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    <article-meta>
      <title-group>
        <article-title>Cytological Image Classification Using Data Reduction</article-title>
      </title-group>
      <fpage>0000</fpage>
      <lpage>0001</lpage>
      <abstract>
        <p>In this paper, the authors investigate data reduction techniques using cytological image data for the purpose of further classification applying modern approaches. Cytological images are widely used in diagnosing cancerous and precancerous conditions of the breast. Classification of the whole image is a rather time consuming process, so the authors apply an approach when quantitative characteristics of micro-objects (cell nuclei) are used for classification. The authors carried out a comparative analysis of the classification of the cytological images based on the quantitative characteristics of their nuclei using modern classifiers. The main criteria for describing micro-objects (cell nuclei) are the following ones: area, perimeter, circumference, maximum width and length, area and perimeter of the bounding box. The structure of the biomedical image classification system is developed, including image processing stages, calculations of quantitative characteristics of micro-objects, data reduction and classification. The principal component method is used as data reduction technique. To classify data the following methods are used: a single-layer perceptron, logistic regression, support vectors machine, and the k-nearest neighbor method. Testing was performed using BPCI2100 database of cytological images of cancerous and precancerous conditions of the breast.</p>
      </abstract>
      <kwd-group>
        <kwd>Classification</kwd>
        <kwd>Principal Component Method</kwd>
        <kwd>Cytology</kwd>
        <kwd>breast precancerous conditions</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        1,2,3,4,5,6 Ternopil National Economic University, 46001, Ukraine
7 Lviv Polytechnic National University, 79000, Ukraine
Cytological and histological images are used to diagnose precancerous and cancerous
conditions of the breast. After a microscopic examination, a specialist can determine
the type of an image. To simplify the analysis process of cytological and histological
images, a number of automated microscopy systems (AMSs) with functions for image
processing were developed. The use of artificial intelligence, in particular artificial
neural networks, support vector machines, etc. show the current trends of
improvement in AMSs [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. This makes the process less time-consuming and allows us to
increase the diagnostic efficiency. The main indicators of the pathology in cytological
specimens are the shape and structure of the cells. The following quantitative
characteristics of the investigated micro-objects such as area, perimeter, circumference,
angle of inclination of the main axis, etc. are used. To calculate them, firstly, the input
image is preprocessed (filtering, histogram alignment). In next stage, the following
segmentation methods are used: threshold segmentation, watershed method, k-means
method or their combinations. When the cytological image is converted into a binary
format, each micro-object is detected and the quantitative characteristics are
calculated. The training sample has a set of features. Array features include redundant and
uninformative features. Therefore, more time is required for classification. So, it is
necessary to reduce the input feature set. The following methods are used for feature
reduction: complete search, depth-first search, breadth-first search, branch-and-bound,
group method of data handling, feature ranking, feature clustering, evolutionary
search, etc. [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. In this paper, the principal component method is used for reduction of
input characteristics. The following methods have been selected as high-level
computer vision tools: support vector method, logistic regression, a single-layer
perceptron, and the k-nearest neighbor method. Support vector method is a method of
analyzing data for classification using directed learning models. Each element of the
training samples is assigned to a certain class. The training algorithm creates a model
that assigns new samples to one of the classes. Formally, the support vector machine
builds a hyperplane, or a set of hyperplanes in high-dimensional space that can be
used for classification, regression and other tasks [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ]. Logistic regression is a
statistical regression method used when a dependent variable is categorical, that is, it can
have only two values [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ]. The idea of logistic regression is that the space of the
original values can be divided by a line into two corresponding classes. The k-nearest
neighbor method assigns objects to the class that most of its k-nearest neighbors
belong to in a multidimensional feature space. This is one of the simplest algorithms for
learning classification models [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ]. A single-layer perceptron is the simplest kind of
artificial neural networks, which is based on a mathematical model of the information
perception by the human brain, and consists of sensors, associative and responsive
components.
      </p>
      <p>The main advantage of using quantitative characteristics for the purpose of
microobject classification is the lack of a subjective human factor. Therefore, an urgent
problem is evaluation of the quantitative characteristics of micro-objects, their
reduction and data classification using modern classifiers to improve diagnostic accuracy.
2</p>
    </sec>
    <sec id="sec-2">
      <title>Literature review</title>
      <p>
        Classification is an important part of the data analysis process, which can be
performed by different algorithms divided into different groups. These groups are based
on machine learning techniques [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ]. Modern approaches to detection and
classification of cell nuclei in cytological images are considered in [
        <xref ref-type="bibr" rid="ref7">7</xref>
        ]. In this paper, the
authors compare classification results obtained using manual markups and deep learning
methods. In [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ], the authors provide a comparative analysis of the results of
cytological image classification using the k-nearest neighbor method and the support vector
method. In the experiments, the shape of the nuclei and the structure of the tissue
were taken into account. The study of the k-nearest neighbor method is relevant in the
field of data mining and machine learning [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ]. Zhao in [
        <xref ref-type="bibr" rid="ref10">10</xref>
        ] developed a new
algorithm based on the use of labeled samples. These methods were used mainly for fast
searching [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ], reducing the dimension, and improving the efficiency of algorithms.
The support vector method is a set of learning methods used for classification and
regression. They belong to the family of generalized linear classification [
        <xref ref-type="bibr" rid="ref12">12</xref>
        ].
In [
        <xref ref-type="bibr" rid="ref13">13</xref>
        ], a hybrid method of combining the support vector method and accelerator
methods was developed. The authors show the effectiveness of the classification, and
the SVM is used as the basic classifier for the data group classification. In [
        <xref ref-type="bibr" rid="ref14 ref15">14-15</xref>
        ],
structures of convolutional neural networks were proposed for the classification of
breast cancer histopathology images regardless of their degree of enlargement. The
advantage of the developed systems on the basis of the proposed structures is the
automation of the diagnostic process and the formation of a database for further
research. Comparison of the quality of the breast cancer detection using magnetic
resonance imaging and immunohistochemical studies is presented in [
        <xref ref-type="bibr" rid="ref16">16</xref>
        ]. A comparative
analysis of approaches to biomedical image analysis is presented in [
        <xref ref-type="bibr" rid="ref17 ref18">17,18</xref>
        ].
      </p>
      <p>The analysis of the above-mentioned publications has shown that scientists pay
considerable attention to the problem of finding the ways of diagnosing precancerous
and cancerous conditions of the breast on the basis of artificial intelligence systems.
However, the complexity of the study and the large number of classifiers require
additional research and comparative analysis, and a considerable amount of data needs to
be reduced in size.
3</p>
    </sec>
    <sec id="sec-3">
      <title>Problem statement</title>
      <p>The purpose of this work is to analyze the existing means of artificial intelligence and
their applications for the classification of cytological images based on the quantitative
characteristics of micro-objects. To achieve this goal, the following tasks must be
accomplished:
1. To reduce data using the principal component method.
2. To develop the structure of classification system of cytological images.
3. To conduct computer experiments in order to carry out a comparative analysis
of the classifiers.</p>
      <p>Formally, the formulation of the problem is as follows. Assume a set of features
(1):</p>
      <p>X  xij  , i  1, m , j  1, n ,
(1)
where n – a number of features, m – a number of their implementations.
In addition, a set of classes P is given.</p>
      <p>To carry out the classification procedure we use a set of classifiers (2):</p>
      <p>C  C1 , C2 , ..., Ct  ,
where t – a number of classifiers.</p>
      <p>After applying the PCA, we obtain a set of components Y   yi  , where Vі  1, m .
Each component is a linear combination of features (3):</p>
      <p>y j  w1 j x1  w2 j x2  ...  wrj xr ,
when r  m .</p>
      <p>Thus, we get a set of components with their contributions yk , I k  , k  1, s , where
s – a number of principal components.</p>
      <p>The classification accuracy  0 is specified. Then, it is necessary to find s value in
such a way:
s  Y s  min Y . (4)</p>
      <p>Y s Y ,  0
4</p>
      <sec id="sec-3-1">
        <title>Principal component analysis</title>
        <p>Input feature matrix X is given:</p>
        <p>
X  </p>
        <p>In columns there are features, they are indexed by j ( j  1, n ), and the lines are
their implementations. They are indexed by i ( і  1, m ).</p>
        <p>The PCA implementation can be presented by a number of steps.
1. Centering and rationing of the output data is performed according to the formula
(6):
xij  xj , (6)</p>
        <p> j
where j – the number of the original variable, i – the implementation number of the
j -th variable, and x j and  j – the arithmetic mean and root mean square deviation
of the x j feature.
2. Calculating the covariance (S) or correlation (R) matrix.</p>
        <p>  x21
covx2 ,x1
S  

cov xn ,x1
cov x1 ,x2
(7)
(8)
(9)
(10)
3. Finding the eigenvalues 1  2  …   p  0 of the matrix S (or R) using
characteristic equation (10):</p>
        <p>det  S   E   0 or det  R   E   0 ,
where E – a unitary matrix (a square matrix with ones on the diagonal and zeros
elsewhere).</p>
        <p>4. Finding the eigenvector for each eigenvalue j . The eigenvector is the solution
to the system of equations (11):
where w – eigenvector.
5. Finding linear combinations for principal components
y j
y j  w1 j x1  w2 j x2  ...  wpj xp .
(11)
(12)
6. Analysis of the contribution of each of the principal components and their
ranking in ascending order.</p>
        <p>The contribution of each component is evaluated by the formula (13):
1  2  ...   p
where j – a number of a component.</p>
        <p>I j 
 j
,
(13)</p>
      </sec>
      <sec id="sec-3-2">
        <title>5 Structure of the cytological image classification module</title>
        <p>
          The lack of clear contours of cell nuclei leads to difficulties in cytological image
processing. Transmission of the digital image from the camera to the microscope and via
communication channels to the computer causes pulse noises, which can often be
classified by the software system as a part of the investigated object. Examples of
cytological images of precancerous and cancerous conditions of the breast are taken
from the BPCI2100 database [
          <xref ref-type="bibr" rid="ref19">19</xref>
          ](Fig. 1).
        </p>
        <p>During the study, the following quantitative characteristics of cell nuclei were
determined: area, perimeter, length, width, circumference, coordinate Xc, coordinate
Yc, length of the major axis, length of the minor axis, angle of inclination of the
major axis to the OX axis, perimeter of a bounding box, coordinate Bx, coordinate By,
bounding box width, bounding box length, bounding box area, aspect ratio.</p>
        <p>The structure of cytological image classification module is shown in Figure 2.
The classification process consists of the following steps:</p>
        <p>1. Filtering the input image. This stage makes it possible to reduce noise. Gaussian
and Median filtering is used to reduce Gaussian and pulse noise, respectively.
Filtering can significantly improve image quality that will have positive impact on the next
stages.</p>
        <p>
          2. Segmentation. A segmentation stage is required to select particular areas in the
image (cell, background nuclei). For cytological images, the best results were shown
by watershed algorithms, k-means, and threshold segmentation. Based on these
algorithms, an algorithm for segmentation of cytological and histological images was
developed [
          <xref ref-type="bibr" rid="ref20">20</xref>
          ]. Quantitative evaluation of image segmentation quality was performed
on the basis of Gromov-Frechet and Gromov-Hausdorff metrics.[
          <xref ref-type="bibr" rid="ref21">21</xref>
          ]
        </p>
        <p>
          Cell nuclei are selected using the image contour selection algorithm developed by
the authors[
          <xref ref-type="bibr" rid="ref22 ref23">22,23</xref>
          ].
        </p>
        <p>After converting the image into the type of “white background – black objects”, the
quantitative characteristics of the particular micro-objects are evaluated.
3. Data reduction. The principal component method is used to reduce the data size.
4. Classification. Data in the form of an array of numbers is fed to the classification
module. The classification module implements the support vector method, logistic
regression, a single-layer perceptron and the k-nearest neighbor method.
Classification results in an associative array that includes data on the parameters of the nuclei
and their corresponding classes.</p>
        <p>To analyze the classification results, ROC-curves were constructed and AUC
coefficients were calculated.
6</p>
      </sec>
      <sec id="sec-3-3">
        <title>Structure of the cytological image classification module</title>
        <p>The software module for testing the cytological image classification techniques is
written in Java programming language and deeplearning4j library.</p>
        <p>An example of the data reduction of the analysis of the cytological image cell
nuclei is given in Figure 3.</p>
        <p>The results of the classification of the cytological images by the support vector
method are shown in Figure 4.</p>
        <p>2 components (AUC = 0.75)</p>
        <p>3 components (AUC = 0.6
5 components (AUC = 0.79)
8 components (AUC = 0.91)</p>
        <p>Classification quality score using the support vector method on the basis of the AUC
coefficient is shown in Figure 5.
ig. 5. Classification quality score using the support vector method</p>
        <p>The analysis of the results in Figure 5 shows that the highest classification
accuracy can be achieved using 8 components. Classification results with the use of a
singlelayer perceptron are shown in Figure 6.</p>
        <p>2 components (AUC=0.27)
3 components (AUC=0.93)
The AUC coefficient shows that the best classification quality is obtained with the
use of 3 components.</p>
        <p>The results of the classification of the cytological images based on multiclass
logistic regression are shown in Figure 7.</p>
        <p>Therefore, the best result is achieved with the use of 3 and 5 components and is
75%.</p>
        <p>Conclusions
1. Using the basic algorithms of low, medium and high levels of computer vision, a
classification structure of cytological images is developed. The developed structure
includes the use of the principal component method to reduce the data size.
2. Applying the principal component method, the input indicators were reduced
which showed that mainly three components are informative.
3. Computer experiments have shown that the best result of the classification of the
quantitative characteristics of the cytological image nuclei is obtained using the 3
major components. The AUC is about 93%.</p>
      </sec>
    </sec>
  </body>
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