title: Assessing inflammatory liver injury in an acute CCl4 model using dynamic 3D metabolic imaging of hyperpolarized [1-(13)C]pyruvate.
abstract: To facilitate diagnosis and staging of liver disease, sensitive and non-invasive methods for the measurement of liver metabolism are needed. This study used hyperpolarized (13)C-pyruvate to assess metabolic parameters in a CCl4 model of liver damage in rats. Dynamic 3D (13)C chemical shift imaging data from a volume covering kidney and liver were acquired from 8 control and 10 CCl4-treated rats. At 12 time points at 5 s temporal resolution, we quantified the signal intensities and established time courses for pyruvate, alanine, and lactate. These measurements were compared with standard liver histology and an alanine transaminase (ALT) enzyme assay using liver tissue from the same animals. All CCl4-treated but none of the control animals showed histological liver damage and elevated ALT enzyme levels. In agreement with these results, metabolic imaging revealed an increased alanine/pyruvate ratio in liver of CCl4-treated rats, which is indicative of elevated ALT activity. Similarly, lactate/pyruvate ratios were higher in CCl4-treated compared with control animals, demonstrating the presence of inflammation. No significant differences in metabolite ratios were observed in kidney or vasculature. Thus this work shows that metabolic imaging using (13)C-pyruvate can be a successful tool to non-invasively assess liver damage in vivo.
authors.affiliation: SRI International, Neuroscience Program, Menlo Park, CA, USA.|Stanford University, Department of Radiology, Stanford, CA, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Josan
authors.affiliation: Stanford University, Department of Radiology, Stanford, CA, USA.|San Francisco State University, Department of Chemistry and Biochemistry, San Francisco, CA, USA.
authors.forename: Kelvin
authors.initials: K
authors.lastname: Billingsley
authors.affiliation: SRI International, Neuroscience Program, Menlo Park, CA, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Orduna
authors.affiliation: Stanford University, Department of Radiology, Stanford, CA, USA.
authors.forename: Jae Mo
authors.initials: JM
authors.lastname: Park
authors.affiliation: Stanford University, Department of Comparative Medicine, Stanford, CA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Luong
authors.affiliation: University of Maryland, Department of Animal and Avian Sciences, College Park, MD, USA.
authors.forename: Liqing
authors.initials: L
authors.lastname: Yu
authors.affiliation: GE Healthcare Applied Sciences Laboratory, Menlo Park, CA, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Hurd
authors.affiliation: SRI International, Neuroscience Program, Menlo Park, CA, USA.|Stanford University, Department of Psychiatry and Behavioral Sciences, Stanford, CA, USA.
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
authors.affiliation: Stanford University, Department of Radiology, Stanford, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Spielman
authors.affiliation: SRI International, Neuroscience Program, Menlo Park, CA, USA.|Stanford University, Department of Radiology, Stanford, CA, USA.|University of Maryland, Department of Diagnostic Radiology and Nuclear Medicine, Baltimore, MD, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
mesh_terms: D000409:Alanine / Q000378:metabolism*; D000818:Animals; D002251:Carbon Tetrachloride; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006505:Hepatitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D019289:Pyruvic Acid / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019275:Radiopharmaceuticals; D019289:Pyruvic Acid; D002251:Carbon Tetrachloride; D000409:Alanine
keywords: CCl4; hyperpolarized 13C; inflammation; liver