Optimization of acoustic parameters and nanodroplet concentration for spatially controlled, reduced energy high intensity focused ultrasound ablation

Background: Perfluorocarbon (PFC)-nanodroplets (ND) provide cavitation sites when vaporized to microbubbles by acoustic energy and lower the power required to ablate tissue by high intensity focused ultrasound (HIFU). However, control over ablation can be problematic. This study explored vaporization, ablation, and PFC-ND concentration in vitro to optimize the acoustic pressure (intensity) and insonation time required for spatially controlled HIFU enhancement. Methods: HIFU (continuous wave; 1MHz; 5–20 s; 2–4 MPa) was applied to albumin-acrylamide gels containing PFC-agent (1:1 mix of volatile decafluorobutane and more stable dodecafluoropentane at 105-107 ND/mL). Controlled ablation was defined as the production of cigar-shaped lesions centered at the acoustic focus. Results: Vaporization field change from “cigar” to “tadpole” began at 5×105, 2.5×106, and 1×107 ND/mL using 4, 3, and 2 MPa, respectively. The volumes of the microbubble clouds (8–200 mm3) and ablation lesions (1–135 mm3) within them were dependent on acoustic intensity, insonation time, and PFC-ND concentration. Conclusions: Ablation within microbubble clouds of predictable size, shape, and location can be generated in gels containing PFC-ND using intensities ≤650 W/cm2. Also, pressures and insonation times can be selected to achieve an ablation lesion of desired size for a given PFC-ND concentration. Demonstrating control is an important step toward developing a useful clinical tool.