症状前多发性硬化症脉络膜丛的影像学特征:回顾性研究。

IF 7.5
Vito A G Ricigliano, Céline Louapre, Emilie Poirion, Annalisa Colombi, Arya Yazdan Panah, Andrea Lazzarotto, Emanuele Morena, Elodie Martin, Michel Bottlaender, Benedetta Bodini, Danielle Seilhean, Bruno Stankoff
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引用次数: 9

摘要

背景和目的:最近的影像学研究提示多发性硬化症(MS)可能累及脉络膜丛(CP)。在这里,我们研究了在症状出现之前,MS的早期阶段是否已经检测到CP改变。方法:本研究回顾性分析27例症状前多发性硬化症患者、97例临床明确多发性硬化症(CDMS)患者和53例健康对照(hc),他们接受了横断面3T-MRI采集;其中22例MS、19例hc和1例症状前MS(在转化为CDMS前8个月评估)也接受了转运蛋白(TSPO) 18F-DPA-714 PET检查,并纳入分析。在3D t1加权图像上手动分割cp进行体积分析。CP 18F-DPA-714摄取,反映炎症,计算为平均标准化摄取值(SUV)。校正年龄、性别、脑室和脑容量的多变量回归检验症状前患者与MS或hc患者CP容量的差异。对于伴有18F-DPA-714 PET的症状前病例,通过Crawford-Howell试验评估CP SUV与MS和hc的差异。为了进一步了解在CP水平上对18F-DPA-714-PET摄取的解释,我们对MS和hc中CP的死后分析进行了表征TSPO表达的细胞定位。结果:与hc患者相比,症状前MS患者的CPs大32% (β = 0.38, p = 0.001),与MS患者的CPs无差异(p = 0.69)。此外,在症状前后来发展为MS的病例的基线扫描中,TSPO PET显示CP炎症比hc高33% (p = 0.04),尽管在实质区域的18F-DPA-714摄取与对照组没有差异。CP死后分析发现MS中CD163+单核吞噬细胞表达TSPO,可能导致18F-DPA-714摄取增加。讨论:我们使用MRI确定了症状前MS阶段CPs的成像特征;此外,我们发现在单个症状前患者中PET增加了CP炎症。这些发现提示CP成像作为早期生物标志物的作用,并论证了血- csf屏障功能障碍在疾病发展中的作用。试验注册信息:apap -20210727144630, eudrac - number: 2008-004174-40;ClinicalTrials.gov: NCT02305264、NCT01651520和NCT02319382。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Imaging Characteristics of Choroid Plexuses in Presymptomatic Multiple Sclerosis: A Retrospective Study.

Imaging Characteristics of Choroid Plexuses in Presymptomatic Multiple Sclerosis: A Retrospective Study.

Imaging Characteristics of Choroid Plexuses in Presymptomatic Multiple Sclerosis: A Retrospective Study.

Imaging Characteristics of Choroid Plexuses in Presymptomatic Multiple Sclerosis: A Retrospective Study.

Background and objectives: Recent imaging studies have suggested a possible involvement of the choroid plexus (CP) in multiple sclerosis (MS). Here, we investigated whether CP changes are already detectable at the earliest stage of MS, preceding symptom onset.

Methods: This study is a retrospective analysis of 27 patients with presymptomatic MS, 97 patients with clinically definite MS (CDMS), and 53 healthy controls (HCs) who underwent a cross-sectional 3T-MRI acquisition; of which, 22 MS, 19 HCs, and 1 presymptomatic MS (evaluated 8 months before conversion to CDMS) also underwent translocator protein (TSPO) 18F-DPA-714 PET and were included in the analysis. CPs were manually segmented on 3D T1-weighted images for volumetric analysis. CP 18F-DPA-714 uptake, reflecting inflammation, was calculated as the average standardized uptake value (SUV). Multivariable regressions adjusted for age, sex, and ventricular and brain volume were fitted to test CP volume differences between presymptomatic patients and MS or HCs. For the presymptomatic case who also had 18F-DPA-714 PET, CP SUV differences with MS and HCs were assessed through Crawford-Howell tests. To provide further insight into the interpretation of 18F-DPA-714-PET uptake at the CP level, a postmortem analysis of CPs in MS vs HCs was performed to characterize the cellular localization of TSPO expression.

Results: Compared with HCs, patients with presymptomatic MS had 32% larger CPs (β = 0.38, p = 0.001), which were not dissimilar to MS CPs (p = 0.69). Moreover, in the baseline scan of the presymptomatic case who later on developed MS, TSPO PET showed 33% greater CP inflammation vs HCs (p = 0.04), although no differences in 18F-DPA-714 uptake were found in parenchymal regions vs controls. CP postmortem analysis identified a population of CD163+ mononuclear phagocytes expressing TSPO in MS, possibly contributing to the increased 18F-DPA-714 uptake.

Discussion: We identified an imaging signature in CPs at the presymptomatic MS stage using MRI; in addition, we found an increased CP inflammation with PET in a single presymptomatic patient. These findings suggest a role of CP imaging as an early biomarker and argue for the involvement of the blood-CSF barrier dysfunction in disease development.

Trial registration information: APHP-20210727144630, EudraCT-Number: 2008-004174-40; ClinicalTrials.gov: NCT02305264, NCT01651520, and NCT02319382.

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