Bubble brilliance - how microbubbles provide contrast in ultrasound imaging

Microbubbles are the contrast agents of ultrasound imaging, enhancing the ultrasound signals as they circulate the blood. The most common microbubbles have a lipid shell and a heavy gas core, making them stable and biologically inert. They are primarily used to diagnose diseases in the liver and heart; but their use is at the cusp of rapid expansion. With microbubbles, traditional limitations with ultrasound imaging are being dismantled by new technologies, such as super-resolution imaging with spatial resolutions below 50 microm and ultrafast imaging with frame rates over 1,000 Hz. These technologies use the enhanced signal of microbubbles to provide incredible images never thought possible by ultrasound.
Despite the incredible potential of microbubbles, there remains huge uncertainty with how microbubbles provide contrast in the human body, leading to two problems: First, it is unclear what microbubble-enhanced images are displaying - are clinicians seeing where all the microbubbles are circulating, or is there a bias with images enhancing one kind of vessel over another? Second, new technologies for imaging cannot be developed without a better understanding.
Although microbubbles are well-described in water their behaviours in blood vessels are not. In water, microbubbles expand and contract to the ultrasound pulse, emitting a unique signal back to the emitter. In a capillary, some hypothesise that this signal is damped, because the bubble has less space to expand into. This could lead to changes in the resonance, strength, and shape of the emitted signal. These questions have implications in contrast as all microbubble signals comes from within vessels, and it is unclear how the signal differs in different sized vessels.
So far, all hypothetical explanations for how microbubbles behave in capillaries have been untested; because no one has found a way to observe microbubble oscillations in capillaries. Microbubbles oscillate at millions of times per second and in capillaries that are embedded in opaque tissue. In the proposed PhD project, the student will use our unique experimental platform to study ultrasound contrast in capillaries and other microvessels. The student will begin by learning how to extract and preserve slices of rat brains (ex vivo model) and create micron-sized capillaries in hydrogels (in vitro model). The microbubbles will be exposed to ultrasound while capturing its radial oscillations and listening to the sound that they emit. The optical and acoustic data will be analysed to explain how microbubbles oscillate and provide contrast in microvessels. We will then develop a microvascular imaging algorithm that boosts signals from microvessels.
By providing the first mechanistic understanding of how microbubbles provide contrast in microvessels, we hope to inspire technologies that will can image the microvasculature and differentiate its many parts.