Brain magnetic resonance imaging is an important tool in the diagnosis and monitoring of multiple sclerosis patients. However, magnetic resonance imaging alone provides limited information for predicting an individual patient’s disability progression. In part, this is because magnetic resonance imaging lacks sensitivity and specificity for detecting chronic diffuse and multi-focal inflammation mediated by activated microglia/macrophages. The aim of this study was to test for an association between 18 kDa translocator protein brain positron emission tomography signal, which arises largely from microglial activation, and measures of subsequent disease progression in multiple sclerosis patients. Twenty-one patients with multiple sclerosis (seven with secondary progressive disease and 14 with a relapsing remitting disease course) underwent T₁- and T₂-weighted and magnetization transfer magnetic resonance imaging at baseline and after 1 year. Positron emission tomography scanning with the translocator protein radioligand ¹¹C-PBR28 was performed at baseline. Brain tissue and lesion volumes were segmented from the T₁- and T₂-weighted magnetic resonance imaging and relative ¹¹C-PBR28 uptake in the normal-appearing white matter was estimated as a distribution volume ratio with respect to a caudate pseudo-reference region. Normal-appearing white matter distribution volume ratio at baseline was correlated with enlarging T₂-hyperintense lesion volumes over the subsequent year (ρ = 0.59, P = 0.01). A post hoc analysis showed that this association reflected behaviour in the subgroup of relapsing remitting patients (ρ = 0.74, P = 0.008). By contrast, in the subgroup of secondary progressive patients, microglial activation at baseline was correlated with later progression of brain atrophy (ρ = 0.86, P = 0.04). A regression model including the baseline normal-appearing white matter distribution volume ratio, T₂ lesion volume and normal-appearing white matter magnetization transfer ratio for all of the patients combined explained over 90% of the variance in enlarging lesion volume over the subsequent 1 year. Glial activation in white matter assessed by translocator protein PET significantly improves predictions of white matter lesion enlargement in relapsing remitting patients and is associated with greater brain atrophy in secondary progressive disease over a period of short term follow-up.

中文翻译：

---

多发性硬化症中神经炎症及其与脑容量和白质病变变化的关系

脑磁共振成像是诊断和监测多发性硬化症患者的重要工具。然而，仅磁共振成像提供了用于预测单个患者的残疾进展的有限信息。部分原因是，磁共振成像缺乏检测活化小胶质细胞/巨噬细胞介导的慢性弥漫性和多灶性炎症的敏感性和特异性。这项研究的目的是测试18 kDa易位蛋白脑正电子发射断层扫描信号之间的关联，该信号主要由小胶质细胞激活引起，并与多发性硬化症患者随后的疾病进展进行了测量。21例多发性硬化症患者（7例继发进行性疾病和14例复发性缓解疾病过程）接受了T₁ -和T ₂ -加权和在基线磁化传递磁共振成像和1年后。在基线时用易位蛋白放射性配体¹¹ C-PBR28进行正电子发射断层扫描。从T ₁和T ₂加权磁共振成像中分割出脑组织和病变体积，并估计正常出现的白质中相对¹¹ C-PBR28的摄取，作为相对于尾状假参考区域的分布体积比。 。基线时正常出现的白质分布体积比与随后一年中T _2-超强病变体积的增加相关（ρ= 0.59，P =0.01）。甲事后分析显示，该关联反映在复发缓解型患者亚组行为（ρ= 0.74，P = 0.008）。相比之下，在继发性进行性患者的亚组中，基线时的小胶质细胞活化与脑萎缩的晚期发展相关（ρ= 0.86，P = 0.04）。包含基线正常出现的白质分布体积比T _2的回归模型所有患者的病灶体积和正常出现的白质磁化转移率的总和，解释了随后1年内病灶增大的变化的90％以上。通过移位蛋白PET评估白质中的胶质细胞活化可显着改善复发缓解患者中白质病变扩大的预测，并在短期随访期间与继发性进行性疾病中更大的脑萎缩相关。