Mapping of lactate and N-acetyl-L-aspartate predicts infarction during acute focal ischemia: In vivo 1H magnetic resonance spectroscopy in rats

Toshihiro Higuchi, Erik J. Fernandez, Andrew A. Maudsley, Hiroaki Shimizu, Michael W. Weiner, Philip R. Weinstein

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


THE TIME COURSE, anatomic distribution, and extent of changes in cerebral lactate, N-acetyl-L-aspartate (NAA), and other metabolite levels were determined by three-dimensional in vivo 1H magnetic resonance spectroscopy and single-voxel spectral analysis after middle cerebral artery occlusion in rats. Increased lactate was detected in the central ischemic region within 1.3 hours after the onset of permanent occlusion (n = 22) or 0.5 hour after the onset of 1 hour of temporary occlusion and then reperfusion (n = 8). Permanent occlusion resulted in persistent lactate elevation and a 25.4 ± 4.1% reduction in the NAA peak after 1.3 hours; NAA was almost completely depleted after 24 hours. Results also demonstrated delayed depletion of all other magnetic resonance spectroscopy-visible 1H metabolites, including creatine, choline, and glutamate, after permanent occlusion. After 1 hour of temporary focal ischemia, lactate returned to nearly normal levels within 0.4 hour after the onset of reperfusion; at 72 hours, a recurrent increase in lactate and a new decrease in NAA were observed, suggesting delayed tissue injury. Histological analysis, performed in 10 rats, demonstrated infarcts that corresponded in distribution to regions of NAA depletion at 72 hours. These findings indicate that lactate elevation is a sensitive early marker of ischemia; however, temporary recovery of lactate accumulation after reperfusion did not predict sustained metabolic recovery. In contrast, NAA depletion within 1.3 hours after the onset of ischemia identified central ischemic regions that were destined for infarction. Potential clinical applications include selection and monitoring of therapeutic intervention, as well as prediction of outcome, in patients with acute stroke.

Original languageEnglish (US)
Pages (from-to)121-130
Number of pages10
Issue number1
StatePublished - Jan 1996
Externally publishedYes


  • Cerebral ischemia
  • Lactate
  • N-Acetyl-L-aspartate
  • Proton MR spectroscopy
  • Rat brain
  • Spectroscopic imaging

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery


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