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Development of Heterogeneous Catalysts for Signal Enhancements in Magnetic Resonance Using Parahydrogen

  • Author(s): McCormick, Jeffrey
  • Advisor(s): Bouchard, Louis-Serge
  • et al.
Abstract

Despite the incredible breadth of utility made possible by nuclear magnetic resonance (NMR) from molecular structure determination to human imaging, the vast majority of its full potential is never used. This is due to the fact that at physiological temperatures, even inside state-of-the-art high field magnets, only a small percentage of possible nuclear spin ensembles contribute to observable signal. The notably low tendency of these spins to align with the static magnetic field, referred to as its polarization, limits achievable spectroscopic image resolution in addition to necessitating costly scan time. Several techniques have been developed to overcome this limitation by producing nuclear spin polarizations several orders of magnitude above thermal equilibrium conditions, referred to as hyperpolarized states. One promising and cost-efficient approach for generating hyperpolarized contrast agents useful in medical imaging is a technique explored in this work known as parahydrogen-induced polarization (PHIP). This technique involves using an isomer of H2 with highly ordered spin order known as parahydrogen (para-H2}) to introduce a hyperpolarized state into a compound of interest such as a traceable metabolite by attaching para-H2 via hydrogenation reaction. Careful optimization is required to prepare unsaturated precursor molecules which hydrogenate into desired products and to ensure that para-H2 spin order is well-coordinated such that hyperpolarization is observed.

Since PHIP's initial observation over three decades ago, it has yet to develop into an established application for human imaging. The critical barriers to this have been predominant optimization in organic solvents and with homogeneous transition metal catalysts, both of which creating toxicity concerns regarding injection of the hyperpolarized product solution into the patient. This work examines the development of heterogeneous nanoparticle catalysts formed from catalytically robust metals such as Pt, Pd and Rh. These catalysts are optimized for production of biologically relevant compounds by PHIP, allowing separation of the catalyst within the timeframe of hyperpolarized signals to produce pure aqueous solutions for medical application. Because the enhanced signal of product 1H nuclei are typically undetectable within seconds, developments towards storing hyperpolarized 1H signals generated by PHIP on adjacent, longer-lived nuclei such as 13C or 15N are of special interest. We demonstrate the first heterogeneous PHIP catalyst optimized for aqueous solutions generating 0.37% 1H polarization and detail the various insights and developments leading to the high 15N polarization of a choline derivative at 12%. These results widen the scope of PHIP probe strategies and significantly advance the possible application of PHIP in clinical imaging.

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