Subclinical Gray Matter Damage: Macro- and Microstructural Findings in Stroke-Free Unilateral Middle Cerebral Artery Occlusion Patients

OBJECTIVE: This study aimed to investigate macrostructural and microstructural damage in the gray matter of stroke-free patients with unilateral middle cerebral artery (MCA) occlusion using three-dimensional T1-weighted imaging (3D T1WI) and Neurite Orientation Dispersion and Density Imaging (NODDI) sequences. METHOD: A total of 56 patients with unilateral MCA occlusion and 60 age- and sex-matched healthy controls underwent 3.0T MRI with 3D T1WI and NODDI sequences. Voxel-based morphometry was applied to quantify regional brain volumes from 3D T1WI data, while Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were derived from NODDI data. Voxel-wise statistical comparisons assessed differences in regional gray matter volume, cortical thickness, NDI, and ODI between groups. RESULTS: Compared with healthy controls, individuals with unilateral MCA occlusion exhibited significant reductions in global gray matter volume and average cortical thickness. Specifically, unilateral MCA occlusion was linked to more extensive regional gray matter volume decreases. Notably, right MCA occlusion was uniquely associated with volume loss in the hippocampus, parahippocampal gyrus, and limbic system. Microstructural analysis revealed that, relative to controls, patients showed reduced NDI primarily in bilateral white matter tracts and decreased ODI in specific cortical regions of the frontal and occipital lobes. CONCLUSIONS: In stroke-free individuals with unilateral MCA occlusion, widespread macrostructural and microstructural damage to the gray matter is observed, affecting bilateral cerebral and cerebellar regions beyond the classic MCA vascular territory. Notably, the limbic system exhibits marked susceptibility, particularly involving the hippocampus, parahippocampal gyrus, and other limbic structures.