Insights into the roles of radiation forces in bubble mediated sonothrombolysis

Abstract

It is increasingly recognized that radiation forces on bubbles are relevant to a range of therapeutic applications such as sonothrombolysis. In this paper, we discuss work using high speed microscopy to investigate the interactions between ultrasound stimulated bubbles and the boundary of biologically relevant materials. Initial studies with fibrin gels (clots), demonstrated that bubbles could be stimulated to deform, penetrate, and damage the fibrin network. This highlighted two distinct processes where radiation forces play a central role: transporting bubbles from a vessel lumen to a target boundary and facilitating therapeutic effects at the target. To investigate the transport process, experimental data were acquired to assess translational bubble dynamics as a function of size and exposure condition, and this data were used to calibrate a model where both shell and history forces are captured. Experiments and modeling showed that both exposure scheme and flow rate can profoundly influence the number and size distribution of bubbles reaching a target site on a vessel boundary. Once at the boundary, cyclical deformations are induced by the bubble extending well into the material, and these are asymmetric on the forcing and recovery cycles. Deformation, as well as penetration and damage are found to be highly dependent on bubble size and exposure schemes. An improved understanding of these complex processes may facilitate improvements in applications involving large vessels, such as sonothrombolysis.