CN114451988A - Microwave ablation real-time carbonization regulation and control method based on bioimpedance - Google Patents

Abstract

The invention discloses a microwave ablation real-time carbonization regulation and control method based on bioimpedance, which comprises the following steps: s1, constructing a biological impedance acquisition device applied to microwave ablation real-time carbonization regulation and control; s2, acquiring real-time change data of the biological impedance in the ablation process; and S3, adjusting the output power of the microwave source according to the change of the biological impedance. The invention has the beneficial effects that: (1) the invention indirectly reflects the coagulation and carbonization conditions of tissues at the ablation part by measuring the biological impedance, and compared with single-point temperature measurement, the biological impedance can reflect the ablation effect of one region between two copper foil electrodes; (2) the invention adopts the high-precision impedance measurement analog front-end chip AD5940 to realize impedance measurement, and the impedance measurement function is easy to be integrated into the existing microwave ablation instrument, so the cost is low; (3) the method has great significance for judging the real-time curative effect of the tumor microwave ablation, and has important value for carrying out carbonization regulation and control on the tumor microwave ablation.

Description

Real-time carbonization control method for microwave ablation based on bioimpedance

technical field

The invention relates to the technical field of microwave ablation precise treatment, in particular to a real-time carbonization control method of microwave ablation based on biological impedance.

Background technique

Microwave thermal ablation therapy is considered to be another new and effective method for the treatment of malignant tumors after surgery, chemotherapy, radiotherapy, immunotherapy, etc. It has played a huge role in tumor treatment and has been widely used in common tumors such as liver cancer, lung cancer, kidney cancer, thyroid cancer, colon cancer, and uterine fibroids. However, there are still many scientific and technical problems that need to be solved in microwave thermal tumor ablation, the most important of which is the real-time efficacy evaluation in microwave ablation therapy. At present, temperature is mainly used as a judging factor for tumor cell inactivation in clinical practice. Thermistors or thermocouples are inserted into the patient's body to measure the temperature of the ablation site. When the temperature reaches 60°C, it is determined that the tissue cells have been necrotic. However, this method can only measure the local temperature of the probe, and cannot reflect the overall temperature of the ablation area, so it cannot reflect the overall inactivation of the tissue in the ablation area, nor the carbonization of the entire tissue at high temperatures. Finding more accurate evaluation factors to achieve real-time evaluation of efficacy has become the key to accurate ablation.

Bioelectrical impedance technology is a detection technology that extracts physiological information related to human physiology and pathological conditions by using the electrical characteristics of biological tissues and organs and their changing laws. Due to the differences in electrical impedance of different biological tissues, the impedance characteristics depend on the composition and structure of biological tissues and the magnitude of the applied signal frequency, so this characteristic can help us better understand the physiological information of biological tissues. Microscopically, cells are composed of cell membranes and intracellular fluid, while cells are filled with extracellular fluid and extracellular matrix. The intracellular fluid and the extracellular fluid are composed of electrolytes with good conductivity, which can be equivalent to resistive components; the cell membrane is composed of phospholipid bilayers and proteins, which can be equivalent to capacitive components. Thus, intracellular fluid, cell membrane and extracellular fluid constitute a three-element bioimpedance model. From a macro perspective, biological tissue is composed of a large number of cells, and measuring the bioimpedance of human tissue can reflect the physiological condition of a large piece of biological tissue between electrodes.

Studies have shown that the pathological changes of human tissues and the inactivation of cells can lead to changes in bioimpedance on a macroscopic scale. During thermal ablation, as the temperature increases, the cell membrane ruptures and intracellular fluid escapes from the cell, resulting in a decrease in impedance; as the temperature continues to rise, the tissue dehydrates and evaporates, followed by carbonization, resulting in impedance significantly increased. The changes in bioimpedance during thermal ablation are significantly associated with coagulation and carbonization of biological tissues.

Impedance measurement instruments currently on the market have high measurement accuracy and wide measurement range, but are expensive, bulky, lack a host computer interface, cannot be integrated into existing microwave ablation instruments, and cannot perform subsequent processing of impedance data.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to provide a real-time carbonization control method for microwave ablation based on bioimpedance, which can reflect the ablation effect of an area between two copper foil electrodes, and is of great significance for evaluating the real-time curative effect of microwave ablation of tumors. Carbonization regulation of tumor microwave ablation is of great value.

In order to solve the above technical problems, the present invention provides a real-time carbonization regulation method for microwave ablation based on bioimpedance, which includes the following steps:

S1. Build a bioimpedance acquisition device for real-time carbonization regulation of microwave ablation;

S2. Obtain real-time change data of bioimpedance during ablation;

S3. Adjust the output power of the microwave source according to the change of the biological impedance.

Preferably, in step (1), the bioimpedance acquisition device includes a copper foil electrode, a high-precision impedance measurement analog front-end chip and an ARM microcontroller; the copper foil electrode is connected to the high-precision impedance measurement analog front-end chip through a wire, and the ARM microcontroller controls High-precision impedance measurement The analog front-end chip performs impedance measurement, receives the returned data and calculates the impedance value. The ARM microcontroller sends the impedance to the host computer for display through the communication module.

Preferably, the copper foil electrodes are attached to the surface of the microwave ablation needle; one of the copper foil electrodes is attached to the rear end of the microwave ablation needle dielectric sleeve 5 mm, and the other copper foil electrode is attached to the rear end of the dielectric sleeve 15 mm, the distance between the two is 10 mm; The copper foil electrodes are respectively connected to the bioimpedance measurement circuit board through wires.

Preferably, the high-precision impedance measurement analog front-end chip uses AD5940; AD5940 has a built-in digital waveform generator and a 12-bit digital-to-analog converter DAC to generate a sinusoidal excitation signal; the on-chip 16-bit, 800kSPS analog-to-digital converter ADC measures a sinusoidal input voltage up to 200kHz, The measurement results can be digitally filtered; the on-chip high-speed transimpedance amplifier HSTIA processes the 200kHz high-bandwidth sinusoidal input signal, and converts the weak current signal into a voltage signal that can be measured by the ADC; the on-chip discrete Fourier transform DFT engine performs the measurement results. DFT calculation, storing real and imaginary part measurements in corresponding registers.

Preferably, the ARM microcontroller selects STM32F411RET6 with a main frequency of 100MHz; the ARM microcontroller uses the serial peripheral interface SPI to communicate with the AD5940; the ARM microcontroller sends control commands to the AD5940 to configure the digital waveform generator, HSTIA of the AD5940 and ADC peripheral, and read the real part and imaginary part measurement results of response voltage and response current from the data FIFO; after reading the measurement results, it is converted into impedance by the ARM microcontroller.

Preferably, the communication module selects CH340C USB to serial port chip, and the baud rate is set to 115200bps.

Preferably, in step (2), the copper foil electrodes are attached to the surface of the microwave ablation needle, and are sent into the isolated pig liver along with the microwave ablation needle; the two copper foil electrodes are respectively connected to the bioimpedance measurement circuit board through wires; When the ablation starts, the microwave source is turned on, and the AD5940 is started at the same time for impedance measurement; AD5940 sends an excitation voltage to the electrode, measures the response voltage and response current and sends them to the ARM microcontroller, which calculates the impedance and sends it to the host computer for impedance Information reading and storage.

Preferably, in step (3), as the microwave ablation proceeds, the cell membrane is ruptured due to the gradual increase of the temperature, the intracellular fluid escapes from the cells, and the ion mobility increases with the increase of the temperature, and the ablation site The impedance gradually decreased to about 400Ω; at a certain point, the further increase in temperature caused the dehydration and evaporation of the tissue at the ablation site, resulting in a significant increase in impedance; after the impedance rose to a certain threshold, the microwave source output was cut off before the carbonization of the ablation site; The tissue fluid around the site diffuses back to the measurement area and will decrease to about 300Ω. At this time, the microwave source is turned on again, and the impedance rises again; this process is repeated until the actual working time of the microwave source reaches the predetermined ablation time.

The beneficial effects of the present invention are: (1) the present invention indirectly reflects the coagulation and carbonization of the tissue at the ablation site by measuring the bioimpedance. Compared with single-point temperature measurement, the bioimpedance can reflect the ablation effect of an area between two copper foil electrodes; (2) The present invention adopts the high-precision impedance measurement analog front-end chip AD5940 to realize impedance measurement, and it is easy to integrate the impedance measurement function into the existing microwave ablation instrument, and the cost is low; (3) The present invention has great significance for evaluating the real-time curative effect of tumor microwave ablation It is of great value for carbonization regulation of tumor microwave ablation.

Description of drawings

FIG. 1 is a schematic flow chart of the method of the present invention.

FIG. 2 is a schematic structural diagram of a collection device of the present invention.

FIG. 3 is a schematic structural diagram of the microwave ablation needle with copper foil electrodes of the present invention.

FIG. 4 is a schematic diagram of the circuit structure of the AD5940 of the present invention.

FIG. 5 is a circuit topology diagram of the impedance measurement of the present invention.

FIG. 6 is a schematic diagram of real-time changes of bioimpedance Ω and time T data in a microwave ablation experiment without carbonization control measures of a certain group of the present invention.

7 is a schematic diagram of real-time changes of bioimpedance Ω and time T data in a certain group of microwave ablation experiments with carbonization control measures of the present invention.

Detailed ways

As shown in Figure 1, a real-time carbonization regulation method for microwave ablation based on bioimpedance includes the following steps:

S1. Build a bioimpedance acquisition device for real-time carbonization regulation of microwave ablation;

S2. Obtain real-time change data of bioimpedance during ablation;

S3. Adjust the output power of the microwave source according to the change of the biological impedance.

As shown in FIG. 2 , it is a schematic diagram of the structure of the bioimpedance acquisition device. 1 is the microwave ablation needle, 2 is the bioimpedance acquisition board, 3 is the host computer, 4 is the 2450MHz solid-state microwave source, and 5 is the isolated pig liver; the microwave ablation needle has copper foil electrodes, which are connected to the biological Impedance acquisition board. The high-precision impedance measurement analog front-end chip of the bioimpedance acquisition board adopts AD5940, and the ARM microcontroller adopts STM32F411RET6.

As shown in Figure 3, it is a schematic diagram of a microwave ablation needle with copper foil electrodes. The copper foil electrodes 6 are attached to the surface of the microwave ablation needle and are located at 5 mm and 15 mm from the rear end of the dielectric sleeve 7 respectively, and the two are connected to the bioimpedance measurement circuit board through wires 8; the copper foil electrodes are inserted into the human body with the microwave ablation needle. In vivo, the impedance of the ablation site is measured.

As shown in Figure 4, it is a schematic diagram of the AD5940 circuit of the present invention. The AD5940 has a built-in digital waveform generator and a 12-bit digital-to-analog converter DAC to generate sinusoidal excitation signals; an on-chip 16-bit, 800kSPS analog-to-digital converter ADC measures sinusoidal input voltages up to 200kHz and can digitally filter the measurement results; on-chip high-speed transimpedance The amplifier HSTIA processes a 200kHz high-bandwidth sinusoidal input signal and converts the weak current signal into a voltage signal that can be measured by the ADC; the on-chip discrete Fourier transform DFT engine performs DFT calculations on the measurement results, and stores the real and imaginary measurement results in in the corresponding register.

As shown in Figure 5, it is a circuit topology diagram of impedance measurement. The waveform generator and DAC generate a sinusoidal excitation signal, and the sinusoidal excitation signal drives the external load impedance after the excitation buffer. The waveform generator internally stores the phase amplitude table of the sine wave, and the frequency control word is set to adjust the counting step size. Every time a pulse appears in the external clock, the phase accumulator performs phase accumulation according to the counting step size. The waveform generator looks up the phase amplitude table according to the phase accumulation result, and the DAC outputs the voltage according to the corresponding amplitude. The output voltage of the excitation buffer is limited by the resistor _Rlim to limit the output current within the safe current that the human body can withstand. The positive and negative input terminals of the differential amplifier or instrumentation amplifier are connected to both ends of the load impedance, and the response voltage U _X of the load impedance is measured. The current _IX through the load impedance flows into the negative input of the transimpedance amplifier, and the transimpedance amplifier converts it into a voltage U _O , the conversion formula is:

U _O = -I _X R _TIA

where R _TIA is the gain resistor of the transimpedance amplifier.

The ADC measures the voltages Ux and Uo respectively, and the impedance to be measured can be calculated using the following formula:

After the measurement result of the ADC is subjected to the DFT operation by the DFT engine, the real part r and the imaginary part i are obtained. Taking the response voltage as an example, the amplitude and phase of the response voltage are:

Similarly, the magnitude and phase of the response current can be obtained. This gives the magnitude and phase of the impedance:

θ _X = θ _U - θ _I

The phase of the current needs to be shifted by 180° to the result obtained by the DFT engine, because the output voltage U _O has a phase shift of 180° during the current-voltage conversion process.

The initialization and workflow of the AD5940 are described below:

S1. Configure the peripherals of AD5940, including system clock frequency, gain resistance R _TIA resistance, excitation sinusoidal signal frequency, sequencer length, DFT points and system interrupts. In the present invention, the resistance value of the gain resistor R _TIA is selected to be 1KΩ, the excitation sinusoidal signal is 25kHz, and the number of DFT points is 8192.

S2. Calibrate the gain resistor R _TIA . Configure the programmable switch matrix, measure the gain resistor R _TIA of AD5940 and the external calibration resistor R _CAL respectively, find the ratio between the gain resistor R _TIA and the calibration resistor R _CAL , and multiply the ratio by the resistance value of the calibration resistor R _CAL , you can Get the value of the actual gain resistor R _TIA . In the present invention, the resistance value of the gain resistor R _TIA is selected to be 10KΩ.

S3. Configure and enable the sequencer. The present invention uses two sequences, namely an initialization sequence and a measurement sequence. The initialization sequence includes initializing the peripheral parameters of the AD5940, and the measurement sequence includes switching the programmable switch matrix and switching the ADC input channel. After the initialization sequence and measurement sequence are written into the SRAM of AD5940, the sequencer is enabled, and the sequencer starts to run the operation stored in advance, thus completing the initialization of AD5940, and AD5940 starts to measure external impedance cyclically.

S4, ARM microcontroller receives the interrupt signal sent by AD5940. When the ARM microcontroller receives the interrupt signal sent by AD5940, it indicates that the data FIFO of AD5940 has been filled with the calculation result of the DFT engine. At this time, the ARM microcontroller reads the data FIFO, obtains the real and imaginary parts of the voltage and current, and converts them into impedance values. After reading, the AD5940 continues the measurement operation and reloads the data FIFO with data.

The following describes the microwave ablation carbonization control test:

Before the experiment, a microwave ablation needle with copper foil electrodes was inserted into the liver for 8 cm to ensure that the entire ablation area was within the liver parenchyma; in multiple data acquisition experiments, the ablation power was selected from 30W, 40W and 50W, and the ablation was started at the beginning of the ablation. At the same time, start the bioimpedance acquisition system.

As shown in FIG. 6 , the bioimpedance Ω and time T data of a certain group of ablation experiments in a bioimpedance-based real-time carbonization control method for microwave ablation according to an embodiment of the present invention change in real time. The experimental ablation power of this group was selected as 40W without carbonization regulation, and the microwave ablation started at 45s. Observing the images, it was found that with the increase of ablation time, the impedance of the ablation site gradually decreased from about 800Ω to about 400Ω, then began to rise at 120s, reached 20kΩ at 300s and maintained at about 20kΩ. Microwave ablation ended at 350s, and the impedance began to rapidly decrease to around 400Ω. After the ablation was completed, the microwave ablation needle was removed, and the liver tissue was cut along the direction in which the microwave ablation needle was inserted. The long diameter of the ablation site was about 5 cm and the short diameter was about 3 cm. There were obvious carbonization marks at the front end of the ablation needle, and the carbonization marks were about 2 cm long. .

As shown in FIG. 7 , the bioimpedance Ω and time T data of a certain group of ablation experiments in a bioimpedance-based microwave ablation real-time carbonization regulation method according to an embodiment of the present invention are changed in real time. The experimental ablation power of this group was 50W, and carbonization was controlled. The microwave ablation started at 12s, and the microwave source was turned off when the impedance rose to about 7kΩ. Observing the images, it was found that with the increase of ablation time, the impedance of the ablation site gradually decreased from about 850Ω to about 500Ω, then began to rise at 65s, reached the threshold for the first time at 115s, and then rapidly decreased to about 400Ω. . The process was repeated 6 times in total, and the microwave ablation ended at 555s. After the ablation was completed, the microwave ablation needle was removed, and the liver tissue was cut along the insertion direction of the microwave ablation needle. The long diameter of the ablation site was about 4 cm and the short diameter was about 2 cm. The carbonization marks at the front end of the ablation needle were significantly reduced, and the carbonization marks only appeared. at the tip of the ablation needle.

Claims (8)

1. A microwave ablation real-time carbonization regulation and control method based on bioimpedance is characterized by comprising the following steps:

s1, constructing a biological impedance acquisition device applied to microwave ablation real-time carbonization regulation and control;

s2, acquiring real-time change data of the biological impedance in the ablation process;

and S3, adjusting the output power of the microwave source according to the change of the biological impedance.

2. The real-time carbonization control method based on the bio-impedance microwave ablation as claimed in claim 1, wherein in the step (1), the bio-impedance acquisition device comprises a copper foil electrode, a high-precision impedance measurement analog front-end chip and an ARM microcontroller; the copper foil electrode is connected with the high-precision impedance measurement simulation front-end chip through a wire, the ARM microcontroller controls the high-precision impedance measurement simulation front-end chip to carry out impedance measurement, returned data are received and an impedance value is obtained through calculation, and the ARM microcontroller sends the impedance to an upper computer through the communication module to display.

3. The real-time carbonization control method based on bioimpedance for microwave ablation according to claim 2, wherein the copper foil electrode is attached to the surface of the microwave ablation needle; one copper foil electrode is attached to the position 5mm away from the rear end of the microwave ablation needle medium sleeve, the other copper foil electrode is attached to the position 15mm away from the rear end of the medium sleeve, and the distance between the two copper foil electrodes is 10 mm; the two copper foil electrodes are respectively connected to the biological impedance measuring circuit board through leads.

4. The real-time carbonization control method based on bioimpedance of claim 2, wherein the high-precision impedance measurement analog front-end chip is AD 5940; an AD5940 built-in digital waveform generator and a 12-bit digital-to-analog converter DAC generate a sinusoidal excitation signal; the on-chip 16-bit 800kSPS analog-to-digital converter ADC measures sinusoidal input voltage up to 200kHz, and digital filtering can be carried out on the measurement result; the on-chip high-speed trans-impedance amplifier HSTIA processes a high-bandwidth sine input signal of 200kHz, and converts a weak current signal into a voltage signal which can be measured by the ADC; and the on-chip Discrete Fourier Transform (DFT) engine performs DFT calculation on the measurement result and stores the real part measurement result and the imaginary part measurement result in corresponding registers.

5. The real-time carbonization control method based on the bio-impedance microwave ablation as claimed in claim 2, wherein the ARM microcontroller selects STM32F411RET6 with a main frequency of 100 MHz; the ARM microcontroller is communicated with the AD5940 by adopting a serial peripheral interface SPI; the ARM microcontroller sends a control instruction to the AD5940, configures a digital waveform generator, an HSTIA (high speed TIA) and an ADC (analog-to-digital converter) peripheral of the AD5940, and reads real part and imaginary part measurement results of response voltage and response current from a data FIFO (first in first out); and after reading the measurement result, the measurement result is converted into impedance by the ARM microcontroller.

6. The real-time carbonization control method for microwave ablation based on bioimpedance of claim 2, wherein the communication module is a CH340C USB serial port chip, and the baud rate is set to 115200 bps.

7. The real-time carbonization control method based on bioimpedance during microwave ablation according to claim 1, wherein in step (2), the copper foil electrode is attached to the surface of the microwave ablation needle and is sent into the in-vitro pork liver along with the microwave ablation needle; the two copper foil electrodes are respectively connected to the biological impedance measuring circuit board through leads; when microwave ablation starts, a microwave source is turned on, and meanwhile, AD5940 is started to carry out impedance measurement; the AD5940 sends out excitation voltage to the electrode, measures response voltage and response current and sends to the ARM microcontroller, and the ARM microcontroller calculates the impedance and sends to the host computer for impedance information reading and storage.

8. The real-time carbonization regulating method based on bioimpedance microwave ablation according to claim 1, wherein in the step (3), the impedance of the ablation part is gradually reduced to about 400 Ω as the microwave ablation is performed; by a certain time, the further temperature rise causes the tissue at the ablation part to be dehydrated and evaporated, and the impedance is obviously increased; after the impedance rises to a certain threshold value, cutting off the output of the microwave source before carbonization occurs at the ablation part; then the impedance is reduced to about 300 omega due to the diffusion of tissue fluid around the ablation part back to the measurement area, and at the moment, the microwave source is turned on again, and the impedance rises again; the process is cycled until the actual on time of the microwave source reaches the predetermined ablation time.

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