诊断超声联合微泡靶向开放单侧大鼠血脑屏障的初步研究

目的初步探讨诊断超声靶向击破微泡开放大鼠单侧血脑屏障通透性的可行性、有效性及安性。方法25只健康SD大鼠，诊断超声经颞骨照射单侧大脑半球，对侧大脑半球作对照。对伊文思蓝外渗范围进行分级和萃取定量。透射电镜观察硝酸镧分布评价血脑屏障超微结构变化，并对双侧脑实质的病理损伤进行评价和分级。结果照射侧大脑半球可见以海马为中心的片状均匀伊文思蓝渗出，而对侧脑实质未见渗出；透射电镜照射侧大脑半球硝酸镧渗出血管并分布于神经纤维间隙，而对照侧未见硝酸镧外漏；超微结构显示少量神经元轻度肿胀。病理组织学观察照射侧大脑半球可见少量红细胞外漏，未见明显组织细胞损伤。结论诊断超声靶向击破微泡能安全有效靶向开放单侧大鼠血脑屏障且呈海马为中心分布，这对于颅内以海马为中心分布疾病的靶向性药物治疗具有潜在的临床价值。

Unilateral opening of blood brain barrier of rat mediated by diagnostic ultrasound and microbubbles

Objective To explore the feasibility, efficacy and safety of unilateral opening of the blood brain barrier using diagnostic ultrasound system （DUS） and microbubbles in normal rats. Methods A trans-temporal bone irradiation at the unilateral hemisphere was performed under DUS combined with venous injection of lipid-coated microbubbles in 25 healthy SD rats. Contralateral hemisphere was used as the control. Pathological changes of brain parenchyma were observed. Evans blue （EB） in brain tissue was observed and quantified in two hemispheres. Lanthanum nitrate was traced in the brain parenchyma by transmission electron microscopy. Results The exudation of EB in brain parenchyma was significantly higher in the irradiated hemisphere than in the contralateral hemisphere. Transmission electron microscopy showed lanthanum nitrate tracer could be detected extravascularly on the sonication side but not on the control side. Ultrastructure showed a small amount of neurons were slightly swelling. A few erythrocytes were leaked without dramatic injuries in the irradiated hemisphere. Conclusion DUS combined with lipid microbubbles can effectively, non-invasively and unilaterally open blood brain barrier, and this technique might be a promising method to assist the targeted delivery of medication when treating hippocampus-centered diseases.