## 2 Materials and Methods  
### Electrical Design of HIFU System  
The first feature of this study was designing a compact electrical circuit to drive the high-power transducer. A single element piezoelectric HIFU transducer (H-148, Sonic Concept, Woodinville, WA, USA) with the electrical power up to 400 W was chosen for the experiment. Several essentially designed parameters for the electrical HIFU system were defined depending on the manufacturer's specification of the transducer. The output signal frequency was fixed at 2 MHz to resonate with the chosen transducer, thus resulting in the highest ultrasonic power. The dual-channel MOSFET switching method was the primary principle to double the acoustic power of the transducer by creating positive-negative voltage output signals [31; 32; 33]. To minimize the overall size of HIFU design, the electrical system was divided into two individual printed circuit boards (PCB)--a power and control board as shown in Figure 1a. The 3D design of the HIFU system with the H-148 commercial transducer is also denoted in Figure 1b. There are several blocks belonging to the control, with the 32-bit microcontroller (PIC32 MX795F512L, Microchip Technology Inc., Austin, TX, USA) acting as the core of the whole system. In order to measure the temperature at the focused point precisely, the 1.1-mm diameter thermocouple probe along with the miniature K-Type panel socket (R-FMTC-K-FF, RS Pro, [PERSON], Hong Kong, China) was used with the accuracy of \(\pm 1\)\({}^{\circ}\)C. The temperature at the thermocouple tip was converted to the electrical signal by 24-bit ADC (AD7739, Analog Device, Northwood, MA, USA) before being transmitted to the microcontroller every 0.5 s through SPI communication. The acquired target temperature was subsequently transferred to the PC through a COM port using USB UART IC (FT232 RL, FTDI Ltd., Glasgow, UK) every 1 s, which was set by a registered timer. The waveform generation block included a resistor set oscillator (LTC1799, Analog Device, Northwood, MA, USA) used to create the low power 5 V-squared signal with a frequency range from 1 kHz to 33 MHz. This operating frequency could be modified by a single digital potentiometer (MCP41100 Microchip Technology Inc., Austin, TX, USA) whose resistance could be programmable by the microcontroller via SPI interface. For setting the output frequency of the electrical system, the value of the corresponding resistance was calculated by the following equation:  
\[R_{SET}=\frac{10k\times 10 MHz}{f_{OUT}}, \tag{1}\]  
As mentioned above, the digital potentiometer needed to be changed to the resistance of 50 k\(\Omega\) to form the frequency of 2 MHz, and the microcontroller was programmed to transmit an amount of the bit required. On the power board, a 2-MHz squared wave input signal with the duty cycle 50%, which coincides with the 5 V TTL standard, was created by waveform generation block, then amplified by a 5 V MOSFET driver (EL7158 ISZ, Renesas Inc., Milpitas, CA, USA) to obtain the high power 5 V signal. The output signal from the previous stage was then further amplified by the 12-V MOSFET driver EL7158 ISZ to generate the 12 V high power signal which is used to excite the switching event of the MOSFET. The 100V MOSFETs (Si4590 DY, Vishay Intertechnology, Malvern, PA, USA) in this model were the dual-type, including NMOS and PMOS as two switching channels. The 12 V squared waveform signal that came from the MOSFET driver was the single input for both of them. Fundamentally, if V_gs > 0, NMOSFET was activated; meanwhile, the PMOSFET was enabled if V_gs < 0. When MOSFET was  
Figure 1: HIFU system: (**a**) schematic diagram (**b**) 3D design. in ON-state, the current from the power supply was supplied to the input pins of MOSFET ICs, leading to the generation of high-power output drive signal for HIFU transducer.