JP2012045122A - Treatment system using radiation and ultrasound in combination - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a treatment system using radiation and ultrasound in combination that generates nitrogen monoxide, acting as the radiosensitizer, by ultrasound irradiation of cancerous tissue and emits therapeutic radiation of the cancerous tissue.SOLUTION: The treatment system 10 using radiation and ultrasound in combination includes: a therapeutic-radiation irradiation device 20 for irradiation with a therapeutic radiation beam; a therapeutic ultrasound irradiation device 30 for irradiating a therapeutic ultrasound beam; a control device 40; an imaging device 50 for displaying a radiation image of a cancerous tissue part of a patient M; and a keyboard 60. The cancerous tissue part is irradiated with the ultrasound beam, and then, cancerous tissue part irradiated with the ultrasound beam is irradiated with an X-ray beam 23a. Nitrogen monoxide (NO) is generated in the cancerous tissue part by the irradiation of the ultrasound beam so as to act as a radiosensitizer. The cancerous tissue part is irradiated with the X-ray beam 23a being the therapeutic radiation, thereby effectively destroying the cancerous tissue.

Description

  The present invention relates to a treatment apparatus for treating cancer by using radiation and ultrasound together.

  Currently, the radiation therapy method is regarded as one of the important treatment methods for cancer. However, conventionally, it is said that the stronger the ischemic state of a cancer tissue, the stronger the radiotherapy resistance (hypoxic radio-resistance) (see Non-Patent Document 1). This is because current radiotherapy methods use oxygen as a radiosensitizer.

In particular, solid cancer has a strong ischemic state in tumor tissue due to abnormal distribution of tumor blood vessels. Therefore, in order to improve the ischemic state and increase the radiosensitivity of cancer tissue, various clinical trials as described below have been attempted. That is,
(1) A method of performing radiation therapy by placing a patient in a hyperbaric oxygen chamber.

  (2) A method in which radiotherapy is performed after increasing the hemoglobin concentration of red blood cells by blood transfusion.

  (3) A method of performing radiation therapy after increasing the hemoglobin concentration of erythrocytes with the hormone (Erythropoietin) produced in the kidney.

  (4) A method of using a nicotinamide preparation as a radiosensitizer instead of oxygen.

However, according to the results of these clinical trials, the above methods (2) and (3) have no effect, and the above methods (1) and (4) have been confirmed to some extent. However, it has not yet spread widely from the viewpoint of cost performance and side effects (see Non-Patent Documents 2, 3, 4, and 5).

  On the other hand, recently, nitric oxide (NO, hereinafter, sometimes simply referred to as NO) has attracted attention as a radiosensitizer that replaces oxygen. In 1958 Gay et al. Reported the effect of NO as a radiosensitizer on cancer cells (see Non-Patent Document 6).

  At that time, NO was only recognized as a toxic gas, and NO was not accepted as a radiosensitizer to replace oxygen. However, recently, it has been reported that NO is an important substance that controls the vascular system, blood coagulation system, nervous system, immune inflammation system, etc. of the living body, and NO has come to attract attention as a radiosensitizer that replaces oxygen. Yes.

  A method for generating NO chemically (see Non-patent Document 7), a method for generating NO by administering cytocan, which is a peptide responsible for mutual communication of cells involved in immune response (see Non-Patent Document 8), insulin A method of generating NO by administering NO (see Non-Patent Document 9), a method of generating NO by electrical stimulation (see Non-Patent Document 10), a method of actually using a low concentration of NO gas (see Non-Patent Document 11) The effectiveness of NO as a radiosensitizer has been confirmed based on many experiments.

  It has also been reported that cancer cells use NO contained in large amounts in cancer cells instead of oxygen for their growth and growth (see Non-Patent Document 12).

Motortram JC: Annual report of the Mount Vernon Hospital and Radium Institute, 1935. Watson ER, Halnan KE, Disces, et al .: Hyperbaric oxygen and radiotherapy: A Medical Research Council tri-in-carcinoma of the cervix. Br J Radiol 51: 879-887, 1978. Overgard J, Hansen HS, Specch L, et al: Five cmpared with six fractions of the radicals of the radically of the sequel. Lancet 362: 933-940, 2003. Henke M, LASIG R, RUBE C, ET AL: Erythropoietin to treat head and neck cancer recipients with an anthropogenic band-bindered. Lancet 362: 1255-1260, 2003. Overgaard J, Hansen HS, Overgaard M, et al: A Randomized, double-blind phhase III study of nimorazole as a hypoxic radiosensitized of primary radiotherapy in supraglottic larynx and pharynx carcinoma: Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85. Radiother Oncol 46: 135-146, 1998. Gray LH, Green FO, Howes CA: Effect of nitric oxide on the radiosensitivity of tumour cell. Nature 182: 952-953, 1958. Jansens MY, Verovski DL, Vanden Berge DL, et al: Radiosensitization of hypoxic tumor cells by S-nitroso-N-acetylpeniclaminative Br J Cancer 79: 1085-1089, 1999. Van den Berge DL, Rider MD, Verovski VN, et al: Chronic hypoxia modulates tumor cell radiosponsic thyrotoxicity-inductivity. Br J Cancer 84: 1122-1125, 2001. Jordan BF, Gregoria V, Demeure RJ, et al: Insulin increases the sensitivity of tumors to irradiation: Involement of an increasein tumor oxygenation mediated by a nitric oxide-dependent decrease of thetumor cells oxygen consumption. Cancer Research 62: 3555-3561, 2002. Jordan BF, Sonveaux P.M. FeronO, et al: Ntric oxide-mediator increaseinuminator flood flow and oxygenation of symmetries INT J Radiate OncolBiophys 55: 1066-1073, 2003. Wardman P, Rothkamm K, Folkes LK, et al: Radio sensing by nitric oxide at low radiation doses. Radiation Research 167: 475-484, 2007. Lala P.M. K. and ChakrabortyC. Role of nitric oxide in carcogenesis and tumour progression. The LANCETOnology 2: 149-156,2001.

  However, at present, an effective method for generating an appropriate amount of NO as a radiosensitizer only in cancer tissues without causing side effects on the living body has not been found. If a method to generate an appropriate amount of NO only in cancer tissue is developed, it will be possible to destroy the cancer tissue by generating NO only in the cancer tissue and projecting radiation to it. May be enhanced to become a breakthrough cancer therapy.

  This invention solves the said subject, and is based on the knowledge that NO which acts as a radiosensitizer can be generated by irradiating a cancer tissue with an ultrasonic wave.

  In addition, since cancer cells use NO contained in a large amount in cancer cells instead of oxygen for their growth and growth (see Non-patent Document 12), radiation treatment is performed in reverse to the NO. It is the original point of the present invention to be used as a radiosensitizer for the law.

  The invention of claim 1 is directed to a therapeutic radiation irradiation apparatus that irradiates a therapeutic radiation beam, a therapeutic ultrasonic irradiation apparatus that irradiates a therapeutic ultrasonic beam, and the ultrasonic wave toward a target cancer tissue site. Radiation and ultrasound combined treatment device comprising a control device for irradiating a beam and irradiating the radiation beam to a cancer tissue site irradiated with the ultrasonic beam, wherein the control device is used for the treatment Cancer in which the nitric oxide is generated by activating the ultrasonic irradiation device to irradiate the cancer tissue site with the therapeutic ultrasonic beam to generate nitrogen monoxide that acts as a radiosensitizer on the cancer tissue site Activating the therapeutic radiation irradiation device on the tissue site to irradiate the therapeutic radiation beam, and destroying the cancer tissue by irradiation with the therapeutic radiation beam under the condition where the nitric oxide acts as a radiosensitizer You It is radiation and ultrasound combined treatment apparatus according to claim.

  The control device includes an ultrasonic parameter setting unit that sets ultrasonic parameters related to the direction, intensity, frequency, waveform, irradiation time, and sound field distribution of the ultrasonic waves emitted from the therapeutic ultrasonic irradiation device.

  And the said control apparatus is provided with the radiation parameter setting means which sets the radiation parameter regarding the direction, irradiation field, intensity | strength, and irradiation time of the radiation beam irradiated from the said therapeutic radiation irradiation apparatus.

  The therapeutic radiation irradiation apparatus includes a radiation source and a high-voltage power source that supplies high-voltage electricity to the radiation source, and is controlled by the control device.

  The therapeutic ultrasonic irradiation apparatus includes a flexible ultrasonic probe that can be adhered and adhered to a body surface near a cancer tissue site of a patient, and a high-frequency oscillator that drives the ultrasonic probe, It is controlled by the control device.

  The ultrasonic probe is formed by attaching one or many segments made of a flexible piezoelectric element such as polyvinylidene fluoride (PVDF) or a piezoelectric transducer such as PZT ceramics on a flexible film. It is configured, can be attached in close contact with the body surface of a cancer tissue site of a patient, and can selectively drive one or a plurality of segments corresponding to the cancer tissue site.

  The therapeutic ultrasonic irradiation apparatus may be a catheter with an ultrasonic probe having an ultrasonic probe attached to the tip.

  The therapeutic ultrasonic irradiation device may be an ultrasonic probe attached to the tip of a holding body having a size capable of passing a trocar punctured into the abdominal cavity of a patient.

  The ultrasonic probe is composed of one or many segments made of a flexible piezoelectric element such as polyvinylidene fluoride (PVDF) or a piezoelectric transducer such as PZT ceramics, and corresponds to a cancer tissue site. One or a plurality of segments may be selectively driven.

  The ultrasonic probe is a laminate in which one or a plurality of element groups each made up of a plurality of segments composed of a flexible piezoelectric element such as polyvinylidene fluoride (PVDF) or a piezoelectric transducer such as PZT ceramics are laminated. And one or a plurality of segments corresponding to a cancer tissue site and one or a plurality of element groups of the laminate may be selectively driven.

  As described above, the radiation and ultrasonic treatment apparatus according to the present invention includes a therapeutic radiation irradiation apparatus that irradiates a therapeutic radiation beam, a therapeutic ultrasonic irradiation apparatus that irradiates a therapeutic ultrasonic beam, and a target. It consists of a control device that irradiates an ultrasonic beam and a radiation beam toward the cancer tissue site, and nitric oxide (NO) is applied to the cancer tissue site by the therapeutic ultrasonic beam applied to the cancer tissue site. Because it is configured to irradiate a treatment radiation beam to a cancer tissue site that has been generated to increase radiosensitivity and become highly sensitive, it can destroy cancer tissue more efficiently than conventional radiotherapy equipment Can do.

The conceptual diagram explaining the basic composition of the radiation and ultrasonic combination treatment apparatus of 1st Embodiment. The figure explaining a mode that the ultrasonic tissue and X-ray beam are irradiated to the cancer tissue site | part of 1st Embodiment. The top view explaining an example of the ultrasonic probe stuck on the patient's body surface of 1st Embodiment. The block diagram explaining the outline of a structure of a control apparatus. The conceptual diagram explaining the basic composition of the radiation and ultrasonic combination treatment apparatus of 2nd Embodiment. The external view which shows an example of the catheter with an ultrasonic probe used by 2nd Embodiment. The conceptual diagram explaining the basic composition of the radiation and ultrasonic combination treatment apparatus of 3rd Embodiment. The external view which shows an example of the ultrasonic probe with which the tip of the cable used in 3rd Embodiment was mounted | worn.

  First, the radiation sensitivity by the irradiation of the ultrasonic beam with respect to a cancer tissue site | part and generation | occurrence | production of nitric oxide (NO) in the said cancer tissue is demonstrated.

  In general, nitric oxide (NO) is synthesized from nitric oxide synthase (NOS) in vivo. Nitric oxide synthase (NOS) plays a physiologically important role in relation to vasodilation, neurotransmission, inflammatory mediators and the like.

  The inventor of the present application created a tumor model by inoculating cultured tumor cells called Gliosarcoma and Glioma subcutaneously in the thigh of a rat, and irradiated this tumor model with an ultrasonic beam. Knowledge of (NO) production was obtained.

  The irradiated ultrasonic beam is a continuous wave with a frequency of 490.6 kHz, and the irradiation time is 30 minutes. At the same time, a NO electrode was inserted into the tumor site, and NO production was measured from 10 minutes before irradiation with the ultrasonic beam to 10 minutes after irradiation. The average value of the maximum increase in irradiation for 30 minutes on the basis of the NO concentration at the time of irradiation with the ultrasonic beam was about 5.5 μM on the 9th day after tumor implantation and about 3.3 μM on the 15th day.

  Compared with the effective NO gas concentration of 70 nM to 140 nM in Wardman et al.'S report of the radiation sensitivity enhancing action using a low concentration of NO gas (see Non-Patent Document 11), this NO concentration is 500 times higher. Therefore, it is sufficient as a radiosensitivity enhancing effect on tumor tissue. In addition, since NO is generated only in the tumor tissue, there is an advantage that there is no side effect on the normal tissue.

  In other words, it has been proved that, when an ultrasonic beam is irradiated onto a tumor tissue, a concentration of NO that temporarily acts on the tumor tissue (cancer tissue) as a radiosensitizer is generated. The radiation referred to here includes X-rays.

  Accordingly, the inventor of the present application irradiates the cancer tissue site by irradiating an ultrasonic beam toward the site including the cancer tissue site and irradiating the cancer tissue site with a therapeutic radiation beam. A new cancer treatment method that destroys cancer tissue by irradiating therapeutic radiation under the condition where NO acting as an agent is generated. A sonic combined therapy device was developed.

  Hereinafter, the radiation and ultrasonic combination treatment apparatus used in this new cancer treatment method will be described. A plurality of embodiments described below are described as an apparatus that emits X-rays as radiation, but radiation other than X-rays, for example, γ-rays (gamma rays) may be used.

[First Embodiment]
FIG. 1 is a conceptual diagram illustrating the basic configuration of a combined radiation and ultrasound treatment apparatus (hereinafter sometimes simply referred to as a treatment apparatus) 10 according to the first embodiment. FIG. 2 illustrates a cancer tissue site Mx. The figure explaining a mode that the ultrasonic beam 31a and the X-ray beam 23a are irradiated. FIG. 3 is a plan view for explaining an example of the configuration of the ultrasonic probe 31 attached to the body surface Ma of the patient M. FIG.

  Radiation and ultrasound combined treatment apparatus 10 includes therapeutic X-ray irradiation apparatus 20 that irradiates a therapeutic X-ray beam, therapeutic ultrasonic irradiation apparatus 30 that irradiates a therapeutic ultrasonic beam, control apparatus 40, An image device 50 that displays an image of a cancer tissue site of a patient M irradiated by an ultrasonic beam or an X-ray beam, and a keyboard 60 that inputs data (information) necessary for operating the treatment device. Is done.

  The therapeutic X-ray irradiation apparatus 20 includes an X-ray source 23 and an X-ray apparatus high-voltage power supply 24 that supplies high-voltage electricity to the X-ray source 23, and is connected to and controlled by a control device 40. The X-ray source 23 is attached to the C-type arm 21 and continuously rotates 360 ° around the bed 22 on which the patient M is placed, and the X-ray source 23 irradiates the cancer tissue site of the patient M from the X-ray source 23. It is configured to be. A drive device 29 that drives the C-arm 21 is connected to and controlled by the control device 40.

  Further, the therapeutic X-ray irradiation apparatus 20 may be provided with an X-ray dose monitor 25 in a part of the bed 22 so that the X-ray beam irradiation is cut off when an X-ray dose higher than a predetermined level is detected.

An example of radiation parameters such as the dose of X-rays irradiated from the X-ray source 23 and the irradiation time is shown below.
X-ray dose: 2 gray (gray is a unit of absorbed dose of radiation), irradiation time: 1 minute, number of irradiations: 5 times a week.

  The therapeutic ultrasonic irradiation apparatus 30 that irradiates a therapeutic ultrasonic beam is configured by arranging a large number of piezoelectric transducer elements 31n on a flexible film that is affixed to the body surface Ma of a cancer tissue site Mx of a patient M. The ultrasonic probe 31 and an ultrasonic probe high-frequency power source 32 that outputs a high frequency of a predetermined frequency for driving the ultrasonic probe.

  The ultrasonic probe 31 is configured by sticking a piezoelectric transducer 31n such as polyvinylidene fluoride (PVDF) or PZT ceramics on a flexible film, and the piezoelectric transducer 31n is composed of a number of segments, In addition to being able to affix and adhere to the body surface Ma of the M cancer tissue part Mx, the irradiation direction of the ultrasonic beam is determined by selectively driving the segment corresponding to the cancer tissue part. It is configured to effectively irradiate the tissue site with the ultrasonic beam.

  The ultrasonic probe is composed of a laminate in which a plurality of elements composed of a plurality of segments made of piezoelectric transducers such as polyvinylidene fluoride (PVDF) and PZT ceramics are laminated, and corresponds to a cancer tissue site. One or a plurality of segments and a laminate may be selectively driven.

  The ultrasonic probe 31 is driven by a high frequency signal output from an ultrasonic probe high frequency power supply 32 that outputs a high frequency of a predetermined frequency. The high frequency power supply 32 for the ultrasonic probe is connected to the control device 40, and the segment of the piezoelectric transducer 31n is determined based on information (position of the cancer tissue site Mx, depth from the body surface Ma, etc.) input from the keyboard 60. It is controlled to selectively drive.

  Examples of ultrasonic parameters such as intensity, frequency, waveform, irradiation time (exposure time), and ultrasonic field distribution of the ultrasonic beam for driving the ultrasonic probe 31 are shown below.

Strength (lspta): 1 mW / cm ² or more.

      Frequency: 10 kHz to 40 MHz.

      Waveform: pulse wave, burst wave, continuous wave, modulated wave (including periodic and irregular changes in amplitude and frequency, noise and their combination).

      Irradiation time (exposure time): 0.01 seconds to 3 hours.

      Ultrasonic beam sound field distribution: focusing, parallel, diffusing, or their combined shape.

  Further, the frequency of the ultrasonic wave is preferably changed constant or periodically, and the change speed is preferably set to 1.0 ms or less by continuous change, random noise change, discontinuous change (flying change), and the like. It is assumed that ultrasonic parameters such as information (intensity, frequency, waveform, irradiation time (exposure time), sound field distribution of ultrasonic beam) for driving the ultrasonic probe 31 are also input from the keyboard 60.

  FIG. 2 is a diagram illustrating a state in which the ultrasonic tissue 31a and the X-ray beam 23a are irradiated to the cancer tissue site Mx, and the cancer tissue site Mx located deeper than the body surface Ma of the patient M is superposed on the cancer tissue site Mx. When the ultrasonic beam 31a is irradiated from the acoustic probe 31, ultrasonic vibration is transmitted to the cancer tissue site Mx. Further, the X-ray beam 23a is irradiated from the X-ray source 23 to the cancer tissue site Mx irradiated with the ultrasonic beam 31a.

  FIG. 3 is a plan view for explaining an example of the configuration of the ultrasonic probe 31 attached to the body surface Ma of the patient M. A hole 31d having a diameter D is formed at the center of the plane of the ultrasonic probe 31, and the X-ray It is configured so as not to prevent the transmission of the beam 23a.

  Further, the ultrasonic probe 31 receives the reflected wave of the ultrasonic beam 31a irradiated to the cancer tissue part Mx, and outputs the received ultrasonic image signal of the cancer tissue part to the image device 50 described later.

  The image device 50 receives the reflected wave of the ultrasonic beam 31a applied to the cancer tissue part Mx, and outputs an ultrasonic image signal of the cancer tissue part Mx, and an ultrasonic image signal output unit 51a. An X-ray image signal output unit 51b that receives an X-ray beam 23a that has passed through the tissue site Mx and outputs an X-ray image signal; and when an ultrasonic image signal is input, the input ultrasonic image signal is used as a cancer tissue. When an X-ray image signal is input, the ultrasonic image display unit 52a that converts and displays the visible image of the site Mx and the input X-ray image signal are converted into a visible image of the cancer tissue site Mx and displayed. The X-ray image display unit 52b is connected to the control device 40 and controlled.

  FIG. 4 is a block diagram for explaining an outline of the configuration of the control device 40. The control device 40 includes a CPU and controls the entire treatment device 10.

  The input / output port of the CPU constituting the control device 40 is for an X-ray device high-voltage power supply 24 that supplies high-voltage electricity to the X-ray source 23, and for an ultrasonic probe that outputs a high frequency of a predetermined frequency for driving the ultrasonic probe 31. A high-frequency power source 32, an X-ray dose monitor 25, a drive device 29 for driving the C-arm 21, an ultrasonic image signal output unit 51a and an ultrasonic image display unit 52a, an X-ray image signal output unit 51b and an X-ray image display unit 52b, And the keyboard 60 are connected, and the CPU is controlled by a predetermined control program.

  Hereinafter, an aspect of cancer tissue treatment by the treatment apparatus 10 and an outline of a control operation executed by the CPU of the control apparatus 40 will be described. First, as a preparation stage, the cancer tissue part of the patient M, the state of the cancer tissue, etc. are examined, and based on the treatment policy determined by the result of the examination, the position of the cancer tissue part Mx and the body surface Ma are determined. Information such as depth and ultrasonic parameters related to the direction, intensity, frequency, waveform, irradiation time, sound field distribution, and the like of the ultrasonic waves emitted from the ultrasonic probe 31 are determined and input from the keyboard 60 to the control device 40. Keep it. Further, X-ray parameters relating to the direction, thickness, intensity, and irradiation time of the X-ray beam irradiated from the X-ray source 23 are determined based on the treatment policy, and are input to the control device 40 from the keyboard 60.

  The patient M is placed on the bed 22. The ultrasonic probe 31 is attached to the body surface Ma corresponding to the cancer tissue site Mx of the patient M, and connected to the ultrasonic probe high-frequency power source 32 that outputs a high frequency of a predetermined frequency. The ultrasonic probe 31 is driven to check whether or not the ultrasonic beam 31a is irradiated from the ultrasonic probe 31 on the body surface Ma toward the cancer tissue site Mx of the patient M. This is because the ultrasonic image signal output unit 51a detects the ultrasonic reflection vibration that the ultrasonic beam 31a preliminarily irradiated from the ultrasonic probe 31 reflects from the cancer tissue site Mx and returns, and displays an ultrasonic image. It outputs to the part 52a and confirms from the image.

  When the ultrasonic vibration is not applied to the position corresponding to the position of the cancer tissue part Mx of the patient M or the depth from the body surface Ma, the plurality of segments constituting the ultrasonic probe 31 are appropriately selected, Adjustment is made so that the ultrasonic vibration is accurately applied to the position corresponding to the position of the cancer tissue site Mx and the depth from the body surface Ma.

  Next, the therapeutic ultrasonic beam 31a is irradiated from the ultrasonic probe 31 on the body surface Ma toward the cancer tissue site Mx of the patient M. The driving of the C-arm 21 is started and the therapeutic X-ray irradiation apparatus 20 is activated. The X-ray beam 23a is irradiated from the X-ray source 23 toward the cancer tissue site Mx irradiated with the therapeutic ultrasonic beam 31a. As the C-arm 21 continuously rotates 360 °, the X-ray beam 23a is concentrated and irradiated on the cancer tissue site Mx.

  Nitric oxide (NO) acting as a radiosensitizer is generated in the cancer tissue site Mx of the patient M irradiated with the ultrasonic beam 31a, and the X-ray beam 23a is concentrated and irradiated there. Therefore, cancer tissue can be effectively destroyed.

  There are irradiation methods such as irradiation of the ultrasonic beam 31a and irradiation of the X-ray beam 23a to the cancer tissue site Mx at the same time or irradiation of the ultrasonic beam and the X-ray beam alternately. The optimal irradiation method shall be determined based on the policy.

  When irradiating the cancer tissue site Mx with an ultrasonic beam, it is separately confirmed whether or not nitric oxide (NO) is generated in the cancer tissue site Mx using a nitric oxide sensor. Good.

[Second Embodiment]
The radiation and ultrasonic combination treatment apparatus of the second embodiment uses a catheter with an ultrasonic probe in which an ultrasonic probe is attached to the distal end of the catheter for irradiation of a therapeutic ultrasonic beam to the cancer tissue site Mx. However, in this respect, it is different from the radiation and ultrasonic combined treatment apparatus of the first embodiment described above. According to the treatment apparatus of the second embodiment, since a catheter with an ultrasonic probe is inserted via a blood vessel into a very close part of a tumor part such as a brain tumor, a therapeutic ultrasonic beam is irradiated only to the tumor. be able to.

  FIG. 5 is a conceptual diagram for explaining a basic configuration of a combined radiation and ultrasound treatment apparatus 80 (hereinafter simply referred to as a treatment apparatus 80) according to the second embodiment, and FIG. 6 is a catheter with an ultrasound probe 81a. 81 is an external view showing an example of an apparatus member 81 having the same function as that of the radiation and ultrasonic combination treatment apparatus of the first embodiment. Note that the catheter with an ultrasonic probe in which an ultrasonic probe is attached to the distal end shown in FIG. 6 is an example of a catheter with an ultrasonic probe, and a piezoelectric transducer is used to irradiate ultrasonic waves from an end surface near the distal end of the catheter. Although it is a catheter with an ultrasonic probe arranged, although not shown in the drawings, a catheter with an ultrasonic probe in which a piezoelectric transducer is arranged to irradiate ultrasonic waves in a radial direction of the catheter from a side surface near the distal end of the catheter It can also be.

  In the second embodiment, for example, in order to treat a brain tumor of the patient M, a catheter 81 with an ultrasonic probe 81 a is inserted via the left lower limb artery blood vessel of the patient M and attached to the distal end of the catheter 81. The ultrasonic probe 81a is brought into contact with the cancer tissue site Mx or the vicinity thereof. The ultrasonic probe 81 a is connected to the ultrasonic probe high-frequency power source 32 to be driven by a wire 83 disposed inside the catheter 81.

  In order to irradiate the cancer tissue site Mx with the X-ray beam 23a, the X-ray source 23 connected to the high-voltage power supply 24 for the X-ray apparatus and the X-ray image signal output unit 51b are arranged near the head of the patient M, An X-ray beam 23a is projected onto the cancer tissue site Mx, and an X-ray image signal is detected.

  In addition, in the treatment apparatus 80 of the second embodiment, similarly to the treatment apparatus 10 of the first embodiment, the cancer tissue site Mx (here, a brain tumor) detected by the ultrasonic probe is used. The X-ray image signal output from the ultrasonic image signal output unit 51a that outputs the ultrasonic reflection vibration, the ultrasonic image display unit 52a that displays the ultrasonic reflection image, and the X-ray image signal output unit 51b is converted into a visible image. An X-ray image display unit 52b for converting and displaying may be provided, but the display is omitted in FIG.

  Whether or not the ultrasonic probe 81a attached to the tip of the catheter 81 has contacted with or reached the target brain tumor Mx is determined by the reflected ultrasonic vibration reflected by the brain tumor Mx detected by the ultrasonic probe 81a. Although it is detected by the ultrasonic image signal output unit 51a (see FIG. 1) and displayed on the ultrasonic image display unit 52a (see FIG. 1), it may be confirmed separately by an X-ray monitor.

  Similarly to the treatment apparatus 10 of the first embodiment, the treatment apparatus 80 of the second embodiment also has an ultrasonic probe 81a, an ultrasonic probe high-frequency power supply 32, an ultrasonic image signal output unit 51a, and an ultrasonic image. The display device 52a, the X-ray device high-voltage power supply 24, the X-ray image signal output unit 51b, the X-ray image display unit 52b, and the like are provided with a control device 40 configured by a CPU. Since it is the same as that of the control apparatus of the treatment apparatus 10 of 1 embodiment and the apparatus member of the same function as the apparatus of 1st Embodiment is attached | subjected the same code | symbol, description is abbreviate | omitted here.

  Hereinafter, an aspect of cancer tissue treatment by the treatment apparatus 80 and an outline of control operation of the treatment apparatus 80 will be described. First, as a preparation stage, the use of a catheter with an ultrasonic probe is determined based on a diagnosis of the site of the cancer tissue of the patient M, the state of the cancer tissue, and the treatment policy determined by the result of the diagnosis.

  Determines ultrasonic parameters related to the direction, intensity, frequency, waveform, irradiation time, sound field distribution, etc. of the ultrasonic wave emitted from the ultrasonic probe, and also determines the intensity and irradiation of the radiation beam emitted from the therapeutic radiation irradiation apparatus. Radiation parameters relating to time are determined, and these parameters are input to the control device.

  A patient M is placed on the bed. The catheter 81 with the ultrasonic probe 81a is inserted via the left lower limb artery blood vessel of the patient M, and the ultrasonic probe 81a attached to the distal end of the catheter 81 is brought into contact with the vicinity of the cancer tissue site Mx (here, brain tumor). .

  Whether or not the ultrasonic probe 81a has reached the vicinity of the target cancer tissue site Mx (in this case, a brain tumor) is irradiated from the X-ray source 23 with the X-ray beam 23a and output from the X-ray image signal output unit 51b. The X-ray image signal is displayed on the X-ray image display unit 52b and confirmed from the image.

  Next, an ultrasonic beam is irradiated from the ultrasonic probe 81a, and at the same time, an X-ray beam 23a is irradiated from the X-ray source 23 near the cancer tissue site Mx (here, a brain tumor). In this case, as in the treatment apparatus 10 of the first embodiment, the X-ray beam 23a is concentratedly irradiated to the cancer tissue site Mx (here, a brain tumor) by 360 ° continuous rotation of the C-arm. It is good to operate.

  Nitric oxide (NO), which acts as a radiosensitizer, is generated in the cancer tissue site Mx (in this case, a brain tumor) of the patient M irradiated with ultrasound, and the X-ray beam 23a is concentrated there. Since it is irradiated, cancer tissue (brain tumor) can be effectively destroyed.

  There are irradiation methods such as irradiation of the ultrasonic beam and X-ray beam to the cancer tissue site Mx at the same time or irradiation of the ultrasonic beam and the X-ray beam alternately. Based on this, the optimum irradiation method is determined.

  When irradiating the cancer tissue site Mx with an ultrasonic beam, it is separately confirmed whether or not nitric oxide (NO) is generated in the cancer tissue site Mx using a nitric oxide sensor. Good.

[Third Embodiment]
The combined radiation and ultrasound treatment apparatus according to the third embodiment is a treatment apparatus mainly suitable for treatment of a cancer tissue site Mx in the abdominal cavity, and a trocar (tubular body) punctured in the abdomen of the patient M is used. The ultrasonic probe is used and disposed at a site very close to the tumor part in the abdominal cavity, and this is different from the radiation and ultrasonic combined treatment apparatus of the first and second embodiments described above. . According to the treatment apparatus of the third embodiment, since an ultrasonic probe can be inserted into a site that is extremely close to the tumor part in the abdominal cavity, it is possible to more selectively irradiate only the tumor part with the therapeutic ultrasonic beam. Can do.

  FIG. 7 is a conceptual diagram for explaining the basic configuration of the radiation and ultrasound combined treatment apparatus 90 (hereinafter, simply referred to as the treatment apparatus 90) of the third embodiment, and FIG. In the external view showing an example of the ultrasonic probe 91a, the same reference numerals are given to the device members having the same functions as those of the radiation and ultrasonic combination treatment device of the first embodiment. Note that the ultrasonic probe 91a attached to the end of the cable 91 shown in FIG. 8 is an example thereof, and is an ultrasonic probe in which a piezoelectric transducer is arranged so as to irradiate ultrasonic waves from the end surface near the end of the cable. In addition, although not shown, an ultrasonic probe in which a piezoelectric transducer is arranged so as to irradiate ultrasonic waves in the radial direction of the cable from the side surface near the tip of the cable can also be used.

  In the third embodiment, for example, in order to treat the cancer tissue site Mx in the abdominal cavity of the patient M, the first trocar 94 and the second trocar 95 are punctured in the abdomen of the patient M by a surgical procedure. Then, the endoscope 96 is inserted into the abdominal cavity using the first trocar 94, and the ultrasonic probe 91a attached to the tip of the cable 91 is inserted using the second trocar 95. The cable 91 of the ultrasonic probe 91a is connected to the high frequency power supply 32 for the ultrasonic probe. As the endoscope 96, an endoscope having a known configuration that has been widely used in the past can be used.

  In order to irradiate the cancer tissue site Mx with the X-ray beam 23a, an X-ray source 23 connected to the high-voltage power supply 24 for the X-ray apparatus is disposed in the vicinity of the cancer tissue site Mx on the abdomen of the patient M. In order to detect an X-ray image transmitted through the cancer tissue site Mx, an X-ray image signal output unit 51b is disposed below the cancer tissue site Mx in the abdomen of the patient M, and the X-ray image signal output unit 51b includes An X-ray image display unit 52b is connected.

  Similarly to the treatment apparatus 10 of the first embodiment, the treatment apparatus 90 of the third embodiment also has an ultrasonic probe 91a, an ultrasonic probe high-frequency power supply 32, an X-ray apparatus high-voltage power supply 24, and an X-ray image. A control device 40 including a CPU that controls the signal output unit 51b, the X-ray image display unit 52b, and the like is provided. In the third embodiment, since the state of contact of the ultrasonic probe 91a with the cancer tissue site Mx can be confirmed by the endoscope 96, the ultrasonic image signal output unit 51a and the ultrasonic image display unit 52a are not provided. However, it is good also as a structure provided with the ultrasonic image signal output part 51a and the ultrasonic image display part 52a.

  The configuration of the control device 40 is the same as the control device of the treatment device 10 of the first embodiment, and the same reference numerals are given to the device members having the same functions as those of the device of the first embodiment. Then, explanation is omitted.

  Hereinafter, an aspect of cancer tissue treatment by the treatment apparatus 90 and an outline of control operation of the treatment apparatus 90 will be described. First, as a preparation stage, based on the diagnosis of the patient's M cancer tissue site, cancer tissue condition, etc. and the treatment policy determined by the results of the examination, the ultrasonic probe is placed in the abdominal cavity using a trocar. The treatment to be placed in the tissue is determined.

  Determines the ultrasonic parameters related to the direction, intensity, frequency, waveform, irradiation time, sound field distribution, etc. of the ultrasonic wave emitted from the ultrasonic probe, and also determines the direction and thickness of the radiation beam emitted from the therapeutic radiation irradiation apparatus. Radiation parameters relating to intensity, irradiation time, and irradiation time are determined, and these parameters are input to the control device.

  A patient M is placed on the bed. A first trocar 94 and a second trocar 95 are punctured into the abdomen of the patient M by a surgical procedure. Then, the endoscope 96 is inserted into the abdominal cavity from the first trocar 94, and the ultrasonic probe 91 a attached to the tip of the cable 91 is inserted from the second trocar 95. A surgical procedure is performed using the endoscope 96, and an ultrasonic wave is passed through an aqueous solution in the vicinity of the cancer tissue site Mx while confirming the position of the cancer tissue site Mx in the abdominal cavity found by the surgical procedure with the endoscope 96. The probe 91a is brought into contact.

  Next, simultaneously with the irradiation of the ultrasonic beam from the ultrasonic probe 91a, the X-ray beam 23a is irradiated from the X-ray source 23 in the vicinity of the cancer tissue site Mx. In this case, similarly to the treatment apparatus 10 of the first embodiment, the X-ray beam may be concentratedly irradiated to the cancer tissue site Mx by 360 ° continuous rotation of the C-arm.

  Nitric oxide (NO), which acts as a radiosensitizer, is generated in the cancer tissue site Mx of the patient M that has been irradiated with ultrasonic waves, and the X-ray beam is concentrated and irradiated there. Cancer tissue can be destroyed.

  There are irradiation methods such as irradiation of the ultrasonic beam and X-ray beam to the cancer tissue site Mx at the same time or irradiation of the ultrasonic beam and the X-ray beam alternately. Based on this, the optimum irradiation method is determined.

  When irradiating the cancer tissue site Mx with an ultrasonic beam, it is separately confirmed whether or not nitric oxide (NO) is generated in the cancer tissue site Mx using a nitric oxide sensor. Good.

  The configuration example of the radiation and ultrasonic combination treatment device of the present invention and the outline of the function of the treatment device have been described above. The combined radiotherapy and ultrasonic treatment apparatus of the present invention is not limited to the above-described configuration, and the present invention includes various embodiments configured without changing the essence of the present invention.

  This invention was developed on the basis of the knowledge that it can generate NO that acts as a radiosensitizer by irradiating an ultrasonic wave to a cancer tissue, and combined radiation and ultrasonic therapy for treating a cancer tissue Device.

10 Radiation and ultrasound combined treatment device (treatment device) of the first embodiment
DESCRIPTION OF SYMBOLS 20 X-ray irradiation apparatus 21 C type arm 22 Bed 23 X-ray source 23a X-ray beam 24 High-voltage power supply for X-ray apparatus 25 X-ray dose monitor 29 Drive apparatus 30 Therapeutic ultrasonic irradiation apparatus 31 Ultrasonic probe 31a Ultrasonic beam 31n Piezoelectric transducer 32 High frequency power supply for ultrasonic probe 40 Control device 50 Image device 51a Ultrasonic image signal output unit 51b X-ray image signal output unit 52a Ultrasonic image display unit 52b X-ray image display unit 60 Keyboard 80 Second implementation In the form of radiation and ultrasonic treatment device (treatment device)
81 Catheter 81a Ultrasonic probe 83 Wire 90 Radiation and ultrasonic combined treatment apparatus (treatment apparatus) of the third embodiment
91 Cable 91a Ultrasonic probe 94 First trocar 95 Second trocar 96 Endoscope M Patient Ma Patient body surface Mx Cancer tissue site

Claims (10)

A therapeutic radiation irradiation device for irradiating a therapeutic radiation beam;
A therapeutic ultrasonic irradiation device for irradiating a therapeutic ultrasonic beam;
Radiation and ultrasound combined treatment comprising a control device that irradiates the target cancer tissue site with the ultrasonic beam and irradiates the radiation beam onto the cancer tissue site irradiated with the ultrasonic beam A device,
The controller activates the therapeutic ultrasonic irradiation device to irradiate the cancer tissue site with a therapeutic ultrasonic beam to generate nitric oxide that acts as a radiosensitizer on the cancer tissue site, The therapeutic radiation beam under the condition where the therapeutic radiation beam is activated by activating the therapeutic radiation irradiation device to the cancer tissue site where nitric oxide is generated, and the nitric oxide acts as a radiosensitizer. Radiation and ultrasound combined treatment device characterized by destroying cancer tissue by irradiation of.   The control device includes ultrasonic parameter setting means for setting ultrasonic parameters related to the direction, intensity, frequency, waveform, irradiation time, and sound field distribution of the ultrasonic waves emitted from the therapeutic ultrasonic irradiation device. The combined treatment apparatus for radiation and ultrasound according to claim 1. The said control apparatus is provided with the radiation parameter setting means which sets the radiation parameter regarding the direction of the radiation beam irradiated from the said therapeutic radiation irradiation apparatus, irradiation field, intensity | strength, and irradiation time. Radiation and ultrasound combined therapy device. The radiotherapy and ultrasonic combined therapy apparatus according to claim 1, wherein the therapeutic radiation irradiation apparatus includes a radiation source and a high voltage power source that supplies high voltage electricity to the radiation source, and is controlled by the control device. . The therapeutic ultrasonic irradiation apparatus includes a flexible ultrasonic probe that can be attached in close contact with a body surface near a cancer tissue site of a patient, and a high-frequency oscillator that drives the ultrasonic probe, and the control device The combined radiotherapy and ultrasonic treatment apparatus according to claim 1, wherein The ultrasonic probe is formed by sticking one or many segments made of a piezoelectric transducer such as polyvinylidene fluoride (PVDF) or PZT ceramics on a flexible film, and is a body surface of a cancer tissue site of a patient. 6. The combined radiotherapy and ultrasonic treatment apparatus according to claim 5, wherein one or a plurality of segments corresponding to a cancer tissue site can be selectively driven. The combined treatment apparatus for radiation and ultrasound according to claim 1, wherein the therapeutic ultrasound irradiation apparatus is a catheter with an ultrasound probe having an ultrasound probe attached to a distal end. 2. The radiation and ultrasonic device according to claim 1, wherein the therapeutic ultrasonic irradiation device is an ultrasonic probe attached to a tip of a holding body having a size capable of passing a trocar punctured into a patient's abdominal cavity. Sonic therapy device. The ultrasonic probe is composed of one or a plurality of segments made of a piezoelectric transducer such as polyvinylidene fluoride (PVDF) or PZT ceramics, and can selectively drive one or a plurality of segments corresponding to a cancer tissue site. The radiotherapy and ultrasonic combination treatment device according to claim 7 or 8. The ultrasonic probe is composed of a laminated body in which a plurality of element groups composed of one or many segments composed of piezoelectric transducers such as polyvinylidene fluoride (PVDF) and PZT ceramics are laminated, and corresponds to a cancer tissue site. 9. The combined radiation and ultrasound treatment apparatus according to claim 7 or 8, wherein the one or more segments and the one or more laminated bodies can be selectively driven.

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