Mechanisms of contrast agent destruction
Mechanisms of contrast agent destruction
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DOI：
10.1109/58.896136
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发表时间：
2001-01-01
影响因子：
3.6
通讯作者：
Ferrara, KW
中科院分区：
文献类型：
--
作者：
Chomas, JE;Dayton, P;Ferrara, KW
超声造影剂的各种应用，包括血管检测、血流灌注评估和药物输送，都需要控制造影剂微泡的破坏。气泡的寿命取决于气泡外壳、气芯和撞击气泡的声波波形的性质。微气泡的破坏有三种机制：破碎、声驱动扩散和静态扩散。破碎是造影剂在微秒级时间尺度上的快速破坏。破碎的主要特征是非常大的膨胀和随后的收缩，导致气泡的不稳定。利用新型脉冲激光光学系统进行的光学研究表明，超声造影剂微泡的最大直径与最小直径之比大于10。超声造影剂微泡的破碎与传输压力有关，超过55%的气泡在峰值负压为2.4 Mpa的情况下发生破碎，而峰值负压为0.8 Mpa的气泡中只有不到10%的气泡发生破碎。当气泡破碎时，从气泡接收的回波在两个脉冲内显著地去相关，从而为通过基于去相关的分析来检测气泡创造了机会。小鼠肿瘤模型的初步发现证实了活体中发生的碎裂。气泡破坏的一个慢得多的机制是扩散，这是由气泡中气体浓度与液体中气体浓度之间的浓度梯度以及气液界面运动的对流效应共同驱动的。由于声驱动的扩散，在辐射过程中，扩散速率增加，从而在声脉冲长度的时间尺度上产生直径变化，从而达到微秒量级。气泡在不被电离时扩散，称为静态扩散。在37摄氏度的水中，初始直径为2微米的气泡预计将在25毫秒内完全溶解。临床超声造影剂通常设计成高分子量的核心，以试图降低扩散速度。预测相同大小的C3F8和C4F10气泡分别在400ms和4000ms内完全溶解。涉及造影剂气体扩散的光学实验支持了理论预测；然而，有壳的造影剂扩散速度要慢得多，没有电离，大约在几分钟到几个小时的数量级。壳层性质通过阻塞气液界面和减少气体向周围液体的传输，对静态扩散速度起着重要作用。辐射后，静态扩散使白蛋白壳剂的直径比脂壳剂的减小程度更大。
Various applications of contrast-assisted ultrasound, including blood vessel detection, perfusion estimation, and drug delivery, require controlled destruction of contrast agent microbubbles. The lifetime of a bubble depends on properties of the bubble shell, the gas core, and the acoustic waveform impinging on the bubble Three mechanisms of microbubble destruction are considered: fragmentation, acoustically driven diffusion, and static diffusion.Fragmentation is responsible for rapid destruction of contrast agents on a time scale of microseconds. The primary characteristics of fragmentation are a very large expansion and subsequent contraction, resulting in instability of the bubble. Optical studies using a novel pulsed-laser optical system show the expansion and contraction of ultrasound contrast agent microbubbles with the ratio of maximum diameter to minimum diameter greater than 10. Fragmentation is dependent on the transmission pressure, occurring in over 55% of bubbles insonified with a peak negative transmission pressure of 2.4 MPa and in less than 10% of bubbles insonified with a peak negative transmission pressure of 0.8 MPa. The echo received from a bubble decorrelates significantly within two pulses when the bubble is fragmented, creating an opportunity for rapier detection of bubbles via a decorrelation-based analysis. Preliminary findings with a mouse tumor model verify the occurrence of fragmentation in vivo.A much slower mechanism of bubble destruction is diffusion, which is driven by both a concentration gradient between the concentration of gas in the bubble compared with the concentration of gas in the liquid, as well as convective effects of motion of the gas-liquid interface. The rate of diffusion increases during insonation, because of acoustically driven diffusion, producing changes in diameter on the time scale of the acoustic pulse length, thus, on the order of microseconds. Gas bubbles diffuse while they are not being insonified, termed static diffusion. An air bubble with initial diameter of 2 mum in water at 37 degreesC is predicted to fully dissolve within 25 ms. Clinical ultrasound contrast agents are often designed with a high molecular weight core in an attempt to decrease the diffusion rate. C3F8 and C4F10 gas bubbles of the same size are predicted to fully dissolve within 400 ms and 4000 ms, respectively. Optical experiments involving gas diffusion of a contrast agent support the theoretical predictions; however, shelled agents diffuse at a much slower rate without insonation, on the order of minutes to hours. Shell properties play a significant role in the rate of static diffusion by blocking the gas-liquid interface and decreasing the transport of gas into the surrounding liquid. Static diffusion decreases the diameter of albumin-shelled agents to a greater extent than lipid-shelled agents after insonation.