Jian Li, Daji Chen, Yongxiang Tang, Zhao Chen, Ming Zhou, Linlin Wan, Ling Xiao, You Fu, Zhiyou He, Zhichao Tang, Zhengqun Hu, Xinrong Yuan, Jinhui Yang, Sudan Zhu, Xuan Guo, Riwei Ouyang, Rong Qiu, Beisha Tang, Jifeng Guo, Hong Jiang, Shuo Hu
{"title":"突触密度降低：通过SynVesT-1 PET成像发现的潜在生物标志物[18F]。","authors":"Jian Li, Daji Chen, Yongxiang Tang, Zhao Chen, Ming Zhou, Linlin Wan, Ling Xiao, You Fu, Zhiyou He, Zhichao Tang, Zhengqun Hu, Xinrong Yuan, Jinhui Yang, Sudan Zhu, Xuan Guo, Riwei Ouyang, Rong Qiu, Beisha Tang, Jifeng Guo, Hong Jiang, Shuo Hu","doi":"10.1002/ana.27179","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to delineate synaptic density alterations in multiple system atrophy (MSA) and explore its potential role as a biomarker for MSA diagnosis and disease severity monitoring using [<sup>18</sup>F]SynVesT-1 positron emission tomography / computed tomography (PET CT).</p><p><strong>Methods: </strong>In this prospective study, 60 patients with MSA (30 patients with MSA-parkinsonian [MSA-P] subtype and 30 patients with MSA-cerebellar [MSA-C] subtype), 30 patients with Parkinson's disease (PD), and 30 age-matched healthy controls (HCs) underwent [<sup>18</sup>F]SynVesT-1 PET/CT for synaptic density assessment. Visual, voxel, and volumetric region of interest (VOI) analyses were used to elucidate synaptic density patterns in the MSA brain and establish diagnostic criteria. The diagnostic performances of both visual and VOI-based diagnostics were evaluated using receiver operating characteristic (ROC) analysis. Spearman correlation analyses were conducted to investigate the relationship between brain synaptic density and disease severity RESULTS: Patients with MSA displayed extensive reductions in synaptic density throughout the brain, notably affecting both primary VOIs (the cerebellum and putamen) and secondary VOIs including the medulla oblongata, ventral tegmental area, and pons. Notably, patients with MSA-C exhibited a remarkable decrease in cerebellar synaptic density, whereas patients with MSA-P demonstrated significant synaptic loss within the posterior putamen. Compared with patients with PD, the patients with MSA show a more pronounced reduction in synaptic density in infratentorial brain regions. VOI-based diagnosis significantly outperformed visual analysis in diagnosing and differentiating MSA and its subtypes. Synaptic density in primary and multiple secondary VOIs correlated significantly with motor scales in patients with MSA.</p><p><strong>Interpretation: </strong>Our study identified widespread synaptic density reductions in MSA, particularly in the basal ganglia and infratentorial region, suggesting [<sup>18</sup>F]SynVesT-1 PET as a potential biomarker for diagnosing and evaluating the disease, and guiding synaptic restoration trials. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1000,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synaptic Density Reductions in MSA: A Potential Biomarker Identified Through [<sup>18</sup>F]SynVesT-1 PET Imaging.\",\"authors\":\"Jian Li, Daji Chen, Yongxiang Tang, Zhao Chen, Ming Zhou, Linlin Wan, Ling Xiao, You Fu, Zhiyou He, Zhichao Tang, Zhengqun Hu, Xinrong Yuan, Jinhui Yang, Sudan Zhu, Xuan Guo, Riwei Ouyang, Rong Qiu, Beisha Tang, Jifeng Guo, Hong Jiang, Shuo Hu\",\"doi\":\"10.1002/ana.27179\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>The objective of this study was to delineate synaptic density alterations in multiple system atrophy (MSA) and explore its potential role as a biomarker for MSA diagnosis and disease severity monitoring using [<sup>18</sup>F]SynVesT-1 positron emission tomography / computed tomography (PET CT).</p><p><strong>Methods: </strong>In this prospective study, 60 patients with MSA (30 patients with MSA-parkinsonian [MSA-P] subtype and 30 patients with MSA-cerebellar [MSA-C] subtype), 30 patients with Parkinson's disease (PD), and 30 age-matched healthy controls (HCs) underwent [<sup>18</sup>F]SynVesT-1 PET/CT for synaptic density assessment. Visual, voxel, and volumetric region of interest (VOI) analyses were used to elucidate synaptic density patterns in the MSA brain and establish diagnostic criteria. The diagnostic performances of both visual and VOI-based diagnostics were evaluated using receiver operating characteristic (ROC) analysis. Spearman correlation analyses were conducted to investigate the relationship between brain synaptic density and disease severity RESULTS: Patients with MSA displayed extensive reductions in synaptic density throughout the brain, notably affecting both primary VOIs (the cerebellum and putamen) and secondary VOIs including the medulla oblongata, ventral tegmental area, and pons. Notably, patients with MSA-C exhibited a remarkable decrease in cerebellar synaptic density, whereas patients with MSA-P demonstrated significant synaptic loss within the posterior putamen. Compared with patients with PD, the patients with MSA show a more pronounced reduction in synaptic density in infratentorial brain regions. VOI-based diagnosis significantly outperformed visual analysis in diagnosing and differentiating MSA and its subtypes. Synaptic density in primary and multiple secondary VOIs correlated significantly with motor scales in patients with MSA.</p><p><strong>Interpretation: </strong>Our study identified widespread synaptic density reductions in MSA, particularly in the basal ganglia and infratentorial region, suggesting [<sup>18</sup>F]SynVesT-1 PET as a potential biomarker for diagnosing and evaluating the disease, and guiding synaptic restoration trials. ANN NEUROL 2025.</p>\",\"PeriodicalId\":127,\"journal\":{\"name\":\"Annals of Neurology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":8.1000,\"publicationDate\":\"2025-01-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/ana.27179\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ana.27179","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Synaptic Density Reductions in MSA: A Potential Biomarker Identified Through [18F]SynVesT-1 PET Imaging.
Objective: The objective of this study was to delineate synaptic density alterations in multiple system atrophy (MSA) and explore its potential role as a biomarker for MSA diagnosis and disease severity monitoring using [18F]SynVesT-1 positron emission tomography / computed tomography (PET CT).
Methods: In this prospective study, 60 patients with MSA (30 patients with MSA-parkinsonian [MSA-P] subtype and 30 patients with MSA-cerebellar [MSA-C] subtype), 30 patients with Parkinson's disease (PD), and 30 age-matched healthy controls (HCs) underwent [18F]SynVesT-1 PET/CT for synaptic density assessment. Visual, voxel, and volumetric region of interest (VOI) analyses were used to elucidate synaptic density patterns in the MSA brain and establish diagnostic criteria. The diagnostic performances of both visual and VOI-based diagnostics were evaluated using receiver operating characteristic (ROC) analysis. Spearman correlation analyses were conducted to investigate the relationship between brain synaptic density and disease severity RESULTS: Patients with MSA displayed extensive reductions in synaptic density throughout the brain, notably affecting both primary VOIs (the cerebellum and putamen) and secondary VOIs including the medulla oblongata, ventral tegmental area, and pons. Notably, patients with MSA-C exhibited a remarkable decrease in cerebellar synaptic density, whereas patients with MSA-P demonstrated significant synaptic loss within the posterior putamen. Compared with patients with PD, the patients with MSA show a more pronounced reduction in synaptic density in infratentorial brain regions. VOI-based diagnosis significantly outperformed visual analysis in diagnosing and differentiating MSA and its subtypes. Synaptic density in primary and multiple secondary VOIs correlated significantly with motor scales in patients with MSA.
Interpretation: Our study identified widespread synaptic density reductions in MSA, particularly in the basal ganglia and infratentorial region, suggesting [18F]SynVesT-1 PET as a potential biomarker for diagnosing and evaluating the disease, and guiding synaptic restoration trials. ANN NEUROL 2025.
期刊介绍：
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
