The threshold for brain damage in rabbits induced by bursts of ultrasound in the presence of an ultrasound contrast agent (Optison®)

The threshold for brain damage in rabbits induced by bursts of ultrasound in the presence of an ultrasound contrast agent (Optison®)
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DOI:
10.1016/s0301-5629(02)00741-x
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发表时间:
2003-01-01
影响因子:
2.9
通讯作者:
Vykhodtseva, N
Vykhodtseva, N
中科院分区:
医学3区
文献类型:
--
作者:
Hynynen, K;McDannold, N;Vykhodtseva, N

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本研究的目的是检验在存在超声造影剂的情况下使用与脑血流量测量中使用的参数相似的参数进行爆破超声(US)会导致组织损伤的假设。10只家兔的大脑中的3-8个位置超声与1.5 MHz,10 μ s的脉冲重复频率为1 kHz,在时间峰值声压振幅范围为2至12.7 MPa。每个位置的总超声处理时间为20 s。在每次超声处理之前,静脉注射一团US造影剂。超声处理后获得对比增强磁共振(MR)图像,以检测大脑中的局部增强。进行全脑组织学评价,并用苏木精和伊红(H和E)、TUNEL和钒酸品红(VAF)染色对切片进行染色,以评价组织效应,包括细胞凋亡和缺血。磁共振成像(MRI)对比增强和组织学结果表明,脑组织损伤诱导的压力振幅水平为6.3 MPa。损伤包括血管壁损伤、出血和最终坏死。在所有测试压力值(低至2 MPa)下,在约一半的超声处理位置中,观察到轻度血管损伤,局限于少数显微组织体积。然而,这些超声处理没有引起任何可检测的组织效应,包括缺血或细胞凋亡。总之,研究表明,目前用于脑血流测量的美国暴露水平低于血脑屏障开放或脑组织损伤的阈值。然而,人们应该意识到,如果暴露水平增加,可能会引起脑损伤。(C)2003年世界医学超声生物学联合会。
The purpose of this study was to test the hypothesis that burst ultrasound (US) in the presence of a US contrast agent using parameters similar to those used in brain blood flow measurements causes tissue damage. The brains of 10 rabbits were sonicated in 3-8 locations with 1.5-MHz, 10-mus bursts repeated at a frequency of 1 kHz at temporal peak acoustic pressure amplitudes ranging from 2 to 12.7 MPa. The total sonication time for each location was 20 s. Before each sonication, a bolus of US contrast agent was injected IV. Contrast-enhanced magnetic resonance (MR) images were obtained after the sonications to detect local enhancement in the brain. Whole brain histological evaluation was performed, and the sections were stained with hematoxylin and eosin (H and E), TUNEL, and vanadium acid fuchsin (VAF) staining to evaluate tissue effects, including apoptosis and ischemia. Both the magnetic resonance imaging (MRI) contrast enhancement and histology findings indicated that brain tissue damage was induced at a pressure amplitude level of 6.3 MPa. The damage included vascular wall damage, hemorrhage and, eventually, necrosis. Mild vascular damage was observed localized in a few microscopic tissue volumes in about half of the sonicated locations at all pressure values tested (down to 2 MPa). However, these sonications; did not induce any detectable tissue effects, including ischemia or apoptosis. As a conclusion, the study showed that the US exposure levels currently used for blood flow measurements in brain are below the threshold of blood-brain barrier opening or brain tissue damage. However, one should be aware that brain damage can be induced if the exposure level is increased. (C) 2003 World Federation for Ultrasound in Medicine Biology.