This thesis is focused on the human brain microstructure mapping using quantitative and diffusion MRI. The T1/T2 quantitative imaging relies on sequences dedicated to the mapping of T1 and T2 relaxation times. Their variations within the tissue are linked to the presence of different water compartments defined by a specific organization of the tissue at the cell scale. Measuring these parameters can help, therefore, to better characterize the brain microstructure. The dMRI, on the other hand, explores the brownian motion of water molecules in the brain tissue, where the water molecules' movement is constrained by natural barriers, such as cell membranes. Thus, the information on their displacement carried by the dMRI signal gives access to the underlying cytoarchitecture. Combination of these two modalities is, therefore, a promising way to probe the brain tissue microstructure. The main goal of the present thesis is to set up the methodology to study the microstructure of the white matter of the human brain in vivo. The first part includes the acquisition of a unique MRI database of 79 healthy subjects (the Archi/CONNECT), which includes anatomical high resolution data, relaxometry data, diffusion-weighted data at high spatio-angular resolution and functional data. This database has allowed us to build the first atlas of the anatomical connectivity of the healthy brain through the automatic segmentation of the major white matter bundles, providing an appropriate anatomical reference for the white matter to study individually the quantitative parameters along each fascicle, characterizing its microstructure organization. Emphasis was placed on the construction of the first atlas of the T1/T2 profiles along the major white matter pathways. The profiles of the T1 and T2 relaxation times were then correlated to the quantitative profiles computed from the diffusion MRI data (fractional anisotropy, radial and longitudinal diffusivities, apparent diffusion coefficient), in order to better understand their relations and to explain the observed variability along the fascicles and the interhemispheric asymmetries. The second part was focused on the brain tissue modeling at the cell scale to extract the quantitative parameters characterizing the geometry of the cellular membranes, such as the axonal diameter and the axonal density. A diffusion MRI sequence was developed on the 3 Teslas and 7 Teslas Siemens clinical systems of NeuroSpin which is able to apply any kind of gradient waveforms to fall within an approach where the gradient waveform results from an optimization under the hypothesis of a geometrical tissue model, hardware and time constraints induced by clinical applications. This sequence was applied in the study of fourteen healthy subjects in order to build the first quantitative atlas of the axonal diameter and the local axonal density at 7T. We also proposed a new geometrical model to model the axon, dividing the axonal compartment, usually modelled using a simple cylinder, into two compartments: one being near the membranes with low diffusivity and one farer from the membranes, less restricted and with higher diffusivity. We conducted a theoretical study showing that under clinical conditions, this new model allows, in part, to overcome the bias induced by the simple cylindrical model leading to a systematic overestimation of the smallest diameters. Finally, in the aim of going further in the physiopathology of the autism, we added to the current 3T imaging protocol the dMRI sequence developed in the framework of this thesis in order to map the axonal diameter and density. This study is ongoing and should validate shortly the contribution of these new quantitative measures of the microstructure in the comprehension of the atrophies of the corpus callosum, initially observed using less specific diffusion parameters such as the generalized fractional anisotropy. There will be other clinical applications in the future.
| Identifer | oai:union.ndltd.org:CCSD/oai:tel.archives-ouvertes.fr:tel-01063198 |
| Date | 23 July 2014 |
| Creators | Lebois, Alice |
| Publisher | Université Paris Sud - Paris XI |
| Source Sets | CCSD theses-EN-ligne, France |
| Language | English |
| Detected Language | English |
| Type | PhD thesis |
Page generated in 0.0018 seconds