In vivo characterization of a new abdominal aortic aneurysm mouse model with conventional and molecular magnetic resonance imaging.

In vivo characterization of a new abdominal aortic aneurysm mouse model with conventional and molecular magnetic resonance imaging.
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DOI:
10.1016/j.jacc.2011.09.017
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发表时间:
2011-12-06
影响因子:
24
通讯作者:
Fayad, Zahi A.
Fayad, Zahi A.
中科院分区:
医学1区
文献类型:
--
作者:
Klink, Ahmed;Heynens, Joeri;Herranz, Beatriz;Lobatto, Mark E.;Arias, Teresa;Sanders, Honorius M. H. F.;Strijkers, Gustav J.;Merkx, Maarten;Nicolay, Klaas;Fuster, Valentin;Tedgui, Alain;Mallat, Ziad;Mulder, Willem J. M.;Fayad, Zahi A.

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目的:应用无创性常规磁共振成像(MRI)和分子磁共振成像(MRI)技术,对活体腹主动脉瘤(AAA)进行检测和定性。胶原蛋白是动脉瘤的基本成分。无创性的胶原蛋白磁共振成像可能是帮助检测和更好地确定AAA的特征并开始干预的机会。我们使用了一种AAA C57BL/6小鼠模型,在该模型中,血管紧张素-II输注和转化生长因子-β中和联合导致了AAA的形成和主动脉破裂的发生率。采用高分辨率多序列磁共振成像研究腹主动脉病变的时间进程。为了能够进行胶原蛋白的分子磁共振成像,静脉注射了带有胶原结合蛋白(CNA-35)的顺磁性/荧光胶束纳米颗粒。体内成像结果通过免疫组织化学和共聚焦荧光显微镜得到证实。高分辨率多序列磁共振成像可以显示主动脉壁的原发纤维化反应。随着动脉瘤的进展,可检测到次级通道或夹层的形成。进一步的分析显示,主动脉直径急剧增加。与非特异性胶束相比,注射CNA-35胶束可显著增强动脉瘤壁上的MR信号。组织学研究表明,在MR信号增强区域存在胶原,共聚焦显微镜证实CNA-35胶束与I型胶原精确共存。此外,在一项概念验证实验中,我们展示了CNA-35胶束在区分稳定的AAA病变和可能快速进展/破裂的动脉瘤方面的潜力。多序列MRI可以纵向监测AAA的进展,而胶原蛋白的存在可以通过纳米颗粒增强的MRI可视化。
To use non-invasive conventional and molecular magnetic resonance imaging (MRI) to detect and characterize abdominal aortic aneurysms (AAAs) in vivo. Collagen is an essential constituent of aneurysms. Non-invasive MRI of collagen may represent an opportunity to help detect and better characterize AAA and initiate intervention. We used an AAA C57BL/6 mouse model where a combination of angiotensin-II infusion and TGF-β neutralization results in AAA formation with incidence of aortic rupture. High-resolution multi-sequence MRI was performed to characterize the temporal progression of AAA. To allow molecular MRI of collagen, paramagnetic/fluorescent micellar nanoparticles functionalized with a collagen-binding protein (CNA-35) were intravenously administered. In vivo imaging results were corroborated with immunohistochemistry and confocal fluorescence microscopy. High-resolution multi-sequence MRI allowed the visualization of the primary fibrotic response in the aortic wall. As the aneurysm progressed, the formation of a secondary channel or dissection was detected. Further analysis revealed a dramatic increase of the aortic diameter. Injection of CNA-35 micelles resulted in a significant higher MR signal enhancement in the aneurysmal wall compared to non-specific micelles. Histological studies demonstrated the presence of collagen in regions of MR signal enhancement and confocal microscopy proved the precise colocalization of CNA-35 micelles with collagen-I. In addition, in a proof of concept experiment, we have shown the potential of CNA-35 micelles to discriminate between stable AAA lesions and aneurysms that were likely to rapidly progress/rupture. Multi-sequence MRI allowed longitudinal monitoring of AAA progression while the presence of collagen was visualized by nanoparticle-enhanced MRI.
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