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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Convolutional Neural Networks</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>© Manvel Avetisian</string-name>
          <email>avetisian@gmail.com</email>
        </contrib>
      </contrib-group>
      <fpage>5</fpage>
      <lpage>9</lpage>
      <abstract>
        <p>This paper presents a neural network architecture for segmentation of medical images. The network trains from manually labeled images and can be used to segment various organs and anatomical structures of interest. We propose an efficient reformulation of a 3D convolution into a series of 2D convolutions in different dimensions. A loss function that directly optimizes intersection-over-union metric popular in medical image segmentation field is proposed. applications in image segmentation, but did not gather</p>
      </abstract>
      <kwd-group>
        <kwd>medical image segmentation</kwd>
        <kwd>convolutional neural networks</kwd>
        <kwd>deep learning</kwd>
        <kwd>convolution</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1 Introduction</title>
      <p>Medical image is a visual representation of the interior
of a body; it reveals internal anatomical structures and
thus can be used for clinical analysis, intervention
planning etc.</p>
      <p>Volumetric</p>
      <p>
        medical images are obtained from
various medical image acquisition technologies, such as
computed
tomography
(CT),
magnetic
resonance
tomography (MRT), etc. These images are represented
by a stack of 2D image slices thus forming a 3D
representation of a body [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ].
      </p>
      <p>Medical image segmentation is an automatic or
semi-automatic process of splitting a medical image
into regions, which</p>
      <p>may correspond to an organ, a
tissue, a tumor, or any other anatomical structure of
interest.</p>
      <p>Some of the</p>
      <p>applications of medical image
segmentation are surgical planning, virtual simulation
of surgeries, tumor detection and segmentation, brain
development study, functional
mapping, automated
classification
blood
cells,
mass
detection
in
mammograms, image registration, heart segmentation
and analysis of cardiac images, border detection in
angiograms of coronary, etc.</p>
      <sec id="sec-1-1">
        <title>Earliest</title>
        <p>medical image segmentation techniques
were based on low-level processing of image data
(comparing gray level values of voxels to one or
multiple thresholds, edge detector filters, unsupervised
clustering algorithms etc.).</p>
        <p>Later, supervised techniques, where training data
(manually labeled examples) is used to train a model,
became
increasingly
popular.</p>
        <p>Examples
of
such
methods are
maximization
maximum
likelihood and
expectation
methods, maximum
a posteriori and</p>
      </sec>
      <sec id="sec-1-2">
        <title>Markov random field</title>
        <p>methods, deformable
models
(active contour models, level set models), atlas-based
models, conditional random field, graph cut algorithms.</p>
        <sec id="sec-1-2-1">
          <title>Proceedings</title>
        </sec>
        <sec id="sec-1-2-2">
          <title>Conference</title>
        </sec>
        <sec id="sec-1-2-3">
          <title>Management</title>
        </sec>
        <sec id="sec-1-2-4">
          <title>Domains”</title>
          <p>the
“Data</p>
          <p>in
(DAMDID/RCDL’2017),
XIX</p>
        </sec>
        <sec id="sec-1-2-5">
          <title>Data</title>
        </sec>
        <sec id="sec-1-2-6">
          <title>Analytics</title>
        </sec>
        <sec id="sec-1-2-7">
          <title>International and</title>
        </sec>
        <sec id="sec-1-2-8">
          <title>Intensive</title>
        </sec>
        <sec id="sec-1-2-9">
          <title>Moscow,</title>
          <p>
            Convolutional
momentum until various new techniques and computing
architectures were developed. In December 2012 CNNs
won ImageNet challenge for the first time. AlexNet [
            <xref ref-type="bibr" rid="ref5">5</xref>
            ]
architecture proposed by Krizhevsky et al. won the
competition by large
          </p>
          <p>
            margin. In subsequent years,
further progress has been made [
            <xref ref-type="bibr" rid="ref6">6</xref>
            ][
            <xref ref-type="bibr" rid="ref7">7</xref>
            ]. Convolutional
neural networks have became technique of choice,
showing state of the art results in computer vision.
          </p>
          <p>A
supervised learning
algorithms experience a
dataset, consisting of examples, each of which contains
features xi and a target yi. For example, popular Iris
dataset contains measurements of various species of iris
plants. A supervised learning algorithm can study the
Iris dataset and learn to classify iris plants into three
different species based on their measurements. In our
task, xi can be a computed tomography medical image,
while yi can be a segmentation of that image done by an
experienced radiologist.</p>
          <p>An artificial neural network consists of many simple
units
called
neurons.</p>
          <p>Neurons
receive
and
send
information via</p>
          <p>weighted connections. Each neuron
calculates weighted sum of inputs and applies nonlinear
activation function f to them:
ℎ( ;  ,  ) =</p>
          <p>∗   +  .</p>
          <p>Historically popular choices for activation functions
were 

ℎ, where
( ) =</p>
          <p>1
1 +  − .</p>
          <p>Recently, one of the most popular activation functions
used in computer vision are rectified linear units
(ReLU) defined as:
( ) =
 ,   ≥
0,  ℎ 
0</p>
          <p>In a simple feed forward architecture, neurons are
organized into groups called layers. Neurons in the first
layer (called input layer) process information from the
environment,
while
neurons in subsequent layers
process information from previous layers. Neurons in
the last layer (called output layer) produce information
of interest. Because of this multi-layered structure,
neural networks show very complex behavior:
 = ℎ(… ℎ(ℎ( ;  1,  1);  2,  2) … ;   ,   ).</p>
          <p>
            The universal approximation theorem states that a
feed-forward network with a single hidden layer
containing a finite number of neurons, can approximate
continuous functions. Thus, the theorem states that
simple neural networks can represent a wide variety of
interesting functions when given appropriate number of
parameters [
            <xref ref-type="bibr" rid="ref1">1</xref>
            ].
          </p>
          <p>
            Convolutional neural networks (CNNs) are type of
artificial neural networks specialized for processing
data that has grid-like topology. Examples of such data
domains include 1D time-series data or 2D or 3D
images. Given two-dimensional image I and kernel K,
convolution operation can be defined as [
            <xref ref-type="bibr" rid="ref1">1</xref>
            ]:
( ∗  )( ,  ) =
          </p>
          <p>( −  ,  −  ) ∗  ( ,  ).</p>
          <p>,
Combining outputs of convolutions from earlier layers
with new convolutions on later layers, a neural network
can learn very complex features. Usually, first layers of
convolutional neural network detect edges and angles,
while later layers detect more complex features like
eyes, hair, wheels, and even deeper layers detect human
faces, cars etc. depending on the task at hand.</p>
          <p>
            If we need to transform data in the direction
opposite to convolution, i.e., from something that has
the shape of the output of some convolution to
something that has the shape of its input while
maintaining a connectivity pattern that is compatible
with said convolution, we can use so called transposed
convolutions or deconvolutions [
            <xref ref-type="bibr" rid="ref14">14</xref>
            ].
          </p>
          <p>In classification task, the final layer of a neural
network computes   scores applying convolutions
to the output of previous layer. The     scores are not
bounded, but we would like to model probability
distribution from them. In order to convert them to
probabilities, a softmax function is used:
e− 
    ( ) = ∑ e−  .</p>
          <p>In order to train a neural network, we minimize a
loss function  ( ,  ,  ;  ) with respect to  , where
 = { 1,  2 … ,  1,  2 … }, x and y are elements of
training set, and  is a prediction of the network. The
loss function used in this paper will be presented in
section 2.</p>
          <p>The minimization of the loss function is achieved by
calculating partial derivatives of the loss function with
respect to parameters of the neural network, and then
applying small changes to the parameters. The most
basic optimization algorithm is stochastic gradient
descent algorithm (SGD), which uses following update
rule:
 
where  is a small constant called learning rate.  is a
hyper parameter of learning algorithm, usually good
values for  are between 0.01 – 10−6.</p>
          <p>=   +
  ( ,  ,  ;   )
∗  ,</p>
          <p>As neural network may have many layers, gradients
of the loss function are computed using
backpropagation algorithm: first we computed gradients
for last layer, and then we compute gradients of
preceding layer using chain rule:</p>
          <p>−1  −1</p>
          <p>If neural network has many layers gradient
information may be lost during this process (this
problem is called vanishing gradients problem). One
solution to this problem is skip connections: we sum
outputs of deeper layers with outputs of more shallow
layers, e.g.:
=
ℎ1 = ℎ( ;  1,  1),
ℎ2 = ℎ(ℎ1;  2,  2),
ℎ3 = ℎ(ℎ2;  3,  3) + ℎ1.</p>
          <p>One of the most useful (and most popular) metrics
in medical image segmentation is
intersection-overunion metric (IoU). For volumes A and B, IoU is
defined as:
| ∩  |
   ( ,  ) = .</p>
          <p>| ∪  |</p>
          <p>
            CNNs can directly classify each pixel of an image
individually, given that we present to it a patch of image
around pixel of interest. However, a drawback of this
naïve sliding window approach is that input patches of
neighboring pixels have a huge overlap, and thus some
convolutions would be computed many times [
            <xref ref-type="bibr" rid="ref2">2</xref>
            ].
          </p>
          <p>
            A significant speedup can be achieved if we present
many pixels to a CNN simultaneously. One of the first
implementations of this idea, that were successful in
medical image segmentation, were Fully Convolutional
Neural Networks (fCNN) [
            <xref ref-type="bibr" rid="ref3">3</xref>
            ]. fCNNs added upsampling
layers to popular classification neural network
architectures, such as AlexNet [
            <xref ref-type="bibr" rid="ref6">6</xref>
            ], VGG16 [
            <xref ref-type="bibr" rid="ref7">7</xref>
            ], and
GoogLeNet [
            <xref ref-type="bibr" rid="ref8">8</xref>
            ]. This solution allowed CNN to produce
a likelihood map for an entire image rather than a single
pixel. The resulting neural network can be applied to an
entire input volume in an efficient fashion [
            <xref ref-type="bibr" rid="ref3">3</xref>
            ].
          </p>
          <p>
            The next iteration of fCNN idea is U-Net
architecture, where a typical convolutional network
architecture (contracting path) is followed by an
upsampling layers (expanding path) where the size of
an image is increased with upconvolutions. The
resulting network forms a U-shape giving the name of
the architecture. Another major improvement are
skipconnections which directly connect contracting and
expanding layers. The architecture showed very good
performance on a different biomedical segmentation
applications. Thanks to use of data augmentation with
elastic deformations, it only needs a very few annotated
images and has a very reasonable training time [
            <xref ref-type="bibr" rid="ref4">4</xref>
            ].
          </p>
          <p>
            The 3D U-Net architecture developed ideas of
UNet further to construct a network for volumetric image
segmentation that learns from sparsely annotated
volumetric images. The implementation replaced all 2D
convolutions of U-Net by 3D convolutions. The authors
showed a successful application of the proposed method
on difficult data set of the Xenopus kidney [
            <xref ref-type="bibr" rid="ref5">5</xref>
            ].
          </p>
        </sec>
        <sec id="sec-1-2-10">
          <title>2.1 Architecture of the neural network</title>
          <p>We used convolution-deconvolution network based on
U-Net architecture. The input is processed by blocks of
convolutional operations. The data is downscaled with
maxpool operations and fed to a next convolutional
block in which we would increase number of channels
twice to alleviate for loss of resolution. We upscale
images with upconvolutions and concatenate data with
signals from inner blocks before processing with
another convolutional block. Thus, the neural networks
forms U-shape with skip connections. Figure 1
summarizes the overall architecture of the neural
network.</p>
          <p>The skip connections were introduced as it is known
that they reduce gradient vanishing problem.</p>
          <p>A convolutional block (see Figure 2) consists of
four 2D convolutions along different axis. This was
done to optimize processing time, as even single 3x3x3
convolution has 27 parameters, while 4 3x3
convolutions have only 36 parameters. Each
convolution is followed by ReLU nonlinearity and a
dropout.</p>
          <p>An upconvolution layer has 1x1 kernel which
upscales the data, after which we concatenate upscaled
data with output of convoltuion block with same size.</p>
        </sec>
        <sec id="sec-1-2-11">
          <title>2.1 Loss function</title>
          <p>
            Our experiments showed that more popular softmax
cross-entropy function is harder to tune, as it optimizes
a metric (accuracy) that we’re not interested in and
needs tuning of weights of examples. In our setting, IoU
metric is much more informative. We extend loss
function presented in [
            <xref ref-type="bibr" rid="ref13">13</xref>
            ] to multiclass setting. The loss
function optimizes IoU metric directly:
 ( ,  ,  ;  ) = ,
∑  1: + ∑  1: − ∑  1: ∗  1:
where y is one-hot encoding of voxel’s label,  is label
probabilities outputted by the network (with softmax
function).  1: denotes  without the first element.
∑  1: ∗  1:
          </p>
        </sec>
        <sec id="sec-1-2-12">
          <title>2.2 Implementation details</title>
          <p>
            The proposed method was implemented using
TensorFlow library in Python 3 language [
            <xref ref-type="bibr" rid="ref4">4</xref>
            ].
          </p>
          <p>A machine with Intel Core i7 6700K CPU, 32 Gb
RAM, and NVidia GeForce GTX 1070 GPU was used
to train a neural network and perform all experiments.</p>
          <p>One of the problems we faced was limited memory
of the video card. During training, we were not able to
process a full image thus we had to split an image into
blocks. This could potentially decrease accuracy for
voxels close to the edges of the split because they
would have less information about their neighbors. Our
experiments showed that this is not a significant
problem. To segment an image with trained model, we
used TensorFlow’s ability to apply convolutions to
inputs of variable size to speed up segmentation.
However, the architecture of our network forced us to
use images with dimensions 23 ∗  , as otherwise
dimensions of upscaled images would not match
original images.</p>
          <p>The neural network showed strong signs of
overfitting. We tested various regularization methods
and obtained best results by using dropout right before
output layer, as well as l2 regularization of
convolutional filters’ weights.</p>
        </sec>
        <sec id="sec-1-2-13">
          <title>2.1 Hyperparameters</title>
          <p>
            We performed an extensive search for optimal
hyperparameters. Our program would select previous
best hyperparameters, randomly generate new ones in
interval [0.1*pbest, 10*pbest], perform 5000 training steps,
and select the network which showed higher IoU score
on validation set. We summarized final
hyperparameters that were used in Table 1.
not beneficial in our case and leads to numerical
instabilities [
            <xref ref-type="bibr" rid="ref5">5</xref>
            ].
          </p>
          <p>In order to minimize numerical problems gradients
were clipped to be less than or equal to 1.0.</p>
        </sec>
      </sec>
    </sec>
    <sec id="sec-2">
      <title>3 Experiments</title>
      <p>
        In order to confirm ability of the neural network to
produce segmentation, we conducted an experiment to
segment heart’s left ventricle using the Cardiac Atlas
Project dataset [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ]. It consists of 83 volumetric MR
images of heart and a mask which highlights region of
interest. Figures 4 and 5 show an example of a slice of
an image from such dataset, as well a mask for that slice
which highlights region of interest. Each image consists
of 10-15 slices of various sizes, with 192x192 and
256x256 being the most frequent ones.
      </p>
      <p>Images in dataset were split to training set,
validation set and test set. Validation set was used to
tune the parameters of the neural network.</p>
      <p>Figure 6 shows segmentation that was obtained
using our convolutional neural network. Our model
showed quality segmentation with IoU = 0.63.</p>
    </sec>
    <sec id="sec-3">
      <title>4 Conclusions</title>
      <p>Our experiment showed that convolutional neural
network is capable of segmenting visually
distinguishable anatomical structures on medical
images. We plan to extend presented model to more
medical image segmentation datasets.</p>
      <p>Support. This research was supported by the Russian
Foundation for Basic Research (grant 16-07-01028).</p>
    </sec>
  </body>
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