Biophysical Basis of the Diffusion-Weighted Magnetic Resonance Signal in the Rat Brain

Nuclear magnetic resonance (NMR) can be used in-vivo in a vast array of applications, such as anatomical imaging (magnetic resonance imaging, MRI), localized chemical composition characterization (magnetic resonance spectroscopy, MRS), cellular structure assessment (diffusion tensor imaging, DTI) and cerebral activity mapping (functional imaging, fMRI) for the most important one. This thesis focused on the development of diffusion NMR spectroscopy and imaging methods at ultra-high magnetic field, with the aim of a better characterization of the diffusion mechanism in-vivo. DTI measures the water molecule displacement due to the thermal agitation in the sample. In cellular tissue, the molecules are restrained in compartments delimited by the cell membranes, which mean that DTI can provide information on the cerebral cellular microstructure. DTI is thus widely used to investigate cerebral disorders such as brain ischemia, trauma, and tumors, as well as the structural changes occurring during brain development and normal aging. However, the presence of water molecules in both the intra- and extra-cellular compartments may bias the assessed structural information. On the other hand, the metabolites, measured by 1H-MRS, are mostly localized in the intracellular compartment, which may provide a more precise insight of the cellular structure. With the availability of high magnetic field systems, 1H-MRS allows the measurement of 15 – 20 metabolites in-vivo in localized region in the order of &icro;l in the rodent brain. These metabolites are involved in cell energy management, neurotransmission, neuro-protection, neuronal development and membrane growth, and thus provide a rather complete status of the brain neurochemical profile. In this context, a diffusion tensor spectroscopy pulse sequence (DT-MRS) was implemented and used to investigate the metabolite diffusion properties in specific brain regions in-vivo at ultra-high magnetic field 14.1 T to benefit from the increased sensitivity and spectral resolution at high B0. The diffusion tensor of 5 metabolites were reconstructed in the corpus-callosum, CC, (NAA, Tau, Glu, Ins and Mac) and 8 in the cortex, Cx, (with in addition Cr, PCr, GABA and GSH). Metabolites apparent diffusion coefficients were significantly higher in the CC (0.115 – 0.153 µm2/ms) than in the Cx (0.087 – 0.107 µm2/ms) and so was the fractional anisotropy (0.51 – 0.62 and 0.34 – 0.51 respectively). In addition, the metabolite preferential diffusion directions showed an excellent agreement with the known rat brain structure. The aforementioned DW-MRS pulse sequence was then combined with an inversion recovery module, allowing direct assessment of the macromolecule (MM) signal, which overlaps with metabolites resonances. An inaccurate estimation of the MM baseline may result in a significant bias during the quantification process. At ultra-high magnetic field, the MM spectral shape becomes more complex, and therefore, the previously repo