Impact of ultrasonic inertial cavitation on the pancreatic tumor stiffness in mice

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the fastest-growing cancers and is predicted to become the second leading cause of cancer-related deaths worldwide by 2030. Ultrasound-induced inertial cavitation (IC) is an emerging therapeutic strategy with promise for treating patients with unresectable tumors. However, the physical impact of IC on tumors remains unclear. In this study, we used orthotopic murine models of pancreatic cancer and employed passive elastography to measure elasticity before and after applying IC to the whole tumor volume. The IC was generated using two focused confocal transducers (center frequency, 1.1 MHz). The output level was adjusted with a real-time feedback loop based on broadband signal acquired with a passive cavitation detector. Cavitation clouds were visualized during treatment using an imaging probe. The results from eight treated mice showed a 24% decrease (p < 0.05) in tumor stiffness after the IC treatment, indicating that the chosen IC sequence can soften the tumor environment. After sacrifice, we utilized second-harmonic imaging microscopy to visualize the collagen network within the tumor, a known contributor to tissue stiffness, and correlated various features of this network (length, width, curvature) with the measured elasticity.