Modeling of thermal effects in antivascular ultrasound therapy

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 microbubbleinduced 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.

Optimization of low-frequency low-intensity ultrasound-mediated microvessel disruption on prostate cancer xenografts in nude mice using an orthogonal experimental design

“…It has been demonstrated that thermal, mechanical, such as cavitation and other non-linear mechanisms, and sonochemical effects are likely to contribute to the anti-vascular activities of microbubbles (7). These acoustic mechanisms may act either to directly or indirectly damage vascular structure by inducing tissue response to the thermal, mechanical or sonochemical effects (7).…”

“…Heating is produced by the absorption of US energy through viscous damping of oscillating microbubbles (7). The network of tumor blood vessels is disorganized and tortuous and is likely to lead to the localized entrapment of microbubbles (7). As a result, the microbubbles are likely to reside in the US beam longer in the tumor tissue compared with the normal tissue.…”

“…In addition, the blood vessel blockage caused in the targeted regions may result in increased heating. This temperature differential in tissues makes it possible to selectively disrupt tumor blood vessels, without causing a significant adverse effect on normal blood vessels (7). Therefore, it may be hypothesized that the thermal effect is an important component of targeting the tumor neovasculature.…”

“…This indicates that cavitation may not be an exclusive factor in USMB, and the participation of heating in the therapeutic process cannot be excluded. Heating is produced by the absorption of US energy through viscous damping of oscillating microbubbles (7). The network of tumor blood vessels is disorganized and tortuous and is likely to lead to the localized entrapment of microbubbles (7).…”

“…In the absence of angiogenesis, tumor growth is restricted to an extremely small volume, and tumor cells do not spread into the circulation (6). Tumor blood vessels are weaker in structure and less competent compared with the blood vessels of the normal tissues (7). Since the survival and growth of solid tumors depends on tumor angiogenesis and physiological defects in the tumor neovasculature, there is considerable interest in developing techniques that target this neovasculature for cancer therapy.…”