Sean Bowen

Assessment of early diabetic renal changes with hyperpolarized [1‐13C]pyruvate

This experimental study explores a novel magnetic resonance imaging/spectroscopic (MRI/MRS) method that measures changes in renal metabolism in a diabetic rat model. This hyperpolarized metabolic MRI/MRS method allows monitoring of metabolic processes in seconds by >10 000‐fold enhancement of the MR signal. The method has shown that the conversion of pyruvate to bicarbonate, i.e. pyruvate dehydrogenase (PDH) activity, is significantly altered in the myocardium already at the onset of diabetes, and the predominant Warburg effect is a valuable cancer maker via the lactate dehydrogenase (LDH) activity. We hypothesize that a similar change in PDH and LDH could be found in the early diabetic kidney.

Hyperpolarized H2O MR angiography

The aim of this study was to demonstrate that dissolution‐ dynamic nuclear polarization is capable of hyperpolarizing water protons and that the signal from the hyperpolarized bolus injection can be exploited in angiographic applications.

Dissolution dynamic nuclear polarization of non-self-glassing agents: spectroscopy and relaxation of hyperpolarized [1-13C]acetate.

The intrinsic physicochemical properties of the sample formulation are the key factors for efficient hyperpolarization through dissolution dynamic nuclear polarization (dissolution-DNP). We provide a comprehensive characterization of the DNP process for Na-[1-(13)C]acetate selected as a model for non-self-glassing agents: the solid-state polarization dynamics of different formulations and the effect of the paramagnetic agent (trityl radical) on the pattern of polarization and the relaxation profile were extensively analyzed. We quantified the effects of the glassing agent and Gd(3+)-chelate on DNP performance. The results reported here describe the constraints of the acetate formulation useful for future studies in this field with non-self-glassing enriched molecules.

Formulation and utilization of choline based samples for dissolution dynamic nuclear polarization.

Hyperpolarization by the dissolution dynamic nuclear polarization (DNP) technique permits the generation of high spin polarization of solution state. However, sample formulation for dissolution-DNP is often difficult, as concentration and viscosity must be optimized to yield a dissolved sample with sufficient concentration, while maintaining polarization during the dissolution process. The unique chemical properties of choline permit the generation of highly soluble salts as well as deep eutectic mixtures with carboxylic acids and urea. We describe the formulation of these samples and compare their performance to more traditional sample formulations. Choline yields stable samples with exceptional polarization performance while simultaneously offering the capability to easily remove the choline after dissolution, perform experiments with the hyperpolarized choline, or anything in between.

Waveguide transition with vacuum window for multiband dynamic nuclear polarization systems

A low loss waveguide transition section and oversized microwave vacuum window covering several frequency bands (94 GHz, 140 GHz, 188 GHz) is presented. The transition is compact and was optimized for multiband Dynamic Nuclear Polarization (DNP) systems in a full-wave simulator. The window is more broadband than commercially available windows, which are usually optimized for single band operation. It is demonstrated that high-density polyethylene with urethane adhesive can be used as a low loss microwave vacuum window in multiband DNP systems. The overall assembly performance and dimensions are found using full-wave simulations. The practical aspects of the window implementation in the waveguide are discussed. To verify the design and simulation results, the window is tested experimentally at the three frequencies of interest.

Enhanced performance large volume dissolution-DNP.

A systematic study of the performance of the dissolution process in dissolution-DNP is presented. A relatively simple set of modifications is made to the standard Hypersense dissolution system to enable polarization of large volume samples. These consist of a large volume sample cup along with supporting modifications to the dissolution head and related components. Additional modifications were made to support the mapping of the temperature/pressure space of the dissolution process as well as enabling the use of large volumes of solvent and improving the robustness of the system. No loss of polarization was observed as sample size was increased to the 1 g capacity of the large volume cup and for a dilution factor as low as 1:10.

Large dose hyperpolarized water with dissolution-DNP at high magnetic field

We demonstrate a method for the preparation of hyperpolarized water by dissolution Dynamic Nuclear Polarization at high magnetic field. Protons were polarized at 6.7T and 1.1K to >70% with frequency modulated microwave irradiation at 188GHz. 97.2±0.7% of the radical was extracted from the sample in the dissolution in a two-phase system. 16±1mL of 5.0M 1H in D2O with a polarization of 13.0±0.9% in the liquid state was obtained, corresponding to an enhancement factor of 4000±300 compared to the thermal equilibrium at 9.4T and 293K. A longitudinal relaxation time constant of 16±1s was measured. The sample was polarized and dissolved in a fluid path compatible with clinical polarizers. The volume of hyperpolarized water produced by this method enables angiography and perfusion measurements in large animals, as well as NMR experiments for studies of e.g. proton exchange and polarization transfer to other nuclei.

Simultaneous imaging of hyperpolarized [1,4-13C2]fumarate, [1-13C]pyruvate and 18F–FDG in a rat model of necrosis in a clinical PET/MR scanner

A co‐polarization scheme for [1,4‐13C2]fumarate and [1‐13C]pyruvate is presented to simultaneously assess necrosis and metabolism in rats with hyperpolarized 13C magnetic resonance (MR). The co‐polarization was performed in a SPINlab polarizer. In addition, the feasibility of simultaneous positron emission tomography (PET) and MR of small animals with a clinical PET/MR scanner is demonstrated. The hyperpolarized metabolic MR and PET was demonstrated in a rat model of necrosis. The polarization and T1 of the co‐polarized [1,4‐13C2]fumarate and [1‐13C]pyruvate substrates were measured in vitro and compared with those obtained when the substrates were polarized individually. A polarization of 36 ± 4% for fumarate and 37 ± 6% for pyruvate was obtained. We found no significant difference in the polarization and T1 values between the dual and single substrate polarization. Rats weighing about 400 g were injected intramuscularly in one of the hind legs with 200 μL of turpentine to induce necrosis. Two hours later, 13C metabolic maps were obtained with a chemical shift imaging sequence (16 × 16) with a resolution of 3.1 × 5.0 × 25.0 mm3. The 13C spectroscopic images were acquired in 12 s, followed by an 8‐min 18F‐2‐fluoro‐2‐deoxy‐d‐glucose (18F–FDG) PET acquisition with a resolution of 3.5 mm. [1,4‐13C2]Malate was observed from the tissue injected with turpentine indicating necrosis. Normal [1‐13C]pyruvate metabolism and 18F–FDG uptake were observed from the same tissue. The proposed co‐polarization scheme provides a means to utilize multiple imaging agents simultaneously, and thus to probe various metabolic pathways in a single examination. Moreover, it demonstrates the feasibility of small animal research on a clinical PET/MR scanner for combined PET and hyperpolarized metabolic MR.

Storage of magnetization as singlet order by optimal control designed pulses.

The use of hyperpolarization to enhance the sensitivity of MRI has so far been limited by the decay of the polarization through T1 relaxation. Recently, methods have been proposed that extend the lifetime of the hyperpolarization by storing the spin order in slowly relaxing singlet states.

Modeling of Schottky barrier diode millimeter-wave multipliers at cryogenic temperatures

We report on the evaluation of Schottky barrier diode GaAs multipliers at cryogenic temperatures. A GaAs Schottky barrier diode model is developed for theoretical estimation of doubler performance. The model is used to predict efficiency of doublers from room to cryogenic temperatures. The theoretical estimation is verified experimentally using a 78 GHz doubler cooled down to 14 K. The observed efficiency improvement due to cooling is approximately 4 % per 100 degrees.