Choi J J, Pernot M, Brown T R, Small S A, Konofagou E E
Department of Biomedical Engineering, Columbia University, New York, USA.
Phys Med Biol. 2007 Sep 21;52(18):5509-30. doi: 10.1088/0031-9155/52/18/004. Epub 2007 Aug 31.
The deposition of gadolinium through ultrasound-induced blood-brain barrier (BBB) openings in the murine hippocampus was investigated. First, wave propagation simulations through the intact mouse skull revealed minimal beam distortion while thermal deposition simulations, at the same sonication parameters used to induce BBB opening in vivo, revealed temperature increases lower than 0.5 degrees C. The simulation results were validated experimentally in ex vivo skulls (m = 6) and in vitro tissue specimens. Then, in vivo mice (n = 9) were injected with microbubbles (Optison; 25-50 microl) and sonicated (frequency: 1.525 MHz, pressure amplitudes: 0.5-1.1 MPa, burst duration: 20 ms, duty cycle: 20%, durations: 2-4 shots, 30 s per shot, 30 s interval) at the left hippocampus, through intact skin and skull. Sequential, high-resolution, T1-weighted MRI (9.4 Tesla, in-plane resolution: 75 microm, scan time: 45-180 min) with gadolinium (Omniscan; 0.5 ml) injected intraperitoneally revealed a threshold of the BBB opening at 0.67 MPa and BBB closing within 28 h from opening. The contrast-enhancement area and gadolinium deposition path were monitored over time and the influence of vessel density, size and location was determined. Sonicated arteries, or their immediate surroundings, depicted greater contrast enhancement than sonicated homogeneous brain tissue regions. In conclusion, gadolinium was delivered through a transiently opened BBB and contained to a specific brain region (i.e., the hippocampus) using a single-element focused ultrasound transducer. It was also found that the amount of gadolinium deposited in the hippocampal region increased with the acoustic pressure and that the spatial distribution of the BBB opening was determined not only by the ultrasound beam, but also by the vasculature of the targeted brain region.
研究了通过超声诱导血脑屏障（BBB）开放使钆在小鼠海马体中的沉积情况。首先，对完整小鼠颅骨进行的波传播模拟显示，波束畸变极小；而在用于体内诱导BBB开放的相同超声参数下进行的热沉积模拟显示，温度升高低于0.5摄氏度。模拟结果在离体颅骨（m = 6）和体外组织标本中得到了实验验证。然后，对体内小鼠（n = 9）注射微泡（Optison；25 - 50微升），并通过完整皮肤和颅骨在左侧海马体处进行超声处理（频率：1.525兆赫兹，压力幅值：0.5 - 1.1兆帕，脉冲持续时间：20毫秒，占空比：20%，持续时间：2 - 4次发射，每次发射30秒，间隔30秒）。在腹腔内注射钆（Omniscan；0.5毫升）后，进行连续的高分辨率T1加权MRI（9.4特斯拉，平面分辨率：75微米，扫描时间：45 - 180分钟），结果显示BBB开放的阈值为0.67兆帕，且在开放后28小时内BBB关闭。随着时间推移监测对比增强区域和钆沉积路径，并确定血管密度、大小和位置的影响。超声处理的动脉或其紧邻区域显示出比超声处理的均匀脑组织区域更大的对比增强。总之，使用单元素聚焦超声换能器，钆通过短暂开放的BBB输送至特定脑区（即海马体）。还发现，海马体区域沉积的钆量随声压增加，且BBB开放的空间分布不仅由超声束决定，还由目标脑区的脉管系统决定。
