Molecular imaging plays a key role in answering clinical needs for personalized medicine. It gives insight into complex biochemical processes at the molecular and cellular level associated with a wide range of disease. While magnetic resonance imaging (MRI) is a renowned modality for clinical diagnosis based on anatomical and/or physiological images, molecular MRI is limited by moderate sensitivity. Thus, in certain cases, contrast agents are administered to enhance the MRI signal. Contrast agents with a strong magnetic field dependence, i.e. a strong nuclear magnetic relaxation dispersion, have been shown to be effective in generating target-specific contrast in MRI. The utilization of this relaxation dispersion requires the adaptation of an MRI scanner to allow for a modulation of the main magnetic field during the imaging sequence, also regarded to as fast field-cycling (FFC). This thesis is devoted to investigate, how to generate novel MRI contrast based on variations in the nuclear magnetic relaxation dispersion around a clinical field strength of 3~T. Such features would be otherwise hidden for conventional MRI. We report the first adaptation of a clinical 3~T MRI system for field-cycling. The presented FFC-MRI system is validated by means of dispersive contrast agents. It can potentially add value to the detection of various biomarkers, as is shown here for the specific case of zinc detection. Moreover, we introduce quadrupole relaxation enhancement as a mechanism of action for a fundamentally new class of reversibly activatable contrast agents with frequency-selective nuclear magnetic relaxation dispersion.
|Qualification||Doctor of Technology|
|Publication status||Published - Jan 2020|