The role of nuclear quadrupole spin resonance in the design of a new class of MRI-contrast agents

The administration of contrast agents (CAs) in magnetic resonance imaging (MRI) is an indispensable technique to improve image quality and contrast and is thus supporting medical diagnostics for many diseases and pathologies. In September 2015, a research project has been started suggesting a novel contrast agent type, relying upon quadrupole relaxation enhancement (QRE) instead of the currently exploited paramagnetic relaxation enhancement (PRE) effect. The former effect is based on a magnetic dipole-dipole interaction between nuclear spins, the latter between proton and electron spins.

Both techniques aim at enhancing the spin-lattice relaxation rate of proton spins in water molecules sensed by MRI. The enhanced relaxation then leads to an increased contrast in the MRI scan. As the QRE effect is intrinsically selective on the strength of the applied magnetic field in a quantized manner, it is expected that QRE-based CAs have the potential to add several useful methodical features to CA-supported MRI. Also, the QRE effect depends on the electronic structure of the QRE-active molecule, which allows for electronic sensitivity. From these properties, two mechanisms are conceivable: First, on-off switching the contrast effect by an external stimulus i.e. shifting the scanner field. Second, molecular imaging due to modulation of the QRE effect upon electronic alterations. Another argument for alternative CAs is that PRE agents mostly contain Gadolinium (Gd) (encapsulated in stable chelates) and can thus not be administrated to patients with kidney diseases. Lately, it has also been reported that Gd-CAs from particular chelates can be found to remain in the brains of healthy patients.

Central research interest of this work is to support proof-of-concept research for QRE-based contrast agents. In particular, focus is set on the role of nuclear quadrupole resonance within the total magnetization transfer effect from the polarized protons via a close by quadrupole nuclei to the lattice. Mostly by the use of nuclear quadrupole resonance (NQR) spectroscopy, promising compounds containing Bismuth (Bi) are preselected, fulfilling basic requirements of the envisaged application. Also, their spin-spin and spin-lattice relaxation behaviour is studied and assessed with respect to their influence on the QRE effect. To support the structural and morphological design of complete nanoparticle systems, made up of QRE active core compounds and a carrier particle, studies are presented discussing the dependence of NQR transitions upon molecular structure. At the end of this work, besides first promising results of the QRE effect of triphenylbismuth nanoparticles in aqueous solution, a guideline regarding physical and chemical properties is outlined which shall be considered in further particle design.
Schlagwörter Nuclear quadrupole resonance, quadrupole relaxation enhancement, MRI contrast agent, nuclear spin relaxation