超微型超顺磁性氧化铁增强磁共振成像评价兔动脉粥样硬化斑块:磁敏感伪影量化的意义(英文)

Ultrasmall superparamagnetic iron oxides for enhanced magnetic resonance imaging to detect atherosclerotic plaques of abdominal aorta in rabbits Role of magnetic susceptibility artifacts quantization

背景:巨噬细浸润目前被认为是动脉粥样硬化斑块不稳定的一个重要标志,具有巨噬细胞靶向功能的新型MR对比剂超微型超顺磁性氧化铁的开发和临床应用,为动脉粥样硬化斑块的功能成像提供了可能。目的:观察静脉内注射超微型超顺磁性氧化铁是否能被高脂喂养所诱发的兔腹主动脉粥样硬化斑块内巨噬细胞所吞噬,所产生的磁敏感伪影是否能被磁共振成像所显示,并且将其量化用于评价动脉粥样硬化斑块稳定性的可行性。设计、时间及地点:随机对照动物实验,于2006-03/2007-03在苏州大学附属第一医院影像中心完成。材料:将20只大白兔按随机数字表法分为2组,实验组15只,正常组5只。实验组采用介入法球囊拉伤+高脂饮食喂养制作腹主动脉粥样硬化模型,4个月后,将实验组15只兔再随机分为2组,超微型超顺磁性氧化铁增强扫描组10只,模型对照组5只。正常组饲以普通饲料。方法:在注射试剂前,各组均进行1次MR扫描。然后,超微型超顺磁性氧化铁增强扫描组经静脉注入超细颗粒超顺磁性氧化铁SHU555C,剂量200μmol/kg,注射后即刻及注射后第1,3,5天4个时间点分别进行1次MRI检查;模型对照组注射生理盐水后仅在第5天进行1次MR扫描;正常组以相同的剂量注入SHU555C后第5天进行MR扫描。MRI检查采用亮血技术时间飞跃法3D快速梯度回波序列。扫描范围包括腹主动脉腹腔干分叉处到髂动脉分叉处。主要观察指标:分别测量和对比各组在不同时间点腹主动脉管壁的信噪比以及注射试剂前后腹主动脉横断面积的缩小值和缩小百分比。腹主动脉标本进行苏木精-伊红和普鲁士蓝染色观察组织学改变。结果:超微型超顺磁性氧化铁增强扫描组注射后腹主动脉明显不规则,管壁可见斑点状信号缺失区,管腔不规则狭窄,以第5天最显著。超微型超顺磁性氧化铁增强扫描组注射前和注射后第5天管壁信噪比差异有显著性意义(P<0.05),SNR明显减低;模型对照组和正常组注射前后管壁SNR差异无显著性意义(P>0.05)。腹主动脉横断面面积测量,3组注射后第5天腹主动脉横断面面积缩小值和缩小百分比总体均数不等(P<0.05),超微型超顺磁性氧化铁增强扫描组与模型对照组、超微型超顺磁性氧化铁增强扫描组与正常组之间有显著性意义(P<0.01),模型对照组与正常组差异无显著性意义(P>0.05)。普鲁士蓝染色显示,超微型超顺磁性氧化铁增强扫描组增厚的动脉管壁和粥样斑块内可见铁颗粒蓄积,被染成紫蓝色斑块状。结论:超微型超顺磁性氧化铁可以被人工高脂喂养所诱发的兔腹主动脉粥样硬化斑块内巨噬细胞吞噬,并且斑块内超微型超顺磁性氧化铁的蓄积量足以产生磁共振所能检测到的磁敏感伪影。磁敏感伪影大小的测量可为评价动脉粥样硬化斑块的稳定性提供量化指标。

BACKGROUND： Macrophages invasiveness is considered as an important marker in atherosclerotic plaques instability, along with the development and application of ultrasmall superparamagnetic iron oxides （USPIOs）, its function of targeting macrophages made the imaging of atherosclerosis possible. OBJECTIVE： To investigate whether USPIOs can be phagocytosed by macrophages in rabbit abdominal aortic atherosclerotic plaques induced by high-cholesterol diet, if phagocytosed, and whether magnetic susceptibility artifacts generated by USPIOs particles in atherosclerotic plaques can be detectable and quantifiable by MRI. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed from March 2006 to March 2007 in Image Center of The First Affiliated Hospital of Soochow University. MATERALS： Twenty rabbit models were randomly divided into experiment group （n=15） and normal group （n=5）. Experiment group was adopted to make the model of rabbit＇s abdominal aortic atheroma by means of balloon injury and man-made high-cholesterol diet. Four months later, 15 rabbit models were assigned into USPIOs enhanced scanning group （n=10） and model control group （n=5）. In addition, 5 normal rabbits were fed with a normal way. METHODS： MR scanning was performed before injection into each group. Superparamagnetic iron oxide SHU 555 C （200 mol/kg） was injected into rabbits of experiment group, while physiological saline into rabbits of model control group. Immediately after injection and at 1, 3, 5 days after injection, 4 times of MRI scanning were performed at each timing respectively in USPIOs enhanced scanning group; at 5 days after model control group was injected with physiological saline, MR scanning was administrated; at 5 days after normal group was injected with same dose of SHU 555, MR scanning was administrated. Three-dimensional time of flight gradient recall echo magnetic resonance angiography sequence was applied for MRI scanning. Scanning range included abdominal aorta celiac trunk crotch and iliac artery crotch. MAIN OUTCOME MEASURES： The signal-to-noise ratio （SNR） of aortic walls was measured at different time points. The numerical value and reduction percentage in transversal area were compared before and after injection. Aortic specimens were stained with hematoxylin-eosin and Prussian blue for histological observations. RESULTS： In USPIOs enhanced scanning group, the wails began to exhibit visible irregularity after the administration of SHU 555 C. These manifestations appeared as wall＇s signal voids and local luminal stenosis, which became more pronounced on 5 days after injection. Although there was no significant difference in wall＇s SNR values between precontrast and 5 days postcontrast image sets obtained in model control group and normal group （P 〉 0.05）, a vast difference was evident in USPIOs enhanced scanning group （P 〈 0.05）. The numerical value and reduction percentage in transversal area had a statistical significance among 3 groups （P 〈 0.05）. Both the numerical value and reduction percentage in transversal area were significantly higher in USPIOs enhanced scanning group compared with model control group and normal group （P 〈 0.01 ）. No significant difference was found between the two later groups （P 〉 0.05）. On histopathological sections with Prussian blue staining of aorta, we observed thickening of intima with marked staining of Fe particles （blue spots and patches） embedded in atherosclerotic plaque. CONCLUSION： USPIOs are phagocytosed by macrophages in rabbit abdominal aortic atherosclerosis induced by high-cholesterol diet in a quantity sufficient to cause magnetic susceptibility artifacts detectable by MRI. The numerical value and reduction percentage in transversal area can be used to quantify unstable atherosclerotic plaques, as well as a surrogate of magnetic susceptibility artifact size.