Double Passive Cavitation Detection

By Daniel King, Graduate Student

Ultrasound contrast agents (UCAs) are microbubbles (typically 1-10 µm in diameter) consisting of a gaseous core surrounded by a thin shell. UCAs respond in the presence of ultrasound by expanding and contracting in an oscillatory cycle; at small amplitudes this response is nearly linear while at larger amplitudes the response becomes nonlinear to the point of transient collapse of the bubble. Recent research has focused on the use of UCAs in a variety of functional ultrasonic applications, such as UCA-enhanced thrombolysis, angiogenesis, and sonoporation. However, there is often much uncertainty over the nature of the microbubble response and hence the physical mechanisms promoting these bioeffects.

The double passive cavitation detection (DPCD) setup is designed to experimentally observe large amplitude behavior of single UCAs through acoustic means. It consists of three confocally aligned transducers, one which is used to insonify and two which are used to passively receive (Figure 1). By comparing the signals collected from the two aligned receive transducers, uncertainty as to the precise location of the microbubbles is reduced compared to similar systems which use only one receive transducer.

Figure 1: The holder and a schematic showing the alignment of the transducers.

After removing the signals which contain no or multiple UCAs as well as those which contain a single UCA outside the confocal region, the signals are classified into two categories. Signals which exhibit a principle response (due to the pulsed insonifying wave) followed by a postexcitation signal (PES) - a broadband spike separated in time from the principle response - are distinguished from those exhibiting only a principle response (Figure 2). It is hypothesized that the PES is caused by the rebound of a free (i.e. unshelled) gas bubble rebound which has escaped from the UCA, hence a signal exhibiting a PES is considered to have transiently collapsed whereas a signal without PES is considered to be in stable oscillation [1].

Figure 2: The upper figures show a signal containing both the principle response and a postexcitation signal; the lower figures show a signal containing only the principle response.

By comparing signals the number of signals with a PES to the total number of single in-focus responses (with PES + principle response only), we observe that the percentage of transient collapse increases as peak rarefactional pressure (PRP) in the confocal region increases (Figure 3). These results can be fit by logistic regression to determine 5%, 50%, and 95% collapse thresholds, which shows that percentage of collapse decreases as the center frequency increases (Figure 4).

Figure 3: Percent of single UCAs with postexcitation (PES) as a function of peak rarefactional pressure (PRP). These results are for a 3 cycle, 2.8 MHz pulse and Definity UCAs.

Figure 4: Thresholds of collapse determined from logistic curves for Definity microbubbles, plotted in peak rarefactional pressure in MPa against frequency in MHz.

References

[1] Ammi, A. Y., Cleveland, R. O., Mamou, J., Wang, G. I., Bridal, S. L. and O'Brien, W. D., Jr. "Ultrasonic Contrast Agent Shell Rupture Detected by Inertial Cavitation and Rebound Signals," IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 53: 126-136 (2006).