Enhanced Mild Hyperthermia Using Focused Ultra-Sound and Microbubbles: An Experimental Study

Traditional cancer treatments like chemotherapy often involve systemic drug injection, affecting healthy tissues and causing unwanted side effects. Focused ultrasound (FUS), with its precise targeting capability, offers a solution by raising the temperature of cancer tissue to 39-45°C. This mild hyperthermia enhances tumor blood flow and improves chemotherapy drug absorption by cancer cells. To optimize this promising approach, a comprehensive understanding of the effects of microbubble-enhanced FUS is crucial. In this study, for the first time, we extensively examined the impact of various FUS parameters—such as frequency, duty cycle, and input voltage—alongside microbubble concentrations on temperature variations. Our goal was to identify optimal conditions for mild hyperthermia applications. The results revealed that increasing ultrasound frequency, duty cycle, driving voltage, and microbubble concentration enhances heating rates and peak temperatures. Microbubble concentrations of 10<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> MBs/mL showed minimal effect, but at 10<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">8</sup> MBs/mL, significant temperature increases were observed, particularly at higher frequencies. To further understand the heating mechanism, we used a hydrophone to monitor acoustic signals during the process. The presence of microbubbles generated substantial broadband noise, indicating that inertial cavitation was a key factor in heating during FUS exposure. The noise signal’s power spectrum demonstrated that a higher duty cycle increased energy intensity, accelerating the heating rate. This study provides critical insights for adjusting ultrasound parameters and microbubble concentrations in clinical mild hyperthermia treatments, potentially enhancing the effectiveness of chemotherapy while minimizing side effects on healthy tissues.