EXTH-21. PRECLINICAL STUDIES OF MICROBUBBLE MEDIATED NON-THERMAL FOCUSED ULTRASOUND FOR INTRACRANIAL TUMOR ABLATION

Abstract PURPOSE We examined using microbubble (MB) mediated focused ultrasound to non-thermally ablate brain tumors. Our hypothesis is that MB inertial cavitation cause mechanical cell damage in the vasculature, resulting in reduction in blood flow, tissue oxygenation, and nutrient delivery. METHODS Luciferase expressing, F98-LN glioma cells were injected into the rat brain and bioluminescent imaging used to measure tumor growth. At 8 days post tumor injection the rats were treated with magnetic resonance guided focused ultrasound (MRgFUS) using a pre-clinical MRgFUS system and tumors localization with CE-T1w and T2w MRI. An experimental MB solution (Microvascular Therapeutics, Tucson, AZ) was injected via a tail vein catheter and the FUS (2x2x8 mm focal spot size) was sonicated at the tumor. The ablation was monitored with real-time T2w MRI (to show blood extravasation) and passive cavitation detectors (PCD, to detect when inertial cavitation occurred). In one set of experiments the rats were sacrificed at various time points to investigate tumor progression post ablation, and in one set of experiments survival of treated rats was compared to un-treated controls. Histology and immunohistochemistry (Ki-67/MIB-1, Biotin, CD 3 and 34, Caspase 3) were performed on the brains. RESULTS The ablation site could accurately be identified on real-time T2w MRI during the treatment, and onset of lesion correlate well with PCD data. Post-treatment CE-T1w MRI showed that the lesion was surrounded by a volume of blood brain barrier (BBB) opening. In most rats, luciferase signal increased for a few days post ablation and then decreased by days 4-8 post ablation. MRI demonstrated tumor ablation, but post treatment edema complicates tumor response. Histological examination is consistent with tumor ablation but no consistent apoptotic, proliferation or vascular marker changes were found on immunohistochemistry. CONCLUSIONS The results are very preliminary but intracranial tumor ablation by MB mediated MRgFUS treatment appears feasible.