Interdisciplinary Hyperpolarization: Chemistry and Physics provide the means to gain new, previously unavailable insights to Biology and Medicine.

Hyperpolarization - An Overview

The magnetic resonance signal is dependent on the alignment of nuclear spins with respect to an outer magnetic field, much like compass needles in the earth's magnetic field. While all compasses point North in the earth's field, only a very small fraction (≈ 2⋅10-12 %) of the spins of the strongest, stable and most abundant nucleus hydrogen (1H e.g. in water), do so. As a result, the corresponding signal that can be detected is very small. As a spin-1/2 particle, 1H has two energy eigenstates with respect to an outer magnetic field, spin up and spin down. In analogy to the compass: there is a small compass needle in the nucleus of hydrogen atoms pointing North or South, and how many spins point in one or the other direction is governed by the well-known Boltzmann relation (..exp(-E/kT)).

In MR, only the population difference of both states - of spins pointing North and South -  contributes to the signal (called polarization P): P = 1 means maximal population difference - all spins point in one direction - and maximum signal (North or South, depending on the spin); P=0 means no population difference - half point North and half point South - no MR signal (Fig. 1).

Unfortunately, the nuclear compass needles are so small, that in the earth magnetic field of ~ 50 microTesla, both levels are almost equally populated. The difference is only P ≈ 10-10. This means that merely 0.00000001 % of all of the spins are polarized (and thus available to contribute to the signal). This is acceptable in the case of 1H MRI where the lack of polarization is offset by the high endogenous concentration, but for MR applications where one is interested in the relative concentrations of a relatively sparse nucleus (such as a 13C labelled biomarker of cancer), this is too little.

Schematic Representation of thermal (left) and hyperpolarization (right). Nuclear spins (1/2) take two energy eigen states. The population of these states is Boltzmann distributed. In thermal equilibrium, in the earth magnetic field (≈50 microT), the population difference for 1H is P ≈ 10-10, at 1 Tesla P ≈ 3*10-6. Hyperpolariaztion circumvents the thermal distribution using various tricks i.e. sources of spin order, including polarized laser light or parahydrogen.

Modern superconducting magnets providing magnetic fields of several Tesla, ≈105 times as strong as the earth's field, and ≈10 - 100 times as strong as magnets lifting cars on scarp yards. This has enabled MRI to become one of the most versatile tools in modern science and medicine. Still, even with these humongous, strong magnetic fields of several Tesla, only a miniscule fraction (≈3 10-6/T) of all nuclear hydrogen spins are polarized. Thus, MR is an inherently insensitive method.

We are the 99.9997 %
On the other hand, there is a great potential. All exciting and ground-breaking results of MR are achieved using only a few millionths of all spins. What can MR do when 100 % of all spins are available instead of merely 0.0003 % of all spins?

The goal of nuclear hyperpolarization is to access this vast majority of nuclear spins, 99.9997 % of 1H per Tesla, which do not contribute to the signal of conventional magnetic resonance imaging.



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