Microstructural and functional impairment of the basal ganglia in Wilson's disease: a multimodal neuroimaging study

Dongning Su; Zhijin Zhang; Zhe Zhang; Yawen Gan; Yingkui Zhang; Xinyao Liu; Jingfeng Bi; Lingyan Ma; Huiqing Zhao; Xuemei Wang; Zhan Wang; Huizi Ma; Shairy Sifat; Junhong Zhou; Wei Li; Tao Wu; Jing Jing; Tao Feng

doi:10.3389/fnins.2023.1146644

Microstructural and functional impairment of the basal ganglia in Wilson's disease: a multimodal neuroimaging study

Front Neurosci. 2023 Apr 20:17:1146644. doi: 10.3389/fnins.2023.1146644. eCollection 2023.

Authors

Dongning Su^#¹, Zhijin Zhang^#¹, Zhe Zhang^#^{2

3}, Yawen Gan¹, Yingkui Zhang^{2

3}, Xinyao Liu^{2

3}, Jingfeng Bi^{2

3}, Lingyan Ma¹, Huiqing Zhao¹, Xuemei Wang¹, Zhan Wang¹, Huizi Ma¹, Shairy Sifat⁴, Junhong Zhou^{5

6}, Wei Li^{1

2}, Tao Wu^{1

2}, Jing Jing^{1

2

3}, Tao Feng^{1

2}

Affiliations

¹ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² China National Clinical Research Center for Neurological Diseases, Beijing, China.
³ Tiantan Neuroimaging Center of Excellence, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ Djavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
⁵ Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Roslindale, MA, United States.
⁶ Harvard Medical School, Boston, MA, United States.

^# Contributed equally.

Abstract

Objectives: Magnetic susceptibility changes in brain MRI of Wilson's disease (WD) patients have been described in subcortical nuclei especially the basal ganglia. The objectives of this study were to investigate its relationship with other microstructural and functional alterations of the subcortical nuclei and the diagnostic utility of these MRI-related metrics.

Methods: A total of 22 WD patients and 20 healthy controls (HCs) underwent 3.0T multimodal MRI scanning. Susceptibility, volume, diffusion microstructural indices and whole-brain functional connectivity of the putamen (PU), globus pallidus (GP), caudate nucleus (CN), and thalamus (TH) were analyzed. Receiver operating curve (ROC) was applied to evaluate the diagnostic value of the imaging data. Correlation analysis was performed to explore the connection between susceptibility change and microstructure and functional impairment of WD and screen for neuroimaging biomarkers of disease severity.

Results: Wilson's disease patients demonstrated increased susceptibility in the PU, GP, and TH, and widespread atrophy and microstructural impairments in the PU, GP, CN, and TH. Functional connectivity decreased within the basal ganglia and increased between the PU and cortex. The ROC model showed higher diagnostic value of isotropic volume fraction (ISOVF, in the neurite orientation dispersion and density imaging model) compared with susceptibility. Severity of neurological symptoms was correlated with volume and ISOVF. Susceptibility was positively correlated with ISOVF in GP.

Conclusion: Microstructural impairment of the basal ganglia is related to excessive metal accumulation in WD. Brain atrophy and microstructural impairments are useful neuroimaging biomarkers for the neurological impairment of WD.

Keywords: Wilson’s disease; basal ganglia; iron; multimodal MRI; neuroimaging biomarker.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 82071422) and the Natural Science Foundation of Beijing Municipality (No. 7212031).