Development of an In-bore DNP Polarizer at 1.5 T Magnetic Field for in vivo MRI and MRS Studies
Final Report Abstract
This project aimed to enhance the NMR signal intensity for MRI applications by means of Dynamic Nuclear Polarization (DNP) at a magnetic field strength of 1.5 T. In contrast to other approaches the hyperpolarization of the nuclear spins of metabolites was achieved with a microwave resonator situated directly inside the bore of the MRI magnet. A DNP polarizer working at a frequency of 42 GHz for aqueous samples was developed, constructed and tested under continuous flow conditions. By this approach the distance between the polarization unit and the target object was minimized, allowing the direct observation of proton polarization in test objects. Additionally, this approach avoided polarization losses which arise if the sample is transferred from a separate polarizing magnet into the MRI magnet by passage effects through low magnetic fields and the differences between polarizing and detection field. Whereas much higher polarizations and volumes can be achieved by approaches, in which the target is polarized at very low temperatures and transferred to the MRI magnet after a fast dissolution process (Dissolution DNP), our approach allows to achieve a stable and continuous flow of polarized target molecules in solution with a fast polarization buildup of the order of seconds, which is of advantage for many MRI and MRS applications. High sensitivity and contrast gain have been achieved on a small flat cell phantom. In principle this method might allow to achieve high contrast without any contrast-agent present in the object of study (with immobilized radicals in the polarizer). Because of the still small flow volume of polarized solute and the fast decay of proton spin polarization, investigations related to flow dynamics in micro-reactor chemical chips might be the first obvious application area of this method. Using IR-preparation allows for significant increasing of both efficiency and flexibility of using a DNP- enhanced magnetization. The CNR of images can be dramatically increased by suppression of TP-background magnetization. Using IR-preparation it is possible to quantify the performance of HP-liquid production and efficiency of using different MR-imaging sequence. It was shown that signal intensity provided by continuous flow DNP-enhanced magnetization can be approximated quantitatively by the solution of a straightforward and simple balance equation. For the IR-SE and IR-SGRE sequences the resulted dependence of the image intensity from the sequence parameters (TR and FA) is qualitatively similar to the results obtained for steady-state and transient-state evolution of magnetization in spoiled GRE and SE sequences. However, the numeric model can be extended to take into account a complex of the DNP-specific factors influencing the MR-signal intensity. In particular, a dependence of DNP enhancement factor from the sample flow rate, temperature variation and relaxation time (taking into account the mutual influences of these parameters) might be considered. The flexibility of the approach was demonstrated, in particular, by including into the numerical model a temperature depended relaxation rate to take into account the effect of heating of the sample inside the resonator cavity. The study shows that using IR-preparation can be potentially effective for the visualization of HP substrate injected in-vivo. Mouse aorta was visualized with injection of HP TEMPOL and IR- preparation was used to suppress signal of tissues. The experiment, however, faced difficulties with proper catheterization and tightening of the inlet in mouse vessels to avoid blocking of the stream and backflow of administered solution. The highly qualified micro-surgery needs to be involved to make possible in-vivo applications. In this proposal we focused on the idea of performing continuous in-bore hyperpolarization of water in a clinical scanner. Although 1H in water is highly abundant, it is of limited use in-vivo because of its relatively short T1 relaxation times. 13C is of major interest here because of the abundant carbon atoms in biomolecules, where they have long relaxation times of 20 sec and more. Therefore, we are currently working on an extension of our polarizer to hyperpolarize the 13C nucleus. Successful pilot experiments have been performed already and will open a new window into hyperpolarized liquid application in biomedical research and, potentially, diagnostics because of the continuous flow of hyperpolarized biomolecules.
Publications
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(2010) Spin-labeled heparins as polarizing agents for dynamic nuclear polarization, ChemPhysChem., 11, 3656-3663
Dollmann, B., Kleschyov, A., Sen, V., Golubev, V., Schreiber, L.M., Spiess, H., Münnemann, K., Hinderberger, D.
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Hyperpolarisationseinrichtung und Verfahren zur Verabreichung eines hyperpolarisierten flüssigen Kontrastmittels. Deutsches Patent Nr. 10 2010 017 568
Krummenacker, J., Denysenkov, V., Schreiber, L., Prisner, T., Münnemann, K.
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Hyperpolarisationseinrichtung und Verfahren zur Verabreichung eines hyperpolarisierten flüssigen Kontrastmittels. PCT WO 2011/160853
Krummenacker, J., Denysenkov, V., Schreiber, L., Prisner, T., Münnemann, K.
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(2012) DNP in MRI: An in-bore approach at 1,5 T, J. Magn. Reson., 215, 94-99
Krummenacker, J., Denysenkov, V., Terekhov, M., Schreiber, L., Prisner, T.F.
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Hyperpolarization apparatus and method for administration of a hyperpolarized liquid contrast agent. US Pat. US2013/0184565
Krummenacker, J., Denysenkov, V., Schreiber, L., Prisner, T., Münnemann, K.
