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‐d3 for injection in 6 minutes. The injected solution was sterile, non‐toxic, pH neutral and contained ≈30 mM [1‐13C]pyruvate‐d3 polarized 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.
Metabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate has shown promise as 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 is dynamic nuclear polarization; however, it is rather expensive and slow. Here, we demonstrate fast (6 min), low-cost production of HP [1-13C]pyruvate-d3 in aqueous solution using Signal Amplification By Reversible Exchange (SABRE), and in vivo metabolic MRI. The injected solution was sterile, non-toxic, pH neutral and contained ≈30 mM [1-13C]pyruvate-d3 polarized to ≈11% (residual 250 mM methanol and 20 µM catalyst). It was obtained by rapid solvent evaporation and metal filtering. The procedure was well tolerated by all four mice studied here. This achievement is a significant step of making HP MRI available to a wider community. Fast, low-cost, and high-throughput parahydrogen-hyperpolarization has become a viable alternative for metabolic MRI of living organisms.
Optical frequency combs based on mode-locked lasers have revolutionized many areas of science and technology, such as precision metrology, optical frequency synthesis, and telecommunications. In recent years, a particular kind of frequency comb has been observed in edge-emitting semiconductor lasers where the phase difference between longitudinal laser modes is fixed but not zero. This results in a linearly chirped output in the time domain with nearly constant intensity. Here, by using coherent beatnote spectroscopy, we show that such a comb regime can also exist in vertical-external-cavity surface-emitting lasers, as evidenced for a specific part of the laser spectrum. Our findings may not only lead to a better understanding of the physics of frequency-modulated combs but also enable comb applications with high optical power per comb line and flexible emission wavelengths.
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‐d3 innerhalb 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.
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