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International Conference on Magnetic Resonance Microscopy

Hyperpolarisation and Biomedical MR II - L-031

Hyperpolarization using paraHydrogen

J. Hövener*
  • Universität Freibung, Department of Radiology, Freiburg, Germany

The hyperpolarization (HP) of nuclear spins promises to overcome the single greatest impediment of magnetic resonance (MR), its low sensitivity: Even for the most sensitive and most commonly used nucleus in MR imaging, hydrogen (1H), no more than 3 ppm of all nuclei effectively contribute to the MR signal in a field of one Tesla.
Over the past decades, various methods were devised to achieve a polarization level in gases1,2 and small molecules in solution3-5 that approaches the order of unity. The latter offers great perspectives for cancer diagnosis and treatment control.6,7 Only recently, a great breakthrough was reported as 13C-pyruvate hyperpolarized by dynamic nuclear polarization was used to detect tumor metabolism in man for the first time8.
This plenary will focus on parahydrogen (pH2) - based HP, a method known for decades as pH2 and synthesis allow dramatically enhanced nuclear alignment (PASADENA), pH2 induced HP (PHIP) as well as signal amplification by reversible exchange (SABRE).9-13
pH2 -based methods are generally very fast and cost efficient, taking advantage of the spin order of pH2 that is a perfectly ordered spin state but MR invisible. pH2 is produced relatively easily by cooling commercial H2 gas to e.g. 25 K in the presence of a catalyst.14 The spin order is made available to a suited molecule either by catalytic addition (Fig. 1 a-c, PASADENA and PHIP) or by a reversible exchange (Fig. 1 d, SABRE). The efficient transfer of para-order to strong and long-lived X-nuclei HP was a breakthrough for PASADENA and SABRE alike.15,16
One of the first biomolecules that was hyperpolarized by pH2 to more than 10 % was succinate.17 Only this year, the HP of 13C-pyruvate and acetate by means of pH2 was reported and constitutes another breakthrough for this method.18
Another unique feature of pH2-HP that was discovered in 2013 is that it allows to continuously hyperpolarize molecules in the liquid phase.19,20 While this effect is, thus far, functional in vitro only, the prospect of continuous HP for low-field molecular MRI is quite intriguing.

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Figure 1: Schematic view of HP by catalytic addition of pH2 to a precursor (a-c) and reversible exchange (d). Note that a J-coupling interaction (3JHC e.g.) is essential to transfer the spin order to other nuclei like 13C.

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18. Reineri, F., Boi, T. & Aime, S. pH2 Polarization of 13C carboxylate resonance in acetate and pyruvate. Nat. Commun. 6, 5858 (2015).
19. Hövener, J.-B. et al. A hyperpolarized equilibrium for magnetic resonance. Nat. Commun. 4, (2013).
20. Hövener, J.-B., et al.. Continuous Re-HP of Nuclear Spins Using pH2: Theory and Experiment. ChemPhysChem 15, 2451-2457 (2014).


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