Nuclear Spin Hyperpolarization

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are extremely powerful analytical tools to study structure and dynamics of materials and living species at macroscopic, microscopic, and molecular scales. However, due to the weak interaction of nuclear magnetic moments with the applied magnetic field (less than 0.2 J/mol), NMR/MRI signals are rather low. For example, even in the magnetic fields that thousands of times larger than the Earth’s magnetic field there is only a net alignment of roughly 1 out of 100,000 nuclear spins. This means that the nuclear spin polarization (%P) is equal to only about 0.001% out of the theoretically possible 100%. This is definitely a problem since it makes NMR/MRI scan times rather long, limits spatial and temporal resolution. Luckily for us, there is a way to overcome this issue – hyperpolarization. Hyperpolarization means a creation of highly polarized or highly magnetized media. Rather than one in a one hundred thousand, how about all of the spins being aligned? Or half of them, or even 10% – it is still much better than 0.001%! So, how can one do that?

Hyperpolarization means a creation of highly polarized or highly magnetized media

There are many ways to make nuclei hyperpolarized. Among the most widely used techniques are spin-exchange optical pumping (SEOP) of noble gases, dynamic nuclear polarization (DNP), chemically-induced dynamic nuclear polarization (CIDNP), parahydrogen-induced polarization (PHIP) and signal amplification by reversible exchange (SABRE). The last two techniques are of my particular interest because they are based on chemical interactions.

Ability to create hyperpolarized molecules presents the fields of medical imaging with an opportunity to dramatically improve our understanding of metabolism. Numerous clinical trials are ongoing. However, not only biomedical applications can benefit from the development of hyperpolarization technologies. Hyperpolarized MRI can bring a new life to the magnetic resonance in the low fields


Parahydrogen-induced Polarization (PHIP)

In 1986 Bowers and Weitekamp proposed a method for achieving very high nuclear polarizations using parahydrogen. Parahydrogen (para-H2) is a nuclear spin isomer of hydrogen molecule with total angular momentum 𝐼 = 0. Though para-H2 itself is NMR-silent (since it has no net magnetic moment), it carries singlet nuclear spin order which may be transformed to observable magnetization by various mechanisms. PHIP employs hydrogenation as such a mechanism. Indeed, upon incorporation of a para-H2 molecule into an asymmetric molecular precursor, the symmetry of the para-H2-nascent nuclear spins becomes broken and the high spin order becomes accessible for manipulations (Figure 1). Since, fundamentally, achieved %𝑃 is not dependent on the external magnetic field and may approach 100%, PHIP can provide enhancements of NMR signals compared to the thermal for various nuclei of up to five orders of magnitude in magnetic fields of modern NMR spectrometers (and even higher enhancements in low and ultra-low magnetic fields).

Figure 1. Parahydrogen-induced Polarization (PHIP).

Signal Amplification By Reversible Exchange (SABRE)

SABRE also uses para-H2 as a source of spin order. However, unlike PHIP, it does not require hydrogenation reaction to polarize the substrate of interest. In the SABRE effect, signal enhancement is endowed by a reversible association of para-H2 and a to-be-polarized substrate with a metal complex, allowing the transfer of nuclear spin order from parahydrogen to the substrate (Figure 2).

Figure 2. Signal Amplification By Reversible Exchange (SABRE).

SABRE is typically observed for nitrogen-containing heterocycles, when a metal complex (typically referred to as the “magnetization transfer catalyst” or simply “catalyst”) is used to briefly bring hydrogen and a substrate into contact with each other and to facilitate exchange with their free forms in solution. Latest advances in SABRE allow polarizing a wide range of vitamins, metabolites, and drugs, making it a promising modality for studying metabolism in vivo by means of NMR/MRI.

The Interplay between Chemistry and Nuclear Spin Dynamics

Precise coherent control over the nuclear spin dynamics made NMR spectroscopy a unique tool that allowed scientists to test quantum mechanics and the basic laws of nature. However, due to the limitations imposed by molecular symmetry, some transformations of nuclear spin states are not possible. The way to overcome this problem and to expand our ability to fully manipulate spin dynamics is to involve chemical reactions.


By combining the coherent control (RF pulses, variations of the magnetic field, etc.) with the ability to govern the incoherent dynamics (e.g., adding the catalysts/inhibitors to facilitate/suppress chemical reactions) one will be able to unlock the full potential and potentially can create nuclear spin states that have not considered to be accessible before.