Image-guided sonothrombolysis in a stroke model with a cavitation delivery and monitoring system

Abstract

Microbubbles (MB) and ultrasound (US) can dissolve intra-arterial thrombi. In order to reproducibly deliver the correct cavitation dose and ensure treatment efficacy and safety, we designed a therapeutic US mode with cavitation monitoring. Therapy delivery and recording of the MB signal are achieved with a sector imaging probe. Monitoring is achieved by spectrally analyzing the MB signal: ultraharmonics are a marker of stable cavitation (SC) and broadband noise characterizes inertial cavitation (IC). We used the system in a pig model. Thrombotic occlusions were created by injecting 4-hour old clots bilaterally into the internal carotids. Forty pigs were randomized to either 2.4 MI, 5 μs pulses with MBs; 1.7 MI, 20 μs pulses with MBs; and 2.4 MI, 5 μs pulses without MBs. Angiographic recanalization rates were compared. Cavitation as a function of MI was estimated in vivo. Dominant SC started at an applied MI of 0.6 (0.3MI in situ after derating by skull attenuation). Dominant IC was estimated to start at an applied MI of 0.9 (0.6 in situ). Thus, all therapy settings were in the IC regime. The 2.4MI + MB setting was the most effective (100% recanalization) vs 38% for the 1.7MI + MB and 50% for 2.4 MI without MBs (both p<0.05 compared to 2.4MI + MB). No signs of hemorrhage were found in any animal. In conclusion, higher IC levels are most effective for thrombus dissolution. Spectral analysis techniques can be used to plan and monitor the therapy.