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Radiation-Force Assisted Targeting Facilitates Ultrasonic Molecular Imaging

机译：辐射力辅助靶向促进超声分子成像。

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摘要

Ultrasonic molecular imaging employs contrast agents, such as microbubbles, nanoparticles, or liposomes, coated with ligands specific for receptors expressed on cells at sites of angiogenesis, inflammation, or thrombus. Concentration of these highly echogenic contrast agents at a target site enhances the ultrasound signal received from that site, promoting ultrasonic detection and analysis of disease states. In this article, we show that acoustic radiation force can be used to displace targeted contrast agents to a vessel wall, greatly increasing the number of agents binding to available surface receptors. We provide a theoretical evaluation of the magnitude of acoustic radiation force and show that it is possible to displace micron-sized agents physiologically relevant distances. Following this, we show in a series of experiments that acoustic radiation force can enhance the binding of targeted agents: The number of biotinylated microbubbles adherent to a synthetic vessel coated with avidin increases as much as 20-fold when acoustic radiation force is applied; the adhesion of contrast agents targeted to α_vβ_3 expressed on human umbilical vein endothelial cells increases 27-fold within a mimetic vessel when radiation force is applied; and finally, the image signal-to-noise ratio in a phantom vessel increases up to 25 dB using a combination of radiation force and a targeted contrast agent, over use of a targeted contrast agent alone.
机译：超声分子成像使用造影剂，例如微泡，纳米颗粒或脂质体，涂有对血管新生，炎症或血栓部位的细胞上表达的受体具有特异性的配体。这些高回声造影剂在目标部位的浓缩会增强从该部位接收到的超声信号，从而促进超声检测和疾病状态分析。在本文中，我们证明了声辐射力可用于将目标造影剂置换到血管壁，从而大大增加了与可用表面受体结合的试剂数量。我们提供了声辐射力大小的理论评估，并表明可以替换生理上相关距离的微米级试剂。此后，我们在一系列实验中表明，声辐射力可以增强靶向药物的结合力：当施加声辐射力时，粘附在涂有抗生物素蛋白的合成容器上的生物素化微泡的数量增加多达20倍；当施加辐射力时，靶向人脐静脉内皮细胞上表达的α_vβ_3的造影剂的粘附力增加了27倍。最后，与单独使用目标造影剂相比，使用辐射力和目标造影剂的组合，幻影血管中的图像信噪比增加到25 dB。

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