<!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>Creating Graph Abstractions for the Interpretation of Combined Functional and Anatomical Medical Images</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Ashnil Kumar</string-name>
          <email>ashnil.kumar@sydney.edu.au</email>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Jinman Kim</string-name>
          <email>jinman.kim@sydney.edu.au</email>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Michael Fulham</string-name>
          <email>michael.fulham@sydney.edu.au</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Dagan Feng</string-name>
          <email>dagan.feng@sydney.edu.au</email>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Department of Molecular Imaging, Royal Prince Alfred Hospital</institution>
          ,
          <addr-line>Sydney</addr-line>
          ,
          <country country="AU">Australia</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Med-X Institute, Shanghai Jiao Tong University</institution>
          ,
          <country country="CN">China</country>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>School of Information Technologies, University of Sydney</institution>
          ,
          <country country="AU">Australia</country>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution>Sydney Medical School, University of Sydney</institution>
          ,
          <country country="AU">Australia</country>
        </aff>
      </contrib-group>
      <fpage>63</fpage>
      <lpage>72</lpage>
      <abstract>
        <p>The characteristics of the images produced by advanced scanning technologies has led to medical imaging playing a critical role in modern healthcare. The most advanced medical scanners combine different modalities to produce multi-dimensional (3D/4D) complex data that is time-consuming and challenging interpret. The assimilation of these data is further compounded when multiple such images have to be compared, e.g., when assessing a patient's response to treatment or results from a clinical search engine. Abstract representations that present the important discriminating characteristics of the data have the potential to prioritise the critical information in images and provide a more intuitive overview of the data, thereby increasing productivity when interpreting multiple complex medical images. Such abstractions act as a preview of the overall information and allow humans to decide when detailed inspection is necessary. Graphs are a natural method for abstracting medical images as they can represent the relationships between any pathology and the anatomical structures they a ect. In this paper, we present a scheme for creating abstract graph visualisations that facilitate an intuitive comparison of the anatomy-pathology relationships within complex medical images. The properties of our abstractions are derived from the characteristics of regions of interest (ROIs) within the images. We demonstrate how our scheme is used to preview, interpret, and compare the location of tumours within volumetric (3D) functional and anatomical images.</p>
      </abstract>
      <kwd-group>
        <kwd>graph abstractions</kwd>
        <kwd>medical imaging</kwd>
        <kwd>image interpretation</kwd>
        <kwd>image comparison</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        Medical imaging plays an indispensable role in modern healthcare for diagnosis
and in the assessment of a patient's response to treatment. Technological
advancements have led to the creation of scanners that combine di erent imaging
modalities into a single device and are capable of producing high resolution and
multi-dimensional (3D/4D) images. The rst mainstream device was the
combination of positron emission tomography (PET) and computed tomography (CT)
to produce a PET-CT scanner that provides volumetric (3D) anatomical (CT)
and functional (PET) data, and enables clinicians to visualise the spatial
relationships between activity in a tumour with PET and the underlying location
from CT [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ].
      </p>
      <p>
        The interpretation of PET-CT images involves the assimilation of
information from both modalities simultaneously. This entails traversing the 3D image
as an ordered set of 2D slices and mentally reconstructing a spatial
understanding of the relationships between the anatomy and any pathology (disease); these
relationships are important for accurate diagnosis, for staging cancer, and
classifying di erent conditions [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. This interpretation process is time consuming since
most modern scanners produce hundreds (sometimes thousands) of slices per
image volume. Alternatively, the images can be fused into a 3D rendering but this
requires several manual image-speci c adjustments, e.g., visibility transfer
functions [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ]. Interpretation is more problematic when clinicians need to interpret
and compare multiple image volumes at the same time, e.g., when comparing
multiple images to assess a patient's response to treatment or when analysing
the results of a clinical image search engine.
      </p>
      <p>
        Existing methods for comparing images can be found as part of medical
image retrieval engines [4{6]. Similar to Google Image Search1, most of these
search engines [
        <xref ref-type="bibr" rid="ref4 ref5">4, 5</xref>
        ] present their retrieved images as a grid. Users then must
inspect and compare the pixel information of these images manually to select the
image most relevant to their query. However, such an approach is not feasible for
volumetric (3D) and multi-modality medical images due to the e ort required
during interpretation (described above).
      </p>
      <p>
        Tory and Moller [
        <xref ref-type="bibr" rid="ref7">7</xref>
        ] recommended several techniques that could assist
humans in interpreting and analysing visualisations. They suggested that enhanced
recognition of higher level patterns in complex information could be achieved by
creating abstractions from the selective omission and aggregation of the original
data. Since graphs are a natural and powerful way of representing relational
information [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ], we propose that medical images could be visualised using graph
abstractions of the complex spatial relationships between pathology and anatomy.
In our prior work [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ], we investigated this possibility by integrating 2D graph
abstractions as part of a medical image retrieval engine. A user study revealed
that the users found the abstractions helpful in determining which images were
relevant to their query [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ]. Users were able to eliminate dissimilar images based
on the tumour locations revealed in the abstraction without needing to inspect
the irrelevant images in detail but the 2D nature of the visualisation meant that
some information was obscured.
      </p>
      <p>
        In this paper we present a scheme for constructing graph abstractions of
relational information derived from medical images. In our method the
properties of the graph abstractions are derived from the visual characteristics of the
1 http://images.google.com
images they represent. Our aim is to create an abstraction that will act as a
summary or preview of the main content of an image and thus enable users to
decide when detailed inspection is necessary, especially in the context of
determining image similarity [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ]. The critical element is to preserve the spatial layout
of the important visual information while simplifying the overall visualisation.
We demonstrate our scheme on PET-CT images of patients with lung cancer.
PET-CT (as given earlier) is representative of modern complex medical images
that stand to bene t most from such abstractions. Our evaluation compares 2D
and 3D graph abstractions of medical images. We also compare the di erent
information from abstractions showing large objects (organs and tumours) and
smaller key points (landmarks).
2
2.1
      </p>
    </sec>
    <sec id="sec-2">
      <title>Methods</title>
      <sec id="sec-2-1">
        <title>Scheme for Creating Graph Abstractions</title>
        <p>
          Given that our examples are patients with lung cancer we chose as ROIs the
tumours and major anatomical structures above the diaphragm. We extracted
the left and right lungs from the CT images using a well-established adaptive
thresholding segmentation algorithm [
          <xref ref-type="bibr" rid="ref12">12</xref>
          ]. We also extracted the brain and
mediastinum from the CT images using manual connected thresholding. The tumours
in the PET images were segmented by rst detecting the locations with a
local peak radiotracer uptake (high image intensity) and then performing 40%
connected thresholding in the neighbourhood of the peaks [
          <xref ref-type="bibr" rid="ref13">13</xref>
          ].
        </p>
        <p>
          We analysed the 3D ROIs and extracted from each the volume (size), centroid
(absolute location), and distance to other ROIs. It is possible to extract more
features from these ROIs, e.g., as described by Kumar et al. [
          <xref ref-type="bibr" rid="ref14">14</xref>
          ]. Here, we
list only those features used speci cally in this paper for creating our graph
abstractions.
        </p>
        <p>
          The visualisation was created as follows:
1. Each object (segmented ROI) was represented by a single node on the graph.
2. The position of each graph node was derived from the coordinates of the
centroid of the ROI.
3. The proximity of the ROIs was used to determine the edge links [
          <xref ref-type="bibr" rid="ref14">14</xref>
          ].
4. The size of each graph node was based upon the volume of the ROIs.
5. The colour of each graph node was determined according to the structure it
represented (e.g., all tumours were given the same colour).
6. The nal position and size of each node (and the lengths of the edge links)
were adjusted according to the size of the rendering.
2.3
We used a 3D equivalent of the Gaussian pyramid method of Lowe [
          <xref ref-type="bibr" rid="ref11">11</xref>
          ] to detect
key points in the form of Di erence-of-Gaussian extrema in each of the image
volumes. Each key point was represented by a 3D coordinate, a scale factor, and
orientation parameters. We ltered the key points to retain only those CT points
that were in proximity to PET key points, and vice versa. Two key points were
determined to be in close proximity if the 3D distance between the coordinates
of the two points was less than or equal to any of their scale factors. This ltering
step eliminated key points that did not contribute to any relationship between
tumour and anatomy.
        </p>
        <p>
          We then extracted scale-invariant feature transform (SIFT) descriptors using
a 3D SIFT feature extractor [
          <xref ref-type="bibr" rid="ref15">15</xref>
          ] on these key points. We used k-means clustering
separately on the PET and CT descriptors to divide these descriptors into 200
groups (100 for CT and 100 for PET) [
          <xref ref-type="bibr" rid="ref16">16</xref>
          ].
        </p>
        <p>The visualisation was created as follows:
1. Each key point was represented by a single node on the graph.
2. The position of each graph node was derived from the key point's 3D
coordinates.
3. Two nodes were linked by an edge if they were in close spatial proximity to
each other. Proximity was determined in the same way as the ltering step
described above.
4. The colour of each node was determined by the group to which its descriptor
belonged. As such, two nodes with descriptors in the same group would have
the same colour.
5. The nal position and size of each node (and the lengths of the edge links)
were scaled according to the size of the rendering.
2.4</p>
      </sec>
      <sec id="sec-2-2">
        <title>Implementation</title>
        <p>
          We produced 2D and 3D visualisations of the graphs derived from our abstraction
scheme. The 2D visualisation of our abstraction was implemented using the Java
Universal Network/Graph (JUNG) library [
          <xref ref-type="bibr" rid="ref17">17</xref>
          ]. The 3D graph abstraction was
implemented using WebCoLa [
          <xref ref-type="bibr" rid="ref18">18</xref>
          ].
3
        </p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>Results and Discussion</title>
      <p>therefore made it possible to compare images based on the arrangement and
groupings of the key points within the images.</p>
      <p>
        Both the object and key point graph abstractions provide new views of the
content of the PET-CT image. The object abstractions depict the location of
the tumours and the structures that they a ect. These abstractions summarise
information that a clinician could potentially use when staging a cancer or when
determining if a patient's prognosis is improving [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. The key point abstractions
can show the complex interrelations within the image. An important property of
these images is when a portion of the graph is not highly connected with other
parts of the graph; then depending on the image features, such components may
be areas of further investigation, e.g. sites of new disease, tumour necrosis, etc.
The 3D abstraction of these key points o ers the opportunity for node merging
or clustering to identify large objects of interest in di erent images because key
points were originally used for object recognition [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ].
      </p>
      <p>A limitation of our abstractions is the densely connected graph (see central
parts of Figures 5 and 6). The densely connected graph is a result of the
vertex layout being dependent upon the physical location of the image key points.
Important information could then be hidden within these dense graphs, e.g.,
tumours within the mediastinum (the mediastinum is the central part of the chest).
Grouping vertices that represent similar image features and that are pairwise
adjacent into a single \super-vertex" would improve clarity in the visualisation of
key points. This is a clique detection problem, which is computationally
expensive.</p>
      <p>
        Another limitation is that our abstractions may obscure detailed pixel
information. However, since each node corresponds to a physical location within the
image, it is possible to create links between the abstractions and the pixel data.
In this manner, the abstraction can be used as a map of the important areas
in the image. We implemented such a map for a PET-CT retrieval engine [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ];
clicking on an abstract node would outline the ROI in multiple views of the
corresponding PET-CT image. Linking nodes on the abstraction to the pixel
data is an interaction that can facilitate a more detailed understanding of the
complex pixel data [
        <xref ref-type="bibr" rid="ref7">7</xref>
        ].
4
      </p>
    </sec>
    <sec id="sec-4">
      <title>Conclusions</title>
      <p>We present a scheme for creating graph abstractions that summarise the content
within medical images. We provided 2D and 3D examples of our abstractions
applied to 3D PET-CT images of patients with lung cancer. Our abstractions
showed how complex image content could be summarised and interpreted.</p>
      <p>In future work, we will adapt our abstractions to more complex diseases, e.g.,
lymphoma, which can have multiple clusters of tumours throughout the body.
The abstraction of these images will be more complex and will require further
optimisation of the properties and graph layout. We will investigate
enhancements to our abstraction by hierarchically grouping related nodes based on the
spatial location of nodes in relation to body regions (head, thorax, abdomen,
limbs) and by clustering cliques into a single representative node.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <ref id="ref1">
        <mixed-citation>
          1.
          <string-name>
            <surname>Townsend</surname>
            ,
            <given-names>D.W.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Beyer</surname>
            ,
            <given-names>T.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Blodgett</surname>
            ,
            <given-names>T.M.:</given-names>
          </string-name>
          <article-title>PET/CT scanners: A hardware approach to image fusion</article-title>
          .
          <source>Semin Nucl Med</source>
          <volume>33</volume>
          (
          <issue>3</issue>
          ) (
          <year>2003</year>
          )
          <volume>193</volume>
          {
          <fpage>204</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref2">
        <mixed-citation>
          2.
          <string-name>
            <surname>Edge</surname>
            ,
            <given-names>S.B.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Byrd</surname>
            ,
            <given-names>D.R.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Compton</surname>
            ,
            <given-names>C.C.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Frtiz</surname>
            ,
            <given-names>A.G.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Greene</surname>
            ,
            <given-names>F.L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Trotti</surname>
          </string-name>
          , A., eds.
          <source>: AJCC Cancer Staging Manual</source>
          . Springer New York (
          <year>2010</year>
          )
        </mixed-citation>
      </ref>
      <ref id="ref3">
        <mixed-citation>
          3.
          <string-name>
            <surname>Jung</surname>
            ,
            <given-names>Y.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Kim</surname>
            ,
            <given-names>J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Eberl</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Fulham</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Feng</surname>
          </string-name>
          , D.D.:
          <article-title>Visibility-driven PET-CT visualisation with region of interest (ROI) segmentation</article-title>
          .
          <source>Visual Comput</source>
          <volume>29</volume>
          (
          <issue>6-8</issue>
          ) (
          <year>2013</year>
          )
          <volume>805</volume>
          {
          <fpage>815</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref4">
        <mixed-citation>
          4.
          <string-name>
            <surname>Deserno</surname>
            ,
            <given-names>T.</given-names>
          </string-name>
          , Guld,
          <string-name>
            <given-names>M.</given-names>
            ,
            <surname>Plodowski</surname>
          </string-name>
          ,
          <string-name>
            <given-names>B.</given-names>
            ,
            <surname>Spitzer</surname>
          </string-name>
          ,
          <string-name>
            <given-names>K.</given-names>
            ,
            <surname>Wein</surname>
          </string-name>
          ,
          <string-name>
            <given-names>B.</given-names>
            ,
            <surname>Schubert</surname>
          </string-name>
          ,
          <string-name>
            <given-names>H.</given-names>
            ,
            <surname>Ney</surname>
          </string-name>
          ,
          <string-name>
            <given-names>H.</given-names>
            ,
            <surname>Seidl</surname>
          </string-name>
          ,
          <string-name>
            <surname>T.</surname>
          </string-name>
          :
          <article-title>Extended query re nement for medical image retrieval</article-title>
          .
          <source>J Digit Imaging</source>
          <volume>21</volume>
          (
          <issue>3</issue>
          ) (
          <year>2008</year>
          )
          <volume>280</volume>
          {
          <fpage>289</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref5">
        <mixed-citation>
          5.
          <string-name>
            <surname>Hsu</surname>
            ,
            <given-names>W.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Antani</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Long</surname>
            ,
            <given-names>L.R.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Neve</surname>
            ,
            <given-names>L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Thoma</surname>
            ,
            <given-names>G.R.:</given-names>
          </string-name>
          <article-title>SPIRS: a web-based image retrieval system for large biomedical databases</article-title>
          .
          <source>Int J Med Inform 78(Supplement 1)</source>
          (
          <year>2009</year>
          )
          <article-title>S13</article-title>
          {
          <fpage>S24</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref6">
        <mixed-citation>
          6.
          <string-name>
            <surname>Kumar</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Kim</surname>
            ,
            <given-names>J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bi</surname>
            ,
            <given-names>L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Fulham</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Feng</surname>
            ,
            <given-names>D.</given-names>
          </string-name>
          :
          <article-title>Designing user interfaces to enhance human interpretation of medical content-based image retrieval: application to PET-CT images</article-title>
          .
          <source>Int J Comput Assist Rad Surg</source>
          <volume>8</volume>
          (
          <issue>6</issue>
          ) (
          <year>2013</year>
          )
          <volume>1003</volume>
          {
          <fpage>1014</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref7">
        <mixed-citation>
          7.
          <string-name>
            <surname>Tory</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Moller</surname>
            ,
            <given-names>T.</given-names>
          </string-name>
          :
          <article-title>Human factors in visualization research</article-title>
          .
          <source>IEEE T Vis Comput Gr</source>
          <volume>10</volume>
          (
          <issue>1</issue>
          ) (
          <year>2004</year>
          )
          <volume>72</volume>
          {
          <fpage>84</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref8">
        <mixed-citation>
          8.
          <string-name>
            <surname>Bunke</surname>
            ,
            <given-names>H.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Riesen</surname>
            ,
            <given-names>K.</given-names>
          </string-name>
          :
          <article-title>Towards the uni cation of structural and statistical pattern recognition</article-title>
          .
          <source>Pattern Recogn Lett</source>
          <volume>33</volume>
          (
          <issue>7</issue>
          ) (
          <year>2012</year>
          )
          <volume>811</volume>
          {
          <fpage>825</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref9">
        <mixed-citation>
          9. Wilson,
          <string-name>
            <surname>M.L.</surname>
          </string-name>
          :
          <article-title>Search user interface design</article-title>
          .
          <source>Synthesis Lectures on Information Concepts</source>
          ,
          <source>Retrieval, and Services</source>
          <volume>3</volume>
          (
          <issue>3</issue>
          ) (
          <year>2011</year>
          )
          <volume>1</volume>
          {
          <fpage>143</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref10">
        <mixed-citation>
          10.
          <string-name>
            <surname>Detterbeck</surname>
            ,
            <given-names>F.C.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bo</surname>
            <given-names>a</given-names>
          </string-name>
          , D.J.,
          <string-name>
            <surname>Tanoue</surname>
          </string-name>
          , L.T.:
          <article-title>The new lung cancer staging system</article-title>
          .
          <source>Chest</source>
          <volume>136</volume>
          (
          <issue>1</issue>
          ) (
          <year>2009</year>
          )
          <volume>260</volume>
          {
          <fpage>271</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref11">
        <mixed-citation>
          11.
          <string-name>
            <surname>Lowe</surname>
            ,
            <given-names>D.G.</given-names>
          </string-name>
          :
          <article-title>Distinctive image features from scale-invariant keypoints</article-title>
          .
          <source>Int J Comput Vision</source>
          <volume>60</volume>
          (
          <year>2004</year>
          )
          <volume>91</volume>
          {
          <fpage>110</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref12">
        <mixed-citation>
          12.
          <string-name>
            <surname>Hu</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Ho</surname>
            <given-names>man</given-names>
          </string-name>
          , E.,
          <string-name>
            <surname>Reinhardt</surname>
            ,
            <given-names>J.</given-names>
          </string-name>
          :
          <article-title>Automatic lung segmentation for accurate quantitation of volumetric X-ray CT images</article-title>
          .
          <source>IEEE T Med Imaging</source>
          <volume>20</volume>
          (
          <issue>6</issue>
          ) (
          <year>2001</year>
          )
          <volume>490</volume>
          {
          <fpage>498</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref13">
        <mixed-citation>
          13.
          <string-name>
            <surname>Bradley</surname>
            ,
            <given-names>J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Thorstad</surname>
            ,
            <given-names>W.L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Mutic</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Miller</surname>
            ,
            <given-names>T.R.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Dehdashti</surname>
            ,
            <given-names>F.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Siegel</surname>
            ,
            <given-names>B.A.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bosch</surname>
            ,
            <given-names>W.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bertrand</surname>
          </string-name>
          , R.J.:
          <article-title>Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer</article-title>
          .
          <source>Int J Radiat Oncol Biol Phys</source>
          <volume>59</volume>
          (
          <issue>1</issue>
          ) (
          <year>2004</year>
          )
          <volume>78</volume>
          {
          <fpage>86</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref14">
        <mixed-citation>
          14.
          <string-name>
            <surname>Kumar</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Kim</surname>
            ,
            <given-names>J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Wen</surname>
            ,
            <given-names>L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Fulham</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Feng</surname>
            ,
            <given-names>D.:</given-names>
          </string-name>
          <article-title>A graph-based approach for the retrieval of multi-modality medical images</article-title>
          .
          <source>Med Image Anal</source>
          <volume>18</volume>
          (
          <issue>2</issue>
          ) (
          <year>2014</year>
          )
          <volume>330</volume>
          {
          <fpage>342</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref15">
        <mixed-citation>
          15.
          <string-name>
            <surname>Toews</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>III</surname>
          </string-name>
          , W.M.W.:
          <article-title>E cient and robust model-to-image alignment using 3d scale-invariant features</article-title>
          .
          <source>Med Image Anal</source>
          <volume>17</volume>
          (
          <issue>3</issue>
          ) (
          <year>2013</year>
          )
          <volume>271</volume>
          {
          <fpage>282</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref16">
        <mixed-citation>
          16.
          <string-name>
            <surname>Zhou</surname>
            ,
            <given-names>X.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Stern</surname>
            ,
            <given-names>R.</given-names>
          </string-name>
          , Muller, H.:
          <article-title>Case-based fracture image retrieval</article-title>
          .
          <source>Int J Comput Assist Rad Surg</source>
          <volume>7</volume>
          (
          <year>2012</year>
          )
          <volume>401</volume>
          {
          <fpage>411</fpage>
        </mixed-citation>
      </ref>
      <ref id="ref17">
        <mixed-citation>
          17.
          <string-name>
            <given-names>O</given-names>
            <surname>'Madadhain</surname>
          </string-name>
          ,
          <string-name>
            <surname>J.</surname>
          </string-name>
          , Fisher,
          <string-name>
            <given-names>D.</given-names>
            ,
            <surname>White</surname>
          </string-name>
          ,
          <string-name>
            <given-names>S.</given-names>
            ,
            <surname>Boey</surname>
          </string-name>
          ,
          <string-name>
            <surname>Y.</surname>
          </string-name>
          :
          <article-title>The JUNG (Java Universal Network/Graph) framework (</article-title>
          <year>2003</year>
          ) http://jung.sourceforge.net/, Last Checked:
          <volume>30</volume>
          /05/
          <year>2014</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref18">
        <mixed-citation>
          18.
          <string-name>
            <surname>Dwyer</surname>
          </string-name>
          , T.:
          <article-title>cola.js: Constraint-Based Layout in the Browser (</article-title>
          <year>2003</year>
          ) http://marvl.infotech.monash.edu/webcola/, Last Checked:
          <volume>28</volume>
          /05/
          <year>2014</year>
          .
        </mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>