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使用胶原蛋白特异性造影剂EP-3600进行心肌灌注的分子磁共振成像:猪模型的初步可行性研究。

Molecular magnetic resonance imaging of myocardial perfusion with EP-3600, a collagen-specific contrast agent: initial feasibility study in a swine model.

作者信息

Spuentrup Elmar, Ruhl Karl M, Botnar Rene M, Wiethoff Andrea J, Buhl Alexandra, Jacques Vincent, Greenfield Matthew T, Krombach Gabriele A, Günther Rolf W, Vangel Mark G, Caravan Peter

机构信息

Department of Diagnostic Radiology, University Hospital, Technical University Aachen, Aachen, Germany.

出版信息

Circulation. 2009 Apr 7;119(13):1768-75. doi: 10.1161/CIRCULATIONAHA.108.826388. Epub 2009 Mar 23.

DOI:10.1161/CIRCULATIONAHA.108.826388
PMID:19307474
Abstract

BACKGROUND

Cardiac magnetic resonance (MR) perfusion imaging during the first pass after intravenous administration of extracellular contrast agents is hampered by the spatial and temporal resolution achievable and by the artifacts seen in ultrafast MR imaging. Furthermore, time-consuming quantitative data analysis is often added. The use of molecular MR imaging with a target-specific contrast agent with perfusion-dependent binding to myocardium may enable prolonged visualization of perfusion defects and thus may help to overcome limitations of currently used first-pass extracellular MR imaging. EP-3600 is a new gadolinium-containing molecular contrast agent that binds reversibly to myocardial collagen.

METHODS AND RESULTS

A significant but nonocclusive coronary artery stenosis was modeled in 7 domestic swine with an undersized MR-compatible balloon positioned in the left anterior descending artery as verified by x-ray angiography. Two animals died before contrast injection as a result of arrhythmias. In 5 swine, high-spatial-resolution gradient echo imaging (approximately 1 x 1 mm(2) in-plane resolution) was performed before and 5, 20, 40, and 60 minutes after intravenous administration of 12.3 micromol/kg EP-3600. Contrast was administered during stress induced by an infusion of 250 mumol x kg(-1) x min(-1) adenosine. Yb-DTPA was administered simultaneously for comparison of myocardium-to-plasma ratios. Images were assessed subjectively by 2 investigators, and signal-to-noise and contrast-to-noise ratios over time were calculated. Normal myocardium showed a significant signal-to-noise ratio increase during the entire examination time. In all animals (n=5), the perfusion defect in the left anterior descending artery territory could be visualized with a high contrast-to-noise ratio for at least 20 minutes after contrast injection. A significantly higher myocardium-to-plasma ratio was found for EP-3600 compared with the control agent Yb-DTPA (0.85+/-0.26 versus 0.22+/-0.08, respectively; P<0.01).

CONCLUSIONS

EP-3600 is a new molecular MR imaging contrast agent that binds to the myocardium and enables prolonged, high-contrast, high-spatial-resolution visualization of myocardial perfusion defects.

摘要

背景

静脉注射细胞外造影剂后的首次通过心脏磁共振(MR)灌注成像受到可实现的空间和时间分辨率以及超快MR成像中出现的伪影的限制。此外,通常还需要耗时的定量数据分析。使用与心肌具有灌注依赖性结合的靶向特异性造影剂进行分子MR成像,可能能够延长灌注缺损的可视化时间,从而有助于克服目前使用的首次通过细胞外MR成像的局限性。EP - 3600是一种新的含钆分子造影剂,可与心肌胶原蛋白可逆性结合。

方法与结果

通过将尺寸过小的与MR兼容的球囊置于左前降支动脉中,在7只家猪中模拟了显著但非闭塞性的冠状动脉狭窄,经X线血管造影证实。2只动物在注射造影剂前因心律失常死亡。在5只猪中,静脉注射12.3 μmol/kg EP - 3600前以及注射后5、20、40和60分钟进行了高空间分辨率梯度回波成像(平面分辨率约为1×1 mm²)。在输注250 μmol·kg⁻¹·min⁻¹腺苷诱导的应激期间给予造影剂。同时给予钇 - 二乙三胺五乙酸(Yb - DTPA)以比较心肌与血浆的比率。由2名研究人员对图像进行主观评估,并计算随时间变化的信噪比和对比噪声比。正常心肌在整个检查时间内显示出显著的信噪比增加。在所有动物(n = 5)中,造影剂注射后至少20分钟,左前降支动脉区域的灌注缺损能够以高对比噪声比可视化。与对照剂Yb - DTPA相比,EP - 3600的心肌与血浆比率显著更高(分别为0.85±0.26和0.22±0.08;P<0.01)。

结论

EP - 3600是一种新的分子MR成像造影剂,可与心肌结合,能够对心肌灌注缺损进行长时间、高对比度、高空间分辨率的可视化。

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