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通过联合C-PBR28正电子发射断层显像(PET)和合成磁共振成像(MRI)对多发性硬化症中微胶质细胞与髓磷脂关系进行体内表征

In vivo characterization of microglia and myelin relation in multiple sclerosis by combined C-PBR28 PET and synthetic MRI.

作者信息

Barletta Valeria T, Herranz Elena, Treaba Constantina Andrada, Mehndiratta Ambica, Ouellette Russell, Granberg Tobias, Klawiter Eric C, Ionete Carolina, Sloane Jacob A, Mainero Caterina

机构信息

Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 Thirteenth Street, Charlestown, Boston, MA, 02129, USA.

Harvard Medical School, Boston, MA, USA.

出版信息

J Neurol. 2023 Jun;270(6):3091-3102. doi: 10.1007/s00415-023-11621-5. Epub 2023 Mar 2.

DOI:10.1007/s00415-023-11621-5
PMID:36859627
Abstract

BACKGROUND

The in vivo relation between microglia activation and demyelination in multiple sclerosis is still unclear.

OBJECTIVE

We combined C-PBR28 positron emission tomography and rapid estimation of myelin for diagnostic imaging (REMyDI) to characterize the relation between these pathological processes in a heterogeneous MS cohort.

METHODS

C-PBR28 standardized uptake values normalized by a pseudo-reference region (SUVR) were used to measure activated microglia. A voxelwise analysis compared C-PBR28 SUVR in the white matter of 38 MS patients and 16 matched healthy controls. The relative difference in SUVR served as a threshold to classify patients' lesioned, perilesional and normal-appearing white matter as active or inactive. REMyDI was acquired in 27 MS patients for assessing myelin content in active and inactive white matter and its relationship with SUVR. Finally, we investigated the contribution of radiological metrics to clinical outcomes.

RESULTS

C-PBR28 SUVR were abnormally higher in several white matter areas in MS. Myelin content was lower in active compared to inactive corresponding white matter regions. An inverse correlation between SUVR and myelin content was found. Radiological metrics correlated with both neurological and cognitive impairment.

CONCLUSION

our data suggest an inverse relation of microglia activation and myelination, particularly in perilesional white matter tissue.

摘要

背景

多发性硬化症中,小胶质细胞激活与脱髓鞘之间的体内关系仍不清楚。

目的

我们结合C-PBR28正电子发射断层扫描和髓鞘快速评估诊断成像(REMyDI),以表征异质性多发性硬化症队列中这些病理过程之间的关系。

方法

使用通过伪参考区域标准化的C-PBR28摄取值(SUVR)来测量活化的小胶质细胞。进行体素分析,比较38例多发性硬化症患者和16例匹配的健康对照者白质中的C-PBR28 SUVR。SUVR的相对差异作为阈值,将患者的病变、病变周围和外观正常的白质分类为活跃或不活跃。对27例多发性硬化症患者进行REMyDI检查,以评估活跃和不活跃白质中的髓鞘含量及其与SUVR的关系。最后,我们研究了放射学指标对临床结局的影响。

结果

多发性硬化症患者的几个白质区域中,C-PBR28 SUVR异常升高。与相应的不活跃白质区域相比,活跃白质区域的髓鞘含量较低。发现SUVR与髓鞘含量呈负相关。放射学指标与神经和认知障碍均相关。

结论

我们的数据表明,小胶质细胞激活与髓鞘形成呈负相关,尤其是在病变周围白质组织中。

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Perilesional neurodegenerative injury in multiple sclerosis: Relation to focal lesions and impact on disability.多发性硬化症的病灶周围神经退行性损伤:与局灶性病变的关系及其对残疾的影响。
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Brain. 2019 Nov 1;142(11):3440-3455. doi: 10.1093/brain/awz287.
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Association of Chronic Active Multiple Sclerosis Lesions With Disability In Vivo.慢性活动性多发性硬化症病灶与体内残疾的关联。
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Profiles of cortical inflammation in multiple sclerosis by C-PBR28 MR-PET and 7 Tesla imaging.多模态 7 特斯拉 MRI 和 C-PBR28 PET 对多发性硬化皮质炎症特征的研究
Mult Scler. 2020 Oct;26(12):1497-1509. doi: 10.1177/1352458519867320. Epub 2019 Aug 1.
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Detrimental and protective action of microglial extracellular vesicles on myelin lesions: astrocyte involvement in remyelination failure.小胶质细胞细胞外囊泡对髓鞘病变的有害和保护作用:星形胶质细胞在髓鞘修复失败中的作用。
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