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<meta name="DC.Title" content="Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis" />
<meta name="DC.Identifier" content="10.3174/ajnr.A5109" />
<meta name="DC.Date" content="2017-05-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2017 by American Journal of Neuroradiology. Indicates open access to non-subscribers at www.ajnr.org" />
<meta name="DC.AccessRights" content="open-access" />
<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging–based iron-susceptibility measures.

MATERIALS AND METHODS: Forty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions.

RESULTS: Compared with controls, patients showed reduced memory ( P &lt; .001) and processing speed ( P = .02) and smaller putamen ( P &lt; .001), globus pallidus ( P = .002), and thalamic volumes ( P &lt; .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen ( P = .003) and globus pallidus ( P = .003). In patients only, thalamus ( P &lt; .001) and putamen ( P = .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus ( P = .03; trend for transverse relaxation rate, P = .10) were still related to cognition.

CONCLUSIONS: Quantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.

DGM
:   deep gray matter
GP
:   globus pallidus
NPtotal
:   composite z-score across neuropsychological tests
PASAT
:   Paced Auditory Serial Addition Test
QSM
:   quantitative susceptibility mapping
R2*
:   transverse relaxation rate
SDMT
:   Symbol Digit Modalities Test
SPART
:   10/36-Spatial Recall Test
SRT
:   Selective Reminding Task" />
<meta name="DC.Contributor" content="E. Fujiwara" />
<meta name="DC.Contributor" content="J.A. Kmech" />
<meta name="DC.Contributor" content="D. Cobzas" />
<meta name="DC.Contributor" content="H. Sun" />
<meta name="DC.Contributor" content="P. Seres" />
<meta name="DC.Contributor" content="G. Blevins" />
<meta name="DC.Contributor" content="A.H. Wilman" />
<meta name="article:published_time" content="2017-05-01" />
<meta name="article:section" content="ADULT BRAIN" />
<meta name="citation_title" content="Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging–based iron-susceptibility measures.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Forty patients with multiple sclerosis (relapsing-remitting, &lt;i&gt;n&lt;/i&gt; = 16; progressive, &lt;i&gt;n&lt;/i&gt; = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Compared with controls, patients showed reduced memory (&lt;i&gt;P&lt;/i&gt; &amp;lt; .001) and processing speed (&lt;i&gt;P&lt;/i&gt; = .02) and smaller putamen (&lt;i&gt;P&lt;/i&gt; &amp;lt; .001), globus pallidus (&lt;i&gt;P&lt;/i&gt; = .002), and thalamic volumes (&lt;i&gt;P&lt;/i&gt; &amp;lt; .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen (&lt;i&gt;P&lt;/i&gt; = .003) and globus pallidus (&lt;i&gt;P&lt;/i&gt; = .003). In patients only, thalamus (&lt;i&gt;P&lt;/i&gt; &amp;lt; .001) and putamen (&lt;i&gt;P&lt;/i&gt; = .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus (&lt;i&gt;P&lt;/i&gt; = .03; trend for transverse relaxation rate, &lt;i&gt;P&lt;/i&gt; = .10) were still related to cognition.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Quantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
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<meta name="citation_author" content="E. Fujiwara" />
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<meta name="twitter:title" content="Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging–based iron-susceptibility measures.

MATERIALS AND METHODS: Forty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions.

RESULTS: Compared with controls, patients showed reduced memory ( P &lt; .001) and processing speed ( P = .02) and smaller putamen ( P &lt; .001), globus pallidus ( P = .002), and thalamic volumes ( P &lt; .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen ( P = .003) and globus pallidus ( P = .003). In patients only, thalamus ( P &lt; .001) and putamen ( P = .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus ( P = .03; trend for transverse relaxation rate, P = .10) were still related to cognition.

CONCLUSIONS: Quantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.

DGM
:   deep gray matter
GP
:   globus pallidus
NPtotal
:   composite z-score across neuropsychological tests
PASAT
:   Paced Auditory Serial Addition Test
QSM
:   quantitative susceptibility mapping
R2*
:   transverse relaxation rate
SDMT
:   Symbol Digit Modalities Test
SPART
:   10/36-Spatial Recall Test
SRT
:   Selective Reminding Task" />
<meta name="og-title" property="og:title" content="Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/38/5/942" />
<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: Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging–based iron-susceptibility measures.

MATERIALS AND METHODS: Forty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions.

RESULTS: Compared with controls, patients showed reduced memory ( P &lt; .001) and processing speed ( P = .02) and smaller putamen ( P &lt; .001), globus pallidus ( P = .002), and thalamic volumes ( P &lt; .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen ( P = .003) and globus pallidus ( P = .003). In patients only, thalamus ( P &lt; .001) and putamen ( P = .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus ( P = .03; trend for transverse relaxation rate, P = .10) were still related to cognition.

CONCLUSIONS: Quantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.

DGM
:   deep gray matter
GP
:   globus pallidus
NPtotal
:   composite z-score across neuropsychological tests
PASAT
:   Paced Auditory Serial Addition Test
QSM
:   quantitative susceptibility mapping
R2*
:   transverse relaxation rate
SDMT
:   Symbol Digit Modalities Test
SPART
:   10/36-Spatial Recall Test
SRT
:   Selective Reminding Task" />
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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">ADULT BRAIN</span></span></div>
  
      <div class="highwire-cite-access"><span class="highwire-citation-access"><i class="highwire-access-icon highwire-access-icon-open-access open-access hw-icon-open-access" title="Open Access" aria-hidden="true"></i><span  class="element-invisible highwire-access-icon highwire-access-icon-open-access" style="">Open Access</span></span></div>
  
      <h1 class="highwire-cite-title" id="page-title">Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">E. Fujiwara</span>, <span class="highwire-citation-author" data-delta="1">J.A. Kmech</span>, <span class="highwire-citation-author" data-delta="2">D. Cobzas</span>, <span class="highwire-citation-author" data-delta="3">H. Sun</span>, <span class="highwire-citation-author" data-delta="4">P. Seres</span>, <span class="highwire-citation-author" data-delta="5">G. Blevins</span> and <span class="highwire-citation-author" data-delta="6">A.H. Wilman</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 2017,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">38 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(5) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">942-948; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A5109 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-54366--61055825892" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">E. Fujiwara </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 Psychiatry (E.F., J.A.K.)</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=E.%2BFujiwara%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=Fujiwara%20E&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%3AE.%2BFujiwara%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/0000-0003-4154-0145" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for E. Fujiwara</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">J.A. Kmech </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 Psychiatry (E.F., J.A.K.)</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=J.A.%2BKmech%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=Kmech%20J&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%3AJ.A.%2BKmech%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/0000-0003-3463-2412" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for J.A. Kmech</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">D. Cobzas </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Computer Science (D.C.)</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.%2BCobzas%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=Cobzas%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.%2BCobzas%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/0000-0003-1318-4868" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for D. Cobzas</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">H. Sun </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>c</span>Biomedical Engineering (H.S., P.S., A.H.W.)</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=H.%2BSun%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=Sun%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"><a href="/search/author1%3AH.%2BSun%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/0000-0003-3436-7831" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for H. 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Seres </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>c</span>Biomedical Engineering (H.S., P.S., A.H.W.)</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.%2BSeres%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=Seres%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.%2BSeres%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/0000-0002-8812-2234" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for P. Seres</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">G. Blevins </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>d</span>Medicine (G.B.), Division of Neurology, University of Alberta, Edmonton, Alberta, Canada</div><div class='author-affiliation'><span class='nlm-sup'>e</span>Northern Alberta Multiple Sclerosis Clinic (G.B.), Edmonton, Alberta, Canada.</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.%2BBlevins%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=Blevins%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.%2BBlevins%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/0000-0002-4598-2672" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for G. 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