JP2002017742A - Ultrasonic therapeutic device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a means for treating only a therapy desired region in a wide range without intensifying adaptive ultrasonic intensity to avoid the possibility of side effect manifestation since a treated region is a small region around a focus and a long time is required for the therapy of a wide region in a device for generating focused ultrasonic waves for ultrasonic coagulation therapy. SOLUTION: This ultrasonic therapeutic device is provided with a supply means 1 for supplying a fluid including a substance interactive with ultrasonic waves such as a substance that increases scattering and reflection of the ultrasonic waves, and a catheter for injecting the fluid into a treated region. Ultrasonic absorption is increased only in the treated region to permit selective ultrasonic therapy.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an ultrasonic therapy apparatus, and more particularly, to a therapy apparatus combined with an apparatus for introducing a substance having an interaction with ultrasonic waves into an arbitrary area to be treated.

[0002]

2. Description of the Related Art Ultrasonic waves have a characteristic that electromagnetic waves, such as lasers and microwaves, can propagate to a deep part of a living body at a wavelength much shorter than the size of the human body and can be focused on any place. ing. Research and development of ultrasonic therapy utilizing this feature are being actively pursued.

[0003] Biological effects of ultrasonic waves that can be utilized for treatment are roughly classified into heating effects and sonochemical effects. The former heating effect is caused by the tissue absorbing ultrasonic waves to generate heat. Medical applications of this heating effect include "thermotherapy", which treats tumors by continuously heating the affected area to about 40 to 50 degrees Celsius, and instantaneous imaging of the affected area using powerful focused ultrasound. It can be broadly divided into "heat coagulation therapy", which raises the temperature to 80 to 100 ° C, which causes tissue degeneration.

[0004] Hyperthermia for tumors is a treatment utilizing the property that tumor cells are weaker to sustained high temperatures (about 43 ° C) than normal cells, but it is possible to slow down the growth of tumors. However, the ability to directly necrotize tumor cells is low, and it is not easy to maintain the temperature required for treatment because the temperature rise in the affected area is governed by the blood flow and heat conduction of the surrounding tissue, and the temperature rise area Inadequate localization has not reached a satisfactory level in terms of poor balance between therapeutic effects and stress on the body (side effects), and in actual clinical settings it has been used as a combination therapy with radiation therapy. Have been done.

[0005] Heat coagulation therapy is a treatment that has been re-emerging in recent years. Intense ultrasound is collected in a small area of millimeters and instantly raises to a temperature that causes tissue degeneration, and differs from the above-mentioned hyperthermia in the temperature reached at the treatment target site and the resulting tissue change . The heat generated in the tissue is carried away by heat conduction and blood flow. In the case of thermocoagulation, the time required for these heat transport and the heat generated by ultrasonic waves to reach an equilibrium state (10 seconds to 1 minute) In a much shorter time, the temperature of the focal region is raised to a temperature equal to or higher than the protein coagulation temperature by high-intensity ultrasonic waves to coagulate.

One of the diseases for which ultrasonic treatment is suitable is prostatic hypertrophy (BPH). BPH is a very common disease in men over the age of 50, with enlargement and distension of prostate tissue compressing and obstructing the urethra, resulting in difficulty and inability to void. In the initial stage, the person feels discomfort, residual urine, and inconvenience. Until now, various less-invasive treatments for BPH have been medically or surgically attempted by various principle methods. In particular, transurethral resection of the prostate (TUR-P), in which a resectoscope is inserted into the urethra and an enlarged prostate tissue is removed by an electric scalpel, has become popular in recent years. It has also been used to treat bladder tumors. Although this is an excellent treatment, intraoperative and postoperative bleeding, perforation of the prostatic capsule, and postoperative infection are seen as complications, and the pursuit of safer treatment is required. Other methods using lasers and microwaves fall short of TUR-P in terms of effectiveness. It is desired to develop a method that is highly effective and has fewer side effects than TUR-P.

[0007] Prostate cancer has been increasing in recent years as well as the increase in prostatic hypertrophy.
-P can be successfully treated but has complications such as bleeding and
There is also a high risk of having sequelae such as disability. Prostate cancer can be treated with radiation therapy,
Serious side effects must be anticipated at doses sufficient to achieve a good therapeutic effect. Further advanced prostate cancer is TU
Although it can be treated with RP or radiation therapy, it can usually relieve symptoms but not cure it. Since less is achieved in these cases, more non-invasive methods are needed.

[0008] Transrectal hypercoagulant therapy, which has recently emerged, is considered to be a suitable indication of the above-mentioned heat coagulation therapy. Utilizing the anatomical feature that the prostate is adjacent to the rectum wall, an applicator capable of generating powerful focused ultrasound is inserted into the rectum and ultrasound is applied to the adjacent prostate across the rectum wall. And coagulates the hypertrophy that presses the urethra from around. It is an excellent concept in that it is possible to treat prostatic hyperplasia and prostate cancer non-invasively.

[0009] In addition to the above-described thermal effects caused by the absorption of ultrasonic waves in tissues, the cavitation phenomenon is known as a non-thermal effect in the action of ultrasonic waves on a living body. . Cavitation is the generation of bubbles in a narrow sense, but often includes the phenomenon of collapse of the bubbles after generation. Irradiation of living tissue with focused ultrasound produces cavitation bubbles that cause various biological effects. The generated air bubbles become a powerful acoustic reflector, and reflect and scatter the irradiated ultrasonic waves. As a result, the ultrasonic absorption in the surrounding tissue where the cavitation bubbles are present is increased, and the temperature rises sharply. Further, it is known that the sudden collapse of cavitation bubbles causes physical and chemical changes in surrounding tissues, causing tissue destruction, biological membrane damage, and the like. In particular, this chemistry
The cavitation bubble, which is a so-called sonochemical action, is a microbubble generated by ultrasonic irradiation. At the moment when the cavitation bubble is collapsed by sound pressure, it is caused by the high temperature of several thousand degrees that is locally generated by the adiabatic compression of the gas inside. Chemistry, and is particularly prominent due to the coexistence of substances having sonochemical activity. The use of this is sonochemotherapy, which is considered to be particularly effective in blood flow-rich tissues where microbubbles are likely to be generated and where drugs can easily reach.

Various methods have been considered to control this cavitation phenomenon. The first possibility is to introduce bubbles into the sound field. It has been known that an ultrasonic contrast agent containing microbubbles has a function of promoting cavitation. In addition, it is conceivable that the use of a substance for stabilizing bubbles prolongs the life of bubbles and promotes generation and growth of bubbles. In this case, a remarkable effect is recognized in a group of xanthene-based dyes such as rose bengal and erythrosine, and it is known that cavitation is promoted.

On the other hand, in the ultrasonic irradiation technique, it is known that cavitation is promoted by irradiating a target region so that a fundamental wave and a second harmonic having twice the frequency of the fundamental wave are simultaneously superimposed. .

[0012]

The area where irreversible thermal denaturation of the tissue is caused by the irradiation of focused ultrasound is a very small volume near the focal point. This is an important point from the viewpoint of avoiding the side effect that the density of the ultrasonic wave is low at the part other than the focal point and does not reach the temperature of thermal denaturation, but the fact that there are few areas that can be treated at one time is widespread. If a treatment area is required, the total treatment time will be longer. Because, when moving on to the next irradiation, it is difficult to avoid side effects unless irradiation is performed after the temperature of the tissue other than the treatment purpose, which has been raised by the previous irradiation, has sufficiently decreased due to the cooling action such as blood flow. It is. On the other hand, even if the ultrasound intensity applied to treat a large area at once is increased, the area that can be treated at one time cannot be significantly expanded, and side effects on tissues other than the desired area of treatment will occur significantly. It is dangerous. Therefore, at present, the treatment efficiency is extremely poor.

An object of the present invention is to selectively promote the ultrasonic absorption of tissue in a desired treatment area without increasing the applied ultrasonic intensity, that is, without increasing the possibility of accompanying side effects. An object of the present invention is to provide an ultrasonic treatment apparatus capable of efficiently treating an affected part by introducing a fluid.

[0014]

According to the present invention, the above object in selective and local ultrasonic treatment of a disease area including a tumor is solved by the following constitution. That is, this treatment device is a means for irradiating at least ultrasonic waves for ultrasonic treatment, a substance that promotes interaction with ultrasonic waves,
For example, a drug containing a substance that promotes ultrasonic scattering can be mixed before or during treatment, if necessary, and a fluid with a catheter or syringe for injecting the drug into the area to be treated. It has a supply device.

More specifically, an imaging means for irradiating and detecting ultrasonic waves for ultrasonic imaging to draw an ultrasonic tomographic image of a treatment area on a screen, and an apparatus for controlling a transmission frequency from a fluid supplied to the treatment area. It has a detection unit for detecting information on distribution and concentration of fluid from a reflected signal of a harmonic component such as a second harmonic, and means for superimposing and displaying the information on an ultrasonic tomographic image.

The means for irradiating the therapeutic ultrasonic wave not only irradiates with a single frequency ultrasonic wave, but also superimposes a second harmonic having twice the frequency of the ultrasonic wave on the fundamental wave as necessary. When the signal intensity of the harmonic component reflected from the fluid falls below the lower limit of the set range and exceeds the upper limit, the harmonic component detection unit issues an alarm signal. Means for informing the operator of the alarm sound and the lighting of the alarm signal to assist the operator in quickly operating the emergency stop switch and the adjustment switch for the therapeutic ultrasonic output.

If the amount of change in the signal level of the harmonic component suddenly changes beyond the set value, a signal is generated from the harmonic component detection unit and emergency treatment ultrasonic irradiation is stopped or at least the therapeutic ultrasound irradiation is stopped. Decreases the intensity of ultrasonic waves.

According to the embodiment of the present invention, the catheter and the injection needle are installed as follows under ultrasonic imaging or, if necessary, under MRI and X-ray observation. That is, the catheter and the injection needle can be placed at appropriate positions to supply the fluid to the treatment target area. The placement of the catheter is performed in the usual way: arteries, veins, lymph vessels,
In addition to adaptation to the canal of the spinal cavity, the urethra, the ureter, and the like, it is performed by puncturing tissue or by an endoscope.

A fluid containing a substance that promotes scattering and reflection of ultrasonic waves provided in the fluid supply unit is supplied to a catheter or an injection needle by a pump, and is injected into a treatment desired area under observation by the ultrasonic imaging. You.

When the treatment is started, the signal level of the harmonic component including the second harmonic with respect to the transmitted ultrasonic wave from the fluid introduced into the treatment area changes during the treatment. When the signal level of the harmonic component falls below or exceeds the preset range, or approaches the extent that the signal level exceeds the preset range, or exceeds the preset value from the area other than the preset area, in many cases, the area where it is desired to avoid damage around the treatment area. An alert signal is triggered when signal reception is seen. This warning signal is visually or audibly perceived by the operator and assists the operator in making a quick correction decision on the treatment plan. In such a situation, if an appropriate treatment continuation instruction or change instruction is not input from the operator to the device, the running of the ultrasonic wave is selectively or additionally completely shut off, or the harmonic component is It has the function of lowering the signal level below the limit value.

As described in the embodiment of the present invention, when the signal level of the harmonic component including the second harmonic with respect to the transmitted ultrasonic wave from the fluid introduced into the treatment area changes during the treatment, it is introduced into the treatment area. This means that the degree of ultrasonic scattering and reflection of the applied fluid fluctuates, and the degree of temperature rise of the tissue due to the absorption of ultrasonic waves in the periphery of the fluid is not constant, and the therapeutic effect varies. In this case, according to the above-described configuration, simultaneous irradiation is performed so that a second harmonic having a frequency twice as high as that of the ultrasonic wave being irradiated is newly obtained for the fluid and is superimposed on the fundamental wave in response to the fluctuation of the harmonic component. And the amount of microbubbles in the fluid can be adjusted. Thereby, the scattering and reflection of the ultrasonic wave of the fluid are maintained, and the therapeutic effect by the ultrasonic absorption to the surrounding tissue is efficiently exhibited.

As described above, in the present invention, it is possible to arbitrarily synthesize, mix, supply, discharge, and store a fluid having an interaction with ultrasonic waves, for example, a substance that scatters and reflects ultrasonic waves, and a fluid containing the same in the treatment target area. The fluid supply means creates a state where ultrasonic scattering or reflection of an arbitrary treatment area is promoted. As a result, the ultrasonic wave propagating in the surrounding tissue is substantially increased, and it is possible to create a state in which the ultrasonic absorption in the tissue is significantly accumulated, and the region where the fluid is efficiently and efficiently introduced Only the ultrasonic treatment can be selectively performed.

[0023]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS As an embodiment of the present invention, a device for treating prostatic hypertrophy and a device for treating liver cancer will be described with reference to the drawings, the configuration of an ultrasonic treatment device, and a fluid supply device. The drug mixing method and the properties of the drug used will be described sequentially.

FIG. 1 shows an embodiment of an apparatus for treating prostatic hypertrophy. This device is a fluid supply device capable of producing a substance interacting with ultrasonic waves, for example, a substance that scatters or reflects ultrasonic waves, and a fluid containing the same immediately before or during treatment, and supplying and discharging the treated area. 1. It is composed of a therapeutic ultrasonic applicator 2 and an apparatus to be described below that drive and control the therapeutic applicator 2 in accordance with the approach to the affected part. A fluid supply catheter and an injection unit can be connected to this fluid supply device, and it is possible to create a fluid supply form that matches the shape of the affected part. For example, use a catheter according to the diameter of the vascular system such as the urethra and portal vein, and use a direct catheter, endoscope, It is possible to perform insertion and injection with a needle. In the example for prostatic hypertrophy shown in FIG. 1, a catheter is inserted along the urethra from the urethra orifice, but the catheter and the injection needle are inserted directly from the perineum without passing through the urethra. A form that reaches the section is also possible.

The ultrasonic therapy applicator 2 which can be inserted into the rectum 33 obtains a focused ultrasonic transducer 3 composed of a plurality of ultrasonic transducers and an ultrasonic image of the prostate and its surrounding organs in the living body. The ultrasound imaging probe 4 is held inside, and the ultrasound is focused from the rectum to the prostate 31 which is the diseased part, and the hypertrophy which presses the urethra 20 from the surroundings is subjected to the ultrasound treatment.

The focused ultrasonic transducer 3 is composed of an ultrasonic transducer made of a plurality of piezoelectric elements and the like, is connected to the transducer operating section 11, and controls the rotational movement and the longitudinal movement of the transducer. Each element of the transducer is connected to an element drive circuit 6 as shown in FIG.
The configuration is such that the amplitude and phase of the high-frequency power applied to each element can be controlled independently for each transducer. Information relating to ultrasonic irradiation is input to the irradiation unit main control unit 8 by an operation from the key input unit 7, and based on the information, the focal position and sound pressure distribution shape of each irradiation sound field corresponding to the selected frequency are defined. The irradiation code signal is provided from the irradiation unit main control unit 8 to the drive phase generation circuit 9. By controlling the phase independently for each element,
It is possible to simultaneously irradiate ultrasonic waves of two or more kinds of frequencies while controlling the phase, not only in the case of irradiation with a single frequency. The generated phase optimized for each element is supplied to the drive signal generation circuit 10. The drive amplitude given to each element is given from the irradiation unit main control unit 8 to the drive signal generation circuit 10. The drive signal optimized for each element is supplied from the drive signal generation circuit 10 to the element drive circuit 6 to drive the element in the transducer. The drive amplitude is also controlled by a signal directly supplied from the irradiation unit main control unit 8 to the element drive circuit 6, and the operation for urgently stopping the ultrasonic irradiation upon occurrence of the above is reliably and easily performed. According to this configuration, for example, when simultaneously irradiating two types of ultrasonic waves, one of the ultrasonic waves corresponds to the second harmonic having a frequency twice as high as the frequency of the other ultrasonic wave (referred to as a fundamental wave). By selecting a sound wave, it becomes possible to simultaneously irradiate the focal region so that the fundamental wave and the second harmonic wave overlap each other while controlling the phases of the fundamental wave and the second harmonic wave.

The ultrasonic imaging probe 4 is configured to be capable of observing a treatment target area and to obtain a plurality of ultrasonic pulse echo tomographic images required for positioning an irradiation target. Each element of the probe is connected to a transmission control unit 12 and a reception focus unit 13 via a transmission / reception amplifier 15. The reception focus circuit 13 is capable of detecting the occurrence and location of a harmonic component such as a second harmonic having a frequency twice as high as the transmission frequency so as to detect the epicenter of the earthquake. A signal indicating the generation position and generation intensity of the ultrasonic wave including the wave component is superimposed on the echo tomographic image on the monitor of the display unit 14 so as to be displayed. That is, it is possible to observe the distribution of the fluid containing the ultrasonic reflecting substance introduced into the treatment target area.

Further, the display section 14 has a function of graphically displaying the signal intensity of the harmonic component at an arbitrary point displayed on the monitor image, and displays the signal at an arbitrary position desired by an operator such as a doctor. The ultrasonic reflection intensity of the drug can be measured. Also, the signal strength display function of this harmonic component
By setting the reference intensity in advance, when the signal under observation has an arbitrary intensity ratio with respect to the reference signal intensity, a color change can be caused, and the operator such as a doctor can be given a drug. Can be visually transmitted.

With the above configuration, it is possible to continue monitoring the ultrasonic reflection intensity of the diseased part even during the treatment, and when the reflection intensity goes out of a predetermined range, an alarm function is activated and an emergency stop is performed. The irradiation can be stopped by pressing a button or the like. That is, when the ultrasonic reflection intensity of the medicine in the treatment area becomes equal to or less than the minimum set value, it has a function of generating a lamp blink and a buzzer sound, and the ultrasonic reflection intensity of the medicine in the treatment area is equal to or less than the minimum set value. By providing a switch for urgently stopping the irradiation in response to the blinking of the lamp and the generation of the buzzer sound, the operator such as a doctor can be quickly acted upon. Similarly, when the reflection intensity is equal to or greater than the maximum set value, the lamp has a function of generating a lamp blink and a buzzer sound. And a switch for urgently stopping irradiation.

In particular, in the case of frequent irradiation of ultrasonic waves often used in an actual treatment form, the above-mentioned alarm function works effectively. That is, the ultrasonic reflection intensity including the harmonic component such as the second harmonic in the treatment area is stored in the time between irradiations, and compared with the ultrasonic reflection intensity after the next irradiation. This makes it easy to issue an alarm when the rate of change of the ultrasonic intensity exceeds a preset range.

The applicator 2 is covered with a latex rubber cover, and has a structure in which a liquid medium can be stored and refluxed by a water leakage prevention plug 5. As this medium, water is usually used as a substance whose acoustic impedance is close to that of the living body in order to improve the consistency between the living body and the ultrasonic vibrator. , So as not to interfere with the transmission of ultrasound
Has been degassed. Further, in order to reduce the effect of the temperature increase on the rectal mucosa, the medium in the applicator is cooled by a cooling medium perfusion unit 16 having a degassing function, and
It is refluxed through two cooling medium circulation ports.

FIG. 2 shows one embodiment of the fluid supply catheter. An inflatable balloon 18 is provided at the distal end of the fluid supply catheter 17. A small balloon 35 is provided on the proximal side of the balloon 18. This balloon 35
Further, a plurality of minute holes 36 are formed in a portion corresponding to the urethra of the prostate part on the proximal side. A small balloon 37 is provided at the front of the catheter 17, just before the prostatic urethra.

This catheter 17 is connected at hand to the fluid supply control device 1 shown in FIG. The fluid supply control device 1 can arbitrarily supply and discharge fluid mixed with various medicines to the catheter 17 by the rotary pumps 22 and 23, and heat and mix the mixed fluid by the temperature adjustment unit 24 and the pressure adjustment unit 25. It is possible to increase or decrease the pressure. The fluid supply control device 1 is connected to the irradiation unit main control unit 8 and can be operated and controlled by a key input unit 7 connected thereto. The fluid supply control device 1 has a function of mixing a drug in accordance with a treatment plan, and a drug, a physiological saline solution, a buffer solution, or the like necessary for the treatment is supplied to the drug supply units 26 and 27, for example, in a vial. And a cassette filled with a necessary gas can be set in the gas supply unit 28. When actually producing a mixed fluid, a compressed gas is injected from the gas supply unit into the medicine supply unit 27 and mixed with the gas. The mixed fluid is guided to the stirring device 29, where the fluid is alternately taken in and out between the drug supply section 26 and the stirring device 29, and a drug gas mixed fluid having a predetermined mixing ratio is created. . Thereafter, immediately, the mixed fluid is supplied to the temperature control unit 24.
And by the pressure adjusting unit 25, heating and pressurizing or depressurizing so as to obtain a desired temperature and pressure,
Supplied to the treatment area.

FIG. 4 shows an embodiment of a container containing a target drug and set in the drug supply section 26 or 27.
A glass container is sealed with a rubber stopper like a vial, and a precisely weighed amount of a drug is stored inside in a fluid state in the form of powder or dissolved or mixed in an appropriate solvent. As shown in FIG. 4, a plurality of powdered or granular individuals of a drug can be separated and stored via a filter 41 so that they do not come into contact with each other and do not undergo a chemical reaction. This filter 41 is composed of fine chemical fibers, has an average pore size of 4 μm,
It blocks the intermixing of two types of powder or granule drugs placed at positions 9 and 40. At the time of treatment, the same as injecting distilled water etc. into the vial,
By injecting a medium such as physiological saline with an injection needle or the like, the drug disposed at the position 39 in FIG. 4 is dissolved,
In addition, since the filter 41 has a structure through which a drug solution having a molecular weight of 10,000 or less passes, the drug arranged at the position 40 is mixed and dissolved as a result, and the two kinds of drugs are completely dissolved.
Thereafter, by being set in the medicine supply unit 27 shown in FIG. 1, the mixture with the gas from the gas supply unit 28 is received. Further, even when the solvent is not injected into the container, it is possible to provide the medicine supply unit 26 with the medicine supply unit 26.
If the solvent is supplied to the container 7, the solvent mixed with the gas is supplied to the medicine supply unit 26 by the agitating device 29, thereby dissolving the two kinds of drugs in the container shown in FIG. Mixing becomes possible.

The procedure for actually treating the prostate 31 is as follows. With the balloon 18 deflated, the fluid supply catheter 17 internally filled with the fluid to be used is inserted into the external urethral opening 19.
It is inserted into the urethra 20 more. At this time, it is desirable to apply a sterile lubricant having lubricity or local anesthesia such as xylocaine jelly to the tip. However, at this time,
Care must be taken not to block the holes in the catheter. After the distal end of the catheter 17 reaches the inside of the bladder 21, the stopcock 30 is operated to inject pure water, physiological saline, or air to inflate the balloon 18. Thereby, the catheter 17 is positioned in the urethra 20 as shown in FIG. Further, by operating the stopcock 30 on the small balloon 35 located at the base of the balloon 18, pure water, physiological saline or air is injected and inflated. Accordingly, the balloon 19 presses the urethra at the boundary between the bladder and the prostate gland from the inside, thereby increasing the retention of the catheter 17 within the urethra 20 and blocking the flow between the urethra 20 and the bladder 21. To facilitate fluid storage. As a result, a site where the micropore 36 of the catheter 17 is opened is located in the prostatic urethra. Further, by injecting a medium such as pure water, physiological saline, or air into the small balloon 37 provided just in front of the catheter 17 just before the prostatic urethra by operating the stopcock 30 and inflating the small balloon 37, Fluid retention in the prostatic urethra can be ensured.

After the applicator 2 shown in FIG. 1 is inserted into the rectum, the reflux pressure of the reflux medium in the applicator is increased to adjust the latex rubber cover so as to be in close contact with the rectum wall. By freely inflating the water bag made of flexible rubber, it becomes possible to adhere along the shape of the rectal mucosa, and it becomes easy to perform ultrasonic imaging and focused ultrasonic irradiation of the prostate periphery. Furthermore, heat generation on the surface of the rectal mucosa caused by ultrasonic irradiation can be suppressed by the reflux cooling medium inside the applicator.

Ultrasonic imaging probe 4 inside applicator
After sufficiently observing the periphery of the prostate, the fluid supply device 1 supplies a fluid having the function of reflecting ultrasonic waves to the fluid supply catheter 17, and the fluid having a function of reflecting ultrasonic waves is supplied from the micropore 36 located in the prostatic urethra. The fluid containing the agent having the function of reflecting the sound waves flows out and fills the prostatic urethra. At this time, as described above, the distribution of the fluid can be clearly observed by detecting a harmonic component such as the second harmonic with respect to the transmission wave, and the supply of the fluid to the treatment area is visually confirmed. I can do it.

Focused ultrasound focuses on the prostatic urethra and produces a peak sound pressure near the focus of about 100 W / cm ² to 1 kW / cm 2.
^In the range of ² , irradiation is performed continuously for 1 to 10 seconds at a time. By repeating this irradiation along the prostatic urethra, the prostate can be treated.

Here, when the reduction coefficient of the signal level of the higher harmonic component such as the second harmonic from the fluid introduced into the treatment area becomes larger than the set value, and when the absolute value of the signal level becomes smaller than the set value. If this happens, the above-described alarm function is activated to notify an operator such as a doctor of a change in signal strength. In this case, preparation is made for simultaneous irradiation of the second harmonic of the ultrasonic wave that has been irradiated. At this time, the phase relationship between the second harmonic and the fundamental wave is set to a phase relationship that emphasizes the peak of the negative pressure. By the alarm function, when the operator of the doctor or the like notified of the change in the signal strength determines that the superimposed irradiation of the second harmonic is selected from the input unit,
The superimposed irradiation of the second harmonic and its fundamental wave is applied to the area where the fluid with the reduced signal intensity is present, thereby promoting the generation and growth of microbubbles including cavitation bubbles, which are the main components of ultrasonic reflection, and the existence life. Can be extended. As a result, the ultrasonic reflection level is restored, and the manifestation of the therapeutic effect is stabilized. Similarly, when the increase factor of the signal level of the harmonic component such as the second harmonic from the fluid introduced into the treatment area is equal to or larger than the set value, and when the absolute value of the signal level is equal to or larger than the set value. The alarm function described above is activated to notify the operator such as a doctor of a change in signal strength. In this case, preparation is made for simultaneous irradiation of the second harmonic of the ultrasonic wave that has been irradiated. At this time, the phase relationship between the second harmonic and the fundamental wave is set to a phase relationship that emphasizes the peak of the positive pressure. When an operator such as a doctor notified of the change in signal strength by the alarm function determines that the superimposed irradiation of the second harmonic is selected from the input unit,
Immediately, the superimposed irradiation of the second harmonic and its fundamental wave is applied to the region where the fluid having the increased signal intensity is present, thereby suppressing the generation and growth of microbubbles including cavitation bubbles which mainly cause ultrasonic reflection, or It is possible to prevent the existing life from being further extended. As a result, the ultrasonic reflection level is kept substantially constant, and the manifestation of the therapeutic effect is stabilized. This function is performed not only by the instruction of the operator such as a doctor as described above, but also by setting in advance, the harmonic component such as the second harmonic from the fluid introduced into the treatment area. When the signal level becomes equal to or higher than the set value, it is possible to automatically perform the second harmonic superimposed irradiation.

In the usual treatment of the prostate, ultrasound is irradiated while the catheter is indwelled. In some cases, a catheter having a fluid supply hole 38 at the tip as shown in FIG. To supply the drug-mixed fluid to the treatment area from the fluid supply hole 38.
At this time, by appropriately combining and inflating the balloons 18, 35 and 37 of the catheter, it is possible to prevent the backflow of the fluid from the treatment area.

Next, an apparatus for treating liver cancer using the present invention will be described with reference to the drawings. FIG.
5 shows one form of ultrasonic treatment for liver cancer 47 occurring in one hepatic lobe. As shown in the figure, a transducer is brought into contact with the surface of the liver, and has an acoustic reflector 48 disposed at a position where the ultrasonic wave emitted from the transducer can be reflected with the affected part in between. The ultrasonic treatment transducer 44 has a configuration in which the imaging ultrasonic probe 42 and the treatment ultrasonic piezoelectric element 43 are integrated with each other.
A cooling medium can pass through the cooling medium supply tube 50 inside the transducer, and is connected to a cooling medium perfusion unit 16 similar to that shown in FIG. In addition to preventing heat generation, it is possible to suppress heat generation in the tissue in contact with the transducer. In addition, if necessary, the cooling medium can be perfused also into a reflector disposed at a position where the ultrasonic wave emitted from the transducer can be reflected with the diseased part interposed therebetween, and the tissue contacted from both sides so as to sandwich the diseased part Heat generation can be suppressed. Note that by using the parallel holding mechanism 49 as shown in FIG. 5, it is possible to always maintain the parallelism between the transducer and the reflector as needed. As shown in FIG. 5, the provision of the soft resin lens layer 45 made of silicon rubber or the like on the surface of the transducer enables the transducer to adhere to the tissue without damaging the tissue.

As described above for the treatment of the prostate, the introduction of the drug-mixed fluid into the affected area is achieved by introducing a catheter into the vascular system such as the urethra, portal vein, and lymphatic vessels.
It is also possible to insert a catheter directly into the affected part or directly flow into the affected part with an injection needle. FIG. 5 shows an example of inserting an injection needle connected to the fluid supply device 1 around liver cancer. 1 shows a configuration for supplying and storing a medicine mixed fluid. That is, as shown in FIG. 5, the injection needle 53 connected to the fluid supply device 1 is inserted around the liver cancer 47 inside the liver 46, and the configuration of the prostate treatment device is described with reference to FIG. Similarly, it becomes possible to introduce the drug mixed fluid around the affected area. As shown in FIG. 5, a catheter having a catheter and an injection needle to be pierced into the treatment area of the fluid supply device 1 is connected to the connection portion 51 by gelatin, agar,
A backflow prevention particle supply unit 52 made of collagen, fibrin, or the like, which can supply microparticles for fluid backflow, is provided, and it is possible to close the removal hole of the injection needle from the affected part.

In the treatment of liver cancer, the approach to the venous system such as the portal vein and the surrounding area of the hepatic artery from the hepatic artery is the same as the fluid supply to the affected area by introducing a catheter from the urethra described with reference to FIG. It is possible. In this case, the fluid supply catheter 17 filled with the fluid to be used is placed in the vicinity of the treatment area through a vessel such as a portal vein or a hepatic artery in accordance with a conventional method of inserting a catheter. At this time, the position of the catheter and the distribution of the fluid can be observed by the imaging probe 42 incorporated in the transducer.
As in the case of the prostate treatment apparatus described above, it is possible to clearly observe by detecting a harmonic component such as the second harmonic with respect to the transmission wave, and to perform fluid supply to the treatment area while visually confirming it. In addition, at the time of catheter insertion, using a tool for assisting catheter operation composed of a metal material such as a guide wire, or using a material containing a radiopaque material such as iodine for the catheter, Alternatively, by mixing a drug containing an X-ray opaque substance such as iodine into a fluid to be introduced into the treatment area, even in X-ray fluoroscopy, it is possible to introduce the catheter and introduce the fluid into the treatment area. It is possible.

FIG. 6 illustrates the structure of the ultrasonic therapy transducer described with reference to FIG. By arranging the treatment piezoelectric elements 54-1 to 5-4 and the one-dimensional imaging probes 55-1 to 4 as shown in the figure, it is possible to make the treatment transducer have a two-dimensional imaging function of the affected part. Become. FIG. 7 shows a pipe 56 through which a cooling medium is perfused inside the transducer shown in FIG. As shown in FIG. 8, by arranging the two-dimensional imaging probe 61 at the center of the transducer in which the piezoelectric elements 57 to 60 having resonance frequencies at different frequencies are arranged in an array, the 2 Two-dimensional imaging observation can be performed. This transducer has a cooling pipe 62 on the back. By this two-dimensional imaging, the catheter and the injection needle introduced into the treatment target area can be observed on a plurality of screens.
Positioning for properly introducing the medicine can be ensured.

The treatment of liver cancer will be described in detail with reference to the following combinations of drugs. Rose Benga, a Lipiodol and Xanthene Derivative Based on Iodized Poppy Oil
An aqueous solution and carbon dioxide gas are set in predetermined drug supply units 26 and 27 and a gas supply unit 28 in the fluid supply control device 1, and a mixed fluid is created in the manner described above. At that time, it is possible to set the mixing ratio of each drug and gas, and in the following examples, lipiodol,
Rose Bengal aqueous solution (dissolved in a neutral buffer such as physiological saline or PBS so that the Rose Bengal concentration is 0.1 mg / ml) and carbon dioxide gas in a volume ratio of 3: 0.3: 1. Mixed. Even when the above-mentioned fluid supply control device 1 is not used, a mixed fluid can be prepared by collecting an appropriate amount of the above-mentioned drug into the manual mixing kit shown in FIG. 9 and mixing it. It is configured such that it can be directly introduced into the supply control device 1.

In the case of this embodiment, the balloon of the catheter is inflated in front of the portal vein branch or arterial branch covering the area of liver cancer, brought into close contact with the inside of the vessel, and a drug mixed fluid is injected from the tip of the catheter. The portal vein or arterial branch covering the liver cancer area is filled with fluid. When ultrasonic irradiation is performed in the above process, ultrasonic scattering and reflection around the portal vein branch or arterial branch filled with the mixed fluid increases, and the continuous ultrasonic irradiation focuses on the fluid distribution area. The temperature of the tissue rises to a temperature at which protein denaturation occurs due to a remarkable increase in the ultrasonic absorption in the tissue in the region defined as above. As a result, tissue degeneration is caused in a region-selective manner only in the region where the introduced mixed fluid is present, so that cancer tissue can be treated. This will be further described with reference to the conceptual diagram shown in FIG. In the case of a tissue that does not include a scatterer as shown in FIG. 10A, when the ultrasonic wave 66 propagates, ultrasonic absorption corresponding to the tissue and the frequency of the ultrasonic wave is observed. However, as shown in FIG.
If 7 is present, the ultrasound is scattered by the scatterer, or is reflected if there is an ultrasound reflector. As a result, the transmission density of ultrasonic waves per unit tissue volume is substantially increased in the case where the scatterer is present rather than the case where the scatterer is not present. Therefore, by the ultrasonic waves irradiated at the same density as without the scatterer, the presence of the scatterer increases the amount of ultrasonic absorption in the tissue,
As a result, the temperature of the tissue increases, and the heat coagulation effect is promoted. In addition, this effect is significantly increased by the cavitation phenomenon. In the present embodiment, the irradiation is performed by ultrasonic irradiation of 1 MHz, but the above-mentioned therapeutic effect can be exhibited by using ultrasonic waves of 100 kHz to 10 MHz. Further, as described in the above-mentioned embodiment of the prostate treatment, two kinds of ultrasonic waves, that is, a fundamental wave and its two
The use of an ultrasonic transducer having the function of superimposing the second harmonic, which simultaneously irradiates the second harmonic having twice the frequency, has a synergistic effect with the effect of stabilizing the microbubbles of the xanthene derivative in the treatment area. , Remarkably prolonging the life of bubbles, maintaining the ultrasonic scattering and reflection effects of the fluid, and exhibiting a stable therapeutic effect. At this time, ATX-7, a kind of porphyrin derivative, was used as a drug shown in the above example.
0 Aqueous solution (dissolved in a neutral buffer such as physiological saline or PBS so that the concentration of ATX-70 becomes 0.2 mg / ml)
Is used, lipiodol, carbon dioxide gas and, if necessary, a xanthene derivative are mixed by the same operation as in the above example, and the mixture is introduced into the treatment area, whereby the therapeutic effect can be improved. That is, by the ultrasonic irradiation by the second harmonic superimposition, the increase or growth of the cavitation bubbles derived from the fluid is promoted, the sonochemical action of the porphyrin derivative is induced, and only in the region where the fluid exists, the active oxygen species And promote the generation of various short-lived radical species, which can cause cancer tissue to become necrotic. This is expected to have a synergistic anti-cancer effect due to a different mechanism of action, not only the destruction effect of cancer tissue due to heat generated by absorption of ultrasonic waves in tissue, but also the anti-cancer effect on cancer tissue by sonochemical action. You. The effect is that the xanthene derivative and the porphyrin derivative not only promote cavitation and enhance the cavitation effect by contributing to the stability of the bubbles, but also cause the gas released from the cavitation bubbles after the collapse of the cavitation bubbles to generate new cavitation bubbles. This is explained by having a property of generating and growing cavitation bubbles in a chain reaction by using the nucleus as a core.

The specific features of the various embodiments of the present invention are as follows.

(1) A therapeutic ultrasonic transducer is brought into contact with an affected part, and when an ultrasonic wave emitted by the transducer propagates through the affected part, an ultrasonic wave having an acoustic reflector that can be arranged at a position where the ultrasonic wave can be reflected. Treatment device.

(2) The transducer has a lens layer made of silicone rubber or resin on the surface that contacts the affected part.

(3) The transducer has a parallelism maintaining mechanism for the acoustic reflector.

(4) Coolant perfuses into the transducer and acoustic reflector.

(5) An ultrasonic therapy apparatus including a catheter configured to be able to fill a fluid therein and a fluid supply device having means for filling the catheter with a fluid containing at least one substance having a high ultrasonic reflection coefficient. .

(6) An ultrasonic therapy apparatus including a catheter configured to be capable of being filled with a fluid and a fluid supply device having means for filling the catheter with a fluid containing at least one cavitation-inducing substance.

(7) The fluid supply device in the above (5) or (6) has a pressure adjusting mechanism capable of increasing or decreasing the pressure of the fluid.

(8) An ultrasonic treatment apparatus having a mechanism for alternately filling a catheter with fluids contained in a plurality of containers. (9) A fluid supply device having a function of placing a fluid backflow preventing substance containing at least one of gelatin, agar, collagen, and fibrin in an insertion cavity after fluid injection. The treatment device according to any one of the preceding claims.

(10) In a mixed fluid of gas and liquid,
It is characterized by containing a bubble stabilizing substance, which is configured to stabilize micronized gas bubbles, maintain the diameter of the bubbles, maintain the existence life of the bubbles, and promote cavitation. A microbubble preparation that can be administered to the body.

(11) The microbubble stabilizing substance in the above (10) includes a porphyrin derivative and a xanthene derivative.

(12) The microbubbles in the above (10)
Carbon dioxide (CO2) is the main gas component.

(13) The microbubbles in the above (10)
Includes a gas mixture containing oxygen molecules (O2).

(14) The preparation of microbubbles in the above (10) contains sodium bicarbonate.

(15) The preparation of microbubbles in the above (10) contains poppy oil or fatty acid.

[0062]

According to the present invention, by supplying a fluid containing a substance that increases the scattering and reflection of ultrasonic waves to the treatment area, it is possible to avoid a secondary injury to tissues other than the treatment area. In addition, the ultrasonic absorption in the treatment area is selectively promoted, and the effect of the ultrasonic treatment is spatially selectively increased.

[Brief description of the drawings]

FIG. 1 is a configuration diagram showing an outline of a prostate treatment system according to an embodiment of the present invention.

FIG. 2 is a diagram showing an embodiment of a catheter which can be inserted into a treatment target region and supply a medical solution.

FIG. 3 is a view showing one embodiment of a catheter that can be inserted into a treatment target region and supply a medical solution.

FIG. 4 is a diagram illustrating a medicine supply bottle that supplies a medicine to a fluid supply device.

FIG. 5 is a configuration diagram showing an outline of a liver cancer treatment system according to an embodiment of the present invention.

FIG. 6 illustrates one embodiment of a therapeutic transducer incorporating an array probe for imaging.

FIG. 7 illustrates one embodiment of piping for passing a cooling medium in a therapeutic transducer.

FIG. 8 illustrates one embodiment of a therapeutic transducer incorporating an array probe for imaging.

FIG. 9 is an explanatory view of a device for manually mixing a fluid.

FIG. 10 is a diagram illustrating the ultrasonic absorption of a living tissue.

[Explanation of symbols]

1 ... fluid supply device 2 ... therapeutic ultrasonic applicator
3: Focused ultrasonic transducer, 4: Ultrasonic imaging probe, 5: Water leak prevention plug, 6: Element drive circuit, 7: Key input unit, 8: Irradiation unit main control unit,
9: drive phase generation circuit, 10: drive signal generation circuit,
DESCRIPTION OF SYMBOLS 11 ... Transducer operation part, 12 ... Transmission control unit, 13 ... Reception focus unit, 14 ... Display part, 15 ... Transceiver amplifier, 16 ... Cooling medium perfusion unit, 17 ... Fluid supply catheter, 18 ... Balloon, 19 ... 20 ... urethra, 21 ... bladder,
Reference numerals 22, 23: rotary pump, 24: temperature adjustment unit, 25: pressure adjustment unit, 26, 27: drug supply unit, 28: gas supply unit, 29: stirring device, 3
0 ... cock, 31 ... prostate, 32 ... sensor unit,
33 ... rectal, 34 ... anus, 35 ... balloon, 3
6 ... fluid supply hole, 37 ... balloon, 38 ... fluid supply hole, 39, 40 ... drug, 41 ... filter, 42
... Ultrasonic probe for imaging, 43 ... Ultrasonic piezoelectric element for treatment, 44 ... Transducer for ultrasonic treatment, 45 ...
Lens layer, 46: liver, 47: liver cancer, 48: acoustic reflector, 49: parallel holding mechanism, 50: cooling medium supply tube, 51: connection part, 52: backflow prevention particle supply part, 53: injection needle, 54 ... Piezoelectric elements for treatment, 55
... an imaging probe, 56 ... cooling pipe, 57-60 ... piezoelectric element, 61 ... imaging probe, 62 ... cooling pipe,
63: syringe, 64: stopcock, 65: fluid mixing section,
66 ... ultrasonic, 67 ... scattering body, 68 ... scattered ultrasonic wave.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Kenichi Kawabata 1-280 Higashi-Koikekubo, Kokubunji-shi, Tokyo Inside the Central Research Laboratory, Hitachi, Ltd. Central Research Laboratory F-term (reference) 4C060 EE03 EE21 JJ27 KK47 MM24

Claims (6)

[Claims] In an ultrasonic therapy apparatus for performing treatment by irradiating a therapeutic region with ultrasonic waves, a drug containing a substance that promotes interaction with ultrasonic waves is mixed and produced before or during the treatment. And a fluid supply device for directly supplying the medicine to the treatment target region via a catheter or a needle. 2. A means for displaying a distribution of an introduced fluid based on a reception intensity of reflected ultrasonic waves including a harmonic component such as a second harmonic from an area to be treated with respect to an irradiated therapeutic ultrasonic wave, and said treatment. The ultrasonic treatment apparatus according to claim 1, further comprising means for changing irradiation conditions such as a frequency, an intensity, a pulse length, and a pulse interval of the ultrasonic waves for use. 3. The display means displays the received signal strength of a harmonic component such as a second harmonic with respect to the therapeutic ultrasonic wave by a numerical value, a color tone, a luminance, or a combination thereof in two dimensions corresponding to the detected position. The ultrasonic therapy apparatus according to claim 2, wherein the information is displayed at a position on a screen. 4. The apparatus according to claim 3, wherein said displaying means displays a signal intensity ratio of the irradiation area under treatment to a reference signal intensity by using a numerical value, a color tone, a luminance, or a combination thereof. Sonic therapy equipment. 5. A means for generating an alarm by blinking a lamp and generating a buzzer sound when the ultrasonic reflection intensity of the medicine in the treatment area falls below a minimum set value and becomes greater than a maximum set value. The ultrasonic therapy device according to claim 1. 6. The ultrasonic therapy apparatus according to claim 5, wherein
An ultrasonic treatment apparatus having a switch for urgently stopping irradiation in response to the generation of an alarm when the ultrasonic reflection intensity of the medicine in the treatment area falls below the minimum setting value and when the ultrasonic reflection intensity exceeds the maximum setting value .