JPS62298342A - Probe contact medium for ultrasonic diagnosis - 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] 3. Detailed description of the invention <Industrial application field> The present invention applies to the case where ultrasound is irradiated to living tissue.

This invention relates to a transparent and adhesive gel suitable as an essential couplant to be interposed between a probe and a living tissue.

<Conventional techniques and problems> Ultrasonic waves are irradiated onto living tissues, and reflected waves (
Diagnosis (i.e. ultrasound) is an important non-invasive test that detects breast cancer, converts it into an electrical signal, amplifies it, and then displays the image on a cathode ray tube through brightness modulation.

Diagnosis of ovarian cancer, uterine fibroid, breast disease, prostate cancer, liver cancer, pancreatic cancer, splenic tumor, bile cancer, liver cirrhosis, pancreatic inflammation, intraocular tumor, vitreous hemorrhage, gallstones, fetal measurement, placental measurement, eye It is widely used for measuring axial length, detecting hematomas, nodules, intraocular foreign bodies, ascites, and blood flow, as well as observing ventricles, atria, septum, tricuspid valves, coronary arteries, etc.

A problem in this case is that it is difficult to bring the ultrasonic oscillation radiation part (probe) into complete contact with the surface of the living tissue. In other words, there is often an air layer (bubbles) between the contact surfaces between the two, and the acoustic impedance of this air (
ρC) is 400 rayl (kgm-2s-), that is, p c (=1,600゜000rayl) of biological soft tissue.
Therefore, most of the ultrasound waves (99.9%) are reflected at the air-tissue interface, and the purpose of diagnosis is not achieved (F.

W, Kremkau (translated by Toshitsugu Kobayashi); ``Principles and Exercises of Ultrasonic Diagnosis'' (t9at) Konpodo).

Attempts to avoid this difficulty include water, castor oil, and olive oil as air exclusion materials (adhesive materials between probes and living tissues).
p c =1,450,000~l,500,000)
etc. as a coupling medium (coapling +media,
The method used for contact 5 surface is famous. The ρC of these materials is close to the value of living tissue, and therefore the ultrasonic reflectance at the interface is calculated to be about 1% or less, but unless the living tissue is completely flat, this air intrusion is difficult to avoid. In this case, an attempt is made to forcefully press the probe against the living tissue, but this is inconvenient for diagnosing the living tissue in its natural form, and compressing the heart during the surgical procedure is not recommended to lower blood pressure. should be avoided as it may cause arrhythmia. As another attempt, wate
The r bag method is well known. That is, it is a method in which a bag filled with deaerated water is interposed between the probe and the living tissue, and even if the water filling thickness is 10 to 20 m+, the attenuation (absorption) of ultrasonic waves in water can be almost ignored. Biopore! As long as a bag material (thin film) is selected that has ρC comparable to a (water), most of the reflection and absorption of ultrasonic waves can be avoided. Honzuke is widely used for breast cancer diagnosis in the supine or sitting position, for example.
There is a problem that the terbag is easily deformed and moved in an inconvenient direction, and it takes time to provide assistance during diagnostic operations (nursing time). In order to avoid this difficulty, the water immersion method (water tank method) is used.
r bath method) is also adopted. In this method, both the prone breast and the probe are immersed in a water tank to ensure that water is interposed between them, and ultrasonic waves are emitted and irradiated. ).

It cannot be applied to the eyeball or any internal organs during surgery.

In order to avoid the drawbacks of the teater bag method and the water bath method, attempts have been made to interpose a layered body of hydrogel (jelly) or sticky hydrocarbon gel.

However, the former (jelly) is easily broken and washed away, and the latter such as silicone gel, styrene-butadiene copolymer/paraffin swelling gel, acrylic acid polymer/polyethylene glycol swelling gel, etc.
In addition to incurring a reflection loss of ~10%, the gel (thickness 10-20%
1n) is intensely attenuated (absorbed), and the loss is 1 to 3d.
Bam-' (20-50% an-'').Agar has a water content of 97-98%, so its impedance is similar to that of living tissue, and like water, the attenuation in the gel is extremely low. Although it is small, it is easy to break because it lacks mechanical strength.

Moreover, since this couplant for ultrasonic diagnosis is applied to a living tissue surface, it is desired that the couplant itself is transparent. That is, in order to immediately determine whether the couplant is properly applied to a desired position (range) on the skin surface or organ tissue surface by fluoroscopy.

It is desirable that the couplant itself be transparent.

However, the various couplants that have been proposed so far have ρC and attenuation characteristics similar to those of biological pores (m<water), are transparent, flexible, break gracefully, and have adhesive properties that are convenient for biological tissues. There is no material that is harmless to living organisms that is both flexible and non-fluid.

<Object of the invention> The present invention has an impedance that is approximately the same as that of living tissue (water).
ρC) and low attenuation (absorption) properties similar to water, and is a non-fluid, flexible, transparent, sticky, and highly water-containing gel that is harmless to living organisms. Provide a couplant.

<Means for solving the problems> According to the present invention, the degree of saponification is less than 95 mol%, 75 mol%
Contains polyvinyl alcohol with an average degree of polymerization of 1,000 or more, and the concentration of the polyvinyl alcohol is 7%
After pouring an aqueous solution of more than 1t% and less than 30vt% into a mold, it is cooled to a temperature of -10°C or less, assimilated, and shaped, and then thawed.A series of freezing and thawing operations is performed. A couplant for an ultrasonic diagnostic probe, which is characterized by being a transparent, sticky, non-flowing, highly water-containing gel, can be obtained by subjecting the gel to a cumulative freezing frequency of 3 to 10 times.

The present invention will be explained in more detail below.

In the present invention, a couplant for ultrasonic diagnosis is produced using a high water content gel by an unspecified method described in detail below.

The polyvinyl alcohol used in the present invention has a saponification degree of less than 95 mol% and 75 mol% or more, preferably 80 to 75 mol%.
It requires 93 mol%. Further, the degree of polymerization of polyvinyl alcohol is required to be 1,000 or more.

In the present invention, first, an aqueous solution containing the aforementioned polyvinyl alcohol is prepared. The concentration of polyvinyl alcohol is more than 7 wt% and less than 30 wt%, preferably 9 to 2
5vt%.

In the present invention, the polyvinyl alcohol aqueous solution is poured into a mold for forming a flat plate or a curved plate, and after cooling and freezing,
Unzip this. A high water content gel that can be used in the present invention can be obtained by repeating this series of freezing and thawing operations so that the cumulative number of times of freezing is 3 to 10. As the cumulative number of times of freezing increases, the fluidity of the obtained high hydrous gel decreases and the hardness improves, but after 11 times of cumulative freezing, this effect almost disappears, so 3 to 10 above are economical. be.

The mold for forming the mold is, for example, 40×40+m.

There are no particular restrictions other than being able to obtain a flat plate of 70 x 70 wn+, 50 x 50 mm, or a single curved plate with a diameter of 40 mm, but depending on the actual situation of clinical use, the thickness (uniformity or thickness distribution) dimensions and shape 11 You can select the radius of curvature, etc. Considering that current barium titanate or crystal resonators have a diameter of 10 to 36n*, a disc (or square or rectangle) with a diameter (or side) of 15 mm or more is desirable. heart during chest surgery,
If the liver, kidneys, etc. are to be diagnosed during laparotomy, in advance.

By manufacturing the mold in consideration of these shapes, a molded product with a desired shape can be obtained, but after obtaining a molded product with a large area, unnecessary portions are cut off.

It can also be made to match a desired shape.

In the present invention, a high water content gel plate is interposed between the probe and the living tissue, but for convenience of operation, the high water content gel plate can also be used by adhering it to the periphery of the probe in advance.

After the high water content gel plate of the present invention has been manufactured using the above procedure, it can be immersed in physiological saline to replace the moisture within the gel with physiological saline. By dissolving it in saline, a hydrogel containing a large amount of physiological saline may be prepared.

Regarding sterilization of the high water content gel of the present invention, the gel can be immersed in a sterilizing agent such as an aqueous chlorhexidine solution and then washed with sterilized physiological saline, or the above-mentioned sterilizing agent immersion operation can be omitted and the gel can be finally packaged and sealed. rear.

Sterilization by gamma irradiation can also be performed.

<Effects of the Invention> The couplant for ultrasonic diagnosis of the present invention can be easily cut into a desired shape at a diagnostic site, if necessary.

In addition, compared to known couplants, it is far superior in terms of water content, reaching over 70% and 80 to 93%, so the impedance (ρC) is extremely close to that of water (or living tissue), and therefore, The reflectance (loss) of ultrasonic waves at the contact interface with living tissue can be kept at 0.5 to 1% or less.

That is, over the entire range of moisture content from 70 to 93%, pc is 1
,450,000-~1,700,000 rayl
, that is, 1,600,000-1,700 of biological soft tissue.
,000 rayl, and the reflection loss of 1 can be practically ignored as described above. This is based on the previously proposed glycerin Cp c ~2,
400,000), liquid paraffin (pc ~ 1,0
00,000-1,300,000), Olive oil Cp
c ~ 1,310,000), silicone rubber (
p c = 1,100,000”l, 200,000
), butadiene-acrylonitrile rubber (pc ~2
.

The couplant (gel) of the present invention can be used, for example, from 10 to 30 nv
Even when used as a thickness of n, ultrasonic attenuation within the gel is extremely small. Its rate of decrease (1~1, 5 d
Ban-', 20-28% am-1,5 MHz
) is a conventionally proposed couplant of butadiene-acrylonitrile rubber (70d BCIll-', 99.
9%a+1-'), natural rubber (155dBan-', 9
9.9% cm-'), castor oil (3-15 dBcm
-', 50-97%Cl1l-'), olive oil (8,
3dBan-', 85% al-'), glycerin (6dBan-'),
Bam-1, 75% cm-').

Although the couplant of the present invention contains a large amount of water,
Because it is non-fluid, it can be stored for long periods as a plate (layer), and it is highly flexible and has a dynamic elastic modulus (E') equivalent to the smooth muscle of the small intestine (below), so it can be stored in the shape of various biological tissues. Close contact (freely deformable close contact) is possible depending on the conditions.

As mentioned above, the couplant of the present invention can be easily obtained by simply subjecting an aqueous polyvinyl alcohol solution to a thermal history in a low temperature range, and is completely free of acids, alkalis, other chemical reagents, cross-linking reagents, etc. that are harmful to living tissues. Not used. Therefore, it does not require much effort to remove harmful substances from products.
Moreover, the heart.

Even if it comes in direct contact with living tissues such as the liver and kidneys for a long time.

Does not cause foreign body reactions such as cell infiltration and inflammation.

As mentioned above, the couplant of the present invention is non-flowing and can withstand repeated use over a long period of time, but since the manufacturing method is simple, it is suitable for cost reduction through mass production.

From the viewpoint of avoiding contamination by bacteria and fungi in the operating room 1 diagnostic room (examination room), the ``disposable method'' is most suitable.

This is because the couplant of the present invention is colorless and transparent.

After being applied to the skin fJ (body surface) surface or a biological tissue surface such as an organ, the applied surface can be seen through.

It is easy to accurately know the area where the couplant is applied, that is, the area where the ultrasonic waves are to be irradiated.

Furthermore, since the couplant of the present invention is highly adhesive, the couplant applied to biological tissue will not fall off unless it is intentionally peeled off.

<Examples> The present invention will be described below with reference to Examples. Note that % is based on weight.

Example 1 Average degree of polymerization 1,000. A 10% aqueous solution of polyvinyl alcohol with a saponification degree of 87% is poured into a glass slit (20 x 5 cm) with a thickness of 18 mm, and the slit is
The obtained frozen body was thawed by cooling to 0°C.

This freezing/thawing operation was repeated eight times to obtain a sticky transparent gel with a water content of 90%. This flat plate was cut (quartered) to obtain 5×5a++ pieces. To these, 2.5 MRa
Although the gel was sterilized by γ-ray irradiation (d), there was no problem with the gel's transparency (visible light transmittance 97% (1+m+)), flexibility, and adhesiveness. These were placed one by one in a sterilized glass bottle under aseptic operation and sealed tightly.

One of the plates was transferred to a bouillon medium and cultured at 37°C for 7 days, but no microorganisms were detected.

The specific gravity (density) of the other sheet was measured and found to be 1.03 at 27°C. Furthermore, regarding this, a method for measuring the angle of total reflection of ultrasonic waves in water (edited by the Japanese Society of Ultrasonics in Medicine, "Pacific Ultrasonic Medicine" p. 180 (1973) Igaku Shoin)
Find the propagation velocity using , and find a value close to that of water, 1,5
00 m s-' was obtained. therefore.

Its ρc is 1,550,000 rayl, that is, water (p
C:=1,500°000), living tissue (p c
= 1,600,000), and I learned that there is almost no reflection loss. Next, we will introduce an ultrasonic output measurement method based on radiation pressure (edited by the Japanese Society of Ultrasonics in Medicine; “Ultrasonic Medicine”).
``P, 6g (1073) Igaku Shoin), the absorption coefficient per this gel law is 1d Bao-' (5MH
z) and learned that the attenuation rate is only about 20% cm-''.

The dynamic elastic modulus (E') of this gel plate was measured and was 0.
OIXlX105N” and small intestinal smooth muscle (0, 2X
10'Nm-''), it is more flexible than the body surface or thoracotomy,
It showed enough free deformability to fit closely to any surface of the organs to be visited during laparotomy. On the other hand, this gel plate was left in a closed container for three months, but it remained in close contact with the bottom of the container and maintained its 18n+m thick shape, confirming that there was no concern about it flowing or dispersing.

Cut a piece of 18 x 20 x 20 mm from this gel plate,
After being placed under the skin of the rabbit's back for one year, it was removed, but no foreign body reactions such as cell infiltration or inflammation were detected. Same <0.
A 3 x 30 x 30 nn fragment was placed between the pericardium and epicardium of a dog for 1 year without any foreign body reaction.

Ratio 1 Bite Example 1 For the five types of couplants that have already been proposed, according to Example 1, the density ρ (kgm-') and the acoustic propagation velocity C (ms-
”], iimbidansul c (rayl, kgm-
``5-13, Measure the attenuation coefficient a' (d B aa-') and calculate the reflectance R [%] at the interface with biological tissue (pc = 1,600,000) and the attenuation (absorption) per couplant 1a11. ) rate A [%an-') was determined.

Glycerin (ρ = 1260. c = 1920. p
c = 2,419°000, R = 4. α' ~6. A=
75), liquid paraffin (p = 835. c = 1
420. p c ~1,186,000. R~3,
α' ~5. A=68), silicone oil (ρ=960,
c=985. ρc=945,600. R=6. a'
~1°A=20), the reflectance exceeded 3% in all cases, and we were impressed by the similarity to the ρC of living tissue. Olive oil - (p
:=904. c=1450. p c ~1,3
11,000. R=1.

α' ~5.3. Although the reflectance of A=85) was low, the attenuation was severe and it was inappropriate. Castor oil (ρ=960°c
=1500. pc=1470. R=0.2. a'
= 10, A = 90) had no problem in avoiding reflections, but the attenuation was extremely significant and was still inappropriate.

All of the above indicate fluidity, including the face, neck, and neck.

The probe can be pasted (applied) on surfaces of biological tissues that are not necessarily flat, such as the waist, abdomen, dorsal narrow area, lower back, crotch, upper abdomen, and lower abdomen, as well as on the surfaces of the heart, liver, etc. during thoracotomy and laparotomy. It was inconvenient to make them come into close contact with each other.

Example 2 Average degree of polymerization 1,200. A 15% aqueous solution of polyvinyl alcohol with a saponification degree of 86.5% was poured into a glass slit (10 x 5 cm) with a thickness of 8 m, and the molded plate obtained by freezing and thawing 10 times was cut into 5 x 50 pieces. did. For each sheet, ρsaw ρQe according to Example 1
R9α′, A was determined.

The reflectance (R) is only 0.35%, and the attenuation rate is also 2.
5% a+1-". In other words, there was no problem in terms of reflection loss, and the attenuation rate was as low as that of olive oil (85% am-1).
, glycerin (75% cn-'), liquid paraffin (6
8%■'''1), which is much lower than castor oil (90%■-゛).

Next, when we measured the dynamic elastic modulus (E') of the above fragment, we found that it was O,OO5 Place it in a polyethylene bag and sterilize it with gamma rays (5, OMrad
) was applied and the package was opened after 3 months, but it was confirmed that the shape of 8IIn in thickness was maintained and no flow and dispersion occurred.

Further, the visible light transmittance of the above fragment was 97% (1 m), indicating a transparency comparable to that of a commercially available soft contact lens.

Furthermore, it was confirmed that even if the above fragments were applied to the chest in a sitting position, the back in a forward bent position, the top of the neck in a forward bent position, the throat in a hyperextended neck position, etc., they would not fall off for at least 30 minutes. .

Comparative Example 2 Ultrasonic properties were measured for three types of soft materials, silicone rubber, natural rubber, and butadiene-acrylonitrile rubber, but silicone rubber Cp c ~1,1
00,000. R=4) and butadiene-acrylonitrile rubber (p C=2,160.0001 R=2
), the reflectance reaches 2% or more, and natural rubber (ρC=1,
500,000. R = 0.2), there is no problem with the reflectance, but the attenuation is extremely severe (A = 99.9%).
cm1).

In addition, all these three types of rubber have a dynamic elastic modulus (E')
reaches more than 5 X I O'Nm-2, and its hardness exceeds that of biological soft tissue (E' ~0.05~1 (10'Nm
)), and was equivalent to or higher than cartilage.

Furthermore, all three types of rubber are opaque, and even if the film is only 1 m thick, it is impossible to see through it after applying it to the skin.

Comparative Example 3 The ultrasonic properties of two types of hydrocarbon gels that have been proposed as couplants that can follow and closely follow the heartbeat without strongly compressing the heart were measured at 25°C and 6MHz.

Silicone gel (1) =970. c=1050.
p c ~1.000,000. Reflectance 5%, α'=
2.7dB■'''1゜EiA attenuation rate 45%cm-'),
Paraffin gel (liquid paraffin-impregnated gel of styreninobutadiene rubber) (p = 870. c = 146
0. p c ~1,270,000. Reflectance 1%,
a' = 7.3 d Ba++-", attenuation rate 82% an
-1) has a problem with either reflection loss or attenuation, and although there is no problem with adhesiveness, there is a problem with transparency (visible light transmittance 40-80% (1nn+)). couplant (reflection loss 1% or less, attenuation rate 3Q%dll-
”, visible light transmittance of 97% (1 mm)) is obvious.

Claims (1)

[Claims] Contains polyvinyl alcohol with a saponification degree of less than 95 mol%, 75 mol% or more, and an average degree of polymerization of 1,000 or more, and
The concentration of the polyvinyl alcohol exceeds 7 wt% and 30
After injecting an aqueous solution of wt% or less into a mold, it is
Transparent, sticky, non-flowing material obtained by cooling and solidifying (freezing) to a temperature of 10°C or less, and then performing a series of freezing and thawing operations to achieve a cumulative freezing frequency of 3 to 10 times. An ultrasonic diagnostic probe couplant characterized by being a highly hydrous gel.