Stimulus-responsive ultrasound contrast agents for clinical imaging: motivations, demonstrations, and future directions.
Stimulus-responsive ultrasound contrast agents for clinical imaging: motivations, demonstrations, and future directions.
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DOI：
10.1002/wnan.1285
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发表时间：
2015-01
影响因子：
8.6
通讯作者：
Mattrey, Robert F.
中科院分区：
文献类型：
--
作者：
Goodwin, Andrew P.;Nakatsuka, Matthew A.;Mattrey, Robert F.
微泡超声造影剂可以以优异的分辨率和信噪比对脉管系统进行成像。微泡的对比度源自它们与超声波的相互作用，以刺激脉冲的谐波频率产生信号；减去周围组织引起的弹性回波可以显着增强这些谐波信号的特异性。非线性声发射是由压力驱动的微泡尺寸波动引起的，在理论描述和经验测量中发现，这种波动取决于封装微泡并使其在周围水环境中稳定的外壳的机械性能。因此，生化诱导的刚性“关闭”状态和灵活的“开启”状态之间的切换提供了一种传感疾病化学标记的机制。在我们的研究中，我们将 DNA 寡核苷酸与稳定的脂质单层偶联，以调节外壳的硬度，从而诱导刺激响应行为。在最初的原理验证研究中，发现信号调制主要来自 DNA 交联，防止微泡尺寸振荡，而不仅仅是抑制信号。接下来，这些微泡被重新设计，在交联链中包含适体序列，这不仅允许感测凝血酶凝血酶，而且还提供了感测血流中其他可溶性生物标志物的通用策略。最后，凝血酶敏感的微泡在兔子模型中得到了验证，这是第一个可以区分活性和非活性血栓以诊断深静脉血栓的超声造影剂的例子。
Microbubble ultrasound contrast agents allow imaging of the vasculature with excellent resolution and signal-to-noise ratios. Contrast in microbubbles derives from their interaction with an ultrasound wave to generate signal at harmonic frequencies of the stimulating pulse; subtracting the elastic echo caused by the surrounding tissue can enhance the specificity of these harmonic signals significantly. The nonlinear acoustic emission is caused by pressure-driven microbubble size fluctuations, which in both theoretical descriptions and empirical measurements was found to depend on the mechanical properties of the shell that encapsulates the microbubble as well as stabilizes it against the surrounding aqueous environment. Thus biochemically-induced switching between a rigid “off” state and a flexible “on” state provides a mechanism for sensing chemical markers for disease. In our research, we coupled DNA oligonucleotides to a stabilizing lipid monolayer to modulate stiffness of the shell and thereby induce stimulus-responsive behavior. In initial proof-of-principle studies, it was found that signal modulation came primarily from DNA crosslinks preventing the microbubble size oscillations rather than merely damping the signal. Next, these microbubbles were redesigned to include an aptamer sequence in the crosslinking strand, which not only allowed the sensing of the clotting enzyme thrombin but also provided a general strategy for sensing other soluble biomarkers in the bloodstream. Finally, the thrombin-sensitive microbubbles were validated in a rabbit model, presenting the first example of an ultrasound contrast agent that could differentiate between active and inactive clots for the diagnosis of Deep Venous Thrombosis.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
2.4
作者：
CHURCH, CC
通讯作者：
CHURCH, CC
影响因子：
1.6
作者：
Hilgenfeldt, S;Lohse, D;Zomack, M
通讯作者：
Zomack, M
DOI：
10.1073/pnas.0601755103
发表时间：
2006-04-18
影响因子：
11.1
作者：
Farokhzad, OC;Cheng, JJ;Langer, R
通讯作者：
Langer, R
影响因子：
3.1
作者：
Benoy, Ina;Salgado, Roberto;Dirix, Luc Y
通讯作者：
Dirix, Luc Y