An investigation of contrast-agent shell-rupture threshold in response to overpressure

The stiffness of ultrasound contrast agent (UCA) shells is a critical parameter that determines responsiveness to acoustic excitation and half-life in circulation. The current study investigates the static pressure threshold for UCA rupture, which potentially can be used to infer the material properties of the UCA-shell. Polymer-shelled UCAs (POINT Biomedical) with a nominal mean diameter of 3 ¿m were subjected to overpressure from 3.5 to 155 kPa over a one hour duration while being imaged using a CCD-based video-microscope (50X magnification) at 1 frame/s. The static pressure corresponding to each image of the UCAs was recorded. A semi-automated post-processing algorithm was employed to determine the size and the static pressure threshold for rupture for each individual UCA. The majority of UCAs did not respond to static pressure change until the threshold for shell rupture was exceeded. Shell rupture resulted in abrupt destruction of the UCA. Eighteen trials resulted in a total of 976 valid UCAs, of which 851 ruptured when subjected to overpressure; 125 remained intact. The rupture pressures for 632 UCAs exhibited a Gaussian distribution (Gaussian group) centered around a mean pressure of 42.9 ± 18.7 kPa. The remaining 219 UCAs (residual group) ruptured at pressures ranging from 86 to 155 kPa with a mean of 118.2 ± 25.9 kPa. The distinctly different rupture behavior exhibited by the Gaussian, residual, and intact groups appeared to be unrelated to UCA diameter, but may have been related to surface defects.