Gas Embolotherapy for the Treatment of Cancer

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

0301278 Bull The delivery of emboli to arterial blood flow with the goal of flow occlusion, or embolotherapy, is a potential means to treat a variety of cancers, particularly heptatocellular carcinoma (HCC). A major difficulty in embolotherapy is restricting delivery of the emboli to the tumor, i.e. minimizing ischemia of healthy tissue, without extremely invasive procedures. The proposal focused on the potential of a novel gas embolotherapy. Liquid droplets, which are small enough to pass through capillaries, are introduced into the vascular flow, and are subsequently vaporized via ultrasound near the tumor allowing gas bubbles, which are considerably larger than the liquid drops from which they originated, to occlude flow in the tumor. This minimally invasive technique will allow selective delivery of gas emboli to the tumor and is well suited to repeated doses and long term use. The proposed research uses computational and experimental studies to provide fundamental understanding of the physical phenomena of vessel occlusion by gas emboli. The research will use advanced computational methods, animal experiments, and benchtop experiments to show proof of concept of this novel gas embolotherapy technique, and will provide optimized strategies for maximum occlusion of flow in tumors. Animal experiments will provide information on the temporal evolution of flow occlusion in VX2 carcinoma following a dose of gas emboli and on the effects of a second dose on flow occlusion. A computational model will be developed for single bifurcations and a branching network of bifurcations. Flow occlusion will be investigated for macro-scale (arteries) and micro-scale (capillaries) bifurcations. The effects of bifurcation orientation, geometry, and size; driving pressure; bubble size; and the presence of surfactants will be investigated to optimize treatment plans and to elucidate the competition between transport mechanisms. Detailed temporal and spatial information on the dynamics of bubbles sticking in tubes and tube networks will be obtained and applied to gas embolotherapy. These predictions will be compared directly to bench top experiments, at both size scales, for validation and refinement of the model.