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<meta name="DC.Title" content="Mitotic Activity in Glioblastoma Correlates with Estimated Extravascular Extracellular Space Derived from Dynamic Contrast-Enhanced MR Imaging" />
<meta name="DC.Identifier" content="10.3174/ajnr.A4623" />
<meta name="DC.Date" content="2016-05-01" />
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<meta name="DC.Description" content="BACKGROUND AND PURPOSE: A number of parameters derived from dynamic contrast-enhanced MR imaging and separate histologic features have been identified as potential prognosticators in high-grade glioma. This study evaluated the relationships between dynamic contrast-enhanced MRI–derived parameters and histologic features in glioblastoma multiforme.

MATERIALS AND METHODS: Twenty-eight patients with newly presenting glioblastoma multiforme underwent preoperative imaging (conventional imaging and T1 dynamic contrast-enhanced MRI). Parametric maps of the initial area under the contrast agent concentration curve, contrast transfer coefficient, estimate of volume of the extravascular extracellular space, and estimate of blood plasma volume were generated, and the enhancing fraction was calculated. Surgical specimens were used to assess subtype and were graded (World Health Organization classification system) and were assessed for necrosis, cell density, cellular atypia, mitotic activity, and overall vascularity scores. Quantitative assessment of endothelial surface area, vascular surface area, and a vascular profile count were made by using CD34 immunostaining. The relationships between MR imaging parameters and histopathologic features were examined.

RESULTS: High values of contrast transfer coefficient were associated with the presence of frank necrosis ( P = .005). High values of the estimate of volume of the extravascular extracellular space were associated with a fibrillary histologic pattern ( P &lt; .01) and with increased mitotic activity ( P &lt; .05). No relationship was found between mitotic activity and histologic pattern, suggesting that the correlation between the estimate of volume of the extravascular extracellular space and mitotic activity was independent of the histologic pattern.

CONCLUSIONS: A correlation between the estimate of volume of the extravascular extracellular space and mitotic activity is reported. Further work is warranted to establish how dynamic contrast-enhanced MRI parameters relate to more quantitative histologic measurements, including markers of proliferation and measures of vascular endothelial growth factor expression.

DCE-MRI
:   dynamic contrast-enhanced MRI
EnF
:   enhancing fraction
GBM
:   glioblastoma multiforme
IAUC60
:   initial area under the contrast agent concentration curve
K trans
:   contrast transfer coefficient
ve
:   volume of the extravascular extracellular space per unit tissue volume
VEGF
:   vascular endothelial growth factor
vp
:   volume of the blood plasma per unit tissue volume" />
<meta name="DC.Contributor" content="S.J. Mills" />
<meta name="DC.Contributor" content="D. du Plessis" />
<meta name="DC.Contributor" content="P. Pal" />
<meta name="DC.Contributor" content="G. Thompson" />
<meta name="DC.Contributor" content="G. Buonacorrsi" />
<meta name="DC.Contributor" content="C. Soh" />
<meta name="DC.Contributor" content="G.J.M. Parker" />
<meta name="DC.Contributor" content="A. Jackson" />
<meta name="article:published_time" content="2016-05-01" />
<meta name="article:section" content="ADULT BRAIN" />
<meta name="citation_title" content="Mitotic Activity in Glioblastoma Correlates with Estimated Extravascular Extracellular Space Derived from Dynamic Contrast-Enhanced MR Imaging" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;A number of parameters derived from dynamic contrast-enhanced MR imaging and separate histologic features have been identified as potential prognosticators in high-grade glioma. This study evaluated the relationships between dynamic contrast-enhanced MRI–derived parameters and histologic features in glioblastoma multiforme.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Twenty-eight patients with newly presenting glioblastoma multiforme underwent preoperative imaging (conventional imaging and T1 dynamic contrast-enhanced MRI). Parametric maps of the initial area under the contrast agent concentration curve, contrast transfer coefficient, estimate of volume of the extravascular extracellular space, and estimate of blood plasma volume were generated, and the enhancing fraction was calculated. Surgical specimens were used to assess subtype and were graded (World Health Organization classification system) and were assessed for necrosis, cell density, cellular atypia, mitotic activity, and overall vascularity scores. Quantitative assessment of endothelial surface area, vascular surface area, and a vascular profile count were made by using CD34 immunostaining. The relationships between MR imaging parameters and histopathologic features were examined.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;High values of contrast transfer coefficient were associated with the presence of frank necrosis (&lt;i&gt;P&lt;/i&gt; = .005). High values of the estimate of volume of the extravascular extracellular space were associated with a fibrillary histologic pattern (&lt;i&gt;P&lt;/i&gt; &amp;lt; .01) and with increased mitotic activity (&lt;i&gt;P&lt;/i&gt; &amp;lt; .05). No relationship was found between mitotic activity and histologic pattern, suggesting that the correlation between the estimate of volume of the extravascular extracellular space and mitotic activity was independent of the histologic pattern.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;A correlation between the estimate of volume of the extravascular extracellular space and mitotic activity is reported. Further work is warranted to establish how dynamic contrast-enhanced MRI parameters relate to more quantitative histologic measurements, including markers of proliferation and measures of vascular endothelial growth factor expression.&lt;/p&gt;" />
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<meta name="twitter:title" content="Mitotic Activity in Glioblastoma Correlates with Estimated Extravascular Extracellular Space Derived from Dynamic Contrast-Enhanced MR Imaging" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: A number of parameters derived from dynamic contrast-enhanced MR imaging and separate histologic features have been identified as potential prognosticators in high-grade glioma. This study evaluated the relationships between dynamic contrast-enhanced MRI–derived parameters and histologic features in glioblastoma multiforme.

MATERIALS AND METHODS: Twenty-eight patients with newly presenting glioblastoma multiforme underwent preoperative imaging (conventional imaging and T1 dynamic contrast-enhanced MRI). Parametric maps of the initial area under the contrast agent concentration curve, contrast transfer coefficient, estimate of volume of the extravascular extracellular space, and estimate of blood plasma volume were generated, and the enhancing fraction was calculated. Surgical specimens were used to assess subtype and were graded (World Health Organization classification system) and were assessed for necrosis, cell density, cellular atypia, mitotic activity, and overall vascularity scores. Quantitative assessment of endothelial surface area, vascular surface area, and a vascular profile count were made by using CD34 immunostaining. The relationships between MR imaging parameters and histopathologic features were examined.

RESULTS: High values of contrast transfer coefficient were associated with the presence of frank necrosis ( P = .005). High values of the estimate of volume of the extravascular extracellular space were associated with a fibrillary histologic pattern ( P &lt; .01) and with increased mitotic activity ( P &lt; .05). No relationship was found between mitotic activity and histologic pattern, suggesting that the correlation between the estimate of volume of the extravascular extracellular space and mitotic activity was independent of the histologic pattern.

CONCLUSIONS: A correlation between the estimate of volume of the extravascular extracellular space and mitotic activity is reported. Further work is warranted to establish how dynamic contrast-enhanced MRI parameters relate to more quantitative histologic measurements, including markers of proliferation and measures of vascular endothelial growth factor expression.

DCE-MRI
:   dynamic contrast-enhanced MRI
EnF
:   enhancing fraction
GBM
:   glioblastoma multiforme
IAUC60
:   initial area under the contrast agent concentration curve
K trans
:   contrast transfer coefficient
ve
:   volume of the extravascular extracellular space per unit tissue volume
VEGF
:   vascular endothelial growth factor
vp
:   volume of the blood plasma per unit tissue volume" />
<meta name="og-title" property="og:title" content="Mitotic Activity in Glioblastoma Correlates with Estimated Extravascular Extracellular Space Derived from Dynamic Contrast-Enhanced MR Imaging" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/37/5/811" />
<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: A number of parameters derived from dynamic contrast-enhanced MR imaging and separate histologic features have been identified as potential prognosticators in high-grade glioma. This study evaluated the relationships between dynamic contrast-enhanced MRI–derived parameters and histologic features in glioblastoma multiforme.

MATERIALS AND METHODS: Twenty-eight patients with newly presenting glioblastoma multiforme underwent preoperative imaging (conventional imaging and T1 dynamic contrast-enhanced MRI). Parametric maps of the initial area under the contrast agent concentration curve, contrast transfer coefficient, estimate of volume of the extravascular extracellular space, and estimate of blood plasma volume were generated, and the enhancing fraction was calculated. Surgical specimens were used to assess subtype and were graded (World Health Organization classification system) and were assessed for necrosis, cell density, cellular atypia, mitotic activity, and overall vascularity scores. Quantitative assessment of endothelial surface area, vascular surface area, and a vascular profile count were made by using CD34 immunostaining. The relationships between MR imaging parameters and histopathologic features were examined.

RESULTS: High values of contrast transfer coefficient were associated with the presence of frank necrosis ( P = .005). High values of the estimate of volume of the extravascular extracellular space were associated with a fibrillary histologic pattern ( P &lt; .01) and with increased mitotic activity ( P &lt; .05). No relationship was found between mitotic activity and histologic pattern, suggesting that the correlation between the estimate of volume of the extravascular extracellular space and mitotic activity was independent of the histologic pattern.

CONCLUSIONS: A correlation between the estimate of volume of the extravascular extracellular space and mitotic activity is reported. Further work is warranted to establish how dynamic contrast-enhanced MRI parameters relate to more quantitative histologic measurements, including markers of proliferation and measures of vascular endothelial growth factor expression.

DCE-MRI
:   dynamic contrast-enhanced MRI
EnF
:   enhancing fraction
GBM
:   glioblastoma multiforme
IAUC60
:   initial area under the contrast agent concentration curve
K trans
:   contrast transfer coefficient
ve
:   volume of the extravascular extracellular space per unit tissue volume
VEGF
:   vascular endothelial growth factor
vp
:   volume of the blood plasma per unit tissue volume" />
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    <title>Mitotic Activity in Glioblastoma Correlates with Estimated Extravascular Extracellular Space Derived from Dynamic Contrast-Enhanced MR Imaging | American Journal of Neuroradiology</title>  
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">S.J. Mills</span>, <span class="highwire-citation-author" data-delta="1">D. du Plessis</span>, <span class="highwire-citation-author" data-delta="2">P. Pal</span>, <span class="highwire-citation-author" data-delta="3">G. Thompson</span>, <span class="highwire-citation-author" data-delta="4">G. Buonacorrsi</span>, <span class="highwire-citation-author" data-delta="5">C. Soh</span>, <span class="highwire-citation-author" data-delta="6">G.J.M. Parker</span> and <span class="highwire-citation-author" data-delta="7">A. Jackson</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">May 2016,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">37 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(5) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">811-817; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A4623 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-14474--6987512434" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">S.J. Mills </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 (S.J.M., G.T., C.S., A.J.)</div><div class='author-affiliation'><span class='nlm-sup'>c</span>Imaging Science and Biomedical Engineering (S.J.M., G.T., G.B., G.J.M.P., A.J.), University of Manchester, Manchester, UK.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=S.J.%2BMills%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=Mills%20S&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AS.J.%2BMills%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-1017-6654" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for S.J. Mills</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">D. du Plessis </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Neuropathology (D.d.P., P.P.), Salford National Health Service Foundation Trust, Salford, UK</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=D.%2Bdu%2BPlessis%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=du%20Plessis%20D&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AD.%2Bdu%2BPlessis%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-3703-0903" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for D. du Plessis</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">P. Pal </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Neuropathology (D.d.P., P.P.), Salford National Health Service Foundation Trust, Salford, UK</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=P.%2BPal%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=Pal%20P&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AP.%2BPal%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-7258-4848" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for P. Pal</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">G. Thompson </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 (S.J.M., G.T., C.S., A.J.)</div><div class='author-affiliation'><span class='nlm-sup'>c</span>Imaging Science and Biomedical Engineering (S.J.M., G.T., G.B., G.J.M.P., A.J.), University of Manchester, Manchester, UK.</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.%2BThompson%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=Thompson%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%3AG.%2BThompson%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-1722-2235" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for G. Thompson</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">G. Buonacorrsi </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>c</span>Imaging Science and Biomedical Engineering (S.J.M., G.T., G.B., G.J.M.P., A.J.), University of Manchester, Manchester, UK.</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.%2BBuonacorrsi%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=Buonacorrsi%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%3AG.%2BBuonacorrsi%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-2431-6563" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for G. Buonacorrsi</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">C. Soh </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 (S.J.M., G.T., C.S., A.J.)</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.%2BSoh%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=Soh%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.%2BSoh%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-3339-1952" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. Soh</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">G.J.M. Parker </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>c</span>Imaging Science and Biomedical Engineering (S.J.M., G.T., G.B., G.J.M.P., A.J.), University of Manchester, Manchester, UK.</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.J.M.%2BParker%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=Parker%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%3AG.J.M.%2BParker%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-2934-2234" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for G.J.M. 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      <div class="highwire-cite-title">Mitotic Activity in Glioblastoma Correlates with Estimated Extravascular Extracellular Space Derived from Dynamic Contrast-Enhanced MR Imaging</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">S.J.</span> <span class="nlm-surname">Mills</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">D.</span> <span class="nlm-surname">du Plessis</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">P.</span> <span class="nlm-surname">Pal</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">G.</span> <span class="nlm-surname">Thompson</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">G.</span> <span class="nlm-surname">Buonacorrsi</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Soh</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">G.J.M.</span> <span class="nlm-surname">Parker</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">A.</span> <span class="nlm-surname">Jackson</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-oa-ind highwire-cite-metadata"><i class="highwire-oa-indicator"></i> </span><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">May 2016, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">37 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(5) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">811-817; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A4623 </span></div>
  
  
  
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