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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_605_Библиотеки_им_академика_М_И_Перельмана.pdf
141Diagnostic Procedures
the fact that light is applied in order to acquire an image [97].Ingeneral, microelectronic advances such as high-speed CMOS or adaptive
optics, more sophisticated reconstructional algorithms, and improved
real-time tracking algorithms that allow the OCT scanner to target a
continuously moving area will help to overcome current limitations
[98]. Furthermore, longer-wavelength OCT may help to improve the
detection of microstructural changes
the additional detection of polarization properties
[99]. Further developments into
[100] and its accom-
panying contrast enhancements will be of particular interest in dentistry
[101]. OCT has a lso shown the potential to match the imaging sensitiv-
ity of histology when carrying out neurosurgical imaging of brain tissue
for tumor examinations. F-F OCT has captured slices of tissue samples
en-face and in 3D at a resolution of 1 µm, with a penetrat ion depth of
around 200 µm
[102].
5.6.2.3 Fourier-Domain Doppler Optical Coherence Tomography
An extension to the conventional F-D OCT, F-D D. OCT is an
OCT modification used to determine objects’ velocities, especially in
blood flow measurements. It can also be applied to estimating
elasticity by detecting relevant phase information in the interference
signal.
Characteristics of the Modification
F-DD.OCTcanbeappliedinT-DOCTandF-DOCT.InT-D
OCT, the Doppler-frequency-shift of the interference modul ation is
directly measured in order to determine the axial velocity component.
However, the simplest and most common methods use the principle of
F-D OCT, and are referred to as phase-resolved Doppler OCT. This
procedure is based on the linear relation between the phase shift of
sequentially detected interference signals and the axial velocity of the
examined sample. Due to high phase-stability of spectral domain F-D
OCT, it is usually the modification of choice for Doppler flow measurements
[103].
Strengths and Weaknesses
The F-D D. OCT allows in vivo real-time 3D flow imaging at a
micron scale and provides finely resolved 4D imaging
displayed bidirectionally in false colors
[105]. Doppler information can be
[104] that can be
combined with regular OCT imaging. Current devices deliver performances of ,50 µm spatial resolution and , 0.6 mm/s velocity precision
[106] (Table 5.11).
142 Biomedical Engineering in Gastrointestinal Surgery
Table 5.11 Key facts for F-D D. OCT
Typical
applications
Strengths and
weaknesses
Recent
developments
Research potential
and future trends
Ophthalmology
Dermatology
Cardiovascular
medicine
Real-time flow
measurements
,50 µm spatial
resolution
,6 mm/s
velocity
precision
In vivo real-
time
imaging
Combination
of Doppler
and regular
OCT
Further clinical
applications
Finer resolution
More advanced
computations
Recent Developments and Current Research
Several useful strategies, such as dual beam F-D D. OCT and narrow
bandwidth phase reference OCT, have been recently reported to increase
F-D D. OCT’s sensitivity. Among other things, it is currently being investigated whether F-D D. OCT can create angiographic images that are capable of substituting for regular fluorescein angiography
[107]. Future
improvements are mainly expected to arise from solving problems with the
computational complexity of image processing, but also from the development of new high-speed swept source lasers
[108]. Additionally, the devel-
opments of new sterile probes and ongoing miniaturization efforts may
allow OCT to offer further applications in intraoperative use
[109].
As a whole, the new technology of OCT has quickly r isen to prominence, and can be expected to gain further relevance in the future. The
full potential of the technology has not yet been exploited. As OCT
matures, new applications will arise and support further g rowth in
the field.
5.6.3 Optical Fluorescence Imaging
Fluorescence imaging or fluorescence microscopy is a valuable technique
for histology and the imaging of living specimens
broad variety of preclinical investigations, and there is great interest in finding further ways to translate the principle into clinical applications
Optical fluorescence imaging provides cellular and subcellular resolutions
and image enhancement in 3D and real-time
is one of the key technologies capable of advancing molecular imaging. It
has also been found to have great use in preclinical research, and has aided
recent advances in proteomics, genomics, and oncology
[110].Itisusedina
[111].
[112]. Fluorescence imaging
[111,113].
143Diagnostic Procedures
In fluorescence imaging, fluorescent markers are employed to enhance
regular images. The markers reflect the light at a specific wavelength and
color. An external light source of a well-defined wavelength, supplies
photon energy which is absorbed by the specimen and molecules. The
absorbed light is reradiated almost immediately at characteristic wavelengths. This characteristic amount of energy makes it possible to identify
the substance imaged
[114]. The readout in optical fluorescence imaging
is usually realized via a spectral sensitive wide-field CCD or a PMT used
for raster-scans
[112].
Targets in fluorescence imaging may be endogenous molecules and
proteins, such as collagen nicotinamide, adenine dinucleotide, flavin, and
porphyrins (autofluorescence)
[115]—so-called endogenous fluorophores.
However, the range of natural fluorophores is small. Artificial markers were
developed to enable excitation of the relevant tissue
[116]. Different mar-
kers are employed according to the nature of the investigation. Examples
include fluorescent dyes that are directly taken up by the targeted cells.
Another commonly used option is to employ specially raised antibodies
that target and label the molecules of interest when induced
[114].
Optical fluorescence imaging can be applied in a trans-illuminating
and an epi-illuminating fashion. In trans-illuminating fluorescence imaging, the examined object is placed between a broad-beam source and the
detector. The light beam induces fluorescence inside the object that is
measured by the detector on the opposite site. In epi-illuminating fluorescence imaging, the object is placed on a base plate. Again, a light source
induces the energy to cause an excited state in the molecules. Unlike
trans-illuminating fluorescence imaging, the readout module that detects
the fluorescence is situated on the same side of the object as the light
source
[112].
Strengths and Weaknesses
Fluorescence is free of radiation and mainly harmless, except for possible toxicity of the markers
molecular processes ex vivo and in vivo
[111]. It enables the imaging of cellular and
[111]. It is cost- and time-
effective and relatively easy to use, as many investigators will already be
familiar with this technique
[117]. In clinical applications, the detection
of fluorescence properties adds increased contrast to white light reflectance imaging. This provides the surgeon with a better foundation to distinguish between different types of tissues
extend from dermatology over oncology to gastroenterology (
[118]. Typical applications
Fig. 5.26).
Perhaps the largest limitation of conducting optical imaging via fluores-
cence is the low penetration depth. Micro- and macroscopic components
144
Biomedical Engineering in Gastrointestinal Surgery
Figure 5.26 Imaging of fluorescence labeling aids tumor excision. (A) Normal white
light: the malignant lesion is invisible; (B) using fluorescence, the lesion can now be
seen; (C) mapping A 1 B enables precise excision. From Orosco RK, Tsien RY, Nguyen
QT. Fluorescence imaging in surgery. IEEE Rev Biomed Eng 2013;6:17887.
in the tissue collectively absorb the light at the visible and ultraviolet wavelengths, limiting the effective penetration depth to a few hundred microns.
Higher penetration depths can be achieved through the use of NIR and
far-red spectra. In this case, detectable signals can be measured after traveling the tissue over the span of several centimeters
[112].
Recent Developments and Current Research
The imaging of fluorescence properties has already gained great
importance in the medical imaging field. So-called “smart probes” are
already able to detect fluorescence and provide the surgeon with intraoperative real-time and high-contrast delineation of healthy and pathologic
tissue. This augmentation enhances the ability to protect structures like
fine nerves and can improve the surgical outcome.
Further more, the development and commercialization of small-animal
fluorescence imaging systems has progressed rapidly over the past decade.
Their vast variety of components and approaches has been used for preclinical assessments of therapeutic methods and medication, as well as for
development in the pharmaceutical sector
[112].
There is a substantial interest of implementing novel optic fluorescence
imaging modalities for clinical use . There, they could efficiently aid in quantitative screening, disease diagnostics, and posttreatment monitoring. For surgical applications, the development of optimal and tissue-specific contrast agents
will help to extend the exploitation of optical fluorescence imaging
[117].
5.6.4 Hyperspectral Imaging
Hyperspectral imaging (HSI) is a technique that analyzes a wide spectrum
of light instead of just assigning primary colors (red, green, blue) to each
pixel. The light striking each pixel is broken down into many different
spectral bands in order to provide more information on what is imaged.
The algorithms and the image processing methodologies associated with
145Diagnostic Procedures
HSI are a product of military research, and were primarily used to identify targets and other objects against background clutter. In the past, HSI
has seen civil applications, and has particularly been useful in satellite
technology. It might become an inexpensive, promising, and quick tool
for the assessment of tissue conditions at diagnosis and during surgery.
The medical applications include forensics, detection of colorectal and
gastric cancer
[119,120] or ulcers [121].
In HSI, the unique color signature of an individual object can be
detected. Unlike other optical technologies that can only scan for a single
color, HSI is able to distinguish the full color spectrum in each pixel.
Therefore, it provides spectral information in addition to 2D spatial
images (
Table 5.12).
Many spectrally sensitive sensors collect hundreds of different narrow, adjacent spectral bands. In medical applications, HSI is often
referred to as medical HSI or MHSI. MHSI provides near-real-time
images of biomarkers in tissue. The key benefit is the potential to better
distinguish between different tissues based on their spectral character istics and colors
[122], as seen in Fig. 5.27.Doctorsdonothavetomake
an educated guess; instead, specific wavelengths can be inter p reted by
the system aut omaticall y. Even the smallest areas of malignant tissue
could be distinguished. Furthermore, the assessment of functional properties can be aided. The color-enhanced images make it possible to
clearly discriminate between different elements in
Fig. 5.28.
With a hyperspectral camera, the light is captured through a lens and
split into different spectral lengths by a dispersive element such as a prism
or a diffraction grating
[123]. Also possible is a recording of different
wavelengths at different positions in the FOV. The heart of the MHSI
camera is a CCD or CMOS detector array that reads out the information
inherent to the captured light (
Fig. 5.29).
Table 5.12 Key facts of HSI
Typical
applications
Dermatology
Gastrointestinal
diseases
Ear, nose and
throat diseases
Strengths and
weaknesses
Additional
Slow
Very expensive
imaging
information
acquisition
rates
Recent
developments
First translations
to medical
application
Introduction of
first
miniaturized
prototypes
Research potential
and future trends
Further
miniaturization
Introduction
to mass
production
Enhanced image
processing
146
Biomedical Engineering in Gastrointestinal Surgery
Figure 5.27 Tumor region. Expert labeling (left) and classifier prediction of tumor
regions (right). From MITI.
Figure 5.28 Hyperspectral imaging of a carcinoma of the larynx: (A) Intraoperative
image: clinical assessment normal 5. blue (black in print), pathologic 5. red (gray
in print); (B) yellow (white in print): falsely negative, blue (black in print): correctly
negative, red (dark gray in print): correctly positive, green (light gray in print): falsely
negative; (C) probability of pathologic lesion: depending upon color intensity, the
likelihood is higher or lower that this pixel is malignant (red, gray in print), or normal
(blue, black in print). Courtesy: Dr. Wiebke Laffers, ENT, University of Bonn.
The camer as can be customized to meet the wavelength or the
application-specific performance needed. Further more, the rig ht
calibration is crucial. The tissue imaged provides a complex multicolor
data set. In order for the analyzing algorithms to extract the color
information needed, the distinct reference spectra have to be implemented precisely.
Strengths and Weaknesses
HSI provides additional diagnostic information that can be exploited
in var iou s dif ferent ways. It can aid in the discrimination bet ween
healthy and malignant tissue
[125].Furthermore,automateddetection
of pathologies is possible. A vast number of potential applications have
been shown for this novel imaging technology—for instance, the accuracy rate of tongue tumor detect ion with computer-aided HSI is 96.5%.
Diagnostic Procedures
147
Figure 5.29 Schematic setup of a hyperspectral camera. From Andor Technology.
Schematic Setup of hyperspectral imaging camera, ,
PR14/011.asp?
. ; [accessed 22.09.16].
http://www.truepr.co.uk/news/at/
Probably the greatest weakness of HSI is the technologies’ immatur ity.
Current devices are highly expensive, large, and difficult to use
[123].
Their low frame rates are another disadvantage negatively affecting the
possibility of further medical application.
Recent Developments and Current Research
Today, most HSI use is confined to laboratories. The devices currently
available are large, expensive, and difficult to handle. Making HSI cheaper, user friendly, and more compact is the major goal in HSI research.
148 Biomedical Engineering in Gastrointestinal Surgery
Further more, existing HSI cameras are only able to scan one line
at the time, mainly due to their design and mechanically moving
components, limiting frame rates. This restraint makes the technology
unsuitable for time-critical applications and requires further research.
On the other hand, extended research is currently being conducted
on microelectronic parts. Innovative designs for CMOS arrays using elements such as Fabry-Pe´rot staircase concepts have helped create the first
miniaturized prototype, sized at a little over 1 cm
3
. This prototype was
first presented at the SPIE Photonics West conference in 2012. Further
miniaturization down to the millimeter scale is needed if the highly interesting opportunity of integrating with endoscopes and other miniature
devices is to be pursued. HSI for medical purposes has not yet reached
mass production and a broad market. If mechanical components are
replaced by etched silicon, production could integrate well with existing
process flow used for chip manufacturing.
Another field of research is the development of algorithms for the
automated detection of malignant tissue
[124].
The technology has great potential for implementation and further
translation into medical applications due to its ability to provide additional
diagnostic information in examined objects
[125]. As a result, HSI will be
increasingly meaningful in the future.
5.6.5 Diffuse Optical Imaging (Near-Infrared Optical Tomography)
Diffuse optical imaging (DOI) is a technique that is also referred to as diffuse optical tomography, near-infrared optical tomography,orfluorescence diffuse
optical tomography. It is used for examination of biological tissues at a mac-
roscopic scale
Table 5.13 Key facts on DOI
Typical
applications
Preclinical
research
Neurology
Oncology
Surgery
[126] (Table 5.13).
Strengths and
weaknesses
High depth
penetration
Portability
Very low
resolution
High frame
rates
Recent
developments
Combination
with new
biomarkers
Research potential
and future trends
Image
reconstruction
Introduction to
clinical practice
Overcoming the
problems of low
resolution
149Diagnostic Procedures
In general, tissue is illuminated with visible or NIR light. The scattered light is received by photodetectors to acquire image information. It
allows tomographic (3D), noninvasive reconstructions of optical tissue
properties for biomedical applications. Besides information about the tissue, the concentration of oxygenated and deoxygenated hemoglobin can
also be measured to get information about spatial variations in oxygenation and blood volume within the tissue. There are continuous wave systems, time-domain systems, and frequency-domain systems.
DOI has various clinical applications: functional brain imaging, imaging for breast cancer
vessels and joints is also possible
[127], or wound imaging [128]. The examination of
[129]. DOI is beginning to be accepted
as a method of choice for studying brain development in infants.
DOI uses visible light or NIR light at a wavelength of 6501000 nm.
It is projected across an object in parallel beams to an array of sensitive
photodetectors. If this is repeated at various angles, a 3D image of the
tissue can be acquired.
In contrast to other tomographic imaging modalities, DOI does not
use cross-sectional images. The reconstruction of 3D images is achieved
by mathematical algorithms, which refer to the so-called forward and
inverse problem. One way to improve the quality of the image reconstruction is to use a priori structural information provided by an alternative imaging modality, such as MRI. This is used to construct a 3D tissue
model which is then used to solve the forward problem—in other words,
to predict the distribution of light at the detector locations.
In general, light interacts with biological tissue predominantly by
absorption and scatter ing. Biological tissue is a highly scattering
medium, causing the photons to take very irregular paths. There are
several molecules that have characteristic absorption spectra. In particular, the spectra of oxyhemoglobin, deoxyhemoglobin, and cytochrome
oxidase differ considerably. Hemoglobin provides an indicator of blood
volume and its oxygenation, whereas the cytochrome enzymes indicate
tissue oxygenation. Like these natural chromophores, th ere are optical
contrast agents such as Indocyanine Green that are used for fluorescence
imaging, which provide high sensitivity and specificity for biomedical
diagnosis
[130].
Strengths and Weaknesses
Red and infrared light passes relatively easily through structures as the
skull, brain, and breast, and is well tolerated in large doses. Unfortunately,
the high scattering results in a very low resolution in the acquired images.
150 Biomedical Engineering in Gastrointestinal Surgery
Current devices provide a spatial resolution of approximately 1 cm3.
Image artifacts are a common problem of DOI. An increase in resolution
is possible, but DOI will never compete with other imaging techniques
like radiography, US, or MRI in terms of spatial resolution. A large
number of measurements are needed in order to minimize these artifacts
[131]. In general, the more accurate the mathematical model,
the more computationally demanding the reconstruction algorithm is.
Consequently, real-time imaging is only possible at the expense of image
quality.
Nevertheless, DOI offers several distinct advantages in terms of sensi-
tivity to functional changes, safety, and costs
[132]. Advantages are the
large optical penetration depth of several centimeters, the high temporal
resolution, the high intrinsic contrast associated with hemoglobin, and
the capability of spectral discrimination of multiple contrast agents
[133].
DOI provides access to a variety of physiological parameters that otherwise are not accessible, including subsecond imaging of hemodynamics
and other fast-changing processes. Furthermore, DOI can be incorporated into compact, portable instrumentation that allows for bedside monitoring at relatively low costs.
Recent Developments and Current Research
Though DOI has been under research for many years, it is still primarily a laboratory-based technique that has still not reached its full
potential in routine clinical use due to technological limitations.
The most recent development is the usage of DOI in conjunction
with upconverting nanoparticles (UCNPs), a recently developed class of
luminescent biomarkers. They are in several aspects superior to organic
dyes and quantum dots. For DOI, the multiphoton process involved in
the upconversion process can be used to obtain images with unprecedented resolution. The unique properties of UCNPs make them
extremely attractive in the field of biophotonics. UCNPs have already
been applied in microscopy, small-animal imaging, multimodal imaging,
and highly sensitive bioassays
[134].
The further capabilities of DOI in optical breast imaging are still
under research. Here, the technique can reveal changes in blood volume
and oxygen saturation that are specific for early stages of cancer. DOI
may identify cancers before they are structurally evident (i.e., visible on
X-ray) because it focuses on these functional changes
[132]. Other medi-
cal studies address the prevention and treatment of Alzheimer’s disease or
stroke rehabilitation.