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使用弹性蛋白特异性分子磁共振成像对主动脉瘤壁完整性进行体内评估。

In vivo assessment of aortic aneurysm wall integrity using elastin-specific molecular magnetic resonance imaging.

作者信息

Botnar René M, Wiethoff Andrea J, Ebersberger Ullrich, Lacerda Sara, Blume Ulrike, Warley Alice, Jansen Christian H P, Onthank David C, Cesati Richard R, Razavi Reza, Marber Michael S, Hamm Bernd, Schaeffter Tobias, Robinson Simon P, Makowski Marcus R

机构信息

From the Division of Imaging Sciences (R.M.B., A.J.W., S.L., U.B., C.H.P.J., R.R., T.S., M.R.M.), BHF Centre of Excellence (R.M.B., S.L., R.R., M.S.M., T.S., M.R.M.), Cardiovascular Division (M.S.M.), Centre for Ultrastructural Imaging (A.W.), Wellcome Trust and EPSRC Medical Engineering Center (R.M.B., S.L., R.R., T.S.), and NIHR Biomedical Research Centre (R.M.B., S.L., R.R., M.S.M., T.S.), King's College London, London, United Kingdom; Philips Healthcare, Guildford, United Kingdom (A.J.W.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Department of Cardiology and Intensive Care Medicine, Heart Center Munich-Bogenhausen, Munich, Germany (U.E.); and Department of Radiology, Charite, Berlin, Germany (B.H., M.R.M.).

出版信息

Circ Cardiovasc Imaging. 2014 Jul;7(4):679-89. doi: 10.1161/CIRCIMAGING.113.001131. Epub 2014 May 28.

Abstract

BACKGROUND

The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, there is still controversy about the management of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter, are needed to assess aortic wall integrity and risk of rupture. Elastin is the key protein for maintaining aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here, we evaluate the usefulness of elastin-specific molecular MRI for the in vivo characterization of AAAs.

METHODS AND RESULTS

To induce AAAs, ApoE(-/-) mice were infused with angiotensin-II. An elastin-specific magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3, and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise ratios and R1-relaxation rates after ESMA administration were in good agreement with ex vivo histomorphometry (Elastica van Gieson stain) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic fibers.

CONCLUSIONS

Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular magnetic resonance imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs.

摘要

背景

在过去几十年中,腹主动脉瘤(AAA)的发病率有所上升。然而,对于中等大小AAA的治疗仍存在争议。因此,除了动脉瘤直径外,还需要新的生物标志物来评估主动脉壁的完整性和破裂风险。弹性蛋白是维持主动脉壁抗张强度和稳定性的关键蛋白质。结构蛋白的逐渐分解,尤其是中层弹性蛋白的分解,导致主动脉壁无法承受腔内血流动力学力量。在此,我们评估弹性蛋白特异性分子磁共振成像在AAA体内特征描述中的作用。

方法与结果

为诱导AAA,给载脂蛋白E基因敲除(ApoE(-/-))小鼠输注血管紧张素II。在输注血管紧张素II 1、2、3和4周后给予弹性蛋白特异性磁共振分子成像剂(ESMA),以评估主动脉的弹性蛋白组成(每组n = 8)。ESMA提供的高信号允许进行高空间分辨率成像,从而准确评估破裂的弹性膜和弹性纤维的代偿性表达。ESMA给药后的体内对比噪声比和R1弛豫率与离体组织形态计量学(弹性纤维染色)和通过电感耦合等离子体质谱法测定的钆浓度高度一致。电子显微镜证实ESMA与弹性纤维共定位。

结论

通过弹性蛋白特异性分子磁共振成像可以很容易地描绘和量化AAA不同阶段弹性蛋白含量的变化。ESMA-MRI为在主动脉扩张前无创检测主动脉破裂部位以及在AAA进展过程中对代偿性修复过程进行体内监测提供了潜力。

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