Parahydrogen-based Hyperpolarization for Biomedicine

NMR is one of the most versatile and useful physical effects used for human imaging, chemical analysis and the elucidation of molecular structures. Yet, the full potential of NMR is hardly ever used, because only a small fraction of the nuclear spin ensemble is polarized - i.e. aligned with the applied static magnetic field. This fraction is termed nuclear spin polarization P. As a result, no more than a few parts per million of all nuclear spins effectively contribute to the signal in all magnetic fields (B0) available for NMR or MRI today. Because P is approximately linear with B0, a stronger field offers some but limited improvements. Hyperpolarization methods seek other means to increase P and thus the MR signal. A unique source of pure spin order is the spin singlet state of dihydrogen, parahydrogen (pH2), which is inherently stable and long-lived. When brought into contact with another molecule, this "spin order on demand" allows enhancing the NMR signal by several orders of magnitude. In contrast to other methods, this process is very fast (seconds) and can take place in the liquid state. Nuclear spin polarization of the order of unity was demonstrated, manifesting as significant NMR and MRI signal enhancement by several orders of magnitude. Considerable progress was made in the past decade in the area of pH2-based hyperpolarization techniques for biomedical applications. It is the goal of this minireview to provide a comprehensive, selective overview of these developments, covering the areas of spin physics, catalysis, instrumentation, contrast agents' preparation and application.