Unfocused ultrasound waves for manipulating and imaging microbubbles

With unfocused plane/diverging ultrasound waves, the capability of simultaneous sampling on each element of an array transducer has spawned a branch known as high-frame-rate (HFR) ultrasound imaging, whose frame rate can be two orders of magnitude faster than traditional imaging systems. Microbubbles are micron-sized spheres with a heavy gas core that is stabilized by a shell made of lipids, polymers, proteins, or surfactants. They are excellent ultrasound scatters and have been used as ultrasound contrast agents, and more recently researched as a mechanism for targeted drug delivery. With the Ultrasound Array Research Platform II (UARP II), the objective of this thesis was to develop and advance several techniques for manipulating and imaging microbubbles using unfocused ultrasound waves. These techniques were achieved by combining custom transmit/receiving sequencing and advanced signal processing algorithms, holding promise for enhanced diagnostic and therapeutic applications of microbubbles. A method for locally accumulating microbubbles with fast image guidance was first presented. A linear array transducer performed trapping of microbubble populations interleaved with plane wave imaging, through the use of a composite ultrasound pulse sequence. This technique could enhance image-guided targeted drug delivery using microbubbles. A key component of targeted drug delivery using liposome-loaded microbubbles and ultrasound is the ability to track these drug vehicles to guide payload release locally. As a uniquely identifiable emission from microbubbles, the subharmonic signal is of interest for this purpose. The feasibility of subharmonic plane wave imaging of liposome-loaded microbubbles was then proved. The improved subharmonic sensitivity especially at depth compared to their counterpart of bare (unloaded) microbubbles was confirmed. Following plane wave imaging, the combination of diverging ultrasound waves and microbubbles was investigated. The image formation techniques using coherent summation of diverging waves are susceptible to tissue and microbubble motion artefacts, resulting in poor image quality. A correlation-based 2-D motion estimation algorithm was then proposed to perform motion compensation for HFR contrast-enhanced echocardiography (CEE). A triplex cardiac imaging technique, consisting of B mode, contrast mode and 2-D vector flow imaging with a frame rate of 250 Hz was presented. It was shown that the efficacy of coherent diverging wave imaging of the heart is reliant on carefully designed motion compensation algorithms capable of correcting for incoherence between steered diverging-wave transmissions. Finally, comparisons were made between the correlation-based method and one established image registration method for motion compensation. Results show that the proposed correlation-based method outperformed the image registration model for motion compensation in HFR CEE, with the improved image contrast ratio and visibility of geometrical borders both in vitro and in vivo.