Histotripsy of VX-2 tumor implanted in a renal rabbit model.

INTRODUCTION Histotripsy is an extracorporeal focused ultrasound (US) technology that uses controlled cavitation to induce nonthermal mechanical tissue fractionation. Feasibility of histotripsy ablation of normal renal tissue in an in vivo rabbit model has previously been demonstrated. Our specific objective in this study was to characterize the histologic effects of histotripsy on VX-2 tumor implanted in the kidneys of an in vivo rabbit model. METHODS VX-2 tumor was implanted below the renal capsule in 15 New Zealand white rabbits. Two weeks after implantation, tumors were localized with diagnostic US imaging. Targeted volumes within the observed tumor were treated with short (3 micros) pulses of 1 MHz acoustic energy at a repetition frequency of 300 Hz. Twenty tumors were treated with histotripsy and 7 served as tumor controls. Three normal kidneys were also treated with histotripsy. Kidneys and lungs were harvested, grossly inspected, and processed for histopathologic analysis. RESULTS Real-time US imaging confirmed presence of cavitation during all histotripsy treatments. Examination of tumor and kidney specimens revealed 100% tumor growth with an average tumor diameter of 7 mm (range 2-12). In 16 of 20 tumors treated with histotripsy, acellular zones of debris and finely disrupted cellular architecture were present on histology. Kidneys harvested 24 hours after treatment revealed an extensive inflammatory reaction. CONCLUSIONS Transcutaneous application of histotripsy to implanted VX-2 tumor in rabbit kidney produced fractionation of malignant tissue. These findings support the further study and development of histotripsy for potential oncologic application.