Low-frequency Ultrasound Penetrates the Cranium and Enhances Thrombolysis In Vitro

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Abstract
Refinements of treatment methods are sought to rapidly reduce the volume of intracranial clots and to decrease patient exposure to possible complications of thrombolytic therapy for intracranial hematomas. We assessed the possibility of adding ultrasonication using model systems including human blood clots and temporal bone in vitro. The transmittance of ultrasound through temporal bone obtained at autopsy was compared between the frequencies 211.5 KHz and 1.03 MHz, using a meter to determine the power delivered. The frequency 211.5 KHz was chosen to assess the ultrasound effect on the weight of 24-hour-old clots prepared from human blood after exposures at 37°C to 2 mg/ml urokinase with no additional treatment, ultrasound, or agitation during an interval of up to 12 hours. At these times, fibrin degradation products also were measured. The transmittance of low-frequency ultrasound (211.5 KHz) through temporal bone was approximately 40%, which is four times higher than that of high-frequency ultrasound (1.03 MHz). Ultrasound but not agitation significantly increased clot lysis (140% of lysis with urokinase alone), with correspondingly increased fibrin degradation products. We conclude that low-frequency ultrasound transmits well through human temporal bone and enhances thrombolysis in vitro. Clinically, this method may be promising for reducing dosages of thrombolytic agents and shortening the period of clot removal.