Nuclear Magnetic Resonance Relaxation - Clinical MRI Mapping Harmonization and Novel Aspects in Ln-based Contrast Agents

This PhD thesis has two major purposes. The first goal is to propose a robust method based on a well-characterized in-scan reference phantom for the validation and harmonization of relaxation time maps acquired through Magnetic Resonance Imaging (MRI) techniques. The second goal is to investigate novel aspects of the relaxation enhancement mechanisms of some lanthanide complexes, used as MRI contrast agents for high-field applications by analyzing their Nuclear Magnetic Relaxation Dispersion (NMRD) profiles. These goals are accomplished by means of 1H Nuclear Magnetic Resonance (NMR) relaxometry and MRI techniques employing different scanners and spectrometers at several magnetic field strengths. As to the first goal, we present a proof-of-concept study focusing on a method for the intra- and inter-center validation and harmonization of data obtained from MRI T1 and T2 maps. The method is suggested for the simultaneous scan of the patient and a set of MnCl2 samples, arranged in a cartridge-like belt configuration, that provide in-scan ground-truth reference values for the recalibration of the maps, regardless of the details of the MRI protocol. The relaxation times of MnCl2 aqueous solutions were first measured by means of an NMR laboratory relaxometer, as a function of concentration and temperature. The obtained T1 and T2 values, once renormalized at the scanner temperature, were used as reference values for the MRI mapping measurements of the MnCl2 relaxation times. By using different clinical MRI scanners and sequences, we found a good agreement for standard and turbo sequences (limits of agreement: 5% for IR, SE, IRTSE; 10% for TSE), while an under-estimation and an over-estimation were found respectively for MOLLI and T2-prep TrueFISP, as already reported in the literature. The linearity of the relaxation rates with the concentration predicted by the Solomon-Bloembergen-Morgan theory was observed for every dataset at all temperatures, except for T2-prep TrueFISP maps results. A phantom study and a preliminary in vivo experiment on an untrained volunteer confirmed the feasibility of map recalibration for MOLLI sequence while questioning the reliability of T2-prep TrueFISP maps, for which further investigations are needed. In the second research project, longitudinal and transverse 1H NMR nuclear relaxivities of Ln(III)-DOTA complexes (with Ln = Gd, Dy, Tb, Er; DOTA = 1,4,7,10 - tetraazacyclododecane - N,N’,N”,N”’ - tetraacetic acid) and Mn(II) aqueous solutions were measured in a wide range of frequencies, 10 kHz - 700 MHz. The experimental data were interpreted by means of models derived from the Solomon-Bloembergen-Morgan theory. The data analysis was performed assuming the orbital angular momentum L = 0 for Gd-DOTA and the aqua ion [Mn(H2O)6]2+ and L ̸= 0 for Dy- DOTA, Tb-DOTA, and Er-DOTA. A refined estimation of the Zero-Field- Splitting barrier Δ and of the modulation correlation time τv was obtained for [Mn(H2O)6]2+ by extending the fitting of NMRD profiles to the low-field regime. The Gd-DOTA fitting parameters resulted in good agreement with the literature, and the fit of transverse relaxivity data confirmed the negligibility of the scalar interaction in the nuclear relaxation mechanism. Larger transverse relaxivities of Dy-DOTA and Tb-DOTA (∼ 10 mM−1s−1) with respect to Er-DOTA (∼ 1 mM−1s−1) were observed at 16 T, compatibly with a shorter residence time of the coordinated water molecule τm, which heavily influences the fluctuation rate of the dipolar electron-nuclear interaction that, in turn, depends on the electronic spin correlation rate and the magnetic anisotropy. The possible employment of Dy-DOTA, Tb-DOTA, and Er-DOTA as negative MRI contrast agents for high-field applications was envisaged by collecting spin-echo images at 7 T. Particularly in Dy- and Tb- derivatives the transverse relaxivity at 16 T is of the order of the Gd- one at 1.5 T.