorescence emission has been reported mainly with respect to collagen, which is distributed in the submucosal layer. By spectrally mea­suring the fluorescence of tissue, it is possible to learn about the relative concentrations and redox states of many molecules and the biochemical state of the tissue, which is not yet fully applied in medicine
[162].
Strengths and Weaknesses
AFI provides a very high sensitivity in early-stage cancer detection. It allows the identification of areas of abnormality in the GI tract that may not be visible under white-light examination. Unfortunately, it has a high false positive rate, which makes follow-up testing necessary (
Table 5.17).
Recent Developments and Current Research
The image quality of AFI still needs to be improved and the false positive rate needs to be decreased further. Additional enhancements are clearly desired in clinical applications, and may be achieved with comput­erized visualization
[163]. The measurement of distinct fluorescence
spectra and a resulting specialized analysis of the tissue and its diseases is a field of current research. Currently, autofluorescence endoscopes have a relatively thick outside diameter (up to 14.8 mm), which might limit maneuverability
[161].
Recent developments cope with the introduction of fluorescence life­time imaging (FLIM) in endoscopes. In 2013, a compact wide-field time­gated FLIM flexible endoscope was presented. It is capable of continuous lifetime imaging of up to three fluorescence emission bands simulta­neously, but has not proven its clinical applicability until now
[164].In
2011, the first confocal FLIM endomicroscope for subcellular confocal imaging was demonstrated
[165]. FLIM allows the characterization of the
biochemical composition of tissue. Fluorescence of organic molecules is
176
Biomedical Engineering in Gastrointestinal Surgery
Figure 5.50 Olympus trimodal imaging(autofluorescence): (A) overview; (B) detec- tion; (C) differentiation. Courtesy: Prof. S. v. Delius, Klinikum rechts der Isar.
not only characterized by the emission spectrum, it has also a characteris­tic lifetime. The lifetime does not depend on the concentration of the chromophore, and allows direct approach to all effects that involve energy transfer.
Combining AFI with other imaging modalities in one device over­comes the problem of the high false positive rates of AFI and necessary follow-up testing. Endoscopic trimodal imaging (ETMI) is a novel endo­scopic technique that combines white-light endoscopy (WLE), magnifica­tion endoscopy, or high-resolution endoscopy (HRE) with AFI and narrow band imaging (NBI) have the ability to switch between these three modalities (
[166]. Trimodal imaging endoscopes
Fig. 5.50).
Currently, ETMI is mostly applied in academic settings, but is expected to see use in the near future as a standard endoscopy technique in gastro­intestinal pathology, with an emphasis on the diagnosis of early-stage gas­trointestinal tract cancers
[115].

5.7.4 Computed Virtual Chromoendoscopy/Narrow Band Imaging (NBI)

Computed virtual chromoendoscopy (CVC) is a technique that digitally enhances the contrast of images of the mucosal surface and highlights the vascular pattern without the need for dye spraying as in conventional chromoendoscopy.
CVC systems make use of the principle that different light spectra have different tissue penetration depths acquired by different light spectra allows early detection of small superfi­cial mucosal lesions that are undetectable using conventional WLE.
It is mainly used in gastrointestinal endoscopy, bronchoscopy, for diag­nosing bladder cancer during cystoscopy, and ENT medicine.
[167]. Thus, the analysis of images
Diagnostic Procedures
177
There are two approaches to CVC image acquisition. In NBI, light of varying spectra is sequentially emitted. However, there are also CVC sys­tems that use normal WLE and reconstruct the images with enhanced contrast by estimating the different light spectra.
NBI endoscopes provide white-light examination and an NBI mode. In NBI endoscopy, the emitted light is directed through bandpass filters, which split the light into excitation wavelengths of blue light (390445 nm) and green light (530550 nm) (
Fig. 5.51). The penetra-
tion depth before being scattered depends on the wavelength of the light. The shorter the wavelength (e.g., blue), the earlier it is reflected. Longer wavelengths (e.g., green) penetrate deeper
[168].
The low brightness of the reflected light requires special high-sensitive dual-mode CCD chips. A video processor decomposes the light by its wavelengths and creates a composite pseudocolor image that is displayed directly on a monitor. In the resulting image, the superficial mucous layers are displayed in blue, the capillary network of the deeper submuco­sal layer in green.
This blue light is particularly useful for detecting tumors, which are often highly vascularized. The green light penetrates deeper than blue light. It is absorbed by blood vessels located deeper within the mucosal layer, and appears cyan on the NBI image. This wavelength allows a bet­ter understanding of the vasculature of suspect lesions (
Fig. 5.52).
Figure 5.51 Narrow band imaging. From Lukes P, Zabrodsky M, Plzak J, Chovanec M, Betka J, Foltynova E, et al. Narrow band imaging (NBI)-endoscopic method for detection of head and neck cancer. In: Amornyotin S, editor. Endoscopy. Rijeka: InTech; 2013.
178 Biomedical Engineering in Gastrointestinal Surgery
Figure 5.52 Mucosal blood vessels displayed in brown and submucosal vessels in cyan. The different colors indicate the different height. Courtesy: Prof. S. v. Delius, Klinikum
rechts der Isar.
Table 5.18 Key facts on narrow band endoscopy Typical applications Strengths and
weaknesses
Recent developments
Research potential and future trends
Pulmonology Gastroenterology Otolaryngology
High contrast
images of mucosal tissue and lesions
Frequently false
positive findings
Trimodal
imaging
Virtual image
enhancement
HD-CCD chips
Combination
with other modalities and virtual image fusion
Narrow band imaging is applied in Olympus Narrow Band Imaging Systems. There are two further CVC systems available: the Fujinon Intelligent Color Enhancement (FICE) and the Pentax iScan. They reconstruct the video images virtually with special algorithms to improve the contrast.
Strengths and Weaknesses
NBI offers a significantly increased diagnostic accuracy compared to WLE and autofluorescence endoscopy. Blue light has less penetration and less scattering, thus enhancing image resolution. Image processing allows high contrast images without the usage of dyes, as would be the case in chromoendoscopy. Dye-sprays like methylene blue, used for polyp char­acterization, have the risk of possible DNA damage, which is avoided using NBI. Nevertheless, NBI can lead to false positive findings in some cases (
Table 5.18).
Recent Developments and Current Research
Advances in CCD technology have resulted in smaller CCDs with an increased number of pixels and increased resolution.
179Diagnostic Procedures
As explained in the discussion of AFI endoscopy, NBI has high poten­tial in combination with other imaging modalities. ETMI is a novel endoscopic technique that combines WLE, magnification endoscopy, or HRE with AFI and NBI
[166]. Trimodal imaging endoscopes have the
ability to switch between these three modalities. The combination of NBI with autofluorescence endoscopy overcomes the main disadvantages of each technique
[115]. Using magnifying HDTV endoscopy in combi-
nation with NBI dramatically improves the sensitivity and specificity of endoscopic examination
[167].

5.7.5 Confocal Endomicroscopy

Confocal endomicroscopy is a novel technology that enables real-time imaging at the cellular level by using miniature optical systems integrated into the tip of a small imaging probe or endoscope “optical biopsy” is sometimes used to underline that the resulting images previously could have only been acquirable using histological or cytologi­cal analysis; in contrast, no tissue is removed in confocal endomicroscopy. The most common endomicroscopy application is confocal laser imaging, which is described in more detail in
Section 5.6.6: Confocal Laser
Scanning.
Confocal endomicroscopy provides instantaneous histopathology dur­ing upper and lower endoscopy. The main applications currently lie in imaging of the gastrointestinal tract, particularly for the diagnosis and characterization of Barrett’s esophagus, pancreatic cysts, and colorectal lesions. It also has high potential in the screening and surveillance of ulcerative colitis and gastric cancer
[170].
In confoca l endomicroscopy, a special confocal optical unit detects backscattered light alone at a precisel y defined h orizontal level (see
Section 5.6.6: Confocal Laser Scanning). This produces high-resolution
microscopic images, making it possible to assess structures up to the size of a cell nucleus. A resolution of 0.53.0 µm, an axial resolution of 310 µm, and a s ubsur face de pth of 250500 µm are possible in this manner
[171]. In most cases, the fluorescein sodium is intravenously
administered as fluorophore for subsequent excitation by a laser light, allowing cell structures to be easily identified. Either scan can be per­formed at the proximal end of a fiber bundle or the distal tip using a piezoelectric fiber scanner, a MEMS scanning device, or a technique called spectral encoding
[172] (Table 5.19).
[169]. The term
180
Biomedical Engineering in Gastrointestinal Surgery
Table 5.19 Key facts on confocal endomicroscopy Typical applications
Strengths and weaknesses
Recent developments
Research potential and future trends
Gastroenterology Oncology
Figure 5.53 (A) Nonneoplastic Barrett mucosa of the esophagus; (B) normal, healthy mucosa of the colon. Courtesy: Prof. A. Meining, University of Ulm.
High resolution High contrast at
certain depths
Low penetration
Dual-axis confocal
endomicroscopy
New specialized
molecular markers
Telepathology Introduction
to new applications
Strengths and Weaknesses
The confocal images have a very high resolution on the order of his-
tology and can be acquired in vivo (
Fig. 5.53). Therefore, it can guide
excisional biopsies for a better diagnostic yield.
Although the depth resolution is very high, confocal endomicroscopy
has, like most optical technologies, a very limited penetration depth
[173].
Confocal endomicroscopy does not provide information about biological behavior either above or below the achieved depth, but cancer may none­theless occur in deeper tissues. Moreover, horizontal cross-sections are an atypical view of the tissue when compared to traditional biopsy specimens that pathologists are accustomed to view. Hence, a specialist must be trained to interpret confocal endomicroscopy images
[171].
Recent Developments and Current Research
There are various applications of confocal endomicroscopy that are still not used in the field of human medicine. In animal models of human diseases, confocal endoscopy has provided molecular imaging of cancer, functional imaging of altered perfusion in malignant and inflammatory