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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Digital Kymography for the Analysis of the Opening and Closure Intervals of Heart Valves</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Sven Friedl</string-name>
          <email>sven.friedl@iis.fraunhofer.de</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Stefan Ko¨nig</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Markus Kondruweit</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Thomas Wittenberg</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Fraunhofer Institute for Integrated Circuits IIS</institution>
          ,
          <addr-line>Erlangen</addr-line>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>University Hospital Erlangen</institution>
        </aff>
      </contrib-group>
      <fpage>144</fpage>
      <lpage>148</lpage>
      <abstract>
        <p>The opening and closure intervals of heart valves are important factors regarding an optimal blood flow. Using endoscopic video recordings of heart valves, digital kymography can be a method to visualize and to describe the opening and closure intervals. Based on an adequate segmentation of the kymograms, a quantitative description becomes available for the opening and closure characteristics. Furthermore, by normalizing the measured results, comparisons of mean heart valve oscillations can be achieved. Here, a comparison of artificial with native heart valves obtained under physiological conditions, indicates clear differences in the opening and closure intervals.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>Introduction</title>
      <p>
        The opening and closure intervals of heart valves are important factors
regarding an optimal blood flow. In particular for artificial heart valves, an analysis
of those intervals is essential to estimate the physiological characteristics and
to evaluate the graft as well as the implantation technique. Digital high speed
recording of artificial heart valves is a young but promising approach to analyze
the movement and behavior of the grafts. For example, Lu et al. [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ] as well
measured the opening and closure times of different artificial valve types using a high
speed camera. Kaminsky et al. [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ] evaluated the flow behind the valves using
high speed videos and particle image velocimetry. As one major prerequisite for
automated measuring analysis is image segmentation, various working groups
have proposed approaches for the delineation of the orifice area. Condurache et
al. [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ] compared threshold-based methods to active contours, whereas
Wittenberg et al. [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ] focused on active contours to analyze the valve movements. Hahn
et al. [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ] used different threshold-based methods to apply a frequency analysis to
evaluate the flattering of the leaflets. Weiß et al. [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ] presented a compact
visualization of the movements based on segmentation by an edge-amplified region
growing. Nearly all of the digital video recordings of heart valves and the
accordant evaluations are restricted to artificial grafts and to experimental setups.
Recently alternative methods are evolving, which are allowing to record heart
valve movements under physiological conditions [
        <xref ref-type="bibr" rid="ref7">7</xref>
        ]. Thus, next to artificial ones,
native heart valves also can be examined and the characteristics of both types
can be compared with each other.
      </p>
    </sec>
    <sec id="sec-2">
      <title>Materials and Methods</title>
      <sec id="sec-2-1">
        <title>Endoscopic Video Recordings</title>
        <p>For this pilot study of methods, endoscopic high speed video recordings of four
native and one artificial porcine aortic heart valve have been available. The
videos have been recorded in explanted pig hearts, which were reanimated and
the heart valves were observed with an endoscopic high speed video camera
with 2000–4000 frames per second. Having multiple recordings for each valve,
depicting approximately two to three systolic phases, in sum, a corpus of 37
phases of native valves and 9 phases of the artificial valve have been analyzed.
2.2</p>
      </sec>
      <sec id="sec-2-2">
        <title>Digital Kymography</title>
        <p>
          The principle of digital kymography is to plot extracted or projected image lines
along a time axis. Thus, image changes, as movements are, can be determined
and visualized in a compact manner. In the field of medical imaging it is applied
in different scenarios as CT reconstruction [
          <xref ref-type="bibr" rid="ref8">8</xref>
          ] or vocal fold analysis [
          <xref ref-type="bibr" rid="ref9">9</xref>
          ].
        </p>
        <p>To generate a kymogram from the high speed video recordings of heart valves,
a line segment</p>
        <p>
          l = fu + rvjr 2 [
          <xref ref-type="bibr" rid="ref1">0, 1</xref>
          ]g
with the vectors u and (u + v) as the end points of l is defined in one initial frame
of the video sequence (Fig. 1, top). In each frame I(t) of the complete sequence
or a defined subsequence, the pixel under the line segment are extracted to
k(t) = l(I(t))
(1)
(2)
        </p>
        <p>Opening interval [ms]
Interval of max. orifice [ms]
Closure interval [ms]</p>
        <p>Native valves
composing the final kymogram K as can be seen for a native aortic valve in
Fig. 1, bottom.
The digital kymogram visualizes the movements of the leaflets in a compact
manner. For a more quantitative description, the orifice area within the
kymograms can be segmented using simple thresholding. Smaller artifacts can be
removed by morphological operations and by regarding only segmented areas
with a significant size. Thus the orifice distance during the phases of opening
and closing can be extracted from the kymograms. Since the horizontal axis of a
kymogram describes the time axis of the video sequence, the orifice opening d(t)
of a leaflet can be determined for each discrete time by calculating the vertical
length of the segmentation.</p>
        <p>With a lack of spatial calibration within the available recordings, normalized
orifice distances are computed according to d′ = d ma1x00(d) to achieve comparable
measures. The resulting normalized distances are plotted along a normalized
time axis t′ defined by t′ = t ∑ ∆t with ∑ ∆t as the sum of the durations of all
100
intervals of one phase.
3</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>Results</title>
      <p>The 37 phases of native and the 9 phases of the artificial heart valves have been
analyzed. Within each of the phases, a digital kymogram has been generated for
all of the three leaflets. In the resulting kymograms, specific intervals are defined
and the corresponding durations are calculated. For the analysis of the opening
and closure of the heart valves, the durations ∆t of the opening interval, of the
phase of maximal orifice and of the closure interval are determined (Fig. 2).</p>
      <p>Examining all kymograms of the native, respectively the artificial valves, the
mean durations of the different intervals can be determined. Table 1 shows the
results for the available recordings. Thus, the differences between the intervals
and in particular the differences of the intervals between native and artificial
valves can be evaluated. In case of the native heart valves, the opening interval
is much shorter than the closure interval. These measures match with the known
physiology of heart valves. For the artificial heart valves, the interval of maximal
orifice is much longer than the opening and closure and the closure interval is
significant shorter than in case of native valves.</p>
      <p>This fact becomes more noticeable, by observing the normalized
measurements of the segmented kymograms. The weighted mean of all normalized
kymogram functions respective to time-dependent orifice opening of the native,
respectively the artificial valves is computed (Fig. 3). The plots are now
containing the movement of a typical mean heart valve and show the quantitative
differences between the artificial and the native valves.
4</p>
    </sec>
    <sec id="sec-4">
      <title>Discussion</title>
      <p>Digital kymography enables a fast, convenient and stable analysis of the
opening and closure intervals of heart valves. The kymogram allows to estimate the
progress of the movements and to measure the durations. With the
segmentation of the kymograms and the normalization of the scales, a more quantitative
description of typical valve movements is possible. The first results with few
recordings indicate clear differences between artificial and native heart valves.
Of course, a final conclusion is not yet possible. Due to the complex and costly
recording technique, the availability of recordings under physiological conditions
is limited. Alternative experimental setups can help to improve and stabilize the
methods, but for a clinical study, physiological conditions are essential. Due to
the architecture of mechanical caged ball valves, the method of digital
kymography as described above is not suitable for those. But for native and artificial
biological valves as well as mechanical leaflet valves, digital kymography enables
a systematic study of the intervals in different heart valve grafts and a
comparison with native ones.</p>
    </sec>
  </body>
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