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

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.