A multisample 7 T dynamic nuclear polarization polarizer for preclinical hyperpolarized MR

Abstract

Dynamic nuclear polarization (DNP) provides the opportunity to boost liquid state magnetic resonance (MR) signals from selected nuclear spins by several orders of magnitude. A cryostat running at a temperature of~1 K and a superconducting magnet set to between 3 and 10 T are required to efficiently hyperpolarize nuclear spins.Several DNP polarizers have been implemented for the purpose of hyperpolarized MR and recent systems have been designed to avoid the need for user input of liquid cryogens. We herein present a zero boil-off DNP polarizer that operates at 1.35 ± 0.01 K and 7 T, and which can polarize two samples in parallel. The samples are cooled by a static helium bath thermally connected to a 1 K closed-cycle 4 He refrigerator. Using a modified version of the commercial fluid path developed for the SPINlab polarizer, we demonstrate that, within a 12-minute interval, the system can produce two separate hyperpolarized 13 C solutions. The 13 C liquid-state polarization of [1-13 C]pyruvate measured 26 seconds after dissolution was 36%, which can be extrapolated to a 55% solid state polarization. The system is well adapted for in vitro and in vivo preclinical hyperpolarized MR experiments and it can be modified to polarize up to four samples in parallel. K E Y W O R D Scarbon-13, cryogen-free, cryostat, dynamic nuclear polarization, hyperpolarization, hyperpolarizer, MRI, MRS | INTRODUCTIONDynamic nuclear polarization (DNP) is currently the most efficient and versatile method for hyperpolarizing nuclear spins of molecules in order to obtain enhanced magnetic resonance (MR) signals in solution. 1,2 Numerous preclinical applications have demonstrated the enormous potential of hyperpolarized 13 C MR for in vivo metabolic imaging, 3,4 and several research hospitals are currently performing studies on patients. 5,6 To achieve a high nuclear spin polarization by DNP, the samples containing the molecules of interest have to be doped with either a stable or a nonpersistent radical and cooled to a temperature of 1-1.5 K in a magnetic field of 3-10 T. 7,8 Moreover, they need to be irradiated with microwaves at a frequency near the electron spin resonance (ESR) of the unpaired electron spin of the selected radical. Finally, to transform the cold samples into solutions containing molecules with hyperpolarized nuclear spins, a dissolution or a thermalization and melting process is required. 2,9 The original dissolution DNP polarizer was implemented using a cryostat with a pumped liquid helium bath, in which the sample was directly inserted. 10 In this system, the temperature of the sample is lowered by dynamically reducing the vapor pressure above the liquid

A cryogen-free, semi-automated apparatus for bullet-dynamic nuclear polarization with improved resolution

“…Dissolution-dynamic nuclear polarization (D-DNP) can provide solutions of hyperpolarized molecules with near-unity spin polarization, corresponding to signal enhancements of > 10 000 in state-of-the-art NMR instruments (Ardenkjaer-Larsen et al, 2003;Ardenkjaer-Larsen et al, 2015;van Bentum et al, 2016;Ardenkjaer-Larsen, 2016;Jannin et al, 2019;Kurzbach and Jannin, 2018;Zhang and Hilty, 2018;Ardenkjaer-Larsen, 2019). Solutions containing hyperpolarized molecules such as pyruvate are now used in a number of clinical trials to measure human metabolism in vivo (Nelson et al, 2013;Comment, 2016;Wang et al, 2019).…”

Hyperpolarization via dissolution dynamic nuclear polarization: new technological and methodological advances

“…Because of the undisputed usefulness in biomedical application, high achievable polarization and relatively long liquidstate T1,n, [1- 13 C]pyruvic acid doped with trityl free radicals has become the most studied and used dDNP sample [49][50][51]. However, a major challenge in extending the range of metabolomic experiments is to find biologically compatible mixtures in which an efficient EPA and the metabolic substrate of interest can be co-dissolved easily and remain well mixed upon freezing.…”

“…A temperature of T = 1.49 K can be attained as a base temperature within 100 to 180 min. More recently, a third version of "cryogen free" dDNP polarizer was introduced by Comment et al [50]. Here, the geometry (see Fig.…”

Comprehensive Literature Review of Hyperpolarized Carbon-13 MRI: The Road to Clinical Application

“…Furthermore, a new commercial 6.7 T pre-clinical polarizer has been introduced—the Spin-Aligner (Polarize IVS, Frederiksberg, DK) in 2018 [ 88 ]. The effectiveness of the polarizers has increased rapidly (from 20% to 40% to 70%), and clinical systems are able to achieve polarization up to 55% [ 89 ], which is twice the polarization used in the first clinical trial [ 7 ]. However, new technological and methodological advances are still needed to improve the polarization method, especially with respect to cost effectiveness and user friendliness [ 11 , 90 , 91 ].…”