Abstract

Purpose: Disorders of brain energy metabolism and neurotransmitter recycling have been implicated in multiple neurological conditions. 13C magnetic resonance spectroscopy (13C MRS) during intravenous administration of 13C-labeled compounds has been used to measure turnover rates of brain metabolites. This approach, however, requires prolonged infusion inside the magnet. Proton decoupling is typically required but may be difficult to implement with standard equipment. We examined an alternative approach to monitor glucose metabolism in the human brain. Methods: 13C-enriched glucose was infused in healthy subjects outside the magnet to a steady-state level of 13C enrichment. Subsequently, the subjects were scanned at 7T for 60min without 1H decoupling. Metabolic modeling was used to calculate anaplerosis. Results: Biomarkers of energy metabolism and anaplerosis were detected. The glutamate C5 doublet provided information about glucose-derived acetyl-coenzyme A flux into the tricarboxylic acid (TCA) cycle via pyruvate dehydrogenase, and the bicarbonate signal reflected overall TCA cycle activity. The glutamate C1/C5 ratio is sensitive to anaplerosis. Conclusion: Brain 13C MRS at 7T provides information about glucose oxidation and anaplerosis without the need of prolonged 13C infusions inside the scanner and without technical challenges of 1H decoupling, making it a feasible approach for clinical research. Magn Reson Med, 2017.

Original languageEnglish (US)
JournalMagnetic Resonance in Medicine
DOIs
StateAccepted/In press - 2017

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Glucose
Citric Acid Cycle
Magnets
Brain
Energy Metabolism
Glutamic Acid
Magnetic Resonance Spectroscopy
Acetyl Coenzyme A
Recycling
Brain Diseases
Bicarbonates
Pyruvic Acid
Intravenous Administration
Neurotransmitter Agents
Protons
Healthy Volunteers
Oxidoreductases
Biomarkers
Equipment and Supplies
Research

Keywords

  • 7 Tesla
  • C bicarbonate
  • C MRS
  • Brain energy metabolism
  • TCA cycle

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Oxidation of [U-13C]glucose in the human brain at 7T under steady state conditions. / Cheshkov, Sergey; Dimitrov, Ivan E.; Jakkamsetti, Vikram; Good, Levi; Kelly, Dorothy; Rajasekaran, Karthik; Deberardinis, Ralph J.; Pascual, Juan M.; Sherry, A. Dean; Malloy, Craig R.

In: Magnetic Resonance in Medicine, 2017.

Research output: Contribution to journalArticle

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abstract = "Purpose: Disorders of brain energy metabolism and neurotransmitter recycling have been implicated in multiple neurological conditions. 13C magnetic resonance spectroscopy (13C MRS) during intravenous administration of 13C-labeled compounds has been used to measure turnover rates of brain metabolites. This approach, however, requires prolonged infusion inside the magnet. Proton decoupling is typically required but may be difficult to implement with standard equipment. We examined an alternative approach to monitor glucose metabolism in the human brain. Methods: 13C-enriched glucose was infused in healthy subjects outside the magnet to a steady-state level of 13C enrichment. Subsequently, the subjects were scanned at 7T for 60min without 1H decoupling. Metabolic modeling was used to calculate anaplerosis. Results: Biomarkers of energy metabolism and anaplerosis were detected. The glutamate C5 doublet provided information about glucose-derived acetyl-coenzyme A flux into the tricarboxylic acid (TCA) cycle via pyruvate dehydrogenase, and the bicarbonate signal reflected overall TCA cycle activity. The glutamate C1/C5 ratio is sensitive to anaplerosis. Conclusion: Brain 13C MRS at 7T provides information about glucose oxidation and anaplerosis without the need of prolonged 13C infusions inside the scanner and without technical challenges of 1H decoupling, making it a feasible approach for clinical research. Magn Reson Med, 2017.",
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author = "Sergey Cheshkov and Dimitrov, {Ivan E.} and Vikram Jakkamsetti and Levi Good and Dorothy Kelly and Karthik Rajasekaran and Deberardinis, {Ralph J.} and Pascual, {Juan M.} and Sherry, {A. Dean} and Malloy, {Craig R.}",
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T1 - Oxidation of [U-13C]glucose in the human brain at 7T under steady state conditions

AU - Cheshkov, Sergey

AU - Dimitrov, Ivan E.

AU - Jakkamsetti, Vikram

AU - Good, Levi

AU - Kelly, Dorothy

AU - Rajasekaran, Karthik

AU - Deberardinis, Ralph J.

AU - Pascual, Juan M.

AU - Sherry, A. Dean

AU - Malloy, Craig R.

PY - 2017

Y1 - 2017

N2 - Purpose: Disorders of brain energy metabolism and neurotransmitter recycling have been implicated in multiple neurological conditions. 13C magnetic resonance spectroscopy (13C MRS) during intravenous administration of 13C-labeled compounds has been used to measure turnover rates of brain metabolites. This approach, however, requires prolonged infusion inside the magnet. Proton decoupling is typically required but may be difficult to implement with standard equipment. We examined an alternative approach to monitor glucose metabolism in the human brain. Methods: 13C-enriched glucose was infused in healthy subjects outside the magnet to a steady-state level of 13C enrichment. Subsequently, the subjects were scanned at 7T for 60min without 1H decoupling. Metabolic modeling was used to calculate anaplerosis. Results: Biomarkers of energy metabolism and anaplerosis were detected. The glutamate C5 doublet provided information about glucose-derived acetyl-coenzyme A flux into the tricarboxylic acid (TCA) cycle via pyruvate dehydrogenase, and the bicarbonate signal reflected overall TCA cycle activity. The glutamate C1/C5 ratio is sensitive to anaplerosis. Conclusion: Brain 13C MRS at 7T provides information about glucose oxidation and anaplerosis without the need of prolonged 13C infusions inside the scanner and without technical challenges of 1H decoupling, making it a feasible approach for clinical research. Magn Reson Med, 2017.

AB - Purpose: Disorders of brain energy metabolism and neurotransmitter recycling have been implicated in multiple neurological conditions. 13C magnetic resonance spectroscopy (13C MRS) during intravenous administration of 13C-labeled compounds has been used to measure turnover rates of brain metabolites. This approach, however, requires prolonged infusion inside the magnet. Proton decoupling is typically required but may be difficult to implement with standard equipment. We examined an alternative approach to monitor glucose metabolism in the human brain. Methods: 13C-enriched glucose was infused in healthy subjects outside the magnet to a steady-state level of 13C enrichment. Subsequently, the subjects were scanned at 7T for 60min without 1H decoupling. Metabolic modeling was used to calculate anaplerosis. Results: Biomarkers of energy metabolism and anaplerosis were detected. The glutamate C5 doublet provided information about glucose-derived acetyl-coenzyme A flux into the tricarboxylic acid (TCA) cycle via pyruvate dehydrogenase, and the bicarbonate signal reflected overall TCA cycle activity. The glutamate C1/C5 ratio is sensitive to anaplerosis. Conclusion: Brain 13C MRS at 7T provides information about glucose oxidation and anaplerosis without the need of prolonged 13C infusions inside the scanner and without technical challenges of 1H decoupling, making it a feasible approach for clinical research. Magn Reson Med, 2017.

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