<!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>Liver Vessel Segmentation Using Gradient Vector Flow</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Caspar J. Goch</string-name>
          <email>c.goch@dkfz-heidelberg.de</email>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Xin Wang</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Hans-Peter Meinzer</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Ingmar Wegner</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Division of Medical and Biological Informatics, DKFZ Heidelberg</institution>
        </aff>
      </contrib-group>
      <fpage>104</fpage>
      <lpage>108</lpage>
      <abstract>
        <p>An accurate segmentation of vascular systems is fundamental for many medical applications. Stability against different contrast levels and noise are very important. In this paper we propose an approach for the segmentation of the vascular system of the liver. It is based on the gradient vector flow (GVF) and Frangis vesselness measure. This method avoids multi-scale analysis and related scale space problems. It was evaluated on ten CT data-sets.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>Introduction</title>
      <p>The segmentation of the vascular tree of the liver is important for diagnosis and
therapy. It is the prerequisite for the calculation of supply areas within the liver
and segmentation of the liver segments. These are the foundation for surgical
planning in the liver.</p>
      <p>
        Many works have been presented for the segmentation of vessels and
similar tube-like structures across various organs [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. Each organ poses different
challenges and requires different approaches.
      </p>
      <p>
        A promising methods is the use of the gradient vector flow technique for
segmenting tube-like structures of different scales. Bauer et al. have so far
tested it on coronary arteries and bronchial trees [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. The advantage of the
gradient vector flow is a diffusion of the edge information. This removes the
need for a multi scale analysis of the image. The range of the edge information
is increased, so that different sizes of vessels behave similar during later analysis
for vesselness.
      </p>
      <p>This work examines whether this approach can be applied to the
segmentation of liver vessels.</p>
    </sec>
    <sec id="sec-2">
      <title>Materials and Methods</title>
      <p>The algorithms discussed here are designed to work on already pre-segmented
and masked liver data. The liver vessel segmentation is achieved by multiple
steps.</p>
      <p>For the segmentation of the vascular system of the liver the vessels have to
be identified. This is achieved by calculating a vesselness for each voxel.</p>
      <sec id="sec-2-1">
        <title>Preprocessing</title>
        <p>A histogram of the image data is calculated. The maximum of the bell shape is
found and the number of voxels with this gray value is saved as nmax. This is
the non-zero gray value range, that is most prominent in the image. The entire
bell shape consists of the gray value ranges of tissue as well as vessels. As vessels
are on average brighter than the surrounding tissue, and the vessels comprise a
much smaller volume, than the liver tissue in itself, so they do not influence the
bell shape distribution in major manner. Trials have shown, that following the
bell shape until the number of voxels with a certain gray value drops to under
45 % of nmax leads to a threshold that minimizes the number of of vascular
voxels that are missed, while significantly reducing the number of false positives.
This value is our lower threshold thlow.
2.2</p>
      </sec>
      <sec id="sec-2-2">
        <title>Tube Detection</title>
        <p>An image containing the gradient of the original image is calculated
Fgrad = ∇I(x1; x2; x3)
(1)
The resulting image is a vector field, where each vector points to the closest
edge.</p>
        <p>The image of a masked liver has steep edges around the liver itself. These
edges can in the course of our further analysis of the image lead to unwanted
responses. To reduce these we suppress any edges between voxel values lower
than the thlow and voxels with a non liver gray value. Typical non liver values
are zero in the masked area and values lower than zero if part of the lung has
falsely been included in the liver segmentation. Edges between non liver values
and values higher than thlow are not suppressed, as they might belong to a vessel
very close to the edge of the segmented area such as vessels joining a vena cava
not included in the liver segmentation.</p>
        <p>
          This gradient vector field is then normalized as suggested in the work by
Bauer and Bischof [
          <xref ref-type="bibr" rid="ref3">3</xref>
          ]. Here normalization is required to account for varying
contrast situations. It reduces the influence of very high gradients as introduced
by pathologies, such as calcifications. While the reduction of these high responses
is desirable a standard normalization would result in unwanted influences by
gradients due to noise in the tissue. To prevent this a custom normalization is
defined, which gives a standard normalization for high gradients and suppresses
low magnitude gradients
        </p>
        <p>Fn(x) =</p>
        <p>F (x) min(|F (x)|; Fmax)
|F (x)|</p>
        <p>Fmax
(2)</p>
        <p>
          On this vector field the gradient vector flow as proposed by Xu and Prince [
          <xref ref-type="bibr" rid="ref4">4</xref>
          ]
is performed.
        </p>
        <p>The vector field V (x) that minimizes the energy for equation (3) is computed</p>
        <p>E(V ) =
∫∫∫
|∇V (x)|2 + |Fn|2|V − Fn|2dx
(3)</p>
        <p>The relevant information is represented in the direction of the resulting
vectors while their magnitude is of no importance. Any vectors with an extremely
small magnitude are removed. Therefore the resulting vector field is further
normalized Vn(x) = V (x)=|V (x)|. To compute from the vector field the vesselness
of structures in the original image we apply an additional gradient filter.</p>
        <p>The resulting matrices are similar to the Hessian matrices H = ∇ ∗ ∇ ∗ I,
but they are not necessarily symmetrical. They are symmetrized by using the
following formula</p>
        <p>Ms(x)ij =
{M (x)ij</p>
        <p>i = j
12 · (M (x)ij + M (x)ji) i ̸= j
(4)</p>
        <p>
          From these matrices a vesselness measure can be calculated. Tube-like bright
structures on a darker background can be identified by the eigenvalue of the
Hessian matrices. For liver vessels the vesselness measure by Frangi [
          <xref ref-type="bibr" rid="ref5">5</xref>
          ] is used.
if 2 &gt; 0 or 3 &gt; 0
o =
{0
(
1 − exp(− R2 A22 )) exp(− R2 B22 ) (1 − exp(− 2Sc22 ))
(5)
By adjusting the variables ; ; c the sensitivity of the vesselness detection can
be adjusted.
2.3
        </p>
      </sec>
      <sec id="sec-2-3">
        <title>Vesselness Evaluation</title>
        <p>The vesselness image obtained so far results in many non zero responses for
structures that are slightly tube like. To reduce such artefacts the vesselness
measure is thresholded to include only objects of sufficient similarity to tubular
structures.</p>
        <p>After reducing the vesselness image to those structures most likely to be
bright tubular structures on darker background the vesselness image is
considered in combination with the original gray value image. The original gray values
of any voxel with a non zero vesselness is compared to the window of likely vessel
gray values as calculated during preprocessing. As any tubular structures falling
outside of this gray value range are unlikely to be liver vessels they are masked
from the vesselness image.</p>
        <p>To further reduce spurious responses and isolated false positives the resulting
vesselness image is analyzed for connected structures.</p>
        <p>These connected areas are then sorted by size and any below a certain size
are dismissed as noise. As vascular systems consist of several thousands of voxels
a value of 500 as proven to be a reasonable threshold.</p>
      </sec>
      <sec id="sec-2-4">
        <title>Vessel Tree Creation</title>
        <p>Depending on the exact anatomical configuration and whether or not the vena
cava is included in the image data the entire vascular tree is detected as a single
connected structure or as several. For the detection we assume, that the detected
structure with the largest volume is the entire vessel tree. For image data where
connecting vessels have been masked out more structures have to be considered
to achieve a complete result.</p>
        <p>
          In addition to the segmentation a root point is required for the creation of a
vessel tree. This could either be detected automatically or set by the user. For
purposes of this work it has been set manually to compare the results with the
ground truth data. Using segmentation and root a vessel tree representation of
the available data is created as described in [
          <xref ref-type="bibr" rid="ref6">6</xref>
          ].
        </p>
        <p>The resulting tree is then pruned to reduce spurious branches:
1. The vessel is very short and does not contain more than two vessel elements.
2. The vessels maximal radius is very small. This indicates either noise, that
represents a false vessel or an existing vessel which is very thin. Such vessels
are pruned to remove false positives while retaining a highly detailed vessel
tree.
3. The vessel has a high mean and maximal angle. Such “corkscrew” shapes
are a typical sign of leakage in the segmentation.
3</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>Results</title>
      <p>The algorithm described in this work has been evaluated on ten data sets, for
each of which a reference tree has been segmented manually by a medical
professional. For the evaluation the fixed values of ( = 0:5; = 0:5; c = 0:5) were
used, which have been found in a prior evaluation.</p>
      <p>Table 1 shows a comparison between the reference trees R and the computed
trees A. The first column is the overall length of all vessels of the computed trees,
the second that of the overall length of all vessels of the reference trees. The
third and forth column show the length where the centerline of one tree is within
the vessel radius of the other. The third column can be read as the specificity,
describing which part of the vessel tree is within the boundaries of the reference
tree, whereas the fourth is the sensitivity, describing how much of the reference
tree is correctly detected.</p>
      <p>As can be derived from table 1 the sensitivity ranges between 55 % and
92 % and the specificity between 35 % and 70 %. Manual comparison of the
corresponding vesseltrees shows, that a likely vessel to be falsely detected is the
vena cava, which is correctly segmented in the reference vessels, but seems to be
to large and uniform to be correctly detected by the proposed method. Also in
those cases where a large part of the reference tree is not within the computed
tree, that is due to the vena cava being masked out, resulting in disconnected
component trees, so that the second branch is detected as a separate object and
discarded before the formation of a vesseltree.</p>
      <p>F
G
H
I
J
K
L
M
N
O</p>
      <p>Length A</p>
      <p>Length R
4</p>
    </sec>
    <sec id="sec-4">
      <title>Discussion</title>
      <p>The presented work shows that the gradient vector flow technique can be used to
segment the vascular system of the liver using the gradient vector flow approach.
By using this method the computationally very intensive multi scale calculations
can be avoided.</p>
      <p>Acknowledgement. This work was supported by the German Research
Foundation (DFG) in the context of the research project “Protektive
Beatmungskonzepte”.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <ref id="ref1">
        <mixed-citation>
          1.
          <string-name>
            <surname>Lesage</surname>
            <given-names>D</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Angelini</surname>
            <given-names>ED</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bloch</surname>
            <given-names>I</given-names>
          </string-name>
          , et al.
          <article-title>A review of 3D vessel lumen segmentation techniques: models, features and extraction schemes</article-title>
          .
          <source>Med Image Anal</source>
          .
          <year>2009</year>
          ;
          <volume>13</volume>
          :
          <fpage>819</fpage>
          -
          <lpage>45</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref2">
        <mixed-citation>
          2.
          <string-name>
            <surname>Bauer</surname>
            <given-names>C</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bischof</surname>
            <given-names>H</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Beichel</surname>
            <given-names>R</given-names>
          </string-name>
          .
          <article-title>Segmentation of airways based on gradient vector flow</article-title>
          .
          <source>In: Proc EXACT; 2009</source>
          . p.
          <fpage>191</fpage>
          -
          <lpage>201</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref3">
        <mixed-citation>
          3.
          <string-name>
            <surname>Bauer</surname>
            <given-names>C</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bischof H</surname>
          </string-name>
          .
          <article-title>Edge based tube detection for coronary artery centerline extraction</article-title>
          .
          <source>Insight J</source>
          .
          <year>2008</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref4">
        <mixed-citation>
          4.
          <string-name>
            <surname>Xu</surname>
            <given-names>C</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Prince JL</surname>
          </string-name>
          .
          <article-title>Snakes, shapes, and gradient vector flow</article-title>
          .
          <source>In: IEEE Trans Image Process</source>
          . vol.
          <volume>7</volume>
          ;
          <year>1998</year>
          . p.
          <fpage>359</fpage>
          -
          <lpage>69</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref5">
        <mixed-citation>
          5.
          <string-name>
            <surname>Frangi</surname>
            <given-names>AF</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Niessen</surname>
            <given-names>WJ</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Vincken</surname>
            <given-names>KL</given-names>
          </string-name>
          , et al.
          <article-title>Multiscale vessel enhancement filtering</article-title>
          .
          <source>In: Proc MICCAI; 1998</source>
          . p.
          <fpage>130</fpage>
          -
          <lpage>7</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref6">
        <mixed-citation>
          6. Scho¨binger M,
          <string-name>
            <surname>Thorn</surname>
            <given-names>M</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Vetter</surname>
            <given-names>M</given-names>
          </string-name>
          , et al.
          <article-title>Robuste Analyse von Gefa¨ßstrukturen auf Basis einer 3D-Skelettierung</article-title>
          .
          <source>In: Proc BVM; 2003</source>
          . p.
          <fpage>76</fpage>
          -
          <lpage>80</lpage>
          .
        </mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>