Effect of Microbubble Ligation to Cells on Ultrasound Signal Enhancement

Abstract

Attachment of targeted microbubbles to rigid surfaces results in damping and a reduction of their acoustic signal, which is not seen when microbubbles are attached to cells. A reliable concentration versus intensity relationship can be expected from microbubble attachment to 2-dimensional surfaces until a very high site density is reached.

Molecular Imaging of Inflammation in Atherosclerosis With Targeted Ultrasound Detection of Vascular Cell Adhesion Molecule-1

“…In these mice, both CEU and en face microscopy were consistent with a diffuse and widespread attachment of VCAM-1-targeted microbubbles, the density of which was within the dynamic range for detection of microbubbles attached to a 2-dimensional surface. 27 The diffuse nature of attachment suggests that a surrogate large vessel may be used for evaluation when vascular inflammatory status is severe, although this was not directly tested. In ApoE Ϫ/Ϫ mice on chow diet, attachment of microbubbles targeted to VCAM-1 was more pronounced in regions of atherosclerotic plaque, consistent with reports on upregulation of VCAM-1 predominantly in regions prone to plaque development.…”

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.…”

Cardiovascular Molecular Imaging

“…However they oscillate less efficiently and generate a smaller amplitude signal compared to freely circulating microbubbles (27,39). On the other hand, it has been shown that attachment of targeted microbubbles to a cell surface such as endothelial cells, will improve stability of microubbles over time without damping the signal (40,41).…”