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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_605_Библиотеки_им_академика_М_И_Перельмана.pdf
151Diagnostic Procedures
As mentioned above, the low spatial resolution is the main disadvantage of DOI. That is why it is a constant field of interest in research. A
high connector density is one approach to counter this problem.
Currently, systems with 24 sources and 28 detectors embedded in a small
(13 3 6 cm) probe array are the state-of-the-art
[129]. However, one of
the most significant improvements in image quality is achieved by optimization of image reconstruction techniques. Image reconstr uction allows
multiple measurements to contribute to each pixel, leading to improvements in spatial resolution, spatial and quantitative accuracy.
The spatial resolution can be enhanced by combining DOI with other
imaging methods. Combination with MRI seems to be particular promising. Optical probes can easily be made to be MRI-compatible, and optical imaging provides complementary information to MRI.
5.6.6 Confocal Laser Scanning
Confocal laser scanning (CLS) or confocal scanning laser is a special kind
of microscopy that uses laser light instead of a bright flash of white light.
The reflected light is captured through a small aperture that allows the
acquisition of high-resolution, high-contrast images at various depths of
an object. The images are reconstructed with a computer and can also be
obtained in a 3D image.
The most common medical application for confocal scanning laser is
the examination of the retina or cornea of the eye, called confocal scanning laser ophthalmoscopy (cSLO) but it is also used in examinations of
the human skin. CLS can also be integrated into endoscopes for applications in gastroenterology (see
The images are obtained by scanning an object point by point with a
focused laser beam. The reflected light has to pass through a small aperture, so only the in-focus area is captured by the detector. The light from
out-of-focus planes is suppressed by the confocal pinhole.
To illuminate a point of the specimen, a beam splitter or dichroic mirror is used. Emitted or refracted light from the illuminated point that
retraces the incident light path (the solid line in
through the confocal pinhole. This confocal effect depends both on the
focused illumination of a single point in the specimen, so that the illuminating intensity f alls off, and on the use of a pinhole in the image plane
to exclude the majority of residual out-of-plane emissions (the dotted
lines in
Fig. 5.30).
Section 5.7.5: Confocal Endomicroscopy).
Fig. 5.30) is captured
152
Biomedical Engineering in Gastrointestinal Surgery
Figure 5.30 Principle of confocal microscopy. From Lee YJ, Wang D, Jow GM.
Confocal microscopy in biomedical and clinical applications. Fu-Jen J Med
2004;2:26371.
A 3D image of the sample is created by successively scanning planes of
different depths and stacking them together. In the examination of cells,
the usage of fluorescent substances are very common.
Modern instruments are equipped with three to five laser systems controlled by high-speed acousto-optic tunable filters, which allow very precise
regulation of wavelength and excitation intensity. Coupled with photomultipliers that feature high quantum efficiency in the near-ultraviolet, visible,
and NIR spectral regions, these microscopes are capable of examining fluorescence emissions ranging from 400 to 750 nm
[136].
Strengths and Weaknesses
Images obtained by CLS are characterized by their high contrast and
resolution. However, the point-to-point acquisition leads to a comparatively slow acquisition speed, which is problematic in medical imaging
due to movements of the considered object (
Table 5.14). There are differ-
ent methods to overcome this disadvantage, such as using adaptive optics
or resonant scanning mirrors
[137].
Table 5.14 Key facts of CLS
Typical applications Strengths and
weaknesses
Recent
developments
153Diagnostic Procedures
Research
potential and
future trends
Ophthalmology
Dermatology
Gastroenterology
Microscopy with
very high
contrast and
resolution
3D-images
reconstructable
Adaptive optics
scanning laser
Endoscopic
confocal
microscopy
Dual-axis
confocal
scanning laser
Combination
of CSL
with other
modalities
MEMS-
technology
Handheld
devices
Recent Developments and Current Research
In the last few years, confocal microscopy has been adapted to flexible
fiber probes that can be used with endoscopic methods to obtain images
of sites that were previously inaccessible. With endoscopic systems such as
those manufactured by Mauna Kea Technologies (Paris, France), it is possible to obtain images of B2.5 µm lateral resolution and 1520 µm axial
resolution at depths up to 80 µm. This progress has been accelerated by
the availability, variety, and low cost of optical fibers, scanners, and light
sources, in particular for semiconductor lasers. The addition of a realtime, high-resolution imaging instrument can help guide tissue biopsy
and reduce pathology costs.
Conventional single-axis confocal microscopes have a trade-off
between resolution, size, and working distance. The need for high resolution requires a larger high-numerical aperture objective, resulting in a
shorter working distance. To overcome the limitations in miniaturizing
CLS optics in particular, a dual-axis confocal architecture has been
developed that uses separate illumination and collection objectives. Two
low-numerical aperture objectives are oriented with the illumination and
collection beams crossed at an angle, which results in a significant reduction of the axial resolution (black oval in
working distance, and a decrease in light scattering
Fig. 5.31), an increase in long
[138,139].
Technological developments allow new designs and improved imaging
capacity. The application of MEMS-technology is, like in many optical
systems, a driving factor of development. The integration of a 2D MEMS
scanner with dual-axis confocal architecture enables the microscope system to be contained in a miniature package while enhancing imaging
performance, so even the development of handheld devices is possible. In
154
Biomedical Engineering in Gastrointestinal Surgery
Figure 5.31 Dual-axis confocal endomicroscopy. From Piyawattanametha W, Wang
TD. MEMS-based dual axes confocal microendoscopy. IEEE J Sel Top Quantum Electron
2010;16(4):80414.
2008, the first fully packaged handheld dual-axis confocal microscope,
capable of 3D reflectance and fluorescence imaging, was presented
[140].
CLS is increasingly used in routine clinical settings for diagnostic purposes and assessment of treatment effects. It has become a valuable
research tool due to its ability to examine mucosal morphology in vivo.
Technological development has matured in the past 10 years significantly
[141], but minimizing the effects of ocular aberrations and imaging arti-
facts are still a matter for further research
[142].
Combining CLS with other technologies is of growing interest for
clinical settings. Simultaneous cSLO/OCT imaging combines two different imaging technologies in one device with various subsequent advantages, including the exact correlation of tomographic and topographic
findings
[141].
5.6.7 Photoacoustic Imaging
Photoacoustic imaging (PAI), also called photoacoustic spectroscopy, is based
on the principle of thermal expansion of an object caused by the absorption
of light. When the emitted light is pulsed, it induces an oscillating movement
in the tissue, resulting in pressure waves that can be interpreted as a sound
Diagnostic Procedures
155
signal. This principle is called the photothermal or photoacoustic effect. PAI
is a promising structural, functional, and molecular imaging modality for a
wide range of biomedical applications. Most of them are still under research,
often only applied in preclinical studies. However, the technology is starting
to see use in clinical settings
[143]. In medical diagnostics, photoacoustic
tomography (PAT), also called optoacoustic tomography, is the main means
of generating 3D images. It has been recognized as a technology with very
high potential for early-stage cancer detection.
Traditional optical imaging methods suffer from scattering in biolog ical tissues (
copy, neither scattered nor reflected light contributes to the signal
Fig. 5.32). In contrast to conventional transmission spectros-
[144].
Using laser pulses to generate elastic pressure waves (US) allows highresolution optical information to be obtained. Ultrasonic scattering is two
to three orders of magnitude weaker than optical scattering
[145,146].
It is necessary to use very short pulses—only if the laser pulse is short
enough will the thermal expansion cause a pressure wave proportional to the
locally absorbed energy density, which is generated by the photoacoustic
effect
[147].
Figure 5.32 Laser-induced photoacoustic effect. (A) A laser pulse irradiates tissue,
the absorbed energy causes local heating. (B) Thermoelastic expansion and generation of pressure waves (ultrasound) which can be detected outside the sample. From
Burgholzer P, Grün H, Sonnleitner A. Photoacoustic tomography: sounding out fluorescent proteins. Nat Photon 2009;3(7):3789.
156 Biomedical Engineering in Gastrointestinal Surgery
The application of a Nd:YAG laser and an optical parametric oscillator
allows light pulses of different spectra and a repetition rate from 10 Hz up
to 100 Hz to be used. Some high-speed PAT systems can even go up to
1000 Hz. Pulse duration in the nanosecond range allows a theoretical resolution of several micrometers in tissue
[145].
Like in US techniques, pressure-sensitive elements such as piezoelectric transducers are used. An image of the photo-generated pressure distribution in the sample is acquired by collecting the US at many different
locations with transducers. The electric signals produced by the transducer are amplified, digitized, transferred to a computer, and processed
using a suitable algorithm. Though the algorithms have already found
application in other imaging modalities such as CT, MRI, and US,
reconstruction is still a major challenge in PAT systems. It arises from the
fact that the location of the acoustic waves’ source is unknown
[147]
Different molecules in the tissue have different absorption spectra,
which are the basis of DOI. PAT is also able to benefit from this effect.
There are developments in multispectral imaging methods for acquiring
images excited with different wavelengths.
Generally, blood is the major absorben t of light in biological tissue,
meaning the signal comes mainly from regions with a high concentration of blood. By using multiwavelength measurements, one can simultaneously quantify concentrations of multiple chromophores of different
colors, such as oxygenated and deoxygenated hemoglobin molecules in
red blood cells. Such quantification of hemoglobin can provide
functional imag i ng of th e concentration and oxygen saturation of
hemoglobin. Both paramete rs are related to hallmarks of cancer, and can
also be used to image brain activity. In addition, extrinsic optical
absorption contrast agents can be used to provide molecular imaging of
biomarkers
[148].
Strengths and Weaknesses
PAT benefits from the same advantages of optical imaging and US
imaging, without the major disadvantages of each technique
[149]
(Table 5.15). It combines the high contrast from light absorption with
the high resolution of the US imaging response signal
[147].Ithasa
high SNR, due to the fact that nonligh t-a bsorbi ng molecules do not
produce a signal, effectively making the images free of background
noise. In contrast to CT or MRI, PAT is nonionizing, does not necessarily require contrast agents, and could potentially deliver real-time
scans with extremely high resolution
[143].
Table 5.15 Key facts of PAI
Typical
applications
Strengths and
weaknesses
Recent
developments
157Diagnostic Procedures
Research potential
and future trends
Oncology Nonionizing
High contrast and
resolution
Limited imaging
penetration depth
Long data collection
times
First
introduction
to clinical use
Reduction of
acquisition
times
4D PAT
Intravascular PAT
Image-guided
therapy
Disadvantages are the long data collection times, from 24 seconds up
to 8 minutes in existing 3D PAT systems
[150]. In general, many optical
techniques suffer from a limited imaging depth compared to MRI or CT.
Until now a maximum imaging depth of 7 cm is possible
still extraordinary for optical imaging systems
[148].
[143], which is
Recent Developments and Current Research
PAT is a very promising technology, with high capabilities and still
extensive research potential
[151].
Long acquisition times are the main challenge in the development of
PAT. Recently, array-based PAT systems have been developed to reduce
the imaging time. In addition, high frame rate PAI has been performed in
2D using LAs
[150].
4D PAT in particular would benefit from shorter acquisition times.
4D PAT techniques generate motion pictures of imaged tissue. There are
already devices integrating time resolution with 3D spatial resolution, but
further research is still needed. Enabling real-time tracking of dynamic
physiological and pathological processes at hundred micrometer- and
millisecond resolutions is already technically possible. It can also be used
to image drug delivery and pharmacokinetics, among other things
[152].
Intravascular photoacoustic applications are another area currently
under research. They have been only performed in ex vivo studies based
on intravascular US catheters, and may be used to detect atherosclerotic
plaque
[153].
The ability to support thermal therapies through image guidance—
during cancer treatment, for instance—has already been demonstrated,
although the thermal maps used have primarily been 2D. Unfortunately,
2D visualizations of heating patterns do not provide sufficient accuracy, so
it was not possible to use PAI to effectively steer the heating focus into
158 Biomedical Engineering in Gastrointestinal Surgery
the tumor. This often left parts of the tumor unheated while generating
too much heat in the surrounding healthy tissues. 3D PAT systems for
the purpose of image-guided therapy are currently under development.
The visualization of 3D temperature distributions is desirable in order to
provide comprehensive temperature monitoring during clinical applications. Currently, they only have been tested with excised tissue or animal
specimens
[150].
There are many promising possible applications for PAT. These
extend to various pathologies such as traumatic brain injury, cancer, and
intestinal fibrosis
[154]. Photoacoustic endoscopy, simultaneous func-
tional and molecul ar PAT, PAT of gene expression, Doppler PAT for
flow me asurement, photoacoustic mapping of sentinel lymph nodes, and
multisc ale PAI are conceivable and in development
[148]. Advanced
studies have identified promising potential in breast cancer diagnostics
[147]. Another application of photoacoustic technology is to link spec-
troscopic PAI to conventional transrectal US for prostate cancer detection and evaluation. PAT may also be used for therapeutic monit oring
in the future
[155].
5.6.8 Conclusion
Optical imaging technologies are a rapidly emerging field in medical
diagnostics. Different technologies have been introduced for a broad
range of new applications during the past decade. A general trend in
medicine is a rising pressure on health care due to an aging population,
especially in developed countries. Changing demographics are resulting
in a higher prevalence of major diseases, as well as an increased pressure
on the health care systems to maintain medical supplies. Therefore, earlystage diagnostics can be crucial. Optical technologies offer great potential
not just due to their—in many cases superior—resolution, but also due to
their inherent ability to save costs compared to conventional methods. In
the short-term, new applications will be introduced as optical imaging
technologies mature. In the long-term, completely new modifications
will be introduced. They are expected to be of even greater value in the
future, especially in some of the most meaningful and fastest-emerging
medical fields like cardiovascular imaging and gastrointestinal oncology. In
fundamental medical research and approaches toward personalized medicine, optical technologies are considered fundamental for driving innovations and developments. The full potential of optical imaging in medicine
Diagnostic Procedures
159
has not yet been exploited. These technologies hold the chance to revolutionize diagnostics and health care in gastrointestinal medicine.
5.7 ENDOSCOPY
Endoscopy is the art to look into the interior of an object. In medicine,
the term is broadly used to describe any examination of the inside of
the body.
In former times, many attempts had been made to look into the interior of the human body, but due to technical limitations, this was mainly
confined to the oral cavity, the rectum, the vagina, ear, and nose.
Among the numerous constraints, one major problem was illumination.
A big step forward was the development of a light source by Bozzini about
200 years ago, but even after Bozzini’s invention of an illumination system,
quite a number of further hurdles had to be overcome (
Further necessities for the exploration of anatomical lumina and cavities are adequate optical systems and auxiliary features like insufflation and
working channels. Nowadays, after a long history of technological innovations (
Table 5.16), dedicated endoscopes are available for literally all
use cases.
Today, two different concepts prevail: the flexible or rigid design.
Beyond, there are two types of image acquisition and transmission.
Normally, the tip of the endoscope is fitted with an objective lens and the
image is transmitted with optical components such as prisms and lenses or
Fig. 5.33).
Figure 5.33 (A) Bozzini’s “Lichtleiter”; (B) exploration tube. From a reprint of Bozzini
1807.
160 Biomedical Engineering in Gastrointestinal Surgery
Table 5.16 Short history of endoscopy
1807 Bozzini Instruments for examinating the oral cavity, the
rectum, and the vagina (light conductor)
1822 Beaumont First human endoluminal endoscopic examination
B1908 David Integration of a bulb into existing endoscopes
1901 von Kelling Endoscopic examination of the peritoneal cavity
1950 Fiber optics—Hopkins Fibroscope
1952 First gastroscope (Olympus, Suguira1Uji)
B1980 Chip-on-the-tip endoscopes
2005 Multichannel endo scopes
2007 Multiarm endoscopic intervention devices
glass fibers to the eyepiece. More frequently, the tip of an endoscope may
be fitted with a camera, which is generally a CCD camera (“chip-on-thetip” design). It converts the optical signals into electrical signals, and
transmits them to the camera controller.
The field of application of endoscopy is multifaceted, as is the design of
endoscopes. The names of these endoscopes indicate the area of use. There
are arthroscopes to look into joints like the knee, ENT endoscopes for the
exploration of ear and nose, gastrointestinal endoscopes for the stomach
and the large bowel, gynecology endoscopes to examine the vagina, laparoscopes to look into the abdominal cavity, neurology endoscopes, pulmonary
endoscopes (so-called bronchoscopes), urology endoscopes (urethroscopes),
and others. Each field additionally has application-specific designs. Both
flexible as well as rigid endoscopes are used.
Minimally invasive surgery (MIS) is one of the best-known therapeutic applications of endoscopy. This comparatively small but increasing field
of application mainly belongs to laparoscopy.
5.7.1 Rigid Endoscopes
Rigid endoscopes are the oldest type on the market. They are used in
the majority of surgical endoscopic applications and enable endoscopists
to visualize the surface of organs, their vessels, or pathological changes
without large incisions of the body and delivering a view even more
clear than wi th the naked eye. The main design criteria are the viewing
angle, depth-of-fi eld, magnifica tion, image brightness, image quality,
distortion, and image size, which have to be appropriately balanced.