Free water imaging as a novel biomarker in Wilson's disease: A cross-sectional study

Abstract

Background: The bi-tensor free water imaging may provide more specific information in detecting microstructural brain tissue alterations than conventional single tensor diffusion tensor imaging. The study aimed to investigate microstructural changes in deep gray matter (DGM) nuclei of Wilson's disease (WD) using a bi-tensor free water imaging and whether the findings correlate with the neurological impairment in WD patients.

Methods: The study included 29 WD patients and 25 controls. Free water and free water corrected fractional anisotropy (FA_T) in DGM nuclei of WD patients were calculated. The correlations of free water and FA_T with the Unified WD Rating Scale (UWDRS) neurological subscale of WD patients were performed.

Results: Free water and FA_T values were significantly increased in multiple DGM nuclei of neurological WD patients compared to controls. WD patients with normal appearing on conventional MRI also had significantly higher free water and FA_T values in multiple DGM nuclei than controls. Positive correlations were noted between the UWDRS neurological subscores and free water values of the putamen and pontine tegmentum as well as FA_T values of the dentate nucleus, red nucleus, and globus pallidus. In addition, the measured free water and FA_T values of specific structures also showed a positive correlation with specific clinical symptoms in neurological WD patients, such as dysarthria, parkinsonian signs, tremor, dystonia, and ataxia.

Conclusions: Free water imaging detects microstructural changes in both normal and abnormal appearing DGM nuclei of WD patients. Free water imaging indices were correlated with the severity of neurological impairment in WD patients.

Keywords: Deep gray matter nuclei; Free water imaging; Neurodegeneration; Wilson's disease.