Sub-megahertz cavitation detection and characterization in mouse brains

Abstract

A key consideration in ultrasound medical device safety is the potential for cavitation related bioeffects. Device testing should address possible cavitation pathways, such as bubble formation, either in the focal region or at the device-tissue interface along with possible consequences regarding both safety and effectiveness. This has been particularly important in a number of emerging transcranial therapies including ablation, neuromodulation, and targeted opening of the blood-brain barrier (BBB) in conjunction with microbubbles. Subharmonic, and ultraharmonic emissions have been identified as indicators of treatment outcome and are a basis for safety and feedback control in BBB disruption. However, there remains a scarcity of baseline cavitation threshold data in the living mammalian brain, particularly at lower ultrasound frequencies. In our ongoing study, we are measuring and evaluating in vivo cavitation response in mice using a passive cavitation detector (PCD) for ultrasound frequencies as low as 40 kHz. Additional measurements are being carried out using a hydrophone imbedded in the brain tissue of mouse cadavers to characterize absolute pressure values as well as evaluate the sensitivity and reliability of the PCD measurements. Analyzed data will be presented along with detailed methodology and potential implications in future product evaluation will be discussed.