During the first 24 h, a clinical improvement was observed in only 45% of patients treated with IVT, but in up to 70% of patients treated R428 in vivo with sono-lysis or IAT. The incidence of SICH was 5% in the IVT group, 0% in the sono-lysis group and 20% in the IAT group. In later sono-lysis studies, the additive effect of echocontrast agents has been tested. The first study with Levovist® (galactose based air microbubbles, Schering, Germany) and Sonovue® (sulphurhexafluoride microbubbles, Bracco, Italy) demonstrated an increase in the percentage
of arterial recanalization and better clinical improvement in acute IS patients treated with sono-lysis in combination with echocontrast agent [44]. This study demonstrated also the safety of echocontrast agent use. SICH occurred in 3.3% in the Levovist® group and in 2.1% in the Sonovue® group. Better improvement of neurological symptoms as well as the improvement of the flow signal in the occluded arteries were showed in the study of Perren et al., using sono-lysis with 2 MHz
transcranial duplex probe in combination with Sonovue® in patients with acute MCA occlusion treated with IVT [45]. The pilot randomized clinical trial with the new generation echocontrast agent (perfluten-lipid microspheres) demonstrated additive effect of echocontrast agent in patients treated MAPK inhibitor with IVT and sono-lysis [46]. Percentage of complete recanalization within 2 h after therapy start was 50% in the group treated with a combination of IVT, sono-lysis and echocontrast agent in comparison with 18% in the control group selected from the CLOTBUST study. Asymptomatic intracerebral hemorrhage was found in 25% of patients in the treatment group and in 33% in the control group. A higher percentage of asymptomatic
hemorrhagic transformation was also associated with a higher percentage of recanalization and better clinical status outcome in this study. No SICH was detected. Similar results with higher recanalization Montelukast Sodium rate, higher percentage of good clinical outcome and also higher number of asymptomatic hemorrhagic transformation were found by Dinia et al., who used the combination of IVT, sono-lysis and administration of echocontrast agent [47]. This result supported the hypothesis that the finding of asymptomatic hemorrhagic transformation of ischemic lesion is a marker of early reperfusion and it is associated with a higher chance of good clinical outcome. These promising results were tested in the TUCSON (Transcranial Ultrasound in Clinical Sonothrombolysis) study. Sono-lysis using 2 MHz transcranial Doppler probe in combination with an echocontrast agent MRX-801 (perfluten-lipid microspheres, ImaRx Therapeutics, Inc., USA) as adjunctive therapy to IVT was used [48]. Although the study showed that administration of a dose of 1.4 ml of MRX-801® in 90-min continuous infusion during the IVT combined with sono-lysis is safe, the study was discontinued due to the higher SICH risk in higher dose of echocontrast agent.