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<meta name="DC.Title" content="Diffusion Tensor Imaging Detects Areas of Abnormal White Matter Microstructure in Patients with Partial Ornithine Transcarbamylase Deficiency" />
<meta name="DC.Identifier" content="10.3174/ajnr.A2122" />
<meta name="DC.Date" content="2010-10-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
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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: OTCD, an X-linked disorder, is the most common of the UCDs. Neonatal onset is associated with uniformly poor outcome. Males with late-onset OTCD show deficits in executive function, motor planning, and working memory. A broad phenotype is observed in heterozygous females. A specific neurobehavioral phenotype with white matter dysfunction and impaired attention and working memory has been described. The extent to which the deficits involve specific pathways in the brain is unknown. We hypothesized that DTI would disclose white matter microstructure in OTCD correlating with cognitive deficits.

MATERIALS AND METHODS: Nineteen adults with partial OTCD and 18 adult control subjects ages 19–59 years participated. MR imaging was performed by using a 3T whole-body scanner. Anisotropy was calculated from the eigenvalues of the diffusion tensor by using the FA metric and was compared between the study and control groups.

RESULTS: FA of the frontal white matter was significantly decreased in subjects, indicating changes in white matter microstructure. There was an inverse relationship between FA and disease severity, but not with age.

CONCLUSIONS: Findings of MR imaging in OTCD are often normal in patients with late-onset disease, heterozygotes, or in those not in hyperammonemic crisis. DTI was more sensitive than FSE T2-weighted imaging for detecting abnormalities in normal-appearing white matter. The extent of abnormality correlated with cognitive deficits. The location of the deficits in the frontal white matter is important because this area connects fibers that are vital to executive function, attention, and working memory.

CTMT
:   Comprehensive Trail Making Test
DT
:   diffusion tensor
DTI
:   diffusion tensor imaging
EPI
:   echo-planar imaging
FA
:   fractional anisotropy index
FLAIR
:   fluid-attenuated inversion recovery
FSE
:   fast spin-echo
FSIQ
:   full-scale IQ
HA
:   hyperammonemia
Incong-Cong
:   incongruent-congruent
IQ
:   intelligence quotient
NA
:   not applicable
OTCD
:   ornithine transcarbamylase deficiency
PIQ
:   performance IQ
ROI
:   region of interest
UCD
:   urea cycle disorder
VIQ
:   verbal IQ
WM
:   white matter" />
<meta name="DC.Contributor" content="A.L. Gropman" />
<meta name="DC.Contributor" content="B. Gertz" />
<meta name="DC.Contributor" content="K. Shattuck" />
<meta name="DC.Contributor" content="I.L. Kahn" />
<meta name="DC.Contributor" content="R. Seltzer" />
<meta name="DC.Contributor" content="L. Krivitsky" />
<meta name="DC.Contributor" content="J. Van Meter" />
<meta name="article:published_time" content="2010-10-01" />
<meta name="article:section" content="Brain" />
<meta name="citation_title" content="Diffusion Tensor Imaging Detects Areas of Abnormal White Matter Microstructure in Patients with Partial Ornithine Transcarbamylase Deficiency" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;OTCD, an X-linked disorder, is the most common of the UCDs. Neonatal onset is associated with uniformly poor outcome. Males with late-onset OTCD show deficits in executive function, motor planning, and working memory. A broad phenotype is observed in heterozygous females. A specific neurobehavioral phenotype with white matter dysfunction and impaired attention and working memory has been described. The extent to which the deficits involve specific pathways in the brain is unknown. We hypothesized that DTI would disclose white matter microstructure in OTCD correlating with cognitive  deficits.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Nineteen adults with partial OTCD and 18 adult control subjects ages 19–59 years participated. MR imaging was performed by using a 3T whole-body scanner. Anisotropy was calculated from the eigenvalues of the diffusion tensor by using the FA metric and was compared between the study and control  groups.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;FA of the frontal white matter was significantly decreased in subjects, indicating changes in white matter microstructure. There was an inverse relationship between FA and disease severity, but not with  age.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Findings of MR imaging in OTCD are often normal in patients with late-onset disease, heterozygotes, or in those not in hyperammonemic crisis. DTI was more sensitive than FSE T2-weighted imaging for detecting abnormalities in normal-appearing white matter. The extent of abnormality correlated with cognitive deficits. The location of the deficits in the frontal white matter is important because this area connects fibers that are vital to executive function, attention, and working  memory.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
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<meta name="citation_publication_date" content="2010/10/01" />
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<meta name="citation_firstpage" content="1719" />
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<meta name="citation_author" content="A.L. Gropman" />
<meta name="citation_author" content="B. Gertz" />
<meta name="citation_author" content="K. Shattuck" />
<meta name="citation_author" content="I.L. Kahn" />
<meta name="citation_author" content="R. Seltzer" />
<meta name="citation_author" content="L. Krivitsky" />
<meta name="citation_author" content="J. Van Meter" />
<meta name="citation_fulltext_world_readable" content="" />
<meta name="twitter:title" content="Diffusion Tensor Imaging Detects Areas of Abnormal White Matter Microstructure in Patients with Partial Ornithine Transcarbamylase Deficiency" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: OTCD, an X-linked disorder, is the most common of the UCDs. Neonatal onset is associated with uniformly poor outcome. Males with late-onset OTCD show deficits in executive function, motor planning, and working memory. A broad phenotype is observed in heterozygous females. A specific neurobehavioral phenotype with white matter dysfunction and impaired attention and working memory has been described. The extent to which the deficits involve specific pathways in the brain is unknown. We hypothesized that DTI would disclose white matter microstructure in OTCD correlating with cognitive deficits.

MATERIALS AND METHODS: Nineteen adults with partial OTCD and 18 adult control subjects ages 19–59 years participated. MR imaging was performed by using a 3T whole-body scanner. Anisotropy was calculated from the eigenvalues of the diffusion tensor by using the FA metric and was compared between the study and control groups.

RESULTS: FA of the frontal white matter was significantly decreased in subjects, indicating changes in white matter microstructure. There was an inverse relationship between FA and disease severity, but not with age.

CONCLUSIONS: Findings of MR imaging in OTCD are often normal in patients with late-onset disease, heterozygotes, or in those not in hyperammonemic crisis. DTI was more sensitive than FSE T2-weighted imaging for detecting abnormalities in normal-appearing white matter. The extent of abnormality correlated with cognitive deficits. The location of the deficits in the frontal white matter is important because this area connects fibers that are vital to executive function, attention, and working memory.

CTMT
:   Comprehensive Trail Making Test
DT
:   diffusion tensor
DTI
:   diffusion tensor imaging
EPI
:   echo-planar imaging
FA
:   fractional anisotropy index
FLAIR
:   fluid-attenuated inversion recovery
FSE
:   fast spin-echo
FSIQ
:   full-scale IQ
HA
:   hyperammonemia
Incong-Cong
:   incongruent-congruent
IQ
:   intelligence quotient
NA
:   not applicable
OTCD
:   ornithine transcarbamylase deficiency
PIQ
:   performance IQ
ROI
:   region of interest
UCD
:   urea cycle disorder
VIQ
:   verbal IQ
WM
:   white matter" />
<meta name="og-title" property="og:title" content="Diffusion Tensor Imaging Detects Areas of Abnormal White Matter Microstructure in Patients with Partial Ornithine Transcarbamylase Deficiency" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/31/9/1719" />
<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: OTCD, an X-linked disorder, is the most common of the UCDs. Neonatal onset is associated with uniformly poor outcome. Males with late-onset OTCD show deficits in executive function, motor planning, and working memory. A broad phenotype is observed in heterozygous females. A specific neurobehavioral phenotype with white matter dysfunction and impaired attention and working memory has been described. The extent to which the deficits involve specific pathways in the brain is unknown. We hypothesized that DTI would disclose white matter microstructure in OTCD correlating with cognitive deficits.

MATERIALS AND METHODS: Nineteen adults with partial OTCD and 18 adult control subjects ages 19–59 years participated. MR imaging was performed by using a 3T whole-body scanner. Anisotropy was calculated from the eigenvalues of the diffusion tensor by using the FA metric and was compared between the study and control groups.

RESULTS: FA of the frontal white matter was significantly decreased in subjects, indicating changes in white matter microstructure. There was an inverse relationship between FA and disease severity, but not with age.

CONCLUSIONS: Findings of MR imaging in OTCD are often normal in patients with late-onset disease, heterozygotes, or in those not in hyperammonemic crisis. DTI was more sensitive than FSE T2-weighted imaging for detecting abnormalities in normal-appearing white matter. The extent of abnormality correlated with cognitive deficits. The location of the deficits in the frontal white matter is important because this area connects fibers that are vital to executive function, attention, and working memory.

CTMT
:   Comprehensive Trail Making Test
DT
:   diffusion tensor
DTI
:   diffusion tensor imaging
EPI
:   echo-planar imaging
FA
:   fractional anisotropy index
FLAIR
:   fluid-attenuated inversion recovery
FSE
:   fast spin-echo
FSIQ
:   full-scale IQ
HA
:   hyperammonemia
Incong-Cong
:   incongruent-congruent
IQ
:   intelligence quotient
NA
:   not applicable
OTCD
:   ornithine transcarbamylase deficiency
PIQ
:   performance IQ
ROI
:   region of interest
UCD
:   urea cycle disorder
VIQ
:   verbal IQ
WM
:   white matter" />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node9836--5" data-node-nid="9836" id="top-node-9836--61681839676" data-pisa="ajnr;31/9/1719" data-pisa-master="ajnr;ajnr.A2122" data-apath="/ajnr/31/9/1719.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a">
  
  
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">A.L. Gropman</span>, <span class="highwire-citation-author" data-delta="1">B. Gertz</span>, <span class="highwire-citation-author" data-delta="2">K. Shattuck</span>, <span class="highwire-citation-author" data-delta="3">I.L. Kahn</span>, <span class="highwire-citation-author" data-delta="4">R. Seltzer</span>, <span class="highwire-citation-author" data-delta="5">L. Krivitsky</span> and <span class="highwire-citation-author" data-delta="6">J. Van Meter</span></span></div>
  
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<div id="hw-article-author-popups-top-node-9836--61681839676" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">A.L. Gropman </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=A.L.%2BGropman%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=Gropman%20A&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%3AA.L.%2BGropman%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">B. 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Kahn </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=I.L.%2BKahn%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=Kahn%20I&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%3AI.L.%2BKahn%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-4"><div class="author-tooltip-name">R. 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<p id="p-2"><strong>BACKGROUND AND PURPOSE:</strong> OTCD, an X-linked disorder, is the most common of the UCDs. Neonatal onset is associated with uniformly poor outcome. Males with late-onset OTCD show deficits in executive function, motor planning, and working memory. A broad phenotype is observed in heterozygous females. A specific neurobehavioral phenotype with white matter dysfunction and impaired attention and working memory has been described. The extent to which the deficits involve specific pathways in the brain is unknown. We hypothesized that DTI would disclose white matter microstructure in OTCD correlating with cognitive  deficits.</p>
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<p id="p-3"><strong>MATERIALS AND METHODS:</strong> Nineteen adults with partial OTCD and 18 adult control subjects ages 19–59 years participated. MR imaging was performed by using a 3T whole-body scanner. Anisotropy was calculated from the eigenvalues of the diffusion tensor by using the FA metric and was compared between the study and control  groups.</p>
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<p id="p-4"><strong>RESULTS:</strong> FA of the frontal white matter was significantly decreased in subjects, indicating changes in white matter microstructure. There was an inverse relationship between FA and disease severity, but not with  age.</p>
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<p id="p-5"><strong>CONCLUSIONS:</strong> Findings of MR imaging in OTCD are often normal in patients with late-onset disease, heterozygotes, or in those not in hyperammonemic crisis. DTI was more sensitive than FSE T2-weighted imaging for detecting abnormalities in normal-appearing white matter. The extent of abnormality correlated with cognitive deficits. The location of the deficits in the frontal white matter is important because this area connects fibers that are vital to executive function, attention, and working  memory.</p>
</div></div><div class="section glossary" id="glossary-1"><h2>Abbreviations</h2><dl id="def-list-1"><dt id="def-item-1">CTMT<span class="def-item-dt-sep"></span></dt><dd>Comprehensive Trail Making Test<span class="def-item-dd-sep"></span></dd><dt id="def-item-2">DT<span class="def-item-dt-sep"></span></dt><dd>diffusion tensor<span class="def-item-dd-sep"></span></dd><dt id="def-item-3">DTI<span class="def-item-dt-sep"></span></dt><dd>diffusion tensor imaging<span class="def-item-dd-sep"></span></dd><dt id="def-item-4">EPI<span class="def-item-dt-sep"></span></dt><dd>echo-planar imaging<span class="def-item-dd-sep"></span></dd><dt id="def-item-5">FA<span class="def-item-dt-sep"></span></dt><dd>fractional anisotropy index<span class="def-item-dd-sep"></span></dd><dt id="def-item-6">FLAIR<span class="def-item-dt-sep"></span></dt><dd>fluid-attenuated inversion recovery<span class="def-item-dd-sep"></span></dd><dt id="def-item-7">FSE<span class="def-item-dt-sep"></span></dt><dd>fast spin-echo<span class="def-item-dd-sep"></span></dd><dt id="def-item-8">FSIQ<span class="def-item-dt-sep"></span></dt><dd>full-scale IQ<span class="def-item-dd-sep"></span></dd><dt id="def-item-9">HA<span class="def-item-dt-sep"></span></dt><dd>hyperammonemia<span class="def-item-dd-sep"></span></dd><dt id="def-item-10">Incong-Cong<span class="def-item-dt-sep"></span></dt><dd>incongruent-congruent<span class="def-item-dd-sep"></span></dd><dt id="def-item-11">IQ<span class="def-item-dt-sep"></span></dt><dd>intelligence quotient<span class="def-item-dd-sep"></span></dd><dt id="def-item-12">NA<span class="def-item-dt-sep"></span></dt><dd>not applicable<span class="def-item-dd-sep"></span></dd><dt id="def-item-13">OTCD<span class="def-item-dt-sep"></span></dt><dd>ornithine transcarbamylase deficiency<span class="def-item-dd-sep"></span></dd><dt id="def-item-14">PIQ<span class="def-item-dt-sep"></span></dt><dd>performance IQ<span class="def-item-dd-sep"></span></dd><dt id="def-item-15">ROI<span class="def-item-dt-sep"></span></dt><dd>region of interest<span class="def-item-dd-sep"></span></dd><dt id="def-item-16">UCD<span class="def-item-dt-sep"></span></dt><dd>urea cycle disorder<span class="def-item-dd-sep"></span></dd><dt id="def-item-17">VIQ<span class="def-item-dt-sep"></span></dt><dd>verbal IQ<span class="def-item-dd-sep"></span></dd><dt id="def-item-18">WM<span class="def-item-dt-sep"></span></dt><dd>white matter</dd></dl></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">Copyright © American Society of Neuroradiology</li></ul><div class="license" id="license-1"><p id="p-1">Indicates open access to non-subscribers at <a href="http://www.ajnr.org">www.ajnr.org</a></p></div><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="http://ajnr-stage2.stage.highwire.org/content/31/9/1719.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div>  </div>

  
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      <div class="highwire-cite-title">Diffusion Tensor Imaging Detects Areas of Abnormal White Matter Microstructure in Patients with Partial Ornithine Transcarbamylase Deficiency</div>  
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    	<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">Oct 2010, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">31 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(9) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1719-1723; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A2122 </span></div>
  
  
  
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      <div class="highwire-cite-title">Diffusion Tensor Imaging Detects Areas of Abnormal White Matter Microstructure in Patients with Partial Ornithine Transcarbamylase Deficiency</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">A.L.</span> <span class="nlm-surname">Gropman</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">B.</span> <span class="nlm-surname">Gertz</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">K.</span> <span class="nlm-surname">Shattuck</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">I.L.</span> <span class="nlm-surname">Kahn</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">R.</span> <span class="nlm-surname">Seltzer</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">L.</span> <span class="nlm-surname">Krivitsky</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">J.</span> <span class="nlm-surname">Van Meter</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">Oct 2010, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">31 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(9) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1719-1723; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A2122 </span></div>
  
  
  
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