Objective: To assess brain iron content measured with SWI-MRI in HD gene expansion carriers (HDGECs).

Background: Huntington’s Disease (HD) results in extensive neuronal cell loss, caused by several mechanisms, of which oxidative damage seems to play a major role. Previous studies suggest that brain iron content is increased in HD since the early stages, and that mutant huntingtin may alter cellular iron homeostasis. Susceptibility Weighted Imaging MRI (SWI-MRI) identifies iron content in brain regions, by exploiting the properties of magnetic susceptibility displayed by contents rich in iron compared with non-iron tissues.

Method: 12 HDGECs (7 asymptomatic and 5 symptomatic, mean age 50.9±12.5, mean CAP score 90.9±25.1), and 12 age-and gender-matched healthy controls (HCs), were enrolled. All subjects underwent 3D high-resolution gradient echo SWI-MRI sequence with a 3-Tesla MRI scanner. High-pass filtered phase shift images were used to analyze regional iron content and bilateral shift values were averaged. Iron content was calculated by transforming the resulting shift value to radians. Neuroimaging data were correlated with clinical and neuropsychological variables. Statistical analysis included Kruskal-Wallis test, Mann-Whitney U test and Spearman test for correlation.

Results: HDGECs showed increased iron content in Substantia Nigra, Red Nucleus, Ventral Striatum, Pallidum, Caudate and Putamen, compared with HCs (all, P<0.05). Asymptomatic HDGECs showed increased phase values, compared with HCs, in the Substantia Nigra (P=0.003), Ventral Striatum (P=0.02), and Putamen (P=0.02). Symptomatic HDGECs showed slightly significantly increased phase values, compared with asymptomatic HDGECs, in Ventral Striatum, Pallidum and Caudate (all P=0.048). Positive correlations were found between iron content in Ventral Striatum, Caudate and Putamen, and CAP score (P<0.005). Phase values in Ventral Striatum, Pallidum, Caudate and Putamen, also correlated with motor and cognitive scores.

Conclusion: Our findings indicate increased iron content in areas affected by HD pathology from early premanifest stages which correlates with the degree of disease burden as quantified with the CAP score. Iron content measured through SWI-MRI can be a valuable cross-sectional biomarker of neuronal damage in HDGECs.This abstract was also submitted for presentation at the 2019 European Academy of Neurology conference.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/quantification-of-regional-iron-content-with-susceptibility-weighted-imaging-in-huntington-disease-expansion-gene-carriers/