Qin Shengping, Ferrara Katherine W
Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
Phys Med Biol. 2006 Oct 21;51(20):5065-88. doi: 10.1088/0031-9155/51/20/001. Epub 2006 Sep 22.
The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble's oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than the UCA diameter. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA's oscillation and the microvessel's acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 microm vessel with a peak negative pressure of 0.1 MPa and a centre frequency of 1 MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with a diameter equal to or greater than 8 microm, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless of the vessel diameter; however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a centre frequency of 1 MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 microm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease; however the circumferential stress is predicted to increase. Decreasing the vessel size or the centre frequency increases the circumferential stress. For the two frequencies considered in this work, the circumferential stress does not scale as the inverse of the square root of the acoustic frequency va as in the mechanical index, but rather has a stronger frequency dependence, 1/va.
现有的超声造影剂(UCA)动力学模型主要聚焦于被无限液体包围的UCA。在假设管道直径远大于UCA直径的情况下,已使用线性微扰法对刚性管道中微泡的振荡进行了初步研究。在药物和基因递送的潜在应用中,可能希望在小血管内使造影剂外壳破碎,在某些情况下使血管壁破裂,从而在该部位释放药物和基因。顺应性小血管对UCA振荡和微血管声学响应的影响尚不清楚。这项工作的目的是提出一个集总参数模型来研究微泡振荡与顺应性微血管之间的相互作用。数值结果表明,在存在UCA的情况下,穿过血管的跨壁压力显著增加,因此预计血管通透性会增强。对于处于8至40微米血管内、峰值负压为0.1MPa且中心频率为1MHz的微泡,观察到微泡振荡频率和最大直径有微小变化。当超声压力增加时,会发生强烈的非线性振荡,血管上的周向应力增加。对于直径等于或大于8微米的顺应性血管,预计在1MHz频率下0.2MPa的峰值负压足以使微泡破碎,而与血管直径无关;然而,对于刚性血管,在1MHz频率下0.5MPa的峰值负压可能不足以使微泡破碎。对于1MHz的中心频率,预计0.5MPa的峰值负压足以超过小(直径小于15微米)顺应性血管中血管破裂的应力阈值。随着血管或周围组织变得更硬,UCA振荡和血管扩张减小;然而预计周向应力会增加。减小血管尺寸或中心频率会增加周向应力。对于本工作中考虑的两个频率,周向应力不像机械指数那样与声频va的平方根成反比,而是具有更强的频率依赖性,即1/va。