Rapid in situ carbon-13 hyperpolarization and imaging of acetate and pyruvate esters without external polarizer

Hyperpolarized 13 C MRI visualizes real-time metabolic processes in vivo. In this study, we achieved high 13 C polarization in situ in the bore of an MRI system for precursor molecules of most widely employed hyperpolarized agents: [1- 13 C]acetate and [1- 13 C]pyruvate ethyl esters in their perdeuterated forms, enhancing hyperpolarization lifetimes, hyperpolarized to P 13C ≈ 28% at 80 mM concentration and P 13C ≈ 19% at 10 mM concentration, respectively. Using vinyl esters as unsaturated Parahydrogen-Induced Polarization via Side-Arm Hydrogenation (PHIP-SAH) precursors and our novel polarization setup, we achieved these hyperpolarization levels by fast side-arm hydrogenation in acetone- d 6 at elevated temperatures (up to 90°C) and hydrogenation pressures (up to 32 bar). We optimized the hyperpolarization process, reducing it to under 10 s, and employed advanced pulse sequences to enhance the polarization transfer efficiency. The hyperpolarization system has a small footprint, allowing it to be positioned in the same magnet, where 13 C MRI is performed. We exemplified the utility of the design with sub-second in situ 13 C MRI of ethyl [1- 13 C]pyruvate- d 6 . However, challenges remain in side-arm cleavage and purification in the MRI system to extract highly polarized aqueous agent solutions. Our results showcase efficient and rapid 13 C hyperpolarization of these metabolite precursors in an MRI system with minimal additional hardware, promising to enhance future throughput and access to hyperpolarized 13 C MRI. Hyperpolarized 13 C MRI visualizes real-time metabolic processes in vivo, however, external polarizers are commonly required to produce hyperpolarized metabolites. Here, using a parahydrogen-based approach, the authors achieved up to 30% 13 C polarization in situ in an MRI system for precursor molecules [1- 13 C]acetate and [1- 13 C]pyruvate ethyl esters in their perdeuterated forms, potentially facilitating future metabolic imaging applications.