Efficacy Estimation of Microbubble-Assisted Local Sonothrombolysis Using a Catheter with a Series of Miniature Transducers.

Peiyang Li,Jie Xu,Wenchang Huang,Yaoyao Cui,Weiwei Shao

doi:10.3390/mi12060612

Abstract

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/cm2, 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.

Highlights

Deep vein thrombosis (DVT) refers to the abnormal formation of thrombi in the deep venous system, which often occurs in the lower extremities [1]
The experiments were conducted in 60 min with bovine blood clots free from cold preservation treatment
We have demonstrated that MB-assisted local sonothrombolysis can realize an equal and even higher absolute thrombolytic rate compared with urokinase alone protocol

Summary

Introduction

Deep vein thrombosis (DVT) refers to the abnormal formation of thrombi in the deep venous system, which often occurs in the lower extremities [1]. When the thrombus of DVT falls off from the site of formation and travels with the reflux of venous blood, it can lead to a potentially serious blockage in the pulmonary artery, termed pulmonary embolism (PE), which is a life-threatening complication of DVT [5]. Is another common, chronic complication of DVT. It is reported that approximately 15–50% of patients with an initial DVT develop PTS [7]. PTS significantly impairs health-related quality of life among patients [8,9], and constitutes a heavy economic burden to both families and the healthcare system [10,11]

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