A recent study published in Parkinsonism and Related Disorders has revealed that free water imaging effectively detects the microstructural alterations present in both standard and abnormal appearing deep gray matter (DGM) nuclei of patients with Wilson’s disease (WD).

Wilson’s disease, a rare autosomal recessive disorder, is characterized by the pathological accumulation of copper, mainly in the liver and brain. 

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Studies related to neuropathological and neuroimaging have reported extensive brain atrophy in patients with WD, particularly in the DGM nuclei. Lately, free water imaging using a bitensor model has evolved to convincingly assess the volume fraction of free water within a voxel. After removing free water impurities, the residual signals provide corrected fractional anisotropy (FAT) in the relevant tissues. 

The current study hypothesized that free water is increased in the DGM nuclei of patients with WD. “We pursued this hypothesis for the finding of free water may have great clinical significance in monitoring disease activity, evaluating the treatment effect and the prognosis of WD,” the authors highlighted. The study enrolled 31 patients with WD and 25 healthy controls from December 2018 to November 2020. 

Study results revealed a significant increase of water and FAT values in multiple DGM nuclei of neurological patients with WD compared to the controls. Moreover, patients with WD with normal results on the regular magnetic resonance imaging (MRI) also reported significantly higher free water and FAT values in multiple DGM nuclei than the controls. “This is the first study to use a bi-tensor free water imaging to evaluate microstructural changes in DGM nuclei of WD patients,” the authors highlighted. 

Furthermore, the measured free water and FAT values of specific structures also positively correlated with specific clinical symptoms in neurological patients with WD, such as dysarthria, parkinsonian signs, tremor, dystonia, and ataxia. Finally, the study reported that free water imaging also identifies microstructural abnormalities, even in patients with a normal appearance on conventional MRI. The results also reflected the neuroinflammation and gliosis in DGM nuclei in the early stage of patients with WD.

The study found correlations between free water imaging indices and neurological impairment in patients with WD.  The authors concluded “as a promising tool, free water imaging deserves further investigation in longitudinal studies to evaluate its role in monitoring disease onset, progression, and treatment efficacy in WD patients.”


Jing XZ, Li GY, Wu YP, et al. Free water imaging as a novel biomarker in Wilson’s disease: a cross-sectional studyParkinsonism Relat Disord. Published online December 1, 2022.