Density abnormalities in normal-appearing gray matter in the middle-aged brain with white matter hyperintense lesions: a DARTEL-enhanced voxel-based morphometry study

Yan Peng,1,* Shenhong Li,2,* Ying Zhuang,3,* Xiaojia Liu,4 Lin Wu,2 Honghan Gong,2 Dewu Liu,1 Fuqing Zhou2 1Burn Center, 2Department of Radiology, The First Affiliated Hospital, Nanchang University, 3Department of Oncology, The Second Hospital of Nanchang, Nanchang, Jiangxi Province, 4Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, People’s Republic of China *These authors contributed equally to this work Background and purpose: Little is known about the structural alterations within gray matter (GM) in middle-aged subjects with white matter hyperintense (WMH) lesions. Here, we aimed to examine the anatomical changes within the GM and their relationship to WMH lesion loads in middle-aged subjects. Participants and methods: Twenty-three middle-aged subjects with WMH lesions (WMH group) and 23 demographically matched healthy control subjects participated in the study. A Diffeomorphic Anatomical Registration Through Exponentiated Liealgebra-enhanced voxel-based morphometry was used to measure the GM density, and the correlations between WMH lesion volume and extracted GM values in abnormal regions were identified by voxel-based morphometry analysis. Results: Compared with the healthy control subjects, the WMH group had a significantly decreased GM density in the left middle frontal gyrus, bilateral anterior cingulate cortex, left and right premotor cortex, and left and right middle cingulate cortex and an increased GM density in the bilateral cerebellum anterior lobe, left middle temporal gyrus, right temporoparietal junction, left and right prefrontal cortex (PFC), and left inferior parietal lobule. A relationship was observed between the normalized WMH lesion volume and the decreased GM density, including the left middle frontal gyrus (ρ=-0.629, P=0.002), bilateral anterior cingulate cortex (ρ=-0.507, P=0.019), right middle cingulate cortex (ρ=-0.484, P=0.026), and right premotor cortex (ρ=-0.438, P=0.047). The WMH lesion loads also negatively correlated with increased GM density in the right temporoparietal junction (ρ=-0.484, P=0.026), left PFC (ρ=-0.469, P=0.032), and right PFC (ρ=-0.438, P=0.047). Conclusion: We observed that lesion load-associated structural plasticity corresponds to bidirectional changes in regional GM density in the WMH group. Keywords: white matter hyperintense lesion, voxel-based morphometry, normal-appearing gray matter, aging