Abstract

Antivascular ultrasound consisting of low-intensity sonication in the presence of circulating microbubbles of an ultrasound contrast agent has been demonstrated to disrupt blood flow in solid cancers. In this study a mathematical framework is described for the microbubble-induced heating that occurs during antivascular ultrasound. Biological tissues are modeled as a continuum of microbubble-filled vasculature, cells, and interstitial fluids with compressibility equal to the sum of the compressibility of each component. The mathematical simulations show that the absorption of ultrasound waves by viscous damping of the microbubble oscillations induced significant local heating of the tissue vasculature. The extent and the rate of temperature increase not only depends on the properties of the microbubbles and the sonication parameters but is also influenced markedly by the blood flow. Slow flow conditions lead to higher tissue temperatures due to a stronger interaction between microbubbles and ultrasound and reduced heat dissipation. Because tumors have slower blood flow than healthy tissue, the microbubble-induced ultrasound antivascular therapy is likely to affect cancerous tissue more extensively than healthy tissue, providing a way to selectively target the vasculature of cancers.

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