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<meta name="DC.Title" content="β-Hydroxybutyrate Detection with Proton MR Spectroscopy in Children with Drug-Resistant Epilepsy on the Ketogenic Diet" />
<meta name="DC.Identifier" content="10.3174/ajnr.A5648" />
<meta name="DC.Date" content="2018-07-01" />
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<meta name="DC.Description" content="BACKGROUND AND PURPOSE: The ketogenic diet, including both classic and modified forms, is an alternative to antiepileptic medications used in the treatment of drug-resistant epilepsy. We sought to evaluate the utility of proton MR spectroscopy for the detection of β-hydroxybutyrate in a cohort of children with epilepsy treated with the ketogenic diet and to correlate brain parenchymal metabolite ratios obtained from spectroscopy with β-hydroxybutyrate serum concentrations.

MATERIALS AND METHODS: Twenty-three spectroscopic datasets acquired at a TE of 288 ms in children on the ketogenic diet were analyzed with LCModel using a modified basis set that included a simulated β-hydroxybutyrate resonance. Brain parenchymal metabolite ratios were calculated. Metabolite ratios were compared with serum β-hydroxybutyrate concentrations, and partial correlation coefficients were calculated using patient age as a covariate.

RESULTS: β-hydroxybutyrate blood levels were highly correlated to brain β-hydroxybutyrate levels, referenced as either choline, creatine, or N -acetylaspartate. They were inversely but more weakly associated with N -acetylaspartate, regardless of the ratio denominator. No strong concordance with lactate was demonstrated.

CONCLUSIONS: Clinical MR spectroscopy in pediatric patients on the ketogenic diet demonstrated measurable β-hydroxybutyrate, with a strong correlation to β-hydroxybutyrate blood levels. These findings may serve as an effective tool for noninvasive monitoring of ketosis in this population. An inverse correlation between serum β-hydroxybutyrate levels and brain tissue N -acetylaspartate suggests that altered amino acid handling contributes to the antiepileptogenic effect of the ketogenic diet.

BHB
:   β-hydroxybutyrate
GABA
:   gamma-aminobutyric acid
KD
:   ketogenic diet
MAD
:   modified Atkins diet" />
<meta name="DC.Contributor" content="J.N. Wright" />
<meta name="DC.Contributor" content="R.P. Saneto" />
<meta name="DC.Contributor" content="S.D. Friedman" />
<meta name="article:published_time" content="2018-07-01" />
<meta name="article:section" content="Pediatrics" />
<meta name="citation_title" content="β-Hydroxybutyrate Detection with Proton MR Spectroscopy in Children with Drug-Resistant Epilepsy on the Ketogenic Diet" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;The ketogenic diet, including both classic and modified forms, is an alternative to antiepileptic medications used in the treatment of drug-resistant epilepsy. We sought to evaluate the utility of proton MR spectroscopy for the detection of β-hydroxybutyrate in a cohort of children with epilepsy treated with the ketogenic diet and to correlate brain parenchymal metabolite ratios obtained from spectroscopy with β-hydroxybutyrate serum concentrations.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Twenty-three spectroscopic datasets acquired at a TE of 288 ms in children on the ketogenic diet were analyzed with LCModel using a modified basis set that included a simulated β-hydroxybutyrate resonance. Brain parenchymal metabolite ratios were calculated. Metabolite ratios were compared with serum β-hydroxybutyrate concentrations, and partial correlation coefficients were calculated using patient age as a covariate.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;β-hydroxybutyrate blood levels were highly correlated to brain β-hydroxybutyrate levels, referenced as either choline, creatine, or &lt;i&gt;N&lt;/i&gt;-acetylaspartate. They were inversely but more weakly associated with &lt;i&gt;N&lt;/i&gt;-acetylaspartate, regardless of the ratio denominator. No strong concordance with lactate was demonstrated.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Clinical MR spectroscopy in pediatric patients on the ketogenic diet demonstrated measurable β-hydroxybutyrate, with a strong correlation to β-hydroxybutyrate blood levels. These findings may serve as an effective tool for noninvasive monitoring of ketosis in this population. An inverse correlation between serum β-hydroxybutyrate levels and brain tissue &lt;i&gt;N&lt;/i&gt;-acetylaspartate suggests that altered amino acid handling contributes to the antiepileptogenic effect of the ketogenic diet.&lt;/p&gt;" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: The ketogenic diet, including both classic and modified forms, is an alternative to antiepileptic medications used in the treatment of drug-resistant epilepsy. We sought to evaluate the utility of proton MR spectroscopy for the detection of β-hydroxybutyrate in a cohort of children with epilepsy treated with the ketogenic diet and to correlate brain parenchymal metabolite ratios obtained from spectroscopy with β-hydroxybutyrate serum concentrations.

MATERIALS AND METHODS: Twenty-three spectroscopic datasets acquired at a TE of 288 ms in children on the ketogenic diet were analyzed with LCModel using a modified basis set that included a simulated β-hydroxybutyrate resonance. Brain parenchymal metabolite ratios were calculated. Metabolite ratios were compared with serum β-hydroxybutyrate concentrations, and partial correlation coefficients were calculated using patient age as a covariate.

RESULTS: β-hydroxybutyrate blood levels were highly correlated to brain β-hydroxybutyrate levels, referenced as either choline, creatine, or N -acetylaspartate. They were inversely but more weakly associated with N -acetylaspartate, regardless of the ratio denominator. No strong concordance with lactate was demonstrated.

CONCLUSIONS: Clinical MR spectroscopy in pediatric patients on the ketogenic diet demonstrated measurable β-hydroxybutyrate, with a strong correlation to β-hydroxybutyrate blood levels. These findings may serve as an effective tool for noninvasive monitoring of ketosis in this population. An inverse correlation between serum β-hydroxybutyrate levels and brain tissue N -acetylaspartate suggests that altered amino acid handling contributes to the antiepileptogenic effect of the ketogenic diet.

BHB
:   β-hydroxybutyrate
GABA
:   gamma-aminobutyric acid
KD
:   ketogenic diet
MAD
:   modified Atkins diet" />
<meta name="og-title" property="og:title" content="β-Hydroxybutyrate Detection with Proton MR Spectroscopy in Children with Drug-Resistant Epilepsy on the Ketogenic Diet" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/39/7/1336" />
<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: The ketogenic diet, including both classic and modified forms, is an alternative to antiepileptic medications used in the treatment of drug-resistant epilepsy. We sought to evaluate the utility of proton MR spectroscopy for the detection of β-hydroxybutyrate in a cohort of children with epilepsy treated with the ketogenic diet and to correlate brain parenchymal metabolite ratios obtained from spectroscopy with β-hydroxybutyrate serum concentrations.

MATERIALS AND METHODS: Twenty-three spectroscopic datasets acquired at a TE of 288 ms in children on the ketogenic diet were analyzed with LCModel using a modified basis set that included a simulated β-hydroxybutyrate resonance. Brain parenchymal metabolite ratios were calculated. Metabolite ratios were compared with serum β-hydroxybutyrate concentrations, and partial correlation coefficients were calculated using patient age as a covariate.

RESULTS: β-hydroxybutyrate blood levels were highly correlated to brain β-hydroxybutyrate levels, referenced as either choline, creatine, or N -acetylaspartate. They were inversely but more weakly associated with N -acetylaspartate, regardless of the ratio denominator. No strong concordance with lactate was demonstrated.

CONCLUSIONS: Clinical MR spectroscopy in pediatric patients on the ketogenic diet demonstrated measurable β-hydroxybutyrate, with a strong correlation to β-hydroxybutyrate blood levels. These findings may serve as an effective tool for noninvasive monitoring of ketosis in this population. An inverse correlation between serum β-hydroxybutyrate levels and brain tissue N -acetylaspartate suggests that altered amino acid handling contributes to the antiepileptogenic effect of the ketogenic diet.

BHB
:   β-hydroxybutyrate
GABA
:   gamma-aminobutyric acid
KD
:   ketogenic diet
MAD
:   modified Atkins diet" />
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      <h1 class="highwire-cite-title" id="page-title">β-Hydroxybutyrate Detection with Proton MR Spectroscopy in Children with Drug-Resistant Epilepsy on the Ketogenic Diet</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">J.N. Wright</span>, <span class="highwire-citation-author" data-delta="1">R.P. Saneto</span> and <span class="highwire-citation-author" data-delta="2">S.D. Friedman</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">July 2018,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">39 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(7) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1336-1340; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A5648 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-61855--6492293949" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">J.N. Wright </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (J.N.W., S.D.F.)</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.N.%2BWright%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=Wright%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.N.%2BWright%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/0000-0002-6349-4330" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for J.N. Wright</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">R.P. Saneto </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Department of Neurology, Division of Pediatric Neurology (R.P.S.), University of Washington and Seattle Children's Hospital, Seattle, Washington.</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.P.%2BSaneto%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=Saneto%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.P.%2BSaneto%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/0000-0002-7250-2347" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for R.P. Saneto</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">S.D. Friedman </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (J.N.W., S.D.F.)</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=S.D.%2BFriedman%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=Friedman%20S&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%3AS.D.%2BFriedman%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/0000-0001-8785-7215" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for S.D. Friedman</a></li></ul></div></div></div>  </div>

  
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    <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" xmlns:xhtml="http://www.w3.org/1999/xhtml" class="section ref-list" id="ref-list-1"><h2 class="">References</h2><ol class="cit-list ref-use-labels"><li><span class="ref-label">1.</span><a class="rev-xref-ref" href="#xref-ref-1-1" title="View reference 1. in text" id="ref-1">↵</a><div class="cit ref-cit ref-journal" id="cit-39.7.1336.1" data-doi="10.1111/j.1528-1167.2008.01821.x"><div class="cit-metadata"><ol class="cit-auth-list"><li>
</li><li><span class="cit-auth"><span class="cit-name-surname">Wheless</span>  <span class="cit-name-given-names">JW</span></span></li></ol><cite>. <span class="cit-article-title">History of the ketogenic diet</span>. <abbr class="cit-jnl-abbrev">Epilepsia</abbr> <span class="cit-pub-date">2008</span>;<span class="cit-vol">49</span>(<span class="cit-supplement">Suppl 8</span>):<span class="cit-fpage">3</span>–<span class="cit-lpage">5</span><span class="cit-pub-id-sep cit-pub-id-doi-sep"> </span><span class="cit-pub-id cit-pub-id-doi"><span class="cit-pub-id-scheme-doi">doi:</span>10.1111/j.1528-1167.2008.01821.x</span><span class="cit-pub-id-sep cit-pub-id-pmid-sep"> </span><span class="cit-pub-id cit-pub-id-pmid"><span class="cit-pub-id-scheme-pmid">pmid:</span>19049574</span></cite></div><div class="cit-extra"><a href="/lookup/external-ref?access_num=10.1111/j.1528-1167.2008.01821.x&amp;link_type=DOI" class="cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref"><span>CrossRef</span></a><a href="/lookup/external-ref?access_num=19049574&amp;link_type=MED&amp;atom=%2Fajnr%2F39%2F7%2F1336.atom" class="cit-ref-sprinkles cit-ref-sprinkles-medline"><span>PubMed</span></a></div></div></li><li><span class="ref-label">2.</span><a class="rev-xref-ref" href="#xref-ref-2-1" title="View reference 2. in text" id="ref-2">↵</a><div class="cit ref-cit ref-journal" id="cit-39.7.1336.2" data-doi="10.1016/j.seizure.2010.10.027"><div class="cit-metadata"><ol class="cit-auth-list"><li>
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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 7 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Jul 2018 </div></div>
      
      
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      <div class="highwire-cite-title">β-Hydroxybutyrate Detection with Proton MR Spectroscopy in Children with Drug-Resistant Epilepsy on the Ketogenic Diet</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">J.N.</span> <span class="nlm-surname">Wright</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">R.P.</span> <span class="nlm-surname">Saneto</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">S.D.</span> <span class="nlm-surname">Friedman</span></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">Jul 2018, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">39 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(7) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1336-1340; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A5648 </span></div>
  
  
  
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