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Abstract #4323

Assessment of Dichloroacetate Effect on TCA Cycle Metabolism in Rat Brain in vivo Using MRSI of Hyperpolarized [2-13C]Pyruvate

Jae Mo Park1, 2, Sonal Josan2, 3, Yi-Fen Yen4, Ralph E. Hurd4, Daniel M. Spielman, 12, Dirk Mayer2, 3

1Electrical Engineering, Stanford University, Stanford, CA - California, United States; 2Radiology, Stanford University, Stanford, CA - California, United States; 3Neuroscience Program, SRI International, Menlo Park, CA - California, United States; 4Applied Science Laboratory, GE Healthcare, Menlo Park, CA - California, United States

Although both [2-13C]Pyr and [1, 2-13C]Pyr have been successfully used as substrates to assess mitochondrial function in cardiac metabolism by measuring products such as [5-13C]glutamate (Glu), which is generated from the tricarboxylic acid (TCA) cycle intermediate alpha-ketoglutarate, the application of [2-13C]Pyr in studies of brain metabolism has been limited as Lac was the only metabolic product that could be detected so far. The aim of this work was to exploit the unsaturable component of Pyr transport into the brain by using a high [2-13C]Pyr concentration and measure the effects on brain metabolism when the Pyr dehydrogenase (PDH) flux is up-regulated by dichloroacetate (DCA), a Pyr dehydrogenase kinase (PDK) inhibitor.

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Keywords

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