Parahydrogen Induced Polarization (PHIP)

NMR and related techniques have become indispensable tools with innumerable applications in physics, chemistry, biology and medicine. One of the main obstacles in NMR is its notorious lack of sensitivity, which is due to the low equilibrium polarization of nuclear spins at ambient temperature. To improve on this deficiency, different hyperpolarization (HP) methods have been established to generate non-Boltzmann spin populations and thus increase NMR signals by several orders of magnitude.
PHIP Spectrum PHIP is a way to achieve hyperpolarization of spin ensembles via a chemical route. It makes use of the parahydrogen symmetry breaking during homogeneously catalyzed hydrogenation of unsaturated substrates, creation of non-equivalent product protons and the re-insertion of parahydrogen spin information into the substrate molecule. Parahydrogen which is the thermodynamically preferred spin isomer of the hydrogen molecule (as opposed to orthohydrogen) can be enriched by cooling under the effect of a paramagnetic catalyst (e.g. charcoal). After a subsequent homogeneous parahydrogenation reaction, PHIP NMR experiments lead to absorption and emission signals and a theoretical signal increase of up to 104, which is in practice limited by relaxation processes. Depending on whether the chemical reaction is conducted in the high or very low magnetic field there are two protocols leading to different signal patterns, named PASADENA (Parahydrogen And Synthesis Allow Dramatically Enhanced Nuclear Alignment) and ALTADENA (Adiabatic Longitudinal Transfer After Dissociation Engenders Nuclear Alignment). In the latter case the resonance frequencies of different nuclei are virtually the same, which enables the transfer of spin order to heteronuclei (13C, 15N, 19F, 31P), which are especially interesting due to their long relaxation time T1. Polarization transfer is the prerequisite for modern MRI applications and can also be triggered selectively by pulse sequences. By using a chiral hydrogenation catalyst it is even possible to create an enantiomerically enriched hyperpolarized compound.

First imaging experiments on model compounds show a substantial advantage in contrast and imaging time. The next step will be to accomplish the transfer of hyperpolarization to heteroatoms in the case of physiologically relevant substrates that might be of diagnostic importance. Experiments along these lines are performed in our laboratory and in cooperation with the University hospital in Mainz.

Contact: K. Münnemann