JP2008086525A - Miniaturized microwave hyperthermia treatment system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a miniaturized microwave hyperthermia treatment system for monitoring spacial temperature distribution by an MR temperature image. <P>SOLUTION: The system is for a hyperthermia therapeutic device system for treating a malignant tumor. The 7T static magnetic field strength is used for sensing the temperature rise by the MR temperature image so that the hyperthermia therapy at 42-43 °C can be monitored. Microwaves are applied to the malignant tumor by a 2.45 GHz microwave generator. The hyperthermia therapeutic device system for treating the malignant tumor has a function of intermittently repeating the turning on/off of a power supply switch to control the temperature of a target region at a target level. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a miniature microwave thermotherapy system for monitoring spatial temperature distribution with MR temperature images.

Recently, various minimally invasive therapies are available for cancer treatment, and hyperthermia is one of these therapies. However, such therapy alone is not always effective for all carcinomas and requires multidisciplinary treatment. Hyperthermia is used to enhance the effects of radiation therapy or chemotherapy (Non-patent Document 1). In randomized controlled trials, hyperthermia has been reported as an effective cancer treatment in combination with radiotherapy or chemotherapy (Non-patent document 2) (Non-patent document 3) (Non-patent document 4) (Non-patent document) Reference 5) (Non-Patent Document 6). Warming techniques and temperature monitoring are the main challenges of this treatment. It is very difficult to accurately measure in-vivo thermometry. The temperature distribution in a living body is generally non-uniform and unpredictable. However, temperature monitoring during hyperthermia is essential for clinical accuracy and safety. It is also important to measure the temperature of the surrounding area to avoid unpredictable hot spots as well as the area of interest, which may cause serious side effects. There are two types of temperature measurement methods, invasive and non-invasive temperature measurement methods. Invasive temperature measurements (temperature probes are inserted into tissue) can cause many problems. Accurate insertion of the sensor into the target site is difficult and probe insertion is invasive to the patient. In addition, insertion may cause tumor bleeding or dissemination (Non-patent document 7) (Non-patent document 8). Furthermore, it is almost impossible to obtain temperature information at many points by invasive temperature measurement. With one or a few limited points of temperature information, the planning of individual treatments is difficult.
Magnetic resonance (MR) temperature images are promising as a non-invasive temperature measurement method. Non-invasive MR temperature images can show temperature changes on 2-dimensional images. There are several methods for temperature monitoring in MR (Non-patent Document 9). This is a method using spin lattice relaxation time (T1), diffusion coefficient, proton resonance frequency (PRF) of tissue water and spectroscopy imaging. The most suitable method for MR temperature monitoring during hyperthermia is the PRF method because it is quantitative, sensitive and accurate (Non-Patent Document 10). We previously developed MR-guided microwave thermocoagulation treatment for liver tumors with an open MR system of 0.5T (Non-Patent Document 11) (Non-Patent Document 12) (Non-Patent Document 13) ( Non-patent document 14). Microwave irradiation did not affect MR images, and the therapeutic effect could be monitored with real-time MR temperature images. MR images and microwaves were found to be compatible.
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  Hyperthermia has been used as one of the multidisciplinary treatments in cancer. And in a randomized controlled trial, it was confirmed that hyperthermia is an effective cancer treatment. However, temperature monitoring during treatment is essential for clinical accuracy and safety. We have developed a simple microwave thermotherapy system using spatial real-time temperature monitoring to improve its efficacy and safety.

  An MR microwave irradiation applicator was used to heat agar phantoms, rabbit thigh muscles and rabbit subcutaneous VX2 tumors using non-invasive MR temperature images. For the MR temperature calculation, the phase difference method using the proton resonance frequency was used. After determining the temperature coefficient and evaluating the accuracy of MR temperature measurement, the temperature distribution by microwave heating over time was examined for each subject. The temperature coefficients for phantom, rabbit muscle, and VX2 tumors were -0.00977, -0.00976, and -0.01027 ppm / ° C, respectively. The 95% confidence intervals for MR and optical thermometers in the three subjects were + 0.318 ° C / 0.339 ° C, + 0.693 ° C / 0.661 ° C, and + 0.564 ° C / 0.526 ° C, respectively. For VX2 tumors, the average tumor temperature was 42.60 ° C. ± 0.14 ° C. The skin surface was 43.27 ± 0.45 ° C. in the 60-minute experiment.

  With this easy-to-use microwave thermotherapy system, effective thermotherapy was performed in phantoms and live animals using MR temperature images.

  The present invention is a thermotherapy apparatus system for malignant tumors. A feature of the present invention resides in that a heating device for performing thermotherapy of a malignant tumor and a device for monitoring a temperature change due to heating are combined. The apparatus for monitoring temperature changes due to heating includes means capable of detecting temperature increase with MR temperature images, and the strength of the magnetic field is 0.5-9T, preferably 1.5-9T, more preferably 6-9T. It is a device with a static magnetic field strength. This allowed monitoring of hyperthermia at 42-43 ° C. Heating is performed by irradiating microwaves with a microwave generator. The microwave is irradiated with a microwave generator of 0.4 to 3 GHz, preferably 1.0 to 2.8 GHz, more preferably 1.5 to 2.5 GHz. Irradiation is not performed continuously but intermittently. This makes it possible to control the target area to a targeted level of temperature. In order to heat intermittently, the microwave generator has a function of repeatedly turning the power switch on and off intermittently.

Materials and Methods Subject The experimental protocol was reviewed and approved by the Shiga Medical University Animal Experiment Committee. In the phantom experiment, an agar phantom (120 × 120 × 50 mm ³ ) was prepared with 2% agar, 0.25 mM Gd-DTPA, 0.9% NaCl and 0.05% NaN ³ . Ten male New Zealand White rabbits were used in animal experiments. Six rabbits were injected subcutaneously in the thigh with 5.0 × 10 ⁶ VX2 tumor cells in 0.4 mL phosphate buffer solution. The tumor grew to a diameter of 10-20 mm in 2 weeks. An agar phantom, untreated rabbit femoral muscle, and subcutaneous femoral tumor were used in the experiment. One animal was used in each group (femoral muscle and subcutaneous tumor) to determine temperature coefficient values and to assess the accuracy of MR temperature images. Other animals were also used to study temperature distribution during microwave thermotherapy.

Equipment preparation
Two types of MR-compatible irradiation type microwave applicators were made using non-magnetic materials. Normally, a 100 x 100 x 70 mm ³ reflector (dipole type (Fig. 1A)) with a half-wave (60 mm) dipole antenna set was used. The distance between antenna and reflector was optimized to minimize the standing wave ratio (SWR). In order to heat a small local area, an applicator (slot type (FIG. 1B)) with a 60 × 90 mm ² slot antenna was created. The applicator was connected to a 0.4 to 3 GHz (2.45) GHz microwave generator MicrotazeOT110M (AlfresaPharma, Osaka, Japan) using a coaxial cable having a length of 4 m (Non-patent Document 11). This microwave generator is available in continuous and intermittent modes. In the intermittent mode, power on for 2 seconds and power off for 2 seconds are repeated alternately. For thermotherapy, it was usually applied intermittently with a power of 60-110W. An optical thermometer, model 3100 (Luxtron, Santa Clara (CA)) was used to measure the absolute temperature of the subject. A 0.3 mm diameter thermometer was inserted with a 20G Teflon needle. Superconducting electromagnet with an opening diameter of 40cm (0.5-9T / 400mm (7.0T / 400mm) / SS (JASTEC, Kobe (Japan))) and 0.5-9T (7.0T) MR scanner [UnityInova (Varian ( MR data using a gradient echo sequence was collected using Palo Alto (CA))). The relative temperature change is calculated from the chemical shift of the temperature-dependent water signal (Non-Patent Document 9). When gradient echo is used, a chemical shift caused by the phase difference occurs during the echo time.
The temperature coefficient α is reported to be about −0.01 ppm / ° C., but can vary depending on the subject (Non-patent Document 15). Temperature coefficient (α) values for agar phantoms, rabbit thigh muscles and subcutaneous tumors are compared to the temperature on the optical thermometer and the average phase shift of the 1HMR signal in 5 × 5 pixels around the thermal probe It was determined individually. Two values were evaluated by Pearson's product moment correlation coefficient. With individual temperature coefficients, MR temperature images were calculated. The 95% confidence interval for the MR temperature image of the optical thermometer was defined as an average of ± 1.96 SD in the Bland-Altman plot (Non-patent Document 16).

Phantom Experiment A dipole-type microwave applicator was installed in an agar phantom in a magnet. Phantom's gradient echo image shows 20 ms repetition time (TR), 8 ms echo time (TE), 20 ° flip angle and 3 mm slice thickness, field of view 150 x 150 mm ² (FOV), 128 Obtained with × 128 matrix and 1 integration. The time required for one image was 4.8 seconds including the time for data storage. The temperature increase was calculated using the α value of the agar phantom, and the real-time MR temperature image was displayed on an external computer. Baseline temperature (room temperature) was lower than body temperature (36.5 ° C), but the temperature increase in the 10 mm depth area was controlled in the range of 5.5 ° C to 6.5 ° C. That corresponds to 42-43 ° C for animals. We referred to the MR temperature image to determine when to turn the microwave generator power switch on and off.

Animal Experiments on Untreated Thigh Muscle Animals were anesthetized with 3% isoflurane of 50% O ² and 50% N ^{2 with} a face mask while maintaining spontaneous breathing. The rabbit's thigh hair was shaved. The thermometer was inserted into an area 10 mm deep from the body surface. A dipole type microwave applicator was installed on the thigh. Other body parts were covered with a blanket to maintain body temperature. Gradient echo images of rabbit thigh muscles were obtained with 20 ms TR, 8 ms TE, 20 ° flip angle, 3 mm slice thickness, 200 x 200 mm ² FOV, 256 x 256 matrix and 1 integration. It was. The time required for one image was 8.2 seconds including the time for data storage. The temperature was calculated using the muscle alpha value, as in the phantom experiment. The target temperature increase was determined from the difference of 42-43 ° C from the baseline absolute temperature with a thermometer. The microwave generator was adjusted by referring to the temperature increase in the 10 mm deep area in the MR temperature image.

Animal experiments on subcutaneously injected VX2 tumors Animals were prepared as in the untreated femoral muscle experiments. In this experiment, a slot type applicator was used to heat only the local tumor area. An optical thermometer was inserted into the center of the tumor. Since the tumor's ¹ HMR signal level was as low as the acquired parameters in the thigh muscle, the tumor's gradient echo image was 40 ms TR, 6 ms TE, 40 ° flip angle, 3 mm slice thickness It was obtained with 150 × 150 mm ² FOV, 128 × 128 matrix and 2 integrations. The acquisition time of one image was 12.5 seconds including the time for data storage. The microwave generator was controlled by referring to the temperature increase at the tumor in the MR temperature image. Other experimental conditions were the same as for untreated femoral muscle.

Results Phantom Experiment No noise appeared in the MR image during microwave radiation. The relationship between the temperature change measured by the optical thermometer and the phase shift of the gradient echo image is shown in FIG. 2A. The correlation between the two values was good (correlation coefficient (r) = 0.997, P <0.0001). The slope of the regression line was 8 ms TE, -8.444 ° phase shift / ° C, corresponding to the temperature coefficient, α, -0.00977 ppm / ° C. The temperature increase from the MR temperature image calculated using this α value was compared with the temperature increase from the optical thermometer. Bland-Altman plots of the two measurement methods are shown in FIG. 2B. The average error of the two methods was -0.0106 ± 0.168 ° C (mean ± SD) and the 95% confidence interval was + 0.318 / -0.339 ° C. Bland-Altman plots did not fit the typical systematic bias pattern.
After evaluating the accuracy and reliability of MR temperature images, various conditions of microwave heating using a dipole-type microwave applicator were studied. Initially, the phantom was heated at 110W in continuous mode. The surface was heated quickly, but the deep part was not heated. When the temperature increase in the 10 mm deep area was maintained at 5.5-6.5 ° C, the surface was heated above 15 ° C. The 20mm deep area was heated to less than 3 ° C. After that, the output power was reduced to 30W in continuous mode. However, the maximum surface temperature increase was still 11 ° C. In 60W intermittent mode, it took about 10 minutes to reach the target temperature in an area of 10mm depth. However, the temperature at the surface was kept within 8 ° C. Moreover, the area of 20 mm depth was 4 ° C or higher. An MR temperature image of the heated agar phantom using this condition is shown in FIG. The region where the temperature difference from the target region was less than 1 ° C. was about 60 mm in the transverse direction and about 20 mm in the vertical direction. The spatial distribution of the temperature spreading around 1 ° C radially around the heating center was clearly shown.

Animal Experiments on Untreated Thigh Muscle Similar to the results of the phantom experiment, the relationship between the temperature change measured with an optical thermometer and the phase shift of the gradient echo image was examined in the untreated rabbit thigh muscle (FIG. 2C). The correlation between the two was significant (r = 0.966, P <0.0001). The slope of the regression line was -8.435 ° phase shift / ° C at 8 ms TE. It corresponded to a temperature coefficient, α, -0.00976 ppm / ° C. The result of the temperature calculation using this α value was compared with the value obtained with an optical thermometer using the Bland-Altman plot (FIG. 2D). The average difference between the two measurements was + 0.0160 ± 0.345 ° C. The 95% confidence interval was + 0.693 / -0.661 ℃. The thigh muscle was heated at 80W using intermittent mode. A typical temperature image of the thigh muscle is shown in FIG. Figure 5 shows the temperature change (average ± SD every 5 minutes) on the surface at the center, the area of 10 mm depth and the area of 20 mm depth, and the surface 20 mm away from the center using three rabbits. It was. In a 10mm deep area, the increase to the target temperature of 42-43 ° C was achieved in 5 minutes. The surface temperature was maintained below 44 ° C and was about 1 ° C higher than the 1 cm deep area. The temperature in the 20 mm deep area gradually increased even when the surface and the 10 mm deep area were in steady state. The temperature difference between the 10 mm and 20 mm areas was less than 1 ° C. at the end of the 30 minute experimental period.

Animal experiments on subcutaneously injected VX2 tumors A slot-type microwave applicator was used to heat subcutaneous VX2 tumors. The correlation between the temperature change measured with an optical thermometer and the phase shift of the gradient echo image was good (r = 0.887, P <0.0001) (FIG. 2E). The slope of the regression line was -6.658 ° phase shift / ° C at 6 ms TE. It corresponded to a temperature coefficient, α, -0.01027 ppm / ° C. A Bland-Altman plot (FIG. 2F) showed that the average difference between the two measurements was + 0.0192 ± 0.272 ° C. The 95% confidence interval was + 0.564 / -0.526 ℃. Five rabbit tumors were heated at 110 W using intermittent mode. Tumor temperature was maintained at 42-43 ° C. for 1 hour. A representative temperature image during heating is shown in FIG. Only the area of the tumor was selectively heated. The temperature change on the lower and upper surface of the tumor as well as the tumor area of one rabbit is shown in FIG. The temperature of most of the tumors was maintained at approximately the target temperature during the 1 hour experiment. Table 1 summarizes the mean, maximum, and minimum temperatures of the tumors after reaching the target temperature level, and the elapsed time in various temperature ranges, to assess the temperature of the entire tumor in five rabbits. Tumor temperature was maintained at 42-43 ° C. for over 80% of the duration of treatment. On the other hand, as shown in Table 2, the surface temperature exceeded 44 ° C. for 8.7 minutes in the 60-minute experiment. No obvious skin burns were observed in any rabbit.

Effect of the Invention In order to detect small temperature increases during thermotherapy with MR temperature images, this study was experimented with MR with a static magnetic field strength of 0.5-9T (7T). It has a much higher static magnetic field strength than a clinical MR scanner. The resonance frequency of the ¹ H signal at 7T is 300 MHz. High magnetic field systems can obtain MR signals with a good signal-to-noise ratio. Also, a high resonance frequency is advantageous for detecting temperature dependent phase shifts. In agar phantoms, rabbit thigh muscles and subcutaneous tumors, the temperature changes measured with an optical thermometer and the phase shift of the gradient echo image correlated very well. The measured temperature coefficient value, α (temperature-dependent water chemical shift) of these objects was consistent with previous reports (Non-Patent Document 15). The 95% confidence interval between the optical thermometer and MR thermometry was determined by Bland-Altman plot for + 0.318 / -0.339 ° C, + 0.693 / -0.661 ° C and + 0.564 /-, respectively, in phantom, untreated muscle and subcutaneous tumor. It was 0.526 ° C. The accuracy and reliability of temperature measurements in a 7T static magnetic field was sufficient in monitoring thermotherapy at 42-43 ° C. And we obtained better results than the previous 0.5T results (Non-patent document 11) (Non-patent document 13) and 2TMR system (Non-patent document 17). However, the accuracy of MR temperature images in live animals was slightly lower than in phantoms. MR temperature calculation by PRF method may be affected by various factors. Among them, the movement of the object is important because the temperature is calculated by the difference between the warming image and the baseline image. In this study, temperature changes below 10 ° C were calculated from slight differences in the phase shift of the MR signal. Animal movements can cause problems because movements in the image plane as well as other parts may affect the static magnetic field on the image plane.
Temperature monitoring during hyperthermia is an indispensable issue for carrying out effective and safe treatment. Unlike other heat treatment means such as thermocoagulation and cryotherapy, thermotherapy does not immediately cause a tissue thermal response. The doctor may not see the intended reaction and may miss serious side effects. It has been reported that the treatment results were good when the tumor was heated more accurately even with only a few internal measurement points (Non-patent document 8) (Non-patent document 18) (Non-patent document 19). Non-patent document 20) (non-patent document 21). Therefore, non-invasive and reliable temperature monitoring of the entire tumor plays an important role in improving this therapeutic effect. Kato et al. (Non-Patent Document 7) reported that measuring the temperature of a tumor with a ± 2 ° C error is useful for clinicians to monitor the state of thermotherapy. From this point of view, MR temperature monitoring can fully support this treatment.
The 0.4-3 GHz (2.45 GHz) microwave generator did not affect MR images received at 300 MHz without using filters or special circuitry even during irradiation. In order to control the temperature to the target level, the power switch was turned on and off intermittently, but noise did not appear in the MR image, and the image could not be distinguished by turning the switch on and off. On the other hand, radiofrequency (RF) heating is more popular than microwave heating in thermotherapy. However, RF irradiation has a significant effect on MR images. Usually, in order to simultaneously perform RF thermotherapy and MR temperature measurement, a device such as a time-sharing circuit or a frequency filter is required (Non-patent Document 22). Microwave heating appeared to be more suitable than RF thermotherapy when using MR temperature images.
We have created two types of applicators for microwave heating. With these applicators, effective heating for hyperthermia treatment in an area of 10 mm depth was obtained. The temperature was well maintained at the target level by monitoring MR temperature images. The skin surface temperature must be monitored to avoid skin burns. When an agar phantom in an area with a depth of 10 mm was heated to 5.5-5.6 ° C in continuous mode, the surface temperature became too high. Using the intermittent mode, deeper areas can be heated without overheating the surface. The heat is dissipated to deeper areas and the surface is cooled while the microwave radiation is turned off.
When a standard dipole type applicator was used, the surface temperature was maintained at 44 ° C. or lower even when the area of 10 mm deep thigh muscle was maintained at 42-43 ° C. In the slot-type applicator, a 10-20 mm diameter tumor area was selectively warmed. Tumor temperature was maintained at about 42-43 ° C. for about 45 minutes of 60-minute treatment with intermittent microwave irradiation. On the other hand, the surface temperature was almost 44 ° C. or lower. And the time above 44 ° C. was 9 minutes for a treatment period of 60 min. It has been reported that most normal tissues including skin are not damaged even when heated at 44 ° C. or lower for 1 hour (Non-patent Document 23). For more heat-sensitive nervous systems, warming the peripheral nerve for more than 30 minutes at 44 ° C (or equivalent "warming") causes temporary dysfunction, which recovers within 4 weeks ( Non-patent document 24). Overheating of the skin surface can be prevented by a coolant. However, thick coolant interferes with microwave heating to deep tissue. Circulating water reduces the accuracy of MR temperature measurements. Cooling by airflow may be effective for the system of the present invention (Non-patent Document 25).
Our microwave applicator for heating is small and easy compared to conventional thermotherapy systems. Local hyperthermia has been performed in breast cancer and the like. We are considering the possibility of using this system for hyperthermia during surgery. Continuous thermal peritoneal perfusion is now performed in several facilities. In most cases it is used in combination with chemotherapy. It is effective to some extent for peritoneal seeding (Non-patent document 26) (Non-patent document 27) (Non-patent document 28). However, the effect is slight for lesions exceeding 2 mm (Non-patent Document 29). Although the temperature of the circulating water is controlled, the actual increase in tissue temperature is not monitored. It may be possible to heat an area of only 1 or 2 mm from the surface of the peritoneum (Non-patent Document 30). If the tissue is heated accurately, intraoperative hyperthermia may be effective for residual tumors. With microwave heating, tumor cells that contain more water are heated more than adipose tissue, which may be effective for tumor cells that are engulfed in adipose tissue. Although further investigation is needed, a miniature microwave thermotherapy system that monitors spatial temperature distribution with MR temperature images may be a promising therapy in minimally invasive therapy.

MR, compatible, radiation type, microwave applicator, dipole type (A) and slot type (B). (A) A 60 mm long dipole antenna is located in the reflector. (B) A 60 x 90 mm 2-slot antenna was constructed with a reflector. Scatter plot with linear regression line between temperature change measured with optical thermometer in agar phantom and phase shift of ¹ H signal in gradient echo image. Bland-Altman plot of temperatures measured with an optical thermometer and MR thermometer in an agar phantom. The Y axis shows the difference between the two methods (MR-optical thermometer). The X axis indicates the middle of the two. The average difference is indicated by a dotted line. The 95% confidence interval is shown as a solid line. Scatter plot with linear regression line between temperature change measured with optical thermometer in rabbit thigh muscle and phase shift of ¹ H signal in gradient echo image. Bland-Altman plot of temperature measured with optical thermometer and MR thermometer in rabbit thigh muscle. The Y axis shows the difference between the two methods (MR-optical thermometer). The X axis indicates the middle of the two. The average difference is indicated by a dotted line. The 95% confidence interval is shown as a solid line. Scatter plot with linear regression line between temperature change measured with optical thermometer in subcutaneous tumor and phase shift of ¹ H signal in gradient echo image. Bland-Altman plot of temperatures measured with optical and MR thermometers in subcutaneous tumors. The Y axis shows the difference between the two methods (MR-optical thermometer). The X axis indicates the middle of the two. The average difference is indicated by a dotted line. The 95% confidence interval is shown as a solid line. A typical MR temperature image of an agar phantom heated with a dipole type applicator. The temperature increase is shown in the right color-coded scale. The arrow indicates the direction of heating from the applicator. Experiments with an agar phantom (results at each part of heating time and rising temperature with microwave output 110W continuous heating (surface, depth 1 cm, depth 2 cm, depth 3 cm, surface 3 cm side, surface 2 cm side) Experiments with an agar phantom (results in each part of heating time and rising temperature with microwave output 30W continuous heating (surface, depth 1 cm, depth 2 cm, depth 3 cm, surface 3 cm side, surface 2 cm side) Results (surface, depth 1 cm, depth 2 cm, depth 3 cm, surface 3 cm side) in each part of heating time and rising temperature in an experiment with an agar phantom (microwave output 60W intermittent heating (2 seconds on, 2 seconds off)) , Surface 2cm side) Representative MR and temperature images of the thigh muscles were heated with a dipole type applicator. The temperature increase and direction of heating are shown as in FIG. Microwave output 80W 30 minutes Intermittent heating (2 seconds on, 2 seconds off) results in each part of heating time and rising temperature (surface center, center depth 1 cm, center depth 2 cm, surface side 2 cm) Continuous change in the temperature of the surface at the center position (×), the area of depth 10 mm (◆) and depth (□) 20 mm, and the surface 20 mm away from the center (○). Three rabbits (A), (B), and (C) were examined. Values are shown as mean ± SD every 5 minutes. Representative MR and temperature images of VX2 subcutaneous tumors were heated with a slot-type applicator. The temperature increase and direction of heating are shown as in FIG. Continuous changes in the temperature of the rabbit tumor (♦), surface (×), and directly under the tumor (□) (Experiment 1 in Tables 1 and 2). The output power was controlled to maintain the temperature of the tumor (♦) at 42-43 ° C.

Claims (1)

A thermotherapy device system for malignant tumors, using 0.5-9T static magnetic field strength to detect temperature increase with MR temperature images, enabling monitoring of thermotherapy at 42-43 ° C, 0.4-3GHz A hyperthermia device for malignant tumors that has the function of intermittently turning on and off the power switch in order to irradiate the microwave with a microwave generator and control the target area to a target level of temperature. system.