Refining Histotripsy: Defining the Parameter Space for the Creation of Nonthermal Lesions With High Intensity, Pulsed Focused Ultrasound of the In Vitro Kidney

Abstract

Focused ultrasound therapy is a promising modality for noninvasive tissue ablation. However, the relative contributions of thermal and cavitational effects are poorly defined. We characterized the ultrasound parameters within which tissue ablation occurs by cavitational mechanisms without significant thermal effect. In vitro porcine kidneys were submerged in degassed water. Tissue ablation was performed by delivering ultrasound (750 kHz and 20 microsecond pulses) of constant spatial peak energy dose (100 J/cm(2)) to adjacent foci in a 3 x 3 grid configuration. For each ablation different intensity (0.11 to 211 kW/cm(2)) and duty cycle (0.04% to 100%) parameters were selected. A thermocouple co-localized with the center of each grid continuously measured temperature. Following ablation each kidney was examined grossly and histologically. Ablated tissue lesions were classified into 4 discrete morphological categories, including blanched--firm, pale, desiccated tissue, disrupted--a cavity containing thin, isochromatic liquid, mixed--a cavity containing pale, thick liquid with minimal blanching and no grossly visible effect. Morphologically similar lesions clustered at separable regions of the ultrasound parameter space. The maximal temperature attained in disrupted lesions was similar to that attained when there was no effect (44.2C and 47.2C, respectively, p = 0.31), although it was significantly lower than the maximal temperatures for desiccated or mixed lesions (67.5C and 59.4C, each p <0.0001). In an in vitro model we defined the ultrasound parameter region within which purely cavitational ablation of tissue is possible with a negligible thermal component. Additional research is needed to optimize the parameters for in vivo cavitational tissue ablation, incorporating the influence of tissue perfusion.