title: Assessment of real-time myocardial uptake and enzymatic conversion of hyperpolarized [1-¹³C]pyruvate in pigs using slice selective magnetic resonance spectroscopy.
abstract: Hyperpolarization of ¹³C-labeled energy substrates enables the noninvasive detection and mapping of metabolic activity, in vivo, with magnetic resonance spectroscopy (MRS). Therefore, hyperpolarization and ¹³C MRS can potentially become a powerful tool to study the physiology of organs such as the heart, through the quantification of kinetic patterns under both normal and pathological conditions. In this study we assessed myocardial uptake and metabolism of hyperpolarized [1-¹³C]pyruvate in anesthetized pigs. Pyruvate metabolism was studied at baseline and during dobutamine-induced stimulation. We applied a numerical approach for spectral analysis and kinetic fitting (LSFIT/KIMOfit), making a comparison with a well-known jMRUI/AMARES analysis and γ-variate function, and we estimated the apparent conversion rate of hyperpolarized [1-¹³C]pyruvate into its downstream metabolites [1-¹³C]lactate, [1-¹³C]alanine and [¹³C]bicarbonate in a 3 T MR scanner. We detected an increase in the apparent kinetic constants (k(PX) ) for bicarbonate and lactate of two-fold during dobutamine infusion. These data correlate with the double product (rate-pressure product), an indirect parameter of cardiac oxygen consumption: we observed an increase in value by 46 ± 11% during inotropic stress. The proposed approach might be applied to future studies in models of cardiac disease and/or for the assessment of the pharmacokinetic properties of suitable ¹³C-enriched tracers for MRS.
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Menichetti
authors.forename: Francesca
authors.initials: F
authors.lastname: Frijia
authors.forename: Alessandra
authors.initials: A
authors.lastname: Flori
authors.forename: Florian
authors.initials: F
authors.lastname: Wiesinger
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lionetti
authors.forename: Giulio
authors.initials: G
authors.lastname: Giovannetti
authors.forename: Giovanni Donato
authors.initials: GD
authors.lastname: Aquaro
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
authors.forename: Jan Henrik
authors.initials: JH
authors.lastname: Ardenkjaer-Larsen
authors.forename: Maria Filomena
authors.initials: MF
authors.lastname: Santarelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Lombardi
mesh_terms: D000409:Alanine / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001794:Blood Pressure; D002247:Carbon Isotopes / Q000032:analysis; D003199:Computer Systems; D004280:Dobutamine; D006019:Glycolysis; D006339:Heart Rate; D007773:Lactates / Q000378:metabolism; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D008956:Models, Chemical; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D034421:Sus scrofa; D013552:Swine
chemical_list: D001639:Bicarbonates; D002247:Carbon Isotopes; D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D004280:Dobutamine; D019289:Pyruvic Acid; D000410:Alanine Transaminase; D000409:Alanine