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Abstract Metronidazole and nimorazole are antibiotics of a nitroimidazole group which also may be potentially utilized as hypoxia radiosensitizers for the treatment of cancerous tumors. Hyperpolarization of¹⁵N nuclei in these compounds using SABRE‐SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei) approach provides dramatic enhancement of detection sensitivity of these analytes using magnetic resonance spectroscopy and imaging. Methanol‐d₄is conventionally employed as a solvent in SABRE hyperpolarization process. Herein, we investigate SABRE‐SHEATH hyperpolarization of isotopically labeled [¹⁵N₃]metronidazole and [¹⁵N₃]nimorazole in nondeuterated methanol and ethanol solvents. Optimization of such hyperpolarization parameters as polarization transfer magnetic field, temperature, parahydrogen flow rate and pressure allowed us to obtain an average¹⁵N polarization of up to 7.2–7.4 % for both substrates. The highest¹⁵N polarizations were observed in methanol‐d₄for [¹⁵N₃]metronidazole and in ethanol for [¹⁵N₃]nimorazole. At a clinically relevant magnetic field of 1.4 T the¹⁵N nuclei of these substrates possess long characteristic hyperpolarization lifetimes (T₁) of ca. 1 to ca. 7 min. This study represents a major step toward SABRE in more biocompatible solvents, such as ethanol, and also paves the way for future utilization of these hyperpolarized nitroimidazoles as molecular contrast agents for MRI visualization of tumors. 

The feasibility of ultrafast (1.7 s) ventilation MRI with a 1 × 1 × 50 mm³voxel size is demonstrated using hyperpolarized propane gas contrast agent in excised rabbit lungs on a 0.35 T clinical MRI scanner without any scanner modification. 

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 Hyperpolarized¹²⁹Xe gas was FDA‐approved as an inhalable contrast agent for magnetic resonance imaging of a wide range of pulmonary diseases in December 2022. Despite the remarkable success in clinical research settings, the widespread clinical translation of HP¹²⁹Xe gas faces two critical challenges: the high cost of the relatively low‐throughput hyperpolarization equipment and the lack of¹²⁹Xe imaging capability on clinical MRI scanners, which have narrow‐bandwidth electronics designed only for proton (¹H) imaging. To solve this translational grand challenge of gaseous hyperpolarized MRI contrast agents, here we demonstrate the utility of batch‐mode production of proton‐hyperpolarized diethyl ether gas via heterogeneous pairwise addition of parahydrogen to ethyl vinyl ether. An approximately 0.1‐liter bolus of hyperpolarized diethyl ether gas was produced in 1 second and injected in excised rabbit lungs. Lung ventilation imaging was performed using sub‐second 2D MRI with up to 2×2 mm²in‐plane resolution using a clinical 0.35 T MRI scanner without any modifications. This feasibility demonstration paves the way for the use of inhalable diethyl ether as a gaseous contrast agent for pulmonary MRI applications using any clinical MRI scanner.