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Antivascular Ultrasound for Cancer Treatment: The Role of Thermal Effects

C Sehgal

C Sehgal*, S Hunt, B Levenback, A Wood, Univ Pennsylvania, Philadelphia, PA

TU-C-144-2 Tuesday 10:30AM - 12:30PM Room: 144

Purpose: Tour previous studies¹ have demonstrated that low-intensity ultrasound (1~2 W/cm², 0.2-0.3 MPa) in the presence of microbubbles disrupt tumor vasculature and behaves as an antivascular agent for the treatment of cancer. Although the antivascular effect is potent and reproducible, the mechanism of action is not fully understood. The goal of this study we evaluate the role of thermal effects in antivascular ultrasound.

Methods: Studies were performed in mice with subcutaneous melanoma (K1735). Antivascular ultrasound (AVUS) therapy was performed at 1 and 3 MHz. During treatment temperature was measured with a fine wire thermocouple. Tumor vascularity (percentage area of perfusion, PAF) was assessed before and after each test and sham treatment with contrast-enhanced Doppler US imaging. Simulations of microbubble induced heating were performed for mono- and polydisperse (lognormal distribution) microbubbles under varying conditions of experiments and blood flow

Results and Conclusions: AVUS reduced the tumor vascularity at both 1 MHz and 3 MHz. The vascularity reduction at 3 MHz was two times greater than with 1 MHz treatment. The enhanced antivascular action at 3 MHz was significant (P=0.02). The measured temperature increase was 5.2 ± 1.4°C for the 1 MHz ultrasound and 10.2 ± 2.7°C for 3 MHz ultrasound. Consistent with the experimental observations modeling showed that microbubble induced temperature increased more rapidly at 3 MHz than at 1 MHz. The observation that there is greater neovascular disruption and temperature change 3 MHz than at 1 MHz suggests that the ultrasound antivascular activity is primarily thermal in nature, although inertial cavitational effects cannot be excluded. The tissue response to antivascular ultrasound injuries could further stimulate an immune response and induce endogenous vaccination.

1. Wood et al, Acad. Rad., 15, 1133, 2008; Levenback et al, JASA, 131, 540, 2012; IEEE Ultrasonics 2012.

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