Dataset Information

Real-time cardiac metabolism assessed with hyperpolarized [1-(13) C]acetate in a large-animal model.

ABSTRACT: Dissolution-dynamic nuclear polarization (dissolution-DNP) for magnetic resonance (MR) spectroscopic imaging has recently emerged as a novel technique for noninvasive studies of the metabolic fate of biomolecules in vivo. Since acetate is the most abundant extra- and intracellular short-chain fatty acid, we focused on [1-(13) C]acetate as a promising candidate for a chemical probe to study the myocardial metabolism of a beating heart. The dissolution-DNP procedure of Na[1-(13) C]acetate for in vivo cardiac applications with a 3 T MR scanner was optimized in pigs during bolus injection of doses of up to 3 mmol. The Na[1-(13) C]acetate formulation was characterized by a liquid-state polarization of 14.2% and a T1Eff in vivo of 17.6 ± 1.7 s. In vivo Na[1-(13) C]acetate kinetics displayed a bimodal shape: [1-(13) C]acetyl carnitine (AcC) was detected in a slice covering the cardiac volume, and the signal of (13) C-acetate and (13) C-AcC was modeled using the total area under the curve (AUC) for kinetic analysis. A good correlation was found between the ratio AUC(AcC)/AUC(acetate) and the apparent kinetic constant of metabolic conversion, from [1-(13) C]acetate to [1-(13) C]AcC (kAcC ), divided by the AcC longitudinal relaxation rate (r1 ). Our study proved the feasibility and the limitations of administration of large doses of hyperpolarized [1-(13) C]acetate to study the myocardial conversion of [1-(13) C]acetate in [1-(13) C]acetyl-carnitine generated by acetyltransferase in healthy pigs.

SUBMITTER: Flori A

PROVIDER: S-EPMC4362963 | biostudies-literature | 2015 May-Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Real-time cardiac metabolism assessed with hyperpolarized [1-(13) C]acetate in a large-animal model.

Flori Alessandra A Liserani Matteo M Frijia Francesca F Giovannetti Giulio G Lionetti Vincenzo V Casieri Valentina V Positano Vincenzo V Aquaro Giovanni Donato GD Recchia Fabio A FA Santarelli Maria Filomena MF Landini Luigi L Ardenkjaer-Larsen Jan Henrik JH Menichetti Luca L

Contrast media & molecular imaging 20140908 3

Dissolution-dynamic nuclear polarization (dissolution-DNP) for magnetic resonance (MR) spectroscopic imaging has recently emerged as a novel technique for noninvasive studies of the metabolic fate of biomolecules in vivo. Since acetate is the most abundant extra- and intracellular short-chain fatty acid, we focused on [1-(13) C]acetate as a promising candidate for a chemical probe to study the myocardial metabolism of a beating heart. The dissolution-DNP procedure of Na[1-(13) C]acetate for in v ...[more]

PMID: 25201079

Similar Datasets

Project description:BackgroundThe heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) 13C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP 13C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy.MethodsWe developed and applied methods for whole-heart imaging of 13C-pyruvate, 13C-lactate and 13C-bicarbonate, following intravenous administration of [1-13C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated 13C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load).ResultsWe demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6 × 6 × 21 mm3 (13C-pyruvate) and 12 × 12 × 21 mm3 (13C-lactate, 13C-bicarbonate). 13C-pyruvate and 13C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial 13C-pyruvate-SNR, 13C-lactate-SNR, 13C-bicarbonate-SNR, 13C-lactate/pyruvate ratio, 13C-pyruvate-to-lactate conversion rate, kPL, and 13C-pyruvate-to-bicarbonate conversion rate, kPB, all had statistically significant increases following oral glucose challenge. kPB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant.ConclusionsWe demonstrate first-in-human regional quantifications of cardiac metabolism by HP 13C-pyruvate MRI that aims to reflect LDH and PDH activity.

Dataset Information

Real-time cardiac metabolism assessed with hyperpolarized [1-(13) C]acetate in a large-animal model.

Publications

Real-time cardiac metabolism assessed with hyperpolarized [1-(13) C]acetate in a large-animal model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets