Amyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease☆
Identifieur interne : 000540 ( Pmc/Checkpoint ); précédent : 000539; suivant : 000541Amyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease☆
Auteurs : Rik Vandenberghe [Belgique] ; Katarzyna Adamczuk [Belgique] ; Patrick Dupont [Belgique] ; Koen Van Laere [Belgique] ; Gaël Chételat [France]Source :
- NeuroImage : Clinical [ 2213-1582 ] ; 2013.
Abstract
Amyloid imaging is currently introduced to the market for clinical use. We will review the evidence demonstrating that the different amyloid PET ligands that are currently available are valid biomarkers for Alzheimer-related
Url:
DOI: 10.1016/j.nicl.2013.03.014
PubMed: 24179802
PubMed Central: 3777773
Affiliations:
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<series><title level="j">NeuroImage : Clinical</title>
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<front><div type="abstract" xml:lang="en"><p>Amyloid imaging is currently introduced to the market for clinical use. We will review the evidence demonstrating that the different amyloid PET ligands that are currently available are valid biomarkers for Alzheimer-related <italic>β</italic>
amyloidosis. Based on recent findings from cross-sectional and longitudinal imaging studies using different modalities, we will incorporate amyloid imaging into a multidimensional model of Alzheimer's disease. Aside from the critical role in improving clinical trial design for amyloid-lowering drugs, we will also propose a tentative algorithm for when it may be useful in a memory clinic environment. Gaps in our evidence-based knowledge of the added value of amyloid imaging in a clinical context will be identified and will need to be addressed by dedicated studies of clinical utility.</p>
</div>
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</TEI>
<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Neuroimage Clin</journal-id>
<journal-id journal-id-type="iso-abbrev">Neuroimage Clin</journal-id>
<journal-title-group><journal-title>NeuroImage : Clinical</journal-title>
</journal-title-group>
<issn pub-type="epub">2213-1582</issn>
<publisher><publisher-name>Elsevier</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24179802</article-id>
<article-id pub-id-type="pmc">3777773</article-id>
<article-id pub-id-type="publisher-id">S2213-1582(13)00035-1</article-id>
<article-id pub-id-type="doi">10.1016/j.nicl.2013.03.014</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Amyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease<sup><xref ref-type="fn" rid="d32e844">☆</xref>
</sup>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Vandenberghe</surname>
<given-names>Rik</given-names>
</name>
<email>rik.vandenberghe@uz.kuleuven.ac.be</email>
<xref rid="af0005" ref-type="aff">a</xref>
<xref rid="af0010" ref-type="aff">b</xref>
<xref rid="af0015" ref-type="aff">c</xref>
<xref rid="cr0005" ref-type="corresp">⁎</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Adamczuk</surname>
<given-names>Katarzyna</given-names>
</name>
<xref rid="af0005" ref-type="aff">a</xref>
<xref rid="af0015" ref-type="aff">c</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dupont</surname>
<given-names>Patrick</given-names>
</name>
<xref rid="af0005" ref-type="aff">a</xref>
<xref rid="af0015" ref-type="aff">c</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Laere</surname>
<given-names>Koen Van</given-names>
</name>
<xref rid="af0020" ref-type="aff">d</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chételat</surname>
<given-names>Gaël</given-names>
</name>
<xref rid="af0025" ref-type="aff">e</xref>
<xref rid="af0030" ref-type="aff">f</xref>
<xref rid="af0035" ref-type="aff">g</xref>
<xref rid="af0040" ref-type="aff">h</xref>
</contrib>
</contrib-group>
<aff id="af0005"><label>a</label>
Laboratory for Cognitive Neurology, Department of Neurosciences, University of Leuven, Belgium</aff>
<aff id="af0010"><label>b</label>
Neurology Department, University Hospitals Leuven, Belgium</aff>
<aff id="af0015"><label>c</label>
Alzheimer Research Centre KU Leuven, Leuven Institute of Neuroscience and Disease, University of Leuven, Belgium</aff>
<aff id="af0020"><label>d</label>
Nuclear Medicine Department, University Hospitals Leuven, Belgium</aff>
<aff id="af0025"><label>e</label>
INSERM, U1077, Caen, France</aff>
<aff id="af0030"><label>f</label>
Université de Caen Basse-Normandie, UMR-S1077, Caen, France</aff>
<aff id="af0035"><label>g</label>
Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France</aff>
<aff id="af0040"><label>h</label>
CHU de Caen, U1077, Caen, France</aff>
<author-notes><corresp id="cr0005"><label>⁎</label>
Corresponding author at: Neurology Department, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Tel.: + 32 16 344280; fax: + 32 16 344285. <email>rik.vandenberghe@uz.kuleuven.ac.be</email>
</corresp>
</author-notes>
<pub-date pub-type="pmc-release"><day>6</day>
<month>4</month>
<year>2013</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was
based on .</pmc-comment>
<pub-date pub-type="epub"><day>6</day>
<month>4</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="collection"><year>2013</year>
</pub-date>
<volume>2</volume>
<fpage>497</fpage>
<lpage>511</lpage>
<history><date date-type="received"><day>13</day>
<month>12</month>
<year>2012</year>
</date>
<date date-type="rev-recd"><day>19</day>
<month>3</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>21</day>
<month>3</month>
<year>2013</year>
</date>
</history>
<permissions><copyright-statement>© 2013 The Authors</copyright-statement>
<copyright-year>2013</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<abstract><p>Amyloid imaging is currently introduced to the market for clinical use. We will review the evidence demonstrating that the different amyloid PET ligands that are currently available are valid biomarkers for Alzheimer-related <italic>β</italic>
amyloidosis. Based on recent findings from cross-sectional and longitudinal imaging studies using different modalities, we will incorporate amyloid imaging into a multidimensional model of Alzheimer's disease. Aside from the critical role in improving clinical trial design for amyloid-lowering drugs, we will also propose a tentative algorithm for when it may be useful in a memory clinic environment. Gaps in our evidence-based knowledge of the added value of amyloid imaging in a clinical context will be identified and will need to be addressed by dedicated studies of clinical utility.</p>
</abstract>
<abstract abstract-type="author-highlights"><title>Highlights</title>
<p><list list-type="simple"><list-item id="u0045"><label>•</label>
<p>Amyloid imaging has been validated as a biomarker for cerebral β amyloidosis.</p>
</list-item>
<list-item id="u0050"><label>•</label>
<p>Biomarkers are essential for progress in therapy for Alzheimer's disease.</p>
</list-item>
<list-item id="u0055"><label>•</label>
<p>They may have a role in clinical diagnosis under specific conditions.</p>
</list-item>
<list-item id="u0060"><label>•</label>
<p>An evidence-based medicine approach will have to prove their added value.</p>
</list-item>
<list-item id="u0065"><label>•</label>
<p>We position amyloid imaging within a multidimensional model of Alzheimer's disease.</p>
</list-item>
</list>
</p>
</abstract>
<kwd-group><title>Keywords</title>
<kwd>Flutemetamol</kwd>
<kwd>Florbetapir</kwd>
<kwd>Florbetaben</kwd>
<kwd>PIB</kwd>
<kwd>Clinic</kwd>
<kwd>Diagnostic</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="f0005"><label>Fig. 1</label>
<caption><p>Tentative clinical algorithm for the utility of amyloid imaging in patients presenting at a memory clinic with a cognitive deficit that is confirmed by clinical assessment of cognitive functions or by neuropsychological evaluation. This algorithm is tentative and subject to further empirical evaluation.</p>
</caption>
<graphic xlink:href="gr1"></graphic>
</fig>
<table-wrap id="t0005" position="float"><label>Table 1</label>
<caption><p>Cohen's d effect size for discriminating between AD and controls (difference between the means of the two study populations divided by the pooled standard deviation). These values are for indicative purposes and, as indicated, may substantially vary between studies depending on the exact processing and analysis method used. For the sake of comparison, the effect size obtained for FDG-PET for discriminating AD from controls in a comparative study of FDG-PET and <sup>11</sup>
C-PIB-PET was 1.53 (<xref rid="bb0520" ref-type="bibr">Ng et al., 2007</xref>
).</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th></th>
<th align="left">Cohen's d effect size</th>
<th align="left">Reference</th>
</tr>
</thead>
<tbody><tr><td align="left"><sup>11</sup>
C-PIB</td>
<td align="left">2.23–3.8</td>
<td align="left"><xref rid="bb0745" ref-type="bibr">Verhoeff et al. (2004)</xref>
, <xref rid="bb0520" ref-type="bibr">Ng et al. (2007)</xref>
and <xref rid="bb0755" ref-type="bibr">Villemagne et al. (2012)</xref>
</td>
</tr>
<tr><td align="left"><sup>11</sup>
C-SB</td>
<td align="left">1.22</td>
<td align="left"><xref rid="bb0745" ref-type="bibr">Verhoeff et al. (2004)</xref>
</td>
</tr>
<tr><td align="left"><sup>18</sup>
F-flutemetamol</td>
<td align="left">2.7</td>
<td align="left"><xref rid="bb0735" ref-type="bibr">Vandenberghe et al. (2010)</xref>
</td>
</tr>
<tr><td align="left"><sup>18</sup>
F-florbetapir</td>
<td align="left">2.3</td>
<td align="left"><xref rid="bb0795" ref-type="bibr">Wong et al. (2010)</xref>
</td>
</tr>
<tr><td align="left"><sup>18</sup>
F-florbetaben</td>
<td align="left">1.37–3</td>
<td align="left"><xref rid="bb0040" ref-type="bibr">Barthel et al. (2011)</xref>
and <xref rid="bb0760 bb0755" ref-type="bibr">Villemagne et al. (2011, 2012)</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="t0010" position="float"><label>Table 2</label>
<caption><p>Within-subject correlations between <sup>11</sup>
C-PIB and <sup>18</sup>
F-labeled ligands (<xref rid="bb0715 bb0735 bb0755 bb0780" ref-type="bibr">Tolboom et al., 2009a; Vandenberghe et al., 2010; Villemagne et al., 2012; Wolk et al., 2012</xref>
). <italic>m</italic>
: region-wise linear slope. <italic>r</italic>
: Pearson correlation coefficient. SUVR: Standardized Uptake Value Ratio; BP: Binding Potential. <italic>Dash</italic>
: not reported.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th></th>
<th colspan="5" align="left">SUVR<hr></hr>
</th>
<th align="left">Global BP<hr></hr>
</th>
</tr>
<tr><th></th>
<th colspan="2" align="left"><sup>18</sup>
F-flutemetamol<hr></hr>
</th>
<th colspan="2" align="left"><sup>18</sup>
F-florbetapir<hr></hr>
</th>
<th align="left"><sup>18</sup>
F-florbetaben<hr></hr>
</th>
<th align="left"><sup>18</sup>
F-FDDNP<hr></hr>
</th>
</tr>
<tr><th></th>
<th align="left">r</th>
<th align="left">m</th>
<th align="left">r</th>
<th align="left">m</th>
<th align="left">r</th>
<th align="left">r</th>
</tr>
</thead>
<tbody><tr><td align="left">Composite</td>
<td align="char">0.91</td>
<td align="char">0.99</td>
<td align="left">0.78</td>
<td align="left">0.33</td>
<td align="left">0.97</td>
<td align="left">0.45</td>
</tr>
<tr><td align="left">Frontal</td>
<td align="char">0.92</td>
<td align="char">1.00</td>
<td align="left">0.81</td>
<td align="left">–</td>
<td align="left">0.94–0.96</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Parietal</td>
<td align="char">0.92</td>
<td align="char">1.01</td>
<td align="left">0.58</td>
<td align="left">–</td>
<td align="left">0.94</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Lateral temporal</td>
<td align="char">0.91</td>
<td align="char">0.99</td>
<td align="left">0.68</td>
<td align="left">–</td>
<td align="left">0.96</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Posterior cingulate</td>
<td align="char">0.91</td>
<td align="char">1.01</td>
<td align="left">0.79</td>
<td align="left">–</td>
<td align="left">0.96</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Anterior cingulate</td>
<td align="char">0.88</td>
<td align="char">0.91</td>
<td align="left">0.81</td>
<td align="left">–</td>
<td align="left">0.94</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Medial temporal</td>
<td align="char">0.83</td>
<td align="char">0.74</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">0.82</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Occipital</td>
<td align="char">0.89</td>
<td align="char">1.03</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">0.92</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Striatum</td>
<td align="char">0.84</td>
<td align="char">0.88</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">0.95</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Subcortical white matter</td>
<td align="char">0.22</td>
<td align="char">0.36</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">0.63</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Pons</td>
<td align="char">0.63</td>
<td align="char">0.50</td>
<td align="left">0.38</td>
<td align="left">–</td>
<td align="left">0.50</td>
<td align="left">–</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="t0015" position="float"><label>Table 3</label>
<caption><p>Test–retest variability of SUVR for <sup>18</sup>
F-labeled amyloid ligands with cerebellum as reference region in AD patients scanned with an interval less than one month (<xref rid="bb0135 bb0390 bb0735 bb0760" ref-type="bibr">Cselényi et al., 2012; Joshi et al., 2012; Vandenberghe et al., 2010; Villemagne et al., 2011</xref>
). Expressed in %. The exact definition of volumes of interest, e.g. the composite cortical VOI, may differ between the studies and the current comparison should therefore be considered an indirect comparison. <italic>Dash</italic>
: not reported.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th></th>
<th colspan="2" align="left"><sup>18</sup>
F-flutemetamol<hr></hr>
</th>
<th colspan="2" align="left"><sup>18</sup>
F-florbetapir<hr></hr>
</th>
<th colspan="2" align="left"><sup>18</sup>
F-florbetaben<hr></hr>
</th>
<th colspan="2" align="left"><sup>18</sup>
F-AZD4694<hr></hr>
</th>
</tr>
<tr><th align="left">AD cases</th>
<th colspan="2" align="left">5<hr></hr>
</th>
<th colspan="2" align="left">10<hr></hr>
</th>
<th colspan="2" align="left">8<hr></hr>
</th>
<th colspan="2" align="left">3<hr></hr>
</th>
</tr>
<tr><th></th>
<th align="left">Mean</th>
<th align="left">SD</th>
<th align="left">Mean</th>
<th align="left">SD</th>
<th align="left">Mean</th>
<th align="left">Range</th>
<th align="left">Mean</th>
<th align="left">SD</th>
</tr>
</thead>
<tbody><tr><td align="left">Composite</td>
<td align="char">1.5</td>
<td align="char">0.7</td>
<td align="left">2.40</td>
<td align="left">1.41</td>
<td align="left">6.2</td>
<td align="left">0.6–12.2</td>
<td align="left">7.5</td>
<td align="left">6.5</td>
</tr>
<tr><td align="left">Frontal</td>
<td align="char">1.4</td>
<td align="char">0.4</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Parietal</td>
<td align="char">2.1</td>
<td align="char">1.8</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Lateral temporal</td>
<td align="char">1.8</td>
<td align="char">0.8</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Posterior cingulate</td>
<td align="char">1.2</td>
<td align="char">0.5</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">7.8</td>
<td align="left">5.3</td>
</tr>
<tr><td align="left">Anterior cingulate</td>
<td align="char">2.0</td>
<td align="char">0.9</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Medial temporal</td>
<td align="char">3.8</td>
<td align="char">2.4</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Occipital</td>
<td align="char">0.9</td>
<td align="char">0.5</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Striatum</td>
<td align="char">0.9</td>
<td align="char">0.5</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Subcortical white matter</td>
<td align="char">3.2</td>
<td align="char">2.1</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
</tr>
<tr><td align="left">Pons</td>
<td align="char">3.1</td>
<td align="char">2.7</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
<td align="left">–</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="t0020" position="float"><label>Table 4</label>
<caption><p>Inter-reader consistency of binary reads (Fleiss' <italic>κ</italic>
). <italic>Dash</italic>
: not reported.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th></th>
<th align="left">AD<hr></hr>
</th>
<th align="left">MCI<hr></hr>
</th>
<th align="left">Controls<hr></hr>
</th>
<th align="left"><italic>κ</italic>
</th>
<th align="left">Reference</th>
</tr>
<tr><th></th>
<th align="left">(n)</th>
<th align="left">(n)</th>
<th align="left">(n)</th>
<th></th>
<th></th>
</tr>
</thead>
<tbody><tr><td align="left"><sup>11</sup>
C-PIB</td>
<td align="left">15</td>
<td></td>
<td align="left">25</td>
<td align="char">0.90</td>
<td align="left"><xref rid="bb0520" ref-type="bibr">Ng et al. (2007)</xref>
</td>
</tr>
<tr><td align="left"><sup>18</sup>
F-flutemetamol</td>
<td align="left">27</td>
<td align="left">20</td>
<td align="left">25</td>
<td align="char">0.96</td>
<td align="left"><xref rid="bb0735" ref-type="bibr">Vandenberghe et al. (2010)</xref>
</td>
</tr>
<tr><td align="left"><sup>18</sup>
F-florbetapir</td>
<td align="left">10</td>
<td></td>
<td align="left">10</td>
<td align="char">0.76</td>
<td align="left"><xref rid="bb0390" ref-type="bibr">Joshi et al. (2012)</xref>
</td>
</tr>
<tr><td></td>
<td align="left">31</td>
<td align="left">51</td>
<td align="left">69</td>
<td align="char">0.58</td>
<td align="left"><xref rid="bb0170" ref-type="bibr">Doraiswamy et al. (2012)</xref>
</td>
</tr>
<tr><td align="left"><sup>18</sup>
F-florbetaben</td>
<td align="left">81</td>
<td align="left">–</td>
<td align="left">69</td>
<td align="char">0.60</td>
<td align="left"><xref rid="bb0040" ref-type="bibr">Barthel et al. (2011)</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="t0025" position="float"><label>Table 5</label>
<caption><p>Numerical results from longitudinal trials with passive immunization using <sup>11</sup>
C-PIB (<xref rid="bb0545 bb0585" ref-type="bibr">Ostrowitzki et al., 2012; Rinne et al., 2010</xref>
).</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th></th>
<th align="left">Number of cases</th>
<th align="left">Initial SUVR</th>
<th align="left">Observed mean difference</th>
</tr>
</thead>
<tbody><tr><td colspan="4" align="left"><italic>Bapineuzumab</italic>
</td>
</tr>
<tr><td align="left">Placebo</td>
<td align="char">9</td>
<td align="char">1.89 (0.19)</td>
<td align="char">+ 0.15</td>
</tr>
<tr><td align="left">0.5, 1 or 2 mg</td>
<td align="char">19</td>
<td align="char">2.06 (0.20)</td>
<td align="char">− 0.09</td>
</tr>
<tr><td colspan="4" align="left">
</td>
</tr>
<tr><td colspan="4" align="left"><italic>Ganteneurumab</italic>
</td>
</tr>
<tr><td align="left">Placebo</td>
<td align="char">4</td>
<td align="char">2.18 (0.17)</td>
<td align="char">+ 0.23</td>
</tr>
<tr><td align="left">60 mg</td>
<td align="char">6</td>
<td align="char">2.86 (0.67)</td>
<td align="char">+ 0.02</td>
</tr>
<tr><td align="left">200 mg</td>
<td align="char">6</td>
<td align="char">2.86 (0.63)</td>
<td align="char">− 0.27</td>
</tr>
</tbody>
</table>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>Belgique</li>
<li>France</li>
</country>
<region><li>Basse-Normandie</li>
<li>Région Normandie</li>
</region>
<settlement><li>Caen</li>
</settlement>
<orgName><li>Université de Caen Basse-Normandie</li>
</orgName>
</list>
<tree><country name="Belgique"><noRegion><name sortKey="Vandenberghe, Rik" sort="Vandenberghe, Rik" uniqKey="Vandenberghe R" first="Rik" last="Vandenberghe">Rik Vandenberghe</name>
</noRegion>
<name sortKey="Adamczuk, Katarzyna" sort="Adamczuk, Katarzyna" uniqKey="Adamczuk K" first="Katarzyna" last="Adamczuk">Katarzyna Adamczuk</name>
<name sortKey="Adamczuk, Katarzyna" sort="Adamczuk, Katarzyna" uniqKey="Adamczuk K" first="Katarzyna" last="Adamczuk">Katarzyna Adamczuk</name>
<name sortKey="Dupont, Patrick" sort="Dupont, Patrick" uniqKey="Dupont P" first="Patrick" last="Dupont">Patrick Dupont</name>
<name sortKey="Dupont, Patrick" sort="Dupont, Patrick" uniqKey="Dupont P" first="Patrick" last="Dupont">Patrick Dupont</name>
<name sortKey="Laere, Koen Van" sort="Laere, Koen Van" uniqKey="Laere K" first="Koen Van" last="Laere">Koen Van Laere</name>
<name sortKey="Vandenberghe, Rik" sort="Vandenberghe, Rik" uniqKey="Vandenberghe R" first="Rik" last="Vandenberghe">Rik Vandenberghe</name>
<name sortKey="Vandenberghe, Rik" sort="Vandenberghe, Rik" uniqKey="Vandenberghe R" first="Rik" last="Vandenberghe">Rik Vandenberghe</name>
</country>
<country name="France"><region name="Région Normandie"><name sortKey="Chetelat, Gael" sort="Chetelat, Gael" uniqKey="Chetelat G" first="Gaël" last="Chételat">Gaël Chételat</name>
</region>
<name sortKey="Chetelat, Gael" sort="Chetelat, Gael" uniqKey="Chetelat G" first="Gaël" last="Chételat">Gaël Chételat</name>
<name sortKey="Chetelat, Gael" sort="Chetelat, Gael" uniqKey="Chetelat G" first="Gaël" last="Chételat">Gaël Chételat</name>
<name sortKey="Chetelat, Gael" sort="Chetelat, Gael" uniqKey="Chetelat G" first="Gaël" last="Chételat">Gaël Chételat</name>
</country>
</tree>
</affiliations>
</record>
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