CIO 2021-19 Nonthermal and Nonionizing Tissue Destruction—Histotripsy’s Novel Mechanism of Tissue Destruction

Purpose: Thermal ablation technologies destroy tissue by temperature changes in proximity to the ablation probes. However, temperature decreases from the probe to the periphery yielding a thermal gradient. This is a potential source of tumor recurrence since the metabolic activity of malignant tissue is greatest at the periphery of the tumor. The lower peripheral temperatures also are subject to a heat sink effect. Additionally, longer energy delivery typically produces less sphericity, especially for microwave. Combined, these factors are a source of local tumor recurrence. Histotripsy is a novel tissue destruction technology that uses focused ultrasound to produce mechanical cell destruction by cavitation that should not be subject to gradient effects. The purpose of the present studies was to evaluate treatment time during histotripsy, on the volume, diameter, and sphericity of tissue destruction.

Material and Methods: Eight anesthetized pigs underwent a total of ten liver parenchyma histotripsy treatments of varying duration followed by euthanasia. XYZ axes were measured, sphericity calculated, and lesions examined histologically. A 4x4x6 mm histotripsy bubble cloud was used.

Results: Histotripsy time increased as the treatment diameter increased from 1.5 to 4 cm but the time per cubic centimeter of treated tissue remained constant at approximately 1 minute /cc for up to 40 mins. Sphericity index averaged 0.97 and did not change as treatment times were increased. Destroyed tissue histologically demonstrated a sharp zone between normal and destroyed tissue.

Conclusions: Histotripsy provides a unique mechanism of cellular destruction using cavitation rather than heat. Unlike thermal approaches, cavitation is a threshold phenomenon that produces complete cellular destruction wherever a bubble cloud is formed. These studies demonstrate tissue destruction by histotripsy is not subject to a gradient effect. Although the time for destruction increases with increasing diameter, the time per unit volume remains constant. Furthermore, the tissue destruction rate and sphericity are constant over time allowing for predictable and precise tissue destruction. Such findings, suggest that local tumor recurrence due to treatment zone unpredictability/heat sink effect should be eliminated by histotripsy.