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<meta name="HW.identifier" content="/ajnr/39/9/1650.atom" />
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<meta name="DC.Language" content="en" />
<meta name="DC.Title" content="Longitudinal Microstructural Changes in Traumatic Brain Injury in Rats: A Diffusional Kurtosis Imaging, Histology, and Behavior Study" />
<meta name="DC.Identifier" content="10.3174/ajnr.A5737" />
<meta name="DC.Date" content="2018-09-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2018 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: Traumatic brain injury is a major public health problem worldwide. Accurately evaluating the brain microstructural changes in traumatic brain injury is crucial for the treatment and prognosis assessment. This study aimed to assess the longitudinal brain microstructural changes in traumatic brain injury in the rat using diffusional kurtosis imaging.

MATERIALS AND METHODS: Diffusional kurtosis imaging was performed in a group of 5 rats at preinjury and 3, 14, and 28 days after traumatic brain injury. The diffusional kurtosis imaging parameters were measured in the bilateral cortex, hippocampus, and corpus callosum. Another 4 groups of 5 rats were used in brain immunohistochemistry analysis of neuron (neuron-specific nuclear protein [NeuN]), astroglia (glial fibrillary acidic protein [GFAP]), microglia (ionized calcium binding adaptor molecule 1 [Iba-1]), and myelin (myelin basic protein [MBP]) in the same area as the diffusional kurtosis imaging parameter measurements. Furthermore, 2 groups of 6 rats underwent a Morris water maze test at 28 days after traumatic brain injury. The diffusional kurtosis imaging parameters, immunohistochemistry results, and Morris water maze test results were compared longitudinally or between traumatic brain injury and control groups.

RESULTS: Compared with baseline, traumatic brain injury in the rat showed higher mean kurtosis and mean diffusivity values in the ipsilateral perilesional cortex and hippocampus and lower fractional anisotropy values in the corpus callosum ( P &lt; .05). The traumatic brain injury group showed higher staining of GFAP and Iba-1 and lower immunohistochemistry staining of NeuN and MBP in all ipsilateral ROIs ( P &lt; .05). There was no significant difference in the contralateral ROIs in diffusional kurtosis imaging parameters or immunohistochemistry results. The Morris water maze test revealed lower platform crossing times in the probe test ( P &lt; .05).

CONCLUSIONS: Our study indicated that there were longitudinal changes in diffusional kurtosis imaging parameters, accompanied by multiple pathologic changes at different time points following traumatic brain injury, and that mean kurtosis is more sensitive to detect microstructural changes, especially in gray matter, than mean diffusivity and fractional anisotropy.

Da
:   axial diffusion
DKI
:   diffusional kurtosis imaging
Dr
:   radial diffusion
FA
:   fractional anisotropy
GFAP
:   glial fibrillary acidic protein
Iba-1
:   ionized calcium binding adaptor molecule 1
IHC
:   immunohistochemistry
Ka
:   axial kurtosis
Kr
:   radial kurtosis
MBP
:   myelin basic protein
MD
:   mean diffusivity
MK
:   mean kurtosis
NeuN
:   neuron-specific nuclear protein
TBI
:   traumatic brain injury" />
<meta name="DC.Contributor" content="M.-L. Wang" />
<meta name="DC.Contributor" content="M.-M. Yu" />
<meta name="DC.Contributor" content="D.-X. Yang" />
<meta name="DC.Contributor" content="Y.-L. Liu" />
<meta name="DC.Contributor" content="X.-E. Wei" />
<meta name="DC.Contributor" content="W.-B. Li" />
<meta name="article:published_time" content="2018-09-01" />
<meta name="article:section" content="Adult Brain" />
<meta name="citation_title" content="Longitudinal Microstructural Changes in Traumatic Brain Injury in Rats: A Diffusional Kurtosis Imaging, Histology, and Behavior Study" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Traumatic brain injury is a major public health problem worldwide. Accurately evaluating the brain microstructural changes in traumatic brain injury is crucial for the treatment and prognosis assessment. This study aimed to assess the longitudinal brain microstructural changes in traumatic brain injury in the rat using diffusional kurtosis imaging.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Diffusional kurtosis imaging was performed in a group of 5 rats at preinjury and 3, 14, and 28 days after traumatic brain injury. The diffusional kurtosis imaging parameters were measured in the bilateral cortex, hippocampus, and corpus callosum. Another 4 groups of 5 rats were used in brain immunohistochemistry analysis of neuron (neuron-specific nuclear protein [NeuN]), astroglia (glial fibrillary acidic protein [GFAP]), microglia (ionized calcium binding adaptor molecule 1 [Iba-1]), and myelin (myelin basic protein [MBP]) in the same area as the diffusional kurtosis imaging parameter measurements. Furthermore, 2 groups of 6 rats underwent a Morris water maze test at 28 days after traumatic brain injury. The diffusional kurtosis imaging parameters, immunohistochemistry results, and Morris water maze test results were compared longitudinally or between traumatic brain injury and control groups.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Compared with baseline, traumatic brain injury in the rat showed higher mean kurtosis and mean diffusivity values in the ipsilateral perilesional cortex and hippocampus and lower fractional anisotropy values in the corpus callosum (&lt;i&gt;P&lt;/i&gt; &amp;lt; .05). The traumatic brain injury group showed higher staining of GFAP and Iba-1 and lower immunohistochemistry staining of NeuN and MBP in all ipsilateral ROIs (&lt;i&gt;P&lt;/i&gt; &amp;lt; .05). There was no significant difference in the contralateral ROIs in diffusional kurtosis imaging parameters or immunohistochemistry results. The Morris water maze test revealed lower platform crossing times in the probe test (&lt;i&gt;P&lt;/i&gt; &amp;lt; .05).&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Our study indicated that there were longitudinal changes in diffusional kurtosis imaging parameters, accompanied by multiple pathologic changes at different time points following traumatic brain injury, and that mean kurtosis is more sensitive to detect microstructural changes, especially in gray matter, than mean diffusivity and fractional anisotropy.&lt;/p&gt;" />
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<meta name="twitter:title" content="Longitudinal Microstructural Changes in Traumatic Brain Injury in Rats: A Diffusional Kurtosis Imaging, Histology, and Behavior Study" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Traumatic brain injury is a major public health problem worldwide. Accurately evaluating the brain microstructural changes in traumatic brain injury is crucial for the treatment and prognosis assessment. This study aimed to assess the longitudinal brain microstructural changes in traumatic brain injury in the rat using diffusional kurtosis imaging.

MATERIALS AND METHODS: Diffusional kurtosis imaging was performed in a group of 5 rats at preinjury and 3, 14, and 28 days after traumatic brain injury. The diffusional kurtosis imaging parameters were measured in the bilateral cortex, hippocampus, and corpus callosum. Another 4 groups of 5 rats were used in brain immunohistochemistry analysis of neuron (neuron-specific nuclear protein [NeuN]), astroglia (glial fibrillary acidic protein [GFAP]), microglia (ionized calcium binding adaptor molecule 1 [Iba-1]), and myelin (myelin basic protein [MBP]) in the same area as the diffusional kurtosis imaging parameter measurements. Furthermore, 2 groups of 6 rats underwent a Morris water maze test at 28 days after traumatic brain injury. The diffusional kurtosis imaging parameters, immunohistochemistry results, and Morris water maze test results were compared longitudinally or between traumatic brain injury and control groups.

RESULTS: Compared with baseline, traumatic brain injury in the rat showed higher mean kurtosis and mean diffusivity values in the ipsilateral perilesional cortex and hippocampus and lower fractional anisotropy values in the corpus callosum ( P &lt; .05). The traumatic brain injury group showed higher staining of GFAP and Iba-1 and lower immunohistochemistry staining of NeuN and MBP in all ipsilateral ROIs ( P &lt; .05). There was no significant difference in the contralateral ROIs in diffusional kurtosis imaging parameters or immunohistochemistry results. The Morris water maze test revealed lower platform crossing times in the probe test ( P &lt; .05).

CONCLUSIONS: Our study indicated that there were longitudinal changes in diffusional kurtosis imaging parameters, accompanied by multiple pathologic changes at different time points following traumatic brain injury, and that mean kurtosis is more sensitive to detect microstructural changes, especially in gray matter, than mean diffusivity and fractional anisotropy.

Da
:   axial diffusion
DKI
:   diffusional kurtosis imaging
Dr
:   radial diffusion
FA
:   fractional anisotropy
GFAP
:   glial fibrillary acidic protein
Iba-1
:   ionized calcium binding adaptor molecule 1
IHC
:   immunohistochemistry
Ka
:   axial kurtosis
Kr
:   radial kurtosis
MBP
:   myelin basic protein
MD
:   mean diffusivity
MK
:   mean kurtosis
NeuN
:   neuron-specific nuclear protein
TBI
:   traumatic brain injury" />
<meta name="og-title" property="og:title" content="Longitudinal Microstructural Changes in Traumatic Brain Injury in Rats: A Diffusional Kurtosis Imaging, Histology, and Behavior Study" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/39/9/1650" />
<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: Traumatic brain injury is a major public health problem worldwide. Accurately evaluating the brain microstructural changes in traumatic brain injury is crucial for the treatment and prognosis assessment. This study aimed to assess the longitudinal brain microstructural changes in traumatic brain injury in the rat using diffusional kurtosis imaging.

MATERIALS AND METHODS: Diffusional kurtosis imaging was performed in a group of 5 rats at preinjury and 3, 14, and 28 days after traumatic brain injury. The diffusional kurtosis imaging parameters were measured in the bilateral cortex, hippocampus, and corpus callosum. Another 4 groups of 5 rats were used in brain immunohistochemistry analysis of neuron (neuron-specific nuclear protein [NeuN]), astroglia (glial fibrillary acidic protein [GFAP]), microglia (ionized calcium binding adaptor molecule 1 [Iba-1]), and myelin (myelin basic protein [MBP]) in the same area as the diffusional kurtosis imaging parameter measurements. Furthermore, 2 groups of 6 rats underwent a Morris water maze test at 28 days after traumatic brain injury. The diffusional kurtosis imaging parameters, immunohistochemistry results, and Morris water maze test results were compared longitudinally or between traumatic brain injury and control groups.

RESULTS: Compared with baseline, traumatic brain injury in the rat showed higher mean kurtosis and mean diffusivity values in the ipsilateral perilesional cortex and hippocampus and lower fractional anisotropy values in the corpus callosum ( P &lt; .05). The traumatic brain injury group showed higher staining of GFAP and Iba-1 and lower immunohistochemistry staining of NeuN and MBP in all ipsilateral ROIs ( P &lt; .05). There was no significant difference in the contralateral ROIs in diffusional kurtosis imaging parameters or immunohistochemistry results. The Morris water maze test revealed lower platform crossing times in the probe test ( P &lt; .05).

CONCLUSIONS: Our study indicated that there were longitudinal changes in diffusional kurtosis imaging parameters, accompanied by multiple pathologic changes at different time points following traumatic brain injury, and that mean kurtosis is more sensitive to detect microstructural changes, especially in gray matter, than mean diffusivity and fractional anisotropy.

Da
:   axial diffusion
DKI
:   diffusional kurtosis imaging
Dr
:   radial diffusion
FA
:   fractional anisotropy
GFAP
:   glial fibrillary acidic protein
Iba-1
:   ionized calcium binding adaptor molecule 1
IHC
:   immunohistochemistry
Ka
:   axial kurtosis
Kr
:   radial kurtosis
MBP
:   myelin basic protein
MD
:   mean diffusivity
MK
:   mean kurtosis
NeuN
:   neuron-specific nuclear protein
TBI
:   traumatic brain injury" />
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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">Longitudinal Microstructural Changes in Traumatic Brain Injury in Rats: A Diffusional Kurtosis Imaging, Histology, and Behavior Study</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">M.-L. Wang</span>, <span class="highwire-citation-author" data-delta="1">M.-M. Yu</span>, <span class="highwire-citation-author" data-delta="2">D.-X. Yang</span>, <span class="highwire-citation-author" data-delta="3">Y.-L. Liu</span>, <span class="highwire-citation-author" data-delta="4">X.-E. Wei</span> and <span class="highwire-citation-author" data-delta="5">W.-B. Li</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">September 2018,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">39 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(9) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1650-1656; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A5737 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-62642--61533141809" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">M.-L. Wang </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 Radiology (M.-L.W., M.-M.Y., X.-E.W., W.-B.L.)</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=M.-L.%2BWang%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=Wang%20M&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%3AM.-L.%2BWang%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/0000-0003-1752-898X" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for M.-L. Wang</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">M.-M. Yu </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 Radiology (M.-L.W., M.-M.Y., X.-E.W., W.-B.L.)</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=M.-M.%2BYu%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=Yu%20M&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%3AM.-M.%2BYu%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/0000-0003-1658-1914" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for M.-M. Yu</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">D.-X. Yang </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Neurosurgery (D.-X.Y., Y.-L.L.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 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=D.-X.%2BYang%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=Yang%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.-X.%2BYang%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/0000-0002-7814-3795" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for D.-X. Yang</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">Y.-L. Liu </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Neurosurgery (D.-X.Y., Y.-L.L.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 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=Y.-L.%2BLiu%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=Liu%20Y&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%3AY.-L.%2BLiu%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/0000-0002-3987-7825" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Y.-L. Liu</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">X.-E. Wei </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 Radiology (M.-L.W., M.-M.Y., X.-E.W., W.-B.L.)</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.-E.%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%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.-E.%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/0000-0001-7289-0098" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for X.-E. 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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 39</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 9 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Sep 2018 </div></div>
      
      
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      <div class="highwire-cite-title">Longitudinal Microstructural Changes in Traumatic Brain Injury in Rats: A Diffusional Kurtosis Imaging, Histology, and Behavior Study</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">M.-L.</span> <span class="nlm-surname">Wang</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">M.-M.</span> <span class="nlm-surname">Yu</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">D.-X.</span> <span class="nlm-surname">Yang</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Y.-L.</span> <span class="nlm-surname">Liu</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">X.-E.</span> <span class="nlm-surname">Wei</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">W.-B.</span> <span class="nlm-surname">Li</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">Sep 2018, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">39 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(9) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1650-1656; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A5737 </span></div>
  
  
  
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      <div class="highwire-cite-title">Longitudinal Microstructural Changes in Traumatic Brain Injury in Rats: A Diffusional Kurtosis Imaging, Histology, and Behavior Study</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">M.-L.</span> <span class="nlm-surname">Wang</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">M.-M.</span> <span class="nlm-surname">Yu</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">D.-X.</span> <span class="nlm-surname">Yang</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Y.-L.</span> <span class="nlm-surname">Liu</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">X.-E.</span> <span class="nlm-surname">Wei</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">W.-B.</span> <span class="nlm-surname">Li</span></span></span></div>
  
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