【作者】 朱默；

【导师】 郭亮； 李勇刚；

【作者基本信息】 苏州大学 ， 影像医学与核医学， 2009， 硕士

【摘要】 背景:动脉粥样硬化(Atherosclerosis, AS)是一种慢性血管炎性疾病,它已成为人类发病率和致死率最高的疾病之一[1]。在影像学领域,MRI凭借其多序列、多参数成像等特点成为对AS斑块检测最有希望的技术。如今,纳米科学的快速发展和纳米技术在生命科学领域的应用,已经正在慢慢改变疾病诊断和治疗的基础[2]。结合纳米科技的靶向MRI技术令人兴奋,它可以探测在斑块内发现的特殊物质,如巨噬细胞,金属基质蛋白酶,氧化低密度脂蛋白,细胞外基质等。USPIO是一种新型纳米级MRI造影剂,它可以被粥样斑块内的巨噬细胞吞噬,使斑块内局部的信号强度下降。本实验利用MR黑血成像序列结合USPIO增强在兔腹主动脉粥样硬化模型上研究MRI对斑块成份的识别能力。目的:1.利用现有条件选出对兔腹主动脉显示最佳的成像线圈;2.建立兔腹主动脉粥样硬化斑块模型;3.利用MR黑血成像序列结合USPIO增强检测兔动脉粥样硬化斑块。方法:健康雄性新西兰大白兔30只,随机分为实验组(A组)20只,对照组(B组)5只和线圈选择组(C组)5只。A组以球囊导管拉伤腹主动脉内膜加高脂饮食的方法建立兔AS模型。B组不做内膜拉伤,给予普通饲料喂养,两组水均自由饮用。实验前期利用C组兔通过不同的线圈成像,确定最优的成像线圈和黑血成像序列的参数。A组和B组与高脂喂养14周后进行MRI检查,包括MRI平扫和USPIO增强MRI扫描。扫描序列包括:TFE T1WI;FSE T2WI,PDWI;FFE T2*WI 3D TOF,增强前后参数相同。增强后每隔24小时连续扫描5天,在FSE T2WI图像上监测血管壁SNR变化情况。兔以空气栓塞法处死,将腹主动脉分离取出,用生理盐水冲洗,10%福尔马林液固定,标本病理学检查包括HE染色和普鲁士兰铁染色。最后将MRI图像与病理进行对照研究,分析血管壁形态,斑块成份和形态以及USPIO在斑块内聚集情况。结果:膝关节正交线圈所获得的图像质量最佳,其余依次为心脏线圈、头线圈及关节包裹线圈。兔模型成功12例,腹主动脉的表面均可见明显的斑块形成,组织切片证实所形成的斑块与人类斑块的成份有很高的相似性,其中亦可见斑块的纤维帽,脂质核心和钙化。部分切片普鲁士兰染色可见铁颗粒聚集。T2WI图像上管壁SNR监测显示,注射USPIO前和以后的连续5天SNR的变化趋势是起始逐渐下降,在第4天达到最低点然后开始回升,证明巨噬细胞对铁颗粒的吞噬峰值在96小时左右。本实验采用的MR黑血与亮血序列对斑块的检出率没有显著差异。模型组兔MRI图像所能发现的异常改变有管腔环形狭窄,呈扁平状或新月状向管腔内突起的斑块。对明显突出于管腔的斑块能基本区分脂质成份和纤维组织,其中脂质成份在T1WI、PDWI、T2*WI是稍高信号,T1WI脂肪抑制不能把脂质的稍高信号完全抑制。在注射USPIO 96小时后T2*WI可见脂质稍高信号降低,病理证实有改变的信号区有铁颗粒聚集。斑块内的纤维帽成份在PDWI显示较清晰。USPIO增强后各序列对纤维帽的分辨能力没有明显增加。结论:1.球囊导管内膜损伤加高脂饮食可以建立可靠的兔腹主动脉粥样硬化模型。2.USPIO颗粒可以被兔AS模型斑块中的巨噬细胞特异性吞噬并引起MRI信号的改变。3.MR黑血成像序列结合USPIO增强能反映兔腹主动脉粥样硬化斑块成份,可用于对AS病变诊断及斑块的评估。更多还原

【Abstract】 Background: Atherosclerosis, a chronic inflammatory vascular disease, is a leading cause of mortality and morbidity worldwide. With multiple sequences and parameters, MRI is emerging as the most useful tool to assess atherosclerosis in imaging area. Now, the rapid progress of nanoscience and the application of nanotechnology are changing the foundations of diagnosis and treatment of this disease. Combined with nanotechnology, targeted MRI is an exiting technique ,which can permit the detection of specific substances commonly found in vulnerable plaques , for example ,macrophages, MMPs, oxidized LDL, extracellular matrix et al. USPIO is a new nano’s MRI contrast agent, which can be phagocytosed by intraplaque macrophages. The accumulation of these iron oxides in macrophages makes focal signal intensity decrease in atherosclerotic plaques. In this experiment, we use MR black-blood pulse sequences with USPIO enhancement to assess atherosclerosis on rabbits’ model.Objective:1.To select best coil for assessing rabbits’ abdominal aorta from our present.2.To establish atherosclerotic rabbit models within abdominal aorta.3.To detect unstable atherosclerotic plaque of atherosclerotic rabbit models by MR black-blood pulse sequences with contrast agent USPIO.Methods: Thirty New Zealand male rabbits were divided randomly into three groups: Practice group (A group, twenty), control group (B group, five) and coil group(C group, five). Atherosclerosis was induced in A group with aortic balloon endothelial injury followed by a high cholesterol diet for fourteen weeks; Control group rabbits were fed basic food without aortic balloon endothelial injury, water free. C group rabbits was used to select best coil for assessing rabbits’ abdominal aorta. After fourteen weeks, the rabbits were examined by MRI and USPIO enhanced MRI for five days on 1.5 T MR scanner (Philips Eclipse). Sequences included T1-weighted turbo field echo, T2-weighted PD-weighted fast spin-echo and T2*-weighted 3D TOF fast field echo. To detect the change of the SNR on vessel wall, we draw the curve chart follow the change of SNR for five days and find the optimal time of reinforcement. After examination, rabbits were killed and abdominal aortas were separated for pathological study, including HE stain and Prussian blue stain. The MR images of atherosclerotic vessel walls were analyzed and compared with corresponding histology.Results: We concluded that knee joint coil is the best one for assessing rabbits’ abdominal aorta. Many plaques can be seen in abdominal aortas of practice group rabbits with fibrous tissue, lipid and necrotic core, calcium, so there is a good similarity between rabbit and human. The different components of the atherosclerotic lesions were demonstrated different MR signals, the lipid rich core appears light on T1WI,PDWI and T2*WI,but dark on T2WI and USPIO enhanced T2*WI image.Conclusion:1.Atherosclerotic plaque model can be successfully established by balloon endothelial injury followed by a high cholesterol diet in rabbit abdominal aorta.2.USPIO can be phagocytosed by macrophages within rabbit’s abdominal aortic plaques and lead to MR signal intensity change.3.USPIO enhanced MR black-blood pulse sequences have a definite value for assessing rabbit’s plaques within abdominal aortic.更多还原