Challenges towards MR imaging of the peripheral inflammatory response in the subacute and chronic stages of transient focal ischemia
Challenges towards MR imaging of the peripheral inflammatory response in the subacute and chronic stages of transient focal ischemia
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DOI：
10.1002/nbm.1553
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发表时间：
2011-01-01
影响因子：
2.9
通讯作者：
Hoehn, Mathias
中科院分区：
文献类型：
--
作者：
Farr, Tracy D.;Seehafer, Joerg U.;Hoehn, Mathias
实验性中风后静脉注射氧化铁纳米颗粒已被证明会在 MRI 图像上的缺血边界产生局灶信号强度变化。这些变化归因于富含铁的血源性巨噬细胞的涌入，尽管有人认为这种效应可能并不总是完全针对炎症细胞。本研究的目的是在与外周炎症反应更相关的亚急性时间范围内研究这种现象。短暂性大脑中动脉闭塞（MCAO）后 6 天，在 Wistar 大鼠中进行成像实验（T(2)-、T(2)*- 和 T(1) 加权序列）。动物静脉注射不同剂量的超小超顺磁性氧化铁（USPIO）纳米粒子（300、600或1000μmol Fe/kg）或盐水和钆，24小时后再次成像。立即对组织进行免疫组织化学处理，使用巨噬细胞标记物 ED-1，并结合普鲁士蓝检测铁。缺血组织的 T(2) 值大幅增加，大脑和周围肌肉的整体对比度增强明显。与之前的报告相反，尽管感兴趣区域分析揭示了缺血半球铁积累的趋势，特别是在 T(2)* 图像的皮质中，但任何图像中的缺血区域均没有焦点信号强度变化的区域。然而，组织学检查显示，尽管整个缺血区域有大量 ED-1 阳性巨噬细胞积聚，但除了接受高剂量 USPIO 纳米粒子的一只动物的脑膜外，这些细胞均未呈普鲁士蓝阳性。这些结果意味着观察到的趋势是血液或脑膜中存在造影剂的结果，而不是含铁炎症细胞的结果。版权所有 (C) 2010 约翰·威利父子有限公司
Intravenous administration of iron oxide nanoparticles after experimental stroke has been shown to produce focal signal intensity changes in the ischemic boundary on MRI images. These changes have been attributed to the influx of iron-laden blood-borne macrophages, although it has been suggested that this effect might not always be completely specific to inflammatory cells. The aim of the present study was to investigate this phenomenon in a subacute time frame that is more relevant to the peripheral inflammatory response. Imaging experiments (T(2)-, T(2)*- and T(1)-weighted sequences) were acquired in Wistar rats 6 days after transient middle cerebral artery occlusion (MCAO). Animals were intravenously infused with different doses of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (300, 600 or 1000 mu mol Fe/kg), or saline and gadolinium, and imaged again 24 h later. Tissue was immediately processed for immunohistochemistry with the macrophage marker ED-1, in combination with Prussian blue for iron. Ischemic tissue exhibited a large increase in T(2) values, and overall contrast enhancement was apparent in the brain and surrounding muscle. In contrast with previous reports, there were no regions of focal signal intensity changes in the ischemic territory in any of the images, although a region of interest analysis revealed a trend towards iron accumulation in the ischemic hemisphere, particularly in the cortex of T(2)* images. However, histological examination revealed that, despite extensive ED-1-positive macrophage accumulation in the entire ischemic territory, none of these cells were Prussian blue positive, except in the meninges of one animal that received a high dose of USPIO nanoparticles. These results imply that the observed trend is a result of the presence of contrast agent in the blood, or meninges, and not iron-containing inflammatory cells. Copyright (C) 2010 John Wiley & Sons, Ltd.