Exploring the Acoustic Parameter Space in Ultrasound Therapy: Defining the Threshold for Cavitational Effects

Focused ultrasound energy is capable of noninvasively, nonthermally ablating tissue. However, the relative contributions of thermal and cavitational effects in the therapeutic use of ultrasound are poorly understood. We sought to identify the ultrasound parameter space within which tissue can be ablated by solely mechanical means (cavitation), without a significant thermal component. Methods: Ultrasound energy (750 kHz, 20 microsecond pulses) was applied sequentially in a 3×3 grid configuration to the cortical tissue of ex vivo porcine kidneys submerged in degassed water. While maintaining constant energy density, intensity (0.11–211 kW/cm²) and duty cycle (0.04%‐CW) were varied widely. A thermocouple co‐localized with the center of each grid provided continuous temperature measurements. Following ablations, the kidneys were examined grossly and histologically. Results: Ablated tissue was classified into one of four discrete morphologic categories: blanched (firm, pale, desiccated tissue), disrupted (cavity containing thin, isochromatic liquid; no blanching), mixed blanched/disrupted (cavity containing pale, thick liquid; minimal blanching), and no grossly visible effect. Morphologically similar lesions clustered together within the ultrasound parameter space. Disrupted lesions had significantly lower maximal temperatures (44.2 °C) than desiccated (67.5 °C; p<0.0001) or mixed (59.4 °C; p<0.0001) lesions. Conclusions: In an ex vivo model, we have defined the ultrasound parameters within which mechanical tissue ablation, with minimal thermal components, is possible. Future research in vivo is directed toward optimizing the parameters for cavitational tissue ablation, and better understanding the impact of tissue perfusion on lesion generation and intralesional temperature rise.