MRI-guided targeted blood-brain barrier disruption with focused ultrasound: Histological findings in rabbits
MRI-guided targeted blood-brain barrier disruption with focused ultrasound: Histological findings in rabbits
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DOI：
10.1016/j.ultrasmedbio.2005.07.010
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发表时间：
2005-11-01
影响因子：
2.9
通讯作者：
Hynynen, K
中科院分区：
文献类型：
--
作者：
McDannold, N;Vykhodtseva, N;Hynynen, K
聚焦超声提供了一种在目标部位无创、可逆地破坏血脑屏障（BBB）的方法。本研究的目的是通过寻找脉冲超声在预先形成的气泡存在下引起的血脑屏障破坏区域的缺血和凋亡，以及寻找超声后长达一个月的延迟效应，来测试该方法的安全性。在磁共振成像（MRI）监测下，对24只家兔的大脑进行脉冲超声暴露（超声：频率= 1.63 MHz，爆发长度= 100 ms, PRF = 1 Hz，持续时间= 20 s，压力幅值0.7 ~ 1.0 MPa）。超声检查前，静脉注射超声造影剂（option (R), GE Healthcare, Milwaukee， WI， USA）。对比增强MR图像证实血脑屏障破坏。全脑组织检查，一般组织采用苏木精和伊红染色，缺血神经元采用钒酸品红-甲苯胺蓝染色，细胞凋亡采用TUNEL染色。观察到的主要影响是在超声位置周围散布的少量外渗红细胞，表明毛细血管受到影响。尽管有这些血管作用，但在某些超声区只有少数细胞表现出凋亡或缺血的迹象。没有检测到缺血或凋亡区域，这将表明一个受损的血液供应是由超声诱导。超声检查后4周，MRI或组织学均未观察到延迟效应。超声诱导的血脑屏障破坏是可能的，而不会引起实质性的血管损伤，从而导致神经元缺血或凋亡死亡。这些发现表明，至少与目前可用的侵入性方法相比，这种方法对于靶向药物递送是安全的。(C) 2005年世界超声医学与生物学联合会。
Focused ultrasound offers a method to disrupt the blood-brain barrier (BBB) noninvasively and reversibly at targeted locations. The purpose of this study was to test the safety of this method by searching for ischemia and apoptosis in areas with BBB disruption induced by pulsed ultrasound in the presence of preformed gas bubbles and by looking for delayed effects up to one month after sonication. Pulsed ultrasound exposures (sonications) were performed in the brains of 24 rabbits under monitoring by magnetic resonance imaging (MRI) (ultrasound: frequency = 1.63 MHz, burst length = 100 ms, PRF = 1 Hz, duration = 20 s, pressure amplitude 0.7 to 1.0 MPa). Before sonication, an ultrasound contrast agent (Optison(R), GE Healthcare, Milwaukee, WI, USA) was injected IV. BBB disruption was confirmed with contrast-enhanced MR images. Whole brain histologic examination was performed using haematoxylin and eosin staining for general histology, vanadium acid fuchsin-toluidine blue staining for ischemic neurons and TUNEL staining for apoptosis. The main effects observed were tiny regions of extravasated red blood cells scattered around the sonicated locations, indicating affected capillaries. Despite these vasculature effects, only a few cells in some of the sonicated areas showed evidence for apoptosis or ischemia. No ischemic or apoptotic regions were detected that would indicate a compromised blood supply was induced by the sonications. No delayed effects were observed either by MRI or histology up to 4 wk after sonication. Ultrasound-induced BBB disruption is possible without inducing substantial vascular damage that would result in ischemic or apoptotic death to neurons. These findings indicate that this method is safe for targeted drug delivery, at least when compared with the currently available invasive methods. (C) 2005 World Federation for Ultrasound in Medicine & Biology.