【作者】 陈梅；

【导师】 张艳；

【作者基本信息】 暨南大学 ， 影像医学与核医学（专业学位）， 2022， 硕士

【摘要】 目的:探究自制超顺磁氧化铁纳米粒子(SPION)的物理性质及不同配比超顺磁碘化油(SPLIP)在体外的稳定性及其在DSA和磁共振(MRI)上的显影性。材料与方法:采用高温裂解法制备SPION,通过透射电子显微镜(TEM)、动态光散射粒度分析仪(DLS)、振动样品磁强计(VSM)对SPION的形貌及磁性能进行表征。将SPION与碘化油结合,合成不同配比的超顺磁性碘化油(SPION:碘化油=1:2,SPION:碘化油=1:1,SPION:碘化油=2:1),在第1天、第7天、第14天及第28天将其与碘化油对比,观察有无颜色及气味变化、分层及沉淀;同时在第1天及第28天进行DSA及磁共振扫描,观察第1天及第28天的DSA显影及磁共振T2信号变化情况,从而探究SPLIP的稳定性。结果:SPION电镜下为类球形,颗粒分布均匀,粒径为241.3nm,Zeta电位为-30.6m V,具有良好的超顺磁性,其饱和磁化强度为22.47emu/g。不同配比的SPLIP在观察期间颜色及气味无变化,亦未出现分层及沉淀,肉眼观察,DSA透视密度未出现改变,MRI扫描信号无明显改变。结论:成功制备出SPION并合成不同配比的SPLIP,SPLIP一般性状稳定,体外磁共振成像显像性良好。目的:对自制超顺磁性氧化铁纳米粒子(SPION)及超顺磁性碘化油(SPLIP)的体外生物安全性进行初步探究。材料和方法:对小鼠肝实质细胞(AML12)及小鼠上皮样成纤维细胞(L929)进行培养,用四甲基偶氮唑蓝(MTT)法对所合成的超顺磁性氧化铁纳米粒子(SPION)及超顺磁性碘化油(SPILP)进行体外细胞毒性验证。结果:自制的超顺磁性氧化铁纳米粒子(SPION)及超顺磁性碘化油(SPILP)对小鼠AML12细胞和L929细胞活性基本无影响,AML12细胞在低浓度超顺磁性氧化铁纳米粒子(SPION1)、高浓度超顺磁性氧化铁纳米粒子(SPION2)、低浓度超顺磁性碘化油(SPION-Mix1)、高浓度超顺磁性碘化油(SPION-Mix2)组的细胞的存活率分别为(97.86±2.48)%、(95.46±5.51)%、(97.14±2.90)%、(97.04±2.65)%。L929细胞在低浓度超顺磁性氧化铁纳米粒子(SPION1)、高浓度超顺磁性氧化铁纳米粒子(SPION2)、低浓度超顺磁性碘化油(SPION-Mix1)、高浓度超顺磁性碘化油(SPION-Mix2)组的细胞的存活率分别为(99.56±1.53)%、(100.72±4.83)%、(89.93±8.29)%、(95.07±4.35)%。结论:自制的超顺磁性氧化铁纳米粒子(SPION)及超顺磁性碘化油(SPILP)具有良好的体外生物安全性。目的:研究使用不同配比的超顺磁性碘化油(SPLIP)在新西兰兔行肝动脉栓塞术的体内安全性并探究术后不同配比的SPLIP在磁共振中的显像性。材料与方法:选取新西兰雄兔12只,均重3.3kg,随机均分到A(普通碘化油)、B(SPION:碘化油=1:2组SPLIP)、C(SPION:碘化油=1:1组SPLIP)、D(SPION:碘化油=2:1组SPLIP)四个组,均经右股动脉插管后将微导管置于肝左或肝右动脉行肝动脉栓塞,每只实验兔均注入0.6ml栓塞材料。完成后立即行磁共振扫描,对比各组间磁共振扫描的显像差异。术前1天及术后7天均抽血检验实验兔肝肾功能,比较术前术后肝肾功能变化,术后观察心肝脾肺肾病理标本。结果:各组实验兔术后行肝脏MR扫描,均未见显著异常信号改变,通过Leonardo后处理对T2信号值进行测定后对比,A组与D组之间差异有统计学意义(t=7.416,P=0.000)。术后7天各组肝肾生化指标均为正常范围,术后肝脏部分呈现不规则形凝固样坏死,其余未见明显异常。结论:不同配比的SPLIP在动物体内具有较好的生物安全性,与普通碘化油有相似的栓塞作用;同时D(SPION:碘化油=2:1组SPLIP)组在术后行MRI扫描时T2信号值降低,结合本团队前期研究,推断其可补充普通碘化油在磁共振成像的显影不足,有利于指导临床实践。更多还原

【Abstract】 Objective:To investigate the physical properties of self-made superparamagnetic iron oxide nanoparticles(SPION)and the stability of superparamagnetic lipiodol(SPLIP)in vitro and its development on DSA and magnetic resonance.Materials and methods: Superparamagnetic iron oxide nanoparticles were prepared pyrolysis.The morphology and magnetic properties of nanoparticles were characterized by transmission electron microscope(TEM),dynamic light scattering particle size analyzer(DLS)and vibrating sample magnetometer(VSM).Superparamagnetic lipiodol(SPION: lipiodol = 1:2,SPION: lipiodol = 1:1,SPION:lipiodol = 2:1)was synthesized by combining superparamagnetic iron oxide nanoparticles with lipiodol.Compare it with lipiodol on the 1st,7th,14 th and 28 th days to observe whether there are color and odor changes,stratification and precipitation.At the same time,DSA and MRI were performed on day 1 and day 28.The changes of DSA development and T2 signal of magnetic resonance on day 1 and day 28 were observed to explore the stability of SPLIP.Results: Superparamagnetic iron oxide was spherical under electron microscope,with uniform particle distribution,particle size of 241.3 nm and zeta potential of-30.6 MV.It has good superparamagnetism and its saturation magnetization is 22.47 EMU / g.During the observation,the color and smell of superparamagnetic iodized oil in different proportions did not change,nor did stratification and precipitation occur.Through visual observation,the DSA fluoroscopy density did not change,and the MRI scanning signal did not change significantly.Conclusion: Superparamagnetic nanoparticles were successfully prepared and different proportions of superparamagnetic lipiodol were synthesized.The general properties of superparamagnetic lipiodol are stable and its in vitro magnetic resonance imaging has good imaging performance.Objective: Making a preliminary exploration about the biosafety of self-made superparamagnetic iron oxide nanoparticles(SPION)and superparamagnetic lipiodol(SPLIP).Materials and methods: Mouse liver parenchymal cells(AML12)and mouse epithelioid fibroblasts(L929)were cultured,and the cytotoxicity of the synthesized superparamagnetic iron oxide and superparamagnetic lipiodol in vitro was verified by MTT method.Results: The self-made superparamagnetic iron oxide and superparamagnetic lipiodol had no effect on the activity of AML12 cells and L929 cells.The survival rates of AML12 cells in low concentration SPION(SPION1),high concentration SPION(SPION2),low concentration SPLIP(SPION-Mix1)and high concentration SPLIP(SPION-Mix2)groups were(97.86 ± 2.48)%,(95.46 ± 5.51)%,(97.14 ±2.90)%,(97.04 ± 2.65)%,respectively.The survival rates of L929 cells in low concentration SPION(SPION1),high concentration SPION(SPION2),low concentration SPLIP(SPION-Mix1)and high concentration SPLIP(SPION-Mix2)groups were(99.56 ± 1.53)%,(100.72 ± 4.83)%,(89.93 ± 8.29)%,(95.07 ± 4.35)%,respectively.Conclusion: The self-made superparamagnetic iron oxide and superparamagnetic lipiodol have good biosafety in vitro.Objective: To study the in vivo safety of different proportions of superparamagnetic lipiodol in hepatic artery embolization in New Zealand rabbits,and to explore the imaging of different proportions of superparamagnetic lipiodol in magnetic resonance imaging after operation.Materials and methods:12 New Zealand male rabbits with an average weight of3.3kg,were randomly divided into four groups: group A(ordinary lipiodol),group B(SPION: lipiodol = 1:2),group C(SPION: lipiodol = 1:1),group D(SPION: lipiodol= 2:1).After intubation through the right femoral artery,the microcatheter was placed in the left or right hepatic artery for hepatic artery embolization.Each experimental rabbit was injected with 0.6ml embolization material.MRI scanning was performed immediately after the operation,and the imaging differences of MRI scanning among the groups were compared.The liver and kidney functions(AST、ALT、UREA、CREA)of experimental rabbits were tested by blood sampling 1 day before operation and 7 days after operation,and the changes of liver and kidney functions before and after operation were compared.The pathological specimens of heart,liver,spleen,lung and kidney were observed after operation.Results: No significant abnormal signal changes were found in the liver MR scanning of experimental rabbits in each group.After measuring the T2 signal value through Leonardo post-processing,there was significant difference between group A and group D(t = 7.416,P = 0.000).The biochemical indexes of liver and kidney in each group were within the normal range 7 days after operation.The liver showed irregular coagulation necrosis after operation,and no obvious abnormalities were found in the rest.Conclusion: Different proportion of SPLIP has good biological safety in animals,and they have similar embolic effect with ordinary lipiodol.At the same time,T2 signal value of group D(SPION: lipiodol = 2:1)decreased during MRI scanning after operation.Combined with the previous research of our team,it is inferred that it can supplement the insufficient development of ordinary lipiodol in magnetic resonance imaging,which is conducive to guiding clinical practice.更多还原