In Vitro and In Vivo Evaluation of a Magnetic Resonance Imaging–guided Focused Ultrasound System for Dissolving Clots in Combination with Thrombolytic Drugs

Abstract

The potential of a magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) system combined with thrombolytic drugs to dissolve clots is investigated using invitro and invivo models. Two spherically focused transducers of 5cm diameter focusing at 10cm and operating at either .5 or 1MHz were used. Doppler ultrasound was used to measure the blood flow during the invivo experiments. The effect of ultrasound intensity, transducer beam area, and frequency on the dissolved volume was investigated. The goal was to maintain a temperature increase of less than 1°C (called safe temperature) at the clot during the application of pulsed ultrasound and at the same time achieve efficient thrombolysis. The MRgFUS technique was proven successful in dissolving clots invitro and invivo. It was found that the volume of dissolved clot increases with acoustic intensity and beam size and decreases with frequency. With this system, it was possible to push ultrasound through a plastic phantom skull using a .5MHz transducer. The beam of ultrasound through the phantom skull was monitored using the MRI technique of fast spoiled gradient. Finally, the thrombus in the invivo model (ear artery) was successfully destroyed with the therapeutic protocols investigated in the invitro models. This study shows that FUS using a single element MR-compatible transducer has the potential to treat clots in synergy with thrombolytic drugs. More advanced MRgFUS systems, such as phased arrays, will have a greater impact in sonothrombolysis.