WO2018158805A1 - Ultrasonic medical apparatus - Google Patents

Abstract

With the purpose of heating an organ or a region of a subject to be treated to a temperature that is necessary for treatment, the ultrasonic medical apparatus (1) according to the present invention includes: an ultrasonic element (2) which outputs ultrasonic waves; a drive unit (3) which drives the ultrasonic element (2) such that the ultrasonic element (2) outputs ultrasonic waves for ablation (W1) with an amplitude that applies a pressure less than a predetermined pressure to tissue (A) to be treated to which a medicine, which has a predetermined boiling point and is bubbled when the predetermined pressure is applied, has been administered, and thereafter outputs ultrasonic waves for bubbling (W2) with an amplitude that applies a pressure equal to or greater than the predetermined pressure thereto; and a temperature determination unit (5) which determines whether the tissue (A) being treated has reached a predetermined temperature higher than the boiling point on the basis of the presence of bubbles after a predetermined time has passed after the ultrasonic waves for bubbling (W2) have been output by the drive unit (3).

Description

Ultrasound medical equipment

The present invention relates to an ultrasonic medical device.

2. Description of the Related Art An ultrasonic treatment method using focused ultrasound (HIFU: High Intensity Focused Ultrasound) in combination with microbubbles is known (for example, see Patent Document 1). HIFU is a technology that focuses ultrasound and forms a focal point with high energy density, and can treat living tissue locally at the focal point.

Microbubbles can be generated using nanodroplets. The nanodroplet is a nanometer-size capsule made of a film of lipid, protein, biodegradable polymer or the like and enclosing a liquid. When ultrasonic waves are radiated to the nanodroplets, the liquid changes to bubbles due to a decrease in pressure, and micrometer-sized bubbles (microbubbles) are generated. The microbubbles vibrate by ultrasonic waves and have a function of promoting the warming action of the living tissue by ultrasonic irradiation. Furthermore, the microbubbles are crushed by ultrasonic waves, and at that time, physical energy is generated.

Thus, for example, in cancer treatment, nanodroplets are accumulated in cancer tissue, and HIFU is irradiated to the cancer tissue, so that the cell cannot be destroyed by itself. Cells can be destroyed. Since the tissue in the region where the nanodroplet is not present is hardly heated by such a low energy HIFU, only the tissue in the region where the nanodroplet is present can be selectively treated.

Japanese Patent No. 5340728

The ultrasonic treatment method of Patent Document 1 has a problem that it is difficult to appropriately control the irradiation amount of the HIFU given to the living tissue because the temperature of the living tissue irradiated with the HIFU cannot be grasped. When the irradiation dose of HIFU is insufficient, the organ or site to be treated cannot be heated to a temperature necessary for treatment. Furthermore, the appropriate amount of ultrasound irradiation varies depending on the organ, the site, and their state.

The present invention has been made in view of the above-described circumstances, and an object of the present invention is to provide an ultrasonic medical device capable of heating an organ or a site to be treated to a temperature necessary for treatment.

According to one embodiment of the present invention, a pressure lower than the predetermined pressure is applied to an ultrasonic element that outputs an ultrasonic wave and a treatment target tissue to which a medicine that has a predetermined boiling point and bubbles when applied with a predetermined pressure is administered. A driving unit that drives the ultrasonic element to output a bubble-forming ultrasonic wave having an amplitude that gives a pressure equal to or higher than the predetermined pressure after outputting the ablation ultrasonic wave having a certain amplitude, and the bubbling by the driving unit And a temperature determination unit that determines whether or not the tissue to be treated has reached a predetermined temperature higher than the boiling point based on the presence or absence of bubbles after a lapse of a predetermined time after the ultrasonic wave is output. Device.

According to this aspect, by outputting ultrasonic waves for ablation with an amplitude that gives a pressure lower than a predetermined pressure to the tissue to be treated, the medicine can be heated to a predetermined temperature without being bubbled. By outputting ultrasonic waves for bubbling with an amplitude that applies a pressure equal to or higher than a predetermined pressure to the site, the drug can be bubbled. When the temperature of the tissue to be treated exceeds the boiling point of the drug, the bubbles remain for a relatively long time, but when the temperature does not exceed the boiling point of the drug, the bubbles disappear instantaneously.

Therefore, the temperature determination unit can determine that the tissue to be treated has reached the predetermined temperature when the bubbles are present after the elapse of a predetermined time after the output of the bubble forming ultrasonic waves, and the bubbles disappear. If it is, it can be determined that the predetermined temperature has not been reached. Thereby, the tissue to be treated can be heated to a temperature necessary for treatment by outputting again the ultrasonic waves for cauterization to the part determined not to reach the predetermined temperature.

1 is a block diagram illustrating an ultrasonic medical apparatus according to an embodiment of the present invention. It is a figure explaining determination of the temperature of the treatment target tissue by the ultrasonic medical device of FIG. It is a flowchart explaining the treatment procedure using the ultrasonic medical device of FIG. It is a flowchart explaining the treatment procedure using the ultrasonic medical device of FIG. It is a figure explaining confirmation of the protection of the adjacent tissue of the treatment target tissue by the ultrasonic medical device of FIG.

An ultrasonic medical device 1 according to an embodiment of the present invention will be described below with reference to the drawings.
As shown in FIG. 1, the ultrasonic medical device 1 according to this embodiment includes an ultrasonic element 2 that generates ultrasonic waves, an ultrasonic wave W1 for ablation by driving the ultrasonic element 2, and an ablation ultrasonic wave. A driving unit 3 that outputs a sound wave W2 and a diagnostic ultrasonic wave W3; an image acquisition unit 4 that receives a reflected echo of the diagnostic ultrasonic wave W3 from the treatment target tissue A and acquires an ultrasonic image of the treatment target tissue A; And a temperature determination unit 5 that determines the temperature of the treatment target tissue A based on the ultrasonic image acquired by the image acquisition unit 4.

The ultrasonic element 2 includes a concave radiation surface 6 and a convex radiation surface 7, and focuses the cauterization ultrasonic wave W 1 and the bubbling ultrasonic wave W 2 on the focus from the concave radiation surface 6. On the other hand, diagnostic ultrasonic waves W3 are output from the convex radiation surface 7.

The ablation ultrasonic wave W1 is an ultrasonic wave having an amplitude that gives the treatment target tissue A a pressure equal to or lower than a predetermined pressure that does not cause the drug (nanodroplets (bubble-forming material)) administered to the treatment target tissue A to be bubbled.
By continuously outputting the ultrasonic wave W1 for cauterization, as shown in FIG. 2, the tissue A to be treated can be heated to a desired temperature without causing the drug to be bubbled. .

The ultrasonic wave W2 for bubbling is a pulsed ultrasonic wave having an amplitude that applies pressure to the drug to form a drug (nanodroplet (bubble-forming material)) administered to the tissue A to be treated. The ultrasonic medical device 1 can bubble the medicine without heating the treatment target tissue A as shown in FIG. 2 by outputting the aeration ultrasonic wave W2 for a short time. ing.
The bubbling ultrasonic wave W2 is a short pulse as much as possible, and is preferably about 1 to 2 cycles, for example. This is to prevent the bubbles generated at the beginning of the waveform of the bubble forming ultrasonic wave W2 from being destroyed at the latter half of the bubble forming ultrasonic wave W2.

Nanodroplets are nanometer-sized capsules made of lipid membranes, proteins, or polymers, and enclosing a liquid. The membrane holds a ligand that specifically binds to a specific component in the living body. The liquid has a boiling point higher than the body temperature (37 ° C.) and lower than the boiling point of water (100 ° C.). In this embodiment, it is assumed that the ultrasonic medical device 1 treats cancer tissue with the ultrasonic wave W1 for ablation. Therefore, the nanodroplet uses a ligand that specifically binds to cancer cells and a liquid having a boiling point at a temperature at which the cancer cells die (for example, 50 ° C.). For example, perfluorobutane or perfluoropentane is used as the nanodroplet. Perfluorobutane and perfluoropentane are easy to mix because of their similar molecular structures. It is possible to adjust to a desired boiling point by using two or more substances having different boiling points and adjusting the mixing ratio.

The nanodroplet is bubbled by being irradiated with the bubble forming ultrasonic wave W2 having an amplitude of a predetermined value or more. When the nanodroplet is irradiated with the bubble forming ultrasonic wave W2, the nanodroplet is bubbled due to a decrease in the negative pressure in the region irradiated with the ultrasonic wave, and microbubbles that are micrometer-sized bubbles are generated. The microbubble has a higher reflectance than the treatment target tissue A with respect to the diagnostic ultrasonic wave W3. Accordingly, in the ultrasonic image based on the reflected echo from the treatment target tissue A of the diagnostic ultrasonic wave W3, the microbubble region has a higher luminance value than the region of the treatment target tissue A.

The driving unit 3 divides the treatment target tissue A to be treated into a plurality of regions, and drives each region so as to sequentially irradiate the ablation ultrasonic wave W1 and the bubbling ultrasonic wave W2. Specifically, the drive unit 3 causes the first region to output the cauterization ultrasonic wave W1 over the first output time, and subsequently causes the bubbling ultrasonic wave W2 to be output over the second output time. Next, the drive unit 3 changes the ultrasonic irradiation position to a second region different from the first region, and outputs the ablation ultrasonic wave W1 and the aeration ultrasonic wave W2. The drive unit 3 performs this operation for all regions.

Next, the drive unit 3 sequentially outputs the diagnostic ultrasonic wave W3 to all the regions when the output of the cauterizing ultrasonic wave W1 and the bubbling ultrasonic wave W2 to all the regions is completed, and the reflected echo is generated. The ultrasonic element 2 is made to receive.

The image acquisition unit 4 amplifies the echo signal output from the ultrasonic element 2, converts the amplitude of the amplified echo signal into a luminance value, and forms an ultrasonic image based on the converted luminance value. It has become.
The temperature determination unit 5 compares the luminance value of each image group acquired by the image acquisition unit 4 with a predetermined threshold, and the region where the luminance value is larger than the threshold is heated to a temperature exceeding the boiling point of the chemical solution. On the other hand, when the luminance value is equal to or lower than the threshold value, it is determined that the temperature is not heated to a temperature exceeding the boiling point of the chemical solution.

Moreover, the temperature determination part 5 outputs to the drive part 3 the area | region corresponding to the pixel determined not to be heated to the temperature exceeding the boiling point of a chemical | medical solution as a temperature unachieved area | region.
When the temperature unreachable region is output from the temperature determination unit 5, the drive unit 3 controls the drive so that the cauterization ultrasonic wave W1 is output again to the temperature unreachable region.

In this case, when the drive unit 3 outputs the ablation ultrasonic wave W1 again to the temperature unachieved region, the drive unit 3 increases and outputs at least one of the output intensity or the output time of the ablation ultrasonic wave W1. It is like that.

The operation of the ultrasonic medical apparatus 1 according to this embodiment configured as described above will be described below.
In order to perform treatment of the treatment target tissue A using the ultrasonic medical device 1 according to the present embodiment, first, as shown in FIGS. 3A and 3B, the user applies a medicine containing nanodroplets to the treatment target. Administer to tissue A (step S1). The administered nanodroplets accumulate in the cancer tissue.

Next, the drive unit 3 sets the region number N to 1 (step S2), the focal point of the ultrasonic element 2 is aligned with the Nth region of the tissue to be treated A (step S3), and the Nth region The ultrasonic waves W1 for cauterization and the ultrasonic waves W2 for bubbling are sequentially irradiated on the surface (steps S4 and S5).
The drive unit 3 determines whether or not the irradiation of ultrasonic waves has been completed for all the preset areas (step S6). If not, the area number N is incremented by one (step S6). S7), the above-described steps S3 to S7 are repeated.

Each region of the treatment target tissue A is heated by irradiating the predetermined region of the treatment target tissue A with the ablation ultrasonic wave W1 for a predetermined time. Since the ultrasonic wave W1 for ablation is an ultrasonic wave having an amplitude that applies a pressure equal to or lower than a predetermined pressure that does not cause the nanodroplet to be bubbled, only the tissue A to be treated is heated while no microbubbles are generated.

On the other hand, by irradiating the bubble forming ultrasonic wave W2 for a sufficiently short time, the nanodroplets are bubbled to generate microbubbles, but the irradiation of the bubble forming ultrasonic wave W2 is limited to a sufficiently short time. By doing so, microbubbles can be generated without heating the tissue A to be treated.

Generated microbubbles disappear as time passes. The disappearance rate of the microbubbles depends on the relationship between the boiling point of the liquid of the nanodroplet and the temperature of the tissue surrounding the microbubbles when the bubbles are formed.

When the temperature of the surrounding microbubbles is equal to the boiling point of the microbubbles, the microbubble extinction rate is set as a threshold, and when the surrounding tissue temperature is equal to or higher than the boiling point of the liquid, the microbubbles are stabilized. Since it continues to exist, the extinction speed is below a predetermined threshold. On the other hand, when the temperature of the surrounding tissue is lower than the boiling point, the microbubbles disappear quickly, so the disappearance rate becomes larger than a predetermined threshold.

When the irradiation of ultrasonic waves by the drive unit 3 is completed for all regions (step S6), the drive unit 3 then irradiates all regions with diagnostic ultrasonic waves W3 (step S8). Then, an ultrasonic image is acquired (step S9). The area number M is set to 1 (step S10).
The temperature determination unit 5 determines the presence or absence of bubbles based on the luminance value of each pixel of the acquired ultrasonic image, so that the region of the treatment target tissue A corresponding to each pixel is heated to a predetermined temperature. It is determined whether or not (step S11). If the Mth region is not sufficiently heated, the region is regarded as a region where the temperature has not been reached, and the region number is output to the drive unit 3 (step S12).

It is determined whether or not the region number M is equal to N, which is all the regions set as treatment target regions, that is, whether or not all regions have been processed (step S13). The area number M is incremented (step S14), and steps S11 to S14 are repeated.

That is, in step S11, it is performed after the elapse of a predetermined time after the irradiation of the bubble forming ultrasonic wave W2, but when the bubble forming ultrasonic wave W2 is irradiated, the temperature of the treatment target tissue A is the boiling point of the liquid 50. When the temperature is higher than or equal to ° C., micro bubbles are detected, and when the temperature of the tissue to be treated A is less than 50 ° C., no micro bubbles are detected.
When the number of the temperature unachieved region is output, the driving unit 3 increases at least one of the output time and the output intensity of the ablation ultrasonic wave W1 (step S15), and the ultrasonic element reaches the temperature unreachable region. 2 is moved (step S16), and the ablation ultrasonic wave W1 is output again (step S17). It is determined by the temperature determination unit 5 whether or not the cautery ultrasonic wave W1 has been re-outputted for all temperature unachieved regions (step S18). Repeated.

Thus, according to the ultrasonic medical device 1 according to the present embodiment, the remaining microbubbles are detected based on the luminance value of the ultrasonic image, and the region where the microbubbles are detected is sufficiently heated. Can be determined. On the other hand, it can be determined that the region where the microbubbles were not detected did not require sufficient heating.
The mechanism that the remaining time is relatively long only when bubbles are formed when the ambient temperature exceeds the boiling point has not been completely clarified yet, but the following hypothesis is currently considered. Perfluorocarbons originally have high oxygen solubility. It is thought that dissolved gas such as oxygen moves into the bubbles from the surrounding medium and precipitates as a gas, so that the composition of the droplets in which the original perfluorocarbon was dominant changes, so it will remain. Yes. In order to emphasize this effect, by irradiating a pulse having a relatively small amplitude and a long length after irradiation with the bubble-forming pulse, the effect of rectifying diffusion is emphasized, so that a greater difference can be given to the remaining time.

That is, the temperature of the treatment target tissue A after the ultrasonic irradiation can be measured for each region only by analyzing the luminance value of the ultrasonic image. Therefore, there is an advantage that an appropriate treatment for the treatment target tissue A can be performed by simply measuring the temperature without using a large-scale apparatus such as MRI.

Furthermore, since the ultrasonic medical device 1 according to this embodiment irradiates the region where no microbubbles are detected with the ablation ultrasonic wave W1 in which at least one of the output time and the output intensity is increased, the heating is performed. There is an advantage that the region where the deficiency is insufficient can be cauterized by the ultrasonic wave W1 for ablation that further enhances the ablation effect.

In the present embodiment, by using the luminance value of the ultrasonic image, it is possible to accurately detect the occurrence of microbubbles not only in the cancer tissue but also in any treatment target tissue A. Therefore, there is an advantage that the treatment target tissue A can be sufficiently heated regardless of the organ, the site, or the state of the treatment target tissue A.

Moreover, in this embodiment, after irradiating the ultrasonic wave W1 for cauterization and the ultrasonic wave W2 for bubbling to all the regions, the ultrasonic image W3 is irradiated to irradiate the ultrasonic waves W3. , After irradiating the ultrasonic wave W1 for cauterization and the ultrasonic wave W2 for bubbling, the ultrasonic image W3 may be irradiated to obtain an ultrasonic image.
In addition, after irradiating the ablation ultrasonic wave W1 and the bubbling ultrasonic wave W2 to a certain number of a plurality of areas instead of all the areas, the diagnostic ultrasonic wave W3 may be irradiated to acquire an ultrasonic image. Good.

Further, in the present embodiment, it was determined that the microbubbles remained in the treatment target area that needed to be heated, and that the microbubbles were sufficiently heated. In addition to this, as shown in FIG. 4, the nanodroplet is administered to the adjacent region adjacent to the treatment target region that does not need to be heated, and the bubbles are not irradiated with the ultrasonic wave W1 for cauterization. It may be confirmed that the adjacent area is protected from being heated by irradiating only the sonicating ultrasonic wave W2 and confirming that no microbubbles remain.

In the present embodiment, the ultrasonic element 2 outputs the ablation ultrasonic wave W1, the bubbling ultrasonic wave W2, and the diagnostic ultrasonic wave W3. However, the ablation ultrasonic wave W1 and the bubbling ultrasonic wave W3 are output. The sound wave W2 may be output from the same region, may be output from a different region, or may be provided as a separate body. The ultrasonic element 2 that outputs the ultrasonic waves W1 for cauterization and the ultrasonic waves W2 for bubbling may be formed by arranging a plurality of ultrasonic element pieces in an array, and the ultrasonic element that outputs ultrasonic waves. The focus may be moved by switching the pieces.

In the present embodiment, the temperature reached by the tissue A to be treated is determined based on the luminance value of the ultrasonic image. Alternatively, if the bubble in the ultrasonic image can be detected, the detection of the bubble is performed. The temperature reached by the tissue A to be treated may be determined based on the presence or absence of.

DESCRIPTION OF SYMBOLS 1 Ultrasonic medical device 2 Ultrasonic element 3 Drive part 5 Temperature determination part A Tissue to be treated W1 Ablation ultrasonic wave W2 Aeration ultrasonic wave W3 Diagnostic ultrasonic wave

Claims (5)

An ultrasonic element that outputs ultrasonic waves;
After outputting ultrasonic waves for ablation having an amplitude that gives a pressure lower than the predetermined pressure to a tissue to be treated to which a drug that is bubbled when a predetermined pressure is applied having a predetermined boiling point is output, A drive unit that drives the ultrasonic element to output a bubble-forming ultrasonic wave having an amplitude that applies pressure;
Temperature determination for determining whether or not the tissue to be treated has reached a predetermined temperature higher than the boiling point based on the presence or absence of bubbles after a lapse of a predetermined time after the ultrasonic wave for bubbling is output by the drive unit And an ultrasonic medical device. The temperature determination unit outputs diagnostic ultrasonic waves to acquire an image of the treatment target tissue, and determines that the treatment target tissue has reached the predetermined temperature when the image has a predetermined luminance value or more. The ultrasonic medical device according to claim 1. The drive unit divides the treatment target tissue into a plurality of regions, and performs the output of the ablation ultrasonic waves and the output of the bubbling ultrasonic waves for each of the regions,
The ultrasonic medical apparatus according to claim 1, wherein the temperature determination unit performs determination after the output of ultrasonic waves to the plurality of regions of the treatment target tissue is completed. When the drive unit determines that the temperature determination unit does not reach the predetermined temperature, the temperature determination unit increases at least one of the output intensity and the output time of the ablation ultrasonic wave, The ultrasonic medical apparatus according to claim 3, wherein the ultrasonic wave for ablation is output to a temperature unachievable region. The drive unit outputs the ultrasonic waves for bubbling to a tissue adjacent to the treatment target tissue,
The ultrasonic medical device according to any one of claims 1 to 4, wherein the temperature determination unit determines whether or not the adjacent tissue is protected based on presence or absence of a bubble state of the adjacent tissue.

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