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<meta name="DC.Title" content="Short-Range Structural Connections Are More Severely Damaged in Early-Stage MS" />
<meta name="DC.Identifier" content="10.3174/ajnr.A7425" />
<meta name="DC.Date" content="2022-03-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2022 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: Long-range connections are more severely damaged and relevant for cognition in long-standing MS. However, the evolution of such coordinated network damage in patients with MS is unclear. We investigated whether short- and long-range structural connections sustained equal damage in early-stage MS.

MATERIALS AND METHODS: Sixteen patients with early-stage MS and 17 healthy controls were scanned by high-resolution, multishell diffusion imaging on 7T MR imaging and assessed cognitively. We investigated macrostructural properties in short- and long-range fibers and of microstructural metrics derived from 2 quantitative diffusion MR imaging models: DTI and neurite orientation dispersion and density imaging.

RESULTS: Patients had significant WM integrity damage—that is, higher radial diffusivity and a lower intracellular volume fraction in the focal WM lesions. Compared with the healthy controls, the patients had noticeable microstructure changes in both short- and long-range fibers, including increased radial diffusivity, mean diffusivity, and axial diffusivity. Z scores further indicated greater damage in the short-range fibers than in the long-range fibers.

CONCLUSIONS: Our findings demonstrate that more severe demyelination preceding axonal degeneration occurs in short-range connections but not in long-range connections in early-stage MS, suggesting the possibility that there are cortical lesions that are undetectable by current MR imaging.

AD
:   axial diffusivity
EDSS
:   Expanded Disability Status Scale
FA
:   fractional anisotropy
f icvf
:   intracellular volume fraction
HC
:   healthy control
MD
:   mean diffusivity
NODDI
:   neurite orientation dispersion and density imaging
ODI
:   Orientation Dispersion Index
RD
:   radial diffusivity" />
<meta name="DC.Contributor" content="H. Wu" />
<meta name="DC.Contributor" content="C. Sun" />
<meta name="DC.Contributor" content="X. Huang" />
<meta name="DC.Contributor" content="R. Wei" />
<meta name="DC.Contributor" content="Z. Li" />
<meta name="DC.Contributor" content="D. Ke" />
<meta name="DC.Contributor" content="R. Bai" />
<meta name="DC.Contributor" content="H. Liang" />
<meta name="article:published_time" content="2022-03-01" />
<meta name="article:section" content="Adult Brain" />
<meta name="citation_title" content="Short-Range Structural Connections Are More Severely Damaged in Early-Stage MS" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Long-range connections are more severely damaged and relevant for cognition in long-standing MS. However, the evolution of such coordinated network damage in patients with MS is unclear. We investigated whether short- and long-range structural connections sustained equal damage in early-stage MS.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Sixteen patients with early-stage MS and 17 healthy controls were scanned by high-resolution, multishell diffusion imaging on 7T MR imaging and assessed cognitively. We investigated macrostructural properties in short- and long-range fibers and of microstructural metrics derived from 2 quantitative diffusion MR imaging models: DTI and neurite orientation dispersion and density imaging.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Patients had significant WM integrity damage—that is, higher radial diffusivity and a lower intracellular volume fraction in the focal WM lesions. Compared with the healthy controls, the patients had noticeable microstructure changes in both short- and long-range fibers, including increased radial diffusivity, mean diffusivity, and axial diffusivity. &lt;i&gt;Z&lt;/i&gt; scores further indicated greater damage in the short-range fibers than in the long-range fibers.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Our findings demonstrate that more severe demyelination preceding axonal degeneration occurs in short-range connections but not in long-range connections in early-stage MS, suggesting the possibility that there are cortical lesions that are undetectable by current MR imaging.&lt;/p&gt;" />
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<meta name="twitter:title" content="Short-Range Structural Connections Are More Severely Damaged in Early-Stage MS" />
<meta name="twitter:card" content="summary_large_image" />
<meta name="twitter:image" content="http://ajnr-stage2.stage.highwire.org/sites/default/files/highwire/ajnr/43/3.cover-source.jpg" />
<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Long-range connections are more severely damaged and relevant for cognition in long-standing MS. However, the evolution of such coordinated network damage in patients with MS is unclear. We investigated whether short- and long-range structural connections sustained equal damage in early-stage MS.

MATERIALS AND METHODS: Sixteen patients with early-stage MS and 17 healthy controls were scanned by high-resolution, multishell diffusion imaging on 7T MR imaging and assessed cognitively. We investigated macrostructural properties in short- and long-range fibers and of microstructural metrics derived from 2 quantitative diffusion MR imaging models: DTI and neurite orientation dispersion and density imaging.

RESULTS: Patients had significant WM integrity damage—that is, higher radial diffusivity and a lower intracellular volume fraction in the focal WM lesions. Compared with the healthy controls, the patients had noticeable microstructure changes in both short- and long-range fibers, including increased radial diffusivity, mean diffusivity, and axial diffusivity. Z scores further indicated greater damage in the short-range fibers than in the long-range fibers.

CONCLUSIONS: Our findings demonstrate that more severe demyelination preceding axonal degeneration occurs in short-range connections but not in long-range connections in early-stage MS, suggesting the possibility that there are cortical lesions that are undetectable by current MR imaging.

AD
:   axial diffusivity
EDSS
:   Expanded Disability Status Scale
FA
:   fractional anisotropy
f icvf
:   intracellular volume fraction
HC
:   healthy control
MD
:   mean diffusivity
NODDI
:   neurite orientation dispersion and density imaging
ODI
:   Orientation Dispersion Index
RD
:   radial diffusivity" />
<meta name="og-title" property="og:title" content="Short-Range Structural Connections Are More Severely Damaged in Early-Stage MS" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/43/3/361" />
<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: Long-range connections are more severely damaged and relevant for cognition in long-standing MS. However, the evolution of such coordinated network damage in patients with MS is unclear. We investigated whether short- and long-range structural connections sustained equal damage in early-stage MS.

MATERIALS AND METHODS: Sixteen patients with early-stage MS and 17 healthy controls were scanned by high-resolution, multishell diffusion imaging on 7T MR imaging and assessed cognitively. We investigated macrostructural properties in short- and long-range fibers and of microstructural metrics derived from 2 quantitative diffusion MR imaging models: DTI and neurite orientation dispersion and density imaging.

RESULTS: Patients had significant WM integrity damage—that is, higher radial diffusivity and a lower intracellular volume fraction in the focal WM lesions. Compared with the healthy controls, the patients had noticeable microstructure changes in both short- and long-range fibers, including increased radial diffusivity, mean diffusivity, and axial diffusivity. Z scores further indicated greater damage in the short-range fibers than in the long-range fibers.

CONCLUSIONS: Our findings demonstrate that more severe demyelination preceding axonal degeneration occurs in short-range connections but not in long-range connections in early-stage MS, suggesting the possibility that there are cortical lesions that are undetectable by current MR imaging.

AD
:   axial diffusivity
EDSS
:   Expanded Disability Status Scale
FA
:   fractional anisotropy
f icvf
:   intracellular volume fraction
HC
:   healthy control
MD
:   mean diffusivity
NODDI
:   neurite orientation dispersion and density imaging
ODI
:   Orientation Dispersion Index
RD
:   radial diffusivity" />
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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">Short-Range Structural Connections Are More Severely Damaged in Early-Stage MS</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">H. Wu</span>, <span class="highwire-citation-author" data-delta="1">C. Sun</span>, <span class="highwire-citation-author" data-delta="2">X. Huang</span>, <span class="highwire-citation-author" data-delta="3">R. Wei</span>, <span class="highwire-citation-author" data-delta="4">Z. Li</span>, <span class="highwire-citation-author" data-delta="5">D. Ke</span>, <span class="highwire-citation-author" data-delta="6">R. Bai</span> and <span class="highwire-citation-author" data-delta="7">H. Liang</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">March 2022,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">43 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(3) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">361-367; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A7425 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-96088--82071186270" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">H. Wu </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>Frpm the Department of Neurology (H.W., X.H., R.W., D.K., H.L.), First Affiliated Hospital</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.%2BWu%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=Wu%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.%2BWu%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="https://orcid.org/0000-0002-3329-5795" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for H. Wu</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">C. Sun </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Key Laboratory of Biomedical Engineering of Ministry of Education (C.S., Z.L.), College of Biomedical Engineering and Instrument Science</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.%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%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.%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="https://orcid.org/0000-0001-7744-1603" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. Sun</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">X. Huang </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>Frpm the Department of Neurology (H.W., X.H., R.W., D.K., H.L.), First Affiliated Hospital</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=X.%2BHuang%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=Huang%20X&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%3AX.%2BHuang%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="https://orcid.org/0000-0001-6306-4667" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for X. Huang</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">R. Wei </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>Frpm the Department of Neurology (H.W., X.H., R.W., D.K., H.L.), First Affiliated Hospital</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=R.%2BWei%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=Wei%20R&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%3AR.%2BWei%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="https://orcid.org/0000-0002-3404-4402" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for R. Wei</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">Z. Li </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Key Laboratory of Biomedical Engineering of Ministry of Education (C.S., Z.L.), College of Biomedical Engineering and Instrument Science</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=Z.%2BLi%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=Li%20Z&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%3AZ.%2BLi%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="https://orcid.org/0000-0002-3737-5725" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Z. Li</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">D. Ke </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>Frpm the Department of Neurology (H.W., X.H., R.W., D.K., H.L.), First Affiliated Hospital</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.%2BKe%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=Ke%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.%2BKe%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="https://orcid.org/0000-0002-6307-0503" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for D. Ke</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">R. Bai </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>c</span>Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Run Shaw Hospital and Interdisciplinary Institute of Neuroscience and Technology (R.B.), School of Medicine, Zhejiang University, Hangzhou, China</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=R.%2BBai%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=Bai%20R&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%3AR.%2BBai%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="https://orcid.org/0000-0003-4246-5984" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for R. 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Liang </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>Frpm the Department of Neurology (H.W., X.H., R.W., D.K., H.L.), First Affiliated Hospital</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.%2BLiang%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=Liang%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.%2BLiang%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="https://orcid.org/0000-0002-3210-1792" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for H. 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      <div class="highwire-cite-title">Short-Range Structural Connections Are More Severely Damaged in Early-Stage MS</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">H.</span> <span class="nlm-surname">Wu</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">C.</span> <span class="nlm-surname">Sun</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">X.</span> <span class="nlm-surname">Huang</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">R.</span> <span class="nlm-surname">Wei</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Z.</span> <span class="nlm-surname">Li</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">D.</span> <span class="nlm-surname">Ke</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">R.</span> <span class="nlm-surname">Bai</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">H.</span> <span class="nlm-surname">Liang</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">Mar 2022, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">43 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(3) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">361-367; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A7425 </span></div>
  
  
  
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