Brain: Neuroimaging features of brain injury in Wilson's disease—a multimodal whole-brain MRI study

Wilson's disease is an autosomal recessive disorder of copper metabolism with neurological and hepatic abnormalities
.

Neuroimaging studies have uncovered a range of abnormal outcomes that increase the understanding of disease mechanisms and provide a research pathway
for disease prognosis and biomarkers that can be used for detection.

However, previous quantitative MRI analyses have focused only on a particular sequence or region of interest and have often stratified
chronically treated patients based on ongoing symptoms rather than initial symptoms.

Results of the study

In this cross-sectional prospective study, we recruited 40 patients with Wilson's disease (ages 16-68 years)
using unbiased whole-brain T1-weighted imagery, FLAIR imagery, DWI, and SWI analysis.

In addition, we subgroup patients based on current symptomatic status, defining patients with neurological manifestations or deterioration in the past 6 months as having an "active type"
.

By combining voxel-based morphological analysis (VBM) and volumetric analysis of the region of interest, we found that the volume of gray matter is small
in the basal ganglion, thalamus, brainstem, cerebellum, anterior thalamus, and orbitofrontal cortex.

Fig.

Calculations using the automatic lesion segmentation algorithm showed no correlation between disease severity and white matter hypersignal (WMHs) volume (Figure 2).

Fig.

Using spatial statistical analysis based on fibrous bundles, an increase in the severity of the condition in chronically treated patients was associated with a decrease in the axial diffusion rate of the leukofibrous bundle and that there was an increase
in serum non-cyanoplasmin-bound (free) copper.

Figure 3 Disease states
based on fiber bundle spatial statistics.

Quantitative susceptibility mapping analysis of the whole brain found that patients with neurological manifestations had iron deposition in the shell core, cingulate gyrus and medial frontal cortex; In patients with chronic treatment, the severity of neurological symptoms is associated with extensive iron deposition in the cortical region (Figure 4
).

Figure 4 Results
of the whole brain quantitative magnetic sensitivity map.

Taken together, our data suggest that a composite indicator of subcortical atrophy provides an effective biomarker for predicting the condition, while abnormal average, axial, and radial spread rates are potential biomarkers
for monitoring the condition.

Finally, iron deposition in the brain associated with copper accumulation may directly lead to neurodegenerative lesions
in Wilson's disease.