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.

Keywords: MRI; MRS; carbon-13; cryogen-free; cryostat; dynamic nuclear polarization; hyperpolarization; hyperpolarizer.

Figure 1

Schematic drawing of the cryostat without insert: (a) helium gas inlet, (b) cryocooler, (c) helium filling capillary, (d) 50-K plate, (e) copper flexible strap, (f) 3-K plate, (g) thermometer on 50-K plate, (h) thermometer on 3-K plate, (i) radiation shields, (j) vacuum can, (k) 1-K plate, (l) RuO₂ thermometer on helium inlet, (m) magnet, (n) input port of 1-K recirculation circuit to high-impedance capillary, (o) output port of 1-K recirculation circuit to dry vacuum pump, (p) 1-K pot, (q) RuO₂ thermometer on 1-K plate, (s) supporting rods, (t) sample tube.

Figure 2

DNP insert designed and used for dissolution DNP; (1) airlock, (2) sample access tube, (3) waveguide, (4) internal baffle, (5) fiberglass tube, (6) gate valve, (7) calibrated RuO₂ thermometer, (8) microwave cavity, (9) sample vial and (10) RF coil.

Figure 3

Flow separator of custom-designed fluid path used for dissolution.

Figure 4

Sample space temperature as a function of the heating power dissipated by the 100-Ω resistor attached to the test insert and immersed in the 85 mL helium bath of the sample space. Note that the field in the superconducting magnet was set to 7 T.

Figure 5

Microwave spectrum measured in a [1-¹³C]pyruvic acid sample doped with 25 trityl radical (AH 111 501) at 7 T and 1.35 K. Each data point has been recorded after 3 h of DNP, when the ¹³C polarization had reached a plateau. The solid line connecting the data points only serves as guide for the eyes.

Figure 6

Series of liquid-state ¹³C spectra recorded in a 600-MHz spectrometer on a 80 mM hyperpolarized [1-¹³C]pyruvate sample (pH 7.2) inside a 5-mm MR tube. Acquisition was initiated 26 s after dissolution and the repetition time was set to 3.3 s with a flip angle of 10°. The two most intense peaks at 173 ppm and 181.6 ppm correspond to [1-¹³C]pyruvate and [1-¹³C]pyruvate hydrate, respectively. The natural abundance [2-¹³C]pyruvate and [2-¹³C]pyruvate hydrate were also observed at 207.8 ppm and 96.5 ppm, respectively.

Figure 7

Temperature evolution of the 3-K (red line) and 1-K (blue line) plates during two consecutive dissolutions experiments initiated at t₀ and t = t₀ +12 min, respectively.

Figure 8

Liquid-state ¹³C polarization of [1-¹³C]pyruvate obtained from hyperpolarized [1-¹³C]pyruvic acid (neat) doped with trityl radical (15 mM - 26 mM) as a function of B₀/T, back-calculated to the time of the dissolution. Five data points (blue circles) were used for the linear fit (least square method) shown in blue: (1) estimated mean ¹³C polarization obtained with HyperSense™ (3.35 T, 1.4 K); (2) reported ¹³C polarization obtained using the original hyperpolarizer by Chen et al. (3.35 T, 1.2 K); (3) estimated mean ¹³C polarization obtained with SPINlab™ (5 T, 0.8 K); (4) reported ¹³C polarization obtained by Yoshihara et al. (7 T, 1 K); (5) reported ¹³C polarization obtained by Jähnig et al. (7 T, 1.4 K). Two additional data points are displayed: (black circle) reported ¹³C polarization obtained by Ardenkjaer-Larsen et al. (6.7 T, 1.4 K); (red circle) ¹³C polarization reported in the present work (7 T, 1.35 K).