University thesis:
Dissertation, Universität Freiburg, 2020
Footnote:
Description:
Abstract: Magnetic resonance (MR) is a powerful modality for medical diagnostics but the low sensitivity limits its use almost solely to imaging of water and fat. The hyperpolarization (HP) of nuclear spins allows enhancing the MR signal of selected molecules by several orders of magnitude. For instance, tumor metabolism can be imaged by following the fate of metabolically active molecules with highly increased sensitivity. To produce HP tracers a dedicated external device, a “polarizer”, is needed. Besides significant costs and complex hardware, a disadvantage of this approach is that a significant fraction of precious HP is lost during the transfer of the tracer to the MRI system. <br>In this thesis, parahydrogen (pH2) induced polarization (PHIP) of carbon-13 of P13C > 10 % was achieved for the first time inside a preclinical 7 Tesla MR imaging (MRI) system. In addition to the MRI system, only little extra hardware was needed at less than 2000 €. The HP tracers hydroxyethyl 1 13C-2,3,3-D-propionate (HEP), tetrafluoropropyl 1-13C-2,2,3,3-D-propionate (TFPP), 1-13C-2,3-D-succinate and 1,2,2-D-ethyl 1 13C-2,2,2-D-acetate were successfully polarized. The highest HP was observed for TFPP with P13C = (30 ± 1) %, corresponding to a signal enhancement factor of (50 ± 2)·103. The longest lifetime of the HP was measured for HEP in D2O with T1 = (78 ± 3) s. The method allowed for a repetitive production of hyperpolarized batches in no more than 15 s. The production and subsequent imaging of hyperpolarized tracers within seconds was demonstrated in a mouse model in vivo. Compared to previous implementations of PHIP, the experimental repetition time and cost of the setup were further reduced by an order of magnitude (≈ 104 → 103 € and ≈ 102 → 101 s).<br>In a related line of this work, the relaxation of pH2, the source of spin order of PHIP, was investigated: The para-to-ortho conversion time, τ_POC, and the longitudinal relaxation time, T1, of H2 were determined in various aqueous solutions, with or without O2, NaCl, hydrogenation catalyst and human blood. The measured values were between τ_POC = 20 to 300 min and T1 = 1.3 to 2 s. Given these remarkably long τ_POC times, PHIP with pH2-saturated solution was implemented and evaluated as an alternative method to achieve a fast hydrogenation.<br>While these results are promising, the relevance of the new methods for biomedical applications has yet to be shown. Certainly, an important step would be the production of biomedically relevant molecules polarized to a level and concentration sufficient for diagnostic application. Still, considering the HP yield, simplicity, low-cost and repetition rate, the method may significantly contribute to the research on and application of hyperpolarized tracers, which have the potential to revolutionize MRI in medical diagnostics