JPH0226567A - Phantom for hyperthermia - Google Patents

Abstract

PURPOSE:To improve long-term stability and mechanical strength and to improve the reproducibility of repeated use by using a highly hydrous gel obtd. by injecting an aq. soln. contg. specific polyvinyl alcohol(PVA) into a casting mold for molding, then cooling the soln. to solidify. CONSTITUTION:The phantom 1 for the skin, the phantoms 2 for the fat and the phantom 3 for the muscle are combined to constitute the phantom A for hyperthermia of a composite type. This phantom A for hyperthermia is formed of the highly hydrous gel obtd. by executing the operations of injecting the aq. soln., which is the aq. soln. contg. the PVA having >=95mol% degree of saponification and >=1000 average degree of polymn. at a concn. of over 8wt.% and <=5wt.% and into which the moisture of the same moisture content as the moisture content in the prescribed biotissue and the quantity of the electrolyte meeting the frequency of a prescribed electromagnetic wave heater are incorporated, into the casting mold for molding and cooling the soln. to <=-10 deg.C to solidify and mold the soln., then thawing the molding.

Description

[Detailed Description of the Invention] <Industrial Application Field> The present invention relates to a phantom for hyperthermia, and more specifically, 11! The present invention relates to a hyperthermia phantom, which is a living tissue equivalent model necessary for preclinical thermotherapy using magnetic waves, especially hyperthermia therapy for cancer.

<Prior art>"Hyperthermia" is generally called "hyperthermia".1 For example, in cancer treatment, the temperature of a tumor site is heated to 41 degrees Celsius or higher using electromagnetic waves. is expected to have a cell-killing effect.

In other words, blood vessels are distributed in normal tissues that are not affected by cancer.

While there is a cooling effect due to blood flow, the tumor site has a -1
'! 2. Various studies have been conducted focusing on the fact that poor blood circulation causes heat to stagnate and cause overheating, and that the thermal sensitivity of the tumor site is not significantly influenced by the histological type of the tumor. .

However, when performing hyperthermia, it is necessary to have a device that can heat any anatomical tumor site as uniformly as possible at a constant temperature for a certain period of time, and a temperature measurement technology that can accurately measure the temperature distribution within the tumor. Research is currently in progress. For example, methods have been proposed in which a thermometer is directly inserted into the tumor site in order to measure the temperature distribution within the tumor, but it is not necessarily medically preferable to directly insert the thermometer into the tumor site. In order to know in advance the relationship between electromagnetic wave irradiation conditions and temperature rise,
It has been proposed to use various phantoms or experimental animals for preclinical purposes.

Although some of them have already been put into practical use, many drawbacks have still been pointed out.

In general, biological composition has electromagnetic properties similar to water, so
Water or high water content gels such as jelly, konnyaku, and agar have been proposed as phantom materials for hyperthermia.

However, the electromagnetic wave characteristics of biocomposition are highly dependent on the frequency used for heating, and therefore it is necessary to adjust the composition of the phantom material to match the frequency of the device used. It is very difficult to reproduce the results because the results vary greatly, and many materials lack long-term stability of physical properties and mechanical strength.Furthermore, since the materials have a high water content, they are prone to rot and mold, so reproducibility is difficult. Also, it has the disadvantage of not being able to withstand long-term use.

Recently, research has been conducted on phantoms that exclude liquid parts such as blood, and for example, tissues with high cell density and high water content such as muscle, skin, and organs, and tissues with low water content such as bones and fat. Although research has been carried out by broadly classifying them, more detailed examination of finer classifications is required.

Furthermore, it is also necessary to consider the heat transfer characteristics of each composition, and various physical properties that can independently adjust the above drawbacks and requests are currently being researched and some have been put into practical use, but there is a method for hyperthermia that solves all of them at the same time. The reality is that the Phantom is completely unknown.

<Problems to be Solved by the Invention> The purpose of the present invention is to easily adjust the frequency dependence of electromagnetic characteristics in electromagnetic wave heating, to make the electromagnetic characteristics equivalent to each tissue of the living body, and to simultaneously improve the heat transfer characteristics. An object of the present invention is to provide a phantom for hyperthermia that can be made equivalent to each tissue of a living body.

Another object of the present invention is to provide a phantom for hyperthermia that has excellent long-term stability and mechanical strength, as well as excellent reproducibility upon repeated use.

Means for Solving the Problems> According to the present invention, a polyvinyl alcohol having a saponification degree of 95 mol% or more and an average polymerization degree of 1,000 or more, and
The concentration of the polyvinyl alcohol exceeds 8 wt% and 50
An aqueous solution containing an electrolyte substance having a water content equal to the water content of a predetermined biological tissue and a predetermined frequency of an electromagnetic wave heating machine, which is less than or equal to wt%, is placed in a mold for forming an arbitrary shape. After injection, the gel is cooled to a temperature of -10°C or lower, solidified, molded, and then thawed. A high water content gel obtained by performing a series of freezing and thawing operations at least once, or the above-mentioned cooling・Without melting the solidified body, the dehydration rate (weight reduction rate of solidified/molded body) is 3w.
A phantom for hyperthermia is provided which is made of a high water content gel obtained by vacuum/partial dehydration of t% or more.

The present invention will be explained in more detail below.

The phantom material for hyperthermia of the present invention is:

An aqueous solution containing polyvinyl alcohol having a saponification degree of 95 mol % or more, preferably 98 mol % or more and a polymerization degree of 1,000 or more is used. The concentration of the polyvinyl alcohol in the aqueous solution is more than 8 wt% and less than 50 wt%, and by adjusting the water content with respect to the polyvinyl alcohol, a water content composition that is the same as the water content of a predetermined biological tissue can be easily prepared. can do. Specifically, the polyvinyl alcohol aqueous solution has an initial water content of 100%, except for partial dehydration during gelation, which will be described later. By adjusting the water content, it is possible to have the same water content as that of a given biological tissue.1 For example, the water content of the skin is 51 to 691%, below, the ureter is 58 wt%, the toughness is 58 wt%, and the Achilles key is 63 wt%.
%, tongue 60-68vt%, prostate 69-76wt%, lens 67-70t*t%, liver 70-'17wt%.

Stomach 80wt%, pancreas 1175wt%, small intestine 80wt%, skeletal muscle 79-80wt%, uterus 80wt%, thymus 82wt%
%, bladder 82 wt%, kidney 111178-81 wt%, etc., the water content can be adjusted to match the living tissue.

By adjusting the water content in this way, it is also possible to make the electromagnetic wave physical properties exhibited by a predetermined biological composition, such as relative dielectric constant, electrical conductivity, thermal conductivity, specific heat, hardness, etc., similar. However, since the heating of a living body by electromagnetic waves differs depending on the frequency, it is necessary to adjust the dielectric constant and electrical conductivity of the polyvinyl alcohol aqueous solution according to the frequency of the electromagnetic wave warming machine used. In this adjustment, by adjusting and adding the amount of electrolyte substance, it becomes possible to heat under conditions equivalent to a predetermined biological tissue at any frequency. Preferred examples of the electrolyte include sodium chloride, potassium chloride, etc. The amount of the electrolyte added varies depending on the frequency used and the target biological tissue, but in the case of muscle, for example, 1 For example, when the frequency of the electromagnetic wave heating machine used is 8 MH, the electrolyte substance is added to the polyvinyl alcohol aqueous solution at 0.50 to 0.60 wt%, 13, 56 MH.
In the case of z, it is 0.70-0.75wt%, 27.12M)
I, 0.75-0.82wt%, 433.9
For 2MHz, 0.85-0.92wt%, 915M
H.

In the case of 1. OO~1. Lout% or 2.45G11
．． In this case, by adjusting the content to 1615 to 1.25 wt%, the conditions can be almost the same as those of a given biological tissue.

In the present invention, a polyvinyl alcohol aqueous solution containing an electrolyte substance prepared according to the frequency is injected into a mold having an arbitrary shape that matches the shape of a human body model or a human local body surface, and the solution is heated to a temperature of -10°C or less. A high water content gel can be obtained by cooling, solidifying, molding, and thawing. At this time, the thawing process may be carried out once, but if a material with high mechanical strength is desired, it is preferable to repeat the freezing and thawing operations. It is particularly desirable to repeat the operation within the range of 2 to 8 times, since there is no change in the effect even if the above-mentioned repetition is repeated 9 times or more, which is economically disadvantageous.

Furthermore, in the present invention, instead of the repeated operations of thawing and freezing,
The mechanical strength of the gel can also be improved by performing vacuum/partial dehydration without melting the cooled solidified material. However, as a phantom for hyperthermia, it is not necessary to obtain a particularly strong gel;
What is the dehydration rate (weight reduction rate of cooled and solidified gel) in partial dehydration?

It is desirable that the content be 3 wt% or more, preferably in the range of 3 to 35 wt%, from the viewpoint of gel shape retention and processability.

The vacuum/partial dehydration refers to dehydration under reduced pressure, and the amount of reduced pressure is not particularly limited, for example, 1 ms Hg or less, preferably 0. lmHg or less,
More preferably 0. It is desirable to reduce the pressure to 08nnHg or less. At this time, to determine the water content of the polyvinyl alcohol aqueous solution.

Although it is necessary to consider the amount of water dehydrated by the vacuum/partial dehydration, the gel water content can be easily adjusted by taking the difference between the initial water content of the aqueous polyvinyl alcohol solution and the dehydration rate.

In the present invention, in order to imitate biological tissues with low water content such as fat and bone, lipids may be mixed into the polyvinyl alcohol aqueous solution and uniformly dispersed.

For example, to simulate adipose tissue with a water content of 40%,
An equal amount of lecithin or tristearin may be dispersed in a 0% polyvinyl alcohol aqueous solution. Furthermore, in order to simulate fat-rich tissues, in order to avoid deterioration of shape retention due to fat, solid fats such as monostearin and tristearin are liquefied by heating and added to a polyvinyl alcohol aqueous solution heated to 70°C or higher. After the suspension is uniformly suspended, the above-described freezing operation is performed to produce a phantom imitating adipose tissue with a water content of 15 to 30 wt%.

In the present invention, it is also possible to add, in addition to the above-mentioned lipids, components that do not inhibit the gelation of polyvinyl alcohol, preferably in an amount of 1/2 or less of the amount of polyvinyl alcohol. Examples of the components that do not inhibit gelation include alcohols such as isopropyl alcohol, glycerin, propylene glycol, and ethyl alcohol, casein, and gelatin.

Proteins such as albumin, lipids such as lecithin, monostearin, tristearin, glucose, agar.

Sugars such as carrageenan or polytris, butyl p-hydroxybenzoate, phthalocyanine blue, organic compounds such as flavanthrone, nickel salts, copper salts, manganese salts, iron salts, graphite, activated carbon, silica/alumina, zeolite,
Inorganic compounds such as calcium silicate, inorganic salts, organic acid salts,
Examples include polyethylene powder and alumina powder.

In the present invention, by adjusting the water content and the amount of electrolyte substance and performing the series of operations described above, it is possible to obtain a high water content gel that imitates various different biological tissues. The high water content gel is
Although it can be used alone as a phantom for hyperthermia, it can also be combined by pasting together high water content gels imitating different biological tissues. At this time, a cyanoacrylate adhesive may be used as the adhesive, but it is preferable to apply an aqueous polyvinyl alcohol solution with a desired water content to the adhesive surface, and then freeze and thaw the adhesive.

Further, in the present invention, it is also possible to embed tubules imitating blood vessels in the high water content gel alone or in the composite. The diameter of the tubule can be about 100 μm to several micrometers, and it can be embedded in even the smallest detail like a blood vessel. In other words, cancer cells generally have almost no blood vessels passing through them, so by placing the above-mentioned tubules in areas other than those imitating cancer cells, and flowing a liquid maintained at a predetermined temperature using a thermostat or the like into the tubules, cancer cells are generated in living organisms. It can be used as a model of cancer. In addition to the above-mentioned blood vessels, it is possible to imitate tissues including biological skeletons, as well as to imitate tissues such as the trachea, esophagus, stomach, bladder, lungs, nasal cavity, oral cavity, etc.
Hyperthermia can create a space or water storage cavity that simulates the ureter, urethra, etc., and is also excellent for examining reflection, scattering, absorption, transmission, and multiple reflection of electromagnetic waves due to air, stored fluid, blood flow, etc. It is also possible to obtain a phantom.

<Examples> The present invention will be described in more detail below with reference to the drawings using examples, but the present invention is not limited thereto.

11L Average degree of polymerization 1000. 39.1% by weight of polyvinyl alcohol (hereinafter referred to as PVA) with a saponification degree of 98.5 mol%, 60% by weight of water, and 0.955% by weight of sodium chloride. After cooling, solidifying and molding at -2.5° C., freezing and thawing were performed twice to produce one skin fan 1-m 1 imitating skin tissue. The obtained skin phantom 1 had a frequency of 433.92 MH, an odor, a dielectric constant (hereinafter referred to as εH) of 49, and an electrical conductivity (hereinafter referred to as σH) of F 1.30 s/m. 15% by weight of PVA similar to 1, 34.7% by weight of water, 50% by weight of tristearin, and 0.45% by weight of sodium chloride were uniformly mixed, and in the same manner as skin phantom 1, 300 x 200 x 10 ■ Two adipose phantoms 2 imitating adipose tissue were prepared.

The obtained fat phantom 2 has a frequency of 433.92M.
At H □ i H45,6,σ) ILr75.3ms
PVA similar to 0-order skin phantom 1, which was /m
24.1% by weight, 75% by weight of water, and 0.9% of sodium chloride
0% by weight were uniformly mixed, and 100 muscle phantoms 3 imitating muscle tissue measuring 300 x 200 x 10 m were prepared in the same manner as the skin phantom 1. The obtained muscle phantom 3 had an iH value of 53 and a σH# of 1.46 s/I11 at a frequency of 433.92 MHz.

Subsequently, the skin phantom 1. fat phantom 2
and muscle phantom 3 were superimposed as shown in FIG. 1 to produce a composite hyperthermia phantom A. The obtained phantom A was heated in advance at 25℃ in a constant temperature bath.
After maintaining the applicator 4 at the upper and lower positions,
Using "Hyperthermia Tagmeso System" 5 (manufactured by Tagmeso, USA, frequency 433.92MHz), heating was performed using electromagnetic waves in an oblique direction for 10 minutes, and a thermo camera and thermometer were used together to measure the heating state by the device. was measured and recorded. Next, when similar measurements were made using Phantom A every 3 days for a month, the values obtained were almost the same.
The obtained hyperthermia phantom A was found to have excellent reproducibility.

PVA with average polymerization degree of 1500 and saponification degree of 99.0 mol%
38.9% by weight, 60% by weight of water, and 0.7% of sodium chloride.
5% by weight, and the long diameter is 280 m and the short diameter is 18 m.
oIIIl and poured into an oval donut mold with a thickness of 5 m and a depth of 200 am. Next time - 20℃
After cooling, solidifying, and molding, freezing and thawing were performed once to produce a skin phantom 1a imitating skin tissue.

The obtained skin phantom 1a has a frequency of 13.56M.
In H, t 144139. aH'=o, 60s
P similar to the skin phantom 1a, which was /m.
15% by weight of VA, 34.7% by weight of water, and tristearin 5
0% by weight and 0.50% by weight of sodium chloride are uniformly mixed, and the long diameter is 270 nm, the short diameter is 170 mm, and the thickness is 2.
The mixture was injected into an elliptical donut mold with a clearness and a depth of 20C) to produce a fat phantom 2a imitating adipose tissue in the same way as the skin phantom 1a. The obtained fat phantom 2a has E at a frequency of 13.56 MH, c.
H~35. O.

σH pressure was 26.3 ms/m. PVA 23.9% by weight and water 75% by weight, similar to skin phantom la.
and 0.70% by weight of sodium chloride, and the long diameter is 230 m, the short diameter is 130 m, and the depth is 200 m.
A muscle phantom 3a imitating muscle tissue was produced in the same manner as the skin phantom 1a.

The obtained muscle phantom 3a has a frequency of 13.56M.
H.

In, lH″F 146 , ty H40, 62
It was s/m.

Subsequently, the skin phantom 1a and the fat phantom 2
A and muscle phantom 3a were assembled as shown in FIG. 2 to produce a composite hyperthermia phantom B imitating the human torso. The obtained phantom B was adjusted to 25°C in a constant temperature layer and then subjected to rRF hyperthermia system.
(Omron, Tateishi Electric Co., Ltd. 2 frequencies 13, 56
A water porous and an applicator (not shown) were installed and heated in the vertical direction (a) as shown in Figure 2 for 15 minutes using a phantom B using a thermometer. Investigating the relationship of temperature distribution along b), skin phantom la and fat phantom 2a.
and the difference in the heating state of the muscle phantom 3a was measured.

The results are shown in Table 1.

Table 1 Measurement from the vertical direction (a) Cancer was assumed to be at a depth of 45 m from the top surface of the composite hyperthermia phantom A produced in Example 1 (inside the muscle phantom 3). The cancer-simulating site 7 has a cylindrical shape with a diameter of 50 mm and a height of 501 IIl, and around it, as shown in FIGS. And constant temperature layer! ! 1
2.13, and was arranged so as to circulate to every detail within the muscle phantom 3 excluding the cancer-simulating region 7.

Next, physiological saline maintained at 37° C. by the constant temperature device 12 is injected into the thin tube 6 by the pump 10 .

The temperature was again maintained at 37° C. through the -°C constant temperature device 13 and then injected into the thin tube 6 using the pump 11. That is, physiological saline maintained at 37° C. was circulated through the thin tube 6 disposed within the muscle phantom 3 using pumps 10 and 11. Subsequently, with physiological saline at 37° C. being circulated in the thin tube 6, applicators (not shown) were installed at the top and bottom of the phantom A using water porous, respectively.
The sample was heated vertically for 20 minutes using an RF Hyperthermia System (Omron, Tateishi Electric Co., Ltd., 2 frequencies, 13.56 MH). At the same time as the heating, temperature distribution was measured using a thermometer. The results are shown in Table 2.

Table 2 Furthermore, when the heating conditions were compared with those of an actual living body using the same apparatus and the same method, almost the same heating conditions as in Example 3 were obtained.

<Effects of the Invention> The hyperthermia phantom of the present invention can easily make the frequency dependence of electromagnetic characteristics during electromagnetic wave heating equivalent to that of each tissue of the living body by adjusting the amount of electrolyte substance, and also has excellent transmission characteristics. It is also effective as a preclinical hyperthermia because its thermal properties can be made equivalent to those of living tissues, even though it contains a large amount of water.

It has excellent long-term stability and mechanical strength even at 37° C., and has good reproducibility upon repeated use, so it is very economically advantageous.

[Brief explanation of the drawing]

Fig. 1 is a side cross-sectional view of the hyperthermia phantom of the present invention, Fig. 2 is a cross-sectional view of an elliptical hyperthermia phantom imitating the human torso, and Fig. 3 is a front part of the hyperthermia phantom equipped with a thin tube. FIG. 4 is a partially transparent sectional view of a side surface of a hyperthermia fan 1-m in which thin tubes are arranged.

Claims (4)

[Claims] (1) Saponification degree of 95 mol% or more, average polymerization degree of 1,00
An aqueous solution containing 0 or more polyvinyl alcohol and a concentration of the polyvinyl alcohol exceeding 8 wt% and 50 wt% or less, the water content being the same as that of a predetermined biological tissue, and the water content of a predetermined electromagnetic wave heating machine. After injecting an aqueous solution containing an amount of electrolyte material that matches the frequency into a mold of any shape, it is cooled to a temperature of -10°C or less, solidified, and
A high water-containing gel obtained by performing a series of freezing and thawing operations at least once in which it is molded and then thawed, or a gel with a high dehydration rate (solidification) without melting the cooled and solidified product.・A phantom for hyperthermia made of a high water content gel obtained by vacuum/partial dehydration of 3wt% or more (weight reduction rate of molded body). (2) The phantom according to claim 1, characterized in that a thin tube imitating a blood vessel is embedded in the high water content gel. (3) The phantom according to claim 2, wherein the capillary is arranged in a portion of the high water content gel other than a portion simulating cancer. (4) The phantom according to claim 1, 2 or 3, which is formed by combining a plurality of the high water content gels imitating different biological tissues.