Colloidal science of ultrasound contrast agents

In this work, the behavior and properties of microbubble ultrasound contrast agents are measured and theoretically analyzed. Among these measurements are the microbubble size distribution, inertial cavitation threshold, and resonance frequency. The size distributions of populations of microbubbles are examined with a variety of different shell compositions. The size distributions are very similar for all the shell compositions measured; they contained a monomodal peak with a nearly Gaussian distribution. The mean size of the microbubbles did not change significantly for the compositional changes made in this study. This same set of microbubble shell compositions is then analyzed for their resonance frequency. This is accomplished by measuring the attenuation of a broadband chirp signal sent through a field of microbubbles and the frequency where the attenuation is the greatest the resonance frequency. It is found that as PEG mole fraction and molecular weight increase, the resonance frequency decreases. These shell compositions are then analyzed for their inertial cavitation threshold pressure and the results show that as PEG mole fraction increases, the inertial cavitation threshold increases. With increasing PEG molecular weight, however, the cavitation threshold decreases. With these experimental cavitation results, a predictive model is desired to explain the data theoretically. Based on the colloidal science principles, a new model for the oscillation of thinly shelled microbubbles is explained. For simple microbubble compositions, a predictive model can be applied for calculating material parameters of the microbubble shell. This equation is shown to hold for the experimental cavitation data collected during the course of this work. Using the information gathered in the previous chapters, a novel contrast agent was designed. The contrast agent is comprised of lipid microbubbles within the aqueous core of polymer shell microcapsules. This combination has the benefit of added patient safety (through the aversion of cell death) while providing similar contrast to commercially available contrast agents. The contrast agent accomplishes this by shielding the microbubbles from the incident sound pressure and preventing their expansion beyond the threshold radius. The design of the contrast agent is also inherently a drug delivery vehicle which caters to both hydrophilic and hydrophobic drugs.