Stand-alone two-phase parahydrogen induced hyperpolarizer for ultra-low and high field MR (2P-PHIP)

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Magnetic resonance (MR) plays a pivotal role in many fields of science, and to enhance its intrinsically low signal several hyperpolarization (HP) techniques were developed For instance, dissolution dynamic nuclear polarization (dDNP) is in a state of preclinical research. It requires low temperatures (~1 K), paramagnetic agents together with microwaves for HP, and the rapid dissolution in a suitable carrier. This makes dDNP technically challenging and essentially a one-shot technique.An alternative HP method is the exploitation of the intrinsic spin order of para hydrogen (pH2 – the spin singlet isomer of H2), which can be transferred to target molecules. pH2 induced polarization (PHIP) makes use of the hydrogenation of target molecules with pH2, whereas signal amplification by reversible exchange (SABRE) allows spin order transfer without the modification of target molecules and enables continuous HP. As pH2 generation is low cost, low instrumentation demands and pH2 can be stored for months, PHIP and SABRE are promising methods of HP for future clinical applications.The project 2P-PHIP aims to the development of a cost-efficient PHIP and SABRE-based stand-alone continuous flow hyperpolarization reactor for biochemistry and future in vivo biomedical applications. In contrast to commercially available dDNP, the reactor will be able to continuously deliver high purity hyperpolarized liquids enabling MR experiments with longer acquisition times and larger quantities. A novel two-phase pH2 induced HP technique with the catalyst retained in a fluorinated phase (or another hydrophobic phase) will be pursued as the most promising route. This approach will facilitate the extraction of hyperpolarized substrates with high purity needed for future in vivo applications. More traditional (single-phase) PHIP and SABRE implementations will also be possible with this polarizer. The stand-alone reactor can be used at ultra-low (µT-range) or high magnetic field (T-range) MR enabling unique features of both regimes. MR at high magnetic fields provide superior spectral resolution, whereas imaging at low magnetic fields is compatible with sensitive implants (i.e. pacemakers). The investigation of HP using non-traditional methods, the direct observation of the HP itself will be carried out using the most sensitive SQUID instrumentation available. As we ultimately aim to in vivo applications, proof-of-concept experiments on biological samples, such as cell cultures, blood or homogenized brain tissue will also be undertaken.The outcome of the 2P-PHIP project will be a multipurpose stand-alone pH2-based polarizer featuring high concentrations of highly polarized substrates with high tracer throughput for in vivo applications.