Xenon Dynamic Nuclear Polarization: from Spin Dynamics to In-Vivo Applications
Hyperpolarization in Magnetic Resonance Imaging addresses the inherently low sensitivity of the imaging modality. The range of hyperpolarization techniques has drastically improved in the last 25 years, exploring a range of functionality including metabolic, perfusion and ventilation substrates. Two central hyperpolarization techniques are Spin Exchange Optical Pumping (SEOP) and Dynamic Nuclear Polarization (DNP), whereas the first is applied while the substrate is in a gaseous state, the latter hyperpolarizes while the substrate is in solid state. Noble gases are particularly well-suited for ventilation pulmonary imaging, some also dissolves and can be imaged beyond the lungs.
While there are reports of using Dynamic Nuclear Polarization to hyperpolarize xenon gas, questions remain on the solid-state mechanisms when using 129Xe as a polarization target. One major concern was the variability in the solid-state polarization levels, lacking a robustness in the sample preparation. An inhomogeneous sample, with clusters of xenon, would consistently achieve lower polarization levels. The clusters' creation was caused by a few different reasons, but the conditions to avoid it were not so straightforward. In this thesis, solid-state polarization of 129Xe with Dynamic Nuclear Polarization was first assessed in a custom-made 5 T polarizer. Using ultrasonication during the sample preparation reduced the creation of xenon clusters, confirmed by an increase in T2 relaxation time. The radical properties were evaluated in DNP conditions, by the electron relaxation times and the electron spin resonance spectrums. In comparison to a sodium [1-13C]acetate sample, the 129Xe samples had a far larger improvement in solid-state polarization when altering the microwave irradiation with frequency modulation. After establishing the sample preparation method, the subsequent step of sublimation was addressed. The sound sublimation output was tested in two labs, ultimately fit for in vivo acquisitions on a clinical scanner.
The developed method of xenon DNP was transposed to a lab environment capable of both DNP and SEOP techniques. The difference in polarizer and scanner equipment required alterations, such as using a trityl instead of a nitroxide radical due to the higher magnetic field of the polarizer. After fitting the sublimation, the resulting hyperpolarized xenon gas was assessed in a clinical scanner, by magnetic resonance spectroscopy and ventilation imaging of Tedlar bags. Due to the robust protocol, an in vivo experiment followed, imaging porcine lungs, a standard benchmark in the hyperpolarization community. All xenon DNP measurements were compared to hyperpolarized xenon gas by SEOP, and while SEOP outperformed in level of detail, DNP still yielded 129Xe signal both in gaseous and dissolved state, an important definition in pulmonary imaging. Overall, this work advances the use of a second hyperpolarization technique for 129Xe, how to adjust it between different lab environments, while also exploring DNP mechanisms.
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