Microbubble-enhanced HIFU therapy for vascularized tumors using Levovist contrast agent

Abstract

High-intensity focused ultrasound (HIFU) has enormous potential in the treatment of cancers; however, there is still plenty of challenges associated with using acoustic energy to treat vascularized tumors. Among them, the blood flow cooling reduces the treatment efficiency significantly and results in a long treatment period. Various studies have shown that the HIFU improves cancer treatment by targeting the cancer tissue. Unfortunately, the issues related to vascularization have remained unsolved. In the present study, through a novel approach, a promising strategy is proposed by injecting Levovist contrast agent solution in the vascularized tumor. The complicated interaction between the Levovist microbubble (MB) and the ultrasonic waves is innovatively modeled by considering the coupled effect of HIFU wave propagation, fluid flow, MB oscillations, and transient heat transfer for a multi-layered porous model of liver tumor. The proposed strategy is evaluated in terms of the extent of irreversible TD and treatment duration. The results reflect the role of MB oscillation on the temperature rise, as injection of a 2 μm-MB during 15 s of HIFU sonication increases the temperature by 9.61% compared to no-MB condition. Meanwhile, the MB oscillation advances the irreversible damage, and tumor cells undergo thermal ablation by 48.94% earlier than the case with no-MB agent. Additionally, it is found that the MB size has a substantial effect on the amount of heat deposition. At an operating condition of 1.25 MHz and 10 W, the viscous power deposition for a 2 μm-MB is3.81 mW, while for a 50 μm-MB, it is reduced to 0.96 mW. On the contrary, the heat source due to the secondary acoustic power deposition is proportional to the MB size, as it increases from 60.5 mW for a 2 μm-MB to 180 mW for a 50 μm-MB, demonstrating a 2.97-fold increase. Eventually, an assessment of the extent of the necrotic area shows an increase at all frequencies by injecting an MB into the tumor area. At an operating condition of 1.5 MHz, oscillation of 2 μm-MB expands the necrotic area by 4.01% compared to the no-MB condition. Based on the obtained results, the injection of Levovist contrast agent solution in the vascularized tumor can be regarded as an effective method for reducing the treatment time and avoiding several sonication.