Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index
Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index
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DOI：
10.1016/j.ultrasmedbio.2007.10.016
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发表时间：
2008-05-01
影响因子：
2.9
通讯作者：
Hynynen, Kullervo
中科院分区：
文献类型：
--
作者：
McDannold, Nathan;Vykhodtseva, Natalia;Hynynen, Kullervo
本文研究了超声频率对超声脉冲与超声造影剂联合作用引起血脑屏障（BBB）破坏阈值的影响。实验中使用脉冲超声在2.04 MHz的峰值压力振幅范围从0.3到2.3 MPa的兔。使用对比增强磁共振成像评价BBB破坏。使用概率单位回归估计BBB破坏的阈值。在光学显微镜下检查具有相似对比度增强量的代表性样品。这些实验的结果与先前使用0.26至1.63 MHz超声频率的研究数据进行了比较。我们发现，以峰值负压幅度表示的BBB破坏阈值（破坏概率估计为50%的值）随频率增加而增加。然而，当暴露量表示为机械指数（现场估计的峰值负压振幅除以频率的平方根）的函数时，它似乎是恒定的。所有频率数据的回归导致机械指数阈值估计值为0.46（95%置信区间：0.42 - 0.50）。对血脑屏障破坏量相似的代表性样本进行组织学检查发现，对于较低的超声频率，每单位面积含有外渗红细胞的区域数量平均显著较低。该数据表明，机械指数是超声诱导的血脑屏障破坏的有意义的度量，至少对于机械指数未考虑的其他参数不变化时是如此。它还表明，较低频率的超声处理产生较少的红细胞外渗每单位面积。
This work investigated the effect of ultrasonic frequency on the threshold for blood-brain barrier (BBB) disruption induced by ultrasound pulses combined with an ultrasound contrast agent. Experiments were performed in rabbits using pulsed sonications at 2.04 MHz with peak pressure amplitudes ranging from 0.3 to 2.3 MPa. BBB disruption was evaluated using contrast-enhanced magnetic resonance imaging. The threshold for BBB disruption was estimated using probit regression. Representative samples with similar amounts of contrast enhancement were examined in light microscopy. Results from these experiments were compared with data from previous studies that used ultrasound frequencies between 0.26 and 1.63 MHz. We found that the BBB disruption threshold (value where the probability for disruption was estimated to be 50%) expressed in terms of the peak negative pressure amplitude increased as a function of the frequency. It appeared to be constant, however, when the exposures were expressed as a function of the mechanical index (peak negative pressure amplitude estimated in situ divided by square root of frequency). Regression of data from all frequencies resulted in an estimated mechanical index threshold of 0.46 (95% confidence intervals: 0.42 to 0.50). Histologic examination of representative samples with similar amounts of blood-brain barrier disruption found that the number of regions containing extravasated red blood cells per unit area was substantially lower on average for lower ultrasound frequencies. This data suggests that the mechanical index is a meaningful metric for ultrasound-induced blood-brain barrier disruption, at least for when other parameters that are not taken into account by the mechanical index are not varied. It also suggests that lower frequency sonication produces less red blood cell extravasation per unit area.