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Updated: Apr 28, 2026
Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI—Application in Premanifest Huntington's Disease
Published on: June 9, 2018
MRI measures of corpus callosum iron and myelin in early Huntington's disease
M Di Paola1, O R Phillips, C Sanchez-Castaneda
1Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy.
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.
Insights
Iron accumulation is not observed in white matter during early Huntington
Area of Science:
- Neuroimaging
- Neurodegenerative Diseases
- Iron Metabolism
Background:
- Increased iron in subcortical gray matter (GM) is linked to neuronal degeneration in Huntington's disease (HD).
- The relationship between iron content and white matter (WM) changes in HD remains unclear.
- It is unknown if WM changes share the same iron accumulation pathology as GM or involve different mechanisms.
Purpose of the Study:
- To investigate iron content in WM of premanifest HD gene carriers (PreHD) and early HD patients.
- To compare WM iron levels between PreHD, early HD, and healthy controls using MRI.
Main Methods:
- Utilized 3T MRI including T1, diffusion tensor imaging (DTI), and T2*-weighted imaging for MR-based relaxometry (R2*).
- Assessed iron deposition indirectly via R2* values.
- Examined myelin breakdown and iron content in 25 PreHD, 25 early HD patients, and 50 healthy controls.
Main Results:
- Myelin breakdown begins in the PreHD stage, without significant iron content differences.
- Iron content reduction was observed in early HD patients, indicated by lower R2* values in the isthmus.
- WM iron reduction in HD is temporally specific, appearing only in the early HD stage, not in PreHD subjects.
Conclusions:
- WM iron levels do not differ between PreHD subjects and controls.
- Iron reduction in callosal WM distinguishes early HD patients from both PreHD subjects and controls.
- WM iron levels may serve as a marker for the disease state in Huntington's disease.
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