JP2014217560A - No sensitization-type radiation cancer treatment system - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an NO sensitization-type radiation cancer treatment system capable of enhancing cancer therapeutic effect without increasing the irradiation dose.SOLUTION: In a nitric monoxide sensitization-type radiation cancer treatment system which applies a radiation beam and an ultrasonic beam, by utilizing the fact that a peak period Tp during which nitric monoxide concentration D is at its maximum occurs with an optimal delay time after an application start time Ts at which application of the ultrasonic beam to generate nitric monoxide was started, the radiation is applied concentratedly during this peak period. In addition, by utilizing the fact that the production of nitric monoxide by application of ultrasonic beam is increased specifically in certain tumor temperature range, the ultrasonic beam for nitric monoxide production is applied after the tumor is preheated to a favorable temperature range.

Description

  The present invention relates to a NO-sensitized radiation cancer treatment system that simultaneously irradiates a cancer tissue from outside the body with a radiation beam and an ultrasonic beam.

  In order to destroy cancer tissue in the body, radiotherapy that irradiates a radiation beam such as X-rays from outside the body is widely adopted as a non-invasive cancer treatment apparatus. According to this radiation therapy, oxygen radicals generated inside the cancer tissue by X-rays damage the DNA of cancer cells.

  However, since the central part of the solid cancer is in a hypoxic environment, it has been difficult to completely kill all cancer cells inside the cancer tissue, particularly cancer stem cells. This problem is improved over the NO sensitizing type radiotherapy described in Patent Document 1 which is the invention of the present inventors.

  According to this NO-sensitized radiotherapy, X-rays are irradiated to a cancer tissue in a state where nitric oxide (NO) is produced in the cancer tissue by irradiation with an ultrasonic beam from outside the body. Nitric oxide has an excellent feature of improving the cancer destruction effect of X-rays even in a hypoxic environment. In other words, if the treatment effect is the same, this NO-sensitized cancer treatment method can reduce the radiation dose compared with the conventional simple X-ray irradiation method, thus improving the standard of living of patients To do.

  However, this NO-sensitized cancer treatment method is also expected to further improve the therapeutic effect and further improve the standard of living of the patient. In other words, it is expected to reduce the total amount of radiation and ultrasonic energy irradiated to the human body. In addition, shortening of device operation time required for cancer treatment is also expected.

Japanese Patent No. 5027910

  One object of the present invention is to provide a NO-sensitized radiation cancer treatment system capable of further improving the cancer treatment effect. Another object of the present invention is to provide a NO-sensitized radiation cancer treatment system capable of reducing the radiation dose and the amount of ultrasonic energy irradiated to a patient. Another object of the present invention is to provide a NO-sensitized radiation cancer treatment system capable of simplifying the device configuration and operation. Yet another object of the present invention is to provide a NO-sensitized radiation cancer treatment system capable of shortening the required apparatus operating time.

  The NO-sensitized cancer treatment system of the first and second inventions is essentially the same as the device disclosed in Patent Document 1. According to this apparatus, nitric oxide is formed in a cancer tissue by irradiation with an ultrasonic beam. This nitric oxide greatly improves the cancer treatment effect of radiation such as X-rays.

  According to the first invention, the peak period of the nitric oxide concentration generated after a predetermined time from the operation start time of the ultrasonic NO generator is estimated, and radiation is irradiated in this peak period. As a result, since radiation irradiation is performed only in the region where the nitric oxide concentration is maximum, the radiation sensitizing effect of nitric oxide (NO) can be enjoyed to the maximum. In other words, the total amount of radiation irradiated can be reduced. This means that it is possible to prevent a decrease in the living level of the patient.

  According to the experiments by the present inventors, the nitric oxide concentration in the cancer tissue measured under a condition where the ultrasonic energy density is constant increases from the start of the irradiation of the ultrasonic beam, and reaches a maximum value after a predetermined time. Then decline. In other words, it was found that after irradiation with the ultrasonic beam, the nitric oxide concentration has a higher peak period than other periods.

  Therefore, it can be seen that if radiation is irradiated during the peak period of this nitric oxide concentration, the radiation dose can be reduced without reducing the cancer treatment effect. In other words, this peak period coincides with the radiation irradiation period. As a result, the radiation dose equivalent to the product of irradiation intensity * irradiation time can be reduced, so that the burden on the patient can be reduced.

  Further, according to the experiments by the present inventors, the temporal position of this peak period and the nitric oxide concentration within this peak period measured from the start of the ultrasonic beam irradiation are the temperature of the cancer tissue to be irradiated. It was found to have a strong correlation with Therefore, by measuring the temperature of the cancer tissue during the peak period or during the irradiation period of the ultrasonic beam for generating nitric oxide, the temporal position of the peak period measured from the start of the irradiation of the ultrasonic beam is estimated. be able to. Of course, other parameters such as the energy density of the ultrasonic beam can also be used to estimate the temporal position of this peak period.

  More specifically, as the cancer tissue temperature rises, the amount of nitric oxide produced increases. However, when the cancer tissue temperature reaches a predetermined maximum temperature, the production amount of nitric oxide rapidly decreases. In the irradiation period of the ultrasonic beam for generating nitric oxide, the cancer tissue temperature is preferably kept in the range of 39-44.5 ° C, more preferably 40-44 ° C.

  Of course, it is possible to increase both the temperature and the nitric oxide concentration rapidly by irradiating an ultrasonic beam having a very high energy density. However, such irradiation with a strong ultrasonic beam leads to problems such as an increase in the size of the ultrasonic device and a rapid rise in body surface temperature.

  According to a preferred embodiment, the cancer tissue is heated by the heating device at least immediately before the operation of the ultrasonic NO generator is started. Thereby, after the start of the ultrasonic NO generator, the nitric oxide concentration in the cancer tissue can be rapidly increased. It is possible to continue the operation of the heating device even after the operation of the ultrasonic NO generator is started.

  According to a preferred embodiment, the heating device is constituted by an ultrasonic heating device that irradiates a cancer tissue with an ultrasonic beam having a higher frequency than that of the ultrasonic NO generator. Thereby, the structures of the ultrasonic NO generator and the heating device are simplified.

  According to our experiments, when the energy density of the ultrasonic beam is constant, the temperature of the cancer tissue rises with an increase in the frequency of the ultrasonic beam. On the other hand, when the energy density of the ultrasonic beam is constant, the nitric oxide concentration in the cancer tissue increases due to a decrease in the frequency of the ultrasonic beam. This means that when an ultrasonic beam is used as the heating means, a large temperature increase can be achieved while suppressing an increase in output of the ultrasonic beam by using a high-frequency ultrasonic beam. Moreover, it means that it is suitable to employ | adopt a low frequency ultrasonic beam for production of nitric oxide.

  By various methods, heating with a high-frequency ultrasonic beam and production of nitric oxide with a low-frequency ultrasonic beam can be performed simultaneously. First, a high-frequency ultrasonic beam and a low-frequency ultrasonic beam can be irradiated simultaneously. Next, irradiation with a high-frequency ultrasonic beam and irradiation with a low-frequency ultrasonic beam can be performed alternately in time. Furthermore, after applying a high-frequency oscillation voltage to a single ultrasonic transducer, a low-frequency oscillation voltage can be applied.

  According to a preferred embodiment, the ultrasonic heating device that outputs a high-frequency ultrasonic beam and the ultrasonic NO generator that outputs a low-frequency ultrasonic beam share a common probe for ultrasonic output.

  According to the second aspect of the invention, the cancer tissue is preheated to a predetermined temperature range before the operation of the ultrasonic NO generator is started. If the cancer tissue is irradiated with an ultrasonic beam for NO production immediately after this preheating, the nitric oxide concentration can be increased rapidly compared to the case without preheating, and the nitric oxide concentration Can be increased. Therefore, an excellent cancer treatment effect can be obtained by irradiating radiation together with the ultrasonic beam for NO production. In other words, if the cancer treatment effect is constant, the total radiation dose can be reduced.

  It is disclosed in Patent Document 1 that the inventors of the present invention have that the radiotherapy effect is remarkably improved when the concentration of nitric oxide in the cancer tissue is large. In particular, nitric oxide kills cancer cells in the hypoxic region inside cancer tissue well.

  According to a preferred embodiment, the temperature of the cancer tissue is maintained at 40-45 ° C. by controlling the output of the heating device or the ultrasonic NO generator during the period of outputting the ultrasonic beam for NO production. . If the temperature of the cancer tissue is lower than 40 ° C., the ability to produce nitric oxide concentration of the cancer tissue is lowered. When the temperature of the cancer tissue exceeds 45 ° C., the ability to produce nitric oxide concentration in the cancer tissue decreases.

  According to a preferred embodiment, the heating device is constituted by an ultrasonic heating device that irradiates a cancer tissue with an ultrasonic beam having a higher frequency than the ultrasonic NO generator. Thereby, the apparatus configuration can be simplified.

  According to a preferred embodiment, the ultrasonic heating device and the ultrasonic NO generator share a common ultrasonic probe. Thereby, the apparatus configuration can be simplified.

  According to a preferred embodiment, the ultrasonic heating device outputs an ultrasonic beam having a frequency in the range of 1 MHz to 10 MHz, and the ultrasonic NO generator is an ultrasonic beam having a frequency in the range of 100 kHz to 1000 kHz. Is output. This facilitates the common use of the heating device and the nitric oxide generator, so that the device configuration and operation can be simplified.

  The ultrasonic beam, for example, by adopting a phased array structure or the like has a good focus convergence property, and thus is excellent for locally heating cancer tissue and the like. Furthermore, since the ultrasonic energy density given to the normal tissue between the body surface and the cancer tissue can be reduced by the focal convergence of the ultrasonic beam, the temperature rise of normal cells can be suppressed.

  According to a preferred embodiment, the low-frequency vibrator for NO production and the high-frequency vibrator for preheating are mounted on a common head. This common head is brought into close contact with the body surface of the human body through the ultrasonic transmission material. This simplifies the device configuration and simplifies operation.

  According to a preferred embodiment, the low-frequency vibrator for NO production and the high-frequency vibrator for preheating are constituted by a common vibrator. This simplifies the device configuration and simplifies operation. Furthermore, since an ultrasonic beam that converges from a large area transducer to the focal point can be employed, normal cells can have a wide beam cross-sectional area. As a result, normal cell heating can be suppressed.

  According to a preferred aspect, the common ultrasonic transducer outputs a high-frequency ultrasonic beam mainly for heating, and then outputs a low-frequency ultrasonic beam mainly for producing nitric oxide. Thereby, size reduction of an ultrasonic device can be achieved, maintaining required preliminary heating and NO production.

  According to a preferred embodiment, the ultrasound beam for warming and NO production can have an energy density of 0.5 W / square cm-1.5 W / square cm in cancer tissue.

  According to a preferred embodiment, the pre-warming vibrator and the ultrasonic vibrator of the ultrasonic NO generator are mounted on a ring-shaped head having a radiation irradiation hole in the center. Thereby, the head which outputs an ultrasonic beam can be made into a simple structure.

FIG. 1 is a schematic block diagram showing an experimental apparatus. FIG. 2 is a diagram showing temporal changes in temperature and NO concentration (D) in a non-heating case. FIG. 3 is a diagram showing temporal changes in temperature and NO concentration (D) in a heating case. FIG. 4 is a diagram showing the relationship between the frequency change of the ultrasonic beam and the NO production dose. FIG. 5 is a diagram showing temporal changes in temperature and NO concentration (D) when a high-frequency ultrasonic beam is used. FIG. 6 is a block diagram of the NO sensitizing radiation cancer treatment system of the embodiment. It is a flowchart which shows the example of control of the NO sensitizing type radiation cancer treatment system of an Example. It is a model perspective view which shows an example of an ultrasonic transducer | vibrator arrangement | sequence. It is a model perspective view which shows the other example of an ultrasonic transducer | vibrator arrangement | sequence.

Description of NO-sensitized radiation cancer therapy First, a brief description of NO-sensitized radiation cancer therapy using X-rays as radiation will be given. According to the NO-sensitized X-ray treatment described in Patent Document 1, both X-rays and an ultrasonic beam are irradiated to a cancer tissue. Nitric oxide (NO) is generated in cancerous tissue by the ultrasonic beam. This nitric oxide greatly improves the cancer treatment effect of X-rays.

  One experimental example of this NO-sensitized X-ray therapy is described below. First, four tumor groups were used as experimental subjects. Each tumor is of the same type. Each of the four tumor groups had an equal average weight (average value of 207.9 mg). The treatment was performed 5 times every other day, and the therapeutic effect was examined based on the tumor weight removed on the 10th day after the end of the treatment. The group irradiated with 2394.5 mg, X alone was 580.6 mg, and the group irradiated with both X-rays and ultrasound was 228.8 mg. From this experimental result, it is understood that the NO-sensitized X-ray therapy is a non-invasive cancer therapy with excellent cancer treatment results.

  It is important that the NO-sensitized X-ray therapy is effective in suppressing the growth of cancer cells in the internal region of cancer tissue, particularly cancer cells in the internal hypoxic region. The internal region of the cancer tissue present in the hypoxic environment is less killed by X-ray irradiation. This is because the generation of oxygen radicals that attack cancer cells is small. According to NO-sensitized X-ray therapy, nitric oxide is generated in the internal region of cancer tissue, and the radicals produced by this nitric oxide attack cancer cells instead of oxygen radicals. Can do.

  It is easily understood that the production of nitric oxide (NO) can improve the X-ray sensitization effect of nitric oxide. However, in order to increase the nitric oxide concentration, the cancer tissue must be irradiated with an ultrasonic beam having a very high energy density. It is not easy to manufacture an ultrasonic device that emits such a powerful ultrasonic beam. Furthermore, the problem that a normal cell adjacent to a cancer tissue is adversely affected by heat or biochemistry due to irradiation with a strong ultrasonic beam is also derived.

  In the end, it is understood that increasing the production of nitric oxide without unduly increasing the energy density of the ultrasound beam is very important in NO-sensitized X-ray therapy. Based on this viewpoint, the present inventors investigated the relationship between the amount of nitric oxide produced in the cancer tissue by the ultrasonic beam and the temperature of the cancer tissue.

Explanation of relationship between temperature and nitric oxide concentration in cancer tissue A tumor model formed by inoculating rat glioma as cultured tumor cells subcutaneously in the thigh of rats was used as an experimental model. In order to change the temperature of the cancer tissue, a U-shaped hot water tube was placed in the vicinity of the cancer tissue. FIG. 1 is a schematic block diagram showing an experimental apparatus. The X-ray irradiation apparatus 1 is disposed above the table 3 on which the rat 2 is placed. The X-ray irradiation apparatus 1 is MBR-1520R (manufactured by Hitachi). The probe 4 for irradiating the ultrasonic beam is disposed below the table 3. An ultrasonic transducer is attached to the upper end surface of the probe 4.

  High frequency power is supplied to this ultrasonic transducer from an oscillation circuit (not shown). An acoustic stand 5 is interposed between the probe 4 and the table 3 in order to transmit an ultrasonic beam emitted from the probe 4. The upper surface of the accor stand 5 is in contact with the lower surface of the tumor 20 of the rat 2 via an ultrasonic jelly. An ultrasonic non-reflective plate 6 is disposed between the X-ray irradiation apparatus 1 and the table 3 to prevent standing waves in the body. An acoustic stand 7 is interposed between the ultrasonic non-reflective plate 6 and the table 3 for transmission of the ultrasonic beam.

  An ultrasonic beam having a frequency of 500 kHz was irradiated from the probe 4 to the entire tumor 20. This ultrasonic beam has an energy density of 1 W / square cm in cancer tissue. The ultrasonic beam was continuously irradiated for 10 minutes. Nitrogen monoxide concentration (D) and temperature (T) in the tumor were measured by inserting a NO sensor and a temperature sensor into the tumor.

  First, the time change of the temperature (T) of the cancer tissue and the NO concentration (D) in the cancer tissue in the non-warming case where no heating was performed was measured. The supply of hot water to the hot water pipe is stopped by a valve. FIG. 2 is a timing chart showing temporal changes in temperature (T) and NO concentration (D) in this non-heating case. The temperature (T) and NO concentration (D) increased with the irradiation of the ultrasonic beam and decreased rapidly with the stop of the irradiation.

  Next, the time change of the temperature (T) of the cancer tissue and the NO concentration (D) in the cancer tissue in the heating case where the heating is performed was measured. Hot water was supplied to the hot water pipe. The temperature of the hot water is about 60 ° C. FIG. 3 is a timing chart showing temporal changes in temperature (T) and NO concentration (D) in this heating case. First, the temperature (T) of the cancer tissue gradually increased due to the supply of hot water.

  Next, when the temperature (T) of the cancer tissue reached about 33 ° C., irradiation with an ultrasonic beam was started. The temperature (T) of the cancer tissue increased rapidly immediately after irradiation with the ultrasonic beam. When the temperature (T) reached about 45 ° C., the irradiation of the ultrasonic beam was stopped. When the irradiation with the ultrasonic beam was stopped, the temperature (T) decreased to about 35 ° C., and then gradually increased by warming with warm water.

  The NO concentration (D) increased very rapidly immediately after irradiation with the ultrasonic beam. The NO concentration (D) reached the maximum concentration value about 3 minutes after the start of irradiation with the ultrasonic beam. Thereafter, the NO concentration (D) decreased rapidly.

  2 and 3, it was found that the NO concentration generated in the tumor by the ultrasonic beam is improved by heating the tumor temperature. The true reason is still unknown to the inventors. However, when the tumor temperature reaches about 43-44 ° C, the fact that the concentration of NO in the tumor decreases sharply suggests that the physiological activity of the cancer cell itself has an influence on the production of NO in the tumor. Yes.

  In other words, it was found that heating of cancer tissue exceeding body temperature is effective for NO production by an ultrasonic beam. Furthermore, it has been found that this NO production is almost stopped when the temperature of the cancer tissue reaches the cancer cell rapid death temperature (for example, 44 ° C.).

  Eventually, it is understood that the nitric oxide concentration in the cancer tissue can be increased by heating the cancer tissue in the NO-sensitized X-ray therapy. Further, it has been found that irradiating a tumor having a suitable temperature range of 39-44 ° C., further 40-43 ° C. with an ultrasonic beam for NO production is suitable for increasing the NO concentration.

  It is important that the cancer region is heated at least before irradiation with an ultrasonic beam for NO production. As a result, nitric oxide is rapidly generated immediately after the start of irradiation of the ultrasonic beam for NO production (Ts), and the maximum value of the nitric oxide concentration is significantly increased.

  Of course, heating can be performed in order to maintain the above-mentioned preferable temperature range even during the irradiation period of the ultrasonic beam for NO production. However, since the ultrasonic beam for NO production itself gives thermal energy to the cancer region, the necessity for heating during the irradiation period of the ultrasonic beam for NO production is relatively small.

  Next, it was found that when a cancer tissue is irradiated with an ultrasonic beam for NO production, the nitric oxide concentration in the cancer region has a peak period (Tp) that is a relatively short period. According to the case where the tumor is not heated, this peak period (Tp) occurs in the vicinity of the time point when the ultrasonic beam irradiation ends. According to the case where the tumor is heated, this peak period (Tp) is delayed by a predetermined time from the ultrasonic beam irradiation start time (Ts). However, referring to FIG. 2 and FIG. 3, it is understood that the peak period of the nitric oxide concentration starts earlier by heating.

  The fact that the temporal center position of the peak period (Tp) shifts with tumor temperature is important. The period of X-ray irradiation is shorter than the ultrasonic irradiation period (Tx) for NO production. In general, the X-ray irradiation period is 2-4 minutes, and the ultrasonic irradiation period for NO production is 10-15 minutes. This means that the best cancer treatment effect can be obtained by performing X-ray irradiation in accordance with the peak period of the generated nitric oxide concentration.

  Preferably, the peak period (Tp) including the highest point of the nitric oxide concentration has a length corresponding to the X-ray irradiation period. This peak period (Tp) can be determined by various methods. The first method is to detect the temperature of the tumor or the nitric oxide concentration, and based on that, estimate the point in time when the nitric oxide concentration is highest. The peak period (Tp) can be set including the point in time when the nitric oxide concentration becomes maximum.

  According to other methods, the peak period (Tp) is estimated from body temperature, room temperature, heat flow generated by the heating device, heat flow generated by the ultrasonic beam for NO production, heat flow generated by X-rays, etc. Is done. In other words, an optimal delay time is set between the irradiation start time (Ts) of the ultrasonic beam for NO production and the X-ray irradiation start time. As a result, it is possible to maximize the cancer treatment effect while suppressing an increase in the X-ray irradiation amount and the ultrasonic beam irradiation amount.

  The present inventors have considered a means for performing tumor warming, particularly pre-warming of the tumor performed before irradiation with an ultrasonic beam for NO production. A known cancer treatment method known as so-called ultrasonic hyperthermia is a cancer treatment method in which cancer cells are thermally necrotized by maintaining a tumor at a high temperature for a long time. However, since this ultrasonic hyperthermia needs to prevent thermal necrosis of normal cells, it has a problem that actual operation is very difficult.

  Similar to the ultrasonic hyperthermia method, the preheating of the tumor can be performed with an ultrasonic beam. However, the preliminary heating using this ultrasonic beam has an advantage that the apparatus configuration can be simplified because both NO production and heating can be performed by the ultrasonic apparatus. However, when this preliminary heating is performed by an ultrasonic beam, both the ultrasonic beam for heating and the ultrasonic beam for NO production are irradiated to the normal tissue adjacent to the cancer tissue. In order to reduce damage to normal tissue by the ultrasonic beam, it is preferable to reduce the sum of the ultrasonic energy for heating and the ultrasonic energy for NO production.

  From the above viewpoint, the present inventors examined the amount of nitric oxide produced by changing the frequency of the ultrasonic beam. The result is shown in FIG. FIG. 4 is a graph showing the relationship between the frequency of the ultrasonic beam and the amount of nitric oxide produced. The experimental conditions are the same as above. It is understood that it is preferable to set the frequency to 1 MHz or less for NO production. However, since the cavitation effect appears at 100 kHz or less and has an adverse acoustic effect on the living body, the frequency range of 100 kHz to 1000 kHz is suitable as the ultrasonic beam for producing NO.

  FIG. 5 shows nitric oxide concentration (D) and tumor temperature (T) in the case where an ultrasonic beam having a frequency of 1 MHz is irradiated. However, heating is not performed. The experimental conditions are the same as the cases shown in FIGS. Comparison of FIG. 2 with FIG. 5 revealed the following facts. First, an ultrasonic beam having a frequency of 500 kHz can achieve a higher nitric oxide concentration than an ultrasonic beam having a frequency of 1000 kHz. However, an ultrasonic beam having a frequency of 1000 kHz has a higher tumor heating effect than an ultrasonic beam having a frequency of 500 kHz.

  After all, it is preferable to have an ultrasonic beam with a high frequency for heating. Specifically, it is preferable to employ an ultrasonic beam of 1 MHz to 10 MHz. Thereby, the heating effect can be improved without increasing the output of the ultrasonic beam.

  According to a preferred operation example of the NO sensitizing radiation cancer treatment system, the tumor is efficiently preliminarily heated by irradiating the tumor with a heating ultrasonic beam of 100 kHz to 1000 kHz for a predetermined time. Preferably, with this warming, the tumor has a temperature of 39-43 ° C.

  Next, the nitric oxide is efficiently generated in the tumor by irradiating the tumor with an ultrasonic beam for NO production of 100 kHz-1000 kHz for a predetermined time. Next, X-rays are irradiated during a peak period (Tp) in which the concentration of nitric oxide in the tumor reaches a peak level. As a result, the cancer treatment effect can be maximized without increasing the dose of X-rays and ultrasonic beams. Note that gamma rays or the like may be employed instead of X-rays.

Device Configuration Example Next, a preferred device configuration example of this NO-sensitized radiation cancer treatment system will be described with reference to the block diagram shown in FIG. The NO-sensitized radiation cancer treatment system shown in FIG. 6 is essentially the same as the experimental apparatus shown in FIG. The X-ray irradiation apparatus 1 is disposed above the table 3. The probe 4 for irradiating the ultrasonic beam is disposed below the table 3.

  An ultrasonic transducer (not shown) is attached to the upper end surface of the probe 4. This ultrasonic transducer irradiates an ultrasonic beam having a predetermined frequency upward with high-frequency power from the oscillation circuit 8. The probe 4 and the oscillation circuit 8 constitute an ultrasonic NO generating device and an ultrasonic heating device for nitric oxide according to the present invention.

  The controller 9 constituting the control device according to the present invention controls the X-ray irradiation device 1 and the oscillation circuit 8. Thus, the X-ray irradiation period, the NO production ultrasonic beam irradiation period, and the heating ultrasonic beam irradiation period are controlled. Of course, the intensity of the X-ray or ultrasonic beam can be controlled.

Operation Control Example An operation control example executed by the controller 9 will be described with reference to a flowchart shown in FIG. First, in step S100, necessary information is read from a sensor (not shown) into the controller. This information includes the X-ray irradiation period (= peak period (Tp)) set by the operator, the ultrasonic beam irradiation period for heating, the ultrasonic beam irradiation period for NO production, the intensity of X-rays, the supersonic wave for heating Examples include the frequency and intensity of the sound beam and the frequency and intensity of the ultrasonic beam for NO production.

  In addition, information such as the detected room temperature is input. In this embodiment, the frequency of the heating ultrasonic beam is 1 MHz and the irradiation energy density is 1 W / 1 square cm. Similarly, the frequency of the ultrasonic beam for NO production is 500 kHz, and the irradiation energy density is 1 W / 1 square cm.

  The controller 9 has a table showing the relationship between this information and the time change curve of the nitric oxide concentration in the tumor. Next, in step S102, using the information collected in step S100 and this table, the delay time from the start point of irradiation of the ultrasonic beam for NO production to the start point of the peak period (Tp) is determined. . That is, step S102 constitutes a peak period estimation unit referred to in the present invention.

  Next, preliminary heating is started by irradiating a heating ultrasonic beam in step S104. Next, in step S106, it is determined whether or not this preliminary heating period has ended. When the preliminary heating period ends, in step S108, irradiation with the ultrasonic beam for NO production is started, so that the nitric oxide concentration increases rapidly.

  Next, in step S110, it is determined whether or not a peak period (Tp), which is a period in which the nitric oxide concentration is the highest, has started. When the peak period (Tp) is started, X-ray irradiation is commanded in step S112. Next, in step S114, it is determined whether or not a predetermined X-ray irradiation period has ended, and when it has ended, the routine is ended. That is, steps S112 and S114 constitute a radiation irradiation command section referred to in the present invention. As a result, by executing the above operation control, excellent cancer treatment results can be realized without increasing the irradiation intensity and irradiation time of X-rays and ultrasonic beams.

Variation Control Examples The apparatus configuration and operation control can have various variations. For example, based on the directly detected tumor temperature and the concentration of nitric oxide in the tumor, the delay time from the start of irradiation of the ultrasonic beam for NO production to the start of the peak period (Tp) can be set. Irradiation of the ultrasonic beam for heating can be performed even after the start of irradiation of the ultrasonic beam for NO production.

Description of Probe 4 The probe 4 used in this example will be described with reference to FIG. FIG. 8 is a schematic perspective view showing the tip of the probe 4. At the tip of the probe 4, an ultrasonic transducer 41 for heating and an ultrasonic transducer 42 for NO production are provided. The ultrasonic transducer 41 outputs a 1 MHz ultrasonic beam, and the ultrasonic transducer 42 outputs a 500 kHz ultrasonic beam.

  A modification of the probe 4 will be described with reference to FIG. FIG. 9 is a schematic perspective view showing the tip of the probe 4. At the tip of the probe 4, an ultrasonic transducer 43 for heating and an ultrasonic transducer 44 for NO production are provided. The heating ultrasonic transducer 43 and the NO producing ultrasonic transducer 44 each formed in a ring shape are coaxially arranged.

  The ultrasonic transducer for heating and the ultrasonic transducer for NO production can be driven alternately. The heating ultrasonic transducer that outputs a high-frequency ultrasonic beam can also serve as an NO producing ultrasonic transducer that outputs a low-frequency ultrasonic beam. In other words, by switching the oscillation voltage applied to the common ultrasonic transducer, the heating ultrasonic beam and the NO production ultrasonic beam can be sequentially output from the common ultrasonic transducer. Furthermore, the shape and arrangement of the ultrasonic transducers can be changed in order to converge the ultrasonic beam to the focal point. The probe 4 may be provided with a hole through which the X-ray beam passes.

1 X-ray irradiation device 2 Rat 3 Table 4 Probe 5 Accor stand 20 Tumor 6 Ultrasonic non-reflective plate 7 Accor stand 8 Oscillation circuit 9 Controller 41-44 Ultrasonic transducer

Claims (9)

A radiation irradiation device that destroys the cancer tissue by irradiating the cancer tissue from outside the patient's body; and
An ultrasonic NO generator that generates nitric oxide (NO) in the cancer tissue by irradiating the cancer tissue from outside the patient's body with an ultrasonic beam for sensitizing nitric oxide;
A control device that starts operation of the radiation irradiation device in a state where nitric oxide is generated in the cancer tissue by operation of the ultrasonic NO generator;
NO sensitizing radiation cancer treatment system comprising
The controller is
A peak period estimation unit that estimates a peak period of a nitric oxide concentration generated after a predetermined time from the operation start time of the ultrasonic NO generator;
A radiation irradiation command section for commanding radiation irradiation to the radiation irradiation apparatus during this peak period;
NO sensitizing radiation cancer treatment system, comprising: A heating device for heating the cancer tissue;
The NO sensitizing radiation cancer treatment system according to claim 1, wherein the control device preheats the cancer tissue by operating the heating device at least before the operation of the ultrasonic NO generator is started.   3. The NO-sensitized radiation cancer treatment according to claim 2, wherein the heating device includes an ultrasonic heating device that irradiates the cancer tissue with an ultrasonic beam having a higher frequency than the ultrasonic NO generator. system.   The NO sensitizing radiation cancer treatment system according to claim 3, wherein the ultrasonic heating device and the ultrasonic NO generator share an ultrasonic output probe. A radiation irradiation device that destroys the cancer tissue by irradiating the cancer tissue from outside the patient's body; and
An ultrasonic NO generator that generates nitric oxide (NO) in the cancer tissue by irradiating the cancer tissue from outside the patient's body with an ultrasonic beam for sensitizing nitric oxide;
A control device that starts operation of the radiation irradiation device in a state where nitric oxide is generated in the cancer tissue by operation of the ultrasonic NO generator;
NO sensitizing radiation cancer treatment system comprising
A heating device for heating the cancer tissue;
The control device operates the heating device at least before starting the operation of the ultrasonic NO generator, so that the temperature of the cancer tissue during the operation of the ultrasonic NO generator is higher than the body temperature, and A NO sensitizing radiation cancer treatment system, characterized in that it is maintained in a predetermined temperature range lower than a predetermined maximum temperature.   The controller controls the temperature of the cancer tissue during operation of the ultrasonic NO generator by controlling the output of the ultrasonic NO generator and the heating device during operation of the ultrasonic NO generator. The NO-sensitized radiation cancer treatment system according to claim 5, which is maintained at 45 ° C.   6. The NO sensitizing radiation cancer treatment according to claim 5, wherein the warming device comprises an ultrasonic warming device that irradiates the cancer tissue with an ultrasonic beam having a higher frequency than the ultrasonic NO generator. system.   The NO sensitizing radiation cancer treatment system according to claim 7, wherein the ultrasonic heating device and the ultrasonic NO generator share an ultrasonic output probe. The ultrasonic heating device outputs a high frequency ultrasonic beam having a frequency within a range of 1 MHz to 10 MHz,
The NO sensitizing radiation cancer treatment system according to claim 9, wherein the ultrasonic NO generator outputs a low-frequency ultrasonic beam having a frequency within a range of 1 MHz to 10 MHz.

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