Nonlinear mixing of two ultrasonic beams for transcranial sonothrombolysis

Evidences of ultrasound enhancement of fibrinolysis - called sonothrombolysis - using acoustic beams in the kHz range pointed out acceleration of enzymatic processes and improvement in the tissue penetration of sound waves in comparison with MHz range trials. However, trials using kHz range increased bleeding rates in strokes cases due to the formation of standing waves in the brain. This paper describes the use of two cofocused ultrasonic beams for transcranial sonothrombolysis. A confocal ultrasound transducer of 3.2 MHz of central frequency generated two independent ultrasonic beams with 20 kHz of difference frequency. The low-frequency acoustic field was mapped using a laser Doppler vibrometer based on the acousto-optic phenomenon. The nonlinear mixing of two cofocused ultrasonic beams generated a 20-kHz acoustic field with lower standing wave formation and higher focusing of the beam in comparison with the focal beam with AM modulation. The findings presented here will assist in the improvement of transcranial sonothrombolysis by focusing the site of excitation on the blood clot to avoid hemorrhage in the brain parenchyma.