Huntington’s Disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats on the exon 1 of the HTT gene. Although genetic origin of HD is well-established, early and predictive biomarkers of disease onset and progression are still lacking. In the present study, we performed a multiparametric longitudinal MRI study on a mouse model of HD. Our results in gluCEST, Magnetization Transfer, morphometry and Diffusion Tensor Imaging revealed early modifications of white matter followed by progressive functional and anatomical changes in HD mice. Such network seems to point out the central role of white matter in HD pathogenesis.