Fundamental studies and novel approaches enabling the generation and characterization of ultrasound and photoacoustic contrast to probe the structure and function of cells, biomaterials and biological systems

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The proposal's objective is to develop techniques to characterize the structure and functional state of cells and tissues using ultrasound, acoustic and photoacoustic techniques. The investigator's work to date has focused on using optical and ultrasound scattering as a means to characterize cells and tissues, with a particular emphasis on the non-invasive detection of cell death. These techniques will be refined based on new knowledge generated from recent theoretical and experimental findings. Part of the proposed work would represent incremental but significant improvements to technical aspects of the ultrasound and optical techniques. Based on our recent findings on how microbubbles respond to ultrasound and, excitingly, how nanobubbles can be used for imaging therapeutic purposes, we propose to make measurements that will confirm the theoretical models we have developed. We have demonstrated the critical role of the bubble shell in these contrast agents and will manipulate the shell properties and measure the bubble response to ultrasound. New photoacoustic techniques will be developed, which will allow for clearer images and more accurate measurements of functional tissue parameters. These are based on sophisticated computer models that consider how a user scans an ultrasound transducer over a target area. Novel photoacoustic approaches are proposed to probe the content of aerosolized material by detecting the photoacoustic waves that travel through the air. To probe the mechanical properties of cells and bubbles, we will use techniques developed from the previous Discovery Grant. We will use an acoustic flow cytometer to measure the scattering from single particles and use models to calculate the relevant properties. Finally, we will further develop a new technique based on the response of cells to vibrations in a microfluidic channel. We discovered that cells exposed to a vibrating substrate create microflows that allow us to probe their mechanical properties. The development of these techniques will aid in the non-invasive and continuous monitoring of the functional states of cells and tissues, with potential applications in medicine.