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Abstract Hyperpolarized¹³C MRI visualizes real-time metabolic processes in vivo. In this study, we achieved high¹³C polarization in situ in the bore of an MRI system for precursor molecules of most widely employed hyperpolarized agents: [1-¹³C]acetate and [1-¹³C]pyruvate ethyl esters in their perdeuterated forms, enhancing hyperpolarization lifetimes, hyperpolarized toP_13C ≈ 28% at 80 mM concentration andP_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-d₆at 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, where¹³C MRI is performed. We exemplified the utility of the design with sub-second in situ¹³C MRI of ethyl [1-¹³C]pyruvate-d₆. 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 rapid¹³C hyperpolarization of these metabolite precursors in an MRI system with minimal additional hardware, promising to enhance future throughput and access to hyperpolarized¹³C MRI. 

Abstract The signal amplification by reversible exchange process (SABRE) enhances NMR signals by unlocking hidden polarization in parahydrogen through interactions with to-be-hyperpolarized substrate molecules when both are transiently bound to an Ir-based organometallic catalyst. Recent efforts focus on optimizing polarization transfer from parahydrogen-derived hydride ligands to the substrate in SABRE. However, this requires quantitative information on ligand exchange rates, which common NMR techniques struggle to provide. Here, we introduce an experimental spin order transfer sequence, with readout occurring at¹⁵N nuclei directly interacting with the catalyst. Enhanced¹⁵N NMR signals overcome sensitivity challenges, encoding substrate dissociation rates. This methodology enables robust data fitting to ligand exchange models, yielding substrate dissociation rate constants with higher precision than classical 1D and 2D¹H NMR approaches. This refinement improves the accuracy of key activation enthalpy ΔH^‡and entropy ΔS^‡estimates. Furthermore, the higher chemical shift dispersion provided by enhanced¹⁵N NMR reveals the kinetics of substrate dissociation for acetonitrile and metronidazole, previously inaccessible via¹H NMR due to small chemical shift differences between free and Ir-bound substrates. The presented approach can be successfully applied not only to isotopically enriched substrates but also to compounds with natural abundance of the to-be-hyperpolarized heteronuclei. 

Abstract Zero- to ultralow-field (ZULF) nuclear magnetic resonance (NMR) is an emerging tool for precision chemical analysis. In this work, we study dynamic processes and investigate the influence of chemical exchange on ZULF NMRJ-spectra. We develop a computational approach that allows quantitative calculation ofJ-spectra in the presence of chemical exchange and apply it to study aqueous solutions of [¹⁵N]ammonium (¹⁵N$${\mathrm{H}}_4^ +$$ $H_4^{+}$) as a model system. We show that pH-dependent chemical exchange substantially affects theJ-spectra and, in some cases, can lead to degradation and complete disappearance of the spectral features. To demonstrate potential applications of ZULF NMR for chemistry and biomedicine, we show a ZULF NMR spectrum of [2-¹³C]pyruvic acid hyperpolarized via dissolution dynamic nuclear polarization (dDNP). We foresee applications of affordable and scalable ZULF NMR coupled with hyperpolarization to study chemical exchange phenomena in vivo and in situations where high-field NMR detection is not possible to implement.