Acoustic response from adherent targeted contrast agents

Abstract

In ultrasonic molecular imaging, encapsulated micron-sized gas bubbles are tethered to a blood vessel wall by targeting ligands. A challenging problem is to detect the echoes from adherent microbubbles and distinguish them from echoes from nonadherent agents and tissue. Echoes from adherent contrast agents are observed to include a high amplitude at the fundamental frequency, and significantly different spectral shape compared with free agents (p<0.0003). Mechanisms for the observed acoustical difference and potential techniques to utilize these differences for molecular imaging are proposed.

A non-linear three-dimensional model for quantifying microbubble dynamics

“…2(c)]. Experimental results reporting the same were first published by Zhao et al 16 (30% fundamental second and 70% fundamental third at 2 MHz/210 kPa). It should be noted that the experimental results were reported for a cloud of microbubble rather than a single microbubble.…”

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

“…Optical imaging was used to confirm bubble adhesion, and high-speed optical imaging was used to visualise the oscillations [86]. The adherent MBs oscillated symmetrically in the plane parallel to the wall (similar to a free-floating MB) and asymmetrically in the plane normal to the wall.…”

Ultrasound contrast agents : dynamics of coated bubbles

“…The first question, as was stated by Lindner [8], is whether bubbles adhering to a target cell produce strong enough acoustic signals. It was found that the response of adherent microbubbles is comparable to that of phospholipid-coated microbubbles [96,97]. However, it remains to be seen if the concentration of adherent microbubbles in vivo will be high enough to produce signals in the order of normal contrast-enhanced ultrasound in perfusion imaging.…”

“…Therefore it would be beneficial to distinguish acoustically between adherent and freely circulating microbubbles. Considerable changes between adherent and non-adherent microbubbles were found, such as a decrease in the acoustic response of adherent microbubbles with respect to non-adherent microbubbles [96] and a change in the spectral response [97]. In chapters 6 and 7 of this thesis it was shown that the close proximity of a wall changes the bubble dynamics.…”

“…the non-invasive detection of a specific disease at a molecular level, it will be crucial to develop methods for selectively detecting adherent UCA microbubbles that have bound to specific molecular targets from freely flowing ones, primarily based on a change in their acoustic response. Considerable differences in the amplitude of oscillations [95,96] and in the spectral response [97] were reported recently. In general, the studies on UCA microbubble dynamics suffer from the lack of control on bubble position, however, and they are therefore based on ensemble averaging and statistical observations of many different bubbles.…”