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-Boltzman spin populations and thus increase NMR signals by several orders of magnitude.

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).¹ 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 appropriate pulse sequences.² By using a chiral hydrogenation catalyst it is even possible to create an enantiomerically enriched hyperpolarized compound.

Among the drugs used to treat epilepsy or for injection narcotics, barbiturates like methohexital or phenobarbital are attractive from the MRI and chemical point of view because of their long T₁ and the straightforward synthesis of model structures from urea and malonic acid derivatives with unsaturated groups to introduce polarization.³ By using the PHIP-INEPT and PHIP-INEPT+ pulse sequence on these compounds we achieved enhancements of several thousands compared to the thermal spectra.

Imaging experiments on model compounds also 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. Furthermore we synthesize and apply water-soluble catalysts on the basis of Rhodium and triphenylphosphine or biphosphine ligands.

¹J. Natterer, J. Bargon, Prog. Nucl. Magn. Reson. Spectrosc., 1997, 31, 293-315
S. B. Duckett, C. J. Sleigh., Prog. Nucl. Magn. Reson. Spectrosc., 1999, 34, 71-92
²S. Mansson et al., Eur. Radiol., 2006, 16, 57-67
³M. Roth, J. Bargon, H. W. Spiess, A. Koch, Magn. Reson. Chem., 2008, 46, 713-717