title: In vivo assessment of intracellular redox state in rat liver using hyperpolarized [1-13C]Alanine.
abstract: The intracellular lactate to pyruvate concentration ratio is a commonly used tissue assay biomarker of redox, being proportional to free cytosolic [NADH]/[NAD+]. In this study, we assessed the use of hyperpolarized [1-13C]alanine and the subsequent detection of the intracellular products of [1-13C]pyruvate and [1-13C]lactate as a useful substrate for assessing redox levels in the liver in vivo.
  
  
  
  Animal experiments were conducted to measure in vivo metabolism at baseline and after ethanol infusion. A solution of 80-mM hyperpolarized [1-13C]alanine was injected intravenously at baseline (n = 8) and 45 min after ethanol infusion (n = 4), immediately followed by the dynamic acquisition of13C MRS spectra.
  
  
  
  In vivo rat liver spectra showed peaks from [1-13C] alanine and the products of [1-13C]lactate, [1-13C]pyruvate, and13C-bicarbonate. A significantly increased13C-lactate/13C-pyruvate ratio was observed after ethanol infusion (8.46 ± 0.58 at baseline versus 13.58 ± 0.69 after ethanol infusion; P < 0.001) consistent with the increased NADH produced by liver metabolism of ethanol to acetaldehyde and then acetate. A decrease in13C-bicarbonate production was also noted, potentially reflecting ethanol-induced mitochondrial redox changes.
  
  
  
  A method to measure in vivo tissue redox using hyperpolarized [1-13C]alanine is presented, with the validity of the proposed13C-pyruvate/13C-lactate metric tested using an ethanol challenge to alter liver redox state. Magn Reson Med 77:1741-1748, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|Department of Radiology, Stanford University, Stanford, California, USA.
authors.forename: Jae Mo
authors.initials: JM
authors.lastname: Park
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Chalermchai
authors.initials: C
authors.lastname: Khemtong
authors.affiliation: Department of Radiology, Stanford University, Stanford, California, USA.
authors.forename: Shie-Chau
authors.initials: SC
authors.lastname: Liu
authors.affiliation: Applied Science Laboratory, GE Healthcare, Menlo Park, California, USA.
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Hurd
authors.affiliation: Department of Radiology, Stanford University, Stanford, California, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Spielman
mesh_terms: D000409:Alanine / Q000737:chemistry*; D000818:Animals; D002247:Carbon Isotopes / Q000737:chemistry*; D003600:Cytosol / Q000378:metabolism; D000431:Ethanol / Q000737:chemistry; D008099:Liver / Q000000981:diagnostic imaging* / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D049268:Positron-Emission Tomography; D019289:Pyruvic Acid / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
chemical_list: D002247:Carbon Isotopes; D000431:Ethanol; D019289:Pyruvic Acid; D000409:Alanine; D010100:Oxygen
keywords: alanine; dynamic nuclear polarization; hyperpolarized; liver; redox