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<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Melanoma multi class segmentation using different U-Net type architectures</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Nojus Dimša</string-name>
          <email>nojus.dimsa@ktu.edu</email>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Agnė Paulauskaitė-Tarasevičienė</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Department of Applied Informatics, Kaunas University of Technology</institution>
          ,
          <addr-line>Studentų 50, Kaunas</addr-line>
          ,
          <institution>Lithuania Department of Applied Informatics, Kaunas University of Technology</institution>
          ,
          <addr-line>Studentų 50, Kaunas</addr-line>
          ,
          <country country="LT">Lithuania</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>Automatic segmentation of skin lesions is the most important step towards the analysis of malignant melanoma, which is a specific kind of skin cancer. Deep learning is one of the most effective approaches to medical image processing applications. The encoder-decoder structures are good for segmentation tasks in particular the U-Net architecture, which is used as a basic architecture for the medical image segmentation networks. Recently, different variants of U-Net type architecture have been provided for improvement in terms of the segmentation results. Therefore, we focused on three U-Net type models, specifically U-Net, U-Net++ and MultiResUNet in order to evaluate their capability and performance on the multi class segmentation of melanoma.</p>
      </abstract>
      <kwd-group>
        <kwd>eol&gt;Melanoma</kwd>
        <kwd>segmentation</kwd>
        <kwd>deep learning</kwd>
        <kwd>U-Net</kwd>
        <kwd>image analysis</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1. Introduction</title>
      <p>
        There are two main types of skin cancer: melanoma and non-melanoma. Melanoma of the skin is
the 19th most commonly occurring cancer in men and women [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. There were nearly 300,000 new cases
in 2018. American Cancer Society estimates 106.110 new cases of skin melanoma and 7180 deaths
from it in 2021[
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. Melanoma misdiagnosis accounts for more malpractice claims than any cancer,
excluding breast cancer. Misdiagnosis of melanoma in an early stage can reduce a patient’s chances of
survival. Although an international staging system for melanoma exists, diagnosing melanoma
accurately and consistently is still a very challenging task. Variability prognosis and diagnosis for
melanoma comes from subjective visual observations used for melanoma prognosis and diagnosis [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ].
Only visual inspection has variable accuracy that leads the patient to undergo other tests and series of
biopsies and complicates the treatment. Computer vision can help in improving accuracy and
consistency of diagnosis. Many researchers have been working on the image processing techniques for
skin cancer detection. Non-invasive diagnosis methods and algorithms can achieve excellent
performance in segmenting skin lesions. Image features to perform skin lesion segmentation usually
include shape [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ], texture [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ], edges [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ], luminance [
        <xref ref-type="bibr" rid="ref7">7</xref>
        ], histogram thresholding [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ], and so on. Many
researches are being carried out on ABCD (Asymmetry, Border, Color, Diameter) rules for the
melanoma skin cancer [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ], [
        <xref ref-type="bibr" rid="ref10">10</xref>
        ], [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ], [
        <xref ref-type="bibr" rid="ref12">12</xref>
        ]. Most often melanoma tends to show asymmetric forms with
diverse colors and structures. However, melanoma can also show symmetric pattern or nonspecific
pattern.
      </p>
      <p>
        Convolutional neural networks (CNNs) as a special type of multi-layer neural networks have become
one of the most widely used models of deep learning and have demonstrated a very high accuracy
results in image segmentation tasks. Various CNN architectures are widely used in solving melanoma
detection and segmentation tasks [
        <xref ref-type="bibr" rid="ref13">13</xref>
        ], [
        <xref ref-type="bibr" rid="ref14">14</xref>
        ], [
        <xref ref-type="bibr" rid="ref15">15</xref>
        ], [
        <xref ref-type="bibr" rid="ref16">16</xref>
        ], [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ]. Some CNN are created specifically for
segmentation of medical images. The purpose of medical image segmentation is to classify the pixels
in an image, thereby recognizing abnormal areas such as tumors, cancer cells or lesions.
      </p>
      <p>
        U-Net is one of the most used architectures for bio-image segmentation and produces promising
results in the domain [
        <xref ref-type="bibr" rid="ref17">17</xref>
        ]. However, some researchers have noticed that classical U-Net model is still
quite simple and convolution in the nodes can be improved. Therefore, some variants of U-Net have
been provided such as R2U-Net [18], UNet 3+ [19], UNet++ [20], H-DenseUnet [21], TMD-Unet [22]
and others. This paper contributes to this field by performing the experimental investigation of multi
class segmentation performance of three different U-Net type structures: classical U-Net, UNet++, and
      </p>
      <sec id="sec-1-1">
        <title>MultiResUNet [23].</title>
      </sec>
    </sec>
    <sec id="sec-2">
      <title>2. Dataset</title>
      <p>Dataset used for this research was obtained from ISIC (International Skin Imaging Collaboration)
archive − an open-source public access archive of skin lesion images including melanoma. The goal of
ISIC melanoma project is to help decrease melanoma-related deaths [24]. ISIC archive downloader
written by Oren Tolmor and Gal Avineri was used to download the images and their masks (Figure 1).
Masks are used to make recognition of object easier. However, only 1084 malignant images had mask
provided, so for remaining images, manual creation of masks was performed. Images in the dataset are
divided into benign and malignant. 9900 benign images and 4291 malignant images were augmented
and used for the training. Data augmentation is used to reduce over-fitting and to increase size of the
dataset. The following augmentations were randomly performed: image rotation from 0 to 360 degrees,
width shift from 0 to 8% of total width, height shift from 0 to 8% of total height, a horizontal flip, a
vertical flip and zoom inside of image between 0 and 20%. The same augmentation process was
performed on training and validation sets.</p>
      <p>a)
b)
Black and white masks for malignant images were replaced with black and grey masks. This was
done because multi class segmentation requires masks to be different color. Images were resized to 256
x 256 px. A single image can contain multiple skin spots (Figure 2c, d, g, h). However only the biggest
one is taken for evaluation. Smaller marks are ignored (Figure 2c, g). In some images irrelevant spots
are hidden (Figure 2d) or painted over (Figure 2h).</p>
      <p>a)
e)
b)
f)
c)
g)
d)
h)</p>
    </sec>
    <sec id="sec-3">
      <title>3. Methods</title>
      <p>We utilize three U-Net type architectures, specifically U-Net, U-Net++, and MultiResUNet in order
to compare their performance on the selected dataset.</p>
    </sec>
    <sec id="sec-4">
      <title>U-Net architecture</title>
      <p>
        U-Net was developed in 2015 for biomedical image segmentation [
        <xref ref-type="bibr" rid="ref17">17</xref>
        ]. Classical U-Net architecture
consists of two paths: down-sampling and up-sampling. Down-sampling path consists of 4 blocks
(Figure 3). Each block applies two 3x3 unpadded convolutions followed by a rectified linear unit (
ReLu) and a 2x2 max pooling operation with stride 2. However Leaky ReLu with α value of 0.3 was
used instead. ReLu unit can end up in a state where it only outputs zeros and that will prevent parts of
neural network from learning. At each block number of feature channels doubles. Up-sampling path
also consists of 4 blocks. Each block in this path up-samples feature map, applies 2x2 convolution
halving number of feature channels, concatenates it with feature map from down-sampling path, and
applies two 3x3 unpadded convolutions followed by Leaky ReLu. In this implementation input layer
receives 256x256 image with 256x256 mask. Final layer of network uses 1x1 convolution with softmax
function to map feature vector to 2 classes. In total, architecture consists of 29 layers. 20 of them being
convolutional followed by Leaky ReLu, 4 max-pooling layers in down-sampling path, 4 up-sampling
layers in up-sampling path, and an output layer. For optimization Adam optimizer was used, with loss
function being categorical cross-entropy.
      </p>
      <p>1 64 64
8
2
1
x
8
2
1
1024 x 16 x16 1024 x 16 x16
256 128
8
2
1
x
8
2
1
4
6
x
4
6
6
5
2
x
6
5
2</p>
      <p>U-Net++ architecture was created in 2020 in order to increase accuracy of medical image
segmentation [20]. This architecture is based on nested and dense skip connections. The idea behind
this architecture is that model can more effectively capture foreground object details when feature maps
from down-sampling path are enriched before concatenation with the corresponding feature maps from
up-sampling path.</p>
      <sec id="sec-4-1">
        <title>Input picture</title>
      </sec>
      <sec id="sec-4-2">
        <title>Output picture</title>
      </sec>
      <sec id="sec-4-3">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-4">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-5">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-6">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-7">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-8">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-9">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-10">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-11">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-12">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-13">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-14">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-15">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-16">
        <title>Conv</title>
      </sec>
      <sec id="sec-4-17">
        <title>Conv</title>
        <p>Conv Conv 3x3 + Leaky</p>
      </sec>
      <sec id="sec-4-18">
        <title>Relu</title>
      </sec>
      <sec id="sec-4-19">
        <title>Concatenate</title>
      </sec>
      <sec id="sec-4-20">
        <title>Upsampling 2x2</title>
      </sec>
      <sec id="sec-4-21">
        <title>MaxPooling 2x2</title>
      </sec>
      <sec id="sec-4-22">
        <title>Conv 1x1, softmax</title>
      </sec>
      <sec id="sec-4-23">
        <title>Input</title>
        <p>MultiResUnet aims to make U-Net suitable for multi-resolutional analysis by incorporating 3x3 and
7x7 convolutions in parallel to the 5x5 convolutions which are resembled by two 3x3 convolutions.
Having 7x7 convolution would increase memory needed to train model so to go around that they will
also be substituted by sequence of 3x3 convolutions [25]. Outputs of these convolutional blocks are
concatenated. A residual connection and 1x1 convolution is added to keep additional spatial information
see Figure 5.</p>
        <p>t
u
p
n
I
5x5
Conv Concatenate Conv Conv Conv
t
u
p
n
I</p>
        <p>Conv Conv Conv
3x3
Conv
7x7
Conv</p>
      </sec>
      <sec id="sec-4-24">
        <title>Concatenate</title>
      </sec>
      <sec id="sec-4-25">
        <title>Concatenate</title>
        <p>Output
3x3
Conv
3x3
Conv
3x3
Conv</p>
        <p>Concatenate</p>
        <p>Concatenate</p>
        <p>Addition
1x1
Conv
t
u
p
t
u
O</p>
        <p>In this U-Net architecture convolutional layers and a residual connection is added to shortcut
connection so instead of just concatenating feature maps from down-sampling paths first they go
through convolutional layers with residual connection and only then are concatenated with the
upsampling feature map Figure 6.
1x1
Conv
1x1
Conv
1x1
Conv
1x1
Conv</p>
        <p>Upsampling
block
64, 128, 256, 512). Number of filters become  ,
,

2</p>
        <p>Each MultiRes model block has parameter  , which sets the number of filters of the convolutional
layers in the block. 
= 1.67   where  is corresponding layer of U-net ( can have values of 32,
and are assigned to the three successive layers.</p>
        <p>Number of convolutional blocks used in the Res paths are gradually reduced from 4 to 1 as model goes
deeper.</p>
      </sec>
    </sec>
    <sec id="sec-5">
      <title>4. Experimental results</title>
      <p>Each of three models was trained for 20 epochs each epoch taking 1773 iterations for training and
500 iterations for validation (Figure 7). Chosen batch size was 8 due to hardware limitations. Original
U-Net managed to get lowest validation loss out of all however it also provides the lowest dice
coefficient score. Unet++ managed to get highest accuracy score and lowest loss out of all models
however it also got highest validation loss. Result depicted in the Figure 7c shows that MultiResUNet
is overtrained after 7 epochs, and therefore the model was retrained for only 10 epochs. This retrained
model got highest loss, validation accuracy and dice coefficient.</p>
      <p>a) U-Net loss function dependencies</p>
      <p>b) U-Net++ loss function dependencies
c) MultiResUNet loss function during 20 epochs
d) MultiResUNet loss function for 10 epochs
while the poorest performance was demonstrated by classic U-Net architecture. MultiResUNet performed</p>
      <sec id="sec-5-1">
        <title>3.70% higher than U-Net and 2.61% than U-Net++ corresponding dice coefficient results.</title>
        <p>One instance of malignant and benign skin lesion from the dataset has been selected to demonstrate
the performance of different U-Net type architectures (Figure 8 and Figure 9). Observing the
segmentation results in the figure 8, we can see that the malignant skin lesion is detected using all three
architectures. Observing the segmentation results in the figure 9, we can see that the benign skin lesion
is detected only by MultiResUnet architecture. When comparing the boundaries of the mask image, we
can observe that contours differ. In all cases models manage to locate and segment skin moles, however
all models output wrong type of mask for both malignant and benign skin lesions reducing dice
coefficient value.</p>
        <p>a) original image and mask
b) U-Net
c) U-Net++
d) MultiResUnet</p>
      </sec>
    </sec>
    <sec id="sec-6">
      <title>5. Conclusions and final remarks</title>
      <p>In this paper, the experimental investigation of multi class melanoma segmentation of three U-Net
type architectures: U-Net, U-Net++ and MultiResUNet is demonstrated. The selected methods were
tested using skin lesion datasets, which contain malignant and benign skin lesions. The overall accuracy
is more or less similar for all models used in the study: the worst performance 84.65% was demonstrated
by the classical U-Net model, and the best accuracy 92.23% was achieved by U-Net++, but this result
is higher only by 0,86% when compared to MultiResUNet. Experimental results have confirmed that
U-Net type architectures are very successful in the single class medical image segmentation, and new
modified architectures can slightly improve the performance results of classical U-Net. However, multi
class segmentation of skin lesions remains a though task.
[18] Z. Lom, C. Yakopcic, T.M. Taha, V.K. Asari, Nuclei Segmentation with Recurrent Residual
Convolutional Neural Networks based U-Net (R2U-Net). In Proceedings of the NAECON 2018—</p>
      <sec id="sec-6-1">
        <title>IEEE National Aerospace and Electronics Conference, USA, 2018, pp. 228–233.</title>
        <p>[19] H. Huang, et.al., UNet 3+: A Full-Scale Connected UNet for Medical Image Segmentation. In
Proceedings of the ICASSP 2020—2020 IEEE International Conference on Acoustics, Speech and</p>
      </sec>
      <sec id="sec-6-2">
        <title>Signal Processing (ICASSP), Barcelona, Spain, 4–8 May 2020; pp. 1055–1059.</title>
        <p>[20] Z. Zhou, Md M. R. Siddiquee, N. Tajbakhsh, and J. Liang. UNet++: A Nested U-Net Architecture
for Medical Image Segmentation, 2018, pp. 1-8. URL: https://arxiv.org/pdf/1807.10165.pdf
[21] X. Li, et. al., UNet: Hybrid Densely Connected UNet for Liver and Tumor Segmentation from CT</p>
        <p>Volumes. IEEE Trans. Med. Imaging 2018, 37, pp. 2663–2674.
[22] S. Tran, C.H Cheng, T.T. Nguyen, M. H. Le, and D. G. Liu, TMD-Unet: Triple-Unet with
MultiScale Input Features and Dense Skip Connection for Medical Image Segmentation, Healthcare
2021, Vol. 9, No. 1, pp. 1-19.
[23] C.Y., Lee, S, Xie, P. Gallagher, Z. Zhang, Z. Tu, Deeply-supervised nets, Artificial Intelligence
and Statistics, 2015, pp. 562–570.
[24] ISIC. The International Skin Imaging Collaboration, URL: ISIC Archive (isic-archive.com)
[25] N. Ibtehaz and M. S.Rahman, MultiResUnet : Rethinking the U-Net Architecture for Multimodal</p>
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      <sec id="sec-6-3">
        <title>Biomedical Image Segmentation, 2019, pp. 1-25. URL: https://arxiv.org/pdf/1902.04049.pdf</title>
      </sec>
    </sec>
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