Concurrent Molecular Magnetic Resonance Imaging of Inflammatory Activity and Extracellular Matrix Degradation for the Prediction of Aneurysm Rupture
Concurrent Molecular Magnetic Resonance Imaging of Inflammatory Activity and Extracellular Matrix Degradation for the Prediction of Aneurysm Rupture
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DOI：
10.1161/circimaging.118.008707
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发表时间：
2019-03-01
影响因子：
7.5
通讯作者：
Makowski, Marcus R.
中科院分区：
文献类型：
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作者：
Brangsch, Julia;Reimann, Carolin;Makowski, Marcus R.
背景：分子磁共振成像是诊断腹主动脉瘤(AAA)的一种很有前途的方法。不同分子影像生物标记物的联合应用可能会提高对破裂风险的评估。本研究探讨双探针分子磁共振成像技术在AAA小鼠模型中显示炎症活动和细胞外基质降解的可行性。方法：将血管紧张素II(Ang II；1000 ng/[kg.min])持续输注的渗透性微泵植入载脂蛋白缺陷小鼠(n=58)体内，诱导AAA。动物被分成两组。在第1组(纵向组，n=13)，在1周后用临床剂量的巨噬细胞特异性氧化铁探针(亚铁缩醇，4mgFe/kg，炎症活动的替代标志物)和弹性蛋白特异性Gd(0.2 mmol/kg，细胞外基质降解的替代标志物)进行一次成像。然后以死亡为终点对动物进行监测。第2组(逐周组)分别于术后1周、2周、3周、4周(n=9)行双探头显像。结果：联合评估炎症活动性和细胞外基质降解是AAA破裂的最强预测指标(敏感性100%；特异性89%；曲线下面积0.99)。来自每个单一探针的信息单独导致预测准确率较低。弹性蛋白和氧化铁探针的体内测量结果与体外组织病理学结果一致(普鲁士蓝染色：R-2=0.96，P
BACKGROUND: Molecular magnetic resonance imaging is a promising modality for the characterization of abdominal aortic aneurysms (AAAs). The combination of different molecular imaging biomarkers may improve the assessment of the risk of rupture. This study investigates the feasibility of imaging inflammatory activity and extracellular matrix degradation by concurrent dual-probe molecular magnetic resonance imaging in an AAA mouse model.METHODS: Osmotic minipumps with a continuous infusion of Ang II (angiotensin II; 1000 ng/[kg.min]) to induce AAAs were implanted in apolipoprotein-deficient mice (N=58). Animals were assigned to 2 groups. In group 1 (longitudinal group, n=13), imaging was performed once after 1 week with a clinical dose of a macrophage-specific iron oxide-based probe (ferumoxytol, 4 mgFe/kg, surrogate marker for inflammatory activity) and an elastin-specific gadolinium-based probe (0.2 mmol/kg, surrogate marker for extracellular matrix degradation). Animals were then monitored with death as end point. In group 2 (week-by-week-group), imaging with both probes was performed after 1, 2, 3, and 4 weeks (n=9 per group). Both probes were evaluated in 1 magnetic resonance session.RESULTS: The combined assessment of inflammatory activity and extracellular matrix degradation was the strongest predictor of AAA rupture (sensitivity 100%; specificity 89%; area under the curve, 0.99). Information from each single probe alone resulted in lower predictive accuracy. In vivo measurements for the elastin-and iron oxide-probe were in good agreement with ex vivo histopathology (Prussian blue-stain: R-2=0.96, P