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The signal enhancement provided by the hyperpolarization of nuclear spins of metabolites is a promising technique for diagnostic magnetic resonance imaging (MRI). To date, most 13 C-contrast agents are hyperpolarized utilizing a complex or cost-intensive polarizer. Recently, the in situ para hydrogen-induced 13 C hyperpolarization was demonstrated. Hydrogenation, spin order transfer (SOT) by a pulsed NMR sequence, in vivo administration, and detection was achieved within the magnet bore of a 7 Tesla MRI system. So far, the hyperpolarization of the xenobiotic molecule 1- 13 C-hydroxyethylpropionate (HEP) and the biomolecule 1- 13 C-succinate (SUC) through the PH-INEPT+ sequence and a SOT scheme proposed by Goldman et al. , respectively, was shown. Here, we investigate further the hyperpolarization of SUC at 7 Tesla and study the performance of two additional SOT sequences. Moreover, we present first results of the hyperpolarization at high magnetic field of 1- 13 C-phospholactate (PLAC), a derivate to obtain the metabolite lactate, employing the PH-INEPT+ sequence. For SUC and PLAC, 13 C polarizations of about 1–2% were achieved within seconds and with minimal equipment. Effects that potentially may explain loss of 13 C polarization have been identified, i.e. low hydrogenation yield, fast T 1 / T 2 relaxation and the rarely considered 13 C isotope labeling effect. 

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.

 

Metabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate is becoming a non‐invasive technique for diagnosing, staging, and monitoring response to treatment in cancer and other diseases. The clinically established method for producing HP pyruvate, dissolution dynamic nuclear polarization, however, is rather complex and slow. Signal Amplification By Reversible Exchange (SABRE) is an ultra‐fast and low‐cost method based on fast chemical exchange. Here, for the first time, we demonstrate not only in vivo utility, but also metabolic MRI with SABRE. We present a novel routine to produce aqueous HP [1‐¹³C]pyruvate‐d₃for injection in 6 minutes. The injected solution was sterile, non‐toxic, pH neutral and contained ≈30 mM [1‐¹³C]pyruvate‐d₃polarized to ≈11 % (residual 250 mM methanol and 20 μM catalyst). It was obtained by rapid solvent evaporation and metal filtering, which we detail in this manuscript. This achievement makes HP pyruvate MRI available to a wide biomedical community for fast metabolic imaging of living organisms.

 

Die metabolische Magnetresonanztomographie (MRT) mit hyperpolarisiertem (HP) Pyruvat wird zu einer vielversprechenden, nicht‐invasiven Technik für die Diagnose, die Charakterisierung und die Überwachung bei Behandlung von Krebs, sowie bei anderen Erkrankungen. Die klinisch etablierte Methode zur Herstellung HP‐Pyruvats, die dynamische Kernpolarisation, ist jedoch ein komplexes und langwieriges Verfahren. Die Signalverstärkung durch reversiblen Austausch (SABRE) ist eine ultraschnelle und kostengünstige Methode, die auf einem schnellen chemischen Austausch beruht. Hier demonstrieren wir zum ersten Mal eine in vivo‐Anwendung, sowie auch metabolische MRT mit SABRE. Wir präsentieren eine neuartige Routine zur Herstellung von wässrigem HP‐[1‐¹³C]Pyruvat‐d₃innerhalb von sechs Minuten, zur Anwendung in lebenden Organismen. Die injizierte Lösung war steril, ungiftig, pH‐neutral und enthielt ≈30 mM [1‐¹³C]Pyruvat‐d₃, polarisiert auf ≈11 % (Rückstände von 250 mM Methanol und 20 μM Katalysator). Es wurde durch schnelle Lösungsmittelverdampfung und Metallfiltrierung gewonnen, die wir in diesem Manuskript ausführlich beschreiben. Diese Ergebnisse machen die HP‐Pyruvat‐MRT für eine breite biomedizinische Gemeinschaft zur schnellen metabolischen Bildgebung von lebenden Organismen verfügbar.