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Design Considerations for Implementing a Hyperpolarizer

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Dynamic Hyperpolarized Nuclear Magnetic Resonance

Part of the book series: Handbook of Modern Biophysics ((HBBT))

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Abstract

Central to all hyperpolarized magnetic resonance (MR) experiments is the preparation and delivery of hyperpolarized molecules and the hardware required to precondition the molecules via low-temperature dynamic nuclear polarization (DNP) for them to reach a state with highly polarized nuclear spins. This chapter aims to introduce concepts needed to understand how to determine the optimal conditions of field and temperature in order to obtain hyperpolarized molecules for in vitro and in vivo MR experiments. Various hyperpolarizers to date will be presented. Strategies to rapidly transfer the highly polarized molecules from a hyperpolarizer to the nuclear magnetic resonance (NMR) or magnetic resonance imaging (MRI) system used to acquire the MR data without substantially reducing the enhanced nuclear spin polarization will be reviewed. The required hardware for quality assurance prior to injection of hyperpolarized compounds into humans will also be presented along with the opportunities offered by the replacement of persistent radicals with nonpersistent photogenerated radicals.

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Abbreviations

BDPA:

1,3-bisdiphenylene-2-phenylallyl

DNP:

Dynamic nuclear polarization

ESR:

Electron spin resonance

MR:

Magnetic resonance

NMR:

Nuclear magnetic resonance

UV–Vis:

Ultraviolet–visible

VTI:

Variable temperature insert

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Further Reading

  • Ardenkjaer-Larsen, J.H., Leach, A.M., Clarke, N., Urbahn, J., Anderson, D., Skloss, T.W.: Dynamic nuclear polarization polarizer for sterile use intent. NMR Biomed. 24(8), 927–932 (2011)

    Article  Google Scholar 

  • Ardenkjaer-Larsen, J.H., Bowen, S., Petersen, J.R., Rybalko, O., Vinding, M., Ullisch, M., Nielsen, N.C.: Cryogen-free dissolution dynamic nuclear polarization polarizer operating at 3.35 T, 6.70 T and 10.1 T. Magn Reson Med. 81(3), 2184–2194 (2019)

    Google Scholar 

  • Baudin, M., Vuichoud, B., Bornet, A., Bodenhausen, G., Jannin, S.: A cryogen-consumption-free system for dynamic nuclear polarization at 9.4 T. J Magn Reson. 294, 115–121 (2018)

    Google Scholar 

  • Cheng, T., Gaunt, A.P., Marco-Rius, I., Gehrung, M., Chen, A.P., van der Klink, J.J., Comment, A.: A multisample 7 T dynamic nuclear polarization polarizer for preclinical hyperpolarized MR. NMR Biomed. 33(5), e4264 (2020)

    Google Scholar 

  • Comment, A., van den Brandt, B., Uffmann, K., Kurdzesau, F., Jannin, S., Konter, J.A., Hautle, P., Wenckebach, W.T., Gruetter, R., van der Klink, J.J.: Design and performance of a DNP prepolarizer coupled to a rodent MRI scanner. Concepts Magn Reson. 31B(4), 255–269 (2007)

    Article  Google Scholar 

  • Wolber, J., Ellner, F., Fridlund, B., Gram, A., Johannesson, H., Hansson, G., Hansson, L.H., Lerche, M.H., Mansson, S., Servin, R., Thaning, M., Golman, K., Ardenkjaer-Larsen, J.H.: Generating highly polarized nuclear spins in solution using dynamic nuclear polarization. Nucl Instrum Meth A. 526(1–2), 173–181 (2004)

    Article  Google Scholar 

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Acknowledgements

This work is part of a project that has received funding from the European Union’s Horizon 2020 European Research Council (ERC Consolidator Grant) under grant agreement no. 682574 (ASSIMILES). The author would like to thank Dr. Adam Gaunt for his suggestions and for proof reading this chapter.

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Authors and Affiliations

  1. Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK

    Arnaud Comment

  2. General Electric Healthcare, Buckinghamshire, UK

    Arnaud Comment

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Correspondence to Arnaud Comment .

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Editors and Affiliations

  1. Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, CA, USA

    Thomas Jue

  2. Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, Baltimore, MD, USA

    Dirk Mayer

Problems

Problems

  1. 1.

    A 13C MR signal enhancement ε of 55,000 was recorded in a phantom containing a solution of hyperpolarized [1-13C]pyruvate placed inside a 3 T MR scanner. The solution was prepared from neat [1-13C]pyruvic acid doped with trityl radicals and placed inside the bore of the scanner 20 s before the hyperpolarized 13C MR measurement. Polarization, dissolution, and neutralization took place in a 7 T hyperpolarizer located in an adjacent room and it took 40 s to transport the solution through the stray field of the scanner. Knowing that the room-temperature T1, 13C of [1-13C]pyruvate in solution is 65 s at 3 T and 50 s in the stray field of the scanner, determine at what temperature the pyruvic acid sample was polarized (hint: use the linear fit from Fig. 2.2).

  2. 2.

    During a conference, a scientist presented a model showing that the optimal T1, e leading to the highest 13C polarization with trityl radical is 300 ms whatever the magnetic field as long as the temperature is in the range 1–1.5 K. You decide to find out experimentally if this is true using your polarizer operating at 1.5 K by measuring the 13C polarization of [1-13C]pyruvic acid as a function of magnetic field knowing that you can set the field anywhere between 0 and 5 T (you also have access to a large set of microwave sources with adjustable frequency that can match the ESR frequency of trityl radical over this whole range of magnetic field). Considering that the T1, e of trityl in [1-13C] pyruvic acid has been measured to be approximately 1 s at 3.35 T and 1.2 K (see Sect. 2.2), do you think that you can test this theoretical model with your polarizer? Estimate the largest 13C polarization you could expect measuring in your polarizer if this model was correct.

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Comment, A. (2021). Design Considerations for Implementing a Hyperpolarizer. In: Jue, T., Mayer, D. (eds) Dynamic Hyperpolarized Nuclear Magnetic Resonance. Handbook of Modern Biophysics. Springer, Cham. https://doi.org/10.1007/978-3-030-55043-1_2

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