Wang Shutao, Karakatsani Maria E, Fung Christine, Sun Tao, Acosta Camilo, Konofagou Elisa
1 Department of Biomedical Engineering, Columbia University, New York, NY, USA.
2 Department of Radiology, Columbia University, New York, NY, USA.
J Cereb Blood Flow Metab. 2017 Feb;37(2):706-714. doi: 10.1177/0271678X16637881. Epub 2016 Jul 20.
The delivery of most therapeutic agents is rendered ineffective for the treatment of brain diseases due to the presence of the blood-brain barrier (BBB). The goal of this study was to investigate the effect of pre-infusion focused ultrasound (FUS) and microbubbles on the distribution of direct brain infusion in vivo. A single-element FUS transducer was used in all sonications, which were carried out immediately prior to direct infusion procedures. Mice received direct infusion of either Gadolinium-labeled albumin (Gd-albumin, 74 kDa) or adeno-associated virus (AAV, ∼4 MDa). The volumes of Gd-albumin at 30 min were deemed comparable ( P = 0.334) between the direct infusion (DI)-only group and the FUS + DI group. At 120 min, the FUS + DI group showed significantly higher contrast-enhanced volume (9.76 ± 0.74 mm) than the DI-only group (7.14 ± 0.34 mm). For mice infused with AAV, the total volume of transduction was estimated as GFP-positive regions and FUS + DI group demonstrated significantly higher ( P = 0.017) transduction efficiency in vivo. In conclusion, enhanced bio-distribution of directly infused agents was observed when the targeted region was pre-conditioned with FUS and microbubbles. Focused ultrasound has the potential, as an adjuvant technique, to significantly enhance direct brain infusion and achieve the desired therapeutic outcomes.
由于血脑屏障（BBB）的存在，大多数治疗药物的递送在治疗脑部疾病时变得无效。本研究的目的是研究预输注聚焦超声（FUS）和微泡对体内直接脑内输注分布的影响。在所有超声处理中均使用了单元素FUS换能器，这些处理在直接输注程序之前立即进行。小鼠接受了钆标记白蛋白（Gd-白蛋白，74 kDa）或腺相关病毒（AAV，约4 MDa）的直接输注。仅直接输注（DI）组和FUS+DI组在30分钟时Gd-白蛋白的体积被认为具有可比性（P = 0.334）。在120分钟时，FUS+DI组的对比增强体积（9.76±0.74 mm）明显高于仅DI组（7.14±0.34 mm）。对于输注AAV的小鼠，转导的总体积通过绿色荧光蛋白（GFP）阳性区域进行估计，FUS+DI组在体内表现出明显更高（P = 0.017）的转导效率。总之，当用FUS和微泡对靶向区域进行预处理时，观察到直接输注药物的生物分布得到增强。聚焦超声作为一种辅助技术，有潜力显著增强直接脑内输注并实现预期的治疗效果。
