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.