Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Yalelaan 2, 3584 CM Utrecht, The Netherlands.
Contrast Media Mol Imaging. 2013 Sep-Oct;8(5):393-401. doi: 10.1002/cmmi.1536.
An increasing amount of studies have provided evidence for vascular remodeling, for example, angiogenesis, after cerebral ischemia, which may play a significant role in post-stroke brain plasticity and recovery. Molecular imaging can provide unique in vivo whole-brain information on alterations in the expression of specific endothelial markers. A possible target for molecular magnetic resonance imaging (MRI) of post-stroke (neo)vascularization is platelet endothelial cell adhesion molecule-1 (PECAM-1). Here we describe significantly increased PECAM-1 mRNA levels in ipsilesional brain tissue at 6 h, 24 h and 3 days after transient middle cerebral artery occlusion in mice, and elevated PECAM-1 staining throughout the lesion at 3, 7 and 21 days post-stroke. The potential of micron-sized particles of iron oxide (MPIO) conjugated with PECAM-1-targeted antibodies, that is, αPECAM-1-MPIO, to expose stroke-induced PECAM-1 upregulation with molecular MRI was assessed. In vitro studies demonstrated that PECAM-1-expressing brain endothelial cells could be effectively labeled with αPECAM-1-MPIO, giving rise to a fourfold increase in MRI relaxation rate R2. Injection of near-infrared fluorescent dye-labeled αPECAM-1 showed target specificity and dose efficiency of the antibody for detection of brain endothelial cells at 3 days post-stroke. However, in vivo molecular MRI at 3 and 7 days after stroke revealed no αPECAM-1-MPIO-based contrast enhancement, which was corroborated by the absence of αPECAM-1-MPIO in post mortem brain tissue. This indicates that this molecular MRI approach, which has been proven successful for in vivo detection of other types of cell adhesion molecules, is not invariably effective for MRI-based assessment of stroke-induced alterations in expression of cerebrovascular markers.
越来越多的研究为脑缺血后的血管重构（例如血管生成）提供了证据，这可能在卒中后脑可塑性和恢复中发挥重要作用。分子成像可以提供特定内皮标志物表达变化的独特体内全脑信息。血小板内皮细胞黏附分子-1 (PECAM-1) 可能是卒中后（新）血管生成分子磁共振成像 (MRI) 的一个潜在靶点。在这里，我们描述了在小鼠短暂性大脑中动脉闭塞后 6 小时、24 小时和 3 天，对侧脑组织中 PECAM-1 mRNA 水平显著增加，并在卒中后 3、7 和 21 天整个病变部位升高 PECAM-1 染色。评估了与 PECAM-1 靶向抗体结合的微米级氧化铁颗粒（MPIO），即 αPECAM-1-MPIO，用于通过分子 MRI 暴露卒中诱导的 PECAM-1 上调的潜力。体外研究表明，PECAM-1 表达的脑内皮细胞可以被 αPECAM-1-MPIO 有效标记，导致 MRI 弛豫率 R2 增加四倍。近红外荧光染料标记的 αPECAM-1 注射显示出抗体对检测卒中后 3 天脑内皮细胞的靶向特异性和剂量效率。然而，卒中后 3 天和 7 天的体内分子 MRI 未显示出基于 αPECAM-1-MPIO 的对比增强，这与死后脑组织中不存在 αPECAM-1-MPIO 相符。这表明，这种分子 MRI 方法已被证明对其他类型细胞黏附分子的体内检测有效，但对于 MRI 基于评估卒中诱导的脑血管标志物表达变化并不总是有效。
