JPS58155845A - Ultrasonic contrast gas bubble generating method and apparatus - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed Description of the Invention] Technical Field of the Invention The present invention relates to a method of mixing microbubbles as a substance with high reflectance into blood, etc. with low reflectance, when measuring or imaging the inside of a living body by reflecting ultrasonic waves. The present invention relates to a method and apparatus for generating contrast bubbles for ultrasound.

Background of the technology When observing tomographic images of a living body using ultrasound reflection, the reflection coefficient of blood is very low compared to the reflection coefficient of other living tissues, so the blood flow in the heart, such as flow velocity, flow direction, flow rate, etc. It is almost impossible to visualize lines etc. on a tomographic map. Also, Doppler blood velocity measurement is prone to errors for the same reason. For this reason, in this type of measurement, a contrast operation (reflection enhancement operation) that mixes a substance with high reflectance and is harmless to living organisms into the blood.
will be held. As a contrast substance, a fine solid or a fine bubble is used since liquid hardly reflects ultrasonic waves.

Prior Art and Problems Conventionally proposed contrast imaging methods utilize the fact that physiological saline containing dissolved air or carbon dioxide gas is injected into a vein, and these gases form microbubbles with high reflectivity in the blood. It is. This will be explained with reference to FIG.

The venous blood contrasted by the injection returns to the right atrium through vein 1 and enters the right ventricle. This enables imaging and Doppler measurement of the right heart system 2 of the heart. However, the bubble then passes through the pulmonary artery 3 and reaches the lungs 4, where it enters the pulmonary capillary 4a with its tube diameter (
Bubbles larger than 8 μm are captured. Bubbles smaller than this will pass through, but the internal pressure of microbubbles is extremely high as they overcome the large surface tension due to the radius of curvature of the microbubbles, so the gas in the bubbles diffuses and dissolves into the blood and disappears. , the microbubbles eventually disappear midway from the pulmonary vein 5 to the left atrium. Generally, microbubbles have a short lifespan, so when intravenously injected into the upper lining, bubbles of 8 μm or less have already disappeared by the time they reach the right atrium. For this reason, contrast imaging of the left heart system 6 cannot be performed. The left heart system 6 transports blood that has taken in oxygen through the lungs 4 to the artery 7.
Since this is an important part of the body 8 that is sent to various organs 8a in the whole body 8, it is strongly desired to image it. If the above injection is performed into the pulmonary vein 5 that enters the left heart system, imaging of the left heart system should be possible, but the pulmonary vein 5 is located deep from the body surface and is adjacent to important arteries 7, etc. Therefore, injection of contrast agent from here is extremely dangerous and impractical. For these reasons, it has been impossible to diagnose the path from the pulmonary vein 5 to the left heart system 6 to the artery 7 to the living body 8 using ultrasound using conventional methods.

In recent years, as a method to improve this point, efforts have been made to search for substances that are harmless to the living body, which are substances that are mixed into the blood when injected into peripheral veins and foam after passing through the pulmonary capillaries, and ultrasonic waves that prevent the disappearance of air bubbles smaller than 8 μm. The use of surfactants, the use of surfactants, and the manipulation of atmospheric partial pressure have been proposed (R, S, Me
ltzer et al., Trans+wlssion of
Ultrasonic Contrast
Through the Lungs, Ult
rasound in Med, &Bio1. +V
o17+N.

,4. pp377-384.1981). However, it has not yet been successfully put into practical use. For example, it is difficult to produce microcapsules smaller than 8 μm using the method of placing air bubbles in microcapsules and passing them through the lungs, and then dissolving the capsules to create air bubbles. It is. Furthermore, in the method of applying ultrasonic waves to create air bubbles in the blood by cavitation, the ultrasonic waves that generate air bubbles are quite powerful and are harmful to living organisms. Also, bubble generation due to ultrasonic waves,
A combination with intravenous injection of effervescent substances such as hydrogen peroxide or ether has also been proposed, but this has also not been realized. The reason is that in this method, vein 1 is connected to right heart system 2.
, the pulmonary artery 3, the pulmonary capillary 4a, and the pulmonary vein 5. This is because there are restrictions on the properties of the contrast agent, and there are also major restrictions from the standpoint of biological safety. .

The present inventors have proposed an ultrasound contrast bubble generation method that eliminates these limitations. The outline of this method is that a gaseous contrast agent (including vapor) is taken into the blood through the capillaries of the lungs through the action of breathing, and microbubbles are created in the blood by differences in component partial pressures and the formation of negative pressure. It is. According to this method, microbubbles with high reflectance are generated throughout the living body, so it becomes possible to image the left heart system, which was previously considered impossible.

However, considering the safety of the living body, it is desirable that the amount of intravenous injection, the amount of inhaled gas components, the degree of pressurization of inhaled air, etc. be as small as possible, and the applied negative static pressure and negative pressure due to ultrasound should also be as low as possible. Although it is desirable to create a negative pressure using only conventional ultrasound waves, there is a strong possibility that the transmission of the ultrasound waves for creating a negative pressure is not effective when measuring blood flow in the heart, etc., because the transmission of the ultrasound waves for creating a negative pressure is obstructed by the air in the lungs.

Purpose of the Invention The present invention increases the reflectance of blood by heating blood at a desired site in a living body using electromagnetic waves, ultrasonic waves, etc. and generating microbubbles in the blood. To reduce the amount of foreign substances injected into the body, to reduce the amount of negative pressure in the surrounding atmosphere and the intensity of ultrasound waves in the case of creating negative pressure, and to provide an alternative method to ultrasound waves for creating negative pressure, which cannot be penetrated by gas in the lungs. It is something.

Structure of the Invention The method for generating contrast bubbles for ultrasound according to the present invention is characterized by heating a desired part of a living body with electromagnetic waves and/or ultrasonic waves, and generating microbubbles in the blood due to the temperature increase. Further, the device is characterized in that it is equipped with an ultrasonic transducer and an electric bridge for generating electromagnetic fields disposed on the surface of the living body, and is configured to apply electromagnetic waves for heating and ultrasonic waves for generating negative pressure to the living body. It is something.

Embodiments of the Invention A technology conventionally known as hyperthermia can be applied to heat a specific site within a living body.Hyperthermia is a technology that converts ultrasonic energy into heat and
Cancer cells are killed by heating the carcinogenic site in the living body intensively or over a wide range by induction heating using electromagnetic waves in the OMHz to microwave range. In other words, the present invention utilizes the fact that cancer cells are sensitive to heat, but normal cells are not so weak, and the present invention also heats with low energy that does not destroy normal cells.

The foaming phenomenon caused by heating is based on the following principle. That is, (1) Decrease in solubility due to temperature rise: The solubility of various gases dissolved in blood decreases as temperature rises, and excess gases (air, rare gases, etc.) are liberated to form bubbles. ■ Vaporization of low boiling point substances due to temperature rise Low boiling point substances (such as ether) in various liquids dissolved in the two-sided liquid vaporize and gasify, creating bubbles. ■Decomposition due to temperature rise: Substances dissolved in blood, such as H2O2, become easier to decompose due to temperature rise, and the decomposition products (02 for H2O2) form bubbles. (2) Promotion of chemical reactions due to temperature rise: A certain substance A dissolved in blood reacts with blood components, such as oxygen, to produce gas, and if this reaction is accelerated by heating, bubbles are produced. Two or more substances A, B,------・-
It is also possible to use a method in which blood components are mixed together and react with each other alone or together with blood components. It is particularly effective to use a substance having a catalytic action such as an enzyme as the component. Next, examples will be given.

Example 1 Microbubbles are generated in the blood of a living body by any one of (1) to (4) or a combination thereof by simply heating a desired part of a living body with electromagnetic waves or ultrasonic waves.

Example 2 In addition to the heating described in Example 1, the entire living body is placed in a negative pressure chamber or a negative pressure area is created locally using ultrasound to promote the generation of bubbles from the blood.

Example 3 Prior to implementing Example 1 or 2, a liquid reflex-enhancing substance is injected into the blood via a vein or the like.

The above-mentioned ether, H2O2, etc. correspond to this enhancing substance. Further, it is also possible to use a microcapsule V, 11 physiological saline solution, etc., which has a container wall made of a substance that easily decomposes or causes a chemical reaction when heated, and has a gas such as CO2 inside.

Example 4 Prior to implementing Example 1 or 2, some or all of the components other than 02 (for example, N2) in the air were replaced with He.

The enhancer is introduced into the blood in advance by ingesting gas substituted with Ne, Ar, Kr+Xe, etc., CO2, H2O, ether, etc. through the lungs.

Example 5 Prior to implementing Example 1 or 2, a living body is placed in the gas of Example 4 or an atmosphere in which it is pressurized, or in an atmosphere in which air is pressurized to increase the concentration of the enhancer in the blood due to respiratory action. I'll keep it. In the case of pressurized air, the phenomenon known as diving disease is used in reverse.

However, the pressure is kept to a level that allows the bubble diameter to pass through the capillary (approximately 8 μm).

Example 6 The region where the atmosphere of Example 4 or 5 is created is limited to the respiratory system (mouth, nose, trachea, lungs) using a mask for intake and exhaust. At this time, by keeping the other living tissues in a normal state, the substance ingested in the lungs becomes easier to foam in other parts, and continuous intake and foaming of the reinforcing substance can be performed.

The embodiments of the method for generating contrast bubbles for ultrasound according to the present invention have been described above. Next, an embodiment of the contrast bubble generating apparatus for ultrasound according to the present invention will be described with reference to FIG. In the figure, numeral 11 is an electrostrictive vibrator plate (or magnetostrictive vibrator plate may be used) such as PZT, and numerals 12 and 13 are metal electrodes formed by plating or the like on both surfaces thereof. These constitute an ultrasonic generator for creating negative pressure, and are driven at 10 KHz to 500 KHz depending on the purpose. The vibrator plate 11 has a concave surface and provides a focused sound field to the target region 8a in the living body 8, thereby forming a negative pressure inside. The solid line area A is this sound field.

15 is a medium such as an ice bag for transmitting ultrasonic vibrations to the living body 8. 14 is a counter electrode that forms a heating electromagnetic field B together with the electrode 13, and is made to have flexibility so as to be in close contact with the living body 8 (
(A coil may also be used.) 16 is, for example, a sector scan type ultrasonic probe, and C is its scan area.

If the ultrasonic waves for forming a negative pressure and the electromagnetic waves for heating have the same frequency, it is sufficient to ground the electrodes 12 and 14 and drive only the electrodes 13. Although the electrodes 13 may be mixed and driven even in different cases, it is preferable that the electrode 13 be grounded, the electrode 12 be used to drive the ultrasonic waves for forming negative pressure, and the electrode 14 be used to drive the electromagnetic field. To drive the independent electromagnetic field B, M H
A frequency on the order of z'' GHz is used. In this example, bubbles are generated in the blood inside the living body 8 through both heating by the electromagnetic field B and negative pressure formation by the sound field A. Alternatively, the transducer plate 11 can be omitted and bubbles can be generated only by the electromagnetic field B. Furthermore, the electromagnetic field B may be a heating sound field by ultrasonic waves.

Effects of the Invention As described above, according to the present invention, microbubbles can be generated in the blood by heating any specific part of the living body using a heating electromagnetic field or a sound field, and the reflectance thereof can be enhanced.
Visualization and flow velocity of blood flow not only in the systemic venous system, but also in the pulmonary vein of the systemic arterial system, the left heart system, various arteries, various organs, various peripheral parts, etc.
It becomes possible to measure flow rate, etc. Further, even when foaming materials are used in combination, the amount of foamed materials can be reduced, and the amount of negative pressure generated by ultrasonic waves can also be reduced, so there is an advantage of increased safety.

[Brief explanation of the drawing]

FIG. 1 is an explanatory diagram of a circulatory system in a living body, and FIG. 2 is an explanatory diagram showing an embodiment of the apparatus of the present invention. In the figure, 8 is a living body, 11 is an electrostrictive vibrator for forming negative pressure, and 12.
13 is an electrode on both sides thereof, 14 is an electromagnetic field forming electrode, A is a negative pressure forming area, and B is a heating electromagnetic field. Applicant Fujitsu Limited Representative Patent Attorney Minoru Aoyagi 3

Claims (8)

[Claims] (1) A method for generating contrast bubbles for ultrasound, which is characterized by heating a desired part of a living body with electromagnetic waves and/or ultrasonic waves, and generating microbubbles in the blood due to the temperature increase. (2) A patent claim characterized in that the generation of microbubbles due to temperature rise is promoted by reducing the ambient pressure of the living body and/or irradiating ultrasonic waves for creating negative pressure to create negative pressure in the living body. The method for generating contrast bubbles for ultrasound according to item 1. (3) The method for generating contrast bubbles for ultrasound according to claim 1 or 2, characterized in that an easily foamable substance is injected into the blood in advance. (4) A patent characterized in that the air obtained by substituting a gas of a substance that easily foams with some or all of the components other than oxygen in the air is breathed into a living organism, and the gas is ingested into the blood in advance. A method for generating contrast bubbles for ultrasound according to claim 1 or 2. (5) Air is pressurized in advance to a level higher than normal pressure, or some or all of the components other than oxygen are replaced with a gas of a substance that is easily foamable, and the air is pressurized to a level higher than normal pressure, and one living body is exposed to the air in that atmosphere. 3. A method for generating contrast bubbles for ultrasound according to claim 1 or 2, characterized in that the blood concentration of the foaming substance is increased by breathing. (6) Ultrasonic contrast imaging according to claim 4 or 5, characterized in that the formation region of the atmosphere ingested into the blood through breathing is limited to the respiratory system of the living body by means of a mask. How to generate bubbles. (7) An ultrasonic device comprising an ultrasonic transducer and an electromagnetic field generating electrode disposed on the surface of a living body, so that electromagnetic waves for heating and ultrasonic waves for generating negative pressure are applied to the living body. Contrast bubble generator. (8) The ultrasound contrast bubble generator according to claim 7, wherein one of the electromagnetic wave generation electrodes and one of the drive electrodes of the negative pressure generation ultrasound transducer are shared.