Sonothromblysis in Combination with Thrombolytic Drugs in a Rabbit Model Using MRI-Guidance

Christakis Damianou,Nicos Mylonas,Kleanthis Ioannides

doi:10.4236/eng.2013.510b071

Abstract

The potential of MRI-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 rabbitin vivois evaluated. A spherically-focused transducers of 5 cmdiameter; focusing at10 cmand operating at 1 MHz was used. A pulsed ultrasound protocol was used that maintains a tissue temperature increase of less than 1℃ 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 to just using rt-PA. The proposed protocol was monitored using Magnetic Resonance Angiography (MRA) every 1 min.

Highlights

The feasibility of ultrasound to enhance thrombolysis was reported in the mid 70s [1,2]
It is speculated that ultrasound accelerates enzymatic fibrinolysis primarily through mechanical mechanisms, by enhancing the effectiveness of thrombolytic drugs, possibly by exposing more binding sites on the fibrin to the recombinant tissue plasminogen activator [5]
The results in this study demonstrate the ability of MRI-guided focused ultrasound (MRgFUS) in combination with recombinant tissue plasminogen activator (rt-PA) to dissolve clots in an in vivo model

Summary

Introduction

The feasibility of ultrasound to enhance thrombolysis was reported in the mid 70s [1,2]. Several in vitro studies (Kimura et al 1994 [3] and Spengos K et al 2000 [4]) have confirmed the above results In the former studies, the range of intensity varied from 0.2 - 2.0 W/cm (spatial peak temporal average intensity) and the frequency from 20 kHz to 2 MHz using unfocused ultrasound. In the study by Frenkel V et al 2006 [12], clots from humans in vitro were ablated using pulse ultrasound with a 1 MHz single element transducer in synergy with rt-PA. In another study (Hölscher T. et al 2011 [14]), clots that were formed in the rabbit marginal ear vein were ablated using pulse ultrasound with a 1 MHz single element transducer in synergy with recombinant tissue plasminogen activator (rt-PA). Focused ultrasound targeting the clot is used with spatial average temporal average (SATA) in situ intensity of 20 W/cm

Materials and Methods

Focused Ultrasound System—MR Imaging

Production of Sample Clots

MRI Parameters

In Vivo Experiments

Discussion