Ultrasound-driven dynamics of microbubbles confined in tissue-mimicking phantoms
Creators: name: Jamburidze, Akaki
Publisher: name: Imperial College London
Year: 2019

description: Ultrasound contrast agent microbubbles are central to biomedical ultrasound field, from diagnostic imaging to therapeutic applications. In diagnostic imaging, microbubbles provide an enhanced contrast compared to the surrounding blood pool and tissue. More recently, advanced surface engineering has allowed microbubbles to be used as effective tools for localised drug and gene delivery. Microbubble dynamics can be precisely controlled by the driving ultrasound waves, allowing for drug payload to be remotely released in the region of interest. Microbubble behaviour, when confined inside the vasculature, is affected by the vessel dimensions and its mechanical properties. In therapeutic applications, microbubbles can also be found outside of the vasculature, surrounded by biological tissue. Microbubble dynamics are influenced by the viscoelastic properties of the surrounding tissues. In order to accurately predict the microbubble behaviour, it is important to understand these changes in the microbubble dynamics. For drug delivery applications, microbubbles can facilitate drug uptake. One of the mechanisms thought responsible, is the microstreaming flow generated by an oscillating bubble. This flow has been studied for non-biomedically relevant bubbles, however experimental data for the flow induced by ultrasound contrast agent microbubbles is lacking. This Thesis investigates microbubble behaviour inside tissue mimicking phantoms. The resonance behaviour of the microbubbles is explored when they are placed in biologically relevant scenarios: embedded inside the phantoms and inside channels of various properties. Microbubbles were embedded inside hydrogel phantoms of different viscoelastic properties, which were used to study the effect of the changing viscoelastic properties on the bubble behaviour. Additionally, from the bubble dynamics, the viscoelastic properties of the phantoms were extracted in the kHz range. These values were compared to the values measured using a conventional rheometer in the low frequency range of a few Hz. In order to investigate the resonance behaviour of microbubbles near viscoelastic boundaries, channels of different dimensions and viscoelastic properties were used. Bubbles were injected into the channels and their resonance behaviour was characterised as a function of changing viscoelastic properties and confinement ratios of the said channels. Lastly, the streaming flow generated by an oscillating ultrasound contrast agent microbubble is studied to help understand this phenomenon and its possible importance in drug delivery. A complex phantom was designed to provide a side-view of the microstreaming events which enabled the visualisation of the streaming patterns. The extent of microstreaming range was examined as a function of the forcing acoustic pressure. The results obtained in this Thesis provide an insight into the change of microbubble dynamics, which can be translated to biomedical microbubbles. The microstreaming flow produced by a contrast agent microbubble has a potential to be translated into biological settings to help elucidate the role of microstreaming in drug delivery.