High-resolution magnetic resonance imaging enhanced with superparamagnetic nanoparticles measures macrophage burden in atherosclerosis.
High-resolution magnetic resonance imaging enhanced with superparamagnetic nanoparticles measures macrophage burden in atherosclerosis.
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DOI：
10.1161/circulationaha.109.891804
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发表时间：
2010-10-26
期刊：
影响因子：
37.8
通讯作者：
Aikawa M
中科院分区：
文献类型：
--
作者：
Morishige K;Kacher DF;Libby P;Josephson L;Ganz P;Weissleder R;Aikawa M
巨噬细胞参与动脉粥样硬化的进展和急性并发症。巨噬细胞成像可以作为一种生物标志物，以确定亚临床炎症病变，预测未来的风险，并帮助评估新的治疗方法。为了检验纳米颗粒增强的高分辨率磁共振成像（MRI）可以测量斑块巨噬细胞积聚的假设，我们在球囊损伤后6个月在胆固醇喂养的新西兰白色兔中使用了巨噬细胞靶向超顺磁性纳米颗粒制剂（单晶氧化铁纳米颗粒-47 [MION-47]）的3-T MRI。体内MRI在T1和T2加权自旋回波图像（T1自旋回波，每只动物20个轴向切片; T2自旋回波，每只动物28个切片）上显示增厚的腹部肿块。注射MION-47后72小时，与造影剂成像前相比，动脉瘤显示出较低的T2信号强度（信号强度比，主动脉壁/肌肉：造影前，1.44±0.26 vs造影后，0.95±0.22; 164层; P<0.01），而T1自旋回波图像显示无显著变化。离体标本的MRI结果相似。组织学研究表明动脉粥样硬化患者铁积聚与免疫反应性巨噬细胞共存。T2自旋回波在体内图像上的信号强度降低的幅度进一步与原位巨噬细胞面积相关（150个切片; r=0.73）。瑞舒伐他汀治疗3个月后，巨噬细胞含量减少（P<0.05），T2信号强度改变逆转（P<0.005）。瑞舒伐他汀治疗兔的信号变化与巨噬细胞负荷降低相关（r=0.73）。体外验证研究表明，人原代巨噬细胞对MION-47的摄取具有浓度依赖性。在施用超顺磁性可吞噬纳米颗粒后，高分辨率MRI中T2信号强度降低的幅度可以评估动脉粥样硬化中的巨噬细胞负荷，从而提供临床上可翻译的工具来识别发炎斑块并监测斑块炎症中的治疗介导的变化。
Macrophages contribute to the progression and acute complications of atherosclerosis. Macrophage imaging may serve as a biomarker to identify subclinical inflamed lesions, to predict future risk, and to aid in the assessment of novel therapies. To test the hypothesis that nanoparticle-enhanced, high-resolution magnetic resonance imaging (MRI) can measure plaque macrophage accumulation, we used 3-T MRI with a macrophage-targeted superparamagnetic nanoparticle preparation (monocrystalline iron oxide nanoparticles-47 [MION-47]) in cholesterol-fed New Zealand White rabbits 6 months after balloon injury. In vivo MRI visualized thickened abdominal aortas on both T1- and T2-weighted spin-echo images (T1 spin echo, 20 axial slices per animal; T2 spin echo, 28 slices per animal). Seventy-two hours after MION-47 injection, aortas exhibited lower T2 signal intensity compared with before contrast imaging (signal intensity ratio, aortic wall/muscle: before, 1.44±0.26 versus after, 0.95±0.22; 164 slices; P<0.01), whereas T1 spin echo images showed no significant change. MRI on ex vivo specimens provided similar results. Histological studies colocalized iron accumulation with immunoreactive macrophages in atheromata. The magnitude of signal intensity reduction on T2 spin echo in vivo images further correlated with macrophage areas in situ (150 slices; r=0.73). Treatment with rosuvastatin for 3 months yielded diminished macrophage content (P<0.05) and reversed T2 signal intensity changes (P<0.005). Signal changes in rosuvastatin-treated rabbits correlated with reduced macrophage burden (r=0.73). In vitro validation studies showed concentration-dependent MION-47 uptake by human primary macrophages. The magnitude of T2 signal intensity reduction in high-resolution MRI after administration of superparamagnetic phagocytosable nanoparticles can assess macrophage burden in atheromata, providing a clinically translatable tool to identify inflamed plaques and to monitor therapy-mediated changes in plaque inflammation.