MPI Campus Seminar: Need for new contrast agents for magnetic resonance: para-hydrogen hyperpolarization

Magnetic resonance imaging (MRI) and nuclear magnetic resonance (NMR) proofed to be useful methods providing vast spatial and spectroscopic information in vitro as well as in vivo. Invention of contrast agents introduced additional dimension for MRI improving resolution and even allows visualizing new features in vivo like cancer cells. However, gadolinium contrast agents that are the most spread and well established contrast agents were found to have negative health effects. In addition, low inherent sensitivity because of low nuclear polarization still limits MRI for detection of mostly protons. Another approach to contrast agents is to use molecules that already exist in the body. However, one needs to make their signals distinctly different from background molecules. In order to accomplish this one can hyperpolarize (HP) molecules of interest leading to >10000-fold higher signals compared to the normal/thermal NMR signal. This could for example be used to turn water into contrast agent for angiography. In addition it opens possibilities to visualize molecule of low concentrations (< 10 mM) like metabolites and observe their dynamic development to study metabolic pathways linked to diseases. Last decade the development of HP methods was boosted by the dissolution Dynamic Nuclear Polarization (dDNP) technology which is the routine way for generating HP metabolites. However, dDNP is an expensive approach (~1M€) with limited throughput (every ~30min) thus hindering development of the field. Here we aim for cost-effective and fast HP method based on reaction of para-hydrogen with unsaturated bonds of a precursor molecule producing polarized protons in the molecule within seconds. Because the HP is transient, it is advantages to transfer polarization to a carbon nucleus where the lifetime of it is much longer (~60 s). In order to achieve this suitable metabolite precursors need to be generated that can be rapidly transformed into hyperpolarized metabolic contrast agents. We direct our efforts to improve the para-hydrogen approach by developing new efficient precursors for the most important metabolites and transfer the HP from protons to any nucleus of interest by novel pulse sequences. Thus, we demonstrate carbon signal enhancements up to 100,000-fold for metabolites at concentration as high as 50 mM which is sufficient for MRI application. Easier availability of HP metabolites would lead to new applications in various research fields and allows us to detect HP signal by cost-efficient equipment.