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<meta name="DC.Title" content="Value of Contrast-Enhanced MRA versus Time-of-Flight MRA in Acute Ischemic Stroke MRI" />
<meta name="DC.Identifier" content="10.3174/ajnr.A5771" />
<meta name="DC.Date" content="2018-09-01" />
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<meta name="DC.Rights" content="© 2018 by American Journal of Neuroradiology" />
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<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Vessel imaging in acute ischemic stroke is essential to select patients with large-vessel occlusion for mechanical thrombectomy. Our aim was to compare the diagnostic accuracy of time-of-flight MR angiography and contrast-enhanced MR angiography for identification of vessel occlusion and collateral status in acute ischemic stroke.

MATERIALS AND METHODS: One hundred twenty-three patients with stroke with large-vessel occlusion before thrombectomy were included in this retrospective study. Before thrombectomy, 3T MR imaging, including conventional 3D TOF-MRA of the intracranial arteries and contrast-enhanced MRA of intra- and extracranial arteries, was performed. Both techniques were assessed independently by 2 neuroradiologists for location of the occlusion, imaging quality, and collateral status. Findings were compared, with subsequent DSA as the reference standard.

RESULTS: Both techniques had good interrater agreement of κ = 0.74 (95% CI, 0.66–0.83) for TOF-MRA and κ = 0.72 (95% CI, 0.63–0.80) for contrast-enhanced MRA. Occlusion localization differed significantly on TOF-MRA compared with DSA ( P &lt; .001), while no significant difference was observed between DSA and contrast-enhanced MRA ( P = .75). Assessment of collaterals showed very good agreement between contrast-enhanced MRA and DSA (94.9% with P = .25), but only fair agreement between TOF-MRA and DSA (23.2% with P &lt; .001).

CONCLUSIONS: Contrast-enhanced MRA offers better diagnostic accuracy than TOF-MRA in acute ischemic stroke. Contrast-enhanced MRA was superior in localizing vessel occlusion within a shorter acquisition time while providing a larger coverage, including extracranial vessels, and a more accurate assessment of collateral status. These results support inclusion of contrast-enhanced MRA in acute stroke MR imaging, perhaps making TOF-MRA superfluous.

CE-MRA
:   contrast-enhanced MRA" />
<meta name="DC.Contributor" content="T. Boujan" />
<meta name="DC.Contributor" content="U. Neuberger" />
<meta name="DC.Contributor" content="J. Pfaff" />
<meta name="DC.Contributor" content="S. Nagel" />
<meta name="DC.Contributor" content="C. Herweh" />
<meta name="DC.Contributor" content="M. Bendszus" />
<meta name="DC.Contributor" content="M.A. Möhlenbruch" />
<meta name="article:published_time" content="2018-09-01" />
<meta name="article:section" content="Extracranial Vascular" />
<meta name="citation_title" content="Value of Contrast-Enhanced MRA versus Time-of-Flight MRA in Acute Ischemic Stroke MRI" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Vessel imaging in acute ischemic stroke is essential to select patients with large-vessel occlusion for mechanical thrombectomy. Our aim was to compare the diagnostic accuracy of time-of-flight MR angiography and contrast-enhanced MR angiography for identification of vessel occlusion and collateral status in acute ischemic stroke.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;One hundred twenty-three patients with stroke with large-vessel occlusion before thrombectomy were included in this retrospective study. Before thrombectomy, 3T MR imaging, including conventional 3D TOF-MRA of the intracranial arteries and contrast-enhanced MRA of intra- and extracranial arteries, was performed. Both techniques were assessed independently by 2 neuroradiologists for location of the occlusion, imaging quality, and collateral status. Findings were compared, with subsequent DSA as the reference standard.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Both techniques had good interrater agreement of κ = 0.74 (95% CI, 0.66–0.83) for TOF-MRA and κ = 0.72 (95% CI, 0.63–0.80) for contrast-enhanced MRA. Occlusion localization differed significantly on TOF-MRA compared with DSA (&lt;i&gt;P&lt;/i&gt; &amp;lt; .001), while no significant difference was observed between DSA and contrast-enhanced MRA (&lt;i&gt;P&lt;/i&gt; = .75). Assessment of collaterals showed very good agreement between contrast-enhanced MRA and DSA (94.9% with &lt;i&gt;P&lt;/i&gt; = .25), but only fair agreement between TOF-MRA and DSA (23.2% with &lt;i&gt;P&lt;/i&gt; &amp;lt; .001).&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Contrast-enhanced MRA offers better diagnostic accuracy than TOF-MRA in acute ischemic stroke. Contrast-enhanced MRA was superior in localizing vessel occlusion within a shorter acquisition time while providing a larger coverage, including extracranial vessels, and a more accurate assessment of collateral status. These results support inclusion of contrast-enhanced MRA in acute stroke MR imaging, perhaps making TOF-MRA superfluous.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
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<meta name="citation_publication_date" content="2018/09/01" />
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<meta name="citation_author" content="T. Boujan" />
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<meta name="citation_author" content="S. Nagel" />
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<meta name="twitter:title" content="Value of Contrast-Enhanced MRA versus Time-of-Flight MRA in Acute Ischemic Stroke MRI" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Vessel imaging in acute ischemic stroke is essential to select patients with large-vessel occlusion for mechanical thrombectomy. Our aim was to compare the diagnostic accuracy of time-of-flight MR angiography and contrast-enhanced MR angiography for identification of vessel occlusion and collateral status in acute ischemic stroke.

MATERIALS AND METHODS: One hundred twenty-three patients with stroke with large-vessel occlusion before thrombectomy were included in this retrospective study. Before thrombectomy, 3T MR imaging, including conventional 3D TOF-MRA of the intracranial arteries and contrast-enhanced MRA of intra- and extracranial arteries, was performed. Both techniques were assessed independently by 2 neuroradiologists for location of the occlusion, imaging quality, and collateral status. Findings were compared, with subsequent DSA as the reference standard.

RESULTS: Both techniques had good interrater agreement of κ = 0.74 (95% CI, 0.66–0.83) for TOF-MRA and κ = 0.72 (95% CI, 0.63–0.80) for contrast-enhanced MRA. Occlusion localization differed significantly on TOF-MRA compared with DSA ( P &lt; .001), while no significant difference was observed between DSA and contrast-enhanced MRA ( P = .75). Assessment of collaterals showed very good agreement between contrast-enhanced MRA and DSA (94.9% with P = .25), but only fair agreement between TOF-MRA and DSA (23.2% with P &lt; .001).

CONCLUSIONS: Contrast-enhanced MRA offers better diagnostic accuracy than TOF-MRA in acute ischemic stroke. Contrast-enhanced MRA was superior in localizing vessel occlusion within a shorter acquisition time while providing a larger coverage, including extracranial vessels, and a more accurate assessment of collateral status. These results support inclusion of contrast-enhanced MRA in acute stroke MR imaging, perhaps making TOF-MRA superfluous.

CE-MRA
:   contrast-enhanced MRA" />
<meta name="og-title" property="og:title" content="Value of Contrast-Enhanced MRA versus Time-of-Flight MRA in Acute Ischemic Stroke MRI" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/39/9/1710" />
<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: Vessel imaging in acute ischemic stroke is essential to select patients with large-vessel occlusion for mechanical thrombectomy. Our aim was to compare the diagnostic accuracy of time-of-flight MR angiography and contrast-enhanced MR angiography for identification of vessel occlusion and collateral status in acute ischemic stroke.

MATERIALS AND METHODS: One hundred twenty-three patients with stroke with large-vessel occlusion before thrombectomy were included in this retrospective study. Before thrombectomy, 3T MR imaging, including conventional 3D TOF-MRA of the intracranial arteries and contrast-enhanced MRA of intra- and extracranial arteries, was performed. Both techniques were assessed independently by 2 neuroradiologists for location of the occlusion, imaging quality, and collateral status. Findings were compared, with subsequent DSA as the reference standard.

RESULTS: Both techniques had good interrater agreement of κ = 0.74 (95% CI, 0.66–0.83) for TOF-MRA and κ = 0.72 (95% CI, 0.63–0.80) for contrast-enhanced MRA. Occlusion localization differed significantly on TOF-MRA compared with DSA ( P &lt; .001), while no significant difference was observed between DSA and contrast-enhanced MRA ( P = .75). Assessment of collaterals showed very good agreement between contrast-enhanced MRA and DSA (94.9% with P = .25), but only fair agreement between TOF-MRA and DSA (23.2% with P &lt; .001).

CONCLUSIONS: Contrast-enhanced MRA offers better diagnostic accuracy than TOF-MRA in acute ischemic stroke. Contrast-enhanced MRA was superior in localizing vessel occlusion within a shorter acquisition time while providing a larger coverage, including extracranial vessels, and a more accurate assessment of collateral status. These results support inclusion of contrast-enhanced MRA in acute stroke MR imaging, perhaps making TOF-MRA superfluous.

CE-MRA
:   contrast-enhanced MRA" />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node62614--5" data-node-nid="62614" id="top-node-62614--61545385586" data-pisa="ajnr;39/9/1710" data-pisa-master="ajnr;ajnr.A5771" data-apath="/ajnr/39/9/1710.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">Extracranial Vascular</span></span></div>
  
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      <h1 class="highwire-cite-title" id="page-title">Value of Contrast-Enhanced MRA versus Time-of-Flight MRA in Acute Ischemic Stroke MRI</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">T. Boujan</span>, <span class="highwire-citation-author" data-delta="1">U. Neuberger</span>, <span class="highwire-citation-author" data-delta="2">J. Pfaff</span>, <span class="highwire-citation-author" data-delta="3">S. Nagel</span>, <span class="highwire-citation-author" data-delta="4">C. Herweh</span>, <span class="highwire-citation-author" data-delta="5">M. Bendszus</span> and <span class="highwire-citation-author" data-delta="6">M.A. Möhlenbruch</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">September 2018,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">39 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(9) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1710-1716; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A5771 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-62614--61545385586" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">T. Boujan </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Neuroradiology (T.B., U.N., J.P., C.H., M.B., M.M.)</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.%2BBoujan%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=Boujan%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.%2BBoujan%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="https://orcid.org/0000-0002-6709-0288" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for T. Boujan</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">U. Neuberger </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Neuroradiology (T.B., U.N., J.P., C.H., M.B., M.M.)</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=U.%2BNeuberger%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=Neuberger%20U&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%3AU.%2BNeuberger%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="https://orcid.org/0000-0002-3085-3886" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for U. Neuberger</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">J. Pfaff </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Neuroradiology (T.B., U.N., J.P., C.H., M.B., M.M.)</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=J.%2BPfaff%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=Pfaff%20J&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%3AJ.%2BPfaff%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="https://orcid.org/0000-0003-0672-5718" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for J. Pfaff</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">S. Nagel </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Neurology (S.N.), University of Heidelberg Medical Center, 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.%2BNagel%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=Nagel%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.%2BNagel%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="https://orcid.org/0000-0003-2471-6647" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for S. Nagel</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">C. Herweh </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Neuroradiology (T.B., U.N., J.P., C.H., M.B., M.M.)</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.%2BHerweh%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=Herweh%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.%2BHerweh%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="https://orcid.org/0000-0002-9223-9662" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. Herweh</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">M. Bendszus </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Neuroradiology (T.B., U.N., J.P., C.H., M.B., M.M.)</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.%2BBendszus%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=Bendszus%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.%2BBendszus%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="https://orcid.org/0000-0002-9094-6769" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for M. Bendszus</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">M.A. Möhlenbruch </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Departments of Neuroradiology (T.B., U.N., J.P., C.H., M.B., M.M.)</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.A.%2BM%C3%B6hlenbruch%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=M%C3%B6hlenbruch%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.A.%2BM%25C3%25B6hlenbruch%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="https://orcid.org/0000-0002-5075-704X" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for M.A. Möhlenbruch</a></li></ul></div></div></div>  </div>

  
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    <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-1"><h2>Abstract</h2><div id="sec-1" class="subsection"><p id="p-2"><strong>BACKGROUND AND PURPOSE:</strong> Vessel imaging in acute ischemic stroke is essential to select patients with large-vessel occlusion for mechanical thrombectomy. Our aim was to compare the diagnostic accuracy of time-of-flight MR angiography and contrast-enhanced MR angiography for identification of vessel occlusion and collateral status in acute ischemic stroke.</p></div><div id="sec-2" class="subsection"><p id="p-3"><strong>MATERIALS AND METHODS:</strong> One hundred twenty-three patients with stroke with large-vessel occlusion before thrombectomy were included in this retrospective study. Before thrombectomy, 3T MR imaging, including conventional 3D TOF-MRA of the intracranial arteries and contrast-enhanced MRA of intra- and extracranial arteries, was performed. Both techniques were assessed independently by 2 neuroradiologists for location of the occlusion, imaging quality, and collateral status. Findings were compared, with subsequent DSA as the reference standard.</p></div><div id="sec-3" class="subsection"><p id="p-4"><strong>RESULTS:</strong> Both techniques had good interrater agreement of κ = 0.74 (95% CI, 0.66–0.83) for TOF-MRA and κ = 0.72 (95% CI, 0.63–0.80) for contrast-enhanced MRA. Occlusion localization differed significantly on TOF-MRA compared with DSA (<em>P</em> &lt; .001), while no significant difference was observed between DSA and contrast-enhanced MRA (<em>P</em> = .75). Assessment of collaterals showed very good agreement between contrast-enhanced MRA and DSA (94.9% with <em>P</em> = .25), but only fair agreement between TOF-MRA and DSA (23.2% with <em>P</em> &lt; .001).</p></div><div id="sec-4" class="subsection"><p id="p-5"><strong>CONCLUSIONS:</strong> Contrast-enhanced MRA offers better diagnostic accuracy than TOF-MRA in acute ischemic stroke. Contrast-enhanced MRA was superior in localizing vessel occlusion within a shorter acquisition time while providing a larger coverage, including extracranial vessels, and a more accurate assessment of collateral status. These results support inclusion of contrast-enhanced MRA in acute stroke MR imaging, perhaps making TOF-MRA superfluous.</p></div></div><div class="section glossary" id="glossary-1"><h2 class="">ABBREVIATION:</h2><dl id="def-list-1"><dt id="def-item-1">CE-MRA<span class="def-item-dt-sep"></span></dt><dd>contrast-enhanced MRA</dd></dl></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2018 by American Journal of Neuroradiology</li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="http://ajnr-stage2.stage.highwire.org/content/39/9/1710.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div>  </div>

  
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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 39</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 9 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Sep 2018 </div></div>
      
      
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