title: Seeking Huntington disease biomarkers by multimodal, cross-sectional basal ganglia imaging.
abstract: Neurodegeneration of the striatum in Huntington disease (HD) is characterized by loss of medium-spiny neurons, huntingtin nuclear inclusions, reactive gliosis, and iron accumulation. Neuroimaging allows in vivo detection of the macro- and micro-structural changes that occur from presymptomatic stages of the disease (preHD). The aim of our study was to evaluate the reliability of multimodal imaging as an in vivo biomarker of vulnerability and development of the disease and to characterize macro- and micro-structural changes in subcortical nuclei in HD. Macrostructure (T1-weighted images), microstructure (diffusion tensor imaging), and iron content (R 2* relaxometry) of subcortical nuclei and medial temporal lobe structures were evaluated by a 3 T scanner in 17 preHD carriers, 12 early-stage patients and 29 matched controls. We observed a volume reduction and microstructural changes in the basal ganglia (caudate, putamen, and globus pallidus) and iron accumulation in the globus pallidus in both preHD and symptomatic subjects; all these features were significantly more pronounced in patients, in whom degeneration extended to the other subcortical nuclei (i.e., thalamus and accumbens). Mean diffusivity (MD) was the most powerful predictor in models explaining more than 50% of the variability in HD development in the caudate, putamen, and thalamus. These findings suggest that the measurement of MD may further enhance the well-known predictive value of striatal volume to assess disease progression as it is highly sensitive to tissue microimpairment. Multimodal imaging may detect brain changes even in preHD stages.
authors.affiliation: Department of Radiology, IRCCS Santa Lucia, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez-Castañeda
authors.forename: Andrea
authors.initials: A
authors.lastname: Cherubini
authors.forename: Francesca
authors.initials: F
authors.lastname: Elifani
authors.forename: Patrice
authors.initials: P
authors.lastname: Péran
authors.forename: Sara
authors.initials: S
authors.lastname: Orobello
authors.forename: Giovanni
authors.initials: G
authors.lastname: Capelli
authors.forename: Umberto
authors.initials: U
authors.lastname: Sabatini
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Squitieri
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016880:Anisotropy; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers; D001931:Brain Mapping; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis*; D021621:Imaging, Three-Dimensional; D007501:Iron / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D005293:Ferritins; D007501:Iron