Methods for Enhancing the High Field in vivo Sensitivity of Long-T1 Nuclear Spins via Dynamic Nuclear Polarization

Abstract

Abstract Dissolution dynamic nuclear polarization (DNP) became a very powerful technique forenhancing nuclear magnetic resonance (NMR) signals of insensitive nuclear spins for ana-lytical chemistry and biomedical research. In this thesis we describe methods and hardwaredevelopments to maximize the NMR signals of substrates of biological interest containinginsensitive nuclear spins with long longitudinal relaxation time T 1 . The overall aim was toextend the acquisition time window of in vivo metabolic studies.The dissolution and transfer procedures of the hyperpolarized molecules from the po-larizer to the imager prior to in vivo measurements lead to unavoidable losses in nuclearpolarization which are difficult to evaluate once the solution has been injected into an animal.We proposed a method to measure the polarization of the hyperpolarized molecules insidethe imager bore, 3s following dissolution, at the time of the injection. Our method includesa radical scavenging process that does not lead to reduced sample concentration and takesplace within a couple of seconds following the dissolution in order to minimize the losses dueto the presence of paramagnetic polarizing agent in the infusate.The stable radicals used as polarizing agents in the solid-state DNP process becomeundesirable in the liquid-state, following dissolution, due to the paramagnetic relaxation effecton the hyperpolarized nuclear spins and their toxicity to biological tissues. We demonstratedthe feasibility of preparing hyperpolarized alcohol aqueous solutions free of stable radicals byusing spin-labeled thermoresponsive hydrophilic polymer networks. We applied this methodto hyperpolarize