Noninvasive in vivo high-resolution magnetic resonance imaging of atherosclerotic lesions in genetically engineered mice

Noninvasive in vivo high-resolution magnetic resonance imaging of atherosclerotic lesions in genetically engineered mice
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DOI:
10.1161/01.cir.98.15.1541
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发表时间:
1998-10-13
期刊:
影响因子:
37.8
通讯作者:
Fuster, V
Fuster, V
中科院分区:
医学1区
文献类型:
--
作者:
Fayad, ZA;Fallon, JT;Fuster, V

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背景-动脉粥样硬化的发病机制目前正在基因工程小动物中进行研究。追踪病理发展的时间进程和/或体内治疗反应的方法是有限的。方法和结果-为了解决这个问题,我们开发了一种无创磁共振显微镜技术来研究活体载脂蛋白e敲除(apoE-KO)小鼠体内的动脉粥样硬化病变(没有先验的病变位置或病变类型知识)。空间分辨率为0.0012 ~ 0.005 mm(3)。apoE-KO小鼠(n = 8)和野生型小鼠(n = 5)的所有图像均显示腹主动脉和髂动脉的管腔和壁。将MR获得的图像与相应的横断面组织病理学进行比较(n = 58)。与组织病理学相比,MR准确地确定了壁面积(斜率= 1.0,r = 0.86)。此外,动脉粥样硬化病变在病变形态和类型方面的特征。病变类型根据形态外观/严重程度通过MR分级,根据AHA分类通过组织病理学分级。MR与组织病理学在病变形状和类型的分级上非常吻合(病变形状斜率= 0.97,r = 0.91;病变类型斜率= 0.64,r = 0.90)。结论:高分辨率磁共振显微镜和基因工程动物的结合是一种强有力的工具,可以在完整的动物模型中连续和无创地研究动脉粥样硬化病变的进展和消退,并应大大加强动脉粥样硬化疾病的基础研究。
Background - The pathogenesis of atherosclerosis is currently being investigated in genetically engineered small animals.Methods to follow the time course of the developing pathology and/or the responses to therapy in vivo are limited. Methods ann Results - To address this problem, we developed a noninvasive MR microscopy technique to study in vivo atherosclerotic lesions (without a priori knowledge of the lesion location or lesion type) in live apolipoprotein E-knockout (apoE-KO) mice. The spatial resolution was 0.0012 to 0.005 mm(3). The lumen and wall of the abdominal aorta and iliac arteries were identified on all images in apoE-KO (n = 8) and wild-type (n = 5) mice on chow diet. Images obtained with MR were compared with corresponding cross-sectional histopathology (n = 58). MR accurately determined wall area in comparison to histopathology (slope = 1.0, r = 0.86). In addition, atherosclerotic lesions were characterized in terms of lesion shape and type. Lesion type was graded by MR according to morphological appearance/severity and by histopathology according to the AHA classification. There was excellent agreement between MR and histopathology in grading of lesion shape and type (slope = 0.97, r = 0.91 for lesion shape; slope = 0.64, r = 0.90 for lesion type).Conclusions - The combination of high-resolution MR microscopy and genetically engineered animals is a powerful tool to investigate serially and noninvasively the progression and regression of atherosclerotic lesions in an intact animal model and should greatly enhance basic studies of atherosclerotic disease.