ACOUSTIC CHARACTERIZATION OF ULTRASOUND CONTRAST AGENTS FOR ADVANCED BIOMEDICAL IMAGING

This thesis introduces the use of a series of new experimental systems, and the corresponding signal processing techniques, to investigate the acoustic properties of ultrasound contrast agents, both in flowing and static conditions. Considered properties include backscatter, attenuation, resonance phenomena, nonlinear oscillation and destruction mechanisms as a function of the applied ultrasound parameters. These properties have been investigated by acoustic and granulometric measurements conducted on a last generation microbubble experimental contrast agent (BR14, Bracco Research SA, Geneva, Switzerland) for frequencies in the medical diagnostic range. In the first part of this work, a new tissue-mimicking phantom was designed, manufactured and employed to evaluate microbubble behavior in very similar conditions to those encountered inside the human body. During these studies microbubbles were insonified by means of a common commercial echograph while flowing through the phantom, that had been inserted into an ad hoc assembled flow circuit, aimed to simulate human microcirculation conditions. In addition, in order to explore possible improvements in signal processing techniques, the echograph was connected to a prototypal platform for acquisition and independent processing of the raw unfiltered radiofrequency signals. In the second part, whose focus was on the determination of microbubble intrinsic properties, microbubbles were studied in static conditions, employing single-element ultrasound probes driven by laboratory devices, offering higher flexibility in terms of generated signal parameters, and linked to high-performance data acquisition boards. In particular, a new methodology has been developed to study microbubble destruction mechanisms and three main patterns have been identified in the microbubble acoustic behavior, also establishing the boundary conditions for the onset of the corresponding underlying phenomena. These findings could represent interesting bases for theoretical modeling of microbubble acoustic behavior from linear oscillation to complete shell disruption. The outcome of each performed study has been also analyzed and interpreted to exploit possible implications for the improvement of current clinical techniques or for the potential development of new ones. A global characterization of the acoustic behavior of the studied contrast agent is finally provided, together with many indications for its effective employment in further in vivo testing and clinical trials.