Passive and active Doppler methods and metrics to quantify inertial cavitation induced by pulsed focused ultrasound

Abstract

Inertial cavitation induced by pulses of nonlinearly distorted focused ultrasound (FUS) at moderate intensity can result in mild mechanical disruption of tissue, short of its complete mechanical disintegration—histotripsy. This effect can be used to enhance diffusion of subsequently systemically administered drugs or biologics. Previously, single-element passive cavitation detection (PCD) of broadband noise emissions was successfully used to quantify tissue disruption and enhancement in drug concentration. This metric, however, has limitations: minimal spatial resolution and challenges with calibration when used at large depths in acoustically variable tissue. To address this, we developed a combination of passive and active Doppler-based methods that relied on relative, rather than absolute signal metrics. Specifically, destructive cavitation behaviors were previously linked to substantial motion of the bubbles during the FUS pulse due to acoustic radiation force and shock scattering. This was reflected in the backscattered FUS harmonics as Doppler shift and measurable from PCD. The bubbles were observed to dissolve within milliseconds following each FUS pulse, thus their distribution could be visualized as an area of rapid change via fast plane wave Doppler ensemble following the FUS pulse. The Doppler power distribution was spatially correlated with the area of tissue disruption in the in vivo experiments. [Work supported by NIH R01CA154451, R01EB025187, and R01EB23910.]