Cryogen-Free dissolution Dynamic Nuclear Polarization polarizer operating at 3.35 T, 6.70 T and 10.1 T

Purpose: A novel dissolution dynamic nuclear polarization (dDNP) polarizer platform is presented. The polarizer meets a number of key requirements for in vitro, pre-clinical and clinical applications. Method: It uses no liquid cryogens, operates in continuous mode, accommodates a wide range of sample sizes up to and including those required for human studies, and is fully automated. Results: It offers a wide operational window both in terms of magnetic field, up to 10.1 T, and temperature, from room temperature down to 1.3 K. The polarizer delivers a 13C liquid state polarization for [1-13C]pyruvate of 70%. The build-up time constant in the solid state is approx. 1200 s (20 min), allowing a sample throughput of at least one sample per hour including sample loading and dissolution. Conclusion: We confirm the previously reported strong field dependence in the range 3.35 to 6.7 T, but see no further increase in polarization when increasing the magnetic field strength to 10.1 T for [1-13C]pyruvate and trityl. Using a custom dry magnet, cold head and recondensing, closed-cycle cooling system, combined with a modular DNP probe, automation and fluid handling systems; we have designed a unique dDNP system with unrivalled flexibility and performance.Comment: 16 pages, 8 figure

A Hyperpolarizable 1H Magnetic Resonance Probe for Signal Detection 15 Minutes after Spin Polarization Storage

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are two extremely important techniques with applications ranging from molecular structure determination to human imaging. However, in many cases the applicability of NMR and MRI are limited by inherently poor sensitivity and insufficient nuclear spin lifetime. Here we demonstrate a cost-efficient and fast technique that tackles both issues simultaneously. We use the signal amplification by reversible exchange (SABRE) technique to hyperpolarize the target1H nuclei and store this polarization in long-lived singlet (LLS) form after suitable radiofrequency (rf) pulses. Compared to the normal scenario, we achieve three orders of signal enhancement and one order of lifetime extension, leading to1H NMR signal detection 15 minutes after the creation of the detected states. The creation of such hyperpolarized long-lived polarization reflects an important step forward in the pipeline to see such agents used as clinical probes of disease

Electron and nuclear spin dynamics in the thermal mixing model of dynamic nuclear polarization

A novel mathematical treatment is proposed for computing the time evolution of dynamic nuclear polarization processes in the low temperature thermal mixing regime. Without assuming any a priori analytical form for the electron polarization, our approach provides a quantitative picture of the steady state that recovers the well known Borghini prediction based on thermodynamics arguments, as long as the electrons-nuclei transition rates are fast compared to the other relevant time scales. Substantially different final polarization levels are achieved instead when the latter assumption is relaxed in the presence of a nuclear leakage term, even though very weak, suggesting a possible explanation for the deviation between the measured steady state polarizations and the Borghini prediction. The proposed methodology also allows to calculate nuclear polarization and relaxation times, once specified the electrons/nuclei concentration ratio and the typical rates of the microscopic processes involving the two spin species. Numerical results are shown to account for the manifold dynamical behaviours of typical DNP samples.Comment: 11 pages, 11 figure

<i>In Vivo</i> phenotyping of tumor metabolism in a canine cancer patient with simultaneous ¹⁸F-FDG-PET and hyperpolarized ¹³C-Pyruvate magnetic resonance spectroscopic imaging (hyperPET):mismatch demonstrates that FDG may not always reflect the Warburg effect

In this communication the mismatch between simultaneous 18F-FDG-PET and a 13C-lactate imaging (hyperPET) in a biopsy verified squamous cell carcinoma in the right tonsil of a canine cancer patient is shown. The results demonstrate that 18F-FDG-PET may not always reflect the Warburg effect in all tumors

A system for accurate and automated injection of hyperpolarized substrate with minimal dead time and scalable volumes over a large range

Over recent years hyperpolarization by dissolution dynamic nuclear polarization has become an established technique for studying metabolism in vivo in animal models. Temporal signal plots obtained from the injected metabolite and daughter products, e.g. pyruvate and lactate, can be fitted to compartmental models to estimate kinetic rate constants. Modeling and physiological parameter estimation can be made more robust by consistent and reproducible injections through automation. An injection system previously developed by us was limited in the injectable volume to between 0.6 and 2.4 ml and injection was delayed due to a required syringe filling step. An improved MR-compatible injector system has been developed that measures the pH of injected substrate, uses flow control to reduce dead volume within the injection cannula and can be operated over a larger volume range. The delay time to injection has been minimized by removing the syringe filling step by use of a peristaltic pump. For 100 ll to 10.000 ml, the volume range typically used for mice to rabbits, the average delivered volume was 97.8% of the demand volume. The standard deviation of delivered volumes was 7 ll for 100 ll and 20 ll for 10.000 ml demand volumes (mean S.D. was 9 ul in this range). In three repeat injections through a fixed 0.96 mm O.D. tube the coefficient of variation for the area under the curve was 2%. For in vivo injections of hyperpolarized pyruvate in tumor-bearing rats, signal was first detected in the input femoral vein cannula at 3–4 s post-injection trigger signal and at 9–12 s in tumor tissue. The pH of the injected pyruvate was 7.1 ± 0.3 (mean ± S.D., n = 10). For small injection volumes, e.g. less than 100 ll, the internal diameter of the tubing contained within the peristaltic pump could be reduced to improve accuracy. Larger injection volumes are limited only by the size of the receiving vessel connected to the pump

Cluster formation restricts dynamic nuclear polarization of xenon in solid mixtures

During dynamic nuclear polarization (DNP) at 1.5 K and 5 T, (129)Xe nuclear magnetic resonance (NMR) spectra of a homogeneous xenon/1-propanol/trityl-radical solid mixture exhibit a single peak, broadened by (1)H neighbors. A second peak appears upon annealing for several hours at 125 K. Its characteristic width and chemical shift indicate the presence of spontaneously formed pure Xe clusters. Microwave irradiation at the appropriate frequencies can bring both peaks to either positive or negative polarization. The peculiar time evolution of (129)Xe polarization in pure Xe clusters during DNP can be modelled as an interplay of spin diffusion and T(1) relaxation. Our simple spherical-cluster model offers a sensitive tool to evaluate major DNP parameters in situ, revealing a severe spin-diffusion bottleneck at the cluster boundaries and a significant sample overheating due to microwave irradiation. Subsequent DNP system modifications designed to reduce the overheating resulted in four-fold increase of (129)Xe polarization, from 5.3% to 21%