Real‐time cardiac metabolism assessed with hyperpolarized [1‐13C]acetate in a large‐animal model
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 [1‐13C]acetate as a promising candidate for a chemical probe to study the myocardial metabolism of a beating heart. The dissolution‐DNP procedure of Na[1‐13C]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[1‐13C]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[1‐13C]acetate kinetics displayed a bimodal shape: [1‐13C]acetyl carnitine (AcC) was detected in a slice covering the cardiac volume, and the signal of 13C‐acetate and 13C‐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 [1‐13C]acetate to [1‐13C]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 [1‐13C]acetate to study the myocardial conversion of [1‐13C]acetate in [1‐13C]acetyl‐carnitine generated by acetyltransferase in h...
Source: Contrast Media and Molecular Imaging - Category: Radiology Authors: Alessandra Flori, Matteo Liserani, Francesca Frijia, Giulio Giovannetti, Vincenzo Lionetti, Valentina Casieri, Vincenzo Positano, Giovanni Donato Aquaro, Fabio A. Recchia, Maria Filomena Santarelli, Luigi Landini, Jan Henrik Ardenkjaer‐Larsen, Luca Meni Tags: Full Paper Source Type: research