Nonthermal ablation in the rat brain using focused ultrasound and an ultrasound contrast agent: long-term effects

OBJECTIVE Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently under investigation as a less invasive alternative to radiosurgery and resection. A major limitation of the method is that its use is currently restricted to centrally located brain targets. The combination of FUS and a microbubble-based ultrasound contrast agent greatly reduces the ultrasound exposure level needed to ablate brain tissue and could be an effective means to increase the "treatment envelope" for FUS in the brain. This method, however, ablates tissue through a different mechanism: destruction of the microvasculature. It is not known whether nonthermal FUS ablation in substantial volumes of tissue can safely be performed without unexpected effects. The authors investigated this question by ablating volumes in the brains of normal rats. METHODS Overlapping sonications were performed in rats (n = 15) to ablate a volume in 1 hemisphere per animal. The sonications (10-msec bursts at 1 Hz for 60 seconds; peak negative pressure 0.8 MPa) were combined with the ultrasound contrast agent Optison (100 µl/kg). The rats were followed with MRI for 4-9 weeks after FUS, and the brains were examined with histological methods. RESULTS Two weeks after sonication and later, the lesions appeared as cyst-like areas in T2-weighted MR images that were stable over time. Histological examination demonstrated well-defined lesions consisting of a cyst-like cavity that remained lined by astrocytic tissue. Some white matter structures within the sonicated area were partially intact. CONCLUSIONS The results of this study indicate that nonthermal FUS ablation can be used to safely ablate tissue volumes in the brain without unexpected delayed effects. The findings are encouraging for the use of this ablation method in the brain.