Transport of Vascular Microbubbles through Multiple Vessel Bifurcations: A Model Study

Abstract

To model vascular bubble transport, we experimentally and theoretically investigated the transport of long gas bubbles suspended in liquid flowing through bifurcating vessel network. This work is motivated by a novel gas embolotherapy that we are developing. In this approach, perflurocarbon microbubbles are selectively formed in vivo and subsequently lodge to occlude blood flow to tumors. The bubbles originate from encapsulated liquid droplets that are small enough to pass through capillaries, allowing intravenous injection. The homogeneity of tumor necrosis depends on the transport and lodging of emboli. We used a bench top experimental model to explore the effects of flow pulsatility, heart rate, gravity, and bifurcation roll angle on bubble splitting and subsequent bubble lodging. We developed a corresponding time-dependent one-dimensional theoretical model. At a bifurcation roll angle of 45-degrees, the most distinct difference in splitting ratios between three physiologic frequencies was observed. The volume of lodged bubbles in the first generation channel was higher increased with roll angle, while bubble volume beyond the second bifurcation decreased with roll angle. The results elucidate the effects of pulsatile flow, and suggest the potential of gas embolotherapy to uniformly occlude blood flow to tumors. These vascular microbubble transport findings are also relevant to air embolism.