Functional activation of pyruvate dehydrogenase in human brain using hyperpolarized [1-13C]pyruvate

Details

• Alternative Title:
  Magn Reson Med
• Personal Author:
  Zaidi, Maheen ; Ma, Junjie ; Thomas, Binu P. ; Peña, Salvador ; Harrison, Crystal E. ; Chen, Jun ; Lin, Sung-Han ; Derner, Kelley A. ; Baxter, Jeannie D. ; Liticker, Jeff ; Malloy, Craig R. ; Bartnik-Olson, Brenda ; Park, Jae Mo
• Description:
  Purpose:
  
  Pyruvate, produced from either glucose, glycogen, or lactate, is the dominant precursor of cerebral oxidative metabolism. Pyruvate dehydrogenase (PDH) flux is a direct measure of cerebral mitochondrial function and metabolism. Detection of [13C]bicarbonate in the brain from hyperpolarized [1-13C]pyruvate using 13C MRI provides a unique opportunity for assessing PDH flux in vivo. This study is to assess changes in cerebral PDH flux in response to visual stimuli using in vivo13C MRS with hyperpolarized [1-13C]pyruvate.
  
  Methods:
  
  From seven sedentary adults in good general health, time-resolved [13C]bicarbonate production was measured in the brain using 90° flip angles with minimal perturbation of its precursors, [1-13C]pyruvate and [1-13C]lactate, to test the hypothesis that the appearance of [13C]bicarbonate signals in the brain reflects the metabolic changes associated with neuronal activation. With a separate group of healthy participants (n = 3), the likelihood of the bolus-injected [1-13C]pyruvate being converted to [1-13C]lactate prior to decarboxylation was investigated by measuring [13C]bicarbonate production with and without [1-13C]lactate saturation.
  
  Results:
  
  In the course of visual stimulation, the measured [13C]bicarbonate signal normalized to the total 13C signal in the visual cortex increased by 17.1 ± 15.9% (P = 0.017) whereas no significant change was detected in [1-13C]lactate. 1H BOLD fMRI confirmed the regional activation in the visual cortex with the stimuli. Lactate saturation decreased bicarbonate-to-pyruvate ratio by 44.4 ± 9.3% (P < 0.01).
  
  Conclusion:
  
  We demonstrated the utility of 13C MRS with hyperpolarized [1-13C]pyruvate for assessing the activation of cerebral PDH flux via the detection of [13C]bicarbonate production.
  
  
• Subjects:
  Adult Bicarbonates Brain Carbon Isotopes Humans Lactic Acid Oxidoreductases Pyruvic Acid
• Keywords:
  Bicarbonate Brain Activation Dissolution Dynamic Nuclear Polarization Functional Magnetic Resonance Spectroscopy Hyperpolarized Pyruvate Pyruvate Dehydrogenase
• Source:
  Magn Reson Med. 91(5):1822-1833
• Pubmed ID:
  38265104
• Pubmed Central ID:
  PMC10950523
• Document Type:
  Journal Article
• Funding:
  S10 RR029119/RR/NCRR NIH HHSUnited States/ ; S10 OD018468/CD/ODCDC CDC HHSUnited States/ ; P30 DK127984/DK/NIDDK NIH HHSUnited States/ ; S10 OD018468/OD/NIH HHSUnited States/ ; P41 EB015908/EB/NIBIB NIH HHSUnited States/ ; R01 NS107409/NS/NINDS NIH HHSUnited States/
• Volume:
  91
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:2a60c53fcad18aa8bca157b0c275ab267700f68501ecb9c6eaf642229f74866944f00c07a7f726165fe8c548226df3631c4b49fa1642999794313b086ac87b9f
• Download URL:
  https://stacks.cdc.gov/view/cdc/151794/cdc_151794_DS1.pdf
• File Type:
  [PDF - 1.25 MB ]