超声Flash技术联合声诺维定向开放小鼠血脑屏障的实验研究  

Study of Flash technique of low-frequency focused ultrasound associated with SonoVue opening the blood brain barrier in mice

作　　者：蒋文军[1] 杨亚利[1] 谢明星[1] 张文竞[1] 吴文谦[1] 王新房[1] 贺林[1] 张静[1] 刘文超[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院超声科湖北省分子影像重点实验室,武汉430022

出　　处：《中华超声影像学杂志》2013年第10期888-892,共5页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金（81000615）

摘　　要：目的 评价超声Flash技术联合声诺维（SonoVue）定向开放小鼠血脑屏障的可行性及安全性.方法 48只小鼠随机分为4组：空白组、微泡组、辐照组、超声辐照＋微泡组,采用超声探头在Flash程序下联合静脉注射声诺维经颅骨定向辐照小鼠一侧基底节区,并利用伊文斯蓝示踪,荧光显微镜下观察脑组织中的伊文斯蓝荧光,定量分析脑组织伊文斯蓝浓度,并通过光镜和电镜观察脑组织大体细胞形态及超微结构改变.结果 空白组、微泡组及辐照组肉眼均未见蓝染,荧光显微镜下未见明显红色荧光.超声辐照＋微泡组基底节辐照区肉眼可见蓝染,镜下见大量红色荧光,脑组织内伊文斯蓝浓度明显高于其他组（P＜0.01）.4组小鼠光镜及电镜观察均未见明显神经元损害及红细胞渗出,超声辐照＋微泡组可见血管周围水肿及内皮细胞内吞饮小泡.结论 超声Flash技术定向辐照联合静脉注射声诺维可无创、安全开放小鼠血脑屏障.Objective To explore the safety and effectiveness of Flash technique of ultrasound associated with SonoVue to open the blood brain barrier（BBB） in mice.Methods Forty-eight mice were randomly divided into four groups：control group,microbubbles group,Flash group、Flash and microbubbles group.The right basal ganglia of the mice was sonicated by the flash procedures of ultrasound,through intact skull,after continuous intravenous injection of SonoVue and Evans blue （EB）.The degree of BBB opening was evaluated quantitatively based on the extravasation of EB and qualitatively under the fluorescence microscope.The safety was inspected by observation of cell morphology under light microscopy and electron microscopy.Results Only in the Flash and microbubbles group,EB extravasation in the sonicated region and significantly red EB fluorescence under fluorescence microscope were shown,which couldn＇t be seen in other three groups.The EB concentration in the sonicated side in this group was also much higher than other groups （P ＜0.01）.In all groups,there were no obvious neuronal damage and erythrocyte extravasation showed by HE staining and electron microscopy.Perivascular edema and vesicle within the cytoplasm of endothelial cells can be seen in the Flash and microbubbles group.Conclusions The BBB can be opened targetedly,safely and noninvasively by Flash procedure of ultrasound with the microbubbles in the mice.

关 键 词：超声检查 微气泡 血脑屏障 

分 类 号：R445.1[医药卫生—影像医学与核医学]