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<meta name="DC.Title" content="Efficacy Assessment of Cerebral Perfusion Augmentation through Functional Connectivity in an Acute Canine Stroke Model" />
<meta name="DC.Identifier" content="10.3174/ajnr.A8320" />
<meta name="DC.Date" content="2024-09-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2024 by American Journal of Neuroradiology" />
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<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of norepinephrine and hydralazine (NEH), a cerebral perfusion augmentation therapy, on RSN integrity in a hyperacute canine stroke model.

MATERIALS AND METHODS: Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Postocclusion, the treatment group received intra-arterial norepinephrine (0.1–1.52 µg/kg/min, adjusted for 25–45 mm Hg above baseline mean arterial pressure) and hydralazine (20 mg). Resting-state fMRI (rs-fMRI) data were acquired with a 3T scanner by using a blood oxygen level dependent-EPI sequence (TR/TE = 1400 ms/20 ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm full width at half maximum), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis and weighted whole-brain ROI-to-ROI connectome, pre- and post-MCAO.

RESULTS: NEH therapy significantly maintained connectivity post-MCAO in the higher-order visual and parietal RSNs, as evidenced by thresholded statistical mapping (threshold-free cluster enhancement P corr &gt; .95). However, this preservation was network-dependent, with no significant ( P corr &lt; .95) changes in the primary visual and sensorimotor networks.

CONCLUSIONS: NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity after ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable end point for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation.

FWE
:   family-wise error
ICA
:   independent component analysis
MCAO
:   middle cerebral artery occlusion
NEH
:   norepinephrine and hydralazine
rs-fMRI
:   resting-state fMRI
RSN
:   resting-state network
TFCE
:   threshold-free cluster enhancement" />
<meta name="DC.Contributor" content="Chisondi S. Warioba" />
<meta name="DC.Contributor" content="Mira Liu" />
<meta name="DC.Contributor" content="Sagada Peñano" />
<meta name="DC.Contributor" content="Timothy J. Carroll" />
<meta name="DC.Contributor" content="Sean Foxley" />
<meta name="DC.Contributor" content="Gregory Christoforidis" />
<meta name="article:published_time" content="2024-09-01" />
<meta name="article:section" content="Neurovascular/Stroke Imaging" />
<meta name="citation_title" content="Efficacy Assessment of Cerebral Perfusion Augmentation through Functional Connectivity in an Acute Canine Stroke Model" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Ischemic stroke disrupts functional connectivity within the brain9s resting-state networks (RSNs), impacting recovery. This study evaluates the effects of norepinephrine and hydralazine (NEH), a cerebral perfusion augmentation therapy, on RSN integrity in a hyperacute canine stroke model.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Postocclusion, the treatment group received intra-arterial norepinephrine (0.1–1.52 µg/kg/min, adjusted for 25–45 mm Hg above baseline mean arterial pressure) and hydralazine (20 mg). Resting-state fMRI (rs-fMRI) data were acquired with a 3T scanner by using a blood oxygen level dependent-EPI sequence (TR/TE = 1400 ms/20 ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm full width at half maximum), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis and weighted whole-brain ROI-to-ROI connectome, pre- and post-MCAO.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;NEH therapy significantly maintained connectivity post-MCAO in the higher-order visual and parietal RSNs, as evidenced by thresholded statistical mapping (threshold-free cluster enhancement &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;corr&lt;/sub&gt; &amp;gt; .95). However, this preservation was network-dependent, with no significant (&lt;i&gt;P&lt;/i&gt;&lt;sub&gt;corr&lt;/sub&gt; &amp;lt; .95) changes in the primary visual and sensorimotor networks.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity after ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable end point for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation.&lt;/p&gt;" />
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<meta name="twitter:title" content="Efficacy Assessment of Cerebral Perfusion Augmentation through Functional Connectivity in an Acute Canine Stroke Model" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of norepinephrine and hydralazine (NEH), a cerebral perfusion augmentation therapy, on RSN integrity in a hyperacute canine stroke model.

MATERIALS AND METHODS: Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Postocclusion, the treatment group received intra-arterial norepinephrine (0.1–1.52 µg/kg/min, adjusted for 25–45 mm Hg above baseline mean arterial pressure) and hydralazine (20 mg). Resting-state fMRI (rs-fMRI) data were acquired with a 3T scanner by using a blood oxygen level dependent-EPI sequence (TR/TE = 1400 ms/20 ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm full width at half maximum), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis and weighted whole-brain ROI-to-ROI connectome, pre- and post-MCAO.

RESULTS: NEH therapy significantly maintained connectivity post-MCAO in the higher-order visual and parietal RSNs, as evidenced by thresholded statistical mapping (threshold-free cluster enhancement P corr &gt; .95). However, this preservation was network-dependent, with no significant ( P corr &lt; .95) changes in the primary visual and sensorimotor networks.

CONCLUSIONS: NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity after ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable end point for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation.

FWE
:   family-wise error
ICA
:   independent component analysis
MCAO
:   middle cerebral artery occlusion
NEH
:   norepinephrine and hydralazine
rs-fMRI
:   resting-state fMRI
RSN
:   resting-state network
TFCE
:   threshold-free cluster enhancement" />
<meta name="og-title" property="og:title" content="Efficacy Assessment of Cerebral Perfusion Augmentation through Functional Connectivity in an Acute Canine Stroke Model" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/45/9/1214" />
<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: Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of norepinephrine and hydralazine (NEH), a cerebral perfusion augmentation therapy, on RSN integrity in a hyperacute canine stroke model.

MATERIALS AND METHODS: Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Postocclusion, the treatment group received intra-arterial norepinephrine (0.1–1.52 µg/kg/min, adjusted for 25–45 mm Hg above baseline mean arterial pressure) and hydralazine (20 mg). Resting-state fMRI (rs-fMRI) data were acquired with a 3T scanner by using a blood oxygen level dependent-EPI sequence (TR/TE = 1400 ms/20 ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm full width at half maximum), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis and weighted whole-brain ROI-to-ROI connectome, pre- and post-MCAO.

RESULTS: NEH therapy significantly maintained connectivity post-MCAO in the higher-order visual and parietal RSNs, as evidenced by thresholded statistical mapping (threshold-free cluster enhancement P corr &gt; .95). However, this preservation was network-dependent, with no significant ( P corr &lt; .95) changes in the primary visual and sensorimotor networks.

CONCLUSIONS: NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity after ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable end point for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation.

FWE
:   family-wise error
ICA
:   independent component analysis
MCAO
:   middle cerebral artery occlusion
NEH
:   norepinephrine and hydralazine
rs-fMRI
:   resting-state fMRI
RSN
:   resting-state network
TFCE
:   threshold-free cluster enhancement" />
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      <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">Neurovascular/Stroke Imaging</span></span></div>
  
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      <h1 class="highwire-cite-title" id="page-title">Efficacy Assessment of Cerebral Perfusion Augmentation through Functional Connectivity in an Acute Canine Stroke Model</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">Chisondi S. Warioba</span>, <span class="highwire-citation-author" data-delta="1">Mira Liu</span>, <span class="highwire-citation-author" data-delta="2">Sagada Peñano</span>, <span class="highwire-citation-author" data-delta="3">Timothy J. Carroll</span>, <span class="highwire-citation-author" data-delta="4">Sean Foxley</span> and <span class="highwire-citation-author" data-delta="5">Gregory Christoforidis</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 2024,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(9) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1214-1219; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A8320 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-110084--61875754508" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Chisondi S. Warioba </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 (C.S.W., M.L., S.P., T.J.C., S.F.), University of Chicago, Chicago, Illinois</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=Chisondi%2BS.%2BWarioba%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=Warioba%20CS&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%3AChisondi%2BS.%2BWarioba%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/0000-0002-4266-2673" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Chisondi S. Warioba</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">Mira Liu </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 (C.S.W., M.L., S.P., T.J.C., S.F.), University of Chicago, Chicago, Illinois</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=Mira%2BLiu%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=Liu%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%3AMira%2BLiu%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/0000-0002-8729-9302" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Mira Liu</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">Sagada Peñano </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 (C.S.W., M.L., S.P., T.J.C., S.F.), University of Chicago, Chicago, Illinois</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=Sagada%2BPe%C3%B1ano%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=Pe%C3%B1ano%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%3ASagada%2BPe%25C3%25B1ano%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">Timothy J. Carroll </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 (C.S.W., M.L., S.P., T.J.C., S.F.), University of Chicago, Chicago, Illinois</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=Timothy%2BJ.%2BCarroll%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=Carroll%20TJ&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%3ATimothy%2BJ.%2BCarroll%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/0000-0003-2113-6284" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Timothy J. Carroll</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">Sean Foxley </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 (C.S.W., M.L., S.P., T.J.C., S.F.), University of Chicago, Chicago, Illinois</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=Sean%2BFoxley%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=Foxley%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%3ASean%2BFoxley%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">Gregory Christoforidis </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Mount Carmel Health (G.C.), Columbus, Ohio.</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=Gregory%2BChristoforidis%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=Christoforidis%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"><a href="/search/author1%3AGregory%2BChristoforidis%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/0000-0003-3800-0340" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Gregory Christoforidis</a></li></ul></div></div></div>  </div>

  
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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 9 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Sep 2024 </div></div>
      
      
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      <div class="highwire-cite-title">Efficacy Assessment of Cerebral Perfusion Augmentation through Functional Connectivity in an Acute Canine Stroke Model</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">Chisondi S.</span> <span class="nlm-surname">Warioba</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Mira</span> <span class="nlm-surname">Liu</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Sagada</span> <span class="nlm-surname">Peñano</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Timothy J.</span> <span class="nlm-surname">Carroll</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Sean</span> <span class="nlm-surname">Foxley</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Gregory</span> <span class="nlm-surname">Christoforidis</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">Sep 2024, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(9) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1214-1219; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A8320 </span></div>
  
  
  
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