Get the Hype: The Physical Bases of Dynamic Nuclear Polarization for Medical Uses
Lucio Frydman

Synopsis

This talk will discuss the physical basis of the DNP NMR/MRI experiment. Attention will focus on alternatives to do the hyperpolarization component in either solutions or in the solid state, focusing in particular on the Overhauser, on the Solid and on the Cross Effects for the sake of maximizing the nuclear polarization. The parameters that each of these methods requires to work best –including their respective advantages and drawbacks– will be explained. On the basis of this, the procedures that may then enable their respective utilization in bioimaging settings will be introduced

Target Audience

Beginning or advanced bioDNP practitioners interested in knowing what happens in different hyperpolarizers, during the various stages of a DNP experiment.

Abstract

The DNP phenomenon, according to which nuclear polarization could be enhanced by ca. 1000x by irradiating nearby electrons in metals, was publicly introduced as a theoretical prediction by A. Overhauser in 1953 [1]. The proposal was met by wide disbelief by an audience that included Bloch, Purcell, Rabi and Bloembergen –but it was proved to be true a few months later by Slichter [2]. While the DNP effect has remained a tool in the arsenals of chemists and physicists the ensuing excitement decayed over intervening decades, until the renaissance that occurred in the early 2000s. Driving this excitement was the advent of high field solids DNP NMR and of Dissolution DNP MRSI [3,4]. While all DNP experiments share the common goal of transferring polarization from electrons to nuclei, different mechanisms operate in the experiments that Slichter, that the solids DNP scientists, and that dissolution DNP, rely upon. The physics underlying these different mechanisms are the Overhauser Effect, the Solid Effect and the Cross Effect, respectively. In this talk their principles will be presented, and the conditions that make one of these approaches preferable over the other will be explained, based on the different conditions in which the sample is studied. Attention will center on methods that optimize the transfer of polarization from unpaired electrons to nuclei in the solid state at cryogenic temperatures in the most complete and rapid way: these are the conditions that predominate in the dissolution DNP approach, which has seen the widest applications in biological and clinical settings. The discussion will also focus on how the subsequent rapid melting of the cryogenic hyperpolarized pellet using hot vapor enables further investigations that would be impossible without DNP; which kind of metabolic substrates are and which ones are not amenable to this kind of procedure, will be rationalized. The overall potential as well as the limitations of various DNP-based approaches for the sake of metabolic studies, will also be briefly evaluated.

Acknowledgements

Our research in this area has been funded by the Israel Science Foundation (ISF grant 965/18) and by the EU Horizon 2020 programme (Marie Sklodowska-Curie Grant 642773)

References

[1] Overhauser, A.W. (1953). "Polarization of Nuclei in Metals". Phys. Rev. 92 (2): 411–415.

[2] Carver, T.R.; Slichter, C.P. (1953). "Polarization of Nuclear Spins in Metals". Phys. Rev. 92 (1): 212–213.

[3] D.A. Hall; D.C. Maus; G.J. Gerfen; S.J. Inati; L.R. Becerra; F.W. Dahlquist; R.G. Griffin (1997) “Polarization-enhanced NMR spectroscopy of biomolecules in frozen solution”, Science, 276: 930-932

[4] Ardenkjær-Larsen, J. H.; Fridlund, B.; Gram, A.; Hansson, G.; Hansson, L.; Lerche, M. H.; Servin, R.; Thaning, M.; Golman, K., (2003) “Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR”. Proc. Natl. Acad. Sci. USA 100 (18): 10158-10163.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)