Altered Intracortical T₁-Weighted/T₂-Weighted Ratio Signal in Huntington's Disease

Huntington's disease (HD) is a genetic neurodegenerative disorder that is characterized by neuronal cell death. Although medium spiny neurons in the striatum are predominantly affected, other brain regions including the cerebral cortex also degenerate. Previous structural imaging studies have reported decreases in cortical thickness in HD. Here we aimed to further investigate changes in cortical tissue composition in vivo in HD using standard clinical T₁-weighted (T₁W) and T₂-weighted (T₂W) magnetic resonance images (MRIs). 326 subjects from the TRACK-HD dataset representing healthy controls and four stages of HD progression were analyzed. The intracortical T₁W/T₂W intensity was sampled in the middle depth of the cortex over 82 regions across the cortex. While these previously collected images were not optimized for intracortical analysis, we found a significant increase in T₁W/T₂W intensity (p < 0.05 Bonferroni-Holm corrected) beginning with HD diagnosis. Increases in ratio intensity were found in the insula, which then spread to ventrolateral frontal cortex, superior temporal gyrus, medial temporal gyral pole, and cuneus with progression into the most advanced HD group studied. Mirroring past histological reports, this increase in the ratio image intensity may reflect disease-related increases in myelin and/or iron in the cortex. These findings suggest that future imaging studies are warranted with imaging optimized to more sensitively and specifically assess which features of cortical tissue composition are abnormal in HD to better characterize disease progression.