A simple animal model for cerebral vasculature rupture due to exposure to intense pressure waves

Abstract

Understanding the threshold of microvasculature rupture in the central nervous system is critical to evaluating the safety of transcranial therapeutic ultrasound procedures, and treatment planning for blast traumatic brain injury. The goal of this study is to determine the threshold for microvasculature rupture in a simple animal model, as a function of the characteristics of the incident pressure-pulse train. An earthworm model was chosen, as a first step in a sequence of increasingly complex models, and because of its readily accessible large vessel. Following anesthetization, the earthworms were sonicated with 3.3 MHz pulse trains from a high-intensity focused ultrasound (HIFU) transducer. A variety of pulse durations, repetition rates, and amplitudes were considered. The pulse duty cycle was kept low (0.0001 to 0.001) to minimize thermal effects. In cases where rupture occurred within 10 min of exposure, the rupture time was recorded. A noticeable threshold for microvascular damage was observed at a peak negative pressure of about 20 MPa. Beyond this pressure, rupture times decreased rapidly with increasing acoustic pressure. The threshold for damage is likely due to the onset of cavitation, though the mechanisms affecting the rupture time require further study.