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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Algorithm for detecting spherulite marker in human blood serum facies</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>O E Malenova</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>L I Trubnikova</string-name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>A S Yashina</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>M L Albutova</string-name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Research-and-Production Association Mars</institution>
          ,
          <addr-line>Solnechnaya Street, 20, Ulyanovsk, Russia, 432022</addr-line>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Ulyanovsk State Technical University</institution>
          ,
          <addr-line>Severny Venetz Street, 32, Ulyanovsk, Russia, 432027</addr-line>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>Ulyanovsk State University</institution>
          ,
          <addr-line>Lev Tolstoy Street, 42, Ulyanovsk, Russia, 432017</addr-line>
        </aff>
      </contrib-group>
      <pub-date>
        <year>2019</year>
      </pub-date>
      <fpage>109</fpage>
      <lpage>113</lpage>
      <abstract>
        <p>One of the effective methods of early medical diagnosis is the method of wedge dehydration. It is based on the analysis of facies images. Facia is a thin film of dried human biological fluids. The presence of special structures (markers) indicates various pathologies of the organism at their earliest stages. In this article, the algorithm for detecting spherulite marker on microscopic images of human serum facies is presented. The presence of spherulites on facies is the norm. However, the atypical form of spherulite is a marker of precancerous diseases: uterine fibroids, endometrial hyperplastic processes and the mammary gland. Due to the visual analysis of the marker, its characteristic features were identified. Then algorithmic detection methods for these features were developed. The decision on the probable presence of a marker was made if there was a combination of features of this marker. As a result of the application of the developed algorithm, most images of atypical spherulites were identified.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1. Introduction</title>
      <p>Currently, early medical diagnostic methods are actively developing. Of particular interest are
methods based on the analysis of human biological fluids (BF). One such method is the wedge
dehydration method. It consists of applying a drop of BF on a specially prepared and degreased slide.
This drop is dried at room temperature in a closed cabinet and the film is formed and called the facies
(from the Lat. Faciens - appearance, shape). The scheme of interaction of the elements of BF is
recorded on the facies. After dehydration, information from the liquid phase is represented as various
structures on the film. These structures are viewable under a microscope.</p>
      <p>
        D.K. Maxwell compiled the first theoretical description of the process of evaporation of a fixed
large droplet flowing in the diffusion mode. In 1877 he considered the case of evaporation of a
spherical drop in the article "Diffusion" [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. L. Bohlen was the first to investigate dehydration in the
field of medicine in 1942. He examined the capillary blood facies with a simple optical microscope
and revealed a connection between the structures in these images and gastrointestinal tumors [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. V.N.
Shabalin and S.N. Shatokhin gave a justification for the possibility of using this method in medical
research [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ]. The development of algorithms for automated image analysis of the BF facies is of
interest. This will allow the use of non-invasive diagnostic methods for mass screening of the
population with low costs and time. The detection algorithms for a number of markers are described in
[
        <xref ref-type="bibr" rid="ref10 ref11 ref5 ref6 ref7 ref8 ref9">5-11</xref>
        ].
      </p>
      <p>In the present work, the algorithm for the detection of spherulite markers is presented. The
presence of spherulites on facies is considered normal. However, the atypical form of spherulite is a
marker of serious diseases. Among them are such as uterine fibroids, hyperplastic endometrial
processes and the mammary gland, which are among the precancerous.</p>
    </sec>
    <sec id="sec-2">
      <title>2. Spherulite detection algorithm</title>
      <p>For the development of a detection algorithm the main features of the spherulite marker were
highlighted. These features distinguish it from the basic structure of facies and other markers.</p>
      <sec id="sec-2-1">
        <title>2.1. Marker description</title>
        <p>
          Spherulite is a complex rounded mineral aggregate. It consists of thin needle-like crystals and found in
nature in the form of balls of radial-radiant structure [
          <xref ref-type="bibr" rid="ref4">4</xref>
          ]. The spherulite looks like a rounded
crystalline formation on the facies in normal conditions. However, it can significantly change its shape
in the presence of pathologies. Spherulites on facies of a healthy person are shown in figure 1.
Spherulites on facies with pathology are shown in figure 2. It is noticeable that spherulites have a
darker background, low variation, and a rounded shape in normal conditions. In pathology, the shape
of a spherulite is different from an ellipse.
        </p>
      </sec>
      <sec id="sec-2-2">
        <title>2.2. Marker detection algorithm</title>
        <p>The algorithm was developed based on the features described above. It consists in the sequential
application of the following operations to the original image.</p>
        <p>• Image segmentation by brightness. Spherulites are darker than the main color of the facies.</p>
        <p>The average brightness of the image is calculated and all areas are darker than they stand out.
• Search the contours of areas with low brightness.
• Search for closed contours.
• Approximation by ellipse of the found closed contours.</p>
        <p>• Decision-making.</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>3. Description of the algorithm</title>
      <p>This paragraph displays the results of the analysis using this algorithm using the example of the image
of the facies shown in figure 2 on the left.</p>
      <sec id="sec-3-1">
        <title>3.1. Image preparation for processing</title>
        <p>
          The color image is loaded into memory when you start the program. The entire image is converted to
grayscale because the marker colors do not carry important information (figure 3). A median filter is
carried out to get rid of random noise [
          <xref ref-type="bibr" rid="ref12">12</xref>
          ]. This reduces the number of false loops in the following
steps.
        </p>
      </sec>
      <sec id="sec-3-2">
        <title>3.2. Image segmentation by brightness</title>
        <p>Sections of the image with brightnesses above the average are removed. The result of the threshold
section is shown in figure 3a.</p>
      </sec>
      <sec id="sec-3-3">
        <title>3.3. Search the contours</title>
        <p>
          Outlining is implemented by the Canny algorithm [
          <xref ref-type="bibr" rid="ref13">13</xref>
          ] with thresholds T1=100 и T2=180. Where T1
and T2 are the thresholds of the minimum and maximum of the algorithm. Remove short borders with
a length of less than 50 pixels using a pixel-by-pixel loop traversal. This is necessary to exclude
random short contours. The bypass is implemented using the “Beetle” algorithm [
          <xref ref-type="bibr" rid="ref14">14</xref>
          ]. The remaining
contours form the set C. The result is shown in figure 3b.
        </p>
      </sec>
      <sec id="sec-3-4">
        <title>3.4. Search for closed contours</title>
        <p>The set of closed contours Cz is selected among the set C of the remaining contours. The definition of
closed loop is implemented using pixel bypass. The criterion of closure is the return of the bypass to
the starting point.</p>
      </sec>
      <sec id="sec-3-5">
        <title>3.5. Approximation by ellipse</title>
        <p>Approximating ellipse E is found for each contour from Cz. It approximates the set of its boundary
points O = {P(i) = (x(i), y(i)), i = 1,..., N} . Consider a second-order curve equation</p>
      </sec>
      <sec id="sec-3-6">
        <title>3.6. Decision-making</title>
        <p>The atypical spherulite marker has large deviations of the boundaries from the approximating ellipse.
In addition, the major and minor axes of the ellipse should be almost equal to the norm.
Therefore, the evaluation form takes place in two stages.</p>
        <p>• The axes of the approximating ellipse are compared. The value r=a/b is considered, where a
and b are the major and minor semiaxes of the ellipse. When r ∈ [1; 1,3) spherulite is
considered normal, with r ∈ [1,3; 3) - with pathology, and for r ∈ [3; ∞) - the contour is
removed from consideration.
• The maximum and minimum distance of the boundary points from the center of the ellipse is
estimated. Spherulite is considered pathological. If one of the thresholds is exceeded, a
message on the presence of a marker is displayed. The threshold is calculated adaptively based
on the size of the approximating ellipse. The minimum distance is defined as 0.8 from the
minor axis and the maximum as 1.2 from the main axis.</p>
      </sec>
    </sec>
    <sec id="sec-4">
      <title>4. Results of experiments</title>
      <p>The algorithm was tested on 200 images of facies of blood serum with x400 optical magnification. As
a result of the test, 86% of the atypical spherulites images were correctly identified. The algorithm
made false detections and chose several structures similar to the desired marker in 11% of the images.
This suggests that in the future it is advisable to expand the set of features of this marker for more
accurate identification. It should be noted that there were other markers among the images from the
list of false alarms. Search for other markers is also included in the tasks of the developed marker
detection software complex.</p>
    </sec>
    <sec id="sec-5">
      <title>5. Conclusions</title>
      <p>In the course of this work, an algorithm and software for the automated detection of facies with
suspicion of finding an atypical spherulite marker was created. Algorithm tests on real facies images
showed acceptable results.</p>
    </sec>
  </body>
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