Topographical metal burden correlates with brain atrophy and clinical severity in Wilson's disease
Sung-Pin Fan,
Ya-Fang Chen,
Cheng-Hsuan Li,
Yih-Chih Kuo,
Ni-Chung Lee,
Yin-Hsiu Chien,
Wuh-Liang Hwu,
Tai-Chung Tseng,
Tung-Hung Su,
Chien-Ting Hsu,
Huey-Ling Chen,
Chin-Hsien Lin,
Yen-Hsuan Ni
Affiliations
Sung-Pin Fan
Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
Ya-Fang Chen
Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
Cheng-Hsuan Li
Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Neurology, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan
Yih-Chih Kuo
Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Neurology, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan
Ni-Chung Lee
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan
Yin-Hsiu Chien
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan
Wuh-Liang Hwu
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan
Tai-Chung Tseng
Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Tung-Hung Su
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Chien-Ting Hsu
Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan; Department of Pediatrics, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan
Huey-Ling Chen
Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan
Chin-Hsien Lin
Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; Corresponding author at: Department of Neurology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan.
Yen-Hsuan Ni
Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan; Corresponding author at: Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 100, Taiwan.
Background: Quantitative susceptibility mapping (QSM) is a post-processing technique that creates brain susceptibility maps reflecting metal burden through tissue magnetic susceptibility. We assessed topographic differences in magnetic susceptibility between participants with and without Wilson's disease (WD), correlating these findings with clinical severity, brain volume, and biofluid copper and iron indices. Methods: A total of 43 patients with WD and 20 unaffected controls, were recruited. QSM images were derived from a 3T MRI scanner. Clinical severity was defined using the minimal Unified Wilson's Disease Rating Scale (M-UWDRS) and Montreal Cognitive Assessment scoring. Differences in magnetic susceptibilities between groups were evaluated using general linear regression models, adjusting for age and sex. Correlations between the susceptibilities and clinical scores were analyzed using Spearman's method. Results: In age- and sex-adjusted analyses, magnetic susceptibility values were increased in WD patients compared with controls, including caudate nucleus, putamen, globus pallidus, and substantia nigra (all p < 0.01). Putaminal susceptibility was greater with an initial neuropsychiatric presentation (n = 25) than with initial hepatic dysfunction (n = 18; p = 0.04). Susceptibility changes correlated negatively with regional brain volume in almost all topographic regions. Serum ferritin, but not serum copper or ceruloplasmin, correlated positively with magnetic susceptibility level in the caudate nucleus (p = 0.04), putamen (p = 0.04) and the hippocampus (p = 0.03). The dominance of magnetic susceptibility in cortical over subcortical regions correlated with M-UWDRS scores (p < 0.01). Conclusion: The magnetic susceptibility changes could serve as a surrogate marker for patients with WD.
