Ex vivo magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in a murine model

Ex vivo magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in a murine model
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DOI:
10.1038/s41598-020-69299-y
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发表时间:
2020-07-24
期刊:
影响因子:
4.6
通讯作者:
Makowski, Marcus R.
Makowski, Marcus R.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mangarova, Dilyana B.;Brangsch, Julia;Makowski, Marcus R.

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腹主动脉瘤(AAA)目前是发达国家的主要死亡原因之一。炎症在疾病进展中至关重要,对AAAs发展中的各种决定因素具有实质性影响。磁性粒子成像(MPI)是一种创新的成像方式,能够高灵敏度地检测磁性纳米粒子(MNP),适合作为血管炎症分子靶向的替代标记物。在这项研究中,载脂蛋白E缺陷小鼠接受了渗透微型泵的手术植入,并持续输注血管紧张素II。分别于术后3周和4周进行体内磁共振成像(MRI)、离体磁共振成像(MPI)和离体磁粒子波谱(MPS)检查。组织学分析,免疫组织学和激光消融电感耦合等离子体质谱法的结果进行了验证。磁共振血管造影使可视化的动脉瘤的发展和扩张的实验组。测量了与组织学面积评估的密切相关性(R = 0.87)。离体MPS显示AAA样本中有大量铁沉积,离体组织病理学测量结果一致性良好(R = 0.76)。离体-MPI和MPS结果高度相关(R = 0.99)。CD 68免疫组织化学染色和Perls普鲁士蓝染色证实了巨噬细胞和MNP的共定位。本研究证明了离体MPI检测AAA炎症的可行性。MNP映射的定量能力确立了MPI作为在实验环境中监测AAA中炎症进展的有前途的工具。
Abdominal aortic aneurysms (AAAs) are currently one of the leading causes of death in developed countries. Inflammation is crucial in the disease progression, having a substantial impact on various determinants in AAAs development. Magnetic particle imaging (MPI) is an innovative imaging modality, enabling the highly sensitive detection of magnetic nanoparticles (MNPs), suitable as surrogate marker for molecular targeting of vascular inflammation. For this study, Apolipoprotein E-deficient-mice underwent surgical implantation of osmotic minipumps with constant Angiotensin II infusion. After 3 and 4 weeks respectively, in-vivo-magnetic resonance imaging (MRI), ex-vivo-MPI and ex-vivo-magnetic particle spectroscopy (MPS) were performed. The results were validated by histological analysis, immunohistology and laser ablation-inductively coupled plasma-mass spectrometry. MR-angiography enabled the visualization of aneurysmal development and dilatation in the experimental group. A close correlation (R = 0.87) with histological area assessment was measured. Ex-vivo-MPS revealed abundant iron deposits in AAA samples and ex-vivo histopathology measurements were in good agreement (R = 0.76). Ex-vivo-MPI and MPS results correlated greatly (R = 0.99). CD68-immunohistology stain and Perls'-Prussian-Blue-stain confirmed the colocalization of macrophages and MNPs. This study demonstrates the feasibility of ex-vivo-MPI for detecting inflammation in AAA. The quantitative ability for mapping MNPs establishes MPI as a promising tool for monitoring inflammatory progression in AAA in an experimental setting.