JP2017148223A - Accuracy control target for photoacoustic wave diagnostic device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a photo acoustic wave diagnostic device target that provides answer approximated to photoacoustic answering of a biological tissue.SOLUTION: A photoacoustic wave diagnostic device target includes: polyamide resins 1, 2; and at least one sort of pigment.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a quality control target for a photoacoustic wave diagnostic apparatus included in a phantom, which is used for quality management of a photoacoustic wave diagnostic apparatus.

The photoacoustic wave diagnostic device displays an image based on a detection signal of an acoustic wave (typically an ultrasonic wave) caused by thermal expansion of an observation target when light is irradiated on a living body serving as a test part. It is a device to do. By this diagnostic apparatus, an inspection object that absorbs light in the test portion, for example, glucose, hemoglobin, etc. contained in blood is examined.
By the way, in a living tissue, when a tumor such as cancer grows, it is known that phenomena such as formation of new blood vessels and an increase in oxygen consumption occur in the living tissue. As a method for evaluating the formation of new blood vessels and the increase in oxygen consumption, there are methods using the light absorption coefficients of oxyhemoglobin (HbO ₂ ) and deoxyhemoglobin (Hb), respectively.
For example, the photoacoustic wave diagnostic apparatus calculates an oxygen saturation from the absorption coefficient ratio of HbO ₂ and Hb at at least two wavelengths, so that there is a region where oxygen consumption is increased, that is, a tumor exists. An area considered to be present can be determined. For example, it is known that the oxygen saturation in the tumor region is about 70%, and it is suggested that there is a correlation between the malignancy of the tumor and the oxygen saturation.
A phantom is used to manage the performance and accuracy of the above-described photoacoustic wave diagnostic apparatus. For example, when the phantom is installed in the photoacoustic wave diagnostic apparatus and observed, it is determined whether or not the performance of the diagnostic apparatus itself is maintained from the acoustic wave signal generated in response to the irradiated light. The phantom has a member called a target, which is a member that absorbs light and generates an acoustic wave signal.
As a phantom used in the photoacoustic wave diagnostic apparatus, the constituent material is required to be a material whose light propagation characteristics and acoustic propagation characteristics approximate to a living tissue. For example, in Patent Documents 1 and 2, there is a blood model in which absorption coefficient and oxygen saturation are simulated in blood, in which a phthalocyanine compound and a plasticizer are contained in a thermosetting urethane resin composed of polyalkylene glycol and polyisocyanate. It is disclosed. By using the blood model disclosed in Patent Documents 1 and 2 as a phantom target, it is possible to provide a phantom that well simulates the absorption coefficient and oxygen saturation of a living body.

JP2011-209691A Japanese Patent Laying-Open No. 2015-2978

  When a photoacoustic effect occurs when light is irradiated to a target of a phantom used in a photoacoustic wave diagnostic apparatus, the target undergoes thermal expansion and a pressure change occurs around it, resulting in an acoustic signal from the target. Occurs. This pressure change can be calculated using the following equation (1).

（式（１）において、ΔＰは、圧力変化を表す。Ｆ（ｚ）は、フルエンス（粒子束密度）を表す。Γは、グリューナイゼン係数を表す。μ_aは、吸収係数を表す。）
尚、式（１）中のパラメータであるＦ（ｚ）は、光の照射の出力によって定まる一定の値であり、Γは、材料固有の定数である。
ここで、ターゲットのグリューナイゼン係数が同じであれば、ターゲットの吸収係数に比例した音響信号が発生する。生体の中でも、血液のように水に近い（水を多量に含む）組織の場合、グリューナイゼン係数は、体温（３７℃）の水に近い値（約０．３）を示す。また生体の中でも、脂肪のような炭化水素化合物を主成分とする組織の場合、グリューナイゼン係数は０．８程度を示す。
ここで、特許文献１及び２に記載の血液モデルは、いずれもウレタン樹脂からなり、そのグリューナイゼン係数は約１．０である。このグリューナイゼン係数は脂肪に対しては近い値であるが、血液のグリューナイゼン係数に対しては近くない値である。このため、特許文献１及び２に記載の血液モデルがいかに生体を模擬した吸収係数を有していても、血液より強い音響信号が発生することとなってしまう。特に、光音響波診断装置は、血液から発せられる光音響信号を観察する装置であるため、より血液に近似したグリューナイゼン係数での模擬が望まれる。
本発明は、上述した課題を解決するためになされるものであり、その目的は、生体組織の光音響応答に近似した応答を示す光音響波診断装置用ターゲットを提供することにある。

(In the formula (1), ΔP represents a change in pressure. F (z) represents a fluence (particle bundle density), Γ represents a Gruneisen coefficient, and μ _a represents an absorption coefficient.)
Note that F (z), which is a parameter in formula (1), is a constant value determined by the output of light irradiation, and Γ is a material-specific constant.
Here, if the Gruneisen coefficient of the target is the same, an acoustic signal proportional to the absorption coefficient of the target is generated. In the case of a tissue that is close to water (including a large amount of water) such as blood in a living body, the Gruneisen coefficient shows a value close to water (about 0.3) at body temperature (37 ° C.). Moreover, in the case of a tissue mainly composed of a hydrocarbon compound such as fat, the Gruneisen coefficient is about 0.8.
Here, each of the blood models described in Patent Documents 1 and 2 is made of urethane resin, and its Gruneisen coefficient is about 1.0. This Gruneisen coefficient is close to the fat, but not close to the blood Gruneisen coefficient. For this reason, no matter how the blood model described in Patent Documents 1 and 2 has an absorption coefficient simulating a living body, an acoustic signal stronger than blood is generated. In particular, since the photoacoustic wave diagnostic apparatus is an apparatus for observing a photoacoustic signal emitted from blood, it is desired to simulate with a Gruneisen coefficient that is more approximate to blood.
The present invention has been made to solve the above-described problems, and an object of the present invention is to provide a target for a photoacoustic wave diagnostic apparatus that exhibits a response approximate to the photoacoustic response of a living tissue.

  The target for a photoacoustic wave diagnostic apparatus of the present invention is characterized by having a polyamide resin and at least one kind of dye.

Since the target for the photoacoustic wave diagnostic apparatus of the present invention has at least one kind of pigment with respect to the polyamide resin, the Gruneisen coefficient is approximated by the Gruneisen coefficient of the living tissue.
Therefore, according to this invention, the target for photoacoustic wave diagnostic apparatuses which shows the response approximated to the photoacoustic response of a biological tissue can be provided.

It is a schematic diagram which shows the example of embodiment of the phantom in this invention. It is a schematic diagram which shows the phantom which has a target. It is a schematic diagram which shows the example of the photoacoustic apparatus used in the case of the measurement of an acoustic signal variation rate. It is a graph which shows the correlation with the absorption coefficient of a test piece, and the density | concentration of a pigment | dye. It is a graph which shows the correlation with the absorption coefficient of a test piece, and the density | concentration of a pigment | dye.

  Hereinafter, embodiments of the present invention will be described. The embodiment described below is merely one of the embodiments of the present invention, and the present invention is not limited to these embodiments.

[Target for photoacoustic wave diagnostic equipment]
The accuracy control target for a photoacoustic wave diagnostic apparatus according to the present invention (hereinafter sometimes simply referred to as a target) has a polyamide resin and at least one kind of pigment.

1. Absorption coefficient and Gruneisen coefficient When performing accuracy control of the photoacoustic wave diagnostic apparatus, the suitable absorption coefficient of the target depends on the target wavelength, but for example, 0.001 when the wavelength is 800 nm. / Mm or more and 5 / mm or less is preferable.

  Here, since the detection performance of the photoacoustic wave diagnostic apparatus is adapted to the absorption coefficient of the living body, in the target for managing the quantitativeness of the apparatus, the range of the absorption coefficient of the target includes a range close to the living body. It is preferable. For example, when the wavelength is 800 nm, the range of the absorption coefficient close to that of the living body is preferably in the range of 0.001 / mm to 0.5 / mm.

  In addition, in the target for the purpose of adjusting the installation position of the target, a clear signal can be obtained even if it is placed at a deep position (a position far from the probe) that does not obstruct an acoustic signal transmitted from another target. It is required to be done. Therefore, in such a case, the absorption coefficient of the target is preferably 0.5 / mm or more and 5 / mm or less, for example, when the wavelength is 800 nm.

  However, according to the equation (1), not only the absorption coefficient of the target but also the Gruneisen coefficient influences the intensity of the acoustic signal emitted from the target. Here, if the Gruneisen coefficient of the target is significantly different from the range of the living body, an acoustic signal more than expected is emitted, and it is difficult to quantitatively evaluate the acoustic signal.

  By the way, the Grueneisen coefficient (Γ) can be theoretically calculated from the following equation (2).

(In formula (2), β represents a body expansion coefficient, c represents the speed of sound, and Cp represents specific heat.)

  Each parameter shown in the above formula (2) used when calculating the theoretical value of Γ is obtained by measuring a target or a composition having the same composition as the target. Specifically, the body expansion coefficient can be obtained indirectly from thermomechanical analysis (TMA). The linear expansion coefficient α is obtained by thermomechanical analysis (TMA). However, since the relationship of β = 3α is established between the body expansion coefficient β and the linear expansion coefficient α, the thermomechanical analysis ( The body expansion coefficient can be obtained from TMA). For this reason, in this invention, when calculating | requiring the theoretical value of a Grueneisen coefficient ((GAMMA)), a body expansion coefficient may be used and a linear expansion coefficient may be used. The sound speed can be determined from the difference in the speed of sound propagation between water and the material in water (the difference in propagation time at a certain distance). On the other hand, the specific heat can be determined by differential scanning calorimetry (DSC).

  According to known literature, the Gruneisen coefficient of blood is about 0.3, and that of fat is about 0.8 (BT Cox et al., Photons Plus Ultrasound: Imaging and Sensing 2009, Proc. Of SPIE Vol. 7177, 717713 (2009)). On the other hand, when the urethane resin disclosed in Patent Documents 1 and 2 is used as a constituent material of the target, Γ is about 1.0, which is similar to fat, but especially about 4 times for blood. It is considered that the intensity of the photoacoustic signal is high.

  On the other hand, the polyamide resin included in the target of the present invention has a sound velocity of 2450 m / s, a linear expansion coefficient of 90 ppm / K, and a specific heat of 1.45 J / g / K. Substituting these parameters into equation (2), the theoretical value of the Gruneisen coefficient of the polyamide resin is 1.1. Therefore, considering only the theoretical value of Γ, it is difficult to think that the polyamide resin is suitable as a target for simulating a living body.

  By the way, the polyamide resin has very little absorption in the near infrared region. Accordingly, the present inventors have further investigated a polyamide resin in which a dye is added to adjust the absorption coefficient. When measured under the same conditions (sample shape, laser intensity, target installation position, etc.) using a photoacoustic apparatus, the polyamide resin has the same acoustic signal as the urethane resin, although the absorption coefficient is almost the same as that of the urethane resin. The present inventor has found that it is lower than urethane resin.

  Although the theoretical value (hereinafter, theory Γ) of the Gruneisen coefficient of a given material is a constant, the actual Gruneisen coefficient of the material may be different from the theoretical value due to various factors. In the following description, this actual Gruneisen coefficient is referred to as an effective Gruneisen coefficient or effective Γ. This effective Γ can be calculated as a relative value when a signal obtained when the target is actually measured with the photoacoustic apparatus and a signal obtained with water are compared.

Specifically, the measurement sample and water are measured by the photoacoustic apparatus under the same conditions. Usually, the measurement sample is immersed in a medium such as water for measurement. Based on the generated sound pressure, the effective Gruneisen coefficient (effective Γ _S ) of the measurement sample can be calculated by the following equation (3).

(In Expression (3), ΔP _S represents the initial sound pressure of the measurement sample, ΔP _W represents the initial sound pressure of water, μ _S represents the absorption coefficient of the measurement sample, and μ _W represents water. Represents absorption coefficient.)
Note that the effective Γ _S can also be obtained by inverse Monte Carlo simulation. In the case of a sample without light scattering, it can also be obtained from the Lambert-Beer law based on the absorbance measured with a spectrophotometer and the optical path length. It should be noted that the Gruneisen coefficient of water (theory Γ _W ) is experienced as described in known literature (Alexander A. Oraevsky et al., APPLIED OPTICS 36 (1) 402-415 (1997)). The formula is obtained.

Also, since water has an extremely small absorption coefficient in the near infrared region, it is desirable to adjust the absorption coefficient by dispersing a dye (carbon black or the like) in water. In the measurement of the acoustic signal performed when determining the initial sound pressure for water, a sample containing water containing a pigment in a tube-shaped sealed container is used as a measurement sample. In this case, the effective Γ of the measurement sample can be measured by placing the measurement sample (resin or the like) in a similar sealed container and measuring. For a measurement sample (hereinafter referred to as “sample B”) that is difficult to put in an airtight container, an acoustic signal is measured in a state where the sample B is directly immersed in a predetermined medium. At that time, a sample (hereinafter referred to as sample A) that can be measured in the sealed container is measured in the sealed container, and an effective Gruneisen coefficient (effective Γ _A ) in the sample A is obtained. Further, the sample A is taken out from the tube and directly immersed in the medium for measurement. From the result of measuring the acoustic signal under the above conditions, the effective Gruneisen coefficient (Γ _B ) of the sample B is obtained using the following equation (4).

(In the formula (4), μ _A represents the absorption coefficient of the sample A. ΔP _A represents the initial sound pressure when the sample A is measured by being directly immersed in the medium. Μ _B is the absorption of the sample B. (ΔP _B represents the initial sound pressure when the sample B is directly immersed in the medium and measured.)

  When the effective Γ of the polyamide resin is calculated by the above-described method, it is about 0.5. Therefore, it shows a value closer to the living body than the urethane resin conventionally used as the constituent material of the target, and is suitable as a target. It became clear that it could be applied.

  As described above, the effective Γ may take a value that deviates from the theory Γ due to various factors. However, the effective Γ of the polyamide resin containing the pigment is significantly different from the theory Γ and closer to the living body. Numerical values are shown.

Thus, as a factor in which the effective Γ of the polyamide resin shows a lower value than the theory Γ, for example, the following factors (a) to (c) can be considered.
(A) Large acoustic attenuation coefficient of the polyamide resin that causes attenuation of the output signal inside the polyamide resin (b) High acoustic impedance of the polyamide resin that causes internal confinement of the output signal (c) Between the urethane resin and the polyamide resin Difference in heat transfer

  The reason why (c) is a factor is that the difference in heat conductivity causes a difference in the speed of density change due to thermal expansion when irradiated with a pulse laser. In addition, although a clear factor is not certain, it is assumed that the polyamide resin expressed a suitable Grueneisen coefficient because these factors acted in combination.

2. Polyamide resin As described above, the effective Grueneisen coefficient of polyamide resin is about 0.5, which is a value approximated to a living body (particularly blood), and is therefore suitable as a target for a photoacoustic wave diagnostic apparatus. Can be used.

  The polyamide resin used as the constituent material of the target of the present invention is preferably nylon 6, nylon 66, nylon 6/66 copolymer, nylon 6T, nylon 6I, nylon 10T, nylon 9T, nylon 46, and their co-weights. A coalescence and a mixture can be mentioned. However, the polyamide resin which is a constituent material of the target in the present invention is not limited to these.

  Polyamide resin is a semi-crystalline polymer and scatters light. Generally, the equivalent scattering coefficient of polyamide resin is 0.1 to 0.5 in the near infrared region having a wavelength of 600 nm or more and 1100 nm or less called a biological window, which is used in a photoacoustic wave diagnostic apparatus, and this range is blood. It is a numerical range close to the equivalent scattering coefficient of a living body. For this reason, it is suitable as a constituent material of the target. The polyamide resin has a very small absorption in the near-infrared light region, particularly in the wavelength range of 600 nm to 1100 nm. For this reason, by appropriately controlling the amount of the dye included in the target, it is possible to easily simulate the change in blood oxygen saturation caused by the absorption coefficient approximated to the living body and hemoglobin. Moreover, since polyamide resin is a thermoplastic resin, it is excellent in workability. For this reason, it can be processed into a wire shape with a submicron diameter that needs to be identified by the photoacoustic wave diagnostic apparatus.

  In addition, you may add well-known additives, such as antioxidant and a plasticizer, in the range which does not impair the effect of this invention. However, in order to prevent the absorption coefficient in the near-infrared region of the polyamide resin from fluctuating depending on the additive, the additive amount is preferably 5% by mass or less, more preferably 1%, based on the polyamide resin. Less than mass%. In the present invention, the additive refers to an additive component other than a dye for controlling the absorption coefficient in the near infrared region.

3. The pigment | dye contained in a pigment | dye target is a substance which has absorption in the near-infrared area | region of the wavelength of 600 nm or more and 1100 nm or less called the window of a living body generally used with a photoacoustic wave diagnostic apparatus. The target constituting the phantom of the present invention can absorb light in the near-infrared region having a wavelength of 600 nm or more and 1100 nm or less by including the dye.

Here, an example of a method for obtaining the oxygen saturation of the target will be described. First, the absorption coefficient of the target at any two wavelengths (λ ₁ , λ ₂ , λ ₁ <λ ₂ ) between 600 nm and 1100 nm is measured. Based on the ratio, the oxygen saturation can be calculated based on the following general formula (5).

(In Formula (5), HbO _{2 [λ1]} is the absorption coefficient of oxyhemoglobin at the wavelength λ ₁ , HbO _{2 [λ2]} is the absorption coefficient of oxyhemoglobin at the wavelength λ ₂ , and Hb _[λ1] is , the absorption coefficient of deoxyhemoglobin at a wavelength λ _1, Hb _[λ2] is the absorption coefficient of deoxyhemoglobin at a wavelength λ _2, μ [λ _1] is the absorption coefficient of the target at the wavelength lambda _1, mu [Λ ₂ ] is the absorption coefficient of the target at the wavelength λ _2. )

In Formula (5), the values of deoxyhemoglobin and oxyhemoglobin can use values in known literature materials (SJ Matcher et al., Analytical Biochemistry 227, p54-68 (1995), etc.). . Therefore, in order to reproduce a predetermined oxygen saturation, it is necessary that the ratio of the absorption coefficient of the target at the predetermined two wavelengths (λ ₁ , λ ₂ ) is a predetermined ratio. Further, the oxygen saturation may be obtained based on the sound pressure of an acoustic signal emitted at a predetermined wavelength instead of the absorption coefficient.

  The following dyes can be suitably used as the dye having such absorption characteristics. Here, the absorption coefficient and oxygen saturation of the target can be appropriately controlled by using one of these dyes alone or in combination of two or more. However, when multiple types of dyes are added, the absorption coefficient ratio at the wavelength used changes over time due to the elution of each dye out of the target and the difference in degradation rate, and the absorption coefficient of the target at each wavelength changes. Oxygen saturation determined by the ratio will change. Therefore, it is preferable to use one type of dye to be added to the target.

  Examples of blue pigments that can be included in the target include phthalocyanine and anthraquinone. In addition to these, metal-substituted or unsubstituted phthalocyanine compounds can also be used. Examples of red dyes that can be included in the target include monoazo, disazo, azo lake, benzimidazolone, perylene, diketopyrrolopyrrole, condensed azo, anthraquinone, quinacridone, and the like. Examples of the green pigment that can be included in the target include phthalocyanine-based, anthraquinone-based, and perylene-based pigments as well as the blue pigment. Examples of the yellow colorant that can be contained in the target include monoazo, disazo, condensed azo, benzimidazolone, isoindolinone, and anthraquinone. Examples of black pigments that can be included in the target include acetylene black, carbon nanotubes, Pigment Black 7, and carbon black. Purple, orange and brown pigments can also be included in the target. Among these dyes, carbon black and metal-substituted phthalocyanine compounds are particularly preferable.

  Carbon black is excellent in stability over time, and can be suitably used for accuracy control of the absorption coefficient. When carbon black is included as a pigment, the oxygen saturation of the target becomes constant, but the oxygen saturation is similar to the 70% oxygen saturation (equivalent to veins) assumed in the living body. Also, it can be suitably used. As described above, when carbon black is used as the pigment to be included in the target, the absorption coefficient and the oxygen saturation corresponding to veins can be stably simulated over a long period of time. When the average primary particle size of carbon black increases, the light scattering increases, and the equivalent scattering coefficient of the target may change depending on the amount of carbon black. Here, since the wavelength used in the photoacoustic wave diagnostic apparatus is about 600 nm, the average primary particle diameter of carbon black is preferably 150 nm or less, which is 1/4 or less of the wavelength. Further, it is more preferable that the average primary particle diameter of carbon black is 30 nm or less because the change in equivalent scattering coefficient when carbon black is blended is less than 0.1.

  Carbon black is thermally stable, has very little deterioration over time, and changes in absorption coefficient and oxygen saturation with time are hardly confirmed. Therefore, it can utilize suitably as a pigment | dye included in the target which evaluates an absorption coefficient and oxygen saturation.

On the other hand, the metal-substituted phthalocyanine compound can change the spectrum shape in the near-infrared region by changing the metal to be substituted and the chemical structure as disclosed in, for example, JP-A-2013-108060. Therefore, the target absorption coefficient ratio at two wavelengths (λ ₁ , λ ₂ ) can be set to a desired value and a wide range of oxygen saturation can be reproduced, so that a metal-substituted phthalocyanine compound is included in the target. Preferred as a dye to be applied. Among them, copper phthalocyanine, which is a copper-substituted phthalocyanine compound, and phthalocyanine vanadium complex, which is a vanadium-substituted phthalocyanine compound, are easily available, and the spectrum shape in the near infrared region has an oxygen saturation of 0% to 100% (deoxyhemoglobin). This is more preferable because it can be freely reproduced from the state of only oxyhemoglobin to the state of only oxyhemoglobin. As described above, when a phthalocyanine compound is used as a pigment to be included in a target, oxygen saturation corresponding to an artery can be stably simulated over a long period of time.

  In addition, since the phthalocyanine compound is inferior to carbon black in heat resistance, it is considered that the absorption coefficient is likely to vary with time. However, in the target of the present invention having a polyamide resin and a phthalocyanine dye, although the decrease in the absorption coefficient itself over time is slightly confirmed, the ratio of the absorption coefficients at a plurality of wavelengths hardly changes, and oxygen saturation The degree does not deteriorate. Therefore, it was found that the phthalocyanine compound can be suitably used as a target for evaluating various values of oxygen saturation.

  In this invention, when the pigment | dye contained in a target is a phthalocyanine compound, it is preferable that a pigment | dye (phthalocyanine compound) is contained 0.000001 mass% or more and 5 mass% or less with respect to the polyamide resin contained in a target. On the other hand, when the pigment | dye contained in a target is carbon black, it is preferable that a pigment | dye (carbon black) is contained 0.000001 mass% or more and 1 mass% or less with respect to the polyamide resin contained in a target. Here, it is more preferable that the phthalocyanine compound is contained in an amount of 0.00001% by mass to 5% by mass with respect to the polyamide resin, since it can be performed from the management of the installation position of the apparatus to the simulation of the absorption coefficient of the living body. Similarly, when carbon black is contained in the polyamide resin in an amount of 0.00005% by mass or more and 0.5% by mass or less, from the management of the installation position of the apparatus to the simulation of the absorption coefficient of the living body can be performed.

  As described above, by appropriately controlling the content of the pigment contained in the target, the absorption coefficient at a predetermined wavelength of the target itself is a range necessary for reproducing a photoacoustic response simulating a living body. It can be controlled to 0.001 mm or more and 0.5 / mm or less. Here, if the absorption coefficient at the predetermined wavelength is lower than that of the living body, it cannot be detected by the apparatus that a part of the light having the predetermined wavelength is absorbed by the target, which causes noise. Further, if the absorption coefficient at the predetermined wavelength greatly deviates from the above range, the detection limit of the probe of the apparatus is exceeded, and the quantitativeness of the detected signal is impaired.

  In addition, when the phthalocyanine compound or carbon black is included in the target within the above-described range, the absorption coefficient at a predetermined wavelength of the target itself is controlled to a range that emits a strong signal necessary for managing the installation position of the phantom. Can do. For example, the extinction coefficient at a wavelength of 800 nm can be controlled to 0.5 / mm or more and 5 / mm or less.

  In the case of the target used to manage the installation position of the phantom, it becomes an obstacle to the signal discrimination of the target for accuracy management, so it is deeper than the target that manages the absorption coefficient and oxygen saturation (position far from the probe). Must be placed. Therefore, in the target used for managing the installation position of the phantom, a large absorption coefficient at which a signal can be clearly detected even from a deep position, for example, the above-mentioned absorption coefficient at a wavelength of 800 nm is 0.5 / mm to 5 / mm. preferable. When the light absorption coefficient is 0.5 / mm or more and 5 / mm or less, even when it is arranged at a deep position (a position far from the probe) used for managing the installation position of the target when irradiated with light, A clear signal is obtained.

  Here, when using a phthalocyanine compound as a pigment | dye, it is preferable that content of the pigment | dye with respect to a polyamide resin shall be 0.05 mass% or more and 5 mass% or less. Thereby, an absorption coefficient range suitable as a target used for management of the installation position of the phantom can be obtained. Similarly, when carbon black is used as the pigment, the pigment content relative to the polyamide resin is preferably 0.01% by mass or more and 0.5% by mass or less. This is because an appropriate absorption coefficient range can be obtained as a target used for managing the installation position of the phantom.

  In particular, in order to simulate the range of 0.05 / mm or more and 0.5 / mm or less, which is close to the range of the absorption coefficient of blood in a living body, as a pigment to be included in the target, phthalocyanine having a large absorption in the near infrared region Vanadium complex and carbon black are preferred. In order to simulate the absorption coefficient in this range, when a phthalocyanine vanadium complex is used as the dye, the dye is included in the range of 0.001% by mass to 0.05% by mass with respect to the polymer compound. More preferred. When carbon black is used as the dye, it is more preferable to include the dye in the range of 0.00005% by mass to 0.01% by mass with respect to the polymer compound.

  The content of carbon black contained in the target can be quantified using a known rubber-carbon black quantification-pyrolysis method, chemical decomposition method (JIS K6227 (1998)), or the like. The content of the phthalocyanine compound contained in the target is to extract the phthalocyanine compound contained using a Soxhlet extraction apparatus, and then use inductively coupled plasma (ICP) emission analysis, nuclear magnetic resonance spectrum, thermogravimetric analysis, etc. The content can be quantified.

4). Target Shape In the present invention, the target shape is not particularly limited as long as it is a shape suitable for accuracy control. For example, a target having a wire shape (columnar shape), a spherical shape, a ring shape, or the like can be preferably used.

5. Method for producing target In the present invention, the target is prepared by adding a dye to the polyamide resin by using a known method such as a hot melt kneading method, a dyeing method, or a method of mixing after dissolving in a common organic solvent. Can be made. Among these methods, a method of first preparing a granular solid having a polyamide resin and a dye by using a hot melt kneading method from the viewpoint that the dye can be stably introduced into the polyamide resin at a low cost. Is preferred. Moreover, when producing the target of a desired shape from this solid substance, well-known methods, such as a hot press method, an injection molding method, an extrusion molding method, a melt spinning method, can be used.

  In order to increase the uniformity of the concentration of the dye contained in the target, it is more preferable to heat-knead and knead the dye and the polyamide resin using a freeze pulverization method or the like.

[Accuracy control phantom]
The target of the present invention is used, for example, as a constituent member of an accuracy control phantom (hereinafter sometimes referred to as a phantom) used in a photoacoustic wave diagnostic apparatus. The phantom of the present invention has a base material and a target included in the base material. Here, the target included in the phantom of the present invention is the target of the present invention. The accuracy management phantom for a photoacoustic wave diagnostic apparatus equipped with the target of the present invention can perform various evaluations based on an acoustic signal transmitted from the target by installing and measuring in the photoacoustic wave diagnostic apparatus. . Specifically, evaluations such as sound pressure distribution evaluation, oxygen saturation evaluation, viewing angle evaluation, resolution evaluation, and resolution evaluation can be performed. For example, in the case of the evaluation of the sound pressure distribution, it is possible to calibrate the apparatus based on the obtained measurement values by measuring the absorption coefficient and the target position using a diagnostic apparatus.

1. Configuration of Quality Control Phantom Hereinafter, an embodiment of the phantom of the present invention will be described with reference to the drawings. FIG. 1 is a schematic diagram showing an example of an embodiment of a phantom in the present invention. 1A is the first embodiment, FIG. 1B is the second embodiment, FIG. 1C is the third embodiment, and FIG. d) is a fourth embodiment. In FIG. 1, the same members are denoted by the same reference numerals.

  FIG. 1A shows that the phantom 10 is an embodiment in which two targets, that is, the first target 1 and the second target 2 are directly immersed in a medium (not shown) such as water. FIG. In the phantom 10 of FIG. 1A, the shape of the targets (1, 2) constituting the phantom 10 is a wire shape. However, the shape of the target (1, 2) can be a spherical shape or a ring shape according to the management purpose. Further, in the phantom 10 of FIG. 1A, the two targets (1, 2) are each fixed to the frame 12.

  The frame 12 for fixing the target (1, 2) is preferably transparent in the wavelength region used in the photoacoustic wave diagnostic apparatus. Specifically, the absorption coefficient is preferably 0.01 / mm or less, which is an average absorption coefficient of the living body in the wavelength region used in the photoacoustic wave diagnostic apparatus. Further, since the acoustic wave transmitted from each of the targets (1, 2) is reflected on the frame 12, an artifact may be generated. Therefore, the acoustic impedance of the frame 12 is ±± from the medium in which the target (1,2,) is immersed. It is preferably within 1.0 MRays, more preferably within ± 0.2 MRays.

  FIGS. 1B to 1D show a phantom 10 of a type in which a target (1, 2) covers its periphery with a material called a base material 11 that approximates the optical and acoustic properties of a living body. . 1B to 1D, two targets (1, 2) are arranged in the base material 11. The shapes of the targets (1, 2) shown in FIGS. 1 (b) to 1 (d) are all wire-like, but a spherical or ring-like target is placed in the base material 11 according to the management purpose. It may be arranged.

  As the shape of the phantom 10 having the base material 11, for example, a rectangular parallelepiped shape shown in FIG. 1 (b), a cylindrical shape shown in FIG. 1 (c), and a cylindrical shape and a hemisphere shown in FIG. Although the shape etc. which combined in the bottom face are mentioned, it is not limited to these. The size and shape of the phantom can be selected appropriately according to the configuration of the photoacoustic wave diagnostic apparatus. When the object is sandwiched between parallel plates and used for accuracy control of a hand-held type diagnostic device, a rectangular or cubic phantom as shown in FIG. 1B is preferable. Further, in the case of a diagnostic device in which the detector is arranged in a columnar shape or a hemispherical shape, a phantom having a shape as shown in FIG. 1C or FIG.

  The base material 11 constituting the phantom 10 is preferably approximated to a living body in terms of acoustic properties and optical properties. As a constituent material of the base material 11, specifically, a resin having acoustic properties close to that of a living body can be suitably used by containing a large amount of water such as hydrogel, but it is excellent in stability over time. Therefore, thermosetting urethane resin and polyvinyl chloride (PVC) plastisol are more preferable.

  In FIGS. 1A to 1D, the targets (1, 2) are arranged with the same height, but the arrangement conditions such as the height can be arbitrarily changed according to the item to be managed. it can. For example, in the case of a phantom that manages the detection capability in the depth direction, the targets (1, 2) can be arranged at different heights (for example, 1 cm intervals).

  Further, the phantom 10 may be provided with a fixing jig part for fixing the phantom 10 to the apparatus and a handle for improving handling. Depending on the diagnostic device, the measurement target may be measured by immersing it in a medium such as water, so that the surface of the target (1, 2) or the surface of the base material 11 in contact with water is waterproof. Or a waterproof film may be provided. Further, a protective film may be provided on the surface of the target (1, 2) or the surface of the base material 11 for the purpose of protecting from damage or contamination.

2. Manufacturing Method of Quality Control Phantom The phantom 10 of FIG. 1A is configured by installing the targets (1, 2) on the frame 12 using means such as heat welding, bonding, and jigs provided on the frame 12, respectively. Produced. Also, the phantom 10 shown in FIGS. 1B to 1D is manufactured by forming the base material 11 so as to include the targets (1, 2).
When the phantom 10 shown in FIGS. 1B to 1D is manufactured, a thermosetting urethane resin can be used as the base material 11. In this case, for example, various additives are added to the polyol and mixed uniformly. Thereafter, a curing agent mainly composed of isocyanate is added and mixed to prepare a liquid mixture. Next, before the fluidity is lost, the prepared mixed solution is poured into a mold having a predetermined phantom shape and cured. In addition, in order to maintain the positional accuracy of the target arrangement, the target (1, 2) is previously arranged at a predetermined arrangement position in the mold before pouring the mixed liquid (liquid thermosetting urethane resin) into the mold. It is preferable.

  When the base material 11 is produced from a thermosetting urethane resin, the curing temperature is preferably 20 ° C. or higher and 150 ° C. or lower. At this time, since the targets (1, 2) in the thermosetting urethane resin may be deformed by heating during curing, the curing temperature is more preferably 20 ° C. or higher and 100 ° C. or lower.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to these Examples.

[Material used for target production]
In the following examples, materials used for producing the target are listed below.

(1) Polymer compounds The polymer compounds used in preparing the target are listed below.
(1a) Polyamide resin A: Mixture of nylon 6/66 resin and nylon 6 (trade name: Amilan (R) non-reinforced grade CM6021M, manufactured by Toray Industries, Inc.)
(1b) Polyamide resin B: Nylon 6 (trade name: Amilan (R) non-reinforced grade CM1017, manufactured by Toray Industries, Inc.)
(1c) Polyamide resin C: Nylon 66 (trade name: Amilan (R) non-reinforced grade CM3001-N, manufactured by Toray Industries, Inc.)
(1d) Thermosetting urethane resin: Thermosetting urethane resin having the following composition: DURANOL (TM) T5652 (manufactured by Asahi Kasei Chemicals Corporation, polycarbonate ol): 82% by mass
-Duranate (TM) TKA-100 (manufactured by Asahi Kasei Chemicals Corporation, curing agent): 13% by mass
-Diisononyl phthalate (manufactured by Tokyo Chemical Industry Co., Ltd., plasticizer): 5% by mass

(2) Dye The dyes used in preparing the target are listed below.
(2a) Carbon black A (added to water): Aqua-Black (R) 162 (Tokai Carbon Corporation, average particle size 110 nm)
(2b) Carbon black B (added to thermosetting urethane resin): Black pigment (manufactured by Exeal Corporation)
(2c) Carbon black C (added to polyamide resin): Amilan (R) non-reinforced grade M040-B2 (manufactured by Toray Industries, Inc., carbon black-containing polyamide resin)
(2d) Carbon black D (added to polyamide resin): Carbon black having an average primary particle size of 24 nm (# 45, manufactured by Mitsubishi Chemical Corporation)
(2e) Copper phthalocyanine: FDR-003 (manufactured by Yamada Chemical Co., Ltd.)
(2f) Vanadium phthalocyanine complex A: FD-40 (manufactured by Yamada Chemical Co., Ltd.)
(2g) Vanadium phthalocyanine complex B: FD-16 (manufactured by Yamada Chemical Co., Ltd.)

(3) Content of the pigment contained in the target The content of the pigment contained in the target was calculated from the charging ratio of the material when producing the test piece.

  About the test piece which has carbon black, content of carbon black which is a pigment | dye was computed with the following method. First, 500 g of a test piece was prepared and heated to 400 ° C. in a heating furnace under a nitrogen stream to thermally decompose the resin component, and then cooled to room temperature under a nitrogen stream. Next, the remaining ash was weighed, and the carbon black content was determined from the weighed ash content. The content of carbon black obtained by this method was in good agreement with the charged concentration of carbon black at the time of preparing the test piece. When preparing a test piece, when using an organic solvent that dissolves the polymer compound in addition to the polymer compound and carbon black, the test piece is dissolved in the organic solvent and then centrifuged. Carbon black was obtained as a precipitate. At this time, when the amount of precipitate was small, the procedure of discarding the supernatant, adding an organic solvent in which the test piece was dissolved, and performing centrifugation was repeated. Thereafter, the precipitate obtained when the organic solvent was washed 3 to 5 times was dried and weighed to determine the content of carbon black contained in the test piece. The content of carbon black obtained by this method was in good agreement with the charged concentration of carbon black at the time of preparing the test piece.

  About the test piece which has a phthalocyanine compound, content of the phthalocyanine compound which is a pigment | dye was computed with the following method. First, a sample obtained by freezing and pulverizing a test piece was placed in a Soxhlet extractor, and acetone was refluxed for 7 hours to extract a phthalocyanine compound contained in the test piece. Next, the solvent contained in the extracted solution was distilled off using a rotary evaporator. When the amount of phthalocyanine obtained by this procedure was insufficient, this procedure was repeated a plurality of times. Next, the obtained extract was analyzed by high frequency inductively coupled plasma optical emission spectrometry, and the amount of metal (vanadium or copper) contained in the extract was quantified. Using the amount of metal in this extract and the amount of metal contained in the phthalocyanine compound, the amount of phthalocyanine compound contained in the test piece was determined. The content of the phthalocyanine compound determined by this method was in good agreement with the charged concentration of the phthalocyanine compound at the time of preparing the test piece.

[Example 1] Manufacture of target A masterbatch was prepared by blending the materials shown below and melt-kneading.
Polyamide resin A: 10 kg
Phthalocyanine vanadium complex A (FD-16): 10 g
Next, the polyamide resin A was blended in the masterbatch so that the content of the dye with respect to the entire composition comprising the polyamide resin A and the phthalocyanine vanadium complex A was 0.004% by mass. Then, the pellet whose content of the pigment | dye with respect to the whole composition is 0.004 mass% was obtained by melt-kneading again. Next, the obtained pellet was extruded to obtain a wire-like target having a diameter of 1 mm.

[Example 2] Production of target In Example 1, the polyamide resin B was used instead of the polyamide resin A, the phthalocyanine vanadium complex B was used instead of the phthalocyanine vanadium complex A, and the content of the phthalocyanine vanadium complex B was composed. It was 0.001 mass% with respect to the whole thing. Except for these, a target was obtained in the same manner as in Example 1.

[Example 3] Production of target In Example 1, the polyamide resin C was used instead of the polyamide resin A, the copper phthalocyanine was used instead of the phthalocyanine vanadium complex A, and the content of copper phthalocyanine relative to the whole composition 0.4 mass%. Except for these, a target was obtained in the same manner as in Example 1.

[Example 4] Manufacture of target The master batch was produced by mix | blending the material shown below, and melt-kneading.
Polyamide resin A: 10 kg
Carbon black A: 10g
Next, after blending the polyamide resin A in the masterbatch so that the content of the pigment relative to the entire composition is 0.002% by mass, the content of the pigment relative to the entire composition is melted and kneaded again. A pellet having a content of 0.002% by mass was obtained. Next, the obtained pellet was extruded to obtain a wire-like target having a diameter of 1 mm.

[Example 5] Manufacture of target In Example 4, 3 g of carbon black B was used in place of carbon black A when producing a master batch. Moreover, when producing a pellet, the polyamide resin A was mix | blended with the said masterbatch so that content of the pigment | dye with respect to the whole composition might be 0.004 mass%. Except for these, a target was obtained in the same manner as in Example 4. In this example (Example 5), when preparing a master batch, melt kneading was performed twice for the purpose of improving the dispersibility of the carbon black B in the polyamide resin A.

[Reference Example 1]
Water having absorption at 800 nm was prepared as a reference sample for calculating the effective Gruneisen coefficient. Specifically, carbon black-containing water was prepared by adding 0.0026 mass% of an aqueous dispersion of carbon black A to pure water. The obtained prepared water was put into a quartz cell having an optical path length of 10 mm, and the absorbance was measured with a spectrophotometer. Using the absorbance, the absorption coefficient at a wavelength of 800 nm of the prepared water was determined from the Lambert-Beer law and found to be 0.3 / mm.

[Comparative Example 1]
Carbon black B (black pigment) was added to a mixed liquid composed of polycarbonate ol and a plasticizer so as to be contained in an amount of 0.0022% by mass with respect to the entire cured product finally obtained. Next, after mixing well using a stirrer so that carbon black B fully disperse | distributes, the hardening | curing agent was added so that it might become 13 mass% with respect to the whole hardened | cured material, and the preparation liquid was obtained. Next, this prepared solution was filled into a φ1 mm tube and cured in the tube to obtain a target.
Separately, the absorbance of a test piece cured in a quartz cell was measured with a spectrophotometer. Using the absorbance, the absorption coefficient at a wavelength of 800 nm was determined from the Lambert-Beer law and found to be 0.1 / mm.

[Comparative Example 2]
In Comparative Example 1, phthalocyanine vanadium complex A was used in place of carbon black B, and the addition amount of phthalocyanine vanadium complex A was prepared so as to be contained in the finally obtained cured product by 0.002% by mass. Except for these, a target was obtained in the same manner as in Comparative Example 1.
Separately, the absorbance of a test piece cured in a quartz cell was measured with a spectrophotometer. Using the absorbance, the absorption coefficient at a wavelength of 800 nm was determined from the Lambert-Beer law and found to be 0.1 / mm.

[Comparative Example 3]
In Comparative Example 1, phthalocyanine vanadium complex B was used in place of carbon black B, and the addition amount of phthalocyanine vanadium complex B was prepared to be contained in the finally obtained cured product by 0.006% by mass. Except for these, a target was obtained in the same manner as in Comparative Example 1.
Separately, the absorbance of a test piece cured in a quartz cell was measured with a spectrophotometer. Using the absorbance, the absorption coefficient at a wavelength of 800 nm was determined from the Lambert-Beer law and found to be 0.3 / mm.

  Here, the measurement method used when evaluating the target produced in the Example and the comparative example is demonstrated.

1. Theoretical Gruneisen Coefficient The theoretical Gruneisen coefficient (theoretical Γ) was determined for the sample having the same composition as the prepared target using Equation (2). The results are shown in Table 1. In addition, the linear expansion coefficient, the sound speed, and the specific heat, which are factors necessary for obtaining the theory Γ, were obtained by the method described below.

(1) Linear expansion coefficient The linear expansion coefficient was calculated | required according to "The linear expansion coefficient test method by the thermomechanical analysis of a plastic" (JIS-K7197 (2012)). Specifically, first, a 5 mm square columnar test piece having a length of 1 cm was prepared from a composition (kneaded material) having the same composition as the target prepared in any of the examples and comparative examples. Next, this test piece is attached to a thermomechanical analyzer (TMA, manufactured by Rigaku Corporation, Thermo Plus EVO TMA8310), and under a nitrogen stream (100 mL / min per minute) at a temperature rising rate of 5 ° C./min. The temperature rise and fall from -40 ° C to 80 ° C was repeated twice. Here, the average linear expansion coefficient at 0 ° C. to 40 ° C. was obtained during the second temperature increase.

(2) Calculation method of sound velocity In constructing an experimental system for evaluating sound velocity, an ultrasonic transducer and a hydrophone shown below were prepared. In addition, the following ultrasonic transducer is used as a probe at the time of acoustic propagation characteristic evaluation.
Ultrasonic transducer (transmitter): Olympus NDT Inc. Made by V303 (center frequency 1MHz)
Hydrophone (receiver): manufactured by Toray Engineering Co., Ltd., needle-type hydrophone Next, the ultrasonic transducer and the hydrophone were each fixed in the water tank by a jig so that the centers of the sound axes coincided with each other. When these were fixed, the distance between the ultrasonic transducer and the hydrophone was 40 mm.
Next, a test piece having a length of 40 mm, a width of 40 mm, and a thickness of 2 mm was prepared from a composition (kneaded material) having the same composition as the target prepared in the examples or comparative examples, and the ultrasonic transducer of the above experimental system was prepared. The test piece was fixed between the hydrophone and the hydrophone. When fixing, the incident angle of the ultrasonic signal to the test piece was set to 0 °. Next, a sine wave of 8 cycles (transmission voltage 100V) is transmitted from the ultrasonic transducer using a function generator (NF1946, manufactured by NF Circuit Design Co., Ltd.), and the received voltage value of the hydrophone when the test piece is installed is oscilloscope. (WaveRunner 64Xi, manufactured by LeCroy Japan Co., Ltd.). Here, the difference in the arrival time of the received wave between when the test piece is installed in the measurement system and when it is not installed is obtained by taking the cross-correlation of the waveform obtained by the oscilloscope, and the sound velocity is calculated from the difference in the arrival time of the received wave. Asked.

(3) Specific heat measurement The specific heat was measured using a differential scanning calorimeter (DSC, manufactured by Hitachi High-Tech Science Co., Ltd., DSC-7020) according to "Method for measuring specific heat capacity of plastic" (JIS K7123 (2012)). The sample container is made of aluminum, heated at a rate of temperature increase of 5 ° C./min under a nitrogen stream, and -20 for an empty container, a container containing a measurement sample, and a container containing a standard substance (sapphire), respectively. The measurement was performed in the range of from 0 to 60 ° C. Here, the specific heat of the measurement sample was calculated from the difference in heat flux at 25 ° C. obtained from the measurement results.

2. Absorption Coefficient, Equivalent Scattering Coefficient, Oxygen Saturation Described below are methods for evaluating the absorption coefficient, equivalent scattering coefficient, and oxygen saturation performed on samples having the same composition as the targets prepared in Examples and Comparative Examples. First, test pieces used in the evaluation test were prepared. In addition, about the system (Examples 1 thru | or 5) containing a thermoplastic resin, the test piece of 50 mm x 50 mm and thickness 2mm (optical path length) was produced by injection molding.
In a system containing a thermosetting resin (for example, Comparative Example 1), a pigment-dispersed liquid polyol added with a curing agent is injected into a quartz cell of 50 mm × 50 mm and an optical path length of 5 mm, and heated at 90 ° C. for 1 hour. A test piece was prepared by curing the resin. Moreover, about water, what was put into the same quartz cell was used as the test sample.
About this test piece or the test sample, the diffuse transmittance and diffuse reflectance, and the light absorbency were calculated | required using the spectrophotometer (The JASCO Corporation make, V-670). Specifically, the wavelength absorption coefficient of the test piece at 800 nm was determined. About the refractive index of each sample, it measured using the refractometer (Anton Paar Co., Ltd. make, Abbemat-MW). For systems containing polyamide resin that scatters light, the variable settings are optimized by the inverse Monte Carlo simulation based on the measured diffuse transmittance and diffuse reflectance so that the difference between the measured value and the calculated value is minimized. The absorption coefficient and the equivalent scattering coefficient at each wavelength were calculated. For test pieces (test samples) such as water with very little light scattering, the absorption coefficient was calculated from the measured absorbance using the Lambert-Beer law. Based on the obtained absorption coefficient, the oxygen saturation was calculated from Equation (5). In calculating the oxygen saturation, the oxygen saturation was calculated from the absorption coefficients of 760 nm and 800 nm. The results are shown in Table 2.

3. Effective Gruneisen Coefficient A phantom having the target produced in the example or the comparative example was produced, and the effective Gruneisen coefficient was evaluated using this phantom.

(1) Phantom FIG. 2 is a schematic diagram showing a phantom having a target obtained in an example or a comparative example. The phantom 10a of FIG. 2 was produced by the method described below. First, the target 3 produced in the example or comparative example was placed at a predetermined position of the mold prepared when producing the phantom 10a shown in FIG. Thereafter, a titanium oxide (SJR-405S, manufactured by Teika Co., Ltd.) and carbon black (black pigment, manufactured by Exeal Corporation) are dispersed in a human skin gel transparent type (manufactured by EXCIAL CORPORATION) to prepare a resin composition. did. At this time, the amounts of titanium oxide and carbon black were adjusted so that the resin composition had an absorption coefficient at a wavelength of 800 nm of 0.005 / mm and an equivalent scattering coefficient of 1.0 / mm. Next, the prepared resin composition was poured into the mold, and the resin composition was cured to obtain phantom 10a.

(2) Evaluation of initial sound pressure FIG. 3 is a schematic diagram showing an example of a photoacoustic apparatus used in measuring the initial sound pressure. 3A is a cross-sectional view showing the configuration of a portion of the photoacoustic apparatus that holds the phantom, and FIG. 3B is a top view of the hemispherical container 21 shown in FIG. is there. In FIG. 3B, the arrangement position of the phantom 25 is also shown. 512 ultrasonic probes 22 constituting the photoacoustic apparatus 20 are arranged in a spiral shape on the hemispherical container 21 at positions along the hemispherical surface. The holding member 24 has a central portion 24a having a recess and an edge portion 24b, and the phantom 25 is disposed on the central portion 24a.

  Although not shown in FIG. 3, when actually performing the measurement, a matching layer such as water is interposed between the hemispherical container 21 and the holding member 24. As shown in FIG. 3A, the phantom 25 is disposed on the holding member 24. However, a matching layer (not shown) such as water is provided as necessary so that air does not enter the phantom 25. It may be introduced into the holding member 24. In the photoacoustic apparatus 20 of FIG. 3, the holding member 24 is a member formed of a resin material such as polyethylene terephthalate. Further, in the photoacoustic apparatus 20 of FIG. 2, the hemispherical container 21 is provided with a space through which the measurement light from the light irradiation unit 23 passes, specifically, a space indicated by reference numeral 21a. And the light irradiation part 23 can irradiate the measurement light 23a toward the phantom 25 from the negative direction of the z-axis. In the photoacoustic apparatus 20 of FIG. 3, the position of the hemispherical container 21 can be changed by an XY stage (not shown). During measurement, the subject (phantom 25) is irradiated with pulsed light (measurement light 23a) while scanning the XY stage, and the generated acoustic wave is detected by the ultrasonic probe 22. A three-dimensional optical ultrasound image can be obtained by reconstructing the data.

  The light irradiation unit 23 is an apparatus that irradiates pulsed light serving as measurement light 23 a that is irradiated to the phantom 25 that is the subject. The light source is preferably a laser light source in order to obtain a large output. However, the present invention is not limited to this, and a light emitting diode, a flash lamp, or the like can be used instead of the laser. In addition, when using a laser as the measurement light 23a, various things, such as a solid laser, a gas laser, a pigment | dye laser, and a semiconductor laser, can be used.

  In order to generate photoacoustic waves effectively, light must be irradiated in a sufficiently short time according to the thermal characteristics of the subject. When the subject is a living body, the pulse width of the pulsed light generated from the light irradiation unit 23 that is a light source is preferably 10 nanoseconds or more and 50 nanoseconds or less. The wavelength of the pulsed light is preferably a wavelength at which light propagates to the inside of the subject. Specifically, in the case of a living body, it is 600 nm or more and 1100 nm or less. Here, a titanium sapphire laser, which is a solid laser, is used for the light irradiation unit 23, and wavelengths of 760 nm and 800 nm are used for measuring oxygen saturation.

  The ultrasonic probe 22 is a member for receiving photoacoustic waves. As the ultrasonic probe 22, known ones such as a capacitive ultrasonic transducer (cMUT) using a micromachine technique (semiconductor process), a piezoelectric ceramic vibrator, or the like can be used.

  The initial sound pressure of the target was quantified from the three-dimensional photoacoustic wave image using the photoacoustic apparatus 20 of FIG.

(3) Effective Gruneisen coefficient First, the effective Gruneisen coefficient of the target of Comparative Example 1 was calculated by the method described below. First, the tube used in Comparative Example 1 was filled with the prepared water prepared in Reference Example 1 and the end was sealed. Next, with respect to the tube filled with the prepared water and the tube obtained in Comparative Example 1 (cured product accommodated in the tube), the initial sound pressure was measured using a photoacoustic apparatus. From the obtained measurement results, the effective Gruneisen coefficient (effective Γ) in Comparative Example 1 was calculated using Equation (3). As a result of the calculation, it was found that the effective Γ is 0.8, which is a value relatively close to the theory Γ (0.9).

  Next, for the phantom including any of the targets manufactured in Examples 1 to 5 and Comparative Examples 2 and 3, the initial sound pressure was determined using the photoacoustic apparatus 20 of FIG. Next, using the obtained initial sound pressure value and the effective Γ in the comparative example 1, the effective Γ in the example and the comparative example was calculated from the equation (4). The results are shown in Table 1.

4). Evaluation of Fluctuation in Absorption Coefficient and Oxygen Saturation after Deterioration Treatment A test piece of 40 mm × 2 mm thickness produced by injection molding was placed in an 80 ° C. thermostat and subjected to deterioration treatment. The absorption coefficient and oxygen saturation of the test piece were evaluated before and after the deterioration test, and “◯” was indicated when the variation rate after the deterioration treatment with respect to the initial value was less than 2%, and “△” was indicated when it was 2% or more and less than 10%. The results are shown in Table 1.

  As in Examples 1 to 5, when the polymer compound contained in the target is a polyamide resin, from Table 1, the effective Γ is both 0.5, which is a lower value than the thermosetting urethane resin system. was. The effective Γ value is close to the Gruneisen coefficient (0.3) of blood compared to the thermosetting urethane resin system, and a polyamide resin is more suitable as a constituent material of the target that simulates the living body. It became clear that there was.

  On the other hand, in Comparative Example 1, the effective Γ was 0.8. This is a value relatively close to the theory Γ (0.9). In Comparative Example 2 and Comparative Example 3, the effective Γ was equivalent to that of Comparative Example 1. When the initial sound pressure was measured for Comparative Examples 2 and 3, it was found that the magnitude of the initial sound pressure was proportional to the pigment concentration.

  Regarding the systems of Examples 1 to 3, that is, the system in which the polyamide resin contains a phthalocyanine compound, it was confirmed that the rate of change was less than 10% although the absorption coefficient was changed by the deterioration treatment. Further, the fluctuation rate of the oxygen saturation before and after the deterioration treatment was very small, less than 2%. From the above results, it was found that a target having a phthalocyanine compound and a polyamide resin is particularly suitable for controlling the accuracy of oxygen saturation.

  About the polyamide resin containing the carbon black of Example 4 and Example 5, the fluctuation coefficient of the absorption coefficient and the oxygen saturation before and after the deterioration treatment were both less than 2%, which was found to be extremely stable. From the above results, it was found that a target having carbon black and polyamide resin is suitable for management of absorption coefficient and oxygen saturation.

From Table 1, the oxygen saturation of the target obtained in Example 1 was 96%, and the absorption characteristics approximated to the oxygen saturation of the artery were shown. The oxygen saturation of the target obtained in Example 2 was 80%. Furthermore, the oxygen saturation of the target obtained in Example 3 was 36%. On the other hand, the oxygen saturation levels of the targets obtained in Example 4 and Example 5 were both 71%, indicating that the absorption characteristics approximated to the venous oxygen saturation level were exhibited.
From the above results, it became clear that the oxygen saturation can be appropriately controlled by adding a phthalocyanine compound or carbon black as a pigment in the target.

[Optical evaluation of dyes]
Optical evaluation of the dye contained in the target was performed by the method described below.

(1) In the case of phthalocyanine compound First, polyamide resin A (10 kg) and phthalocyanine vanadium complex A were blended and melt-kneaded to prepare a master batch. Next, the polyamide resin A was mix | blended with the said masterbatch. Then, pellets were obtained by melt-kneading again. Next, the obtained pellet was molded to produce a plate-shaped test piece. Optical evaluation was performed using the test piece thus obtained. For the optical evaluation, an inverse Monte Carlo simulation was used, but a sample having a high absorption when measured by a spectrophotometer was measured with a reduced thickness.

  In addition, when mix | blending phthalocyanine vanadium complex A, the density | concentration of the phthalocyanine vanadium complex A contained in a test piece is 0.00005 mass% with respect to the polyamide resin A, 0.001 mass%, 0.003 mass%, The blending amount of the phthalocyanine vanadium complex A was adjusted to be 0.004% by mass, 0.006% by mass, 0.008% by mass, 0.02% by mass, 0.05% by mass, or 0.1% by mass. .

  FIG. 4 is a graph showing the correlation between the absorption coefficient of the test piece and the concentration of the dye (phthalocyanine vanadium complex A). As shown in FIG. 4, there is a high correlation between the concentration of the phthalocyanine compound, which is a pigment, and the absorption coefficient of the test piece (correlation coefficient 0.992), and the absorption of the test piece can be adjusted by adjusting the concentration. It became clear that the coefficient could be controlled. Moreover, the same correlation was confirmed also about the phthalocyanine vanadium complex B used in Example 2, and the copper phthalocyanine used in Example 3.

  From the above results, when the phthalocyanine compound is added in an amount of 0.000001 mass% to 5 mass% with respect to the polyamide resin, the absorption coefficient at 800 nm of the target is 0.001 / mm to 0.5 / It was found that control was possible within a range of mm or less. Further, when the phthalocyanine compound is added at a ratio of 0.05% by mass or more and 5% by mass or less with respect to the polyamide resin, the absorption coefficient at 800 nm of the target is 0.5 / mm which is necessary for management of the installation position of the phantom. It was found that control was possible even in the range of 5 / mm or less.

  By the way, the phthalocyanine vanadium complex used in Example 1 and Example 2 has a higher absorption coefficient in the near infrared region than the copper phthalocyanine used in Example 3. For this reason, it was found that by adding a small amount to the polyamide resin, an absorption coefficient in the range of 0.05 / mm to 0.5 / mm, which is close to the blood absorption coefficient range, can be reproduced. That is, it was found that when a phthalocyanine vanadium complex is used as a pigment, a range close to the range of the absorption coefficient of blood in a living body can be reproduced by including 0.001% by mass to 0.05% by mass with respect to the polyamide compound. .

(2) In the case of carbon black First, polyamide resin A (10 kg) and carbon black A were blended and melt-kneaded to prepare a master batch. Next, the polyamide resin A was mix | blended with the said masterbatch. Then, pellets were obtained by melt-kneading again. Next, the obtained pellet was molded to produce a plate-shaped test piece. Optical evaluation was performed using the test piece thus obtained. The optical evaluation method is the same as that for the phthalocyanine compound.

  When the carbon black A is blended, the concentration of the carbon black A contained in the test piece is 0.0001% by mass, 0.0005% by mass, 0.002% by mass, 0.00% with respect to the polyamide resin A. The blending amount of the carbon black A was adjusted to be 004 mass%, 0.008 mass%, 0.05 mass%, or 0.1 mass%.

  FIG. 5 is a graph showing the correlation between the absorption coefficient of the test piece and the concentration of the pigment (carbon black A). As shown in FIG. 5, there is a high correlation between the concentration of carbon black as a pigment and the absorption coefficient of the test piece (correlation coefficient 0.993), and the absorption of the test piece can be adjusted by adjusting the concentration. It became clear that the coefficient could be controlled.

  From the above results, when carbon black is added in an amount of 0.000001% by mass to 1% by mass with respect to the polyamide resin, the absorption coefficient at 800 nm of the target is 0.001 / mm or more, which is necessary for simulating the living body, to be 0.00. It was found that control was possible within a range of 5 / mm or less. In addition, when carbon black is added in an amount of 0.01% to 0.5% by weight with respect to the polyamide resin, the range of 0.5 / mm to 5 / mm, which is necessary for managing the installation position of the phantom, etc. It turned out to be controllable. In other words, in the case of carbon black, it was found that a range close to the range of the absorption coefficient of blood in a living body can be reproduced by including 0.00005% by mass to 0.01% by mass with respect to the polyamide resin.

[Evaluation of equivalent scattering coefficient]
The equivalent scattering coefficient at a wavelength of 800 nm of a test piece produced with the same composition as that of the example (Examples 1 to 5) was obtained. Here, the equivalent scattering coefficient of the polyamide resin A was 0.2 / mm, the polyamide resin B was 0.25 / mm, and the polyamide resin C was 0.3 / mm. From the above results, it is clear that Nylon 6/66, Nylon 6 and Nylon 66 used as polyamide resin all show an equivalent scattering coefficient similar to a living body and can be suitably used as a target for an accuracy control phantom. It was.

[Relationship between target thickness, absorption coefficient, and oxygen saturation]
By extruding the polyamide resin containing the pigment used in any of Examples 1 to 5, the diameter was 0.1 mm, 0.2 mm, 0.3 mm, 0.5 mm, 1 mm, 2 mm, 3 mm, and A wire-like target having a thickness of 5 mm could be produced. Moreover, when the initial sound pressure was measured about the produced wire target using the photoacoustic wave apparatus, the initial sound pressure showed the intensity | strength proportional to the absorption coefficient. Moreover, when the oxygen saturation was calculated using the initial sound pressure generated when irradiating light with wavelengths of 760 nm and 800 nm, it was in good agreement with the oxygen saturation shown in Table 2 obtained with the plate-like test piece. .

[Example 6] Manufacture of phantom A phantom having the shape of the base material shown in FIG. First, a total of four targets, one each produced in Examples 1 to 4, were placed at predetermined positions of a mold prepared when producing the phantom 10 shown in FIG. Thereafter, a titanium oxide (SJR-405S, manufactured by Teika Co., Ltd.) and carbon black (black pigment, manufactured by Exeal Corporation) are dispersed in a human skin gel transparent type (manufactured by EXCIAL CORPORATION) to prepare a resin composition. did. At this time, the amounts of titanium oxide and carbon black were adjusted so that the resin composition had an absorption coefficient at a wavelength of 800 nm of 0.005 / mm and an equivalent scattering coefficient of 1.0 / mm. In addition, about the optical physical property of this resin composition, it calculated | required from said reverse Monte Carlo simulation. Next, phantom 10 was obtained by pouring the prepared resin composition into the above mold and curing the resin composition. The base material 11 constituting the phantom 10 is a member made of a thermosetting urethane resin obtained by reacting polyalkylene glycol and isocyanate, the sound velocity is 1400 m / s, and the acoustic attenuation coefficient is 0.35 dB / s. It was MHz / cm. For this reason, the phantom obtained in the present example was able to obtain acoustic properties that approximated fat of a living body.
Moreover, when the phantom obtained in the present Example was measured using the photoacoustic apparatus 20 of FIG. 3, the initial sound pressure according to each absorption coefficient and the oxygen saturation corresponding to the kind of pigment | dye were confirmed. .

  From the above results, it was revealed that the target of the present invention is suitable as a target for a photoacoustic wave diagnostic apparatus.

  The target of the present invention can be used as a constituent member of an accuracy management phantom used for accuracy management and calibration of a photoacoustic wave diagnostic apparatus.

  1 (2): Target, 10: Phantom, 11: Base material, 12: Frame

Claims (11)

  A target for a photoacoustic wave diagnostic apparatus, comprising a polyamide resin and at least one kind of pigment.   The target for a photoacoustic wave diagnostic apparatus according to claim 1, wherein the dye is carbon black or a phthalocyanine compound. The pigment is carbon black;
The target for a photoacoustic wave diagnostic apparatus according to claim 1 or 2, wherein the carbon black is contained in an amount of 0.000001 mass% to 1 mass% with respect to the polyamide resin.   The target for a photoacoustic wave diagnostic apparatus according to claim 3, wherein an average primary particle diameter of the carbon black is 150 nm or less. The dye is a phthalocyanine compound;
The target for a photoacoustic wave diagnostic apparatus according to claim 1 or 2, wherein the phthalocyanine compound is contained in an amount of 0.000001 mass% to 5 mass% with respect to the polyamide resin.   The target for a photoacoustic wave diagnostic apparatus according to claim 5, wherein the phthalocyanine compound is a phthalocyanine vanadium complex or copper phthalocyanine.   The target for a photoacoustic wave diagnostic apparatus according to claim 5 or 6, wherein the phthalocyanine compound is a phthalocyanine vanadium complex.   The target for a photoacoustic wave diagnostic apparatus according to any one of claims 1 to 7, wherein the polyamide resin is nylon 6/66, nylon 6, or nylon 66.   An accuracy management phantom for a photoacoustic wave diagnostic apparatus, comprising: a medium; and the target for a photoacoustic wave diagnostic apparatus according to any one of claims 1 to 8, which is immersed in the medium.   An accuracy management phantom for a photoacoustic wave diagnostic apparatus, comprising: a base material; and the target for the photoacoustic wave diagnostic apparatus according to any one of claims 1 to 8 provided in the base material. .   The quality control phantom for a photoacoustic wave diagnostic apparatus according to claim 10, wherein the base material is made of a thermosetting urethane resin.

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