Relationship between cavitation and loss of echogenicity from ultrasound contrast agents

Abstract

Ultrasound contrast agents (UCAs) have the potential to nucleate cavitation and promote both beneficial and deleterious bioeffects in vivo. Previous studies have elucidated the pulse-duration dependent pressure amplitude threshold for rapid loss of echogenicity due to UCA fragmentation. Previous studies have demonstrated that UCA fragmentation was concomitant with inertial cavitation. The purpose of this study was to evaluate the relationship between stable and inertial cavitation thresholds and loss of echogenicity of UCAs as a function of pulse duration. Determining the relationship between cavitation thresholds and loss of echogenicity of UCAs would enable monitoring of cavitation based upon the on-screen echogenicity in clinical applications. Two lipid-shelled UCAs, echogenic liposomes (ELIP) and Definity®, were insonified by a clinical ultrasound scanner in duplex spectral Doppler mode at four pulse durations (“sample volumes”) in both a static system and a flow system. Cavitation emissions from the UCAs insonified by Doppler pulses were recorded using a passive cavitation detection system and stable and inertial cavitation thresholds ascertained. Loss of echogenicity from ELIP and Definity® was assessed within regions of interest on B-mode images. A numerical model based on UCA rupture predicted the functional form of the loss of echogenicity from ELIP and Definity®. Stable and inertial cavitation thresholds were found to have a weak dependence on pulse duration. Stable cavitation thresholds were lower than inertial cavitation thresholds. The power of cavitation emissions was an exponential function of the loss of echogenicity over the investigated range of acoustic pressures. Both ELIP and Definity® lost more than 80% echogenicity before the onset of stable or inertial cavitation. Once this level of echogenicity loss occurred, both stable and inertial cavitation were detected in the physiologic flow phantom. These results imply that stable and inertial cavitation are necessary in order to trigger complete loss of echogenicity acoustically from UCAs and this finding can be used when planning diagnostic and therapeutic applications.

Exploiting flow to control thein vitrospatiotemporal distribution of microbubble-seeded acoustic cavitation activity in ultrasound therapy

“…In this paper we have confirmed that the reported improvement is directly correlated with the persisting MB-seeded acoustic cavitation activity (figures 3,6). (Radhakrishnan et al 2013). Thus, by defining the number of the emitted ultrasound cycles at a specific pressure, one can adjust the longevity of FUS-MBs interactions and control the spatiotemporal distribution of acoustic cavitation.…”

Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

“…At a 0.34 MPa pressure exposure, it is likely that NO was released from the bubble liposomes gradually over a number of acoustic cycles. Radhakrishnan et al 60 have detected loss of echogenicity from contrast agents at acoustic pressures below the stable and inertial cavitation thresholds. In their experiments using Definity ® and echogenic liposomes, the onset of stable and inertial cavitation was concomitant with an 80% loss of echogenicity.…”

“…This was likely due to the quenching of excess NO by hemoglobin, a reaction well documented in vivo. 16,40,65 Because free hemoglobin quenches NO a thousand times faster than hemoglobin within intact erythrocytes, 60,69 the presence of free hemoglobin in the bath likely resulted in a weaker vasorelaxation than expected in vivo in the absence of hemolysis.…”

Scavenging dissolved oxygen via acoustic droplet vaporization

“…A piecewise linear fit of the mean grayscale value as a function of the peak rarefactional pressure was used to define the acoustic droplet vaporization threshold. The threshold was defined as the rarefactional pressure amplitude corresponding to the intersection between the first two lines of the piece-wise linear fit based on previous studies [3,31] (Figure 2b). The threshold was determined for four vials of the PFP droplets (one measurement per vial) and the mean and standard deviation of the thresholds were computed after confirming the normality of the data using the Jarque Bera test in MATLAB ® (Mathworks, Natick, MA, USA).…”