Ultrasound-Assisted Thrombolysis for Stroke Therapy

Abstract

Background and Purpose-Ultrasound has been shown to increase recombinant tissue plasminogen activator thrombolysis through stable cavitation, or sustained bubble activity, but this mechanism needs further optimization. Use of low-frequency ultrasound in combination with microbubbles stabilized against dissolution, in the form of ultrasound contrast agents, has resulted in greater lytic efficacy in vitro. Summary of Review-This article reviews the motivation for developing ultrasound-enhanced thrombolysis and the existing evidence for its potential as an intervention for ischemic stroke. Stable cavitation is discussed and current in vitro and ex vivo studies of bubble-mediated recombinant tissue plasminogen activator clot lysis are summarized. Conclusions-Ultrasound-driven stable cavitation nucleated by an infusion of an echo contrast agent facilitates recombinant tissue plasminogen activator thrombolysis. Optimization of this gently effervescent phenomenon has the potential to reduce the morbidity and mortality of victims of ischemic stroke.

Acoustic characterization of echogenic liposomes: Frequency-dependent attenuation and backscatter

“…[59][60][61][62] Cavitation has been associated with enhanced thrombolysis, sonoporation, drug release, and drug delivery across the blood-brain barrier. [63][64][65][66] ELIPs have also been investigated as a cavitation nucleation agent in addition to their role as a diagnostic ultrasound contrast agents.…”

Low-Power 2-MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage in Rats

“…In other studies, continuous exposure to 2-MHz US alone had a signal-of-efficacy on recanalization rate and clinical outcomes, indicating that US might work even without tPA [15,16]. In addition, reduction of infarct volume by means of combined high-frequency US and microbubbles has been reported in a MCAO rat model [17,18]. However, whether high-frequency US alone is effective in reducing ischemic brain damage without any harmful effects has not yet been assessed in an animal ischemic stroke model.…”

A Review on Molecular Mechanisms of Reocclusion Following Thrombolytic Therapy in Ischemic Stroke Patients

“…Mechanical dissociation of clot [39] or use of ultrasound methods [40] are proposed in some of the literatures. Continues monitoring with transcranial Doppler (TCD) in combination with tPA therapy show higher recanalization rate than tPA without the use of TCD [41].…”