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<meta name="DC.Title" content="Revisiting the Pathophysiology of Intracranial Hemorrhage in Fetuses with Chiari II Malformation: Novel Imaging Biomarkers of Disease Severity?" />
<meta name="DC.Identifier" content="10.3174/ajnr.A8331" />
<meta name="DC.Date" content="2024-10-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2024 by American Journal of Neuroradiology" />
<meta name="DC.AccessRights" content="restricted" />
<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) has emerged as a notable concern in Chiari II malformation (CM II), yet its origins and clinical implications remain elusive. This study aims to validate the in utero prevalence of ICH in CM II and investigate contributing factors, and visualize the findings in a network format.

MATERIALS AND METHODS: A single-center retrospective review of fetal MRI scans obtained in fetuses with CM II (presenting January 2007 to December 2022) was performed for ICH utilizing EPI-T2* blood-sensitive sequence. Fetuses with aqueduct stenosis (AS) were included as a control group. The incidence of ICH and corresponding gestational ages were compared between CM II and AS cases, and morphometric measurements (inner/outer CSF spaces, posterior fossa, venous structure) were compared among the 4 1:1 age-matched groups: CM II+ICH, CM II-ICH, AS+ICH, and AS-ICH. Additionally, a co-occurrence network was constructed to visualize associations between phenotypic features in ICH cases.

RESULTS: A total of 101 fetuses with CM II and 90 controls with AS at a median gestational age of 24.4 weeks and 22.8 weeks ( P = .138) were included. Prevalence of ICH in fetuses with CM II was higher compared with the AS cases (28.7% versus 18.9%, P = .023), accompanied by congested veins (deep vein congestion mainly in young fetuses, and cortical veins may also be affected in older fetuses). ICH was notably correlated with specific anatomic features, essentially characterized by reduced outer CSF spaces and clivus-supraocciput angle. The co-occurrence network analysis reveals complex connections including bony defects, small posterior fossa dimensions, vermis ectopia, reduced CSF spaces, as well as venous congestion and venous sinus stenosis as pivotal components within the network.

CONCLUSIONS: The high prevalence of ICH—detected by fetal MRI—among fetuses with CM emphasizes the pathophysiologic importance of venous congestion, ICH, and vasogenic edema. As indicators of disease severity, these features may serve as helpful additional imaging biomarkers for the identification of potential candidates for fetal surgery.

AS
:   aqueduct stenosis
CM II
:   Chiari type II malformation
ICH
:   intracranial hemorrhage
PCA
:   principal component analysis
SSFP
:   steady-state free precession
SSSFE
:   single-shot fast spin-echo" />
<meta name="DC.Contributor" content="Hui Shi" />
<meta name="DC.Contributor" content="Daniela Prayer" />
<meta name="DC.Contributor" content="Patric Kienast" />
<meta name="DC.Contributor" content="Farjad Khalaveh" />
<meta name="DC.Contributor" content="Johannes Tischer" />
<meta name="DC.Contributor" content="Julia Binder" />
<meta name="DC.Contributor" content="Michael Weber" />
<meta name="DC.Contributor" content="Marlene Stuempflen" />
<meta name="DC.Contributor" content="Gregor Kasprian" />
<meta name="article:published_time" content="2024-10-01" />
<meta name="article:section" content="Pediatric Neuroimaging" />
<meta name="citation_title" content="Revisiting the Pathophysiology of Intracranial Hemorrhage in Fetuses with Chiari II Malformation: Novel Imaging Biomarkers of Disease Severity?" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Intracranial hemorrhage (ICH) has emerged as a notable concern in Chiari II malformation (CM II), yet its origins and clinical implications remain elusive. This study aims to validate the in utero prevalence of ICH in CM II and investigate contributing factors, and visualize the findings in a network format.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;A single-center retrospective review of fetal MRI scans obtained in fetuses with CM II (presenting January 2007 to December 2022) was performed for ICH utilizing EPI-T2* blood-sensitive sequence. Fetuses with aqueduct stenosis (AS) were included as a control group. The incidence of ICH and corresponding gestational ages were compared between CM II and AS cases, and morphometric measurements (inner/outer CSF spaces, posterior fossa, venous structure) were compared among the 4 1:1 age-matched groups: CM II+ICH, CM II-ICH, AS+ICH, and AS-ICH. Additionally, a co-occurrence network was constructed to visualize associations between phenotypic features in ICH cases.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;A total of 101 fetuses with CM II and 90 controls with AS at a median gestational age of 24.4 weeks and 22.8 weeks (&lt;i&gt;P&lt;/i&gt; = .138) were included. Prevalence of ICH in fetuses with CM II was higher compared with the AS cases (28.7% versus 18.9%, &lt;i&gt;P&lt;/i&gt; = .023), accompanied by congested veins (deep vein congestion mainly in young fetuses, and cortical veins may also be affected in older fetuses). ICH was notably correlated with specific anatomic features, essentially characterized by reduced outer CSF spaces and clivus-supraocciput angle. The co-occurrence network analysis reveals complex connections including bony defects, small posterior fossa dimensions, vermis ectopia, reduced CSF spaces, as well as venous congestion and venous sinus stenosis as pivotal components within the network.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;The high prevalence of ICH—detected by fetal MRI—among fetuses with CM emphasizes the pathophysiologic importance of venous congestion, ICH, and vasogenic edema. As indicators of disease severity, these features may serve as helpful additional imaging biomarkers for the identification of potential candidates for fetal surgery.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
<meta name="citation_publisher" content="American Journal of Neuroradiology" />
<meta name="citation_publication_date" content="2024/10/01" />
<meta name="citation_mjid" content="ajnr;45/10/1562" />
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<meta name="citation_issn" content="0195-6108" />
<meta name="citation_issn" content="1936-959X" />
<meta name="citation_doi" content="10.3174/ajnr.A8331" />
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<meta name="citation_volume" content="45" />
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<meta name="citation_article_type" content="Research Article" />
<meta name="citation_section" content="Pediatric Neuroimaging" />
<meta name="citation_firstpage" content="1562" />
<meta name="citation_lastpage" content="1569" />
<meta name="citation_author" content="Hui Shi" />
<meta name="citation_author_institution" content="aFrom the Department of Radiology (H.S.), Zhu Jiang Hospital, Southern Medical University, Guangzhou, China" />
<meta name="citation_author" content="Daniela Prayer" />
<meta name="citation_author_institution" content="bDepartment of Biomedical Imaging and Image-guided Therapy (D.P., P.K., J.T., M.W., M.S., G.K.), Medical University of Vienna, Vienna, Austria" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0003-4612-2356" />
<meta name="citation_author" content="Patric Kienast" />
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<meta name="citation_author" content="Farjad Khalaveh" />
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<meta name="twitter:title" content="Revisiting the Pathophysiology of Intracranial Hemorrhage in Fetuses with Chiari II Malformation: Novel Imaging Biomarkers of Disease Severity?" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) has emerged as a notable concern in Chiari II malformation (CM II), yet its origins and clinical implications remain elusive. This study aims to validate the in utero prevalence of ICH in CM II and investigate contributing factors, and visualize the findings in a network format.

MATERIALS AND METHODS: A single-center retrospective review of fetal MRI scans obtained in fetuses with CM II (presenting January 2007 to December 2022) was performed for ICH utilizing EPI-T2* blood-sensitive sequence. Fetuses with aqueduct stenosis (AS) were included as a control group. The incidence of ICH and corresponding gestational ages were compared between CM II and AS cases, and morphometric measurements (inner/outer CSF spaces, posterior fossa, venous structure) were compared among the 4 1:1 age-matched groups: CM II+ICH, CM II-ICH, AS+ICH, and AS-ICH. Additionally, a co-occurrence network was constructed to visualize associations between phenotypic features in ICH cases.

RESULTS: A total of 101 fetuses with CM II and 90 controls with AS at a median gestational age of 24.4 weeks and 22.8 weeks ( P = .138) were included. Prevalence of ICH in fetuses with CM II was higher compared with the AS cases (28.7% versus 18.9%, P = .023), accompanied by congested veins (deep vein congestion mainly in young fetuses, and cortical veins may also be affected in older fetuses). ICH was notably correlated with specific anatomic features, essentially characterized by reduced outer CSF spaces and clivus-supraocciput angle. The co-occurrence network analysis reveals complex connections including bony defects, small posterior fossa dimensions, vermis ectopia, reduced CSF spaces, as well as venous congestion and venous sinus stenosis as pivotal components within the network.

CONCLUSIONS: The high prevalence of ICH—detected by fetal MRI—among fetuses with CM emphasizes the pathophysiologic importance of venous congestion, ICH, and vasogenic edema. As indicators of disease severity, these features may serve as helpful additional imaging biomarkers for the identification of potential candidates for fetal surgery.

AS
:   aqueduct stenosis
CM II
:   Chiari type II malformation
ICH
:   intracranial hemorrhage
PCA
:   principal component analysis
SSFP
:   steady-state free precession
SSSFE
:   single-shot fast spin-echo" />
<meta name="og-title" property="og:title" content="Revisiting the Pathophysiology of Intracranial Hemorrhage in Fetuses with Chiari II Malformation: Novel Imaging Biomarkers of Disease Severity?" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/45/10/1562" />
<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: Intracranial hemorrhage (ICH) has emerged as a notable concern in Chiari II malformation (CM II), yet its origins and clinical implications remain elusive. This study aims to validate the in utero prevalence of ICH in CM II and investigate contributing factors, and visualize the findings in a network format.

MATERIALS AND METHODS: A single-center retrospective review of fetal MRI scans obtained in fetuses with CM II (presenting January 2007 to December 2022) was performed for ICH utilizing EPI-T2* blood-sensitive sequence. Fetuses with aqueduct stenosis (AS) were included as a control group. The incidence of ICH and corresponding gestational ages were compared between CM II and AS cases, and morphometric measurements (inner/outer CSF spaces, posterior fossa, venous structure) were compared among the 4 1:1 age-matched groups: CM II+ICH, CM II-ICH, AS+ICH, and AS-ICH. Additionally, a co-occurrence network was constructed to visualize associations between phenotypic features in ICH cases.

RESULTS: A total of 101 fetuses with CM II and 90 controls with AS at a median gestational age of 24.4 weeks and 22.8 weeks ( P = .138) were included. Prevalence of ICH in fetuses with CM II was higher compared with the AS cases (28.7% versus 18.9%, P = .023), accompanied by congested veins (deep vein congestion mainly in young fetuses, and cortical veins may also be affected in older fetuses). ICH was notably correlated with specific anatomic features, essentially characterized by reduced outer CSF spaces and clivus-supraocciput angle. The co-occurrence network analysis reveals complex connections including bony defects, small posterior fossa dimensions, vermis ectopia, reduced CSF spaces, as well as venous congestion and venous sinus stenosis as pivotal components within the network.

CONCLUSIONS: The high prevalence of ICH—detected by fetal MRI—among fetuses with CM emphasizes the pathophysiologic importance of venous congestion, ICH, and vasogenic edema. As indicators of disease severity, these features may serve as helpful additional imaging biomarkers for the identification of potential candidates for fetal surgery.

AS
:   aqueduct stenosis
CM II
:   Chiari type II malformation
ICH
:   intracranial hemorrhage
PCA
:   principal component analysis
SSFP
:   steady-state free precession
SSSFE
:   single-shot fast spin-echo" />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node110818--5" data-node-nid="110818" id="top-node-110818--6271073156" data-pisa="ajnr;45/10/1562" data-pisa-master="ajnr;ajnr.A8331" data-apath="/ajnr/45/10/1562.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">Pediatric Neuroimaging</span></span></div>
  
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      <h1 class="highwire-cite-title" id="page-title">Revisiting the Pathophysiology of Intracranial Hemorrhage in Fetuses with Chiari II Malformation: Novel Imaging Biomarkers of Disease Severity?</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">Hui Shi</span>, <span class="highwire-citation-author" data-delta="1">Daniela Prayer</span>, <span class="highwire-citation-author" data-delta="2">Patric Kienast</span>, <span class="highwire-citation-author" data-delta="3">Farjad Khalaveh</span>, <span class="highwire-citation-author" data-delta="4">Johannes Tischer</span>, <span class="highwire-citation-author" data-delta="5">Julia Binder</span>, <span class="highwire-citation-author" data-delta="6">Michael Weber</span>, <span class="highwire-citation-author" data-delta="7">Marlene Stuempflen</span> and <span class="highwire-citation-author" data-delta="8">Gregor Kasprian</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">October 2024,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(10) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1562-1569; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A8331 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-110818--6271073156" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Hui Shi </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (H.S.), Zhu Jiang Hospital, Southern Medical University, Guangzhou, China</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=Hui%2BShi%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=Shi%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 last"><a href="/search/author1%3AHui%2BShi%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">Daniela Prayer </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Department of Biomedical Imaging and Image-guided Therapy (D.P., P.K., J.T., M.W., M.S., G.K.), Medical University of Vienna, Vienna, Austria</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=Daniela%2BPrayer%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=Prayer%20D&amp;link_type=AUTHORSEARCH" target="_blank" class="" 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class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>c</span>Department of Neurosurgery (F.K.), Medical University of Vienna, Vienna, Austria</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=Farjad%2BKhalaveh%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=Khalaveh%20F&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%3AFarjad%2BKhalaveh%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 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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 45</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 10 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Oct 2024 </div></div>
      
      
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Hui</span> <span class="nlm-surname">Shi</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Daniela</span> <span class="nlm-surname">Prayer</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Patric</span> <span class="nlm-surname">Kienast</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Farjad</span> <span class="nlm-surname">Khalaveh</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Johannes</span> <span class="nlm-surname">Tischer</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Julia</span> <span class="nlm-surname">Binder</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Michael</span> <span class="nlm-surname">Weber</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Marlene</span> <span class="nlm-surname">Stuempflen</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Gregor</span> <span class="nlm-surname">Kasprian</span></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">Oct 2024, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(10) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1562-1569; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A8331 </span></div>
  
  
  
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Hui</span> <span class="nlm-surname">Shi</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Daniela</span> <span class="nlm-surname">Prayer</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Patric</span> <span class="nlm-surname">Kienast</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Farjad</span> <span class="nlm-surname">Khalaveh</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Johannes</span> <span class="nlm-surname">Tischer</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Julia</span> <span class="nlm-surname">Binder</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Michael</span> <span class="nlm-surname">Weber</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Marlene</span> <span class="nlm-surname">Stuempflen</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Gregor</span> <span class="nlm-surname">Kasprian</span></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">Oct 2024, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(10) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1562-1569; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A8331 </span></div>
  
  
  
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