Brain iron accumulation in Wilson disease: a post mortem 7 Tesla MRI - histopathological study

Area of Science:

• Neurology
• Radiology
• Pathology

Background:

• Wilson disease (WD) is a genetic disorder causing copper accumulation.
• T2/T2*-weighted (T2*w) MRI often shows basal ganglia hypointensity in WD, suggesting paramagnetic deposits.
• The exact composition of these deposits (copper vs. iron) remains unclear.

Purpose of the Study:

• To investigate the neuropathological basis of T2*w MRI hypointensity in WD.
• To determine if basal ganglia hypointensity in WD is associated with copper or iron deposition.
• To correlate MRI findings with quantitative measurements of iron and copper in brain tissue.

Main Methods:

• Utilized 7T-MRI on brain slices from WD and control cases.
• Acquired high-resolution T2*w images and reconstructed R2* parametric maps.
• Examined histopathology using Turnbull iron staining and immunohistochemistry, correlating with R2* values and metal concentrations.

Main Results:

• T2*w hypointensity in the globus pallidus and putamen correlated with iron staining.
• WD cases showed increased iron and copper in the putamen compared to controls.
• R2* values correlated significantly with iron concentration, but not copper concentration, in the basal ganglia.

Conclusions:

• T2/T2*w MRI hypointensity in the basal ganglia of Wilson disease patients is primarily due to iron deposition.
• This study clarifies the role of iron in WD-related MRI signal abnormalities.
• Findings emphasize the importance of considering iron overload in the interpretation of basal ganglia MRI in WD.