Microbubble ultrasound contrast agent as an enhancer of high intensity focused ultrasound (HIFU) therapy for liver cancer
Fuminori Moriyasu Department of Gastroenterology & Hepatology
Tokyo Medical University
Tokyo, Japan
Abstract:
INTRODUCTION:
Microbubble contrast agents have been used clinically for diagnosis of ultrasound contrast imaging. It is known that microbubbles enhance the effect of high intensity focused ultrasound (HIFU) therapy when HIFU energy is exposed to the cancer tissue which contains microbubbles.
PURPOSE:
Purpose of this study is to optimize the dose of microbubble contrast agent which enhances most effectively the HIFU effect.
MRTHODS:
Ultrasound contrast agent, perflubutane microbubble (Sonazoid, GE Health Care, Milwaukee, USA) was used for enhancer of HIFU treatment. Sonazoid was injected intravenously to 32 rabbits varying the dose from 0.00015-0.015 ml/kg body weight. The liver was retrieved after sacrificing rabbits 30 minutes after Sonazoid injection. HIFU energy was exposed to the liver in ex vivo raging the power of HIFU energy from 15 to 300 Watts. HIFU effects were evaluated by measuring the echogenic area on the ultrasound imaging obtained just after HIFU exposure. Pathological changes were evaluated using formalin fixed tissues.
RESUTS:
The size of HIFU effect was widened according to the power of HIFU and the dose of microbubbles. The optimal dose of Sonazoid for maximum HIFU effect enhancement was 0.007 ml/kgBW, which was equal to 1/20 of the optimal dose for contrast ultrasound imaging. The HIFU effect was decreased when the Sonazoid dose was over the optimal dose.
DISCUSSION:
Sonazoid microbubbles are accumulated in the liver after intravenous injection. This is explained by the phenomenon of phagocytosis of Sonazoid microbubbles by the macrophage living in the sinusoidal space. Therefore, Sonazoid microbubble is suitable for enhancing HIFU effects in the liver as cavitation nuclei. Over dose than the optimal tissue concentration of microbubbles might disturb penetration of HIFU energy by gas existence. Ablation area can be increased up to several tens times larger than without microbubbles.
Keywords: HIFU, microbubble, ultrasound, cavitation, liver cancer
