Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Department of Veterinary Medicine, Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Freie Universität Berlin, Königsweg 67, Building 21, 14163, Berlin, Germany.
Sci Rep. 2020 Feb 24;10(1):3231. doi: 10.1038/s41598-020-59842-2.
Abdominal aortic aneurysm (AAA) remains a fatal disease. Its development encompasses a complex interplay between hemodynamic stimuli on and changes in the arterial wall. Currently available biomarkers fail to predict the risk of AAA rupture independent of aneurysm size. Therefore, novel biomarkers for AAA characterization are needed. In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance imaging (MRI) with an albumin-binding probe to assess changes in vascular permeability at different stages of aneurysm growth. Two imaging studies were performed: a longitudinal study with follow-up and death as endpoint to predict rupture risk and a week-by-week study to characterize AAA development. AAAs, which eventually ruptured, demonstrated a significantly higher in vivo MR signal enhancement from the albumin-binding probe (p = 0.047) and a smaller nonenhancing thrombus area compared to intact AAAs (p = 0.001). The ratio of albumin-binding-probe enhancement of the aneurysm wall to size of nonenhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%). More advanced aneurysms with higher vascular permeability demonstrated an increased uptake of the albumin-binding-probe. These results indicate that MRI with an albumin-binding probe may enable noninvasive assessment of vascular permeability in murine AAAs and prediction of rupture risk.
腹主动脉瘤(AAA)仍然是一种致命的疾病。它的发展涉及到血流动力学刺激和动脉壁变化之间的复杂相互作用。目前可用的生物标志物不能独立于动脉瘤大小预测 AAA 破裂的风险。因此,需要用于 AAA 特征描述的新型生物标志物。在这项研究中,我们使用 AAA 的小鼠模型来研究磁共振成像(MRI)与白蛋白结合探针相结合的潜力,以评估在动脉瘤生长的不同阶段血管通透性的变化。进行了两项成像研究:一项具有随访和死亡作为终点的纵向研究,以预测破裂风险,以及一项每周研究以表征 AAA 的发展。最终破裂的 AAA 显示出明显更高的白蛋白结合探针的体内 MR 信号增强(p=0.047),以及与完整 AAA 相比更小的无增强血栓区域(p=0.001)。动脉瘤壁与无增强血栓区域的白蛋白结合探针增强的比值对 AAA 破裂具有很高的敏感性/特异性(100%/86%)。具有更高血管通透性的更高级别的动脉瘤显示出白蛋白结合探针摄取的增加。这些结果表明,白蛋白结合探针的 MRI 可能能够对小鼠 AAA 中的血管通透性进行非侵入性评估,并预测破裂风险。