Low-frequency therapeutic ultrasound with varied duty cycle: effects on the ischemic brain and the inner ear

Sonothrombolysis is a promising modality for acute stroke treatment. In vitro data suggest a duty cycle dependence of sonothrombolytic efficacy of low-frequency applications. The aim of our study was to examine its impact on safety issues in a rat model of middle cerebral artery occlusion. Rats were exposed to transcranial 60-kHz ultrasound with varied duty cycles. To determine effects on the inner ear, the acoustic threshold was determined in additional healthy animals (acoustic evoked potentials). A short duty cycle (20%) resulted in significant adverse effects (ischemic volume, hemorrhage, functional outcome), which was not observed in longer duty cycle (80%). Continuous-wave insonation produced high rates of mortality and subarachnoid hemorrhage. Hearing was impaired independent of duty cycle. In conclusion, cerebral side effects may be efficiently reduced by modulation of pulsed parameters, which is in line with data on an improved efficacy with longer duty cycle. However, side effects on the auditory system were found to be independent of parameter settings.