Method development and automated analysis of ultrasound images of phase-shift bubbles.
Abstract
Ultrasound mediated drug delivery is an important tool in the fight againstcancer. A new concept called Acoustic Cluster Therapy (ACT ) is underdevelopment, and two pilot imaging studies have been performed on prostatecancer xenografts in mice. A large amount of raw ultrasound data has beenrecorded, but existing software can not perform the required image processing.The ACT concept is based on clusters of microbubbles and microdroplets.When exposed to diagnostic ultrasound, the microdroplets become microbubbles.This phase-shift from liquid to gas is followed by a microbubble growth to30μm. These phase-shift bubbles get stuck in the small capillaries of thetumor vasculature.A complete program has been developed in MATLAB® to process theraw ultrasound data. The program is tailored to the unique properties ofthe phase-shift bubbles, and is able to reduce noise and motion artefacts, tovisualize the contrast agent, and to count the number of ultrasound activatedphase-shift bubbles. The program produces high quality videos, displayingboth free flowing contrast agent and identified, stuck phase-shift bubbles.The program was validated against a synthesized data set, and we foundthat the program counted accurately up to 2 bubbles/mm2. A saturationwas experienced above this threshold, and too few bubbles were counted.The program was applied to a data set of 16 tumors, divided into fourgroups based on different ACT cluster dose and activation ultrasoundsettings. A significant difference (p = 0.023) was found between the differentdoses, while no significant difference (p = 0.146) was found between thedifferent activation ultrasound settings. There was neither a correlation betweenthe tumor size and the number of stuck phase-shift bubbles. The results showvery good correlation with the resultss obtained from manual counting.