Distinct virtual histology of grey matter atrophy in four neuroinflammatory diseases

作者：Jun Sun, Min Guo, Li Chai, Siyao Xu, Yuerong Lizhu, Yuna Li, Yunyun Duan, Xiaolu Xu, Shan Lv, Jinyuan Weng, Kuncheng Li, Fuqing Zhou, Haiqing Li, Yongmei Li, Xuemei Han, Fu‐Dong Shi, Xinghu Zhang, De‐Cai Tian, Zhizheng Zhuo, Yaou Liu · 发表于：Brain · 年份：2024 · DOI：10.1093/brain/awae138 · 被引用次数：11 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Barrier Structure and Function Studies、Atherosclerosis and Cardiovascular Diseases

Grey matter (GM) atrophies are observed in multiple sclerosis, neuromyelitis optica spectrum disorders [NMOSD; both anti-aquaporin-4 antibody-positive (AQP4+) and -negative (AQP4-) subtypes] and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Revealing the pathogenesis of brain atrophy in these disorders would help their differential diagnosis and guide therapeutic strategies. To determine the neurobiological underpinnings of GM atrophies in multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD and MOGAD, we conducted a virtual histology analysis that links T1-weighted image derived GM atrophy and gene expression using a multicentre cohort of 324 patients with multiple sclerosis, 197 patients with AQP4+ NMOSD, 75 patients with AQP4- NMOSD, 47 patients with MOGAD and 2169 healthy control subjects. First, interregional GM atrophy profiles across the cortical and subcortical regions were determined using Cohen's d between patients with multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD or MOGAD and healthy controls. The GM atrophy profiles were then spatially correlated with the gene expression levels extracted from the Allen Human Brain Atlas, respectively. Finally, we explored the virtual histology of clinical-feature relevant GM atrophy using a subgroup analysis that stratified by physical disability, disease duration, number of relapses, lesion burden and cognitive function. Multiple sclerosis showed a severe widespread GM atrophy pattern, mainly involving subcorti...