Unbinding of targeted ultrasound contrast agent microbubbles by secondary acoustic forces

Unbinding of targeted ultrasound contrast agent microbubbles by secondary acoustic forces
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DOI:
10.1088/0031-9155/56/19/002
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发表时间:
2011-10-07
影响因子:
3.5
通讯作者:
Versluis, Michel
Versluis, Michel
中科院分区:
工程技术2区
文献类型:
--
作者:
Garbin, Valeria;Overvelde, Marlies;Versluis, Michel

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超声造影剂微泡的靶向分子成像是通过将靶向配体结合在气泡涂层上来实现的,并且允许对受疾病影响的组织进行特异性成像。更好地理解在超声作用期间作用于气泡的声力与其他力(例如,G.由于血流的剪切、靶向配体与细胞膜上的受体的结合)可以帮助提高该技术的功效。本工作的重点是二次声辐射力的影响,它导致气泡相互吸引,并可能影响目标气泡的粘附。首先,我们研究了超声造影剂微泡的平移动力学接触(但不粘附)的半刚性膜由于二次声辐射力。一个方程的运动,有效地占膜的接近开发,和模型的预测进行比较,从光学记录中提取的实验数据在1500万帧每秒。一个时间平均模型也提出和验证。在本文的第二部分中,由于二次声辐射力的目标,粘附气泡的平移的初步结果。粘附的气泡也被发现移动由于二次声辐射力,并观察到恢复力,使它们回到它们的初始位置。为了增加次级声辐射力的大小,达到阈值,在该阈值以上,靶向微泡的粘附被破坏。这表明,在超声激活期间,次级声辐射力可导致粘附气泡分离并改变与组织结合的靶向造影剂的空间分布。虽然分子间键断裂的细节仍然难以捉摸,这项工作促使使用二次声辐射力来测量目标微泡的粘附强度。
Targeted molecular imaging with ultrasound contrast agent microbubbles is achieved by incorporating targeting ligands on the bubble coating and allows for specific imaging of tissues affected by diseases. Improved understanding of the interplay between the acoustic forces acting on the bubbles during insonation with ultrasound and other forces (e. g. shear due to blood flow, binding of targeting ligands to receptors on cell membranes) can help improve the efficacy of this technique. This work focuses on the effects of the secondary acoustic radiation force, which causes bubbles to attract each other and may affect the adhesion of targeted bubbles. First, we examine the translational dynamics of ultrasound contrast agent microbubbles in contact with (but not adherent to) a semi-rigid membrane due to the secondary acoustic radiation force. An equation of motion that effectively accounts for the proximity of the membrane is developed, and the predictions of the model are compared with experimental data extracted from optical recordings at 15 million frames per second. A time-averaged model is also proposed and validated. In the second part of the paper, initial results on the translation due to the secondary acoustic radiation force of targeted, adherent bubbles are presented. Adherent bubbles are also found to move due to secondary acoustic radiation force, and a restoring force is observed that brings them back to their initial positions. For increasing magnitude of the secondary acoustic radiation force, a threshold is reached above which the adhesion of targeted microbubbles is disrupted. This points to the fact that secondary acoustic radiation forces can cause adherent bubbles to detach and alter the spatial distribution of targeted contrast agents bound to tissues during activation with ultrasound. While the details of the rupture of intermolecular bonds remain elusive, this work motivates the use of the secondary acoustic radiation force to measure the strength of adhesion of targeted microbubbles.