IRM microscopique 3D de la migration de cellules tumorales et tractographie du cerveau de souris : applications à un modèle de glioblastome Glio6 et de schizophrénie MAP6

Abstract : This thesis aims to develop magnetic resonance imaging (MRI) techniques to detectneurological damage at the microscopic level in animal models. Two mouse models were examined inparticular human glioblastoma model (Glio6) and a schizophrenia mouse model (MAP6 model). Themethodologies developed were centered around 3D fast diffusion tensor imaging (DTI) with highspatial resolution for ex vivo and in vivo applications in rodents. In Glio6 model, the migration oftumor cells in the corpus callosum was early detected and quantified while no signs were visible onconventional anatomical MRI. Tractography identified deficits of some tracts and their connectivity inthe MAP6 model. Inhomogeneous alterations were detected, especially with a drastic reduction of thecorticospinal pathway. Theses results highlight the crucial role of the MAP6 protein in the braindevelopment. The "Super Resolution" post-proccesing was developed and applied in vivo to MAP6mouse model. Tractography imaging comparable to that obtained ex vivo (in 59h) was obtained in lessthan one hour, paving the way for in vivo longitudinal studies as brain development studies orevaluation of new therapies. On the other hand, a in vivo cellular MRI method has been established.The principle is based on the combined measurement of cell relaxivities in vitro, to obtain in vivo cellconcentrations based on relaxation parameters. Using the U87 glioma model and U937 magneticallylabeled cells, the results showed that a wide range of cell concentrations can be quantified and thebiodistribution of U937 cells around the tumor is heterogeneous, information essential to study theeffectiveness of cell therapy.
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Ulysse Gimenez. IRM microscopique 3D de la migration de cellules tumorales et tractographie du cerveau de souris : applications à un modèle de glioblastome Glio6 et de schizophrénie MAP6. Cancer. Université Grenoble Alpes, 2015. Français. ⟨NNT : 2015GREAS026⟩. ⟨tel-01766455⟩

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