<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD v1.0 20120330//EN" "JATS-archivearticle1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Segmentation of vessel tree from cine-angiography images for intraoperative clinical evaluation.</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Salvatore Scaramuzzino</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Salvatore De Rosa</string-name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Ciro Indol</string-name>
          <email>indolfig@unicz.it</email>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Francesco Calimeri</string-name>
          <email>calimerig@mat.unical.it</email>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Maria Francesca Sp</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Department of Experimental and Clinical Medicine, University of Catanzaro, Italy, at the time of the study</institution>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Department of Mathematics and Computer Science, University of Calabria</institution>
          ,
          <country country="IT">Italy</country>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>Division of Cardiology, Department of Medical and Surgical Sciences, University of Catanzaro</institution>
          ,
          <country country="IT">Italy</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>The assessment of vascular complexity in the lower limbs provides relevant information about peripheral artery diseases, with a relevant impact on both therapeutic decisions and on prognostic estimation. Such evaluation is currently carried out by human operators via visual inspection of cine-angiograms, resulting in con icting results and scorings that are largely operator-dependent, mostly because of the technical di culties in the quanti cation of vascular network and its ow capability. We propose a new method to automatically segment the vessel tree from cine-angiography video for intraoperative clinical evaluation, in order to improve the clinical interpretation of the complexity of vascular collaterals in Peripheral Arterial Occlusive Disease (PAOD) patients.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        The assessment of vascular complexity in the lower limbs provides relevant
information about peripheral artery diseases; in fact, vascular collaterals act as a
sort of natural bypass system, sustaining tissue perfusion downward of vascular
occlusion [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. Intuitively, they can exert a protective impact on limb ischemia,
thus reducing symptoms and improving the outcome in patients with Peripheral
Arterial Occlusive Disease (PAOD) [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ].
      </p>
      <p>In current clinical practice, cine-angiography is widely used to assess the
vascular complexity in the lower limbs, in order to obtain relevant information
about PAOD. Therapeutic decisions and prognostic forecasts, in fact, are based
on visual inspection of such images. Despite its wide use, this technique
remains a largely operator-dependent process, also prone to errors mostly due to
misinterpretations. Indeed, besides the hard task of identifying the vessel tree,
video images feature the presence of surgical instruments, tools, electrode
cables, catheters, etc., that makes the correct automatic evaluation even more
challenging. In this work we de ne a new methodology for automatic vessel tree
identi cation from a set of images obtained subdividing cine-angiography videos
in di erent frames, with the goal of fostering more reliable clinical assessments
in the described scenario. In particular, we aim at making use of Convolutional
Neural Networks (CNNs) for the segmentation of the vascular tree over a set of
images extracted during the cine-angiography process.</p>
      <p>
        Interestingly, to the best of our knowledge, this is one of the rst attempts
to segment vessels in the ilio-femoral district on a set of 2-D frames. In fact, the
method presents several challenges: (i) non-trivial image pre-processing
operations are needed in order to elaborate and extract a set of static image from the
cine-angiography video; (ii) ne-tuning of CNN parameters in each layers, in
order to reach a high segmentation accuracy as described in [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ]; (iii) assemble
the segmented images to create the original cine-angiography video for
intraoperative application.
2
      </p>
    </sec>
    <sec id="sec-2">
      <title>Proposed Approach</title>
      <p>
        The main goal of this work is to provide a new approach for automatic vessel
segmentation from cine-angiography videos. The work ow of the proposed
framework, illustrated in Figure 1, can be divided into three steps: (i) pre-processing
operations build a set of images from cine-angiography videos and increase vessel
enhancement, (ii) a fully convolutional deep neural network architecture called
\U-net" [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ] used in [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ] is used to segment the vascular tree from the video frames,
and (iii) sequences of segmented static images are combined to reconstruct the
cine-angiography videos for the intraoperative application. It is worth noting
that we start from the approach of [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ] in order to provide clinicians with a
different tool for segmenting ilio-femoral district; indeed, di erently from the cited
work, the cine-angiography video is subdivided into di erent frames instead of a
static reconstructed image. Then, U-net perform segmentation on di erent kind
of dataset.
3
      </p>
    </sec>
    <sec id="sec-3">
      <title>Pre-processing of ilio-femoral images</title>
      <p>
        Ilio-femoral images show some lighting variations, poor contrast and noise. To
reduce these imperfections and generate images more suitable for extracting
blood vessels, we applied following preprocessing steps:
{ Contrast Limited Adaptive Histogram Equalization [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ]
{ Gamma correction [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ]
{ Background homogenization
      </p>
      <p>As shown in Fig. 2, the resulting image shows an improvement of the lighting
variations and the contrast between background and vessels. These preprocessing
steps are necessary to remove noise and artifacts from the image in order to
improve segmentation accuracy and detection of blood vessels.</p>
    </sec>
    <sec id="sec-4">
      <title>Network Description</title>
      <p>
        The U-net model is a fully convolutional network with symmetrical structure,
composed of a contracting and an up-sampling part. The contracting path
consists of the repeated application of two 3 3 convolutions and a 2 2 maxpooling
operation with stride 2 for downsampling. The expansive path consists of an
upsampling of the feature map followed by a two 3 3 convolutions. In the nal
layer, a 1 1 convolution is used to map all 64 component feature vectors to the
desired number of classes [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ]. All layers use Recti ed Linear Unit (ReLU) [
        <xref ref-type="bibr" rid="ref7">7</xref>
        ],
except for the last layer, where Softmax [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ] is used in order to select the best
scoring category; hence, for each pixel it returns the probability to be part of a
vessel or not. The U-net architecture adapted by [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ] is showed in Figure 3.
The U-net [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ] was trained on 30; 600 tiles extracted from cine-angiographies. The
ground truth used to accomplish the supervised learning was represented by a
manual segmentation executed by an expert clinician. Data acquisition, as well
as, data annotation, was executed the Interventional Cardiology Units of Magna
Graecia University Hospital (Catanzaro, Italy) and at Federico II University
Hospital (Naples, Italy).
      </p>
      <p>For the real daily usage, once a DICOM le has been read, automatic
segmentation of a 60 seconds cine-angiography (357 frames) takes, on the average, 90
seconds with an AUC mean value of 0:988 0:006. As a result, original images
with the highlited vessel tree is shown to the clinicians.
Considering that the cineangiography is an invasive procedure, the time
available for collecting all data and de ning a correct prognosis is usually quite
short. Hence, a shorter timescale is needed for improving the clinical
interpretation of the complexity of vascular collaterals in PAOD patients. Our proposed
method features an intraoperative application to identify vascular abnormalities,
thanks to a robust segmentation process of the cine-angiography video during
the surgery.</p>
      <p>By looking to this enhanced cine-angiography, operators can better visualize
the vessels and evaluate condition of patients more easily. Structures that are
not of interest (such as catheters and cables) are correctly recognized as \non
vessel" and excluded from the nal segmentation. Finally, given that the process
result to be e cient enough to grant the generation of such enriched images
also on ordinary hardware, the proposed work ow is already applicable into any
typical intraoperative scenario.</p>
      <p>Further e orts will be spent to both improve the segmentation accuracy and
speed-up the process in order to obtain a more accurate and fast, up to real-time,
segmentation work ow.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <ref id="ref1">
        <mixed-citation>
          1.
          <string-name>
            <surname>Prior</surname>
            <given-names>B.M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Lloyd</surname>
            <given-names>P.G.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Ren</surname>
            <given-names>J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Li</surname>
            <given-names>H.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Yang</surname>
            <given-names>H.T.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Laughlin</surname>
            <given-names>M.H.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Terjung</surname>
            <given-names>R.L.</given-names>
          </string-name>
          ,
          <article-title>\Time course of changes in collateral blood ow and isolated vessel size and gene expression after femoral artery occlusion in rats,"</article-title>
          <source>American Journal of PhysiologyHeart and Circulatory Physiology</source>
          , vol.
          <volume>287</volume>
          (
          <issue>6</issue>
          ), pp.
          <source>H2434{H2447</source>
          ,
          <year>2004</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref2">
        <mixed-citation>
          2.
          <string-name>
            <surname>McDermott M.M.</surname>
          </string-name>
          ,
          <string-name>
            <surname>Liu</surname>
            <given-names>K.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Carroll</surname>
            <given-names>T.J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Tian</surname>
            <given-names>L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Ferrucci</surname>
            <given-names>L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Li</surname>
            <given-names>D.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Carr</surname>
            <given-names>J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Guralnik</surname>
            <given-names>J.M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Kibbe</surname>
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Pearce</surname>
            <given-names>W.H.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Yuan</surname>
            <given-names>C.</given-names>
          </string-name>
          , \
          <article-title>Super cial femoral artery plaque and functional performance in peripheral arterial disease: walking and leg circulation study (WALCS III),"</article-title>
          <source>JACC: Cardiovascular Imaging</source>
          , vol.
          <volume>4</volume>
          (
          <issue>7</issue>
          ), pp.
          <volume>730</volume>
          {
          <issue>739</issue>
          ,
          <year>2011</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref3">
        <mixed-citation>
          3.
          <string-name>
            <surname>Bruno</surname>
            <given-names>P.</given-names>
          </string-name>
          , Za no
          <string-name>
            <given-names>P.</given-names>
            ,
            <surname>Scaramuzzino</surname>
          </string-name>
          <string-name>
            <given-names>S.</given-names>
            , De Rosa S.,
            <surname>Indol</surname>
          </string-name>
          <string-name>
            <given-names>C.</given-names>
            ,
            <surname>Calimeri</surname>
          </string-name>
          <string-name>
            <given-names>F.</given-names>
            ,
            <surname>Spadea</surname>
          </string-name>
          <string-name>
            <surname>M. F.</surname>
          </string-name>
          , \
          <article-title>Using CNNs for Designing and Implementing an Automatic Vascular Segmentation Method of Biomedical Images,"</article-title>
          <year>2018</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref4">
        <mixed-citation>
          4.
          <string-name>
            <surname>Ronneberger</surname>
            , Olaf,
            <given-names>Fischer P.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Brox</surname>
            <given-names>T.</given-names>
          </string-name>
          , \
          <article-title>U-net: Convolutional networks for biomedical image segmentation," International Conference on Medical image computing and computer-assisted intervention</article-title>
          , Springer, Cham, pp.
          <volume>234</volume>
          {
          <issue>241</issue>
          <year>2015</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref5">
        <mixed-citation>
          5.
          <string-name>
            <surname>Reza</surname>
            <given-names>A. M.</given-names>
          </string-name>
          , \
          <article-title>Realization of the contrast limited adaptive histogram equalization (CLAHE) for real-time image enhancement," Journal of VLSI signal processing systems for signal, image and video technology</article-title>
          , vol.
          <volume>38</volume>
          (
          <issue>1</issue>
          ), pp.
          <volume>35</volume>
          {
          <issue>44</issue>
          ,
          <year>2004</year>
        </mixed-citation>
      </ref>
      <ref id="ref6">
        <mixed-citation>
          6.
          <string-name>
            <surname>Farid</surname>
            <given-names>H.</given-names>
          </string-name>
          , \
          <article-title>Blind inverse gamma correction</article-title>
          .
          <source>IEEE Transactions on Image Processing,"</source>
          vol.
          <volume>10</volume>
          (
          <issue>10</issue>
          ), pp.
          <volume>1428</volume>
          {
          <issue>1433</issue>
          ,
          <year>2001</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref7">
        <mixed-citation>
          7.
          <string-name>
            <surname>Dahl</surname>
            <given-names>G. E.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Sainath</surname>
            <given-names>T. N.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Hinton</surname>
            <given-names>G. E.</given-names>
          </string-name>
          , \
          <article-title>Improving deep neural networks for LVCSR using recti ed linear units and dropout,"</article-title>
          <source>IEEE International Conference</source>
          , pp.
          <volume>8609</volume>
          {
          <issue>8613</issue>
          ,
          <year>2013</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref8">
        <mixed-citation>
          8.
          <string-name>
            <surname>Gold</surname>
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Rangarajan</surname>
            <given-names>A.</given-names>
          </string-name>
          , \
          <article-title>Softmax to softassign: Neural network algorithms for combinatorial optimization,"</article-title>
          <source>Journal of Arti cial Neural Networks</source>
          , vol.
          <volume>2</volume>
          (
          <issue>4</issue>
          ), pp.
          <volume>381</volume>
          {
          <issue>399</issue>
          ,
          <year>1996</year>
          .
        </mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>