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      <h1 class="highwire-cite-title" id="page-title">Dynamic Contrast-Enhanced MR: Importance of Reaching the Washout Phase</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">P. Alcaide-Leon</span> and <span class="highwire-citation-author" data-delta="1">À. Rovira</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 2013,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">34 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(5) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">E58-E59; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A3556 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-12476--6771808978" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">P. Alcaide-Leon </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>MR Unit
Department of Radiology
Passeig de la Vall d'Hebron
Barcelona, Spain</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.%2BAlcaide-Leon%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=Alcaide-Leon%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.%2BAlcaide-Leon%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">À. Rovira </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Hospital Universitari Vall d'Hebron
Barcelona, Spain</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=%C3%80.%2BRovira%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=Rovira%20%C3%80&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%3A%25C3%2580.%2BRovira%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 read with great interest the recent study published in the <em>American Journal of Neuroradiology</em> on November 22, 2012, entitled “T1-Weighted Dynamic Contrast-Enhanced MR Evaluation of Different Stages of Neurocysticercosis and Its Relationship with Serum MMP-9 Expression.”<sup><a id="xref-ref-1-1" class="xref-bibr" href="#ref-1">1</a></sup></p><p id="p-2">In the Materials and Methods section, the authors describe their dynamic contrast-enhanced (DCE) study protocol as follows: “A series of 384 images during 32 time points for 12 sections were acquired (temporal resolution, 5.65 seconds).” However, 32 time points × 5.65 seconds of temporal resolution results in a 3-minute-long DCE-MR study. The specific pharmacokinetic model and the postprocessing software used for calculation of the transfer constant (<em>K</em><sup>trans</sup>); rate constant between extracellular extravascular space and blood plasma (K<sub>ep</sub>); and leakage space (V<sub>e</sub>) are not stated in the article.</p><p id="p-3">We have been using DCE-MR imaging as a part of our tumor protocol since 2010. We usually perform a 4-minute DCE study. With a study of this length, the washout phase is not usually reached in brain tumors. Inflammatory lesions such us neurocysticercosis are known to wash out much later than tumors as the result of their low permeability surface area product (PS).</p><p id="p-4">In their article published in 1991, Tofts and Kermode<sup><a id="xref-ref-2-1" class="xref-bibr" href="#ref-2">2</a></sup> generated families of tracer concentration in tissue [Ct(t)] curves from their equation and demonstrated that for fixed permeability, increasing V<sub>e</sub> has no effect on the initial slope but does affect the maximum concentration reached and delays the time to peak enhancement. From this assessment, we infer that reaching the washout phase is needed to obtain V<sub>e</sub> and K<sub>ep</sub>.</p><p id="p-5">To confirm our hypothesis, we performed a 14-minute DCE study in a patient with pilocytic astrocytoma. Maximum enhancement is reached at 5.8 minutes, and a slow washout curve then begins. We performed 2 different K<sub>ep</sub> calculations: the first one by use of the first 3 minutes of the DCE study and the second one by use of the whole 15-minute sequence. Resulting K<sub>ep</sub> values are as different as K<sub>ep</sub> (3-minute DCE): 0.50 minutes<sup>−1</sup> and K<sub>ep</sub> (14-minute DCE): 0.13 minutes<sup>−1</sup>. T1 kinetic analysis was based on the 2-compartment extended pharmacokinetic model of Tofts and Kermode by use of nordicICE software (NordicImagingLab, Bergen, Norway) (<a id="xref-fig-1-1" class="xref-fig" href="#F1">Figs 1</a> and <a id="xref-fig-2-1" class="xref-fig" href="#F2">2</a>).</p><div id="F1" class="fig pos-float  odd"><div class="highwire-figure"><div class="fig-inline-img-wrapper"><div class="fig-inline-img"><a href="http://ajnr-stage2.stage.highwire.org/content/ajnr/34/5/E58/F1.large.jpg?width=800&amp;height=600&amp;carousel=1" title="Kep map obtained at 14 minutes in a cerebellar pilocytic astrocytoma (left image). Green curve represents the time&#x2013;signal intensity curve of a region of interest (red circle in left image); red curve represents measured arterial input function; blue line corresponds to the last image considered for calculation (14 minutes) (right image). Kep value calculated for the whole 14-minute DCE study was 0.13 minutes&#x2212;1." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-130772352" data-figure-caption="&lt;div class=&quot;highwire-markup&quot;&gt;&lt;div xmlns=&quot;http://www.w3.org/1999/xhtml&quot;&gt;K&lt;sub&gt;ep&lt;/sub&gt; map obtained at 14 minutes in a cerebellar pilocytic astrocytoma &lt;em&gt;(left image). Green curve&lt;/em&gt; represents the time&#x2013;signal intensity curve of a region of interest &lt;em&gt;(red circle in left image); red curve&lt;/em&gt; represents measured arterial input function; &lt;em&gt;blue line&lt;/em&gt; corresponds to the last image considered for calculation (14 minutes) &lt;em&gt;(right image).&lt;/em&gt; K&lt;sub&gt;ep&lt;/sub&gt; value calculated for the whole 14-minute DCE study was 0.13 minutes&lt;sup&gt;&#x2212;1&lt;/sup&gt;.&lt;/div&gt;&lt;/div&gt;" data-icon-position="" data-hide-link-title="0"><span class="hw-responsive-img"><img class="highwire-fragment fragment-image lazyload" alt="Fig 1." src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" data-src="http://ajnr-stage2.stage.highwire.org/content/ajnr/34/5/E58/F1.medium.gif" width="440" height="260"/><noscript><img class="highwire-fragment fragment-image" alt="Fig 1." src="http://ajnr-stage2.stage.highwire.org/content/ajnr/34/5/E58/F1.medium.gif" width="440" height="260"/></noscript></span></a></div></div><ul class="highwire-figure-links inline"><li class="download-fig first"><a href="http://ajnr-stage2.stage.highwire.org/content/ajnr/34/5/E58/F1.large.jpg?download=true" class="highwire-figure-link highwire-figure-link-download" title="Download Fig 1." data-icon-position="" data-hide-link-title="0">Download figure</a></li><li class="new-tab"><a href="http://ajnr-stage2.stage.highwire.org/content/ajnr/34/5/E58/F1.large.jpg" class="highwire-figure-link highwire-figure-link-newtab" target="_blank" data-icon-position="" data-hide-link-title="0">Open in new tab</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/40104" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div><div class="fig-caption" xmlns:xhtml="http://www.w3.org/1999/xhtml"><span class="fig-label">Fig 1.</span> <p id="p-6" class="first-child">K<sub>ep</sub> map obtained at 14 minutes in a cerebellar pilocytic astrocytoma <em>(left image). Green curve</em> represents the time–signal intensity curve of a region of interest <em>(red circle in left image); red curve</em> represents measured arterial input function; <em>blue line</em> corresponds to the last image considered for calculation (14 minutes) <em>(right image).</em> K<sub>ep</sub> value calculated for the whole 14-minute DCE study was 0.13 minutes<sup>−1</sup>.</p><div class="sb-div caption-clear"></div></div></div><div id="F2" class="fig pos-float  odd"><div class="highwire-figure"><div class="fig-inline-img-wrapper"><div class="fig-inline-img"><a href="http://ajnr-stage2.stage.highwire.org/content/ajnr/34/5/E58/F2.large.jpg?width=800&amp;height=600&amp;carousel=1" title="Kep map obtained at 3 minutes in a cerebellar pilocytic astrocytoma (left image). Green curve represents the time&#x2013;signal intensity curve of a region of interest (red circle in left image); red curve represents measured arterial input function; blue line corresponds to the last image considered for calculation (3 minutes) (right image). At 3 minutes, the washout phase has not been reached and Kep value in this region of interest was 0.50 minutes&#x2212;1." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-130772352" data-figure-caption="&lt;div class=&quot;highwire-markup&quot;&gt;&lt;div xmlns=&quot;http://www.w3.org/1999/xhtml&quot;&gt;K&lt;sub&gt;ep&lt;/sub&gt; map obtained at 3 minutes in a cerebellar pilocytic astrocytoma &lt;em&gt;(left image). Green curve&lt;/em&gt; represents the time&#x2013;signal intensity curve of a region of interest &lt;em&gt;(red circle in left image); red curve&lt;/em&gt; represents measured arterial input function; &lt;em&gt;blue line&lt;/em&gt; corresponds to the last image considered for calculation (3 minutes) &lt;em&gt;(right image).&lt;/em&gt; At 3 minutes, the washout phase has not been reached and K&lt;sub&gt;ep&lt;/sub&gt; value in this region of interest was 0.50 minutes&lt;sup&gt;&#x2212;1&lt;/sup&gt;.&lt;/div&gt;&lt;/div&gt;" data-icon-position="" data-hide-link-title="0"><span class="hw-responsive-img"><img class="highwire-fragment fragment-image lazyload" alt="Fig 2." src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" data-src="http://ajnr-stage2.stage.highwire.org/content/ajnr/34/5/E58/F2.medium.gif" width="440" height="252"/><noscript><img class="highwire-fragment fragment-image" alt="Fig 2." src="http://ajnr-stage2.stage.highwire.org/content/ajnr/34/5/E58/F2.medium.gif" width="440" height="252"/></noscript></span></a></div></div><ul class="highwire-figure-links inline"><li class="download-fig first"><a href="http://ajnr-stage2.stage.highwire.org/content/ajnr/34/5/E58/F2.large.jpg?download=true" class="highwire-figure-link highwire-figure-link-download" title="Download Fig 2." data-icon-position="" data-hide-link-title="0">Download figure</a></li><li class="new-tab"><a href="http://ajnr-stage2.stage.highwire.org/content/ajnr/34/5/E58/F2.large.jpg" class="highwire-figure-link highwire-figure-link-newtab" target="_blank" data-icon-position="" data-hide-link-title="0">Open in new tab</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/40126" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div><div class="fig-caption"><span class="fig-label">Fig 2.</span> <p id="p-7" class="first-child">K<sub>ep</sub> map obtained at 3 minutes in a cerebellar pilocytic astrocytoma <em>(left image). Green curve</em> represents the time–signal intensity curve of a region of interest <em>(red circle in left image); red curve</em> represents measured arterial input function; <em>blue line</em> corresponds to the last image considered for calculation (3 minutes) <em>(right image).</em> At 3 minutes, the washout phase has not been reached and K<sub>ep</sub> value in this region of interest was 0.50 minutes<sup>−1</sup>.</p><div class="sb-div caption-clear"></div></div></div><p id="p-8">To sum up, the effect of not collecting for long enough to reach the washout phase would be that V<sub>e</sub> and K<sub>ep</sub> would be imprecise (ie, poor repeatability), and the performance of those biomarkers would be compromised. Available DCE software provides K<sub>ep</sub> and V<sub>e</sub> maps even without the data needed to support those calculations, and we should be aware of this fact.</p><div class="section ack" id="ack-1">
<h2>Acknowledgments</h2>
<p id="p-9">We thank Professor Paul Tofts for his help.</p>
</div><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-34.5.E58.1"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Gupta</span>  <span class="cit-name-given-names">RK</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Awasthi</span>  <span class="cit-name-given-names">R</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Garg</span>  <span class="cit-name-given-names">RK</span></span>, </li><li><span class="cit-etal">et al</span></li></ol><cite>. <span class="cit-article-title">T1-weighted dynamic contrast-enhanced MR evaluation of different stages of neurocysticercosis and its relationship with serum MMP-9 expression</span>. <abbr class="cit-jnl-abbrev">AJNR Am J Neuroradiol</abbr> <span class="cit-pub-date">2012</span> <span class="cit-month">November</span> <span class="cit-day">22</span>, <span class="cit-comment">2012 [Epub ahead of print]</span></cite></div><div class="cit-extra"></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-34.5.E58.2" data-doi="10.1002/mrm.1910170208"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Tofts</span>  <span class="cit-name-given-names">PS</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Kermode</span>  <span class="cit-name-given-names">AG</span></span></li></ol><cite>. <span class="cit-article-title">Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging, 1: fundamental concepts</span>. <abbr class="cit-jnl-abbrev">Magn Reson Med</abbr> <span class="cit-pub-date">1991</span>;<span class="cit-vol">17</span>:<span class="cit-fpage">357</span>–<span class="cit-lpage">67</span></cite></div><div class="cit-extra"><a href="/lookup/external-ref?access_num=10.1002/mrm.1910170208&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=2062210&amp;link_type=MED&amp;atom=%2Fajnr%2F34%2F5%2FE58.atom" class="cit-ref-sprinkles cit-ref-sprinkles-medline"><span>PubMed</span></a></div></div></li></ol></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2013 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. 34</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 5 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 May 2013 </div></div>
      
      
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