Ultrasound-enhanced thrombolysis using Definity® as a cavitation nucleation agent
Ultrasound-enhanced thrombolysis using Definity® as a cavitation nucleation agent
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DOI：
10.1016/j.ultrasmedbio.2008.01.016
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发表时间：
2008-09-01
影响因子：
2.9
通讯作者：
Holland, Christy K.
中科院分区：
文献类型：
--
作者：
Datta, Saurabh;Coussics, Constantin-C.;Holland, Christy K.
以前已经显示超声与血栓溶解剂协同作用，如重组组织纤溶酶原激活剂（rt-PA），以加速血栓溶解。在该体外研究中，在120 kHz的脉冲超声暴露期间，使用市售造影剂Depletion（R）来促进和维持空化的成核。超谐波信号，宽带发射和谐波的基本声测量通过使用聚焦水听器作为被动空化检测器，并用于量化空化活动的水平。将悬浮在人血浆中的人全血凝块暴露于rt-PA、去甲肾上腺素和超声的组合，超声峰-峰压力振幅范围被选择为将凝块暴露于不同程度的空化活性。通过测量治疗前后的凝块质量损失来确定溶栓疗效，并与空化活性的程度相关。rt-PA和纤溶酶原的渗透深度也进行了评价，在空化微泡的存在下，使用双抗体荧光成像技术。对于用120-kHz超声（0.32-MPa峰-峰压力振幅）、rt-PA和由Depletion（R）成核的稳定空化处理的凝块，观察到最大的质量损失（26.2%）。在质量损失和超谐波信号之间观察到显著相关性（r = 0.85，p < 0.0001，n = 24）。最大的平均穿透深度的rt-PA（222 μ m）和纤溶酶原（241 μ m）的存在下，观察到稳定的空化活性。稳定的空化活性在促进溶栓过程中起重要作用，可以通过监测空化活性来评价溶栓治疗的效果。
Ultrasound has been shown previously to act synergistically with a thrombolytic agent, such as recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. In this in vitro study, a commercial contrast agent, Definity (R), was used to pro-mote and sustain the nucleation of cavitation during pulsed ultrasound exposure at 120 kHz. Ultraharmonic signals, broadband emissions and harmonics of the fundamental were measured acoustically by using a focused hydrophone as a passive cavitation detector and used to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity(D and ultrasound at a range of ultrasound peak-to-peak pressure amplitudes, which were selected to expose clots to various degrees of cavitation activity. Thrombolytic efficacy was determined by measuring clot mass loss before and after the treatment and correlated with the degree of cavitation activity. The penetration depth of rt-PA and plasminogen was also evaluated in the presence of cavitating microbubbles using a dual-antibody fluorescence imaging technique. The largest mass loss (26.2%) was observed for clots treated with 120-kHz ultrasound (0.32-MPa peak-to-peak pressure amplitude), rt-PA and stable cavitation nucleated by Definity (R). A significant correlation was observed between mass loss and ultraharmonic signals (r = 0.85, p < 0.0001, n = 24). The largest mean penetration depth of rt-PA (222 pm) and plasminogen (241 mu m) was observed in the presence of stable cavitation activity. Stable cavitation activity plays an important role in enhancement of thrombolysis and can be monitored to evaluate the efficacy of thrombolytic treatment.