Previous MRI studies reported iron accumulation within the striatum of Huntington’s disease (HD). However, the pattern and origin of iron accumulation is poorly understood. This study characterized the histopathological correlates of iron-sensitive ex vivo MRI in HD brains. We delineated the pattern and co-localization of iron with specific cells such as microglia and astrocytes.
T2*-weighted 7T MRI was performed on postmortem tissue of the striatum of three controls and 10 HD patients followed by histology. In addition, tissue of three controls and 14 HD patients was selected to identify the cellular localization of iron using stainings for iron, myelin, microglia and astrocytes.
Compared to controls, the striatum of HD patients was more hypointense on MRI and showed a more intense histopathological staining for iron. T2*-weighted MRI also identified large focal hypointensities (arrows) within the striatum of HD patients which frequently co-localized with enlarged perivascular spaces (fig1). Microscopically, iron was predominantly found within reactive astrocytes (fig2).
Fig1. Representative T2*-weighted MRI of striatal tissue of two controls and four HD cases. Scale=1cm.
Fig2. Histological examples in two control and three HD striata. The iron staining showed a very similar pattern as the staining for astrocytes.
Scale= 50µm; Scale zoom=25µm.
Ex vivo MRI showed that the HD striatum was characterized by large focal hypointensities that co-localized with enlarged perivascular spaces. Histopathology showed reactive astrocytes as the predominant source of the increase of iron within the striatum. These results are important for the interpretation and understanding of underlying mechanisms of T2*-weighted MRI in HD.