Distinct virtual histology of grey matter atrophy in four neuroinflammatory diseases,Brain

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Distinct virtual histology of grey matter atrophy in four neuroinflammatory diseases
Brain ( IF 14.5 ) Pub Date : 2024-05-03 , DOI: 10.1093/brain/awae138
Jun Sun _{1,

2} , Min Guo _{1,

2} , Li Chai _{1,

2} , Siyao Xu _{1,

2} , Yuerong Lizhu _{1,

2} , Yuna Li _{1,

2} , Yunyun Duan _{1,

2} , Xiaolu Xu _{1,

2} , Shan Lv _{1,

2} , Jinyuan Weng ₃ , Kuncheng Li ₄ , Fuqing Zhou ₅ , Haiqing Li ₆ , Yongmei Li ₇ , Xuemei Han ₈ , Fu-Dong Shi _{9,

10} , Xinghu Zhang ₁₁ , Decai Tian ₁₁ , Zhizheng Zhuo _{1,

2} , Yaou Liu _{1,

2}

Affiliation

Department of Radiology, Beijing Tiantan Hospital, Capital Medical University , Beijing, 100070 , P.R. China
Tiantan Image Research Center, China National Clinical Research Center for Neurological Diseases , Beijing, 100070 , P.R. China
Department of Medical Imaging Product, Neusoft, Group Ltd. , Shenyang, 110179 , P.R. China
Department of Radiology, Xuanwu Hospital, Capital Medical University , Beijing, 100053 , P. R. China
Department of Radiology, The First Affiliated Hospital, Nanchang University , Nanchang, Jiangxi Province, 330006 , P. R. China
Department of Radiology, Huashan Hospital, Fudan University , Shanghai, 200040 , China
Department of Radiology, The First Affiliated Hospital of Chongqing Medical University , Chongqing, 400016 , P. R. China
Department of Neurology, China–Japan Union Hospital of Jilin University , Changchun, Jilin Province, 130031 , P. R. China
China National Clinical Research Center for Neurological Diseases , Beijing, 100070 , P. R. China
Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital , Tianjin, 300052 , P. R. China
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University , Beijing, 100070 , P. R. China

Gray matter (GM) atrophies were observed in multiple sclerosis, neuromyelitis optica spectrum disorders (both anti-aquaporin-4 antibody-positive [AQP4+], and -negative [AQP4-] subtypes NMOSD), 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 multicenter cohort of 324 patients with multiple sclerosis, 197 patients with AQP4+ NMOSD, 75 patients with AQP4- NMOSD, 47 patients with MOGAD, and 2,169 healthy controls (HCs). First, interregional GM atrophy profiles across the cortical and subcortical regions were determined by Cohen’s d between patients with multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, MOGAD and HCs. Then, the GM atrophy profiles were spatially correlated with the gene expressions extracted from the Allen Human Brain Atlas, respectively. Finally, we explored the virtual histology of clinical feature relevant GM atrophy by subgroup analysis that stratified by physical disability, disease duration, number of relapses, lesion burden, and cognitive function. Multiple sclerosis showed severe widespread GM atrophy pattern, mainly involving subcortical nuclei and brainstem. AQP4+ NMOSD showed obvious widespread GM atrophy pattern, predominately located in occipital cortex as well as cerebellum. AQP4- NMOSD showed mild widespread GM atrophy pattern, mainly located in frontal and parietal cortices. MOGAD showed GM atrophy mainly involving the frontal and temporal cortices. High expression of genes specific to microglia, astrocytes, oligodendrocytes, and endothelial cells in multiple sclerosis, S1 pyramidal cells in AQP4+ NMOSD, as well as S1 and CA1 pyramidal cells in MOGAD had spatial correlations with GM atrophy profiles were observed, while no atrophy profile related gene expression was found in AQP4- NMOSD. Virtual histology of clinical feature relevant GM atrophy mainly pointed to the shared neuronal and endothelial cells among the four neuroinflammatory diseases. The unique underlying virtual histology patterns were microglia, astrocytes, and oligodendrocytes for multiple sclerosis; astrocytes for AQP4+ NMOSD; and oligodendrocytes for MOGAD. Neuronal and endothelial cells were shared potential targets across these neuroinflammatory diseases. These findings might help their differential diagnosis and optimal therapeutic strategies.

更新日期：2024-05-03

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