Investigation of Water Mobility using Diffusion-Sensitive MRI: The Role of q-Space Imaging, High b-Values and Diffusion Time

Abstract: Nuclear magnetic resonance (NMR) diffusometry provides important information about molecular motion on a microscopic scale. The advantage of NMR diffusometry is its ability to characterise microstructures non-invasively. This has made the method important not only in chemistry, biochemistry and materials science, but also in medicine. Diffusion-weighted magnetic resonance imaging (DW-MRI) has been used for about 20 years at specialised radiology departments worldwide. One of the most important clinical features of DW-MRI is its ability to reveal ischaemic lesions within minutes of the onset of an infarct. Surprisingly, the mechanism behind the observed image contrast has not yet been completely explained. As the performance of clinical MRI scanner hardware improves, methods originally developed for experimental NMR spectrometers can be applied to studies of human tissue in vivo. This will benefit patients by improving the diagnostic capability of MRI. The aim of the studies described in this doctoral thesis was to use DW-MRI measurements to develop and evaluate methods for studies of the microstructural environment of diffusing water molecules in vivo. The experiments were primarily performed using a 3T clinical head scanner, but additional phantom measurements were carried out using an NMR spectrometer. In one of the studies, multiple sclerosis (MS) patients were examined and q-space-related parameters were evaluated with respect to image contrast. A closer examination of the limitations of the q-space method using both phantom measurements and extensive Monte Carlo simulations was performed in an additional project. The knowledge obtained was applied to investigations of a biological phantom in which compartments sizes restricting the diffusion of water were quantified using a clinical scanner. Based on the understanding gained from the simulations and phantom measurements, a slightly different approach, based on the use of different diffusion times, was used in a volunteer study to investigate the possible effects of restricted diffusion in nerve tissue in vivo. This approach was pursued in a preliminary study of patients with ischaemic lesions, and the results revealed water exchange between different water pools within the lesions.