Contrast agents

Introduction

Microbubbles have shown great promise as ultrasound contrast agents. There are extremely sensitive: under the right ultrasound frequency, called the resonance frequency, a single micron-sized bubble oscillates in a highly nonlinear way which make it possible to detected it. They are currently used in a range of clinical applications including cardiovascular diseases and cancer.

We had interest in studying the physical behaviour of these microbubbles and their effects on micro-vascular imaging and quantification, particularly their interaction with ultrasound  and in vivo environment (e.g. surrounded or attached to a vascular wall).

We are currently working on nano-sized phase-change droplets which can be vaporised into bubbles by ultrasound and/or light. While microbubbles are confined within vessels, such nano-sized droplets could leak out of the vessel and extend the ultrasound contrast to extravascular space.

Current Projects

• Project – Acoustic Wave Sparsely-Activated Localisation Microscopy (AWSALM).

Previous Work

• Project – Phase-change contrast agents.

One challenge of the microbubble mediated ultrasound techniques is that microbubbles are limited to intravascular applications due to their relatively large size compared to the particle extravasation size limit (e.g. 100-750 nm for tumour vessels). However phase-change contrast agents (PCCA), in the form of nano-scale droplets (peak size: 200–300 nm), provide a safe approach extending the ultrasound contrast beyond the vasculature. We developed such contrast agents and methodologies for characterising them acoustically and optically, and explored their potential application in both ultrasound and photo acoustic imaging. This is a collaboration with Prof. Terry Matsunaga from University of Arizona.

• Project – Bubbles responses in different size vessels.

When used in vivo, microbubble ultrasound contrast agents (UCAs) are distributed in vessels of different sizes. However the current understanding of the response of UCAs in vessels of various diameters is still limited. Such knowledge is important for quantitative contrast enhanced ultrasound imaging and therapy. In particular, the contribution of UCAs in different sized vessels to the overall received signal from a perfused region in vivo is not clear and better understanding of the scaling of UCA response with vessel size would be a first step in this direction. Small blood vessels play a significant role in disease progression in the form of neovascularisation supplying cancer tumor or atherosclerotic lesions, thus quantifying UCA signal in these would inform staging during diagnosis on the imaging side and help for UCA-mediated drug delivery on the therapy side.  We are worked on both experimental and modelling approaches to study these phenomena.