In vivo characterization of white matter pathology in premanifest huntington's disease
2018
OBJECTIVE: Huntington's disease (HD) is a
monogenic, fully penetrant neurodegenerative disorder, providing an ideal model for understanding brain changes occurring in the years prior to disease onset. Diffusion tensor imaging (DTI) studies show widespread
white matterdisorganization in the early pre-manifest stages (pre-HD). However, while DTI has proved informative, it provides only limited information about underlying changes in tissue properties. Neurite Orientation Dispersion and Density Imaging (NODDI) is a novel MRI technique for characterizing axonal pathology more specifically, providing metrics that separately quantify axonal density and axonal organization. Here, we provide the first in vivo characterization of
white matterpathology in pre-HD using NODDI. METHODS: Diffusion-weighted MRI data that support DTI and NODDI were acquired from 38 pre-HD and 45 control participants. Using whole-brain and region-of-interest analyses, NODDI metrics were compared between groups and correlated with clinical scores of disease progression. Whole-brain changes in DTI metrics were also examined. RESULTS: The pre-HD group displayed widespread reductions in axonal density compared with control participants; this correlated with measures of clinical disease progression in the body and
genuof the
corpus callosum. There was also evidence in the pre-HD group of increased coherence of axonal packing in the
white mattersurrounding the
basal ganglia. INTERPRETATION: Our findings suggest that reduced axonal density is one of the major factors underlying
white matterpathology in pre-HD, coupled with increased local organization in areas surrounding the
basal ganglia. NODDI metrics show promise in providing more specific information about the biological processes underlying HD and neurodegeneration per se.
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