Design, characterization, and performance of a dual aperture, focused ultrasound system for microbubble-mediated, non-thermal ablation in rat brain

Submegahertz ultrasound (US) with microbubbles (µB) can ablate brain tissue: a low amplitude (< 1 MPa) alternative to thermal ablation. Single element transducers at transcranial frequencies have broad axial profiles compared to the size of targets in small animals. Thus, we sought a system to ablate millimeter volumes in normal and tumorous rat brain non-thermally using US and µB. The system consisted of two transducers oriented at 120°, driven at different frequencies (F = 837 kHz, ΔF = 30 Hz) to reduce the depth-of-field by 78%. To monitor cavitation, a passive detector (650 kHz) was confocally aligned with the therapy field. Targets were registered stereotactically. µB injections (100, 200, and 400 µl/kg) with 5-minute sonications proceeded at acoustic pressures relative to the in vivo cavitation threshold (0.3–0.6 MPa) determined a priori. Following MRI and sacrifice (1 h, 4 days, 10 days), tissue was fixed and stained. At 1 h, small lesions (<2 mm) were selectively comprised of stenotic capillaries ...