The effect of boundary proximity on the response of individual ultrasound contrast agent microbubbles

Abstract

The effect of boundary proximity on ultrasound contrast agent microbubble emissions can play an important role in the context of both targeted microbubble imaging and contrast imaging of microvascular perfusion. In this study, individual microbubbles (n = 104) were insonicated as a function of distance from either a polystyrene membrane (OpticellTM) or a compliant agarose boundary up to offset distances of 1000 µm by use of an optical trapping setup. An ‘acoustic spectroscopy’ approach was employed, which entailed transmitting a sequence of tone bursts with centre frequencies ranging from 4 to 13.5 MHz to determine the frequency and amplitude of maximum radial response (fMR and AMR, respectively). For the OpticellTM case, microbubble response exhibited a distinctly oscillatory pattern with increasing offset distance, with an average maximal change in peak frequency and scattered pressure amplitude of 29.6% and 73.2%, respectively, as compared to their values adjacent to the boundary. For the agarose case, microbubbles exhibited an increase in fMR and a decrease in AMR with respect to their values in free space. Simulations indicate the oscillatory dependence on OpticellTM distance stems from wavelength-dependent interference phenomena. A recent analytical bubble-boundary model is in broad agreement with the relative AMR changes due to the more compliant agarose layer, however underestimates the change in relative fMR at the boundary.