title: MRI measures of corpus callosum iron and myelin in early Huntington's disease.
abstract: Increased iron in subcortical gray matter (GM) structures of patients with Huntington's disease (HD) has been suggested as a causal factor in neuronal degeneration. But how iron content is related to white matter (WM) changes in HD is still unknown. For example, it is not clear whether WM changes share the same physiopathology (i.e. iron accumulation) with GM or whether there is a different mechanism. The present study used MRI to examine iron content in premanifest gene carriers (PreHD, n = 25) and in early HD patients (n = 25) compared with healthy controls (n = 50). 3T MRI acquisitions included high resolution 3D T1, EPI sequences for diffusion tensor imaging (DTI) as an indirect measure of tissue integrity, and T2*-weighted gradient echo-planar imaging for MR-based relaxometry (R2*), which provides an indirect measure of ferritin/iron deposition in the brain. Myelin breakdown starts in the PreHD stage, but there is no difference in iron content values. Iron content reduction manifests later, in the early HD stage, in which we found a lower R2* parameter value in the isthmus. The WM iron reduction in HD is temporally well-defined (no iron differences in PreHD subjects and iron differences only in early HD patients). Iron level in callosal WM may be regarded as a marker of disease state, as iron does not differentiate PreHD subjects from controls but distinguishes between PreHD and HD.
authors.affiliation: Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Di Paola
authors.forename: O R
authors.initials: OR
authors.lastname: Phillips
authors.forename: C
authors.initials: C
authors.lastname: Sanchez-Castaneda
authors.forename: A
authors.initials: A
authors.lastname: Di Pardo
authors.forename: V
authors.initials: V
authors.lastname: Maglione
authors.forename: C
authors.initials: C
authors.lastname: Caltagirone
authors.forename: U
authors.initials: U
authors.lastname: Sabatini
authors.forename: F
authors.initials: F
authors.lastname: Squitieri
mesh_terms: D000328:Adult; D003337:Corpus Callosum / Q000378:metabolism*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology*; D021621:Imaging, Three-Dimensional; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009186:Myelin Sheath / Q000473:pathology*; D011569:Psychiatric Status Rating Scales
chemical_list: D007501:Iron
keywords: Huntington's disease; corpus callosum; diffusion tensor imaging; iron; magnetic resonance-based relaxometry; white matter