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181Diagnostic Procedures
disease by coupling fluorophobes to specific antibodies, and high­resolution in vivo morphological diagnosis
[169]. Fields of ongoing
research are the development of molecular markers for in vivo immuno­histochemistry and the application of confocal microscopy to intraabdom­inal organs in humans. Confocal endomicroscopy is evolving as a novel technique for rapid intravital diagnosis of gastrointestinal neoplastic dis­eases at the microscopic level, and has the potential to allow molecular imaging in humans in the future
[169].
Dual-axis confocal microscopy is seen as the major technological improvement of CLS, and is applicable in endoscopy. Dual-axis confocal endomicroscopy has the ability to perform deep 3D optical sectioning using simple and inexpensive optical components and light sources
[173].
As a completely new application, confocal endomicroscopy could play a central role in the emerging area of telepathology.

5.7.6 Endoscopic Optical Coherence Tomography

The technical details of OCT are described in Section 5.6.2: Optical Coherence Tomography.
Endoscopic imaging probes are key devices for internal high­resolution OCT scanning of luminal structures and hollow organs. The modalities usually find application in early-state or precancer detection in the urinary and gastrointestinal tract, cardiology, and in examining other microstructural anatomy and features in places like the ears parts of the head and neck are also in the range of application—for instance, when patients are undergoing surgeries in the upper respiratory organs
[174176]. OCT is a powerful imaging technology because it
provides real-time imaging in situ without the need for tissue excision like in conventional biopsy. OCT can be employed in capsule endoscopy, and a number of different devices have been introduced that can be dis­tinguished by the case that encloses the technical components: rigid endoscopes such as biopsy needles, flexible endoscopic devices for uses like gastrointestinal imaging, and catheters for intravascular examinations
[86,177]. The integration of OCT in clinical procedures benefits signifi-
cantly from OCT being fiber-based. In situations where OCT finds application in a clinical environment, it is of high importance that the technical setup remains operational or that applicability can be restored within minutes after use or after it has been moved inside the hospital environment.
[174]. Other
182
Biomedical Engineering in Gastrointestinal Surgery
Figure 5.54 Stationary-fiber rotary probe with unobstructed 360 degrees view for OCT. From Chang S, Murdock E, Mao Y, Flueraru C, Disano J. Stationary-fiber rotary
probe with unobstructed 360° view for optical coherence tomography. Opt Lett 2011;36 (22):43924.
As mentioned, OCT can be applied in rigid/flexible endoscopes to bring the high-resolution properties of OCT to internal imaging (
Fig. 5.54).
Flexible endoscopic OCT has great potential, and is still finding appli­cation in many different fields of internal imaging. These fields extend from cancer diagnosis in the gastrointestinal and urinary tract and exami­nations of the respiratory organs to identify issues like reductions in gas exchange efficiency to intravascular imaging
[86,179]. Rotary probes
with a diameter of approximately 1 mm and a transparent housing are inserted into the ROI either noninvasively or invasively. In intravascular OCT, a thin flexible tube or catheter is pushed in and pulled back inside the artery
[97]. As with the other devices, the catheter also has a small
rotating tip from which the light is emitted in order to generate circum­ferential OCT images of the insides of blood vessels
[178].
Biopsy needles are another way to enable transcutaneous micron scale OCT. They can be inserted into solid tissue and organs to allow imaging of their internal microstructures with minimal trauma
[180]. They suit a
variety of different applications in which transdermal OCT imaging is required, such as in mammographic cancer detection
[86]. Biopsy needles
for OCT usually consist of a needle-shaped housing defining a bore, in which an optical fiber is positioned. Parts of the needle housing are trans­parent to allow a beam director to emit light outward and receive the backscattered light. A motor or other actuating device again causes motion to move or rotate parts of or the entire optical fiber and beam director in order to allow a scanning of the specimen
[181].
183Diagnostic Procedures
Strengths and Weaknesses
This technology is of special interest because of the high image and depth resolution provided by OCT imaging. This gives it advantages over standard endoscopy that can only visualize surface features, making it a valuable tool for detecting conditions like prevalent esophageal, stomach, and colon cancer
[175].
Conventional procedures like MRI or US do not have a sufficient resolution to identify atherosclerotic plaque at an early stage provides a resolution of approximately 10 µm compared to intravascular US
[86], enabling it to provide additional
structural information as seen in the images below
[33], which is much higher
[182,183] (Fig. 5.55).
[94]. OCT
Endoscopic OCT (EOCT) has also become a very valuable tool in gastrointestinal imaging, with a wide range of applications. One of the main advantages in most of its applications remains the fact that it can be used where excisional biopsy would be hazardous or impossible, providing information similar to that g ained from histology
[94]
(Table 5.20).
Figure 5.55 Comparison of intravascular US (left) and intraaorticoptical coherence tomography (right). From Tahara S, Morooka T, Wang Z, Bezerra HG, Rollins AM, Simon
DI, et al. Intravascular optical coherence tomography detection of atherosclerosis and inflammation in murine aorta. Arterioscler Thromb Vasc Biol 2012;32(5):11507.
Table 5.20 Key facts on EOCT
Typical applications Strengths and
weaknesses
Cardiovascular
medicine
Gastroenterology
Oncology
High resolution,
wide range of applications
Low depth
penetration
Recent developments
High frame rates Better
reconstruction
Research potential and future trends
Integration of F-F
OCT setup Miniaturization Avoidance of
direct contact to
the tissue
184 Biomedical Engineering in Gastrointestinal Surgery
Recent Developments and Current Research
Catheter-based OCT has been made commercially available world­wide, and has found an active user base that is continuously increasing
[33]. The latest devices that have been introduced allow imaging with
frame rates up to 400 fps with a diameter at the tip of 1.1 mm. During ex vivo testing, complete 3D volumetric images of an entire coronary artery were achieved at a pull-back speed of 100 mm/s
[95].
Further more, recent advances have been made in reconstructional algo­rithms, providing enhanced imaging of stent struts among other things
[184]. Sophisticated data fusion methodologies with other imaging
modalities to help further understanding of plaque characteristics and vessel pathophysiology are also of great potential
[185].
The standard F-F OCT setup did not match miniaturization require­ments for in situ needle imaging. Therefore, a new development has been introduced where an external interferometer processing the in-depth scan information is coupled with an internal common-path interferometer at the tip that collects the backscattering light from the tissue. This makes it possible to bring full-field technology into optical needle-biopsy, provid­ing resolutions of almost 1 µm and revealing information about malignant tissue en-face and on a cellular level
[186]. Other superminiaturized opti-
cal biopsy needles capable of acquiring 3D OCT images have also been demonstrated, and achieve an outer diameter of 0.31 mm by using an all­fiber probe. The astigmatism ratio was brought down to 1.8, resulting in a working distance of 300 µm and a depth-of-field of 550 µm
[187].
Another current challenge in EOCT is the implementation of optics that avoid direct contact with inflamed tissue in imaging areas like the tympanic membrane. A possible approach to this problem could be an extended working distance by allowing manual adjustments in focus
[174].
The high sensitivity and depth resolution might allow EOCT to sub­stitute for several biopsy applications on a broad basis, and reduce the role of conventional endoscopy in general
[188].

5.7.7 Endoscopic Ultrasound

Endoscopic ultrasound (EUS) is a technique combining endoscopy and US in order to obtain images and information from the digestive tract and the respiratory system and their surrounding tissue and organs EUS has the ability to identify the component layers of the bowel wall, which can be used for the staging of gastrointestinal cancer
[189].
[190].
Diagnostic Procedures
185
In addition to the evaluation of esophageal, gastric, and rectal cancer, EUS is mainly used for the assessment of pancreatic diseases, but other fields of application are under investigation
[191]. Other uses of EUS
include studying blood flow and guiding biopsies such as fine needle aspi­ration, in which tissue samples can be obtained by passing a special needle into tissue, lymph nodes, or suspicious tumors
The technical principles of diagnostic US are described in
[192].
Section 5.4:
Diagnostic Ultrasound.
In EUS, the endoscope is inserted into the respiratory system or into the upper or lower digestive tract and the US transducer generates high­quality images of the organs inside the body
[189]. EUS probes consist of
a small US transducer, which is installed on the tip of an endoscope (
Fig. 5.56). Two different designs are available. Linear probes consist of a
number of transducers in multiple rows, providing a segmental image of the anatomy. Radical probes deliver a 360 degrees panorama of the ana­tomical environment. The endoscope has a flexible shaft with a central wire, which is responsible for rotating the mechanical transducer. It is sur­rounded by oil, which serves as an acoustic interf ace with tissue,
Figure 5.56 (A) Tip of a linear EUS probe; (B) linear EUS image; (C) tip of a rotating scanner; (D) radial EUS image. All from MITI.
186 Biomedical Engineering in Gastrointestinal Surgery
providing 360 degrees imaging perpendicular to the axis of the probe. Depending on the purpose, EUS probes range from 2 to 2.9 mm in diameter for miniature probes applicable through the endoscope working channel to 12 mm for echoendoscopes, 12 to 30 MHz in frequency, and 170 to 220 cm in length
[193].
Strengths and Weaknesses
Images obtained by EUS are more accurate and more detailed than those obtained by conventional US due to the proximity of the EUS transducer to the tissue of interest. EUS offers further a high accuracy in detecting small lesions and assessing the size of tumors, and helps the surgeons to determine the extent of spread of certain cancers
[189].
Recent Developments and Current Research
EUS is a relatively new diagnostic tool and is still in its development stage (
Table 5.21). Research concerning EUS involves increasing US
image quality and finding more sophisticated interventional endoscopic devices
[194]. A recent development is the combination of real-time elas-
tography with EUS. This relatively new technique allows the evaluation of tissue stiffness with the intent of better characterizing lesions during EUS examinations
[195].
In the future, endoscopy is expected to become even more relevant. Numerous technological enhancements and a general trend in medicine toward minimally invasive diagnostics and surgery support the growing relevance of endoscopy and EUS.

5.7.8 Wireless Capsule Endoscopy

Capsule endoscopy is a technology that uses a swallowed video capsule to take photographs of the inside of the gastrointestinal tract: examinations of the esophagus, stomach, colon, and the small and large intestines are the main applications. Conventional endoscopes are inserted transorally or
Table 5.21 Key facts of EUS Typical
applications
Gastroenterologic
and pulmonary oncology
Strengths and weaknesses
Accurate and
detailed images
High
penetration depth
Recent developments
Combination of
real-time EUS and elastography
Research potential and
Increasing image
quality
More
interventional devices
Diagnostic Procedures
187
transanally, which can be undesirable for the patient, especially as the small intestine can be very difficult to reach during a classic endoscopic examination. Wireless capsule endoscopes (WCE) are rapidly emerging devices that help to overcome the possible discomfort of oral or anal insertion from a classic endoscope and allow easier access to narrow parts in the gastrointestinal tract. The first capsule endoscopes were developed in the middle of the 1990s and were approved for clinical use at the beginning of the 21st century the gold standard in evaluating diseases in the small intestine
[196]. Since then, they have emerged to be
[197],but
WCEs are also suited for investigating other parts of the gastrointestinal tract. In terms of application, the most common indications include bleedings in the gastrointestinal tract and Crohn’s diseases, but cancer detection, especially in the small intestine, is also possible.
The capsule has a size of around 26 mm 3 11 mm
[196]. The essential
components are inside an ingestible coating with an optical dome, behind which LEDs are situated to provide the necessary lighting. An image sen­sor translates the signals acquired through a short-focus lens, which are later processed by a microcontrol unit (
Fig. 5.57).
The information is then transmitted via a radiofrequency transmitter to electrodes placed on the abdomen of the patient. Finally, the images are stored in a receiving box as seen in comes from a cell battery inside the capsule
Fig. 5.58. The necessary energy
[199].
At the beginning of the procedure, the capsule is swallowed by t he patient after the receiving sensors are placed on their abdomen and
Figure 5.57 Small intestine capsule endoscope. From Olympus Press Center. Small intestinal capsule endoscope. Available from ,
press_centre/press_releases/medical/small_intestinal_capsule_endoscope_.jsp?view 5 img
2013 [accessed 23.09.16].
https://www.olympus.de/corporate/de/
. ;
188
Biomedical Engineering in Gastrointestinal Surgery
Figure 5.58 Capsule endoscope image receiving box. From MITI.
connected to the data recorder. The capsule travels through the whole gastrointestinal tract, dr iven by peristalsis. During that time the patient can move freely and co ntinue with his/her daily routines. Of n ote, 50,00060,000 dig ital images are acquired and sent to t he data recorder worn around the chest. The images are then a nalyze d in a workstation after the patient returns to the clinic. The capsule is dis­posable and usually passes out of the p atient’s gastrointestinal t ract unnoticed. It is possible to a pply the procedure in children as young as 2yearsold
Real-time imaging is also feasible
[196].
[200], but in WCE only 2D images
are acquired. Therefore, 3D reconstruction algorithms are employed in order to gain 3D information and display of the wall of the gastrointesti­nal tract. One possible approach is reconstruction using the so-called shape from shading technique are extracted from differences in gray shades if as little information as only one picture is available
[201], where surface and depth information
[202]. It can be applied even
[203].
Strengths and Weaknesses
WCE overcomes the problem of conventional tools not being able to
conveniently explore the complete gastrointestinal tract
[201], especially
Table 5.22 Key facts on WCE Typical applications Strengths
and weaknesses
Recent developments
189Diagnostic Procedures
Research potential and future trends
Gastroenterology
(especially the small intestine)
Increased
patient comfort
Accesses
difficult
Low energy
supply
Low frame
rates
Introduction
of first locomotion
Wireless power
supply
Energy saving
components
Better
locomotion
the small intestine, where conventional endoscopy carries the risk of intestinal perforation and cross-contamination. The procedure is completely pain-free for the patient and is considered rather safe with a complication rate of 13%. The most feared complication is capsule retention removal
[204], which can theoretically lead to the need for surgical
[197] (Table 5.22).
The disposability of the capsule has the advantage of improving hygiene. In conventional gastrointestinal screening, sterilization can be a major concern if the same endoscope is used in multiple persons.
Compared to conventional endoscopes, the low frame rate of 218 fps, low image resolution, and limited working time due to the constraints in energy supply are limiting factors shorten the working time to approximately 9 hours
[199]. The battery cells
[205] and influences
the choice of inherent components such as the image sensor. CMOS is often the sensor of choice over the more light-sensitive CCD sensors due to its lower power consumption
[206]. Probably the biggest limitation is
that WCE is a purely diagnostic tool, and cannot be used to perform pro­cedures like biopsies
[196]. Some similar technologies in the form of
ingested capsules have begun to make approaches toward biomonitoring and smart drug delivery
[58].
Recent Developments and Current Research
The limited power supply is still a bottleneck for capsule endoscopes
and their performance
[199]. Wireless power supply could offer a promis-
ing solution and might help to increase performance by allowing for the integration of high power components which would increase resolution
[207]. There have been several approaches to energy savings in WCE, like
190 Biomedical Engineering in Gastrointestinal Surgery
processor steered shut-down times that would allow image acquisition to be paused while the capsule passes an area of lower interest for the proce­dure in question. Different inventions have been introduced in recent years that could potentially help to overcome problems with necessary power transfer in capsule endoscopy. These approaches show an efficiency in volt­age and power transmitted of 82.14% and 83.50%, respectively
[208].
Improving the quality factor of the coils employed might effectively increase the system’s efficiency.
On the other hand, a tethered capsule endoscope employing OCT has recently been introduced. The capsule is mainly suited for imaging the esophagus, after which the capsule reaches the stomach driven by nothing but peristalsis and can be pulled out using the elastic tether. The images are superior to other high-resolution devices and tethered capsules could provide a possible cheap alternative for dischargeable capsules with enhanced image quality
[209].
These developments go hand in hand with the necessity of finding approaches for capsule locomotion
[199]. The capsule previously traveled
passively using natural peristalsis. Therefore, the position of the device and the imaging of the area of interest could not be controlled. Active locomotion inside the gastrointestinal tract is very difficult to achieve because the tissue is soft and viscoelastic.
How ever, a number of inno vations have been introduced that enable cap­sule steering and navigation. For instance, the Fraunhofer Institute for Biomedical Engineering in Sulzbach/Germany has introduced a magnetic steerable capsule in cooperation with their industrial partner, Giv en Imaging Ltd., from Yokneam/Israel. The imaging capsule was partly filled with a mag­netic material and can be remotely controlled from the outside with a comple­mentary magnetic paddle. In initial tests, it was possible to control the imaging time inside the esophagus from only a few seconds up to 10 minutes. Further, almost 80% of the stomach walls were imaged, which has never been possible using conventional capsules. Steering brings the additional advantage of imag­ing at multiple angles and obtaining close-ups of the areas of interest.
Engineers are working continuously to overcome a number of chal­lenges associated with these devices
[189]. With further approaches in
active locomotion, the development of a microrobotic capsule capable of conducting microsurgeries and biopsies could be possible, ultimately replacing conventional capsule and tube endoscopes
[199].
The 50,000 images acquired during one examination create another
problem, making the analysis of the results a very time-consuming task
[201]