Fayad Z A, Fallon J T, Shinnar M, Wehrli S, Dansky H M, Poon M, Badimon J J, Charlton S A, Fisher E A, Breslow J L, Fuster V
Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY, USA
Circulation. 1998 Oct 13;98(15):1541-7. doi: 10.1161/01.cir.98.15.1541.
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.
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 mm3. 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).
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.
目前正在通过基因工程改造的小动物研究动脉粥样硬化的发病机制。在体内追踪病变发展的时间进程和/或对治疗反应的方法有限。
为解决这一问题，我们开发了一种无创磁共振显微镜技术，用于研究载脂蛋白E基因敲除（apoE-KO）活体小鼠体内的动脉粥样硬化病变（无需事先了解病变位置或病变类型）。空间分辨率为0.0012至0.005立方毫米。在喂食普通饲料的apoE-KO小鼠（n = 8）和野生型小鼠（n = 5）的所有图像上均能识别腹主动脉和髂动脉的管腔和管壁。将磁共振成像获得的图像与相应的横断面组织病理学图像（n = 58）进行比较。与组织病理学相比，磁共振能准确测定管壁面积（斜率 = 1.0，r = 0.86）。此外，还根据病变形状和类型对动脉粥样硬化病变进行了特征描述。磁共振根据形态外观/严重程度对病变类型进行分级，组织病理学则根据美国心脏协会（AHA）分类进行分级。在病变形状和类型分级方面，磁共振与组织病理学之间具有高度一致性（病变形状：斜率 = 0.97，r = 0.91；病变类型：斜率 = 0.64，r = 0.90）。
高分辨率磁共振显微镜与基因工程动物相结合，是在完整动物模型中连续、无创地研究动脉粥样硬化病变进展和消退的有力工具，应能大大加强动脉粥样硬化疾病的基础研究。
