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Abstract

Non-invasive biological tissue information is vital for medical diagnostics and treat- ment monitoring. While standard 1H magnetic resonance imaging (MRI) methods show detailed morphological information, 23Na MRI provides additional biochemical information about the tissue. Sodium nuclei have spin 3/2 and, therefore, can exhibit higher quantum coherence signals. Multi-quantum (MQ) imaging offers additional information compared to standard SQ sodium, which focuses on tissue sodium concentration (TSC), e.g., it is hard to discern edema and tumor regions, both exhibiting higher TSC. 23Na triple-quantum (TQ) signals are of high interest to probe the molecular environment in tissues and alleviate this problem. The focus of this thesis was on the 23Na TQ signal from preclinical investigations on cells via a simulation study and, finally, a transfer of preclinical and simulation find- ings into the development of an optimal clinical MQ imaging sequence, CRISTINA. First, the physiological importance was studied at ultra-high field, 9.4 T, to gain in- sight into TQ signal changes under different cellular conditions. An MR-compatible bioreactor setup allowed for finely tunable TQ signal monitoring of cell lines human liver cells (HEP G2) and neonatal cardiomyocytes of mice. Both cell lines showed a TQ signal in vital state, under standard perfusion [0.26%,15σ], normalized to the SQ signal. Hypertrophy was simulated with oxygen and nutrient stop and resulted in a TQ signal to 56% of the initial value [0.15%,24σ]. Re-perfusion resulted in a come back of the TQ signal to 92% of the initial value. Reference measurements without cells as well as dead cells showed a TQ signal of [0.06%,1σ and 0.016%,1σ]. Further, the long-standing debate of TQ signal connection to intracellular space was investigated based on liposomal cell-phantoms and it was shown that the TQ signal in liposomes was related to the interaction of the sodium ions with the double lipid membrane, which is constituted of negatively charged fatty acids. A single-voxel localization technique was developed on the preclinical system as the first step in the direction of a clinical sequence and tested on phantoms and in-vivo rat. Second, simulation of different phase-cycle schemes of the standard three-pulses coherence transfer technique was performed. A unified framework was developed to compare and find an optimum. Destructive effects of B0 inhomogeneity were investigated and verified for Ω(Hz) = (kπ + ξ)/(τ1), k ∈ Z. Stimulated echo signal stood as further potential biases but resulted in a continuous offset after Fourier Transformation. Third, knowledge from part I and II was transferred to develop an efficient clinical vii MQ imaging method: CRISTINA, a 2D Cartesian MQ, multi-echo imaging sequence for clinical use. A Multi-parameter fit routine provided T2 relaxations maps and ratio of TQ to SQ signals which could be of interest to monitor pathologies in future. CRISTINA was tested and optimized on phantoms and in vivo on 5 healthy brain volunteers. A linear relationship was found for the ratio TQ over SQ signal against agar concentrations (R2 =0.87, p-value = 0.0007) as well as for the SQ signal against TSC (R2 =0.75, p-value = 0.006).