Local biological tissue evaluation device and local biological tissue evaluation method

Abstract

This local biological tissue evaluation device comprises: a phase angle variation amount measurement unit which includes a sensor provided with a plurality of electrodes that can be spaced apart from each other on the skin of a subject, applies a current or a voltage between the electrodes in a state in which each of the electrodes is in contact with the skin, measures a voltage on the basis of a current-applied voltage measurement pattern when the current is applied, measures a current on the basis of a voltage-applied current measurement pattern when the voltage is applied between the electrodes, and measures a feature amount obtained on the basis of a variation amount of a phase angle for the current-applied voltage measurement pattern or the voltage-applied current measurement pattern; a phase angle Jacobian matrix creation unit which creates a phase angle Jacobian matrix on the basis of the current-applied voltage measurement pattern or the voltage-applied current measurement pattern; and an image reconstruction unit which uses the phase angle difference and the phase angle Jacobian matrix to image a phase angle distribution inside the living body of the subject.

Description

Local biological tissue evaluation device and local biological tissue evaluation method

[0001] The present invention relates to a local biological tissue evaluation device and a local biological tissue evaluation method. This application claims priority to Japanese Patent Application No. 2023-149511, filed on September 14, 2023, the contents of which are incorporated herein by reference.

[0002] Evaluating the quality of local tissues such as muscles and internal organs is important for maintaining and promoting daily health. For example, the local muscle quality of each muscle compartment is an important factor in maintaining physical function to avoid the risk of lifestyle-related diseases and improve quality of life.

[0003] Generally, muscle quality is evaluated using three muscle quality indices: muscle aging (MA), fatty infiltration (FI), and muscle cross-sectional area (CSA). These muscle quality indices vary significantly depending on the muscle compartment (also called compartment, each with its own name). Therefore, clinically, it is desirable to evaluate the muscle quality indices of each compartment locally, rather than globally, throughout the entire organism. Furthermore, from the perspective of daily monitoring, a minimally invasive, inexpensive, and simple evaluation method is obviously more desirable. Until now, evaluation of local muscle quality indices has been performed using immunohistochemistry, magnetic resonance imaging, dual-energy X-ray absorptiometry, ultrasound, and the like.

[0004] For example, muscle aging (MA) is assessed invasively by immunohistochemistry, which involves snap-freezing muscle tissue and then delineating hundreds of muscle fibers using a threshold function. Fatty infiltration (FI) is calculated automatically from images obtained by magnetic resonance imaging. Muscle cross-sectional area (CSA) is obtained by transmission intensity using dual-energy X-ray absorptiometry.

[0005] However, these conventional methods for assessing local muscle quality indices are either invasive, radioactive, expensive, and large-scale, making them impractical for daily monitoring.

[0006] On the other hand, bio-impedance analysis (BIA) is a minimally invasive, inexpensive, and simple method for evaluating muscle quality, although it is a method for evaluating global muscle quality indices. In bio-impedance analysis (BIA), four electrodes are generally placed in contact with the limbs of a living body, a current is applied from two of the electrodes, and a voltage is measured from the other two electrodes. The phase angle (θ) between the applied current (I) and the measured voltage (V) is measured, and a portion of the global muscle quality index is evaluated. Here, the phase angle (θ) is calculated using the resistance component of the impedance (the real part of the complex impedance) Z' and the reactance component of the impedance (the imaginary part of the complex impedance) Z'', as follows: θ = tan －１ (Z" / Z') Bioelectrical impedance analysis (BIA) roughly evaluates the global fat infiltration (FI) and muscle volume (not muscle cross-sectional area) from the global phase angle (θ), but does not locally evaluate the three muscle quality indices of each compartment.

[0007] Furthermore, as a minimally invasive, inexpensive, simple, and local field evaluation method, Non-Patent Document 1 proposes capacitively coupled dielectric spectroscopy tomography (C4D = Capacitive Coupled Contactless Conductivity Detection) based on phase angle measurement and a phase angle Jacobian matrix (phase angle sensitivity matrix) for air-borne powder transport pipelines in factories, etc., and discloses a phase angle imaging technique.

[0008] Y. Jiang and M. Soleimani, “Capacitively Coupled Phase-based Dielectric Spectroscopy Tomography” Sci. Rep. , vol. 8, no. 1, p. 17526, 2018

[0009] The method of Non-Patent Document 1 is intended for the evaluation of local fields in industrial products and is not intended for muscle quality indexes. Furthermore, according to the IEC (International Electrotechnical Commission) standard, to compensate for the application of non-contact capacitance tomography, a high voltage of 1 V is applied at an applied voltage frequency f = 10 kHz to 15 MHz to measure the current I, and the high voltage is applied via a sensor. Furthermore, the method of Non-Patent Document 1 uses the Jacobian matrix J calculated from the difference with saline as the background conductivity. However, because local biological tissue (local biological tissue) is a frequency-dependent substance, simply applying the method of Non-Patent Document 1 to a living body makes it difficult to evaluate the quality of the local biological tissue. Ultimately, even if this method is applied to a living body, imaging is difficult.

[0010] The present invention has been made in consideration of the above circumstances, and aims to provide a local biological tissue evaluation device and a local biological tissue evaluation method that are minimally invasive, inexpensive, simple, and capable of evaluating the quality of local biological tissue.

[0011] In order to solve the above problems, the present invention proposes the following means: <1> A local biological tissue evaluation device according to aspect 1 of the present invention includes a sensor including a plurality of electrodes that can be placed on the skin of a subject at intervals, and applies a current or a voltage between the electrodes with the electrodes in contact with the skin, measures the voltage based on a current-application-voltage measurement pattern when the current is applied, and measures the current based on a voltage-application-current measurement pattern when the voltage is applied between the electrodes, and is equipped with a phase angle fluctuation measurement unit that measures a feature amount obtained based on the phase angle fluctuation amount for the current-application-voltage measurement pattern or the voltage-application-current measurement pattern, a phase angle Jacobian matrix creation unit that creates a phase angle Jacobian matrix based on the current-application-voltage measurement pattern or the voltage-application-current measurement pattern, and an image reconstruction unit that uses the feature amount and the phase angle Jacobian matrix to create an image of the phase angle distribution inside the living body of the subject. <2> Aspect 2 of the present invention is the local biological tissue evaluation device of Aspect 1, wherein the phase angle Jacobian matrix creation unit creates an equation relating mesh coordinates of the subject's measurement location and the nth mesh in the mth measurement pattern, and derives, as elements of the phase angle Jacobian matrix as a solution of the equation, the current, potential, and phase angle of impedance, which is the ratio of the voltage to the current, at each mesh coordinate. <3> Aspect 3 of the present invention is the local biological tissue evaluation device of Aspect 1 or 2, wherein the feature amount is a phase angle difference expressed by the following equation (1): Δθ ｍ = θ ｍ (f) -θ ｍ (f ０ ) ...Equation (1) In the above equation (1), Δθ ｍ : Phase angle difference θ in the mth current application voltage measurement pattern or the mth voltage application current measurement pattern ｍ (f): Phase angle θ of high frequency f in the m-th current application voltage measurement pattern or the m-th voltage application current measurement pattern ｍ (f ０ ) the mth current application voltage measurement pattern or the mth voltage application current measurement pattern ０The phase angle of . <4> Aspect 4 of the present invention is the local biological tissue evaluation device of any of Aspects 1 to 3, which may further include a local biological tissue evaluation unit that evaluates the local biological tissue using the imaged phase angle distribution. <5> Aspect 5 of the present invention is the local biological tissue evaluation device of any of Aspects 1 to 4, which may include a local biological tissue aging evaluation unit that calculates a spatial average of the phase angle distribution from the phase angle distribution. <6> Aspect 6 of the present invention is the local biological tissue evaluation device of any of Aspects 1 to 5, which may include a local biological tissue fatty infiltration evaluation unit that creates a local biological tissue phase angle distribution that is a phase angle distribution of the local biological tissue by assigning the phase angle distribution to each local biological tissue of the subject. <7> Aspect 7 of the present invention is the local biological tissue evaluation device of Aspect 6, which may include the local biological tissue fatty infiltration evaluation unit that calculates a spatial average of the local biological tissue phase angle distribution from the local biological tissue phase angle distribution. <8> Aspect 8 of the present invention relates to the local biological tissue evaluation device of Aspect 6 or 7, wherein the local biological tissue evaluation unit may further include a local biological tissue cross-sectional area evaluation unit that calculates a local biological tissue cross-sectional area ratio after performing a binarization process on the local biological tissue phase angle distribution. <9> A local biological tissue evaluation method of Aspect 9 of the present invention includes a first step of using a sensor including a plurality of electrodes that can be placed on the skin of a subject at intervals, applying a current or a voltage between the electrodes with the electrodes in contact with the skin, measuring the voltage based on a current-applied-voltage measurement pattern when the current is applied, and measuring the current based on a voltage-applied-current measurement pattern when the voltage is applied between the electrodes, and measuring a feature amount obtained based on a fluctuation amount of the phase angle for the current-applied-voltage measurement pattern or the voltage-applied-current measurement pattern, a second step of creating a phase angle Jacobian matrix based on the current-applied-voltage measurement pattern or the voltage-applied-current measurement pattern, and a third step of imaging the phase angle distribution inside the subject's living body from the phase angle difference and the phase angle Jacobian matrix.<10> Aspect 10 of the present invention is the local biological tissue evaluation method of Aspect 9, wherein in the second step, an equation relating mesh coordinates of the subject's measurement location and the nth mesh in the mth measurement pattern is created, and the current, potential, and phase angle of impedance, which is the ratio of the voltage to the current, at each mesh coordinate may be derived as elements of a phase angle Jacobian matrix as a solution of the equation. <11> Aspect 11 of the present invention is the local biological tissue evaluation method of Aspect 9 or 10, wherein the feature amount may be a phase angle difference expressed by the following equation (2): Δθ. ｍ = θ ｍ (f) -θ ｍ (f ０ ) ...Equation (2) In the above equation (2), Δθ ｍ : Phase angle difference θ in the mth current application voltage measurement pattern or the mth voltage application current measurement pattern ｍ (f): Phase angle θ of high frequency f in the m-th current application voltage measurement pattern or the m-th voltage application current measurement pattern ｍ (f ０ ) the mth current application voltage measurement pattern or the mth voltage application current measurement pattern ０ and the phase angle of . <12> Aspect 12 of the present invention is the local biological tissue evaluation method of any one of Aspects 9 to 11, which may further include a fourth step of evaluating the local biological tissue using the imaged phase angle distribution. <13> Aspect 13 of the present invention is the local biological tissue evaluation method of Aspect 12, wherein the fourth step may include calculating a spatial average of the phase angle distribution from the phase angle distribution. <14> Aspect 14 of the present invention is the local biological tissue evaluation method of Aspect 12 or 13, wherein the fourth step may include creating a local biological tissue phase angle distribution, which is a phase angle distribution of the local biological tissue, by assigning the phase angle distribution to each local biological tissue of the subject. <15> Aspect 15 of the present invention is the local biological tissue evaluation method of Aspect 14, wherein the fourth step may include performing a binarization process on the local biological tissue phase angle distribution and then calculating a local biological tissue cross-sectional area ratio.

[0012] According to the above aspects of the present invention, each of the above aspects of the present invention can provide a local biological tissue evaluation device and a local biological tissue evaluation method that are minimally invasive, inexpensive, simple, and capable of evaluating the quality of local biological tissue.

[0013] It is a functional block diagram of a local biological tissue evaluation device according to one embodiment of the present invention. It is a schematic diagram showing the phase angle variation measurement unit shown in FIG. 1, a measurement method of the phase angle difference by the phase angle variation measurement unit, and a control unit. It is a flowchart showing the flow of measuring the measured phase angle difference Δθm based on a current application voltage measurement pattern. Φ 5 is a flowchart for creating J. (a) shows an example of electrode placement and mesh on the calf, (b) shows a diagram of classification of cross-sectional positions of elements in the calf, (c) shows a current application and voltage measurement pattern, (d) shows the created resistance Jacobian matrix, (e) shows the created reactance Jacobian matrix, and (f) shows the created phase angle Jacobian matrix, according to the flow shown in FIG. Φ 10 is a diagram showing an example of J(f). p and its binary phase angle distribution Φ p 1 is a diagram showing an example of an image of a muscle. 2 is a flowchart of a local biological tissue evaluation method according to one embodiment of the present invention. 3 is a diagram showing the structure of the muscle used in the simulation of muscle quality evaluation. 4 is a diagram showing the calculated phase angle distribution image Φ. 5 is a diagram showing the results of the spatial average phase angle <Φ> of each muscle compartment. 6 is a binarized phase angle distribution image. 7 is a diagram showing the local muscle cross-sectional area ratio of each muscle compartment. 8 is a schematic diagram of the device used in Experimental Example 2. 9 is a diagram showing the calculated phase angle distribution image. 10 is a diagram showing the spatial average phase angle <Φ> of each subject. 11 is an ultrasound image of each subject for comparison. 12 is a diagram showing the spatial average phase angle <Φ> of the first muscle compartment of each subject. ｐ1 >, the spatially averaged phase angle of the second compartment <Φ ｐ２ >, spatially averaged phase angle of the third compartment <Φ ｐ３ >, spatially averaged phase angle of the fourth muscle compartment <Φ ｐ４ >, Local fatty infiltration uFI obtained from ultrasound images. Binarized phase angle images for each subject.

[0014] A localized biological tissue evaluation device 100 according to one embodiment of the present invention will be described below with reference to the drawings. In the following description, muscle will be used as an example of biological tissue. However, biological tissue is not limited to muscle. Examples of biological tissue include the heart, lungs, liver, kidneys, spleen, pancreas, stomach, small intestine, large intestine, bladder, and gallbladder. In the following description, muscle includes three types of muscle: skeletal muscle that moves the body, smooth muscle present in blood vessel walls, and cardiac muscle that constitutes the heart. However, skeletal muscle may be referred to as muscle.

[0015] 1 , the local biological tissue evaluation device 100 includes a control unit 30, a phase angle variation measurement unit 10, and a calculation and evaluation unit 50. The calculation and evaluation unit 50 includes a phase angle Jacobian matrix creation unit 51, an image reconstruction unit 52, and an output unit 56. The local biological tissue evaluation device 100 may further include a local biological tissue evaluation unit 60. The local biological tissue evaluation unit 60 includes a local biological tissue aging evaluation unit 53, a local biological tissue fatty infiltration evaluation unit 54, and a local biological tissue cross-sectional area evaluation unit 55. The calculation evaluation unit 50 of the local biological tissue evaluation device 100 includes, for example, a central processing unit (CPU), read-only memory (ROM), random access memory (RAM), and hard disk drive (HDD) / solid state drive (SSD). The phase angle Jacobian matrix creation unit 51, image reconstruction unit 52, local biological tissue evaluation unit 60, and output unit 56 are realized by the CPU executing a predetermined program. The program may be acquired via a recording medium or a network. Alternatively, a dedicated hardware configuration may be used to realize the configuration of the local biological tissue evaluation device 100. Each unit will be described below.

[0016] (Control Unit 30) The control unit 30 will be described using FIG. 2. FIG. 2 is a schematic diagram showing the phase angle variation measurement unit 10 shown in FIG. 1, the method for measuring a phase angle difference using the phase angle variation measurement unit 10, and the control unit 30. FIG. 2 is a schematic diagram of the control unit 30 with the sensor 20 placed on the subject's leg. Here, an example is described in which the sensor is in contact with the subject's leg, but the measurement site of the subject in the present invention is not limited to the leg. The control unit 30 is composed of, for example, a current application device (or a voltage application device) (not shown) that applies a current (or a voltage application device) and a multiplexer (not shown) that switches the wiring connected to each electrode. The current application device or voltage application device may be an impedance analyzer or the like. Here, the impedance analyzer has the function of applying a current or a voltage by changing the applied frequency and amplitude.

[0017] 2 , the control unit 30 is connected to one or more sensors 20 and electrodes 21 via electric wires 41. The sensor 20 includes a plurality of electrodes 21 (shown as an example with Q=16 electrodes) that can be placed on the skin of the subject at intervals, and a support 25 that holds the electrodes 21. The control unit 30 uses one or more sensors 20 and applies a predetermined current or voltage between the electrodes 21 of the sensor 20 while each electrode 21 is in contact with the skin of the subject.

[0018] The multiplexer has a function of determining a current application / voltage measurement pattern (or a voltage application / current measurement pattern). That is, two of the electrodes are selected, a current or a voltage is applied, and two of the electrodes are selected, and a voltage or a current is measured, as will be described later in connection with the phase angle fluctuation measurement unit 10.

[0019] When applying current, the current is applied and the voltage is measured based on a predetermined current application / voltage measurement pattern (a pattern in which two electrodes are selected in turn from a large number of electrodes, a current is applied, and the voltage is measured in sequence).When applying voltage, the voltage is applied and the current is measured based on a predetermined voltage application / current measurement pattern (a pattern in which two electrodes are selected in turn from a large number of electrodes, a voltage is applied, and the current is measured in sequence).

[0020] Hereinafter, when a current is applied and a voltage is measured, the features of the present invention will be described mainly with respect to the current application and voltage measurement pattern, and a detailed description of the case when a voltage is applied and a current is measured may be omitted.

[0021] Examples of current application and voltage measurement patterns include the adjacent electrode method, the counter electrode method, and the reference method.

[0022] The control unit 30 may use, for example, a CPU to execute a predetermined program and control the multiplexer and the current application device (or the voltage application device, or the impedance analyzer).

[0023] Here, the number Q of the electrodes 21 is, for example, 3 or more, and preferably 8 or more. There is no particular upper limit, but the number Q of the electrodes 21 is preferably 32 or less. The number Q of the electrodes 21 may be 16 or less. To improve the accuracy of the concentration distribution, a larger number of electrodes is preferable. The arrangement positions of the electrodes 21 are not particularly limited. The electrodes 21 may be arranged so as to surround the subject (here, around the legs), or some of the electrodes may be arranged unevenly without surrounding the subject, and the electrode spacing may be uniform or uneven. Such electrode bias and unevenness are corrected in the calculation of the Jacobian matrix, which will be described later.

[0024] The electrodes 21 are electrically connected to the control unit 30. The material and shape of the electrodes 21 are not particularly limited as long as they can apply a current or voltage to the skin of the subject. Examples of materials for the electrodes 21 include metals such as Au, Ag, Cu, and stainless steel, conductive polymers, fibers whose surfaces are coated with metals, and fibers whose surfaces are coated with conductive polymers. The shape of the electrodes 21 in a plane perpendicular to the direction of current application so that each electrode 21 comes into contact with the skin is not particularly limited, but may be, for example, circular or polygonal. The electrodes 21 are preferably non-invasive electrodes.

[0025] The method for electrically connecting the electrodes 21 and the control unit 30 is not particularly limited, and any known electrical connection method can be used. In this embodiment, each electrode 21 and the control unit 30 are connected by an electric wire 41.

[0026] The support 25 is not particularly limited as long as it can hold the electrodes 21. It is preferable that the support 25 be capable of placing the electrodes 21 on the skin of the subject. Here, "capable of being placed on the skin of the subject" means that each electrode 21 is placed so as to come into contact with the skin when the subject wears the sensor 20.

[0027] The support 25 preferably allows a predetermined pressure to be applied to the electrode 21 so that the electrode 21 can be tightly attached to the subject. This improves the adhesion between the electrode 21 and the subject, allowing for more accurate application of current or voltage and measurement of voltage or current. The material of the support 25 is not particularly limited, and is preferably an insulating material such as elastomer, leather, or cloth. The shape of the support 25 is not particularly limited, and examples thereof include a band shape.

[0028] (Phase Angle Fluctuation Measurement Unit 10) The phase angle fluctuation measurement unit 10 will be described with reference to FIG. 2. The phase angle fluctuation measurement unit 10 measures a feature value obtained based on the fluctuation of the phase angle in the current-applied voltage measurement pattern or the voltage-applied current measurement pattern. As described above with reference to the control unit 30, the phase angle fluctuation measurement unit 10 selects two of the electrodes according to the current-applied voltage measurement pattern (or voltage-applied current measurement pattern) determined by the multiplexer, measures the voltage or current, and measures, for example, the phase angle difference. This is a major feature of the local biological tissue evaluation device 100 according to this embodiment. The phase angle difference is an example of the feature value. The phase angle fluctuation measurement unit 10 includes, for example, a voltage measurement device (not shown) and a current measurement device (not shown) that can accurately measure the temporal changes in voltage and current, and measures the phase angle difference. The voltage measurement device and the current measurement device may be an impedance analyzer. An impedance analyzer is a device that measures the measurement voltage (applied voltage) and the applied current (measurement current) by changing the applied frequency and amplitude, and then measures the phase angle difference. In particular, the ratio (V / I) of the measured voltage V to the applied current I is called impedance Z, its real part is called resistance Z', and its imaginary part is called reactance Z'', and these terms will be used hereafter in the explanation.

[0029] Here, a method for measuring the measured phase angle difference Δθm will be described with reference to FIG. 3. FIG. 3 is a flowchart showing the flow of measuring the measured phase angle difference Δθm based on a current application voltage measurement pattern. First, an application current pattern (1≦m≦M) is set (S101), and at least two application frequencies (low frequency is f ０ , and high frequency is denoted as f), and low frequency f ０ The applied current I ｍ (f ０ ) and a low frequency f ０ The measured voltage V ｍ (f ０ ) is measured (S102), and further, the applied current I ｍ (f) and measure the voltage V ｍ At this time, a time lag occurs between the applied current and the measured voltage, and as a result, the low frequency f ０ Resistance Z' ｍ (f ０ ) and low frequency f ０ Reactance Z'' ｍ (f ０ ), and the resistance Z' at high frequency f ｍ (f) and the reactance Z'' at high frequency f ｍ (f) is calculated (S104, S105). Next, the phase angle calculation formula θ m =tan －１ (Z'' m / Z' m ) using low frequency f ０ Measured phase angle θ ｍ (f ０ ) and the measured phase angle θ of high frequency f ｍ (f) is calculated (S106, S107, S108). ０ Measured phase angle θ ｍ (f ０ ) and the measured phase angle θ of high frequency f ｍ From (f), the measured phase angle difference Δθm Δθ ｍ = θ ｍ (f) -θ ｍ (f ０) is measured (S109). A major feature of this embodiment is that the measured phase angle difference Δθm is measured in this manner.

[0030] Below, an example will be described in which voltage is measured using the adjacent method in the local biological tissue evaluation device 100 of this embodiment. Note that, although the following describes an example of measurement using one sensor 20, measurement can also be performed in the same way when two or more sensors 20 are used.

[0031] The phase angle variation measurement unit 10 may control the control unit 30 internally only to perform the impedance measurement, or may control the control unit 30 in accordance with a program executed by the calculation evaluation unit 50 to perform the impedance measurement. The results of the impedance measurement are sent to the calculation evaluation unit 50. There are no particular limitations on the method of transmitting information to the calculation evaluation unit 50. The information may be sent from the control unit 30 to the calculation evaluation unit 50 via a wire, or may be sent to the calculation evaluation unit 50 via other transmission means.

[0032] (Phase Angle Jacobian Matrix Creation Unit 51) The phase angle Jacobian matrix creation unit 51 creates a phase angle Jacobian matrix based on a current application / voltage measurement pattern or a voltage application / current measurement pattern. Φ This is a flowchart for creating J. The phase angle Jacobian matrix (phase angle sensitivity matrix) is a sensitivity matrix that indicates, as an angle, how much the measured voltage when a current is applied (or the measured current when a voltage is applied) delays or advances in time relative to changes in the spatially distributed electrical properties (conductivity, permittivity) relative to a reference, and must be determined in advance as a known value. The phase angle Jacobian matrix of a subject varies depending on the spatial distribution of the subject's electrical properties and body shape, etc., and if the subject's phase angle Jacobian matrix is ​​known, the phase angle distribution can be calculated.

[0033] As shown in Figure 4, the phase angle Jacobian matrix ΦThe procedure for creating J involves first creating mesh coordinates obtained by dividing the contour ∂Ω of the subject's measurement location and the internal body Ω, which have been measured or estimated in advance (S201). Here, the internal body of the subject refers to the size of muscle compartments, bones, fat, etc., inside the limbs, inside the trunk, etc. The contour ∂Ω and the internal body Ω may be created using (1) pre-taken X-ray images or MRI images of the subject's own internal body, such as the limbs or trunk, as the basis. Alternatively, (2) mesh coordinates may be created using an X-ray image or MRI image database of average internal body images, such as the limbs or trunk, taking into account gender, nationality, age, weight, height, BMI, etc., as the basis. Furthermore, (3) the X-ray image or MRI image database of (2) may be customized based on the subject's own characteristics, such as BMI, to create mesh coordinates assuming that it is an X-ray image or MRI image of the subject's own internal body.

[0034] Next, a current application / voltage measurement pattern (or voltage application / current measurement pattern) is determined based on the contour ∂Ω (S202). There are m (1≦m≦M) possible patterns for selecting two electrodes for applying current and two electrodes for measuring voltage, where M is the total number of measurement patterns. The relationship between m and the superscripts i, j, k, and l, which will be used hereinafter, will be described. These letters i, j, k, and l indicate that a current is applied between the i-th and j-th electrodes and a voltage is measured between the k-th and l-th electrodes, and this pattern is called the m-th measurement pattern.

[0035] Next, the resistance Jacobian matrix Ｚ’ J and the reactance Jacobian matrix Ｚ’’ J is created (S203, S204). Here, the reactance Jacobian matrix in the n-th mesh in the m-th application measurement pattern is Ｚ’’ J ｍ ｎ and the resistance Jacobian matrix Ｚ’ J ｍ ｎThere are various methods for calculating this, but the Gesselowitz formula shown in the following equation (1) can be used. Here, Z on the left side represents impedance, which is a complex number, and includes its resistance component (the real part of the complex impedance) Z' and its reactance component (the imaginary part of the complex impedance) Z''. n represents the mesh number, and i, j, k, and l correspond to the mth measurement pattern. Referring to Figure 5 described below, i and j are electrodes to which current is applied, and k and l are electrodes to which voltage is measured.

[0036] Furthermore, on the right side of the following equation (1), u indicates the electric potential of each mesh number n, ∇ is called a differential operator (nabla) and indicates differentiation in space, and u(I ｉ，ｊ ) is the distribution of the potential in the field when a current is applied between the i-th and j-th electrodes, and u(I ｋ，ｌ ) is the distribution of the electric potential in the field when a current is applied between the kth and lth electrodes. I ｉ，ｊ is the i-th electrode e ｉ and the jth electrode e ｊ (i=1, 2, ..., E-1, j=i+1, i+2, ..., E (i≠j)) is the applied current between ｋ，ｌ is the kth electrode e ｋ and the lth electrode e ｌ ∇u(I ｉ，ｊ ) and ∇u(I ｋ，ｌ ) means the gradient of each potential (i.e., the electric field), which is a vector value, and · indicates the dot product, so this operation becomes a scalar value. By integrating this scalar value with the bio-cross-sectional field Ω, the resistance Jacobian matrix Ｚ’ J ｍ ｎ , and the reactance Jacobian matrix Ｚ’’ J ｍ ｎ In the above formula (2), Ω may be a two-dimensional region or a three-dimensional region, and in the case of a two-dimensional region, the integral represents a surface integral, and in the case of a three-dimensional region, the integral represents a volume integral.

[0037] Finally, the phase angle Jacobian matrix Φ J ｍｎ Here, the element of the phase angle Jacobian matrix in the nth mesh in the mth measurement pattern is created (S205). Φ J ｍ ｎ There are several methods for calculating the reactance Jacobian matrix. Ｚ’’ J ｍ ｎ is the resistance Jacobian matrix Ｚ’ J ｍ ｎ The method of dividing by the phase angle Jacobian matrix element in the nth mesh in the mth measurement pattern will be explained. Φ J ｍ ｎ is expressed by the following formula (2).

[0038]

[0039] As described above, the phase angle Jacobian matrix creation unit 51 creates an equation relating the mesh coordinates of the subject's measurement location and the nth mesh in the mth measurement pattern, and derives the current, potential, and phase angle of impedance, which is the ratio of the voltage to the current, at each mesh coordinate as elements of the phase angle Jacobian matrix as a solution of the equation. The above is about the elements of the phase angle Jacobian matrix in the nth mesh in the mth measurement pattern, and by repeating this, the phase angle Jacobian matrix of Ω inside the subject's body can be calculated. Φ For all meshes n (1≦n≦N) and measurement patterns m (1≦m≦M), the elements of the phase angle Jacobian matrix in Eq. Φ J ｍ ｎ is obtained, the phase angle Jacobian matrix Φ J can be expressed as a matrix as shown in the following formula (3), and the nth mesh in the following formula (3) Φ J ｎ is expressed by the following formula (4). Formula (4) is a column vector Φ Jn, and T in equation (4) means transposition.

[0040]

[0041] Phase angle Jacobian matrixΦ Regarding the method of using J, it is possible to predict and calculate many shapes and positions of muscle compartments in advance and store them as a database, and then select the appropriate phase angle Jacobian matrix from the database. Φ Alternatively, some phase angle Jacobian matrices may be selected from a database using machine learning or the like. Φ Combine J to create a new phase angle Jacobian matrix Φ Furthermore, the subject's own phase angle Jacobian matrix J may be created on the spot without using a database. Φ The generated phase angle Jacobian matrix J may be generated. Φ J is sent to the local biological tissue evaluation unit 60 via the image reconstruction unit 52. In the following explanation, the calf is used as an example, but the present invention is not limited to analysis of the inside of the calf.

[0042] As in the method for creating mesh coordinates described in (1) above, the phase angle Jacobian matrix is ​​calculated based on an MRI image of the subject's calf taken in advance. Φ For example, let us consider the method of creating J, the phase angle Jacobian matrix, Φ A method for creating the J will now be described. FIG. 5( a) is an MRI cross-sectional image of a subject's calf showing the cross-sectional structure of the calf. From this image, the mesh numbers and positions of the contour ∂Ω and the internal body Ω are determined according to (S201) in FIG. 4. FIG. 5( b) is a diagram showing the classification of the cross-sectional positions of elements within the calf from the image of FIG. 5( a). As shown in FIG. 5( b), the calf is composed of skin, fat, bone, and four broad compartments. In detail, to evaluate the quality of local tissue in the calf, it is preferable to classify the four compartments as follows: first compartment (gastrocnemius), second compartment (soleus), third compartment (tibialis posterior, flexor digitorum longus, and flexor pollicis longus), and fourth compartment (anterior compartment, extensor digitorum longus, and peroneus longus), as shown in FIG. 5( b). Classification beyond these four compartments is also possible.

[0043] 5(c) is a diagram showing an example of the mesh numbers and positions of the electrodes 21 determined for the contour ∂Ω determined in (S201) according to (S202) in FIG. 4, and the determined mesh numbers and positions of the electrodes 21 inside the living body Ω. For example, based on the MRI image shown in FIG. 5(a), the electrode positions (indicated by ● marks) on the surface of the subject are determined, and a mesh is then created, as shown in FIG. 5(c). The electrode positions may be arranged at equal intervals on the surface of the living body, or may be arranged at non-equidistant intervals.

[0044] FIG. 5(d) shows the resistance Jacobian matrix of the calf in the m-th measurement pattern. Ｚ’ Specifically, for the mesh determined in (S202), frequency-dependent conductivity and permittivity are assigned to each of the first to fourth muscle compartments, and in accordance with (S203), the resistance Jacobian matrix of the resistance component of the impedance (the real part of the complex impedance) Z' is calculated using the above formula (1). Ｚ’ Looking for J.

[0045] FIG. 5(e) shows the reactance Jacobian matrix of the calf in the m-th measurement pattern. Ｚ’’ Specifically, for the mesh determined in (S202), frequency-dependent conductivity and permittivity are assigned to each of the first to fourth muscle compartments, and in accordance with (S204), the reactance Jacobian matrix of the reactance component of the impedance (the imaginary part of the complex impedance) Z″ is calculated using the above-mentioned equation (1). Ｚ’’ Looking for J.

[0046] FIG. 5(f) shows the phase angle Jacobian matrix of the calf in the m-th measurement pattern. Φ This is an example of J. According to (S205), the phase angle Jacobian matrix is ​​calculated using the above formula (2). Φ Looking for J.

[0047] FIG. 5(f) shows the phase angle Jacobian matrix of the calf in the m-th measurement pattern, and the phase angle Jacobian matrix of Equation (3) Φ J stores all M measurement patterns.

[0048] (Image Reconstruction Unit 52) ​​The image reconstruction unit 52 uses the feature amount and the phase angle Jacobian matrix measured by the phase angle variation measurement unit 10 to image the phase angle distribution inside the living body of the subject. For example, the phase angle Jacobian matrix creation unit image reconstruction unit 52 uses the measured phase angle difference Δθm and the phase angle Jacobian matrix Φ J ｎ The phase angle distribution Φ is visualized using the following equation (5): ｎ Here, based on the Gauss-Newton method, the phase angle Jacobian matrix Φ Although a method for imaging the phase angle distribution Φ using J will be described, the present invention is not limited to the Gauss-Newton method.

[0049] Phase angle distribution Φ of the i-th iteration by the Gauss-Newton method ｉ and the phase angle distribution Φ of the (i+1)th iteration ｉ＋１ The relationship between these is expressed by the following formula (6): In the following formula (6), R is a regularization matrix, λ is a relaxation coefficient scalar (for example, obtained by the L-curve method), Δθ is a measured phase angle difference expressed by the following formula (7), and the selected low frequency f ０ and the high frequency f. In the following equation (7), m (1≦m≦M) refers to the mth pattern among a total of M current application voltage measurement patterns (or voltage application current measurement patterns). The measured phase angle difference Δθm of the mth pattern is expressed by the following equation (8). In the present invention, as a preliminary step to evaluating the quality of local biological tissue, the phase angle distribution Φ inside the subject's living body is imaged. For example, taking muscle as an example of local biological tissue, when there is little intramuscular fat and high muscle density, the value of the phase angle distribution Φ is large, and therefore, a muscle compartment with an overall large phase angle distribution Φ can be evaluated as having higher muscle quality. This is merely a case where muscle is used as an example of local biological tissue, and the evaluation of local biological tissue quality based on phase angle difference can be appropriately modified depending on the local biological tissue of interest.

[0050]

[0051] The phase angle distribution Φ of the subject imaged by the image reconstruction unit 52 is sent to the local biological tissue evaluation unit 60 .

[0052] (Local biological tissue evaluation unit 60) The local biological tissue evaluation unit 60 includes at least one of a local biological tissue aging evaluation unit 53, a local biological tissue fat infiltration evaluation unit 54, and a local biological tissue cross-sectional area evaluation unit 55. Each unit of the local biological tissue evaluation unit 60 will be described below. In the following, muscle is sometimes described as an example of biological tissue, but the present invention is not limited to muscle. Furthermore, when muscle is used as an example, the terms muscle aging and muscle cross-sectional area may be used, but in the present invention, these can be replaced with the general terms aging and cross-sectional area.

[0053] (Local biological tissue aging evaluation unit 53) In order to quantitatively evaluate muscle aging (MA), the local biological tissue aging evaluation unit 53 calculates the spatial average of the phase angle distribution Φ from the phase angle distribution Φ obtained by imaging. For example, the spatial average of the phase angle distribution Φ (spatial average phase angle <Φ>) may be calculated using the following formula (9). Hereinafter, the symbol < > may be used to indicate the spatial average. In this formula (9), n indicates the mesh number, and N indicates the sum of the meshes. Depending on the magnitude of the spatial average phase angle <Φ>, muscle aging, which is an index of muscle quality, can be evaluated at the local position where the sensor is placed, rather than globally as in the conventional method.

[0054] (Local biological tissue fatty infiltration evaluation unit 54) To quantitatively evaluate fatty infiltration (FI), the local biological tissue fatty infiltration evaluation unit 54 assigns the phase angle distribution Φ of the subject imaged by the image reconstruction unit 52 to each local biological tissue of the subject. For example, when evaluating local fatty infiltration (FI) in muscle compartments, the phase angle distribution Φ is assigned to each muscle compartment. The method of assignment to each local biological tissue will be explained using the following formula (10). In this formula (10), the subscript p (1≦p≦P) is the compartment number, and as mentioned above, taking the calf compartment as an example, P (the maximum value of p) is preferably about 4, and specifically, p=1 can be the first compartment (gastrocnemius), p=2 the second compartment (soleus), p=3 the third compartment (tibialis posterior, flexor digitorum longus, and flexor pollicis longus), and p=4 the fourth compartment (anterior, extensor digitorum longus, and peroneus longus). pis the mesh number in the pth compartment, and N p indicates the total number of meshes in the p-th compartment. The local biological tissue fatty infiltration evaluation unit 54 preferably assigns a phase angle distribution Φ to each local biological tissue (for example, a calf compartment) as in equation (10) and calculates the spatial average of the phase angle distribution Φ within each local biological tissue (for example, within a compartment). When evaluating fatty infiltration within a compartment, the local biological tissue fatty infiltration evaluation unit 54 calculates the spatial average of the phase angle distribution Φ within each local biological tissue (for example, within a compartment) as in equation (11) below. p＝１ >,<Φ p＝２ >,<Φ p＝３ >, and <Φ p＝４ The local tissue fatty infiltration evaluation unit 54 can evaluate the quality of each local tissue by calculating the phase angle distribution Φ p and the spatial average phase angle of each local biological tissue < Φ p > to at least one of the local biological tissue cross-sectional area evaluation unit 55 and the output unit 56.

[0055]

[0056] (Local biological tissue cross-sectional area evaluation unit 55) In order to quantitatively evaluate the biological tissue cross-sectional area ratio, the local biological tissue cross-sectional area evaluation unit 55 calculates the local biological tissue phase angle distribution Φ p A binarization process is performed on the local biological tissue cross-sectional area ratio to calculate the local biological tissue cross-sectional area ratio. The binarization process for the local biological tissue cross-sectional area ratio is not particularly limited to a particular type. Examples of binarization processes include Otsu's binarization method, Kittler-Illingworth method, K-means method, and fuzzy clustering method. Here, a method for calculating the local biological tissue cross-sectional area ratio by binarization process based on Otsu's binarization method will be described as an example. Otsu's binarization method is a problem of finding a threshold value that minimizes the intra-class variance, which is defined as the weighted sum of the variances of two classes.

[0057] Fig. 6 shows the phase angle distribution Φ p and its binary phase angle distribution Φ p The symbol ^ indicates binarization. The phase angle distribution Φ in the pth section is shown in Fig. p From the binarized phase angle distribution Φp First, let us consider the process of calculating the optimal threshold ε ＊ and calculate the optimum threshold value ε as shown in the following formula (12): ＊ Based on this, n in the p-th partition p Φ in the mesh p The value of n is converted into two values ​​(a high-intensity phase angle value and a low-intensity phase angle value). p is the nth mesh number in the pth partition, 1≦n p ≦N p The optimal threshold ε ＊ Before calculating, we will explain the count function α. ​​For example, the count function α has two arguments. The first is Φ p is a function that counts the total number of meshes in α(Φ p ^{Φn p <ε}) and is called the first counting function. The second is Φ, which is larger than ε. p is a function that counts the total number of meshes in α(Φ p ^{Φn p >ε}) and is called the second counting function. That is, the first counting function α is expressed as Φn p < Φ when ε p The second count function α indicates the total number of meshes, and Φn p Φ when >ε p Next, we will explain the intensity variance γ(ε) as a function of the threshold variable ε. The threshold variable ε in ( ) indicates that it is a function of γ. The intensity variance γ is expressed by the following formula (17). α in formula (17) ０ (ε) is expressed by the following formula (13), which is the first count function α divided by the total number of meshes in the p-th section, and is a weight indicating the mesh occupancy rate that indicates ε or less. １ (ε) is expressed by the following formula (15), and is the second count function α divided by the total number of meshes in the pth section, and is a weight indicating the mesh occupancy rate indicating ε or more. β0(ε) in formula (17) is expressed by the following formula (14), and indicates the class variance indicating ε or less. β in formula (17) １(ε) is expressed by the following formula (16) and indicates the class variance indicating ε or more. Ultimately, the intensity variance γ(ε) as a function of the threshold variable ε is expressed by the following formula (17).

[0058]

[0059] Optimal threshold ε ＊ is expressed by the following equation (18), for example, using the intensity variance γ(ε). In this case, the threshold variable ε that maximizes the sum of the squares of the intensity variance γ(ε) is defined as the optimal threshold ε. ＊ Here, the threshold variable ε is expressed as ε = xΔε using an appropriately determined small threshold Δε and the number of steps x (1≦x≦X), and ε can take a value of (0≦ε≦1). Finally, the binary phase angle distribution Φ p From the above, the local tissue cross-sectional area ratio (here, the local muscle cross-sectional area ratio) φ is calculated using the following formula (19): A in the following formula (19) is a function that converts the number of meshes in ( ) into an area, and Φn in ( ) of the numerator p ≧ε ＊ indicates the number of meshes showing the phase angle distribution of high intensity in the pth section, and Φ in the ( ) of the denominator Ｎｐ indicates the total number of meshes in the p-th section. Consequently, the left side of this equation φ indicates the cross-sectional area ratio of the local biological tissue. This cross-sectional area ratio φ of the local biological tissue is sent to the output unit 56.

[0060]

[0061] (Output unit 56) The output unit 56 outputs the spatial average phase angle <Φ> calculated by the local biological tissue aging evaluation unit 53, the phase angle distribution Φ of the local biological tissue calculated by the local biological tissue fatty infiltration evaluation unit 54, and the spatial average phase angle <Φ> of the local biological tissue aging evaluation unit 53. p and the spatial average phase angle of each local biological tissue < Φ p >, and output at least one of the cross-sectional area ratios of the local biological tissue calculated by the local biological tissue cross-sectional area evaluation unit 55. The output destination may be a display unit such as a liquid crystal display, or a storage device such as a HDD.

[0062] (Local biological tissue evaluation method) Next, a local biological tissue evaluation method using the local biological tissue evaluation device 100 will be described. Fig. 7 shows a flowchart of the local biological tissue evaluation method according to this embodiment. The local biological tissue evaluation method according to this embodiment uses a sensor including a plurality of electrodes 21 that can be placed on the skin of a subject at intervals from one another, applies a current or voltage between the electrodes 21 with each electrode 21 in contact with the skin of the subject, measures the voltage based on a current-application-voltage measurement pattern when applying a current, or measures the current based on a voltage-application-current measurement pattern when applying a voltage between the electrodes 21, and measures a feature amount, for example, a measured phase angle difference Δθ, obtained based on the amount of variation in the phase angle for the current-application-voltage measurement pattern or the voltage-application-current measurement pattern in a first step S301; and calculates a phase angle Jacobian matrix Δθ based on the current-application-voltage measurement pattern or the voltage-application-current measurement pattern. Φ A second step S302 of creating J, and calculating the measured phase angle difference Δθ and the phase angle Jacobian matrix Φ and a third step S303 of imaging the phase angle distribution Φ inside the living body of the subject from J. The local living tissue evaluation method according to this embodiment may further include a fourth step S304 of evaluating the local living tissue using the imaged phase angle distribution Φ.

[0063] (First Step S301) In the first step S301, the impedance of the subject is measured using the phase angle variation measurement unit 10. Specifically, a sensor including multiple electrodes that can be placed on the subject's skin at intervals is used, and with each electrode 21 in contact with the subject's skin, a current or voltage is applied between each electrode 21. When a current is applied, the voltage is measured based on a current application / voltage measurement pattern, and when a voltage is applied between each electrode 21, the current is measured based on a voltage application / current measurement pattern. Then, the measured phase angle difference Δθ is measured.

[0064] (Second Step S302) In the second step S302, a phase angle Jacobian matrix is ​​generated using the phase angle Jacobian matrix generator 51 based on the current application voltage measurement pattern or the voltage application current measurement pattern. Φ Create a J.

[0065] (Third Step S303) In the third step S303, the measured phase angle difference Δθ measured in the first step and the phase angle Jacobian matrix obtained in the second step are Φ From J, the image reconstruction unit 52 is used to image the phase angle distribution Φ inside the subject's living body.

[0066] (Fourth Step S304) In the fourth step, the biological tissue is evaluated using the phase angle distribution imaged in the third step. In the fourth step, for example, at least one of the following three processes is performed.

[0067] (First Processing S304A of Fourth Step) In the first processing S304A of the fourth step, muscle aging is evaluated from the phase angle distribution Φ obtained in the third step S303 using the local biological tissue aging evaluation unit 53 (muscle aging (MA) evaluation). In this processing, the spatial average of the phase angle distribution Φ may be calculated from the phase angle distribution Φ inside the subject's living body.

[0068] (Second Processing S304B of Fourth Step) In the second processing S304B of the fourth step, the local biological tissue fatty infiltration evaluation unit 54 is used to assign the phase angle distribution Φ obtained in the third step S303 to each local biological tissue of the subject, thereby obtaining a local biological tissue phase angle distribution Φ p (local fatty infiltration (FI) evaluation). This allows local fatty infiltration (FI) to be evaluated. The phase angle distribution Φ of the local biological tissue p From the phase angle distribution Φ of the local tissue p The spatial average of may be calculated.

[0069] (Third process S304C of fourth step) In the third process S304C of the fourth step, the local tissue cross-sectional area evaluation unit 55 performs binarization processing on the phase angle distribution of the local tissue, and then calculates the local tissue cross-sectional area ratio (local muscle cross-sectional area (CSA) evaluation). This allows the local muscle cross-sectional area (CSA) to be evaluated.

[0070] The above has described the local biological tissue evaluation device 100 and local biological tissue evaluation method according to this embodiment. The local biological tissue evaluation device and local biological tissue evaluation method according to this embodiment evaluate local biological tissue by contacting electrodes with the skin of a subject, and are therefore minimally invasive, inexpensive, and simpler than conventional methods.

[0071] According to the local biological tissue evaluation device and local biological tissue evaluation method of this embodiment, it is possible to obtain the phase angle distribution and the spatial average of the phase angle distribution inside the subject's living body, so that it is possible to quantitatively evaluate, for example, the state of muscle aging.

[0072] According to the local biological tissue evaluation device and local biological tissue evaluation method of this embodiment, it is possible to obtain the spatial average of the phase angle distribution of each local biological tissue, and therefore it is possible to quantitatively evaluate, for example, the state of local fat infiltration in each muscle compartment.

[0073] According to the local biological tissue evaluation device and local biological tissue evaluation method of this embodiment, the cross-sectional area of ​​the local biological tissue of a subject can be obtained, and therefore, for example, the local muscle cross-sectional area ratio of each muscle compartment can be quantitatively evaluated.

[0074] The local biological tissue evaluating device 100 includes the local biological tissue aging evaluating unit 53, the local biological tissue fatty infiltration evaluating unit 54, and the local biological tissue cross-sectional area evaluating unit 55, but it does not have to include the local biological tissue fatty infiltration evaluating unit 54 and the local biological tissue cross-sectional area evaluating unit 55. Furthermore, the local biological tissue evaluating unit 60 only needs to have a function according to the biological tissue.

[0075] In the local biological tissue evaluation method according to this embodiment, the fourth step S304 includes the first step S304A, the second step S304B, and the third step S304C, but any one of these steps may be included. For example, the second step S304B and the third step S304C may not be included.

[0076] (Example) Next, an example of an experiment using the local biological tissue evaluation device shown in FIG. 1 will be described in order to verify the effectiveness of the local biological tissue evaluation device of the present disclosure, but the present invention is not limited to the following experimental example.

[0077] (Experimental Example 1) First, a simulation was performed. Figure 8 shows the structure of the muscle used in the simulation of muscle quality evaluation. Here, the muscle was divided into four compartments: the first compartment (gastrocnemius), the second compartment (soleus), the third compartment (tibialis posterior, flexor digitorum longus, flexor pollicis longus, etc.), and the fourth compartment (anterior, extensor digitorum longus, and peroneus longus). Figure 8(a) is a schematic cross-sectional view of a high-quality muscle with little intramuscular fat. Figure 8(b) is a schematic cross-sectional view of a low-quality muscle with much intramuscular fat.

[0078] A simplified Maxwell's equation was used for the simulation. The equations used are the following equations (20) and (21). In the following equations (20) and (21), E [V / m] is the electric field, Φ [V] is the electric potential, ω [rad / s] is the applied angular frequency, which is 2πf (f [Hz] is the applied frequency), and ε [F / m] is the dielectric constant. The following equations (22) to (25) were used as boundary conditions. In the following equations (22) to (25), ∂Ω ｃａｌｆ is the boundary of the calf other than the cross section surrounded by the electrodes. ０ [A] is the electrode current, and n is the boundary normal vector. ｅ is the electrode boundary. ∂Ω ｅｉ and ∂Ω ｅｊ is the boundary between the i-th electrode and the j-th electrode.

[0079]

[0080]

[0081] FIG. 9 shows a phase angle distribution image Φ calculated using the local biological tissue evaluation device of the present disclosure. FIG. 9(a) is a phase angle distribution image for high-quality muscle calculated from the schematic cross-sectional view of FIG. 8(a), and FIG. 9(b) is a phase angle distribution image for low-quality muscle calculated from the schematic cross-sectional view of low-quality muscle in FIG. 8(b). In this figure, higher brightness indicates higher phase angles; that is, as shown in FIG. 9, it is possible to visualize the location of high-quality muscle in each muscle compartment. Furthermore, to quantitatively evaluate muscle quality, the spatially averaged phase angle of each muscle compartment was calculated. The obtained results are shown in FIG. 10. In FIG. 10, <Φ> is the overall spatially averaged phase angle, and <Φ ｐ1 > is the spatially averaged phase angle of the first compartment, and <Φ ｐ２ > is the spatially averaged phase angle of the second compartment, and <Φ ｐ３ > is the spatially averaged phase angle of the third compartment, and <Φ ｐ４ Φ is the spatially averaged phase angle of the fourth compartment. Also, "High Quality" in the figure refers to the high-quality muscle shown in Figures 8(a) and 9(a), and "Low Quality" refers to the low-quality muscle shown in Figures 8(b) and 9(b). In Figure 10, muscle quality can be quantitatively evaluated, i.e., <Φ>, <Φ ｐ1 >,<Φ ｐ２ >,<Φ ｐ３ >,<Φ ｐ４ >It is possible to quantitatively determine which muscle compartments have more or less high-quality muscle.

[0082] FIG. 11 shows a binarized phase angle distribution image Φ calculated using the local biological tissue cross-sectional area evaluation unit of the present disclosure. p ^, where high phase angles are shown in black. Figure 11(a) is a phase angle distribution image for high-quality muscle, and Figure 11(b) is a phase angle distribution image for low-quality muscle. In Figure 11, it was confirmed that the black areas (areas with high phase angles) increased in the case of high-quality muscle. For quantitative evaluation, the local muscle cross-sectional area ratio (CSA ratio) between each compartment was calculated using equation (19). The results are shown in Figure 12. As shown in Figure 12, the high-quality muscle exhibited higher CSA ratios in all cases of the first, second, third, and fourth compartments.

[0083] (Experimental Example 2) Figure 13 shows a schematic diagram of the equipment used in Experimental Example 2. This experimental equipment includes an impedance analyzer (HIOKI IM 3570) as a current-voltage measurement unit, a 6-channel multiplexer, an analog multiplexer / demultiplexer, a sensor (EIT sensor), and a personal computer as a calculation and evaluation unit. The impedance analyzer's four ports (Lc, Lp, Hp, and Hc) were expanded to 16 ports. Coaxial cables were used to connect the 16-channel multiplexer and the 16 electrodes in the EIT sensor. The complex impedance measured by the impedance analyzer was transmitted to the PC via USB communication.

[0084] Fourteen healthy subjects without musculoskeletal disorders (male, age 30±7 years, height 173.5±6.5 cm, BMI: 32.2±10.4 kg / m) were recruited. ２ This experiment was conducted on the subject. The measurement protocol consisted of two stages: the first stage was a stage in which measurements were made using the local biological tissue evaluation device of the present disclosure, and the second stage was a stage in which measurements were made using an ultrasound system (manufactured by GE Healthcare) for comparison. All measurements were taken with the subject in a seated position.

[0085] 14 shows phase angle distribution images Φ for 14 subjects calculated by the phase angle Jacobian matrix creation unit 51 and the local biological tissue aging assessment unit 53, and are labeled S1 to S14 in order of age starting from the youngest subject. In this figure, whiter areas indicate higher phase angles, and darker areas indicate lower phase angles, making it possible to see which locations in which muscle compartments are of high quality.

[0086] Figure 15 shows the spatially averaged phase angle <Φ> for each subject calculated using equation (9), with the values ​​indicated by the squares and the y-axis on the left. Although there are individual differences, younger subjects generally tend to have higher Φ values ​​than older subjects. For reference, the global phase angle calculated using a body composition analyzer (product name: InBody S20) is indicated by the circles and the y-axis on the right. Although there are individual differences, a similar trend can be seen.

[0087] Figure 16 shows ultrasound images of the calf of each subject. The area surrounded by the dashed line represents a representative region of the first compartment (gastrocnemius muscle), with white to gray representing fat and black representing muscle fibers. Using these ultrasound images, local fat infiltration (uFI) and local muscle cross-sectional area (uCSA) were calculated (u represents ultrasound). uFI is defined as the ratio of the number of meshes representing muscle fibers to the number of meshes occupied by fat in the ultrasound image. A low uFI value indicates a low proportion of fat and high muscle quality, while a high uFI value indicates a high proportion of fat and low muscle quality. uCSA is the number of black muscle fiber meshes relative to the number of meshes in the area surrounded by the dashed line in the ultrasound image of Figure 16. A high uCSA value indicates a high proportion of muscle fibers and high muscle quality.

[0088] FIG. 17 shows the spatially averaged phase angle of the first compartment of each subject. ｐ1 >, the spatially averaged phase angle of the second compartment <Φ ｐ２ >, spatially averaged phase angle of the third compartment <Φ ｐ３ >, spatially averaged phase angle of the fourth muscle compartment <Φ ｐ４ > shows the local fat infiltration uFI obtained from ultrasound images. This figure shows which muscle compartments have high phase angles in each subject. Although there are individual differences, this tendency tends to decrease with age, which is reasonable considering the general aging phenomenon. On the other hand, in the ultrasound images, the youngest subject had the fewest gray meshes, and uFI increased with age, although there were individual differences. These results were qualitatively consistent with the results of the phase angle images.

[0089] Looking at the details further, ｐ1 The average value of 0.29 for Φ was the highest in each compartment. This is thought to be because the first compartment has the largest muscle fibers that generate muscle force. ｐ３ > was the lowest value. This is presumably because the muscle fibers in the third compartment are small. Although there are individual differences, the uFI value increased with age. This is thought to be due to an increase in fat in the muscle. The spatial average phase angle of the first muscle compartment <Φ ｐ1 >, the spatially averaged phase angle of the second compartment <Φ ｐ２ >, spatially averaged phase angle of the third compartment <Φｐ３ >, spatially averaged phase angle of the fourth muscle compartment <Φ ｐ４ Although there were individual differences, the trend in the results was similar to that of local fatty infiltration uFI obtained from ultrasound images.

[0090] Figure 18 shows binarized phase angle images for each subject calculated using the local tissue cross-sectional area evaluation unit of the present disclosure. In this figure, gray indicates positions with low phase angles, and black indicates positions with high phase angles. As shown in Figure 18, it can be seen qualitatively that younger subjects have the largest black mesh areas.

[0091]

[0092] Among the three muscle quality indices, we focus on regional muscle aging (MA). Table 1 shows the results of an independent t-test on the spatially averaged phase angle (Φ) between the young and older subject groups. The null hypothesis was that the values ​​of Φ were equal for the young and older subject groups. Because t = 3.9544 > 0 was greater than t = 0.025(12) = 2.1790, the null hypothesis was rejected. As a result, we can conclude that Φ is significantly associated with regional muscle aging (n = 14, p < 0.001) in the young subject group (age ≤ 30) and the older subject group (age > 30). Furthermore, the Φ of the young subject group was significantly higher than that of the older subject group.

[0093]

[0094] Among the three muscle quality indices, we will focus on and discuss the local fatty infiltration (FI). Table 2 shows that the spatial average phase angle of each muscle compartment was < Φ between the young and older subject groups. p The results of an independent t-test are shown for the younger and older subject groups, respectively, for the younger group and the older group, respectively, and for the ultrasound-based focal fat infiltration (uFI). p The t values ​​of each muscle compartment (<Φ ｐ1 >=3.4412>0,<Φ ｐ２ >=2.2478>0,<Φ ｐ３ >=2.9055>0,<Φ ｐ４>=3.2504>0) was greater than t0.025(12)=2.1790. Furthermore, the null hypothesis that the uFI values ​​of the younger and older subject groups are equal was rejected because the uFI t-value -4.2448<0 was less than t0.025(12)=2.1790. From the above results, <Φ p It can be concluded that <Φ> and uFI were significantly associated with local muscle aging in both young (age ≤ 30) and older (age > 30) subject groups (n = 14, p < 0.05). Furthermore, <Φ> in the younger subject group was significantly higher than in the older subject group. In contrast, uFI in the younger subject group was significantly lower than in the older subject group.

[0095]

[0096] Among the three muscle quality indices, we will focus on the local muscle cross-sectional area (CSA) and discuss it. The subjects were divided into two groups, a young group and an older group, and the local muscle cross-sectional area (CSA) obtained by the local biological tissue evaluation method of the present invention was compared between the two groups. φＭ An independent t-test was performed on the ultrasound muscle area uCSA. Table 3 shows the results of the independent t-test. The null hypothesis was that the φ p The value of t for each compartment (φ ｐ1 =3.4412>0,φ ｐ２ =2.2478>0,φ ｐ３ =2.9055>0,φ ｐ４ = 3.2504 > 0) was greater than t0.025(12) = 2.1790. Also, the t-value of uCSA, 2.8216 > 0, was greater than t0.025(12) = 2.1790. Therefore, the null hypothesis that the uCSA values ​​of the younger and older subject groups are equal was rejected. φ p It can be concluded that uCSA and uCSA are significantly associated with local muscle aging (n=14, p<0.05) in the younger subject group (age ≤ 30) and the older subject group (age > 30). Furthermore, φ in the younger subject group pand uCSA were significantly higher than those in the older subject group.

[0097] The above results confirmed that there is a high correlation between the age of the subject group and muscle aging (MA), local fatty infiltration (FI), and local muscle cross-sectional area (CSA). Generally, the younger the subject, the higher the quality of the local biological tissue. Also, since there was a high correlation with the results of ultrasound images, it is presumed that the quality of local biological tissue, such as within a muscle compartment, can be evaluated by using the local biological tissue evaluation device disclosed herein.

[0098] 10 Phase angle variation measurement unit, 50 Calculation evaluation unit, 51 Phase angle Jacobian matrix creation unit, 52 Image reconstruction unit, 53 Local biological tissue aging evaluation unit, 54 Local biological tissue fat infiltration evaluation unit, 55 Local biological tissue cross-sectional area evaluation unit, 56 Output unit

Claims

1. A local biological tissue evaluation device comprising: a sensor having a plurality of electrodes that can be placed on the skin of a subject at intervals from each other, applying a current or voltage between each of the electrodes with each of the electrodes in contact with the skin, measuring a voltage based on a current application voltage measurement pattern when applying the current, and measuring a current based on a voltage application current measurement pattern when applying the voltage between each of the electrodes, and a phase angle fluctuation measurement unit that measures a feature obtained based on the phase angle fluctuation for the current application voltage measurement pattern or the voltage application current measurement pattern; a phase angle Jacobian matrix creation unit that creates a phase angle Jacobian matrix based on the current application voltage measurement pattern or the voltage application current measurement pattern; and an image reconstruction unit that uses the feature and the phase angle Jacobian matrix to image the phase angle distribution inside the living body of the subject.

2. The local biological tissue evaluation device of claim 1, wherein the phase angle Jacobian matrix creation unit creates an equation relating the mesh coordinates of the subject's measurement location and the nth mesh in the mth measurement pattern, and derives the phase angle of the current, potential, and impedance, which is the ratio of the voltage to the current, at each mesh coordinate as elements of the phase angle Jacobian matrix as a solution of the equation.

3. The local biological tissue evaluation device according to claim 1 or 2, wherein the characteristic amount is a phase angle difference expressed by the following formula (1): Δθ ｍ = θ ｍ (f) -θ ｍ (f ０ ) ... (1) In the above formula (1), Δθ ｍ θ: Phase angle difference in the m-th current application voltage measurement pattern or the m-th voltage application current measurement pattern ｍ (f): Phase angle θ of high frequency f in the m-th current application voltage measurement pattern or the voltage application current measurement pattern ｍ (f ０ ) the low frequency f in the m-th current application voltage measurement pattern or the voltage application current measurement pattern ０ is the phase angle of 4. A local biological tissue evaluation device according to claim 1 or 2, further comprising a local biological tissue evaluation unit that evaluates local biological tissue using the imaged phase angle distribution.

5. A local biological tissue evaluation device according to claim 4, wherein the local biological tissue evaluation unit includes a local biological tissue aging evaluation unit that calculates a spatial average of the phase angle distribution from the phase angle distribution.

6. The local biological tissue evaluation device according to claim 4, further comprising a local biological tissue fat infiltration evaluation unit that creates a local biological tissue phase angle distribution, which is a phase angle distribution of local biological tissues, by assigning the phase angle distribution to each local biological tissue of the subject.

7. The local biological tissue evaluation device according to claim 6, wherein the local biological tissue fatty infiltration evaluation unit calculates a spatial average of the local biological tissue phase angle distribution from the local biological tissue phase angle distribution.

8. The local biological tissue evaluation device according to claim 6, further comprising a local biological tissue cross-sectional area evaluation unit that calculates a local biological tissue cross-sectional area ratio after the local biological tissue evaluation unit performs a binarization process on the local biological tissue phase angle distribution.

9. A method for evaluating local biological tissue comprising: a first step of using a sensor having a plurality of electrodes that can be placed on the skin of a subject at intervals, applying a current or voltage between the electrodes with each of the electrodes in contact with the skin, measuring the voltage based on a current-application-voltage measurement pattern when applying the current, and measuring the current based on a voltage-application-current measurement pattern when applying the voltage between the electrodes, and measuring a feature value obtained based on a fluctuation in phase angle for the current-application-voltage measurement pattern or the voltage-application-current measurement pattern; a second step of creating a phase angle Jacobian matrix obtained based on the current-application-voltage measurement pattern or the voltage-application-current measurement pattern; and a third step of imaging the phase angle distribution inside the subject's living body from the feature value and the phase angle Jacobian matrix.

10. A method for evaluating local biological tissue as claimed in claim 9, wherein in the second step, an equation is created that relates the mesh coordinates of the subject's measurement location and the nth mesh in the mth measurement pattern, and the current, potential, and phase angle of impedance, which is the ratio of the voltage to the current, at each mesh coordinate are derived as elements of a phase angle Jacobian matrix that is the solution of the equation.

11. The method for evaluating a local biological tissue according to claim 9 or 10, wherein the characteristic amount is a phase angle difference expressed by the following formula (2): Δθ ｍ = θ ｍ (f) -θ ｍ (f ０ ) ... (2) In the above formula (2), Δθ ｍ θ: Phase angle difference in the m-th current application voltage measurement pattern or the m-th voltage application current measurement pattern ｍ (f): Phase angle θ of high frequency f in the m-th current application voltage measurement pattern or the voltage application current measurement pattern ｍ (f ０ ) the low frequency f in the m-th current application voltage measurement pattern or the voltage application current measurement pattern ０ is the phase angle of 12. A method for evaluating local biological tissue according to claim 9 or 10, further comprising a fourth step of evaluating the local biological tissue using the imaged phase angle distribution.

13. The method for evaluating local biological tissue according to claim 12, wherein in the fourth step, a spatial average of the phase angle distribution is calculated from the phase angle distribution.

14. A local biological tissue evaluation method as described in claim 12, wherein in the fourth step, the phase angle distribution is assigned to each local biological tissue of the subject, thereby creating a local biological tissue phase angle distribution which is a phase angle distribution of the local biological tissue.

15. A method for evaluating a local biological tissue according to claim 14, wherein in the fourth step, a binarization process is performed on the local biological tissue phase angle distribution, and then a local biological tissue cross-sectional area ratio is calculated.

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