Li Peiyang, Huang Wenchang, Xu Jie, Shao Weiwei, Cui Yaoyao
Academy for Engineering & Technology, Fudan University, Shanghai 200240, China.
Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
Micromachines (Basel). 2021 May 26;12(6):612. doi: 10.3390/mi12060612.
Intravascular ultrasound has good prospects for clinical applications in sonothrombolysis. The catheter-based side-looking intravascular ultrasound thrombolysis (e.g., Ekosonic catheters) used in clinical studies has a high frequency (2 MHz). The lower-frequency ultrasound requires a larger-diameter transducer. In our study, we designed and manufactured a small ultrasound-based prototype catheter that can emit a lower frequency ultrasound (1.1 MHz). In order to evaluate the safety and efficacy of local low-frequency ultrasound-enhanced thrombolysis, a microbubble (MB) was introduced to augment thrombolysis effect of locally delivered low-intensity ultrasound. The results demonstrated that combination of ultrasound and MB realized higher clot lysis than urokinase-only treatment (17.0% ± 1.2% vs. 14.9% ± 2.7%) under optimal ultrasound settings of 1.1 MHz, 0.414 MPa, 4.89 W/cm, 5% duty cycle and MB concentration of 60 μg/mL. When urokinase was added, the fibrinolysis accelerated by MB and ultrasound resulted in a further increased thrombolysis rate that was more than two times than that of urokinase alone (36.7% ± 5.5% vs. 14.9% ± 2.7%). However, a great quantity of ultrasound energy was required to achieve substantial clot lysis without MB, leading to the situation that temperature accumulated inside the clot became harmful. We suggest that MB-assisted local sonothrombolysis be considered as adjuvant therapy of thrombolytic agents.
血管内超声在超声溶栓的临床应用中具有良好前景。临床研究中使用的基于导管的侧视血管内超声溶栓（如Ekosonic导管）频率较高（2兆赫）。较低频率的超声需要更大直径的换能器。在我们的研究中，我们设计并制造了一种基于小型超声的原型导管，其能够发射较低频率的超声（1.1兆赫）。为了评估局部低频超声增强溶栓的安全性和有效性，引入了微泡（MB）以增强局部递送的低强度超声的溶栓效果。结果表明，在1.1兆赫、0.414兆帕、4.89瓦/平方厘米、5%占空比和MB浓度为60微克/毫升的最佳超声设置下，超声与MB联合使用实现的血栓溶解率高于仅使用尿激酶治疗（17.0%±1.2%对14.9%±2.7%）。当加入尿激酶时，MB和超声加速的纤维蛋白溶解导致溶栓率进一步提高，比单独使用尿激酶高出两倍多（36.7%±5.5%对14.9%±2.7%）。然而，在没有MB的情况下，需要大量超声能量才能实现实质性的血栓溶解，导致血栓内部温度积累的情况变得有害。我们建议将MB辅助局部超声溶栓视为溶栓剂的辅助治疗方法。
