Application of cavitation promoting surfaces in management of acute ischemic stroke.

High frequency, low intensity ultrasound has the potential to accelerate the clearance of thrombotic occlusion in the absence of cavitation. At high frequency ultrasound, high acoustic pressures, >5.2MPa, are required to generate cavitation in thrombus.

Sonothrombolysis: an emerging modality for the treatment of acute ischemic and hemorrhagic stroke.

To date, it is believed that rapid removal of impedances hindering normal blood circulation in the brain would salvage ischemic tissue. Hence, most treatment modalities undergoing clinical evaluation for treatment of stroke are focused on faster recanalization in acute ischemic stroke or faster hematoma mass reduction in hemorrhagic stroke. Therapeutic ultrasound is among the promising emerging modalities being clinically evaluated to meet this purpose.

Potentiating intra-arterial sonothrombolysis for acute ischemic stroke by the addition of the ultrasound contrast agents (Optison™ & SonoVue(®)).

Transcranial ultrasound in combination with intravenously administered ultrasound contrast agents (UCA) in the presence or absence of recombinant tissue plasminogen activator (rt-PA) has been widely evaluated as a new modality for treatment of ischemic stroke. Despite the successful demonstration of accelerated clot lysis there are inherent limitations associated with this modality such as inconsistency in temporal window thickness and/or potential serious cardiopulmonary reactions to intravenous administration of UCA that prevent broad application to ischemic stroke populations. As a complementary modality, we evaluated potential lysis enhancement by intra-arterial ultrasound with concurrent intra-clot delivery of UCA and rt-PA.

Effect of modulated ultrasound parameters on ultrasound-induced thrombolysis.

The potential of ultrasound to enhance enzyme-mediated thrombolysis by application of constant operating parameters (COP) has been widely demonstrated. In this study, the effect of ultrasound with modulated operating parameters (MOP) on enzyme-mediated thrombolysis was investigated. The MOP protocol was applied to an in vitro model of thrombolysis.

Stability of alteplase in presence of cavitation.

Several experimental studies have demonstrated that ultrasound (US) can accelerate enzymatic fibrinolysis and this effect is further enhanced in the presence of ultrasound contrast agents (UCA). Although UCA have been shown to be safe when administered to ischemic stroke patients, safety information of these agents in the thrombolysis setting is limited. Therefore, in this study we investigated potential adverse effects of acoustic cavitation generated by UCA on alteplase (t-PA), the drug used for treatment of ischemic stroke patients.

Cavitational mechanisms in ultrasound-accelerated fibrinolysis.

The role of both inertial and stable cavitation was investigated during in vitro ultrasound-accelerated fibrinolysis by recombinant tissue plasminogen activator (rt-PA) in the presence and absence of Optison. A unique treatment configuration applied ultrasound, rt-PA and Optison to the interior of a plasma clot. Lysis efficacy was measured as clot weight reduction.

Absence of biological damage from prolonged exposure to intravascular ultrasound: a swine model.

Ultrasound (US) has been used in IMS II (intravascular US) and CLOTBUST (transcranial US) clinical trials for thrombolysis. During the treatment, in addition to the targeted thrombus, other biological components, such as blood and vessel walls are subjected to long durations of US exposure. In this study we explored evidence of biological damage due to mechanical forces or thermal effects of US exposure at the frequency, intensity and duration employed for thrombolysis treatment.

Effect of ultrasound on enzymatic activity of selected plasminogen activators.

Introduction: Ultrasound has been shown to accelerate enzymatic fibrinolysis with adjunctive plasminogen activators. Additionally, ultrasound is known for interaction with biological substances on molecular level in sonodynamic therapy and sonochemistry. Therefore, we investigated the possibility of ultrasound affecting the biological activity of plasminogen activators used in thrombolysis treatment.