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      <div class="highwire-cite-overline"><span  class="highwire-cite-metadata-article-type highwire-cite-metadata">Reply</span><span class="separator-pipe"></span><span  class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Letter</span></span></div>
  
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">H.A. Marquering</span>, <span class="highwire-citation-author" data-delta="1">C.B. Majoie</span> and <span class="highwire-citation-author" data-delta="2">P.J Nederkoorn</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 2012,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">33 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(1) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">E15; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A2946 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-11741--61360241883" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">H.A. Marquering </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=H.A.%2BMarquering%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=Marquering%20H&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AH.A.%2BMarquering%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">C.B. Majoie </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.B.%2BMajoie%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=Majoie%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 last"><a href="/search/author1%3AC.B.%2BMajoie%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">P.J Nederkoorn </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.J%2BNederkoorn%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=Nederkoorn%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 last"><a href="/search/author1%3AP.J%2BNederkoorn%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</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 fulltext-view"><span class="highwire-journal-article-marker-start"></span><p id="p-1">We thank Drs Sarikaya and McKinney for their response to our article entitled “The Relation of Carotid Calcium Volume with Carotid Artery Stenosis in Symptomatic Patients”<sup><a id="xref-ref-1-1" class="xref-bibr" href="#ref-1">1</a></sup> and would hereby like to respond to some of their very meaningful discussion points.</p><p id="p-2">We certainly agree that there is a large difference in the definition of the domain between our study and the 2 studies performed by their group.<sup><a id="xref-ref-2-1" class="xref-bibr" href="#ref-2">2</a>,<a id="xref-ref-3-1" class="xref-bibr" href="#ref-3">3</a></sup> In our study, we have correlated the calcium volume with the degree of stenosis of the carotid artery in a population of high-risk patients with recent neurologic symptoms. In the studies of Sarikaya et al<sup><a id="xref-ref-3-2" class="xref-bibr" href="#ref-3">3</a></sup> and McKinney et al,<sup><a id="xref-ref-2-2" class="xref-bibr" href="#ref-2">2</a></sup> the relation between carotid artery stenosis and calcium volume was investigated in a more “general” patient population.</p><p id="p-3">The difference in patient population follows from the different objectives. Sarikaya et al<sup><a id="xref-ref-3-3" class="xref-bibr" href="#ref-3">3</a></sup> and McKinney et al<sup><a id="xref-ref-2-3" class="xref-bibr" href="#ref-2">2</a></sup> investigated the role of calcium volume in screening patients at risk, whereas our study explored the possibility of using calcium volume to identify stenoses of &gt;70%. In current clinical practice, the degree of stenosis of the internal carotid artery is used in the decision to perform carotid endarterectomy, because it is the strongest predictor of its effect.<sup><a id="xref-ref-4-1" class="xref-bibr" href="#ref-4">4</a>,<a id="xref-ref-5-1" class="xref-bibr" href="#ref-5">5</a></sup> With such a difference in objectives and in patient domain, it is actually not surprising to observe a spectrum effect.<sup><a id="xref-ref-6-1" class="xref-bibr" href="#ref-6">6</a></sup> However, the extent of this effect was beyond our expectations.</p><p id="p-4">The second issue that was addressed by Sarikaya and McKinney is that in our article, we presented the diagnostic accuracy for thresholds different from the optimal value reported in their articles, 0.06 cm<sup>3</sup>. We actually used a whole range of thresholds, including 0.06 cm<sup>3</sup>, as presented in the receiver operating characteristic analysis curve (Fig 3 in our article). This curve shows that for all thresholds, the diagnostic accuracy is rather poor. We presented the diagnostic accuracy for 0.03 and 0.09 cm<sup>3</sup> to illustrate the outer ends of the range of sensitivity and specificity of the calcium volume−based stenosis detection for our patient population. However, a direct comparison would benefit from the presentation of the values for the 0.06-cm<sup>3</sup> threshold.</p><p id="p-5">We acknowledge Sarikaya and McKinney for observing the weak correlation of calcium volume and the degree of stenosis of the carotid artery on the unaffected side, as opposed to the absence of such a correlation on the affected side. This suggests a stronger correlation of calcium volume and degree of stenosis in asymptomatic patients or arteries. We also thought this was a puzzling finding. Hypothetically, it may express a relation of plaque composition and potential neurologic symptoms. Actually, we have performed a study in the same patient population in which we correlated the intracranial calcium volume burden with intracranial stenosis, which we hope to publish soon. In this study, we actually confirmed the correlation of calcium volume and stenosis in the intracranial arteries. We agree with Sarikaya and McKinney that the role of carotid artery calcium volume and its relation with various neurologic symptoms requires additional research effort.</p><div class="section ref-list" id="ref-list-1"><h2>References</h2><ol class="cit-list ref-use-labels"><li><span class="ref-label">1.</span><a class="rev-xref-ref" href="#xref-ref-1-1" title="View reference 1. in text" id="ref-1">↵</a>

<div class="cit ref-cit ref-journal" id="cit-33.1.E15.1" data-doi="10.3174/ajnr.A2519"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Marquering</span>  <span class="cit-name-given-names">HA</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Majoie</span>  <span class="cit-name-given-names">CB</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Smagge</span>  <span class="cit-name-given-names">L</span></span>, </li><li><span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">The relation of carotid calcium volume with carotid artery stenosis in symptomatic patients</span>. <abbr class="cit-jnl-abbrev">AJNR Am J Neuroradiol</abbr> <span class="cit-pub-date">2011</span>;<span class="cit-vol">32</span>:<span class="cit-fpage">1182</span>–<span class="cit-lpage">87</span></cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpuciI7czo1OiJyZXNpZCI7czo5OiIzMi83LzExODIiO3M6NDoiYXRvbSI7czoxOToiL2FqbnIvMzMvMS9FMTUuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9" class="cit-ref-sprinkles cit-ref-sprinkles-ijlink"><span><span class="cit-reflinks-abstract">Abstract</span><span class="cit-sep cit-reflinks-variant-name-sep">/</span><span class="cit-reflinks-full-text"><span class="free-full-text">FREE </span>Full Text</span></span></a></div></div></li><li><span class="ref-label">2.</span><a class="rev-xref-ref" href="#xref-ref-2-1" title="View reference 2. in text" id="ref-2">↵</a>

<div class="cit ref-cit ref-journal" id="cit-33.1.E15.2" data-doi="10.1007/s00234-004-1301-4"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">McKinney</span>  <span class="cit-name-given-names">AM</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Casey</span>  <span class="cit-name-given-names">SO</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Teksam</span>  <span class="cit-name-given-names">M</span></span>, </li><li><span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">Carotid bifurcation calcium and correlation with percent stenosis of the internal carotid artery on CT angiography</span>. <abbr class="cit-jnl-abbrev">Neuroradiology</abbr> <span class="cit-pub-date">2005</span>;<span class="cit-vol">47</span>:<span class="cit-fpage">1</span>–<span class="cit-lpage">9</span></cite></div><div class="cit-extra"><a href="/lookup/external-ref?access_num=10.1007/s00234-004-1301-4&amp;link_type=DOI" class="cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref"><span>CrossRef</span></a><a href="/lookup/external-ref?access_num=15650832&amp;link_type=MED&amp;atom=%2Fajnr%2F33%2F1%2FE15.atom" class="cit-ref-sprinkles cit-ref-sprinkles-medline"><span>PubMed</span></a></div></div></li><li><span class="ref-label">3.</span><a class="rev-xref-ref" href="#xref-ref-3-1" title="View reference 3. in text" id="ref-3">↵</a>

<div class="cit ref-cit ref-journal" id="cit-33.1.E15.3"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Sarikaya</span>  <span class="cit-name-given-names">B</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Lohman</span>  <span class="cit-name-given-names">B</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">McKinney</span>  <span class="cit-name-given-names">AM</span></span>, </li><li><span class="cit-etal">et al.</span></li></ol><cite> <span class="cit-article-title">Correlation between carotid bifurcation calcium burden on non-enhanced CT and percent stenosis, as confirmed by digital subtraction angiography</span>. <abbr class="cit-jnl-abbrev">Br J Radiol</abbr> <span class="cit-pub-date">2011</span> <span class="cit-month">9</span> <span class="cit-day">6</span>. <span class="cit-comment">[Epub ahead of print]</span></cite></div><div class="cit-extra"></div></div></li><li><span class="ref-label">4.</span><a class="rev-xref-ref" href="#xref-ref-4-1" title="View reference 4. in text" id="ref-4">↵</a>

<div class="cit ref-cit ref-journal" id="cit-33.1.E15.4" data-doi="10.1056/NEJM199811123392002"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Barnett</span>  <span class="cit-name-given-names">HJ</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Taylor</span>  <span class="cit-name-given-names">DW</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Eliasziw</span>  <span class="cit-name-given-names">M</span></span>, </li><li><span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis: North American Symptomatic Carotid Endarterectomy Trial Collaborators</span>. <abbr class="cit-jnl-abbrev">N Engl J Med</abbr> <span class="cit-pub-date">1998</span>;<span class="cit-vol">339</span>:<span class="cit-fpage">1415</span>–<span class="cit-lpage">25</span></cite></div><div class="cit-extra"><a href="/lookup/external-ref?access_num=10.1056/NEJM199811123392002&amp;link_type=DOI" class="cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref"><span>CrossRef</span></a><a href="/lookup/external-ref?access_num=9811916&amp;link_type=MED&amp;atom=%2Fajnr%2F33%2F1%2FE15.atom" class="cit-ref-sprinkles cit-ref-sprinkles-medline"><span>PubMed</span></a></div></div></li><li><span class="ref-label">5.</span><a class="rev-xref-ref" href="#xref-ref-5-1" title="View reference 5. in text" id="ref-5">↵</a>

<div class="cit ref-cit ref-journal" id="cit-33.1.E15.5" data-doi="10.1016/S0140-6736(97)09292-1"><div class="cit-metadata"><cite><span class="cit-article-title">Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST)</span>. <abbr class="cit-jnl-abbrev">Lancet</abbr> <span class="cit-pub-date">1998</span>;<span class="cit-vol">351</span>:<span class="cit-fpage">1379</span>–<span class="cit-lpage">87</span></cite></div><div class="cit-extra"><a href="/lookup/external-ref?access_num=10.1016/S0140-6736(97)09292-1&amp;link_type=DOI" class="cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref"><span>CrossRef</span></a><a href="/lookup/external-ref?access_num=9593407&amp;link_type=MED&amp;atom=%2Fajnr%2F33%2F1%2FE15.atom" class="cit-ref-sprinkles cit-ref-sprinkles-medline"><span>PubMed</span></a></div></div></li><li><span class="ref-label">6.</span><a class="rev-xref-ref" href="#xref-ref-6-1" title="View reference 6. in text" id="ref-6">↵</a>

<div class="cit ref-cit ref-journal" id="cit-33.1.E15.6" data-doi="10.1093/fampra/cmn051"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Willis</span>  <span class="cit-name-given-names">BH</span></span></li></ol><cite>. <span class="cit-article-title">Spectrum bias: why clinicians need to be cautious when applying diagnostic test studies</span>. <abbr class="cit-jnl-abbrev">Fam Pract</abbr> <span class="cit-pub-date">2008</span>;<span class="cit-vol">25</span>:<span class="cit-fpage">390</span>–<span class="cit-lpage">96</span></cite></div><div class="cit-extra"><a href="/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiZmFtcHJhY3QiO3M6NToicmVzaWQiO3M6ODoiMjUvNS8zOTAiO3M6NDoiYXRvbSI7czoxOToiL2FqbnIvMzMvMS9FMTUuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9" class="cit-ref-sprinkles cit-ref-sprinkles-ijlink"><span><span class="cit-reflinks-abstract">Abstract</span><span class="cit-sep cit-reflinks-variant-name-sep">/</span><span class="cit-reflinks-full-text"><span class="free-full-text">FREE </span>Full Text</span></span></a></div></div></li></ol></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2012 by American Journal of Neuroradiology</li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div></div>  </div>

  
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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 33</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 1 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Jan 2012 </div></div>
      
      
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    	<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">Jan 2012, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">33 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(1) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">E15; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A2946 </span></div>
  
  
  
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    	<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">Jan 2012, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">33 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(1) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">E15; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A2946 </span></div>
  
  
  
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