Noninvasive and localized blood-brain barrier disruption using focused ultrasound can be achieved at short pulse lengths and low pulse repetition frequencies
Noninvasive and localized blood-brain barrier disruption using focused ultrasound can be achieved at short pulse lengths and low pulse repetition frequencies
复制标题
DOI：
10.1038/jcbfm.2010.155
复制
发表时间：
2011-02-01
影响因子：
6.3
通讯作者：
Konofagou, Elisa E.
中科院分区：
文献类型：
--
作者：
Choi, James J.;Selert, Kirsten;Konofagou, Elisa E.
结合微泡的超声方法已被用于脑药物输送、中风治疗和脑血流成像。尽管在这些领域取得了进展，但关于破坏血脑屏障（BBB）的超声参数范围的问题仍然存在。在这项研究中，研究了几种情况来增强或减少血脑屏障破坏的可能性。脉冲聚焦超声（频率：1.5 MHz，压力：0.46 MPa，脉冲重复频率（PRF）： 0.1至25 Hz，脉冲长度（PL）： 0.03至30毫秒）是无创的，在循环预制微泡存在的左半球预定区域局部给予（Definity, Lantheus Medical Imaging， N. Billerica， MA， USA; 0.01, 0.05, 0.25 μ L/g）。在PRFs低至1hz时观察到3-kDa右旋糖酐的Trans-BBB递送，而在5hz及以上时观察到一致的递送。传输速度低至33微秒。虽然输送的葡聚糖浓度随着PL的增加而增加，但这也增加了结果分布的异质性。总之，在广泛的条件下确定了破坏血脑屏障的关键参数。研究还发现，通过缩短PL或降低PRF来减少发射声周期的总数，可以促进传递的葡聚糖在空间上的更均匀分布。脑血流与代谢杂志（2011）31,725-737；doi: 10.1038 / jcbfm.2010.155;2010年9月15日在线发布
Ultrasound methods in conjunction with microbubbles have been used for brain drug delivery, treatment of stroke, and imaging of cerebral blood flow. Despite advances in these areas, questions remain regarding the range of ultrasound parameters that disrupt the blood-brain barrier (BBB). In this study, several conditions were investigated to either enhance or reduce the likelihood of BBB disruption. Pulsed focused ultrasound (frequency: 1.5 MHz, pressure: 0.46 MPa, pulse repetition frequency (PRF): 0.1 to 25 Hz, pulse length (PL): 0.03 to 30 milliseconds) was noninvasively and locally administered to a predetermined region in the left hemisphere in the presence of circulating preformed microbubbles (Definity, Lantheus Medical Imaging, N. Billerica, MA, USA; 0.01, 0.05, 0.25 mu L/g). Trans-BBB delivery of 3-kDa dextran was observed at PRFs as low as 1 Hz, whereas consistent delivery was observed at 5 Hz and above. Delivery was demonstrated at a PL as low as 33 microseconds. Although the delivered dextran concentration increased with the PL, this also increased the heterogeneity of the resulting distribution. In conclusion, key parameters that disrupt the BBB were identified out of a wide range of conditions. Reducing the total number of emitted acoustic cycles by shortening the PL, or decreasing the PRF, was also found to facilitate a more spatially uniform distribution of delivered dextran. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 725-737; doi:10.1038/jcbfm.2010.155; published online 15 September 2010