Sonothrombolysis Using Microfluidically Produced Microbubbles in a Murine Model of Deep Vein Thrombosis

Area of Science:

• Biomedical Engineering
• Medical Imaging
• Vascular Biology

Background:

• Current anticoagulant and thrombolytic therapies for deep vein thrombosis (DVT) carry significant risks.
• Sonothrombolysis, utilizing microbubbles, ultrasound, and thrombolytics, is an emerging technique for clot dissolution.
• Previous studies suggest larger microbubbles enhance clot dissolution, but efficacy in venous models is less understood.

Purpose of the Study:

• To evaluate the efficacy of sonothrombolysis using large microbubbles in a murine model of pre-existing deep vein thrombosis (DVT).
• To assess the potential of microfluidically produced microbubbles for ultrasound-assisted venous clot management.

Main Methods:

• Sonothrombolysis was performed on mice with DVT using 18 μm microbubbles and recombinant tissue plasminogen activator (rt-PA) administered via tail vein catheter.
• Ultrasound was applied to the abdominal region for 30 minutes.
• Three-dimensional ultrasound scans and histological analysis were used to quantify thrombus volume before and after treatment.

Main Results:

• Sonothrombolysis treatment resulted in a significant reduction of residual thrombus volume to 20%, compared to 52% in untreated controls.
• Histological analysis confirmed a substantial decrease in DVT volume after the ultrasound-assisted therapy.
• Microfluidically generated large microbubbles demonstrated effectiveness in reducing venous thrombi.

Conclusions:

• Large microbubbles, produced via microfluidics, are effective in ultrasound-assisted sonothrombolysis for treating deep vein thrombosis.
• This method shows promise as a safe and effective alternative for managing venous thromboembolism.
• Further research into microbubble-enhanced ultrasound therapy is warranted for clinical translation.