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<meta name="DC.Title" content="Imaging Biomarkers in Acute Ischemic Stroke Trials: A Systematic Review" />
<meta name="DC.Identifier" content="10.3174/ajnr.A4208" />
<meta name="DC.Date" content="2015-01-29" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
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<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Imaging biomarkers are increasingly used to provide a better understanding of the pathophysiology of acute ischemic stroke. However, this approach of routinely using imaging biomarkers to inform treatment decisions has yet to be translated into successful randomized trials. The aim of this study was to systematically review the use of imaging biomarkers in randomized controlled trials in patients with acute ischemic stroke, exploring the purposes for which the imaging biomarkers were used.

MATERIALS AND METHODS: We performed a systematic review of imaging biomarkers used in randomized controlled trials of acute ischemic stroke, in which a therapeutic intervention was trialed within 48 hours of symptom onset. Data bases searched included MEDLINE, EMBASE, strokecenter.org, and the Virtual International Stroke Trials Archive (1995–2014).

RESULTS: Eighty-four studies met the criteria, of which 49 used imaging to select patients; 31, for subgroup analysis; and 49, as an outcome measure. Imaging biomarkers were broadly used for 8 purposes. There was marked heterogeneity in the definitions and uses of imaging biomarkers and significant publication bias among post hoc analyses.

CONCLUSIONS: Imaging biomarkers offer the opportunity to refine the trial cohort by minimizing participant variation, to decrease sample size, and to personalize treatment approaches for those who stand to benefit most. However, within imaging modalities, there has been little consistency between stroke trials. Greater effort to prospectively use consistent imaging biomarkers should help improve the development of novel treatment strategies in acute stroke and improve comparison between studies.

### Abbreviations

RCT
:   randomized controlled trial
TCD
:   transcranial Doppler" />
<meta name="DC.Contributor" content="G.W.J. Harston" />
<meta name="DC.Contributor" content="N. Rane" />
<meta name="DC.Contributor" content="G. Shaya" />
<meta name="DC.Contributor" content="S. Thandeswaran" />
<meta name="DC.Contributor" content="M. Cellerini" />
<meta name="DC.Contributor" content="F. Sheerin" />
<meta name="DC.Contributor" content="J. Kennedy" />
<meta name="article:published_time" content="2015-01-29" />
<meta name="article:section" content="BRAIN" />
<meta name="citation_title" content="Imaging Biomarkers in Acute Ischemic Stroke Trials: A Systematic Review" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Imaging biomarkers are increasingly used to provide a better understanding of the pathophysiology of acute ischemic stroke. However, this approach of routinely using imaging biomarkers to inform treatment decisions has yet to be translated into successful randomized trials. The aim of this study was to systematically review the use of imaging biomarkers in randomized controlled trials in patients with acute ischemic stroke, exploring the purposes for which the imaging biomarkers were used.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;We performed a systematic review of imaging biomarkers used in randomized controlled trials of acute ischemic stroke, in which a therapeutic intervention was trialed within 48 hours of symptom onset. Data bases searched included MEDLINE, EMBASE, strokecenter.org, and the Virtual International Stroke Trials Archive (1995–2014).&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Eighty-four studies met the criteria, of which 49 used imaging to select patients; 31, for subgroup analysis; and 49, as an outcome measure. Imaging biomarkers were broadly used for 8 purposes. There was marked heterogeneity in the definitions and uses of imaging biomarkers and significant publication bias among post hoc analyses.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Imaging biomarkers offer the opportunity to refine the trial cohort by minimizing participant variation, to decrease sample size, and to personalize treatment approaches for those who stand to benefit most. However, within imaging modalities, there has been little consistency between stroke trials. Greater effort to prospectively use consistent imaging biomarkers should help improve the development of novel treatment strategies in acute stroke and improve comparison between studies.&lt;/p&gt;" />
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<meta name="citation_author" content="G.W.J. Harston" />
<meta name="citation_author_institution" content="From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia." />
<meta name="citation_author" content="N. Rane" />
<meta name="citation_author_institution" content="From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia." />
<meta name="citation_author" content="G. Shaya" />
<meta name="citation_author_institution" content="From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia." />
<meta name="citation_author" content="S. Thandeswaran" />
<meta name="citation_author_institution" content="From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia." />
<meta name="citation_author" content="M. Cellerini" />
<meta name="citation_author_institution" content="From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia." />
<meta name="citation_author" content="F. Sheerin" />
<meta name="citation_author_institution" content="From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia." />
<meta name="citation_author" content="J. Kennedy" />
<meta name="citation_author_institution" content="From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia." />
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<meta name="twitter:title" content="Imaging Biomarkers in Acute Ischemic Stroke Trials: A Systematic Review" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Imaging biomarkers are increasingly used to provide a better understanding of the pathophysiology of acute ischemic stroke. However, this approach of routinely using imaging biomarkers to inform treatment decisions has yet to be translated into successful randomized trials. The aim of this study was to systematically review the use of imaging biomarkers in randomized controlled trials in patients with acute ischemic stroke, exploring the purposes for which the imaging biomarkers were used.

MATERIALS AND METHODS: We performed a systematic review of imaging biomarkers used in randomized controlled trials of acute ischemic stroke, in which a therapeutic intervention was trialed within 48 hours of symptom onset. Data bases searched included MEDLINE, EMBASE, strokecenter.org, and the Virtual International Stroke Trials Archive (1995–2014).

RESULTS: Eighty-four studies met the criteria, of which 49 used imaging to select patients; 31, for subgroup analysis; and 49, as an outcome measure. Imaging biomarkers were broadly used for 8 purposes. There was marked heterogeneity in the definitions and uses of imaging biomarkers and significant publication bias among post hoc analyses.

CONCLUSIONS: Imaging biomarkers offer the opportunity to refine the trial cohort by minimizing participant variation, to decrease sample size, and to personalize treatment approaches for those who stand to benefit most. However, within imaging modalities, there has been little consistency between stroke trials. Greater effort to prospectively use consistent imaging biomarkers should help improve the development of novel treatment strategies in acute stroke and improve comparison between studies.

### Abbreviations

RCT
:   randomized controlled trial
TCD
:   transcranial Doppler" />
<meta name="og-title" property="og:title" content="Imaging Biomarkers in Acute Ischemic Stroke Trials: A Systematic Review" />
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<meta name="og-description" property="og:description" content="BACKGROUND AND PURPOSE: Imaging biomarkers are increasingly used to provide a better understanding of the pathophysiology of acute ischemic stroke. However, this approach of routinely using imaging biomarkers to inform treatment decisions has yet to be translated into successful randomized trials. The aim of this study was to systematically review the use of imaging biomarkers in randomized controlled trials in patients with acute ischemic stroke, exploring the purposes for which the imaging biomarkers were used.

MATERIALS AND METHODS: We performed a systematic review of imaging biomarkers used in randomized controlled trials of acute ischemic stroke, in which a therapeutic intervention was trialed within 48 hours of symptom onset. Data bases searched included MEDLINE, EMBASE, strokecenter.org, and the Virtual International Stroke Trials Archive (1995–2014).

RESULTS: Eighty-four studies met the criteria, of which 49 used imaging to select patients; 31, for subgroup analysis; and 49, as an outcome measure. Imaging biomarkers were broadly used for 8 purposes. There was marked heterogeneity in the definitions and uses of imaging biomarkers and significant publication bias among post hoc analyses.

CONCLUSIONS: Imaging biomarkers offer the opportunity to refine the trial cohort by minimizing participant variation, to decrease sample size, and to personalize treatment approaches for those who stand to benefit most. However, within imaging modalities, there has been little consistency between stroke trials. Greater effort to prospectively use consistent imaging biomarkers should help improve the development of novel treatment strategies in acute stroke and improve comparison between studies.

### Abbreviations

RCT
:   randomized controlled trial
TCD
:   transcranial Doppler" />
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      <h1 class="highwire-cite-title" id="page-title">Imaging Biomarkers in Acute Ischemic Stroke Trials: A Systematic Review</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">G.W.J. Harston</span>, <span class="highwire-citation-author" data-delta="1">N. Rane</span>, <span class="highwire-citation-author" data-delta="2">G. Shaya</span>, <span class="highwire-citation-author" data-delta="3">S. Thandeswaran</span>, <span class="highwire-citation-author" data-delta="4">M. Cellerini</span>, <span class="highwire-citation-author" data-delta="5">F. Sheerin</span> and <span class="highwire-citation-author" data-delta="6">J. Kennedy</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">January 2015,  </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A4208 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-50947--6840705821" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">G.W.J. Harston </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia.</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=G.W.J.%2BHarston%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=Harston%20G&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%3AG.W.J.%2BHarston%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">N. Rane </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia.</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=N.%2BRane%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=Rane%20N&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%3AN.%2BRane%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-2"><div class="author-tooltip-name">G. Shaya </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia.</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=G.%2BShaya%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=Shaya%20G&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%3AG.%2BShaya%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-3"><div class="author-tooltip-name">S. Thandeswaran </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia.</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.%2BThandeswaran%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=Thandeswaran%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 last"><a href="/search/author1%3AS.%2BThandeswaran%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-4"><div class="author-tooltip-name">M. Cellerini </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia.</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.%2BCellerini%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=Cellerini%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 last"><a href="/search/author1%3AM.%2BCellerini%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-5"><div class="author-tooltip-name">F. Sheerin </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Radcliffe Department of Medicine (G.W.J.H., G.S., S.T., J.K.), University of Oxford, Oxford, United Kingdom; Department of Neuroradiology (N.R., M.C., F.S.), Oxford University Hospitals NHS Trust, Oxford, United Kingdom; and Neurointervention Service (N.R.), Royal Melbourne Hospital, Melbourne Health, Victoria, Australia.</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=F.%2BSheerin%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=Sheerin%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 last"><a href="/search/author1%3AF.%2BSheerin%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-6"><div class="author-tooltip-name">J. 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      <div class="highwire-cite-title">Imaging Biomarkers in Acute Ischemic Stroke Trials: A Systematic Review</div>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">G.W.J.</span> <span class="nlm-surname">Harston</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">N.</span> <span class="nlm-surname">Rane</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">G.</span> <span class="nlm-surname">Shaya</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">S.</span> <span class="nlm-surname">Thandeswaran</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">M.</span> <span class="nlm-surname">Cellerini</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">F.</span> <span class="nlm-surname">Sheerin</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">J.</span> <span class="nlm-surname">Kennedy</span></span></span></div>
  
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