Correlation of rupture dynamics to the nonlinear backscatter response from polymer-shelled ultrasound contrast agents

Abstract

Polymer-shelled ultrasound contrast agents (UCAs) may expel their encapsulated gas subject to ultrasound-induced shell buckling or rupture. Nonlinear oscillations of this gas bubble can produce a subharmonic component in the ultrasound backscatter. This study investigated the relationship between this gas-release mechanism and shell-thickness-to-radius ratios (STRRs) of polymer-shelled UCAs. Three types of polylactide-shelled UCAs with STRRs of 7.5, 40, and 100 nm/μm were studied. Each UCA population had a nominal mean diameter of 2 μm. UCAs were subjected to increasing static overpressure ranging from 2 to 330 kPa over a duration of 2 h in a custom-designed test chamber while being imaged using a 200× magnification video microscope at a frame rate of 5 frames/s. Digitized video images were binarized and processed to obtain the cross-sectional area of individual UCAs. Integration of the normalized cross-sectional area over normalized time, defined as buckling factor (Bf), provided a dimensionless parameter for quantifying and comparing the degree of pre-rupture buckling exhibited by the UCAs of different STRRs in response to overpressure. The UCAs with an STRR of 7.5 nm/μm exhibited a distinct shell-buckling phase before shell rupture (Bf < 1), whereas the UCAs with higher STRRs (40 and 100 nm/μm) did not undergo significant prerupture buckling (Bf ≈ 1). The difference in the overpressure response was correlated with the subharmonic response produced by these UCAs. When excited using 20-MHz ultrasound, individual UCAs (N = 3000) in populations that did not exhibit a buckling phase produced a subharmonic response that was an order of magnitude greater than the UCA population with a prominent pre-rupture buckling phase. These results indicate the mechanism of gas expulsion from these UCAs might be a relevant factor in determining the level of subharmonic response in response to high-frequency ultrasound.

Fig. 1

Schematic of the experimental setup for the overpressure study. Changes in the morphology of UCAs subjected to static overpressures in a glycerol-filled chamber were observed with a video microscope.

Fig. 2

Schematic diagram of the experimental setup for UCA-backscatter study. Individual UCAs were passed through the focal region of a 20-MHz transducer and their responses to 20-MHz, 20-cycle tonebursts were recorded.

Fig. 3

Sequence of images showing buckling and subsequent rupture with the corresponding pressure values for the three types of UCAs.

Fig. 4

(a) The area under the curve of normalized area versus normalized time gives the buckling factor (B_f). Illustration of the difference in buckling factors for UCAs with lower STRR (PB127) and higher STRR (PH37). (b) ANOVA analysis of B_f values for the three UCA types.

Fig. 5

Buckling and rupture pressures for the three UCA types.

Fig. 6

SHS computed from backscatter measurements of individual UCAs for the three UCA types in response to a 20-MHz, 20-cycle tone-burst excitation. Data were taken from [18].