Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging
Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging
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DOI：
10.1007/s00401-016-1636-z
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发表时间：
2017-01-01
影响因子：
12.7
通讯作者：
Hametner, Simon
中科院分区：
文献类型：
--
作者：
Dal-Bianco, Assunta;Grabner, Guenther;Hametner, Simon
在多发性硬化症（MS）中，铁在一些慢性脱髓鞘病变边缘的活化小胶质细胞/巨噬细胞内积累，形成边缘。在7 T时基于敏感性的磁共振成像中，铁负载的小胶质细胞/巨噬细胞在病变边缘诱导信号减弱，并与缓慢扩张的病变有关。我们的目的是确定(1)哪些病变类型和阶段与其边缘的铁积累有关，(2)病变边缘的哪些细胞积累铁，它们的激活状态是什么，(3)通过7t磁共振成像（MRI）检测病变边缘铁积累的可靠性如何，以及(4)与没有边缘的病变相比，有边缘的病变是否会随着时间的推移而扩大。对28例MS患者双半球脑切片进行铁、髓磷脂、小胶质细胞/巨噬细胞染色。在组织学检查之前，这28例中有4例在7 T时使用死后敏感性加权成像。在体内，7名MS患者每年接受神经系统检查和7次T MRI检查，持续3.5年，采用液体衰减反转恢复/敏感性加权成像融合序列。病理上，我们发现铁环周围缓慢扩张和一些不活跃的病变，但几乎没有在再髓鞘阴影斑块周围。轮辋铁主要存在于具有促炎激活状态的小胶质细胞/巨噬细胞中，而很少存在于星形胶质细胞中。死后敏感性加权成像的组织学验证显示，当边缘可见时，铁负载小胶质细胞的定量阈值。与不活跃的病变相比，缓慢扩张的病变明显超过了这个阈值（p = 0.003）。我们首次发现，与没有边缘的病变相比，3.5年后边缘病变在体内显著扩大（p = 0.003）。因此，反映慢性病变活动性的MS病变带边缘的缓慢扩张可能在未来成为MS疾病活动性的MRI标志物。
In multiple sclerosis (MS), iron accumulates inside activated microglia/macrophages at edges of some chronic demyelinated lesions, forming rims. In susceptibility-based magnetic resonance imaging at 7 T, iron-laden microglia/macrophages induce a rim of decreased signal at lesion edges and have been associated with slowly expanding lesions. We aimed to determine (1) what lesion types and stages are associated with iron accumulation at their edges, (2) what cells at the lesion edges accumulate iron and what is their activation status, (3) how reliably can iron accumulation at the lesion edge be detected by 7 T magnetic resonance imaging (MRI), and (4) if lesions with rims enlarge over time in vivo, when compared to lesions without rims. Double-hemispheric brain sections of 28 MS cases were stained for iron, myelin, and microglia/macrophages. Prior to histology, 4 of these 28 cases were imaged at 7 T using post-mortem susceptibility-weighted imaging. In vivo, seven MS patients underwent annual neurological examinations and 7 T MRI for 3.5 years, using a fluid attenuated inversion recovery/susceptibility-weighted imaging fusion sequence. Pathologically, we found iron rims around slowly expanding and some inactive lesions but hardly around remyelinated shadow plaques. Iron in rims was mainly present in microglia/macrophages with a pro-inflammatory activation status, but only very rarely in astrocytes. Histological validation of post-mortem susceptibility-weighted imaging revealed a quantitative threshold of iron-laden microglia when a rim was visible. Slowly expanding lesions significantly exceeded this threshold, when compared with inactive lesions (p = 0.003). We show for the first time that rim lesions significantly expanded in vivo after 3.5 years, compared to lesions without rims (p = 0.003). Thus, slow expansion of MS lesions with rims, which reflects chronic lesion activity, may, in the future, become an MRI marker for disease activity in MS.