Methods for Molecular Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy using Hyperpolarized Nuclei

Since the introduction 10 years ago of the dissolution method, Dynamic Nuclear Polarization (DNP) became a widely applied and powerful technique to enhance nuclear magnetic resonance (NMR) signals of low naturally abundant, insensitive nuclear spins for analytical chemistry and biomedical research. The aim of DNP is to obtain a very high degree of polarization on the nuclei of interest in cryogenic conditions (i.e. 1 K ), a hundred or more times higher than the thermal polarization. Then, trough a fast dissolution process the molecules hosting the nuclear spins are mixed in a room temperature solution and, since their polarization is conserved if their relaxation times are long enough, they can be used for in vitro or in vivo experiments with a SNR enhanced by 104 times or more. Although the DNP technique was established about 60 years ago, the hardware and cryogenic equipment needed to perform DNP and the subsequent dissolution, still are a technological challenge. In this thesis we will cover different DNP aspects, ranging from hardware installation, software development, solid state measurement, in vitro and in vivo experiments and a possible application of DNP to MRI studies of granular materials. A new DNP cryostat was developed and tested to determine its cryogenic performances and then optimized for fast cooldown, helium holdtime and overall minimal operational consumption. We will show the characteristics of the cryostat and the performances on standard operations like cooling and DNP at 1 K . Another important aspect the development tackled was automation. The management of the system was condensed in a single electronic box capabile to handle the interface with all the cryostat instruments. This box is driven by a single common USB port trough a custom made software interface we developed. Although a few manual operations are still needed, we achieved a high degree of automation. The solid state polarization enhancement ε is defined as the ratio between the DNP enhanced and the thermal polarization signals. It can be determined by measuring the DNP enhanced signal after the system stabilizes in the polarized state (i.e. after about 5 buildup time) and thermal polarization signal after the spins have fully relaxed to equilibrium (i.e. after about 5T1). As a first application of the new system, we present a method that exploits the behavior of steady states magnetization produced with trains of evenly spaced pulses, at constant flip angle. This method allows to precisely determine the thermally polarized signal of a sample with known T1 and a given flip angle in a small fraction (as low as half of a T1 or less depending on the requested accuracy) of the time needed in the usual "wait 5 T1 and pulse" scheme. The main drawback of the dissolution DNP is that the large polarization achieved will ineluctably relax towards its thermal equilibrium value in a few times T1, that for typical 13C labeled molecules is shorter than a minute. On the ot