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: R2=0.96, P<0.001; Elastica van Giesson stain: R2=0.79, P<0.001). Contrast-to-noise ratio measurements for the iron oxide and elastin-probe were in good agreement with inductively coupled mass spectroscopy ( R2=0.88, R2=0.75, P<0.001) and laser ablation coupled to inductively coupled plasma-mass spectrometry. CONCLUSIONS This study demonstrates the potential of the concurrent assessment of inflammatory activity and extracellular matrix degradation by dual-probe molecular magnetic resonance imaging in an AAA mouse model. Based on the combined information from both molecular probes, the rupture of AAAs could reliably be predicted.

中文翻译：

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并发分子磁共振成像的炎症活动和细胞外基质降解预测的动脉瘤破裂。

背景技术分子磁共振成像是用于表征腹主动脉瘤（AAA）的一种有前途的方式。不同分子成像生物标记物的组合可以改善对破裂风险的评估。这项研究调查了在AAA小鼠模型中通过同时进行的双探针分子磁共振成像对炎症活性和细胞外基质降解进行成像的可行性。方法将连续注入Ang II（血管紧张素II； 1000 ng / [kg·min]）以诱导AAAs的渗透性微型泵植入载脂蛋白缺乏的小鼠（N = 58）中。将动物分为2组。在第1组（纵向组，n = 13）中，在1周后使用临床剂量的巨噬细胞特异性氧化铁基探针（ferumoxytol，4 mgFe / kg，炎症活性的替代标记）和弹性蛋白特异性g基探针（0.2 mmol / kg，细胞外基质降解的替代标记）。然后以死亡为终点监测动物。在第2组（逐周组）中，在1、2、3和4周后使用两种探针进行成像（每组n = 9）。在一次磁共振过程中评估了这两种探针。结果炎性活性和细胞外基质降解的综合评估是AAA破裂的最强预测因子（敏感性100％；特异性89％；曲线下面积0.99）。仅来自每个单个探针的信息导致较低的预测准确性。弹性蛋白和氧化铁探针的体内测量与离体组织病理学非常吻合（普鲁士蓝染色：R2 = 0.96，P <0.001; Elastica van Giesson染色：R2 = 0。79，P ＜0.001）。氧化铁和弹性蛋白探针的对比噪声比测量与电感耦合质谱法（R2 = 0.88，R2 = 0.75，P <0.001）和激光烧蚀耦合电感耦合等离子体质谱法非常吻合。结论本研究证明了在AAA小鼠模型中通过双探针分子磁共振成像同时评估炎症活动和细胞外基质降解的潜力。根据来自两种分子探针的综合信息，可以可靠地预测AAA的破裂。结论本研究证明了在AAA小鼠模型中通过双探针分子磁共振成像同时评估炎症活动和细胞外基质降解的潜力。根据来自两种分子探针的综合信息，可以可靠地预测AAA的破裂。结论本研究证明了在AAA小鼠模型中通过双探针分子磁共振成像同时评估炎症活动和细胞外基质降解的潜力。根据来自两种分子探针的综合信息，可以可靠地预测AAA的破裂。