Local and reversible blood-brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications
Local and reversible blood-brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications
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DOI：
10.1016/j.neuroimage.2004.06.046
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发表时间：
2005-01-01
期刊：
影响因子：
5.7
通讯作者：
Vykhodtseva, N
中科院分区：
文献类型：
--
作者：
Hynynen, K;McDannold, N;Vykhodtseva, N
这项研究的目的是检验以下假设，即在存在超声对比剂的情况下爆发超声波会破坏血脑屏障（BBB）的声学参数，适合通过头骨完全无创的暴露。 10毫秒的暴露量是在22只兔子的大脑中，频率为690 kHz，重复频率为1 Hz，峰值稀有压力振幅幅度高达3.1 MPa。总暴露时间（超声）时间为20 s。在每次超声处理之前，对超声造影剂的推注注入静脉注射。超声波后获得对比增强的MR图像，以通过大脑的局部增强来检测局部BBB破坏。用H＆E，TUNEL和钒酸富氏蛋白酶（VAF） - 甲苯胺蓝色染色对脑部切片进行染色。此外，在超声处理之前，将辣根过氧化物酶（HRP）注入四只兔子，并进行了透射电子显微镜。 MRI对比度增强表明，在0.4 MPa的压力振幅下，BBB破坏约为50％。在0.8 MPa，90％；在1.4 MPa时，100％的超声位置显示出增强。 4小时生存后的组织学发现表明，在2.3 MPa或更高的压力振幅水平下，大约70-80％的超声波位置诱导了脑组织坏死。然而，在较低的压力振幅下，可以看到少量的红细胞渗出区域。电子显微镜的发现证明了通过跨内皮和硬膜内皮路线通过容器壁的HRP通过。这些结果表明，BBB的完全无创局灶性破坏是可能的。 （c）2004 Elsevier Inc.保留所有权利。
The purpose of this study was to test the hypothesis that burst ultrasound in the presence of an ultrasound contrast agent can disrupt the blood-brain barrier (BBB) with acoustic parameters suitable for completely noninvasive exposure through the skull. The 10-ms exposures were targeted in the brains of 22 rabbits with a frequency of 690 kHz, a repetition frequency of 1 Hz, and peak rarefactional pressure amplitudes up to 3.1 MPa. The total exposure (sonication) time was 20 s. Prior to each sonication, a bolus of ultrasound contrast agent was injected intravenously. Contrast-enhanced MR images were obtained after the sonications to detect localized BBB disruption via local enhancement in the brain. Brain sections were stained with H&E, TUNEL, and vanadium acid fuchsin (VAF)-toluidine blue staining. In addition, horseradish peroxidase (HRP) was injected into four rabbits prior to sonications and transmission electron microscopy was performed. The MRI contrast enhancement demonstrated BBB disruption at pressure amplitudes starting at 0.4 MPa with approximately 50%; at 0.8 MPa, 90%; and at 1.4 MPa, 100% of the sonicated locations showed enhancement. The histology findings following 4 h survival indicated that brain tissue necrosis was induced in approximately 70-80% of the sonicated locations at a pressure amplitude level of 2.3 MPa or higher. At lower pressure amplitudes, however, small areas of erythrocyte extravasation were seen. The electron microscopy findings demonstrated HRP passage through vessel walls via both transendothelial and paraendothelial routes. These results demonstrate that completely noninvasive focal disruption of the BBB is possible. (C) 2004 Elsevier Inc. All rights reserved.