Automated transfer and injection of hyperpolarized molecules with polarization measurement prior to in vivo NMR

Abstract

Hyperpolarized magnetic resonance via dissolution dynamic nuclear polarization necessitates the transfer of the hyperpolarized molecules from the polarizer to the imager prior to in vivo measurements. This process leads to unavoidable losses in nuclear polarization, which are difficult to evaluate once the solution has been injected into an animal. We propose a method to measure the polarization of the hyperpolarized molecules inside the imager bore, 3 s following dissolution, at the time of the injection, using a precise quantification of the infusate concentration. This in situ quantification allows for distinguishing between signal modulations related to variations in the nuclear polarization at the time of the injection and signal modulations related to physiological processes such as tissue perfusion. In addition, our method includes a radical scavenging process that leads to a minor reduction in sample concentration and takes place within a couple of seconds following the dissolution in order to minimize the losses due to the presence of paramagnetic polarizing agent in the infusate. We showed that proton exchange between vitamin C, the scavenging molecule and the deuterated solvent shortens the long carboxyl (13)C longitudinal relaxation time in [1-(13)C]acetate. This additional source of dipolar relaxation can be avoided by using deuterated ascorbate. Overall, the method allows for a substantial gain in polarization and also leads to an extension of the time window available for in vivo measurements.

Development and performance of a 129-GHz dynamic nuclear polarizer in an ultra-wide bore superconducting magnet

“…As such, this NMR signal loss may be attributed to other factors. Nevertheless, certain improvements can be made, such as sample preparation, dissolution liquid handling and shortening the transfer time [34]; the use of magnetic rails [35] on the dissolution liquid path can be used to minimize the T 1 -related polarization losses in the liquid-state.…”

LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer

“…13 C]glutamine injection (Cabella et al 2013;Cheng et al 2013). [5][6][7][8][9][10][11][12][13] C]glutamine was hyperpolarized using dissolution dynamic nuclear polarization (DNP) and rapidly injected into DEN-treated Lrh-1 hep−/− and Lrh-1 hep+/+ mice followed by real-time recording of its conversion to [5][6][7][8][9][10][11][12][13] C]glutamate (Fig.…”

Direct noninvasive estimation of myocardial tricarboxylic acid cycle flux in vivo using hyperpolarized 13C magnetic resonance

“…A total volume of 300 μL of this solution was inserted, in the form of 10 μL frozen beads (prepared in liquid nitrogen), into a 5 T custom-designed DNP polarizer prefilled with liquid helium [38]. The 13 C nuclei were dynamically polarized for 2 h at 1.15 K. Following a previously described automated process [39], the beads were rapidly dissolved in 6 mL of pressurized, heated D 2 O and the resulting solution was transferred within 2 s into a separator/infusion pump located inside an actively shielded 31-cm diameter horizontal bore 9.4 T magnet (Magnex Scientific, Abingdon, UK) [40]. The separator/infusion pump was prefilled with 0.6 mL of phosphate buffered saline and heparin.…”