Device for researching relation between tissue temperature and electrical impedance

Abstract

A device for studying the relation between tissue temperature and electrical impedance comprises a tissue placing container, a heating and heat preservation subsystem and a tissue temperature and electrical impedance testing subsystem, and has the characteristics that (1) various general instruments are not stacked any more, the subsystems are controlled in a centralized mode, accurate synchronization is facilitated, and (2) the degree of automation is high, temperature adjustment is convenient, and time and labor are saved. The whole temperature adjusting scheme and the whole testing scheme can be set at a computer end at one time, and manual control is not needed in the middle process; (3) the highest heating power is high and can reach 2kW or even higher, and rapid heating is supported; heat transfer modes are various, water bath heating comprises heat radiation and heat conduction modes, and the heat transfer efficiency is high; and (5) due to large specific heat of water, heat preservation and constant temperature of tissues are facilitated, measurement of low-frequency impedance is facilitated, and impedance spectrum measurement of frequencies below 100Hz is successfully covered.

Description

Technical Field

[0001] This invention relates to an apparatus for studying the relationship between tissue temperature and electrical impedance.

[0002] The background of this research device is related to HIFU (high-intensity focused ultrasound). HIFU, also known as ultrasonic scalpel, is a thermotherapy method where the focal temperature needs to be monitored. Too low a temperature will not achieve the desired effect, while too high a temperature will inevitably increase trauma and pain. Monitoring tissue temperature based on relative changes in tissue electrical impedance during HIFU treatment is a research direction that has received considerable attention in the industry. The fundamental scientific question involved is whether and how tissue temperature relates to its electrical impedance, which requires the development of appropriate equipment for research. Background Technology

[0003] In 2018, Ding Heping et al. studied the tissue temperature monitoring technology based on the relative change of impedance during HIFU treatment [1]. Based on the function signal generator (Agilent 33250A) generating a continuous sine wave signal with a center frequency of 1.13MHz, after being amplified by the power amplifier (E&I2200L), the HIFU focused ultrasound transducer was driven to generate a focused sound beam that acted on the gel, causing the gel to simulate the increase of internal tissue temperature. During the experiment, two silver electrodes were symmetrically placed on both sides of the gel in a cylindrical mold and connected to an impedance analyzer (Agilent 4294A) through wires to detect the overall change of impedance of the gel under the action of HIFU. The impedance analyzer imported the measured impedance data into the computer through the IntuiLink program to complete the real-time impedance measurement. The experiment used a number of readily available general-purpose instruments to build the experimental device, but the experimental device could not test the tissue temperature.

[0004] Reference [2] constructed a HIFU irradiation temperature measurement experimental system, which mainly includes a signal source, power amplifier, high-precision three-dimensional scanning mechanism, thermocouple, probe hydrophone, digital oscilloscope, programmable computer, temperature recorder, silencing water tank and HIFU transducer, etc. This experimental device measures and records tissue temperature, but does not measure the tissue impedance at different temperatures. Reference [3] only performed simulation and did not involve the measurement device.

[0005] The closest to this application is the experimental setup for studying the relationship between tissue electrical impedance and temperature characteristics in reference [5]. The heating chamber of this device uses two 300W quartz heating tubes for heating, and the temperature inside the chamber is controlled by an intelligent PID temperature controller (XMT81 model, Tenghui Instrument Factory). The liver tissue to be tested is placed in an impedance test box, which is fixed to an iron plate above the quartz heating tubes by clamps. To prevent uneven heating of the liver tissue, the bottom of the test box does not touch the iron plate but is suspended by clamps. The thermocouple temperature probe of a Fluke 17B digital multimeter (temperature measurement accuracy of 0.1℃) is directly inserted into the tissue to detect the tissue temperature in real time. To ensure measurement accuracy, the biological tissue needs to be cut relatively thinly and small to ensure uniform heating. The temperature probe is placed at the center of the two measuring electrodes of the impedance test box. The impedance value of the liver tissue is continuously monitored using an Agilent 4294A impedance analyzer. The measurement data of the Agilent 4294A precision impedance analyzer is output to a portable computer via a data cable (GBI to USB). The AC impedance value of 201 frequency points (100Hz to 10MHz) is measured at each temperature point. Obviously, there are many areas for improvement in this research device: (1) It is a collection of various general-purpose instruments. The heating temperature controller, thermocouple temperature measuring multimeter, and impedance meter are relatively independent and not centrally controlled, which makes it inconvenient to accurately synchronize tissue temperature and impedance measurements; (2) The degree of automation is low, and it is not convenient to adjust the temperature. Each temperature point must be manually operated on the temperature controller interface. Starting or stopping the measurement of tissue temperature and impedance spectrum at a set temperature point also requires manual control; (3) The heating efficiency is limited. The upper limit power of the two 300W heating tubes is insufficient when rapid heating is required; (4) The heat transfer method is singular. It relies only on the heat radiation of the iron plate to the test box, so the heat transfer efficiency will not be high; (5) When measuring low-frequency impedance, it takes a long time to measure the impedance at a frequency point. For example, the impedance measurement at 0.1Hz takes at least 10 seconds. Therefore, the test of low-frequency impedance requires good heat preservation measures, but the method in this literature does not have such measures, which is why it does not cover frequencies below 100Hz.

[0006] References

[0007] [1] Ding Heping, Su Huidan, Ma Qingyu, Guo Gepu: Tissue temperature monitoring technology based on relative change of electrical impedance in high-intensity focused ultrasound therapy, Journal of Nanjing Normal University (Natural Science Edition), Vol. 41, No. 2, June 2018, pp. 39-46

[0008] [2] Chen Ning, Zhao Peng, Wang Yuebing, Cao Yonggang: Study on the temperature rise of phantom tissues under high-intensity focused ultrasound, Acta Metrologica Sinica, Vol. 42, No. 12, December 2021, pp. 1636-1643

[0009] [3] Guo Gepu, Su Huidan, Ding Heping, Ma Qingyu: High-intensity focused ultrasound temperature monitoring technology based on electrical impedance tomography, Acta Physica Sinica, Vol.66, No.16(2017)164301-1-12

[0010] [4] Ma Yixin, Li Hua, Huang Ningning, Cui Daxiang: A HIFU system based on impedance measurement and its usage method, Patent Application No. 201910073328.9, Application Date 2019.01.25

[0011] [5] Cai Hua, You Fusheng, Shi Xuetao, Fu Feng, Liu Ruigang, Tang Chi, Dong Xiuzhen: Study on electrical impedance temperature characteristics of isolated fresh rabbit liver tissue, Medical and Health Equipment, November 2010, Vol. 31, No. 11, pp. 8-11 Summary of the Invention

[0012] Purpose of the invention

[0013] This paper proposes a device for studying the relationship between tissue temperature and electrical impedance. Unlike existing research devices that aggregate multiple general-purpose instruments, this device integrates a tissue heating and insulation subsystem, a tissue AC impedance spectroscopy subsystem, and a temperature measurement subsystem. The final centralized measurement and control are achieved by a single host computer, which improves the degree of automation. It eliminates the need for manual operation on the temperature control interface for each temperature setting, and also eliminates the need for manual operation to start or stop impedance temperature measurement at each set temperature. It supports greater heating efficiency and stronger isothermal performance, and supports low-frequency impedance spectroscopy testing in the 0.1Hz-100Hz frequency band.

[0014] Technical solution

[0015] A device for studying the relationship between tissue temperature and electrical impedance includes a tissue placement container, a heating and insulation subsystem, and a tissue temperature and electrical impedance testing subsystem. The device is characterized by: (1) the tissue placement container arranging the tissue to be tested, a thermocouple sensor for measuring tissue temperature, and an electrode for measuring tissue electrical impedance; (2) the heating and insulation subsystem using a water bath for heating and insulation, with an electric heating tube and a water temperature sensor arranged in the water bath, and a control circuit board with a microcontroller as its core controlling the heating of the water in the water bath to achieve water temperature testing and insulation, and a host computer configuring the heating and insulation scheme for the microcontroller; (3) the tissue temperature and electrical impedance testing subsystem collecting tissue temperature and electrical impedance spectrum data, with a data acquisition board with a microcontroller as its core transmitting the collected data to the host computer; (4) the tissue placement container being placed in the water bath via a shelf, and the control circuit board of the heating and insulation subsystem and the data acquisition board of the tissue temperature and electrical impedance testing subsystem being centrally located in the same control box, with one end connected to the water bath and the tissue placement container, and the other end connected to the host computer. The device block diagram is shown below. Figure 1 As shown.

[0016] According to the above-described apparatus for studying the relationship between tissue temperature and impedance, a tissue placement container is arranged with the tissue to be tested, a thermocouple sensor for measuring tissue temperature, and electrodes for measuring tissue impedance. Its characteristics are: (a) the electrodes for measuring tissue impedance have four electrodes, corresponding to the four-electrode impedance testing method. One pair of electrodes is used to apply AC excitation to the tissue, and another pair of electrodes is used to measure the voltage between two points on the tissue to calculate the AC impedance value. The four electrodes are arranged at the bottom of the tissue placement container, and the tissue is placed on top of the electrodes during measurement. (b) The thermocouple sensor is used to measure tissue temperature, and the probe is inserted into the center of the tissue during measurement. (c) The tissue placement container is electrically insulated. A schematic diagram of the tissue placement container is shown below. Figure 2 As shown.

[0017] According to the above-described device for studying the relationship between tissue temperature and electrical impedance, the heating and insulation subsystem adopts a water bath for heating and insulation. The water bath is equipped with electric heating tubes and water temperature sensors. The control circuit board with a microcontroller as the core controls the heating of the water in the water bath, realizes water temperature testing and water insulation. The host computer configures the heating and insulation scheme to the microcontroller. Its features are: (a) the host computer provides a comprehensive heating and insulation scheme, including setting several water temperature control points and how long each set temperature point is kept warm, i.e., programmable temperature control, rather than relying on manual temperature control like a general water bath; (b) the heating rod is controlled by the microcontroller and relays to turn on and off, and the heating power is adjustable in the range of 0 to 2 kW.

[0018] According to the above-described device for studying the relationship between tissue temperature and electrical impedance, a tissue temperature and electrical impedance testing subsystem collects tissue temperature and electrical impedance spectrum data. A data acquisition board with a microcontroller as the core transmits the collected data to a host computer. Its features are: (a) the electrical impedance spectrum tested at each tissue temperature, including the resistance spectrum and the reactance spectrum, can cover the frequency range of 0.1Hz to 1000Hz; (b) when the thermocouple tests the tissue temperature, it measures one channel of the voltage signal between the two electrodes of the thermocouple probe and simultaneously measures one channel of the cold junction temperature related signal to compensate for the calculation of the tissue temperature value.

[0019] According to the above-described apparatus for studying the relationship between tissue temperature and electrical impedance, a tissue placement container is placed in a water bath via a shelf. The control circuit board of the heating and insulation subsystem and the data acquisition board of the tissue temperature and electrical impedance testing subsystem are all centrally located in the same control box. One end of the control box is connected to the water bath and the tissue placement container, and the other end is connected to a host computer. The control box is characterized by: (a) a 220V AC power input socket on the rear panel, connected to a relay inside the control box; a power output socket via the relay, connected to the heating rod in the water bath; and a water temperature probe interface, for a total of three interfaces; (b) a 5-interface control box front panel, including one interface for inputting the tissue impedance voltage signal, two interfaces for inputting the thermocouple electrode pair voltage and the cold junction temperature compensation voltage signal, respectively, and two communication interfaces for communication with the host computer. A schematic diagram of the control box is shown below. Figure 3 As shown.

[0020] Beneficial effects

[0021] The prototype device developed according to this technical solution is detailed in the following embodiments. Experimental studies have shown that the device developed according to this technical solution can be used to study the relationship between tissue temperature and electrical impedance. It can conveniently and accurately measure the values ​​of tissue temperature and electrical impedance simultaneously, covering the range of 0.1Hz to 1kHz without any problems.

[0022] Fresh, isolated porcine liver tissue was used in the experiment. The tissue was cut into pieces measuring 5cm × 4cm × 1cm, washed in physiological saline solution, wiped clean with paper towels, and then placed in an acrylic container. A thermocouple was inserted 0.5cm into the center of the tissue. The container was placed on a rack inside a water bath, and the thermocouple was fixed in place by an iron stand clamp. The maximum heating rod power was set to 1kW, and the water level in the water bath exceeded the upper surface of the tissue. The water temperature was set within a range of 26-98℃, with measurements taken every 2℃ from 26-60℃ and every 1℃ from 60-98℃. Data acquisition was performed when the temperature difference between the actual and set water temperatures was within 0.1℃. At each set temperature, the tissue impedance spectrum was measured using a sweep frequency test. Ten frequency points were set within the 1Hz-1kHz range for the tissue impedance spectrum testing: 1, 2, 5, 10, 20, 50, 100, 200, 500, and 1000Hz, with an excitation sinusoidal signal amplitude of 320mV.

[0023] The tissue was heated from 24℃ to 77℃, and the temperature-impedance coefficient relationship curves at different frequency points were obtained as follows: Figure 4 As shown. By Figure 4It can be seen that at 24-30℃, TIVF fluctuates around -3%; at 31-50℃, TIVF fluctuates around -2%; at 51℃, the rate of decrease in tissue impedance begins to increase, and the TIVF curve rises, reaching its peak at 65℃; at 66℃, the rate of decrease in impedance slows down, and the TIVF curve shows a downward trend, fluctuating around 0 at the end of the experiment. All frequency points reach their TIVF peak at 65℃, with the minimum peak value occurring at 1000Hz. The variation patterns of the tissue temperature-impedance coefficient are similar at all frequency points, and the TIVF difference is very small at the peak points, proving that significant results can be obtained in studying the relationship between tissue temperature and impedance within the 1Hz-1kHz range. Impedance changes significantly when coagulative necrosis occurs in tissue, demonstrating the feasibility of monitoring tissue temperature using changes in tissue impedance.

[0024] Compared with the apparatus in reference [5], the advantages of this experimental apparatus are obviously: (1) This apparatus is no longer a collection of various general instruments, and each subsystem is centrally controlled, which is convenient for precise synchronization; (2) It has a high degree of automation and is convenient for temperature adjustment. The entire temperature adjustment scheme and test scheme can be set at once on the computer, and the intermediate process does not require manual operation; (3) The maximum heating power is large, which can reach 2kW or even higher, and supports rapid heating; (4) There are various heat transfer methods. Water bath heating includes not only thermal radiation but also thermal conduction, and the heat transfer efficiency is high; (5) Due to the large specific heat of water, it is conducive to the preservation and constant temperature of tissues and to the measurement of low-frequency impedance, and successfully covers the impedance spectrum measurement of frequencies below 100Hz. Attached Figure Description

[0025] Figure 1 This application contains a structural block diagram of the apparatus for studying the relationship between temperature and electrical impedance.

[0026] Figure 2 This application presents a schematic diagram of the container for the tissue. The example used is pig liver tissue.

[0027] Figure 3 The schematic diagram of the control box in this application is shown. One panel has three interfaces: 220VAC INPUT, 220VAC OUTPU, and temperature control thermometer, used for the water bath heating and insulation subsystem; the other panel has three interfaces: cold junction thermometer, thermocouple thermometer, and tissue impedance, used for the tissue temperature and impedance measurement subsystem, as well as two host computer communication interfaces: detection USB and temperature control USB, used for communication between the measurement subsystem and the heating and insulation subsystem, respectively.

[0028] Figure 4 This is a schematic diagram illustrating the relationship between tissue temperature and electrical impedance variation coefficients at different frequency points. The horizontal axis represents temperature, and the vertical axis represents the relative impedance variation index (TIVF). Detailed Implementation

[0029] Example

[0030] Based on the above technical solution, a device for studying the relationship between tissue temperature and electrical impedance was developed, including a tissue placement container, a heating and insulation subsystem, and a tissue temperature and electrical impedance testing subsystem. Specific implementation features are as follows:

[0031] (1) The tissue placement container is made of electrically insulating acrylic material. A T-type thermocouple (accuracy 0.5℃) is used to measure tissue temperature. Silver electrodes are used to measure tissue impedance. There are four electrodes for measuring tissue impedance, corresponding to the four-electrode impedance testing method. One pair of electrodes is used to apply AC excitation to the tissue, and another pair is used to measure the voltage between two points on the tissue to calculate the AC impedance value. The four electrodes are arranged at the bottom of the tissue placement container. During measurement, the tissue being measured is placed on top of the electrodes, and the probe of the thermocouple sensor is inserted into the center of the tissue during measurement. See [link to documentation]. Figure 2 As shown.

[0032] (2) The heating and heat preservation subsystem adopts a water bath for heating and heat preservation. Electric heating tubes and water temperature sensors are arranged in the water bath. The control circuit board with the microcontroller as the core controls the heating of the water in the water bath, realizes water temperature testing and heat preservation. The host computer configures the heating and heat preservation scheme to the microcontroller. The host computer provides a complete heating and heat preservation scheme, including setting several water temperature control points and how long to keep each set temperature point warm. That is, it is fully program-controlled and no manual operation is required in the middle process. Two 1kW heating rods are controlled by the microcontroller and relays to control their on and off. The heating power is adjustable in the range of 0 to 2kW. The water temperature sensor is based on the tmp117 chip.

[0033] (3) Tissue temperature and electrical impedance testing subsystem: collects tissue temperature and electrical impedance spectrum data. The data acquisition board with microcontroller as the core transmits the collected data to the host computer. The electrical impedance spectrum tested at each tissue temperature, including resistance spectrum and reactance spectrum, can cover the frequency range of 0.1Hz to 1000Hz. When the thermocouple tests the tissue temperature, it measures one channel of voltage signal between the two electrodes of the thermocouple probe and simultaneously measures one channel of cold junction temperature signal (based on the LMT70 chip to convert the cold junction temperature into one voltage) to compensate for the calculated tissue temperature value.

[0034] (4) The tissue placement container is placed in the water bath via a shelf. The control circuit board of the heating and insulation subsystem and the data acquisition board of the tissue temperature and impedance testing subsystem are all housed in the same control box. One end of the control box is connected to the water bath and the tissue placement container, and the other end is connected to the host computer. The rear panel of the control box has one 220V AC power input socket, which connects to the relay inside the control box. It also has one power output socket connected to the heating rod in the water bath and a water temperature probe interface. The front panel of the control box includes five interfaces: one for inputting the impedance voltage signal for tissue measurement, two for inputting the thermocouple electrode pair voltage and the cold junction temperature compensation voltage signal, respectively, and two communication interfaces for communication with the host computer. See the schematic diagram of the control box. Figure 3 As shown.

Claims

1. A device for studying the relationship between tissue temperature and electrical impedance, comprising a tissue holding container, a heating and holding subsystem, a tissue temperature and electrical impedance testing subsystem, characterized in that, (1) The tissue placement container is arranged with the measured tissue, a thermocouple sensor for measuring the temperature of the tissue, and electrodes for measuring the electrical impedance of the tissue, (2) The heating and insulation subsystem uses a water bath to heat and insulate, an electric heating tube and a water temperature sensor are arranged in the water bath, a single-chip microcomputer-based control circuit board controls the heating of the water in the water bath and realizes water temperature testing and insulation, the host computer configures a heating and insulation scheme for the single-chip microcomputer, (3) The tissue temperature and electrical impedance testing subsystem collects tissue temperature and electrical impedance spectrum data, and a single-chip microcomputer-based data acquisition board transmits the collected data to the host computer, (4) The tissue placement container is placed in the water bath through a holder, and the control circuit board of the heating and insulation subsystem and the data acquisition board of the tissue temperature and electrical impedance testing subsystem are placed in the same measurement and control box, one end of the measurement and control box is connected with the water bath and the tissue placement container, and the other end is connected with the host computer.

2. The apparatus for investigating the relationship between tissue temperature and electrical impedance according to claim 1, wherein the tissue placement container is arranged to hold the tissue to be measured, a thermocouple sensor for measuring the temperature of the tissue, and electrodes for measuring the electrical impedance of the tissue. (a) The electrodes for measuring the electrical impedance of the tissue are four electrodes corresponding to the four-electrode impedance testing method, one pair of electrodes is used to apply an alternating excitation to the tissue, and the other pair of electrodes is used to measure the voltage between two points of the tissue to calculate the alternating electrical impedance value, the four electrodes are arranged at the bottom of the tissue placement container, and the tissue is placed on the electrodes during measurement, (b) The thermocouple sensor is used to measure the temperature of the tissue, and the probe is inserted into the center of the tissue during measurement, (c) The tissue placement container is electrically insulated.

3. The device for studying the relationship between tissue temperature and electrical impedance according to claim 1, wherein the heating and holding subsystem adopts a water bath kettle, an electric heating tube and a water temperature sensor are arranged in the water bath kettle, a single-chip microcomputer is used as the core of a control circuit board to control the heating of the water in the water bath kettle, realize water temperature testing and water holding, and an upper computer configures a heating and holding scheme for the single-chip microcomputer, characterized in that, (a) The host computer provides a package of heating and insulation schemes, including setting several water control temperature points and the insulation time for each set temperature point, i.e. programmed temperature adjustment, instead of manual temperature adjustment as in general water baths, (b) The heating rod is controlled by a single-chip microcomputer and a relay to turn on and off, and the heating power is adjustable in the range of 0-2 kW.

4. The device for studying the relationship between tissue temperature and electrical impedance according to claim 1, the tissue temperature and electrical impedance testing subsystem, the data acquisition board with a single-chip microcomputer as the core transmits the collected data to the upper computer, characterized in that, (a) The electrical impedance spectrum tested at each tissue temperature includes the resistance spectrum and the reactance spectrum, and can cover the frequency range of 0.1 Hz-1000 Hz, (b) When the thermocouple measures the temperature of the tissue, one channel of the voltage signal between the two poles of the thermocouple probe is measured, and one channel of the cold end temperature related signal is measured to compensate for the calculation of the tissue temperature value.

5. The device for studying the relationship between tissue temperature and electrical impedance according to claim 1, wherein the tissue placement container is placed in the water bath through the rack, the control circuit board of the heating and holding subsystem and the data acquisition board of the tissue temperature and electrical impedance testing subsystem are placed in the same measurement and control box, one end of the measurement and control box is connected with the water bath and the tissue placement container, and the other end is connected with the upper computer. (a) The rear panel of the measurement and control box has one 220V AC power input socket, one relay inside the measurement and control box, one power output socket through the relay connected to the heating rod in the water bath, and one water temperature probe interface, a total of three interfaces; (b) The front panel of the measurement and control box includes five interfaces, one for measuring the electrical impedance voltage signal input of the tissue, two for the voltage input of the thermocouple electrode pair and the cold end temperature compensation voltage signal input, respectively, and two communication interfaces for communication with the host computer.

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