TY - JOUR
T1 - Altered brain iron content and deposition rate in Huntington’s disease as indicated by quantitative susceptibility MRI
AU - Chen, Lin
AU - Hua, Jun
AU - Ross, Christopher A.
AU - Cai, Shuhui
AU - van Zijl, Peter C.M.
AU - Li, Xu
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2019/4
Y1 - 2019/4
N2 - Altered brain iron content in the striatum of premanifest and manifest Huntington’s disease (HD) has been reported. However, its natural history remains unclear. This study aims to investigate altered brain iron content in premanifest and early HD, and the iron deposition rate in these patients through a longitudinal one-year follow-up test, with quantitative magnetic susceptibility as an iron imaging marker. Twenty-four gene mutation carriers divided into three groups (further-from-onset, closer-to-onset and early HD) and 16 age-matched healthy controls were recruited at baseline, and of these, 14 carriers and 7 controls completed the one-year follow-up. Quantitative magnetic susceptibility and effective transverse relaxation rate ((Formula presented.)) were measured at 7.0 Tesla and correlated with atrophy and available clinical and cognitive measurements. Higher susceptibility values indicating higher iron content in the striatum and globus pallidus were only observed in closer-to-onset (N = 6, p < 0.05 in caudate and p < 0.01 in putamen) and early HD (N = 9, p < 0.05 in caudate and globus pallidus and p < 0.01 in putamen). Similar results were found by R* 2 measurement. Such increases directly correlated with HD CAG–age product score and brain atrophy, but not with motor or cognitive scores. More importantly, a significantly higher iron deposition rate (11.9%/years in caudate and 6.1%/years in globus pallidus) was firstly observed in closer-to-onset premanifest HD and early HD as compared to the controls. These results suggest that monitoring brain iron may provide further insights into the pathophysiology of HD disease progression, and may provide a biomarker for clinical trials.
AB - Altered brain iron content in the striatum of premanifest and manifest Huntington’s disease (HD) has been reported. However, its natural history remains unclear. This study aims to investigate altered brain iron content in premanifest and early HD, and the iron deposition rate in these patients through a longitudinal one-year follow-up test, with quantitative magnetic susceptibility as an iron imaging marker. Twenty-four gene mutation carriers divided into three groups (further-from-onset, closer-to-onset and early HD) and 16 age-matched healthy controls were recruited at baseline, and of these, 14 carriers and 7 controls completed the one-year follow-up. Quantitative magnetic susceptibility and effective transverse relaxation rate ((Formula presented.)) were measured at 7.0 Tesla and correlated with atrophy and available clinical and cognitive measurements. Higher susceptibility values indicating higher iron content in the striatum and globus pallidus were only observed in closer-to-onset (N = 6, p < 0.05 in caudate and p < 0.01 in putamen) and early HD (N = 9, p < 0.05 in caudate and globus pallidus and p < 0.01 in putamen). Similar results were found by R* 2 measurement. Such increases directly correlated with HD CAG–age product score and brain atrophy, but not with motor or cognitive scores. More importantly, a significantly higher iron deposition rate (11.9%/years in caudate and 6.1%/years in globus pallidus) was firstly observed in closer-to-onset premanifest HD and early HD as compared to the controls. These results suggest that monitoring brain iron may provide further insights into the pathophysiology of HD disease progression, and may provide a biomarker for clinical trials.
KW - Huntington’s disease
KW - QSM
KW - brain atrophy
KW - brain iron deposition
KW - cross-sectional study
KW - longitudinal study
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U2 - 10.1002/jnr.24358
DO - 10.1002/jnr.24358
M3 - Article
C2 - 30489648
AN - SCOPUS:85057882848
SN - 0360-4012
VL - 97
SP - 467
EP - 479
JO - Journal of neuroscience research
JF - Journal of neuroscience research
IS - 4
ER -