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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Approach to Automatic Segmentation of Atherosclerotic Plaque in B-images Using Active Contour Algorithm Adapted by Convolutional Neural Network to Echogenicity Index Computation</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Jiri Blahuta</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Tomas Soukup</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Petr Sosik</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Silesian University in Opava, The Department of Computer Science</institution>
          ,
          <addr-line>Opava</addr-line>
          ,
          <country country="CZ">Czech Republic</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>The presented paper is dedicated to image processing of ultrasound B-images in neurosonology. Atherosclerotic plaques in in-vitro B-images are analyzed in this study. The content is divided into two core parts. The first one is focused on computing Echo-Index value inside the atherosclerotic plaque as a defined Region of Interest. From achieved results is obvious that the EchoIndex is well-reproducible value in general. Totally of 278 images were analyzed by two non-experienced observers and by an experienced sonographer to validate the result. Basic statistical descriptors were calculated to judge the level of agreement. In this part, the ROI were selected manually. The second part is focused on approach to automatic selection of the ROI. Manual drawing of the border is time-consuming. Our idea is to use active contour algorithm (ACM; Active Contour Model) to eliminate the black background from the displayed plaque. Using ACM can be useful way to select ROI automatically. The main issue is to separate the shape of the plaque from neighbor structures, especially from the bottom of the tube. To adapt ACM, the principle of the convolutional neural network can be used to extract the feature of the shape to select a correct ROI. Thus, CNN can be trained and learnt to adapt number of iterations of the ACM (or another parameter) based on supervised learning from properly bordered examples. The main disadvantage is time-consuming process and high performance to be needed to train and learn the CNN. In fact, in this study, there is no real design of CNN but the primary goals are defined to realize in future.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        In recent few decades, ischemic stroke caused by
atherosclerosis is one of the top causes of the mortality
worldwide. In modern neurology, ultrasound B-imaging is
one of the diagnostic tools to detect atherosclerotic plaques
in general. The diagnostic ultrasound [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ] is a fast,
noninvasive examination which is also combined with
another modalities, such as CT or MRI. The atherosclerotic
plaques are well displayed in B-image but the limitation is
to understand their complex structure to find some
markers to predict severe problems. Increased echogenicity of
the plaque can be one of the detectable features as well.
Principles and methods of neurosonology are described in
[
        <xref ref-type="bibr" rid="ref2">2</xref>
        ].
      </p>
      <p>In 2011, we developed a software tool B-MODE
Assist using binary thresholding algorithm to detect
hyperechogenicity of the substantia nigra. Due to general
properties of B-images in grayscale, the software can be used
also for the atherosclerotic plaques but in slightly adapted
form.</p>
    </sec>
    <sec id="sec-2">
      <title>1.1 Input B-images</title>
      <p>For this research, a set of 278 B-images (in-vitro) is
processed. In Fig. 1, an example of the B-image in which the
plaque is displayed, is stated.</p>
      <p>Our recent research has been based on computing the
echogenicity index (called Echo-Index) to comparison of
the risk of the plaque using our developed software and a
visual assessment by an experienced sonographer.
2</p>
      <sec id="sec-2-1">
        <title>Echogenicity Index in A Free-Hand ROI</title>
        <p>
          The echogenicity index (Echo-Index) is one numeric value
which could corresponds with the echogenicity grade. The
Echo-Index is computed in closed Region of Interest, in
this case in the atherosclerotic plaque. To obtain the
EchoIndex, we use own developed software tool B-MODE
Assist, originally developed for substantia nigra echogenic
area computation. Hyperechogenic substantia nigra is a
detectable parkinsonic marker in B-image. The algorithm
is fully described in our previous publications, e.g. [
          <xref ref-type="bibr" rid="ref3">3</xref>
          ] and
[
          <xref ref-type="bibr" rid="ref6">6</xref>
          ]. The important clinical study based on this software
have been published in 2014 [
          <xref ref-type="bibr" rid="ref4">4</xref>
          ] and [
          <xref ref-type="bibr" rid="ref6">6</xref>
          ]. The basic
principle can be described by the following steps:
1. Load an input image (in bitmap or DICOM format)
which is converted into 8-bit grayscale depth
automatically
2. Select a window in which the examined structure is
shown, i.e. atherosclerotic plaque
3. Select a Region of Interest (in the case of
atherosclerotic plaques, ROI of a free shape); the ROI is a
binary mask
4. Inside the ROI, the area is computed according to
threshold
(a) The area is computed as the number of
remaining pixels after binary thresholding algorithm
(b) For each threshold T in the range of 0 to 255,
the number of pixels is computed
(c) The number of pixels is converted into real mm2
according to displayed scale, i.e. the window
size in step 2 (the size of 20 20 mm is used)
5. All values of the area for all 256 thresholds are drawn
as a "curve" (256 isolated values); see Fig. 2.
        </p>
        <p>
          In the case of analysis of the substantia nigra, this
algorithm was genuinely useful. The speed of decreasing of
the area inside the ROI has been observed. For substantia
nigra, an equal shape of the ROI is used; an elliptical shape
with area of 50 mm2. It was sufficient for clinical studies,
e.g. [
          <xref ref-type="bibr" rid="ref5">5</xref>
          ] to statistical analysis of the echogenicity grade of
the substantia nigra.
        </p>
        <p>In the case of atherosclerotic plaques, the main
difference is the fact that ROI is selected by a free-hand shape
and the area is different for each plaque. In Fig. 2, six
different shapes of the plaque are presented as a closed ROI
selected in the window 20 20 mm.</p>
        <p>The idea of the Echo-Index is considered as a number
which can describe echogenicity grade inside the plaque;
inside the free-hand ROI. Let H is the brightness value of
a pixel and T to be the threshold then AT is the computed
area for each threshold T in the range of 0 T 255. The
sum is computed
255
AREASU M = å AT</p>
        <p>T =0
and the AREASU M value is divided by 100</p>
        <p>Due to the principle of binary thresholding, for lower
echogenicity grade, the Echo-Index should be lower and
for higher echogenicity the Echo-Index should be higher.
This is an assumption which proceeds from the principle
of binary thresholding. Thus, in the case of low
echogenicity, for low T threshold the computed area should be very
low and vice versa. In consequence of this principle, the
sum for low echogenicity is low and for high echogenic
ROI the sum is higher. During the future work it should be
confirmed whether this idea is correct or not; especially in
comparison with visual assessment.
2.1</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>General Reproducibility Assessment of the</title>
    </sec>
    <sec id="sec-4">
      <title>Echo-Index</title>
      <p>
        The goal of the pilot study [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ] was to prove the
reproducibility of the index; total of 284 B-images were
analyzed using this software with this following conditions:
• 2 independent non-experienced observers measured
all images two times
• each observer measured for 2 weeks; for one week
the first has been performed (278 images) and for
following week the second measuring has been
performed (the same set of 278 images)
• all images have the same resolution but the algorithm
can be used for different resolution
      </p>
      <p>The reproducibility of the Echo-Index has been proved
as well-acceptable in general considering inexperience in
neurosonology of both of the observers. The Echo-Index
does not evince significant difference in case of the same
image analyzed by each observer; each of them draws ROI
slightly in different shape. Table 1 shows an example of
computed Echo-Index for 22 images between 2 observers;
there are no significant differences due to similarly drawn
ROI manually by each observer.</p>
      <p>Some images from the set were also analyzed by an
experienced sonographer; ROI drawn precisely; and very
similar values for Echo-index have been achieved.
• range, variance for Echo-Index values measured by
observer1 - first measurement R11, var11
• range, variance for Echo-Index values measured by
observer1 - second measurement R12, var12
• range, variance for Echo-Index values measured by
observer2 - first measurement R21, var21
• range, variance for Echo-Index values measured by
observer2 - second measurement R22, var22
• maximum and mean difference between two
observers max(obs), mean(obs)
• correlation coefficient between Echo-Index values
from 2 observers robs
• maximum and mean difference between
measured values from observer1 between two weeks
max(obs12w)
• maximum and mean difference between
measured values from observer2 between two weeks
max(obs22w)
• correlation coefficient of the Echo-Index values from
observer1 between 2 weeks robs1
• correlation coefficient of the Echo-Index values from
observer2 between 2 weeks robs2
Obtained results are summarized in Table 2.</p>
      <p>Maximum values are stated in absolute value because
the difference of the Echo-Index between observers or
measurement can be also negative. In the case of
measurement during the first phase (week), for 220 values
from 278, i.e. 79.1 %, the difference under 100 between
observers has been achieved. In the case of the second
phase, for 214 values from 278, i.e. 76.9 %, the
difference under 100 between observers has been achieved.
Due to achieved results, the Echo-Index can be considered
as well-reproducible value between 2 independent,
nonexperienced observers and also between 2 measurements
from the same observer.
In general, the basic idea "smaller Echo-Index means
lower echogenicity" which was not confirmed from the
point of view of an experienced sonographer, who
compared images with different plaque risk level in which
different echogenicity grade is obvious and there is no
significant correlation between visual assessment and computed
Echo-Index.</p>
    </sec>
    <sec id="sec-5">
      <title>The idea of decision-making system to risk assessment based on Echo-Index value</title>
      <p>
        Although the Echo-Index seems like a reproducible value,
it must be thoroughly examined if the value corresponds
with visual assessment by an experienced sonographer.
The idea is to create a decision-making expert system
using a knowledge base of echogenicity grades determined
by experienced sonographer. In the future, the
decisionmaking system can be developed to use as a tool to
evaluate the probability risk of the plaque in accordance with
Echo-index value in determined intervals. A draft of the
system were presented in [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ]. Some real case studies to use
ultrasound imaging to judge risk level of the
atherosclerosis are summarized in [
        <xref ref-type="bibr" rid="ref10">10</xref>
        ].
3
      </p>
      <sec id="sec-5-1">
        <title>Active Contour to Detect The Plaque</title>
        <p>This part of the paper is focused on automatic selection of
the ROI instead of manual process. A manual selection
of the plaque is used up to now. However, each selection
of the plaque takes up to 2 minutes, see in Fig. 2 that
some shapes are relatively simple but another one are very
complex to its exact selection.</p>
        <p>
          We need to find a way how to select the plaque from the
input B-image (Fig. 3) automatically. The idea is based
on removing the black solid background; B-image can be
comprised of the background in the major. Put differently,
it is desired to detect edges of the plaque to select the
Region of Interest in which the Echo-Index is computed. The
active contour algorithm is one of the segmentation
techniques which is used to detect the background and to
extract the foreground of the image. It is based on the
iterative process. In many recent studies were demonstrated
that active contour segmentation technique is well
applicable for medical images against its complex
morphological structure. One of many studies focused on using active
contour segmentation in clinical image processing is
available in [
          <xref ref-type="bibr" rid="ref7">7</xref>
          ].
        </p>
        <p>The goal of the active contour is to remove the black
background and to extract the border of the plaque. See in
Fig. 1. As a result, the goal is to execute the steps 1 to 3
automatically. The algorithm is based on iterative steps to
acquire the edge which separates segmented objects in the
image.
The sensitivity is the primary parameter; how
sensitive the detection is. Thus, what is considered as
background and what is considered as foreground bordered by
the edge. For example, we tried to segment the plaque
using threshold level segmentation with 3 different
thresholds (T = 15, T = 25 and T = 40). You can see in Fig. 4
that higher threshold level has the influence on segmented
area.
In the case of T = 40, the plaque is segmented as
isolated object with no bottom of the tube. To get an
optimal result, the threshold is important. In the case of active
contour, the number of iterations is an important
parameter like the threshold. At the beginning, initial mask is set
and increasing of iterations produces better border of the
object.
In Fig, 4 is demonstrated that after thresholding there are
many isolated objects with small area. We need to create a
ROI mask which is one closed boundary (one segmented
object). Using Active Contour could be a useful way to
perform it.</p>
        <p>Initially, ACM with 25 iterations has been performed.
See Fig. 5 in which the results are demonstrated for 2
different images.</p>
        <p>The results can be used in general but as an
experimental study to further improvement. Firstly, we need to
separate the plaque from the tube bottom. See Fig. 6 for some
examples of the segmented masks.</p>
        <p>Surely, we can increase the number of iterations in the
algorithm but no one object is get. When higher number
of iterations is used, the border is get more precisely but
still more than one segment is obtained.
3.2</p>
      </sec>
    </sec>
    <sec id="sec-6">
      <title>Area Detection Using Clickable Input</title>
      <p>
        Better results of the ACM were achieved with
semiautomatic input. After selection of the window with the
plaque, click into the plaque to understanding which
segment is useful for us and set the threshold level (as H
intensity level). This level is automatically computed by Otsu
algorithm which can be well applicable as a segmentation
method for medical images, for example in a study from
2012 [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ]. The principle of the ACM is to find gradient to
separate edges and the background. In Fig. 8 a magnified
segment in which the border between plaque is displayed.
If we can set the threshold H, the sensitivity can be
adjusted; which H is the lowest value of the background.
      </p>
      <p>In Fig. 9 initial rectangle ROI and segmented area using
ACM after only 10 iterations is shown.
B-images have a complex structure with a lot of isolated
pixels caused by noise and artifacts, see Fig. 7. To faster
and more accurate results of ACM, the brightness
enhancement can be recommended as a pre-processing phase
at the beginning. The idea is to "clear" image from isolated
pixels and enhance the brightness to better finding the
contour. Let H to be brightness of the pixel. For example, all
pixels with H &lt; 20 can be set as H = 0 (as the background)
and all pixels with H &gt; 80 are transformed as H + 30. The
effect is presented in Fig. 10.</p>
      <p>In Fig. 8 there are results after for H = 20 and click into
the plaque. The results are more accurate in comparison
with using ACM for the whole image.</p>
      <p>The main benefit of this transformation is to eliminate
noise in low echogenicity levels but some image artifacts
are enhanced too. Although it can be useful pre-processing
phase to achieve better ACM results.
4</p>
      <sec id="sec-6-1">
        <title>Adaptation of Active Contour Using A</title>
      </sec>
      <sec id="sec-6-2">
        <title>Convolutional Neural Network</title>
        <p>
          Due to limitations mentioned above, the algorithm should
be adaptable to find an appropriate border of the plaque.
The result of the active contour algorithm depends
primarily on brightness of the image. In other words, it is
necessary to adapt the algorithm to achieve the best
sensitivity in accordance with brightness of the input image.
Using a neural network is one of the ideas how to improve
border finding. In 2018, we published a pilot study with
an experimental draft of a feed-forward neural network to
recognize the shape of the plaque using edge detection
operators [
          <xref ref-type="bibr" rid="ref9">9</xref>
          ]. The approach using CNN is different, based
on feature recognition from a training set. The principle
of the convolution mask is designed to extract some
features. Earlier, we also implemented a simple neural net
to detection of the ROI of substantia nigra based on
training and learning of the coordinates of the ROI to put the
elliptical ROI mask [
          <xref ref-type="bibr" rid="ref6">6</xref>
          ].
        </p>
        <p>The goal of the CNN is to train and to learn the shape of
the plaque using active contour algorithm; in other words
to estimation of the active contour properties to find the
best contour of the plaque in B-image. In image
processing, CNN represent an eminently suitable tool for
automatic segmentation using deep learning, not only for
medical images.</p>
        <p>
          The idea is inspired from the research [
          <xref ref-type="bibr" rid="ref12">12</xref>
          ] in which
CNN are used to adaptive learning of the active contour
parameters. In this case, the CNN which sets the threshold
and the desired segmented area could be designed.
According to complex structure of B-images, deep learning
methods can be applied with CNN which are designed to
extract feature maps for segmentation.
4.1
        </p>
      </sec>
    </sec>
    <sec id="sec-7">
      <title>What We Expect from Using CNN</title>
      <p>CNN should work as a supervised learning model.
Therefore, we can use correctly drawn borders for training and
learning process of the CNN. The convolutional layer of
the CNN is designed to extract the features using a
convolution kernel operation, e.g. 5 5. In Fig. 11 a simplified
model of CNN is illustrated. The convolutional layer is
based on computing 2-D convolution. Let f (x; y) is an
input image, g(x; y) to be an output image and the w to be
the convolution kernel, 2-D convolution is computed by
g(x; y) = w
f (x; y)
(3)
on 2-D image. There are usually more than one
convolutional layer in CNN to detect edges, gradient to higher
level of segmented objects.</p>
      <p>In Fig, 11 there is an example of the process what we
need. No classification of the object is necessary, only to
extract the mask to learn ACM model.</p>
      <p>Design of the CNN is nontrivial, long-term process due
to complexity of B-images. The goal is to interconnect
the CNN with ACM algorithm to reliable detection of the
plaque separately from neighbor objects (bottom of the
tube). To training and learning, correct examples of plaque
borders will be used. Interconnection with ACM could
automatically help predict number of iterations to achieve
better segmentation results of the plaque. Design, training,
learning and testing of CNN are time-consuming tasks for
which we need a large dataset.
Although automatic ROI selection is useful and faster,
there is one meaningful relation between ROI and
computed Echo-Index. To Echo-Index computing, currently
only manual selection of the ROI is used. So, each ROI
was precisely selected, and the difference between
observers was minimal. In the case of automatic selection,
ROI can be selected inaccurately in comparison with
manual border drawing so Echo-Index could be different.
Observe the example in Fig. 12 between manual and
ACMbased border. In the case of ACM, ROI is selected
including black background inside; it is undesirable. Currently,
manual selection is more accurate but this a starting point
to develop the ACM boosted by CNN to create an
automatic segmentation of the plaque.</p>
      <p>Due to this fact, the goal is minimize difference between
manual drawing and using ACM with trained CNN to
optimize the accuracy. Using CNN could predict an optimal
number of iterations from training set of correctly selected
ROI.
5</p>
      <sec id="sec-7-1">
        <title>Conclusions, Motivation to Improve and</title>
      </sec>
      <sec id="sec-7-2">
        <title>Future Work</title>
        <p>This paper is divided into two main parts. The first one
is focused on reproducibility of the Echo-Index between
two non-experienced observers for atherosclerotic plaques
in B-images. In all images, the plaque was selected
manually.</p>
        <p>In the second part, the approach to automatic plaque
selection instead of manual drawing the border, is discussed.
Using active contour segmentation algorithm with
possibility to improve the accuracy using a convolutional neural
network (CNN) could be useful.</p>
        <p>In general, the Echo-Index can be considered as a
wellreproducible value. From achieved statistical results
between two non-experienced observers in sonography, there
is no significant difference. However, Echo-Index is not
usable from the clinical point of view because there is
satisfactory correlation between Echo-index and visual
assessment of the echogenicity grade which should be an
indicator of the risk level in general. So, lower Echo-Index
value does not correspond to lower echogenicity and vice
versa.</p>
        <p>The second part is dedicated to automatic ROI selection
to eliminate manual drawing the border. Currently, it is
only idea to do it. It seems that using active contour
algorithm could be useful. In addition, it can be supported by
CNN to smart adaptation of the ACM parameters.
However, this is time-consuming task to effective learn the
CNN. It is one of the key goals for future work to improve
automatic detection of the atherosclerotic plaque without
manual drawing of the border. Faster and reliable solution
using artificial intelligence components is expected.</p>
        <p>This research is supported by the project IT4Innovations
Excellence in Science - LQ1602 and data supported by
Ministry of Health of the Czech Republic, grants nr.
1628628A.</p>
      </sec>
    </sec>
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