In Vitro and In Vivo evaluation of a magnetic resonance imaging-guided focused ultrasound system for dissolving clots in combination with thrombolytic drugs.

BACKGROUND: The potential of a magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) system combined with thrombolytic drugs to dissolve clots is investigated using in vitro and in vivo models. METHODS: Two spherically focused transducers of 5 cm diameter focusing at 10 cm and operating at either .5 or 1 MHz were used. Doppler ultrasound was used to measure the blood flow during the in vivo experiments. RESULTS: 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. CONCLUSIONS: The MRgFUS technique was proven successful in dissolving clots in vitro and in vivo. 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 .5 MHz transducer. The beam of ultrasound through the phantom skull was monitored using the MRI technique of fast spoiled gradient. Finally, the thrombus in the in vivo model (ear artery) was successfully destroyed with the therapeutic protocols investigated in the in vitro 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.

MRI-guided sonothrombolysis of rabbit carotid artery.

The potential of magnetic resonance imaging-guided focused ultrasound (MRgFUS) combined with the thrombolytic drug recombinant tissue plasminogen activator (rt-PA) to dissolve clots in the carotid of a New Zealand rabbit in vivo is evaluated. A spherically focused transducer of 5-cm diameter, focusing at 10 cm and operating at 1 MHz, was used. A pulsed ultrasound protocol was used that maintains a tissue temperature increase of less than 1 °C in the clot (called safe temperature). MRgFUS has the potentials to dissolve clots that are injected in the carotid of rabbits in vivo. It was found that the time needed for opening the carotid artery using ultrasound and rt-PA was decreased compared with just using rt-PA. The time needed for opening the artery decreases with increasing acoustic intensity. With an intensity of 20 W/cm2 (spatial average temporal average), which is not causing artery heating, the time needed to completely open the artery was 70 minutes. The proposed protocol was monitored using magnetic resonance angiography every 1 minute.