Non-destructive Evaluation of Ultrasound Contrast Agent

Abstract: Clinical ultrasound imaging techniques can be greatly improved by the use of ultrasound contrast agents (UCAs). While microbubbles (MBs) without shell are unstable and cannot be used for practical applications,a shell produced from biocompatible polyvinylalcohol (PVA) significantly improves chemical versatility and stability. The oscillation characteristics of a UCA are strongly dependent on concentration, applied pressure and viscoelastic parameters of the shell. Modifications in the shell as incorporation of antibodies or targeted molecules affect the bubble oscillation and resonance frequency of the MB suspension. In this presented work a tool for systematic characterization of UCAs is developed. Linear acoustic behaviour of PVA shelled MBs is examined. The acoustic driving pressure is kept below 100 kPa. The MB concentration is 1·10^{6} ml^{-1}. Attenuation and phase velocity profiles of ultrasound waves propagating through the UCA are measured using six narrow-band single crystal transducers that cover a frequency range between 1 and 15 MHz. The oscillation of a single bubble is modeled as a linear oscillator adapting HOFF’s model suitable for allshell thicknesses. The suspension is modeled through superposition of single bubbles. Knowing all parameters the resonance frequency of a MB suspension can be predicted. The model is fitted to experimental data to determine the viscoelastic shell parameters. The shell thickness is challenging to determine exactly and assumed to be either proportional to the outer shell radius or constant. Assuming a proportional shell thickness the calculated resulting shell parameters were shear modulus G_s = 14.5 MPa, shear viscosity η_s = 0.322 Pa·s and shell thickness d_s = 16 % of the outer radius. When instead assuming a constant shell thickness the determined parameters were in similar order of magnitude. Resonance frequency of the suspension was determined to 11.6 MHz. The developed tool can be used to characterize MBs with a modified shell independently of shell thickness and to predict resonance frequency of gas or air filled UCAs with known shell parameters.