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Ultrasonic imaging is a relatively cheap, reliable diagnostic technique. When taking into account the absolute hospital operating expenses, X-ray and ultrasound have approximately the same price per examination. Other imaging techniques are roughly three times as expensive, except for catheterization, which is twenty times as expensive. However, X-ray is a less desirable imaging technique than ultrasound, due to the negative radiation effects. Therefore, novel ultrasound-based imaging techniques are being developed that may compete with other imaging techniques. In clinical ultrasound, blood cells cannot be differentiated from surrounding tissue, due to the low acoustic impedance difference between blood cells and their surroundings. Since imaging blood flow and measuring organ perfusion are desirable for diagnostic purposes, a contrast agent has been added to the blood that helps to differentiate between blood and other tissue types. Ultrasound contrast agents consist of low-solubility gas microbubbles encapsulated by a stabilizing shell. With mean diameters below 6 micron, these microbubbles are small enough to pass through the lung capillaries. Ultrasonic contrast-enhanced imaging applications depend on the detectability of microbubbles. The detectablility in turn depends on the ultrasonic pulsing scheme, which in turn depends on the predictability of the contrast microbubble behaviour. At acoustic pulse lengths and pressures much higher then allowed in diagnostic imaging, ultrasound has therapeutic applications, such as tumour treatment and lithotripsy. But also at clinical diagnostic settings, ultrasound may be used in therapy. It has been proven by numerous groups, that the cellular uptake of drugs and genes is increased, when the region of interest is under ultrasound insonification, and even more when a contrast agent is present. This increased uptake has been attributed to the formation of transient porosities in the cell membrane, which are big enough for the transport of drugs into the cell. The transient permeabilisation and resealing of a cell membrane is called sonoporation. Combining ultrasound contrast agents with therapeutic substances may lead to a simple and economic method to instantly cure upon diagnosis, using conventional echo machines. Currently, physical models describing contrast microbubble behaviour have limited predictive power. In this project, new models will be developed for encapsulated microbubble oscillation, coalescence, and disruption. Using camera footage of contrast microbubbles during ultrasound insonification and ultrasonographic imaging, the effectiveness of the models is quantified. With the results of this project, the optimal ultrasound transmitting signal can be defined for medical imaging, as well as the optimal contrast agent shell properties for therapeutic applications.An experimental setup will be built for simultaneous optical and acoustical observations of ultrasound contrast agents. Based on our observations of bubble oscillation, coalescence, fragmentation, and jetting, new predictive models will be developed and validated. Since the use of ultrasound contrast agents has become increasingly popular, and their applications have been multiplied, a new safety standard in ultrasonic imaging will have to be defined in the near future. This project will result in a sharper definition of a safety index.An inroad to enhanced perfusion imaging by a UK-led group would have significant financial ramifications for the NHS as well as clear health benefits to the UK population at large. The noninvasivity of contrast-based methods would be a further benefit to patients. The low costs of ultrasound equipment and ultrasound contrast agents will certainly lead to an increased use of ultrasound-based therapy.
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