Huntington's disease is an inherited neurodegenerative disease characterized by motor, cognitive and psychiatric symptoms. There is a limited number of methods allowing precise follow up of disease progression. Clinical assessments along with neuroimaging techniques are likely the most robust criteria to characterize disease severity in patients. Currently, the best biomarker of disease progression is the atrophy of the striatum as measured by MRI. Unfortunately, such morphological alterations of brain structures are long-term consequences of alterations that occurred several years before onset of symptoms and they do not provide relevant information about the biological mechanisms linked to Huntington's disease pathogenesis.
The group of Julien Flament is working on a new MRI modality, called CEST for Chemical Exchange Saturation Transfer, allowing in vivo mapping of some brain metabolites with a good spatial resolution. In the framework of a translational project funded by ANR (HDeNERGY project), CEST imaging has been applied to monitor glutamate distribution in the brain of Huntington's disease mouse model. The team demonstrated in a study published in NeuroImage in June 2016 the potential of CEST imaging as a good biomarker of the disease. Thanks to the good spatial resolution, CEST imaging revealed that the corpus callosum was severely affected in mice, suggesting that this structure could be highly vulnerable in the context of Huntington's disease.
© Julien Flament
Thanks to the good spatial resolution of CEST imaging, mice brain were segmented in several regions of interest (top panel). For each structure, the variation of glutamate level was measured between a group of control mice and heterozygous mice (bottom left) and between control mice and homozygous mice (bottom right) for the gene coding the mutant huntingtin protein. Variation maps reveal stronger alterations in the homozygous group and also a major alteration of the corpus callosum in both groups.