Multiphoton imaging of ultrasound/Optison mediated cerebrovascular effects in vivo
Multiphoton imaging of ultrasound/Optison mediated cerebrovascular effects in vivo
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DOI：
10.1038/sj.jcbfm.9600336
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发表时间：
2007-02-01
影响因子：
6.3
通讯作者：
Bacskai, Brian J.
中科院分区：
文献类型：
--
作者：
Raymond, Scott B.;Skoch, Jesse;Bacskai, Brian J.
微泡造影剂增强的超声（US）可以短暂破坏血脑屏障（BBB），损伤最小，提供了一种非侵入性的技术，局部药物输送到大脑深处。由于以前使用的成像方式的限制，中断的机制和时间轮廓尚不清楚。在这项研究中，我们用多光子显微镜监测了超声诱导的血脑屏障破坏，提供了关于透化机制和超声暴露的即时效应的高分辨率时间和空间信息。用开颅术制备麻醉的C57小鼠，并静脉内注射荧光染料以允许脉管系统和BBB完整性的可视化。在暴露于低强度US（f = 1.029 MHz，功率= 0.2 W）的同时静脉注射Optison（一种微泡造影剂），通过颅窗对动物进行成像。我们观察到超声暴露时的小动脉血管收缩破坏血流并持续长达5分钟; BBB破坏通过两个特征性不同的过程发生-血管周围荧光沿受影响血管的长度逐渐增加（沿着分钟），而血管壁无明显破裂，或在选定的病灶区域迅速增加（秒）。这些数据证实了先前的研究，表明内皮细胞转胞吞作用增加，紧密连接破坏，并显示血管收缩，这可能通过改变脑血流量来改变BBB通透性。
Ultrasound (US) enhanced with microbubble contrast agents may transiently disrupt the blood-brain barrier (BBB) with minimal damage, providing a technique for noninvasive, localized drug-delivery deep within the brain. The mechanism and temporal profile of disruption are not understood, owing to the limitations of imaging modalities used previously. In this study, we monitored US- induced BBB disruption with multiphoton microscopy, providing high- resolution temporal and spatial information about the permeabilization mechanism and immediate effects of US exposure. Anesthetized C57 mice were prepared with a craniotomy and injected intravenously with fluorescent dyes to permit visualization of the vasculature and BBB integrity. The animals were imaged through a cranial window while exposed to low- intensity US (f = 1.029MHz, power = 0.2 W) with a coincident intravenous injection of Optison (a microbubble contrast agent). We observed arteriolar vasoconstriction on US exposure that disrupted blood flow and lasted up to 5 mins; BBB disruption occurred via two characteristically distinct processes-perivascular fluorescence gradually increased (over minutes) along the length of the affected vessel without apparent rupture of the vessel wall or rapidly (seconds) increased in select, focal regions. These data corroborated previous studies suggesting increased endothelial transcytosis and breached tight junctions and demonstrated vasoconstriction, which might alter BBB permeability by modifying cerebral blood flow.