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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Extracting the Fine Structure of the Left Cardiac Ventricle in 4D CT Data</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>A Semi-Automatic Segmentation Pipeline</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Juliane Dinse</string-name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Daniela Wellein</string-name>
          <email>daniela.wellein@medizin.uni-leipzig.de</email>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Matthias Pfeifle</string-name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Silvia Born</string-name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Thilo Noack</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Matthias Gutberlet</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Lukas Lehmkuhl</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Oliver Burgert</string-name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Bernhard Preim</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Herzzentrum Leipzig</institution>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Institut fu ̈r Simulation und Graphik, Otto-von-Guerike-Universita ̈t Magdeburg</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>Neurochirurgische Klinik, Universita ̈tsklinikum Tu ̈bingen</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution>VCM/ICCAS, Universita ̈t Leipzig</institution>
        </aff>
      </contrib-group>
      <fpage>264</fpage>
      <lpage>268</lpage>
      <abstract>
        <p>We propose a pipeline for the segmentation of the left cardiac ventricle (LV) in 4D CT data based on the random walker (RW) algorithm. A segmentation of the LV allows to extract clinical relevant parameters such as ejection fraction (EF) and volume over time (VoT), supporting diagnostic and therapy planning. The presented pipeline works aside approaches incorporating annotated databases, statistical shape modeling or atlas-based segmentation. We have tested our segmentation approach on six clinical 4D CT datasets including different pathologies and typical artifacts and compared the segmentation results to manually segmented slices. We achieve a minimum sensitivity of 86% and specificity of 96%. The resulting EF and VoT is comparable to known reference values and reflects the present pathologies correctly. Additionally, we tested three different routines for thresholding the RW probability maps. An interview with surgical and radiological experts together with high sensitivity scores indicates the superiority of the fixed threshold selection method - especially in the presence of pathologies. The segmentation is also correct near problematic fine structures such as cardiac valves, papillary muscles and the apex of the heart.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>A segmentation of the left cardiac ventricle (LV) in 4D CT data is necessary for
a functional analysis of the heart. Clinical parameters are often approximated
and/or only estimated in end-diastole and end-systole. With the opportunity to
measure the ejection fraction (EF) and the volume over time (VoT),
diagnostics and therapy planning can be supported. For such an analysis the correct
segmentation of cardiac fine structures such as the valves, the papillary muscle
(PM), the apex and the heart’s inner myocardium, is important.</p>
      <p>
        For the segmentation of the LV various approaches exist. Jolly et al. combine
edge, region and shape information for the segmentation of the left ventricle
in MRI [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. Zheng et al. use a database of models and an automatic fitting
to segment all four cardiac chambers in CT data [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. For the fitting they use
manually defined landmarks to deform the control points of the models according
to the data. Kirisli et al. propose a multi-atlas-based segmentation of the whole
heart in 3D CTA data [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ]. They match atlas information and data using a
non-rigid registration framework.
      </p>
      <p>Unlike the presented segmentation approaches, we focus on a correct
segmentation of the above mentioned cardiac structures. The proposed semi-automatic
pipeline allows the inspection (and correction) of all intermediate results to
incorporate expert knowledge of the segmenting radiological and surgical experts.
2</p>
    </sec>
    <sec id="sec-2">
      <title>Materials and Methods</title>
      <p>We evaluated our segmentation pipeline on six clinical 4D CT datasets with 10
or 20 time steps. The dimensions of the datasets have been 512x512x254 111
and pixel size was 0.36-0.58mm with a slice distance of 0.67-1.00mm. The
pathologies present in the datasets include coronary artery disease, aortic
stenosis, and restricted, dilated, and hypertrophic cardiomyopathy (cardiac muscle is
too less/too much compacted). Two of the datasets included a metallic mitral
valve replacement, and therefore a high degree of metal artifacts.</p>
      <p>
        The proposed pipeline has been integrated into the volume data processing
and visualization platform VolV [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ] which has already been applied to
segmentation in neurosurgical intervention planning [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ]. The pipeline consists of three
main steps: pre-processing, random walker (RW), and post-processing (Fig. 1).
Pre-processing includes anisotropic filtering [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ] and an edge enhancement
filtering, implemented as the difference image between the original and the mean
filtered data. The main step of the pipeline is the RW algorithm, which is
formulated on a graph and has strong connections to electrical circuit and
potential theory. Its input are labeled voxels belonging to two classes: LV and
non-LV structure, i.e. background. The algorithm analytically determines the
probability that a random walker starting at each unlabeled voxel will first reach
one of the pre-labeled voxels [
        <xref ref-type="bibr" rid="ref7">7</xref>
        ]. Output of RW is a probability map in which
each voxel is assigned to the label with the highest probability. To initialize
the pipeline (Fig. 1), the user has to label a few voxels of the LV and all other
anatomical structures (background) only for t = 1. The labeling does not require
any delineation of object boundaries and can be inexact, and, therefore quick.
      </p>
      <p>In the post-processing step, the RW probability map is thresholded to generate
the final LV segmentation for the current time step. We used three different
thresholding approaches: a manual threshold selection, fixing the threshold to a
specific probability and calculating the minimum in the histogram of each time
step. Also, a set of labeled seed points for the next time step is generated by
reducing the segmentation results of the LV and the background with multiple
erosions.</p>
      <p>For evaluation, three slices in every time step of each of the six datasets
(capturing the valves, the papillary muscles, and the cardiac apex) have been
manually segmented, which leads to an overall number of 3 90 = 270 slices.
The sensitivity (SE) and specificity (SP) for each dataset and each
thresholding method is computed. The volume over time and the ejection fraction
together with its mean squared error to the manual segmentation (MSEEF ) are
calculated and compared to known reference values. In an interview, four
surgical/radiological experts have ranked the segmentation results of the different
thresholding methods and rated them according to the correct detection of the
previously mentioned fine structures.
3</p>
    </sec>
    <sec id="sec-3">
      <title>Results</title>
      <p>In the interview the clinical experts preferred the segmentation results of
the fixed threshold routine in four out of six datasets. They also confirmed the
overall correct detection of the cardiac fine structures.
4</p>
    </sec>
    <sec id="sec-4">
      <title>Discussion</title>
      <p>The previously given SE and SP values correlate with the expert ratings, which
indicate, that in our case three manually segmented slices might be enough
to measure the segmentation quality. A high SE and SP with a low standard
deviation lets us conclude, that the performance is constantly high throughout all
tested datasets. The VoT curves (Fig. 4) reflect the general pump (dys-)function
of the present pathologies. In DS4 the restrictive cardiomyopathy leads to a delay
in proper blood filling in the diastole. This results in a decreased slope of the
VoT for the second half of the heart cycle.</p>
      <p>
        The obtained EF values also reflect the underlying pathologies. In DS6 the
EF is below 50% for the fixed thresholding. A value, that corresponds to the
present dilated cardiomyopathy, in which the amount of blood being pumped
out of the LV in the diastole is reduced. In addition, we compared the MSEEF
to the results presented by Zheng et al. [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. On six datasets with 10 time steps
each, they obtained an MSEEF of 2:3% ( 1:6). Our MSEEF of 2:2% for fixed
thresholding is comparable, but one has to mention, that this measure is
computed in relation to only three manually segmented slices, which might not be
enough to deduce the volume of the LV.
      </p>
      <p>In some of the datasets, the plane of the mitral valves, that delineates the LV,
is not correctly detected with our pipeline. The dysfunction of the mitral valve
leads to the leaflets hitting the cardiac wall and, therefore, they are not detected
in the segmentation. In addition, the rapid and inconsistent movement of the</p>
      <p>DS5</p>
      <p>DS6
mitral valve makes them undetectable in some datasets and, the segmentation
leaks into the atrium. Furthermore, the PM could be wrongly segmented as
belonging to the LV, when the connections between myocardium and PM are
too small in the datasets or the contrast between those two structures is too high
(PM not dark enough).</p>
      <p>To conclude, our pipeline provides a segmentation of the LV that is
independent from atlas or large database information. The segmentation quality is high
also in the presence of pathologies and artifacts and is able to correctly detect
cardiac fine structures. These findings could also be confirmed in an interview
with clinical experts.</p>
      <p>
        A promising future work approach would be to use the grey value frequencies
in a weighting function for the RW. This was proposed by Grady and Jolly [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ],
who have shown that their approach outperforms purely intensity-based
weighting functions.
      </p>
    </sec>
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