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<meta name="DC.Title" content="Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype" />
<meta name="DC.Identifier" content="10.3174/ajnr.A5313" />
<meta name="DC.Date" content="2017-08-10" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2017 American Society of Neuroradiology" />
<meta name="DC.AccessRights" content="restricted" />
<meta name="DC.Description" content="BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.

MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22–53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog ( SHH ) TP53 wild type, wingless ( WNT ), and non- WNT/ non- SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study.

RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT -activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus ( P = .03), intraventricular macrometastases ( P = .02), and hemorrhage ( P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%–100.0% and 62.6%–95.3%). WNT -activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2–22.3 cm3 versus 35.1–47.6 cm3; P = .03). Hemorrhage was exclusively present in non- WNT/ non- SHH medulloblastomas ( P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04).

CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

### Abbreviations

AUC
:   area under the curve
CE
:   contrast-enhanced
CMB
:   classic medulloblastoma
DNMB
:   desmoplastic/nodular medulloblastoma
SHH
:   sonic hedgehog
WHO
:   World Health Organization
WNT 
:   wingless" />
<meta name="DC.Contributor" content="V.C. Keil" />
<meta name="DC.Contributor" content="M. Warmuth-Metz" />
<meta name="DC.Contributor" content="C. Reh" />
<meta name="DC.Contributor" content="S.J. Enkirch" />
<meta name="DC.Contributor" content="C. Reinert" />
<meta name="DC.Contributor" content="D. Beier" />
<meta name="DC.Contributor" content="D.T.W. Jones" />
<meta name="DC.Contributor" content="T. Pietsch" />
<meta name="DC.Contributor" content="H.H. Schild" />
<meta name="DC.Contributor" content="E. Hattingen" />
<meta name="DC.Contributor" content="P. Hau" />
<meta name="article:published_time" content="2017-08-10" />
<meta name="article:section" content="ADULT BRAIN" />
<meta name="citation_title" content="Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Eligible preoperative MRIs from 28 patients (11 women; 22–53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities &lt;i&gt;sonic hedgehog&lt;/i&gt; (&lt;i&gt;SHH&lt;/i&gt;) &lt;i&gt;TP53&lt;/i&gt; wild type, &lt;i&gt;wingless&lt;/i&gt; (&lt;i&gt;WNT&lt;/i&gt;), and non-&lt;i&gt;WNT/&lt;/i&gt;non-&lt;i&gt;SHH&lt;/i&gt; medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;There were 19 &lt;i&gt;SHH TP53&lt;/i&gt; wild type (69%), 4 &lt;i&gt;WNT&lt;/i&gt;-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus (&lt;i&gt;P&lt;/i&gt; = .03), intraventricular macrometastases (&lt;i&gt;P&lt;/i&gt; = .02), and hemorrhage (&lt;i&gt;P&lt;/i&gt; = .04), when combined, could identify &lt;i&gt;WNT&lt;/i&gt; medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%–100.0% and 62.6%–95.3%). &lt;i&gt;WNT&lt;/i&gt;-activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2–22.3 cm&lt;sup&gt;3&lt;/sup&gt; versus 35.1–47.6 cm&lt;sup&gt;3&lt;/sup&gt;; &lt;i&gt;P&lt;/i&gt; = .03). Hemorrhage was exclusively present in non-&lt;i&gt;WNT/&lt;/i&gt;non-&lt;i&gt;SHH&lt;/i&gt; medulloblastomas (&lt;i&gt;P&lt;/i&gt; = .04; &lt;i&gt;n&lt;/i&gt; = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; &lt;i&gt;P&lt;/i&gt; = .04).&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.&lt;/p&gt;" />
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<meta name="citation_author_institution" content="From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany." />
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<meta name="twitter:title" content="Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype" />
<meta name="twitter:card" content="summary" />
<meta name="twitter:description" content="BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.

MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22–53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog ( SHH ) TP53 wild type, wingless ( WNT ), and non- WNT/ non- SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study.

RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT -activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus ( P = .03), intraventricular macrometastases ( P = .02), and hemorrhage ( P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%–100.0% and 62.6%–95.3%). WNT -activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2–22.3 cm3 versus 35.1–47.6 cm3; P = .03). Hemorrhage was exclusively present in non- WNT/ non- SHH medulloblastomas ( P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04).

CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

### Abbreviations

AUC
:   area under the curve
CE
:   contrast-enhanced
CMB
:   classic medulloblastoma
DNMB
:   desmoplastic/nodular medulloblastoma
SHH
:   sonic hedgehog
WHO
:   World Health Organization
WNT 
:   wingless" />
<meta name="og-title" property="og:title" content="Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/early/2017/08/10/ajnr.A5313" />
<meta name="og-site-name" property="og:site_name" content="American Journal of Neuroradiology" />
<meta name="og-description" property="og:description" content="BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.

MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22–53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog ( SHH ) TP53 wild type, wingless ( WNT ), and non- WNT/ non- SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study.

RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT -activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus ( P = .03), intraventricular macrometastases ( P = .02), and hemorrhage ( P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%–100.0% and 62.6%–95.3%). WNT -activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2–22.3 cm3 versus 35.1–47.6 cm3; P = .03). Hemorrhage was exclusively present in non- WNT/ non- SHH medulloblastomas ( P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04).

CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

### Abbreviations

AUC
:   area under the curve
CE
:   contrast-enhanced
CMB
:   classic medulloblastoma
DNMB
:   desmoplastic/nodular medulloblastoma
SHH
:   sonic hedgehog
WHO
:   World Health Organization
WNT 
:   wingless" />
<meta name="og-type" property="og:type" content="article" />
<meta name="og-image" property="og:image" content="" />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node55737--5" data-node-nid="55737" id="top-node-55737--61826918778" data-pisa="ajnr;ajnr.A5313v1" data-pisa-master="ajnr;ajnr.A5313" data-apath="/ajnr/early/2017/08/10/ajnr.A5313.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a">
  
  
      <div class="highwire-cite-overline"><span  class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span  class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">ADULT BRAIN</span></span></div>
  
      <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="ajnr;ajnr.A5313" data-atom-uri="/ajnr/early/2017/08/10/ajnr.A5313.atom" data-request-view="full"></span></div>
  
      <h1 class="highwire-cite-title" id="page-title">Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">V.C. Keil</span>, <span class="highwire-citation-author" data-delta="1">M. Warmuth-Metz</span>, <span class="highwire-citation-author" data-delta="2">C. Reh</span>, <span class="highwire-citation-author" data-delta="3">S.J. Enkirch</span>, <span class="highwire-citation-author" data-delta="4">C. Reinert</span>, <span class="highwire-citation-author" data-delta="5">D. Beier</span>, <span class="highwire-citation-author" data-delta="6">D.T.W. Jones</span>, <span class="highwire-citation-author" data-delta="7">T. Pietsch</span>, <span class="highwire-citation-author" data-delta="8">H.H. Schild</span>, <span class="highwire-citation-author" data-delta="9">E. Hattingen</span> and <span class="highwire-citation-author" data-delta="10">P. Hau</span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">August 2017,  </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A5313 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-55737--61826918778" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">V.C. Keil </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=V.C.%2BKeil%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Keil%20V&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AV.C.%2BKeil%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0001-8699-3506" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for V.C. Keil</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">M. Warmuth-Metz </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=M.%2BWarmuth-Metz%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Warmuth-Metz%20M&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AM.%2BWarmuth-Metz%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-3544-319X" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for M. Warmuth-Metz</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">C. Reh </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=C.%2BReh%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Reh%20C&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AC.%2BReh%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-6298-8224" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. Reh</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">S.J. Enkirch </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=S.J.%2BEnkirch%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Enkirch%20S&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AS.J.%2BEnkirch%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-5819-0308" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for S.J. Enkirch</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">C. Reinert </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=C.%2BReinert%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Reinert%20C&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AC.%2BReinert%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-1085-1442" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. Reinert</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">D. Beier </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=D.%2BBeier%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Beier%20D&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AD.%2BBeier%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-3336-157X" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for D. Beier</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">D.T.W. Jones </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=D.T.W.%2BJones%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Jones%20D&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AD.T.W.%2BJones%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-2036-5141" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for D.T.W. Jones</a></li></ul></div><div class="author-tooltip-7"><div class="author-tooltip-name">T. Pietsch </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=T.%2BPietsch%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Pietsch%20T&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AT.%2BPietsch%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-9252-8923" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for T. Pietsch</a></li></ul></div><div class="author-tooltip-8"><div class="author-tooltip-name">H.H. Schild </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=H.H.%2BSchild%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Schild%20H&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AH.H.%2BSchild%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-4264-0121" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for H.H. Schild</a></li></ul></div><div class="author-tooltip-9"><div class="author-tooltip-name">E. Hattingen </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=E.%2BHattingen%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Hattingen%20E&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AE.%2BHattingen%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-8392-9004" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for E. 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Hau </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=P.%2BHau%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Hau%20P&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AP.%2BHau%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-3894-5053" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for P. Hau</a></li></ul></div></div></div>  </div>

  
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    <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div xmlns:xhtml="http://www.w3.org/1999/xhtml" class="contributors"><ol class="contributor-list" id="contrib-group-1"><li class="contributor" id="contrib-1"><span class="name">V.C. Keil</span><a id="xref-aff-1-1" class="xref-aff" href="#aff-1"></a>, </li><li class="contributor" id="contrib-2"><span class="name">M. Warmuth-Metz</span><a id="xref-aff-1-2" class="xref-aff" href="#aff-1"></a>, </li><li class="contributor" id="contrib-3"><span class="name">C. Reh</span><a id="xref-aff-1-3" class="xref-aff" href="#aff-1"></a>, </li><li class="contributor" id="contrib-4"><span class="name">S.J. Enkirch</span><a id="xref-aff-1-4" class="xref-aff" href="#aff-1"></a>, </li><li class="contributor" id="contrib-5"><span class="name">C. Reinert</span><a id="xref-aff-1-5" class="xref-aff" href="#aff-1"></a>, </li><li class="contributor" id="contrib-6"><span class="name">D. Beier</span><a id="xref-aff-1-6" class="xref-aff" href="#aff-1"></a>, </li><li class="contributor" id="contrib-7"><span class="name">D.T.W. Jones</span><a id="xref-aff-1-7" class="xref-aff" href="#aff-1"></a>, </li><li class="contributor" id="contrib-8"><span class="name">T. Pietsch</span><a id="xref-aff-1-8" class="xref-aff" href="#aff-1"></a>, </li><li class="contributor" id="contrib-9"><span class="name">H.H. Schild</span><a id="xref-aff-1-9" class="xref-aff" href="#aff-1"></a>, </li><li class="contributor" id="contrib-10"><span class="name">E. Hattingen</span><a id="xref-aff-1-10" class="xref-aff" href="#aff-1"></a> and </li><li class="last" id="contrib-11"><span class="name">P. Hau</span><a id="xref-aff-1-11" class="xref-aff" href="#aff-1"></a></li></ol><ol class="affiliation-list"><li class="aff"><a id="aff-1" name="aff-1"></a><address>From the Department of Radiology and Neuroradiology (V.C.K., C.R., S.J.E., H.H.S., E.H.), University Hospital Bonn, Bonn, Germany; Institute for Diagnostic and Interventional Neuroradiology (M.W.-M.), University Hospital Würzburg, Würzburg, Germany; Department of Neuropathology (T.P.), Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, Bonn, Germany; Wilhelm Sander-Therapieeinheit NeuroOnkologie (C.R., P.H.) and Department of Neurology (C.R., P.H.), University Hospital Regensburg, Regensburg, Germany; Department of Neurology (D.B.), University Hospital Odense and Clinical Institute, University of Southern Denmark, Odense, Denmark; Department of Neurology (D.B.), University of Regensburg, Regensburg, Germany; and Deutsches Krebsforschungszentrum (D.T.W.J.), Division of Pediatric Neurooncology, Heidelberg, Germany.</address></li></ol><ol class="corresp-list"><li class="corresp" id="corresp-1">Please address correspondence to Vera C. Keil, MD, <span class="addr-line">Universitätsklinik Bonn, Radiologische Klinik, Sigmund-Freud-Str 25, D-53127 Bonn, Germany</span>; e-mail: <span class="em-link"><span class="em-addr">vera.keil{at}ukbonn.de</span></span></li></ol></div></div></div>  </div>

  
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