Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany (J.B., C.R., J.O.K., L.C.A., B.H., M.R.M.).
Department of Veterinary Medicine, Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Freie Universität Berlin, Germany (J.B., C.R., C.T.-R.).
Circ Cardiovasc Imaging. 2019 Mar;12(3):e008707. doi: 10.1161/CIRCIMAGING.118.008707.
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.
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.
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=0.96, P<0.001; Elastica van Giesson stain: R=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 ( R=0.88, R=0.75, P<0.001) and laser ablation coupled to inductively coupled plasma-mass spectrometry.
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.
分子磁共振成像是一种很有前途的方法，可以用于描述腹主动脉瘤（AAA）。结合不同的分子成像生物标志物可能会提高对破裂风险的评估。本研究旨在通过在 AAA 小鼠模型中进行双重探针分子磁共振成像，研究同时成像炎症活性和细胞外基质降解的可行性。
向载脂蛋白缺陷型小鼠（N=58）植入持续输注血管紧张素 II（Ang II；1000ng/[kg·min]）的渗透微泵以诱导 AAA。动物被分为 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探针（ferumoxytol，4mgFe/kg，炎症活性的替代标志物）和弹性蛋白特异性钆基探针（0.2mmol/kg，细胞外基质降解的替代标志物）进行一次成像。然后以动物死亡为终点进行监测。在第 2 组（每周组）中，在第 1、2、3 和 4 周后（每组 n=9）分别进行两种探针的成像。两种探针均在 1 次磁共振检查中进行评估。
炎症活性和细胞外基质降解的联合评估是 AAA 破裂的最强预测因素（敏感性 100%；特异性 89%；曲线下面积，0.99）。单独使用每种探针的信息导致预测准确性较低。体内测量的弹性蛋白和氧化铁探针与离体组织病理学具有很好的一致性（普鲁士蓝染色：R=0.96，P<0.001；弹力纤维 Van Gieson 染色：R=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（R=0.88，R=0.75，P<0.001）和激光烧蚀耦合电感耦合等离子体质谱法具有很好的一致性。
本研究证明了在 AAA 小鼠模型中通过双重探针分子磁共振成像同时评估炎症活性和细胞外基质降解的潜力。基于两种分子探针的综合信息，可以可靠地预测 AAA 的破裂。
