Bubble-enhanced ultrasound and radiation in healthy brain tissue: Exploring the parameter space for a novel neurosurgical tool

Combined microbubble-mediated focused ultrasound (μB-FUS) and radiation therapy (RT) have been used to treat solid tumors. We have observed that μB-FUS+RT also leads to incision-less, targeted ablation in healthy brain tissue. This novel neurosurgical approach may minimize radiation doses (20–70 Gy) needed for radiosurgery and improve the ability to tailor surgery compared to μB-FUS ablation. Here, we studied the effect of μB-FUS and RT on lesioning in healthy rats. The striatum was targeted with pulsed FUS (273 kHz; ∼5 × 5 mm2; Definity μBs, 20 μl/kg). Acoustic pressures were modulated using a μB emissions-based controller (max 183 kPa). T1- and T2-weighted 7T MRI were used to confirm FUS effects. ∼1 h after FUS, RT (3 × 3 mm2) was delivered to the target. Lesion progression was monitored using T2-w MRI. 7 treatment groups (n = 4 locations/group) were tested: (1) μB-FUS-only, (2–4) RT-only (8, 12, and 15 Gy), and (5–7) μB-FUS+RT. 72 h after μB-FUS+RT, lesions were seen at all targets for 12 and 15 Gy and 2/4 targets for 8 Gy. Lesions were well colocalized with the overlap of the two treatment modalities, measuring ∼3 × 3 mm2, and persisted until day 21. Edema in the μB-FUS-only group resolved within 7 days, and no T2 effects were observed in the RT-only groups. Preliminary analyses indicate that mild edema on T2-w MRI immediately following μB-FUS may be predictive of successful μB-FUS+RT treatment outcomes. Ongoing work is aimed at understanding the effect of μB-FUS parameters, and the mechanisms of cell death and lesion progression.