JP5896759B2 - Biological arterial endothelial function measuring device - Google Patents

Description

  The present invention relates to an arterial endothelial function measuring apparatus for measuring an index value for evaluating the endothelial function of a living artery, and more particularly to a technique for normalizing the index value to make it objective.

  Arterial endothelial function measuring devices that measure arterial endothelial function based on stimulating the arterial endothelium by resuming blood flow are known. However, since the index value obtained in this way includes individual differences, sufficient evaluation accuracy cannot be obtained. On the other hand, a biological arterial endothelial function measuring device that normalizes and outputs the index value has been proposed. This living body arterial endothelial function measuring device, for example, as shown in Patent Document 1, changes in the shape of the artery due to the expansion of the artery caused by the blood flow resumed at the time of release of blood transfusion to the living artery, for example, blood vessels While measuring the amount of change in diameter and calculating an index value for evaluating the arterial endothelial function based on the amount of change, the shear is calculated from the blood flow velocity in the artery that rapidly increases at the time of releasing the blood transduction and then decays Sequentially measure stress, calculate an integral value of a predetermined section from the time point of the blood transfusion release of the change curve indicating the change of the shear stress after the blood transfusion release, and normalize the index value based on the integral value Is.

Japanese Patent No. 3785084

  By the way, at the time of measurement by the living body arterial endothelial function measuring apparatus as described above, in the artery, generally, the blood flow is resumed after releasing the blood pressure, and the peak of the blood flow velocity of the blood flow is after the blood flow is resumed. It is observed every few seconds to several tens of seconds, then decelerates and returns to the blood flow velocity at rest. In order to calculate the shear stress in the living body arterial endothelial function measuring device, it is necessary that the blood flow velocity of the blood flow after the release of blood is correctly measured.

  However, at the time of measurement of the living body arterial endothelial function measuring device as described above, there is no guarantee that the position of the blood vessel will return to the original position even after the blood transfusion is released by moving the position of the blood vessel due to the blood pressure by the compression band. Immediately after releasing the blood transfusion, it may be necessary to follow the measurement position of the probe that can measure the blood flow velocity of the blood vessel. For this reason, there are many problems that the blood flow velocity immediately after the release of blood transfusion cannot be measured well, the shear stress cannot be obtained accurately, and the accuracy of the index value after normalization cannot be sufficiently obtained. .

  The present invention has been made against the background of the above circumstances, and its object is to provide a biological arterial endothelial function measuring device capable of obtaining a highly accurate index value after normalization. is there.

  As a result of various analyzes and examinations, the present inventor has reached the following facts as a background. That is, in the living body arterial endothelial function measuring apparatus as described above, the top curve among the change curves indicating the blood flow velocity measured from the probe often includes noise and cannot be measured accurately. Of the change curves, I noticed a tendency for the base curve to be measured accurately with relatively little noise. Then, a constant indicating the change in the measured value of the base of the change curve, which is well measured, is obtained, and the peak of the change curve is estimated based on the constant. It was found that it was possible to obtain a highly accurate evaluation value after normalization based on the amount of arterial endothelial stimulation obtained from the curve by approximating the change curve when the flow velocity was measured. The present invention has been made based on this finding.

  In order to achieve this object, the gist of the present invention is that (a) a change in the shape of the artery due to the expansion of the artery caused by the blood flow resumed at the time of release of blood transfusion to the artery of the living body is measured. And calculating an index value for evaluating the arterial endothelial function based on the shape change, while sequentially measuring the blood flow velocity in the artery that rapidly increases at the time of releasing the blood transfusion and then decays, and based on the blood flow velocity Calculating the arterial endothelial stimulation amount, normalizing the index value based on the arterial endothelial stimulation amount and outputting the normalized value, (b) rapidly increasing at the time of releasing the hemostasis and then decaying A constant indicating a change in a predetermined base is obtained from the change curve indicating the blood flow velocity or the change curve indicating the arterial endothelial stimulation value calculated from the blood flow velocity, and the change curve is calculated based on the constant. Estimate the top And calculates the arterial endothelium stimulating amount based on at least a top portion thereof was estimated.

  According to the living body arterial endothelial function measuring device of the present invention, a change curve indicating the blood flow velocity that rapidly increases at the time of releasing the blood transfusion and then decays or a change curve indicating the arterial endothelial stimulation value calculated from the blood flow velocity A constant indicating a predetermined change in the base is obtained, the top of the change curve is estimated based on the constant, and the arterial endothelial stimulation amount is calculated based on at least the estimated top. For this reason, since the top of the change curve is estimated based on the constant, the noise is removed by being approximated to the top of the change curve of the theoretical value. As a result, the arterial endothelial stimulation amount is calculated based on at least the estimated peak of the noise-free change curve, so that the arterial endothelial stimulation amount can be accurately quantified as compared with the prior art, and high accuracy. The index value after normalization can be obtained.

  Preferably, (c) the base and the top of the change curve are included in the descending section of the change curve, and (d) the top of the descending section is the attenuation indicated by the base of the descending section. It has the same attenuation constant as the curve, and is calculated as an attenuation curve from the descending start point of the change curve. For this reason, the top of the falling section of the change curve can be approximated to a theoretical attenuation curve by the same attenuation constant as the attenuation curve indicated by the base of the falling section.

  Preferably, (e) the base and the top of the change curve are included in an ascending section of the change curve, and (f) the top of the ascending section is an increase rate indicated by the base of the ascending section. Is calculated as an ascending line that continues until the descending start point of the change curve. For this reason, the top of the rising section of the change curve can be approximated to the rising line of the theoretical value by the increasing rate indicated by the base of the rising section.

  Preferably, (g) the arterial endothelial stimulation value is a shear rate of the inner wall of the artery calculated on the basis of the blood flow velocity, and (h) the arterial endothelial stimulation amount is after the release of the hemostasis. It is an integral value of a predetermined section from the time point of releasing the blood transfusion of the change curve indicating the change in the shear rate. For this reason, the top of the change curve indicating the shear rate calculated based on the blood flow velocity is estimated, and the integral value of the predetermined interval from the time of the blood transfusion release of the change curve having the estimated top is the arterial. Since it is calculated as the endothelial stimulation amount, the arterial endothelial stimulation amount can be quantified correctly as compared with the conventional art. Further, as compared with the case where shear stress is used, the shear rate is not affected by the viscosity of blood flow, so that higher accuracy can be obtained.

  Preferably, the normalization is a ratio of the index value to the arterial endothelial stimulation amount. For this reason, since the ratio of the index value to the arterial endothelial stimulation amount in which the index value is normalized by the arterial endothelial stimulation amount can be used, the arterial endothelial function can be correctly evaluated as compared with the conventional art. .

It is a figure explaining the whole structure of the vascular endothelial function test | inspection apparatus which is one Example of the biological artery endothelial function measuring apparatus of this invention. It is a figure explaining the control function with which the vascular endothelial function test | inspection apparatus of FIG. 1 was equipped. It is a figure explaining the positional relationship of the ultrasonic probe with which the electronic control apparatus of FIG. 2 was equipped, and the blood vessel. It is sectional drawing which looked at the upper right arm which is an ultrasonic image measurement object of the electronic controller of FIG. 2 from the wrist side. It is a figure explaining the 3 layer structure of the blood vessel wall which is an ultrasonic image measurement object of the electronic controller of FIG. It is a figure which shows an example of the image displayed on an image display apparatus based on the information measured by the electronic control apparatus of FIG. It is sectional drawing which looked at the upper right arm mounted in the upper limb holding | maintenance apparatus at the time of measurement of the vascular endothelial function test | inspection apparatus of FIG. 1 from the wrist side. It is sectional drawing which shows the state in the blood vessel virtually, in order to obtain | require the formula of the blood flow velocity distribution in the blood vessel. It is sectional drawing which shows the state in the blood vessel virtually, in order to obtain | require the formula of the shear velocity distribution in the blood vessel. Based on the change curve of the solid line formed by the time-dependent change of the shear rate and the blood vessel diameter at the time of measurement by the vascular endothelial function test apparatus of FIG. 1, and a constant indicating the change of the predetermined base of the change curve of the shear rate. It is a figure which compares and shows the change curve of the broken line which estimated the top part of the change curve. It is a figure explaining the integrated value of the change curve of the broken line with which the top was estimated in FIG. It is a figure which shows the flowchart explaining the control action in the vascular endothelial function test | inspection apparatus of FIG.

  Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings. In the following embodiments, the drawings are appropriately simplified or modified for easy understanding, and the dimensional ratios, shapes, and the like of the respective parts are not necessarily drawn accurately.

  FIG. 1 is a diagram illustrating an overall configuration of a vascular endothelial function testing device 10 which is an embodiment of a living body arterial endothelial function measuring device according to the present invention. This vascular endothelial function test apparatus 10 is an FMD (FMD) that measures the diameter, inner film thickness, plaque, blood flow velocity, etc. of a blood vessel based on an ultrasonic reflection signal output to some blood vessels of a living body. Flow-Mediated Dilation (Blood Dependent Vasodilation Response) measurement, a bed 14 for laying a living subject (measured person) 12 and a side of the subject 12 lying on the bed 14 The upper limb holding device 16 for placing the upper limb 30 of the subject 12 to be projected to and the ultrasonic sensor 22 held by the sensor holder 20 to the skin from above the skin 34 of the upper limb 30 of the subject 12 The electronic control device 18 that measures a transverse cross-sectional image (short axis image) or a vertical cross-sectional image (long axis image) of the blood vessel 36 positioned directly below 34, and blocks blood flow in the blood vessel 36 (see FIG. 2) at the measurement site. Because of its measurement site A pressurizing device 24 that compresses a portion on the upstream side or the downstream side (downstream side in FIG. 1), and a base 28 on which devices such as the upper limb holding device 16 and the sensor holder 20 are placed. ing.

FIG. 2 is a functional block diagram illustrating the control function of the electronic control unit 18. The ultrasonic sensor 22 shown in FIG. 2 is an ultrasonic oscillator that generates a predetermined ultrasonic wave with respect to the blood vessel 36 and biological information related to the blood vessel 36 based on a reflected wave reflected from the blood vessel 36 with respect to the ultrasonic wave. That is, two parallel first row short-axis ultrasonic array probes I and 2 short-axis ultrasonic array probes J for detecting blood vessel conditions (blood vessel parameters) and their longitudinal central portions are connected. H-shaped ultrasonic probe 38 having a long-axis ultrasonic array probe K that is arranged on a flat or flat probe surface, and a multi-axis drive device for positioning the ultrasonic probe 38 40. FIG. 3 is a diagram showing the relationship between the ultrasonic probe 38 and the blood vessel 36. As shown in FIG. 3, the first short axis ultrasonic array probe I and the second short axis ultrasonic array probe are shown. probe J, and ultrasonic array probe for K long axis, for example a number which is composed of piezoelectric ceramic pieces of ultrasonic transducers (ultrasonic oscillators) to a ₁ ~a _n are linearly arranged Are each formed in a longitudinal shape.

FIG. 4 is a cross-sectional view of the right upper arm 32 of the upper limb 30 as viewed from the hand (wrist) side. As shown in FIG. 4, the upper arm 32 includes a brachial artery M1, a biceps brachialis M2, a triceps brachialis M3, a humerus M4, a brachial muscle M5, a triceps brachii long head M6, and the like. For example, the blood vessel 36 that is the brachial artery M1 has a three-layer structure including an intima L ₁ , a media L ₂ , and an adventitia L ₃ as shown in FIG. The images obtained using ultrasound respect individual vessels 36, reflected from the tunica L ₂ because very weak, the inner layer L ₁ and the adventitia L ₃ is displayed. In the actual image, the inside of the blood vessel 36 and the inner membrane L ₂ are displayed in black, the inner membrane L ₁ and the outer membrane L ₃ are displayed in white, and the tissue is displayed in black and white spots. The intima L ₁ is displayed much thinner than the outer membrane L ₃ and is relatively difficult to display in the image. On the other hand, the rate of change of the intima diameter is used for FMD evaluation. desired.

  Returning to FIG. 2, the vascular endothelial function testing device 10 includes an image display device 44, an ultrasonic drive control circuit 46, and a drive motor control circuit 48. The vascular endothelial function testing device 10 is centrally controlled by an electronic control device 18 constituted by a so-called microcomputer, and a drive signal is supplied from the ultrasonic drive control circuit 46 by the electronic control device 18 and is super-controlled. Ultrasonic waves are emitted from the first short-axis ultrasonic array probe I, the second short-axis ultrasonic array probe J, and the long-axis ultrasonic array probe K of the ultrasonic probe 38 of the ultrasonic sensor 22. While being radiated, the ultrasonic reflection detected by the ultrasonic array probe I for the first short axis, the ultrasonic array probe J for the second short axis, and the ultrasonic array probe K for the long axis By receiving the signal and processing the ultrasonic reflection signal, an ultrasonic image under the skin 34 of the subject 12 is generated and displayed on the image display device 44.

In the electronic control unit 18, an ultrasonic drive control unit 50 that controls generation of ultrasonic waves by the ultrasonic sensor 22 via the ultrasonic drive control circuit 46, and detection processing of reflected waves received by the ultrasonic sensor 22 are performed. A detection processing unit 52 to perform, a Doppler signal processing is performed on the signal detected by the detection processing unit 52, and a blood flow velocity u in the blood vessel 36, that is, a maximum blood flow velocity u _max is calculated, B-mode signal processing A B-mode signal processing unit 56 that performs display, a display control unit 58 that performs display control for displaying an image based on the signal processed by the B-mode signal processing unit on the image display device 44, and a multi-axis via a drive motor control circuit 48. A drive motor control unit 60 that controls the drive of the drive device 40, a pressurization control unit 62 that controls the operation of the pressurization device 24, and an image of the blood vessel 36 are measured. Based on the blood flow velocity u calculated by the blood vessel diameter measuring unit 64 and the Doppler signal processing unit 54 that calculates the lumen diameter d of the blood vessel 36, that is, the maximum blood flow velocity u _max , the shear velocity μ (arterial endothelial stimulation value) ( 1 / sec), a shear rate curve complementing unit 68 that complements the change curve B formed by the shear rate μ calculated by the shear rate calculating unit 66, that is, the top B1 of the shear rate curve, and A control function such as an FMD value normalization unit 70 that integrates the shear rate curve complemented by the shear rate curve complementing unit 68 and normalizes the FMD value based on the integrated value is provided.

  As shown in FIG. 6, the image display device 44 includes a first short-axis image display region T1 for displaying an ultrasonic image by the first short-axis ultrasonic array probe I, and a second short-axis ultrasonic array. A second short-axis image display area T2 for displaying an ultrasonic image by the probe J and a long-axis image display area T3 for displaying an ultrasonic image by the long-axis ultrasonic array probe K are provided. . Furthermore, the first short-axis image display region T1, the second short-axis image display region T2, and the long-axis image display region T3 are provided with a common vertical axis indicating the depth dimension from the skin 34. Further, as described above, when an ultrasonic image of the blood vessel 36 is generated, the electronic control device 18 (drive motor control unit 60) causes the ultrasonic probe 38 to be in a predetermined position with respect to the target blood vessel 36. The multi-axis drive device 40 supplied with the drive signal from the drive motor control circuit 48 is driven and positioned. The predetermined position is a position where the first short-axis ultrasonic array probe I and the second short-axis ultrasonic array probe J are perpendicular to the target blood vessel 36 and the long-axis ultrasonic probe. The acoustic array probe K is a position parallel to the blood vessel 36.

  As shown in FIG. 7, the sensor holder 20 does not deform the blood vessel 36 located directly below the skin 34 from above the skin 34 of the upper arm 32 of the subject 12 at a desired position in the three-dimensional space, that is, a predetermined position. The ultrasonic sensor 22 is held in a desired posture so as to be lightly touched. It is well known as a coupling agent between the end face of the ultrasonic probe 38 of the ultrasonic sensor 22 and the skin 34 as a coupling agent for suppressing ultrasonic attenuation, reflection and scattering at the boundary surface, and clarifying an ultrasonic image. The jelly (ultrasonic jelly) 72 and the like are interposed.

  The pressurizing device 24 drives and compresses a site upstream or downstream (downstream in FIG. 1) of the measurement site by the electronic control device 18 in order to block the blood flow of the blood vessel 36 in the upper limb 30 of the subject 12. A blood cuffing device, comprising a cuff 74 wound around a limb such as the upper limb 30 of the subject 12 and a cuff pressure control device (not shown) for controlling the cuff pressure of the cuff 74. ing. The cuff 74 is configured such that the cuff pressure can be changed by, for example, air pressure. The cuff pressure control device includes an electric pressurization pump coupled to the cuff 74, an exhaust cock provided with an electromagnetic release valve, and a pressure. A cuff pressure of the cuff 74 is provided via the operation of the pressurizing pump and the exhaust cock in conjunction with the driving of the ultrasonic sensor 22 in accordance with a command from the electronic control unit 18 (pressurizing control unit 62). Control to pressurize or release.

When the blood vessel state is measured by the vascular endothelial function testing device 10, the ultrasonic drive control circuit 46 is arranged, for example, in a line constituting the first short-axis ultrasonic array probe I according to a command from the electronic control device 18. and a large number of ultrasonic transducers a ₁ ~a _n, a predetermined phase difference for each a ₁ ~a ₁₅ of the ultrasonic transducer a ₁ et certain number of the ultrasonic transducer group for example of 15 the end By applying beamforming driving that is simultaneously driven at a frequency of about 10 MHz while being applied, a converging ultrasonic beam is sequentially emitted toward the target blood vessel 36 in the arrangement direction of the ultrasonic transducers, and the ultrasonic transducer is 1 A reflected wave for each radiation when the ultrasonic beam is scanned while being shifted one by one is received and input to the electronic control unit 18. In addition, the radiation surface of the first short axis ultrasonic array probe I, the acoustic lens (not shown) for converging the ultrasonic beams in a direction perpendicular to the array direction of the ultrasonic transducer a ₁ ~a _n Is provided. The ultrasonic beam is then converged by the beamforming drive and the acoustic lens, as described above, the longitudinal-shaped convergent cross section in the direction orthogonal to the array direction of the ultrasonic transducer a ₁ ~a _n is formed. Longitudinal direction of the converging cross-section, the arrangement direction of the ultrasonic transducer a ₁ ~a _n in plan view, and with respect to the radial direction of the beam, which is a direction orthogonal respectively. The electronic control unit 18 (display control unit 58) synthesizes an image based on the reflected wave, and generates a cross-sectional image (short axis image) or a vertical cross-sectional image (long axis image) of the blood vessel 36 under the skin 34. And displayed on the image display device 44.

  The blood vessel diameter measuring unit 64 measures an endothelial diameter (lumen diameter) d which is the diameter of the endothelium 76 of the blood vessel 36 shown in FIG. 5 from the image of the blood vessel 36 shown in FIG.

In the shear rate calculation unit 66, the shear rate μ is calculated based on the blood flow velocity u (maximum blood flow velocity u _max ) calculated by the Doppler signal processing unit 54. Here, a method of calculating the shear rate μ will be described below with reference to FIGS. 8 and 9.

  First, an expression of the velocity distribution of the blood flow velocity in the blood vessel 36, that is, the blood flow velocity u is obtained with reference to FIG. FIG. 8 assumes that the shape of the blood vessel 36 is cylindrical and the blood flow in the blood vessel 36 is a laminar flow. The axial direction of the blood vessel 36 is the x direction, and the radial direction of the blood vessel 36 is r. The direction. Thereby, the velocity distribution of the blood flow velocity u in two minute sections dx in the x direction in the blood vessel 36 can be expressed as Expression (1). In the equation (1), R is the radius of the blood vessel, that is, the radius d / 2 of the inner peripheral surface of the endothelium 76 of the blood vessel 36. Further, dp is the amount of change (P1-P2) in the two pressures P1, P2 in the two minute sections dx in the x direction in the blood vessel 36. Μa is a viscosity coefficient.

In the present embodiment, the Doppler signal processing unit 54 performs frequency analysis on the transmission wave transmitted from the ultrasonic sensor 22 and the reception wave received by the ultrasonic sensor 22 by well-known FFT analysis, and the maximum blood flow velocity u. _max is calculated. That is, the FFT analysis shows the Doppler shift frequency on the vertical axis, the luminance as its energy, and a curve connecting the maximum luminance by superimposing the results of sampling measurement at regular time intervals on the time axis is the blood vessel center (r = 0) The time distribution of the maximum blood flow velocity is shown. Next, an average value u _max of the maximum blood flow velocity at which the positional maximum blood flow velocity changes during one heartbeat is obtained. The average value u _{max of the} maximum blood flow velocity is a value calculated by integrating the positional maximum blood flow velocity that changes during one heartbeat and dividing the integrated value by the time of one heartbeat. is there.

  Next, an equation for the velocity distribution of the shear velocity μ in the blood vessel 36 is obtained with reference to FIG. The shear rate μ can be expressed by the equation (2). When the equation (1) is substituted into the equation (2) and differentiated, the following equation (3) is calculated. In Equation (3), it is assumed that r ≧ 0.

Finally, the shear rate μ of the artery inner wall surface (r = R) M7 of the blood vessel 36 is calculated from the equation (3). That is, in this embodiment, the shear rate μ is set to −2 (u _max / R), the maximum blood flow velocity u _max measured from the Doppler signal processing unit 54 and the blood vessel 36 measured from the blood vessel diameter measuring unit 64. The shear rate μ is calculated from the measured value of half the diameter d of the inner peripheral surface of the endothelium 76, that is, the blood vessel radius R.

  FIG. 10 is a diagram showing a change curve B showing a change over time in the shear rate μ and a change curve C showing a change over time in the diameter d of the endothelium 76 of the blood vessel 36 as solid lines when measured by the vascular endothelial function test apparatus 10. . According to the change curve B shown in FIG. 10, the shear rate μ is substantially constant when the measurement site is compressed by the cuff 74, and the blood flow is resumed by the cuff 74 being suddenly released and increases. The peak is observed around several seconds to several tens of seconds after the blood flow is resumed, and then decelerates and returns to around the shear rate μ at rest. Further, in FIG. 10, a change curve D formed based on a measurement value ideally measured from the ultrasonic probe 38, that is, a theoretical value, is indicated by a one-dot chain line.

  As shown in FIG. 10, there is a relatively large difference between the top B1 of the change curve B measured from the ultrasonic probe 38 and the top D1 of the change curve D at the time of measurement by the vascular endothelial function test apparatus 10. There is a lot of noise in the curve of the apex B1. Further, there is no relatively large difference between the measured value of the base B2 of the change curve B and the theoretical value of the base D2 of the change curve D, and the measured value of the base B2 is relatively noisy. There are few and measured well. In addition, the area | region E of FIG. 10 shows the area | region where the measurement of the shear rate (micro | micron | mu) of the change curve B has not been performed successfully.

  In the shear rate curve complementing unit 68, a change curve B formed based on the shear rate μ calculated by the shear rate calculating unit 66 is converted into a predetermined base B2 of the change curve B, that is, a well-measured base B2. A constant (A, τ) indicating a change in the value is obtained, and the top B1 of the change curve B is complemented, that is, estimated based on the constant (A, τ). Here, a supplementing method, that is, an estimating method of the top B1 of the change curve B will be described below with reference to FIG.

First, the slope of the base B2 at the rising portion of the change curve B, that is, the increase rate A indicated by the base B2 in the rising section of the shear rate μ is calculated based on the equation (4). Note that μ0 is the base shear rate, which is a stable value measured before blood cuffing with the cuff 74. Further, t0 _max is a time when the cuff 74 is suddenly released, and μ1 is a shear speed value at a predetermined time t1 _max of the base B2 in the rising section of the change curve B.

Next, the value of the maximum shear rate μ _max of the apex F1 of the change curve F is estimated using the calculated increase rate A. That is, assuming that the time t _max when the maximum shear rate μ ′ _max after the sudden release of the cuff 74 is measured at the top B1 of the change curve B is the time when the maximum shear rate μ _max of the change curve F is measured, the maximum shear rate mu _max at t _max is calculated by the following equation (5). Then, the top B1 of the rising section of the change curve B is complemented as a rising line G1 in which the top F1 of the rising section continues until the change curve F starts to descend. That is, the top B1 of the rising section of the change curve B is connected to the measured value (t1 _max , μ1) of the change curve B and the estimated value (t _max , μ _max ) estimated based on the equation (5). Estimated as a straight line. The base F2 in the rising section of the change curve F and the base B2 in the rising section of the change curve B have the same value.

  Next, the top B1 of the descending section of the change curve B is complemented. That is, the attenuation curve G2 from the descending start point of the change curve F is estimated using the measured values (t1, μ2) of the base B2 in the descending section of the change curve B. The change with time in the shear rate μ is expressed by the equation (6). This is because the circulatory system of the living body that is symmetric with respect to the measurement constitutes a first-order lag system that can be replaced by vascular capacitance and vascular resistance.

Substituting the measured value (t1, μ2) of the base B2 into the equation (6), the time constant (attenuation constant) τ (τ <0) is calculated. Then, using the calculated time constant τ and equation (6), the decay curve G2, that is, the top B1 of the descending section of the variation curve B is estimated from the beginning of the descending of the variation curve F. Here, t is the elapsed time after the maximum shear rate μ _max is measured. Further, in the change curve F of the descending section, in this embodiment, not only the top B1 of the descending section of the change curve B is estimated but also the base B2 is estimated. However, the base F2 in the descending section of the change curve F and the base B2 in the descending section of the change curve B have substantially the same value, and only the top B1 of the descending section of the change curve B may be estimated.

  As a result, the top B1 of the change curve B is complemented by the broken change curve F shown in FIG. 10, that is, the top F1. The top F1 of the change curve F is not relatively different from the theoretical value of the top D1 of the change curve D. That is, the change curve F is not relatively different from the theoretical value of the change curve D.

In the FMD value normalization unit 70, the blood vessel diameter d of the subject 12 is first measured by the blood vessel diameter measurement unit 64 with respect to the blood vessel 36, and then the blood flow of the blood vessel 36 at the measurement site is blocked by the pressurizer 24. Therefore, the cuff 74 is maintained at a stage where the upstream or downstream site of the measurement site is pressed for a predetermined time and the upstream or downstream site of the measurement site is shifted to the blood-feeding state. The blood vessel diameter is rapidly released, and the blood vessel diameter measurement unit 64 measures the blood vessel diameter after filling from the blood-feeding state of the target blood vessel 36 (maximum blood vessel diameter after release of ischemia) d _max . Then, a blood vessel diameter change rate H (index value) (%) [= 100 × (d _max −d) / d] representing FMD (blood flow-dependent vasodilatation reaction) after ischemic reactive hyperemia is calculated. The Then, as shown in FIG. 11, the integration of the interval from the time of release of the change curve F, ie, t0 _max, to the time t2, for example, when the maximum blood vessel diameter d _max after release of the drive is measured, ie, the interval including at least the apex F1. The value (arterial endothelial stimulation amount) AUC (Area Under the Curve) is calculated and the change rate H (%) of the blood vessel diameter is divided by the integrated value AUC to normalize the normalized blood vessel diameter. The change rate H is displayed on the image display device 44. Then, based on the normalized blood vessel diameter change rate H, the endothelial function of the target blood vessel 36 is evaluated.

Note that the equation (6) has the property that even if time integration is performed, the following equation (7) is obtained and the shape does not change. Therefore, how much the integral value AUC of the shear rate μ increases with respect to the base can be easily estimated by calculation of (A × τ). 11, the increment of the integral value of the leading edge from the release after _{t0 max} cuff 74 until the time _{t max} for the maximum shear rate is measured is A × _t ^max 2/2, the maximum shear rate μ The increase amount of the integrated value AUC in the descending section from the start of the decrease of the shear rate μ after the _max is measured until the shear rate μ becomes stable is simply A × τ.

  Here, the measurement process in the vascular endothelial function test apparatus 10 of the present embodiment will be described using the flowchart shown in FIG.

  In step S10 (hereinafter, step S is abbreviated as S) corresponding to the blood vessel diameter measuring unit 64 and the shear rate calculating unit 66, the endothelial diameter d of the blood vessel 36 before blood pressure is measured, and the base shear rate μ0 is measured. .

  Next, in S11, air is fed into the cuff 74 using the pressurizing device 24, and blood feeding is started. In S12, the blood crushing by the cuff 74 in S11 is continued until a predetermined blood feeding time elapses. In S13, the cuff 74 is suddenly released when the predetermined blood feeding time in S12 has elapsed. These S11, S12, and S13 correspond to the pressurization control unit 62.

  In S14 corresponding to the shearing speed calculation unit 66, the shearing speed μ calculated at the same time as the blood transfusion release in S13 is integrated. In S15, it is determined whether or not a predetermined integration time has elapsed. If the determination in S15 is negative, S14 is repeated and the integration of the shear rate μ in S14 is continued. However, if the determination in S15 is affirmed, in S16 corresponding to the blood vessel diameter measuring unit 64, the blood vessel diameter after release of the blood transfusion is measured at the same time as the predetermined integration time has elapsed.

Next, in S17 corresponding to the shear rate calculation unit 66, a change curve B indicating the change over time of the measured shear rate μ is displayed on, for example, the image display device 44, and a rising section of the change curve B is predetermined. The increase rate A and the time constant τ are calculated from the measured value (t1 _max , μ1) of the base B2 and the measured value (t1, μ2) of the base B2 that is predetermined in the descending section.

  Next, in S18 corresponding to the shear rate curve complementing unit 68, the top B1 of the descending section of the change curve B is complemented and increased using the increase rate A and time constant τ calculated in S17 and the equation (6). The top B1 of the rising section of the change curve B is complemented using the rate A and the equation (5), and the change curve F is displayed on the image display device 44, for example.

In S19, S20, and S21 corresponding to the FMD value normalization unit 70, the blood vessel diameter change rate H / AUC that is the normalized FMD value is calculated. That is, in S19, the integral value AUC of the shear rate of the section from the time t0 _max at the time of the tourniquet release to the time t2 at which the maximum blood vessel diameter d _max after the tourniquet release is measured is calculated in S19. In S20, the change rate H of the blood vessel diameter is calculated from the measured values of the blood vessel diameter d before the blood transfusion and the maximum blood vessel diameter d _max after the blood transfusion is released.

  In S21, the change rate H (%) of the blood vessel diameter is normalized by being divided by the integral value AUC of the shear velocity calculated in S19. For example, the image display device 44 has the normalized blood vessel diameter. The change rate H / AUC (%) is displayed.

According to the vascular endothelial function test device 10 of the present embodiment, the blood flow velocity u that rapidly increases at the time of releasing the blood transfusion and then decays, that is, the shear velocity μ (arterial endothelial stimulation value) calculated from the maximum blood flow velocity u _max is shown. Constants A and τ indicating changes in the base B2 determined in advance in the change curve B are obtained, and the top B1 of the change curve B is estimated based on the constants A and τ, and at least based on the estimated top F1. An integral value AUC (arterial endothelial stimulation amount) of the shear rate μ is calculated. For this reason, since the top B1 of the change curve B is estimated based on the constants A and τ, the noise is removed by being approximated to the top D1 of the change curve D of the theoretical value. Thus, since the integral value AUC of the shear rate μ is calculated based on at least the estimated peak F1 of the change curve F without noise, the integral value AUC can be quantified correctly as compared with the conventional case. In addition, a highly accurate index value after normalization can be obtained.

  Further, according to the vascular endothelial function testing device 10 of the present embodiment, the base B2 and the top B1 of the change curve B are included in the descending section of the change curve B, and the top B1 of the descending section is the descending It has the same time constant (attenuation constant) τ as the attenuation curve G2 indicated by the base B2 of the section, and is calculated as an attenuation curve G2 from the descending start point of the change curve F. For this reason, the estimated peak B1 of the falling section of the change curve B can be approximated to a theoretical attenuation curve by the same time constant τ as the attenuation curve G2 indicated by the base B2 of the falling section.

  Further, according to the vascular endothelial function testing device 10 of the present embodiment, the base B2 and the top B1 of the change curve B are included in the rising section of the change curve B, and the top B1 of the rising section is the rise. The increase rate A is the same as the increase rate A indicated by the base B2 of the section, and is calculated as an ascending line G1 that continues until the descent start point of the change curve F. For this reason, the top B1 of the rising section of the change curve B can be approximated to the rising line of the theoretical value by the increasing rate A indicated by the base B2 of the rising section.

Further, according to the vascular endothelial function test apparatus 10 of the present embodiment, the arterial endothelial stimulation value is the shear velocity μ of the inner wall surface M7 calculated based on the blood flow velocity u, that is, the maximum blood flow velocity u _max , The amount of arterial endothelial stimulation is the integral of the interval from the blood transfusion release time t0 _{max on the} change curve F showing the change in the shear rate μ after the blood transfusion release to the time t2 when the maximum blood vessel diameter d _max after the blood transfusion release is measured. The value AUC. For this reason, the apex B1 of the change curve B indicating the shear rate μ calculated based on the maximum blood flow velocity u _max is estimated, and the drive is performed from the blood transfusion release time point t0 _max of the change curve F having the estimated apex F1. Since the integrated value AUC of the interval up to time t2 when the maximum blood vessel diameter d _max after blood release is measured is calculated as the arterial endothelial stimulation amount, the arterial endothelial stimulation amount can be quantified correctly as compared with the conventional art. . Further, compared to the case where shear stress is used, the shear rate μ is not affected by the viscosity of the blood flow, so that higher accuracy can be obtained.

  In addition, according to the vascular endothelial function testing device 10 of the present embodiment, the normalization of the change rate H (%) of the vascular diameter is performed by changing the change rate H of the vascular diameter to the integral value AUC of the arterial endothelial stimulation amount, that is, the shear rate μ %). For this reason, the ratio of the change rate H (%) of the blood vessel diameter to the integrated value AUC of the shear rate μ, in which the change rate H (%) of the blood vessel diameter is normalized by the integral value AUC of the shear rate μ, can be used. Thus, the arterial endothelial function can be correctly evaluated as compared with the conventional case.

  As mentioned above, although the Example of this invention was described in detail based on drawing, this invention is applied also in another aspect.

  In the vascular endothelial function testing device 10 of the present embodiment, the shear rate μ is used as the arterial endothelial stimulation value, but for example, the integrated value of the blood flow velocity u may be directly used as the arterial endothelial stimulation value. Furthermore, the blood flow volume obtained from the blood flow velocity of the blood vessel 36 or the integrated value of shear stress may be used as the arterial endothelial stimulation value. In addition, the temporal change of the blood flow volume and blood flow velocity u of the blood vessel 36 can be expressed in the same manner as the equation (6) shown in this embodiment, and the top of the change curve is suitably estimated as in this embodiment. can do. Further, the blood flow velocity may be measured at the same timing within the cycle in synchronization with the pulse cycle.

  In the vascular endothelial function testing apparatus 10 of the present embodiment, the base shear rate μ0 is measured before the blood transfusion, but may be a value when it does not change stably in time after the blood transfusion is released, for example. . The vascular endothelial function testing device 10 of the present embodiment includes steps S18 and S20. However, since the shear rate curve, that is, the change curve F is integrated in step S28, it is not always necessary.

  In the vascular endothelial function testing device 10 of the present embodiment, the index value H (%) is calculated based on the rate of change of the diameter of the blood vessel 36, but other evaluation methods may be used. For example, the change in the cross-sectional area of the blood vessel 36 Rate is also acceptable.

  Further, in the vascular endothelial function testing device 10 of the present embodiment, the arterial endothelial stimulation amount is calculated as the integral value AUC of the shear rate μ, but simply, the arterial endothelial stimulation value at the start of the descent of the change curve F, that is, The maximum shear rate μmax may be used as the arterial endothelial stimulation amount.

  Further, in the vascular endothelial function test apparatus 10 of the present embodiment, the example of measuring the brachial artery has been described, but the present invention is not limited to this, for example, an artery that can be measured from the epidermis surface of the upper limb 14, or The same applies to the measurement of other lower limb blood vessels and the like, and has an effect.

In the vascular endothelial function testing device 10 of the present embodiment, the shear rate curve complementing unit 68 uses the time t _{max at} which the maximum shear rate μmax of the change curve F is measured as the maximum shear rate μ at the top B1 of the change curve B. time when 'but max had a measured time t _max, for example, a certain time up to the shear rate μmax is stipulated time t _max to be determined statistically or experimentally in advance has elapsed after occlusion of the artery open (For example, 10 seconds after the cuff 74 is suddenly released).

Further, in the vascular endothelial function testing device 10 of the present embodiment, the Doppler signal processing unit 54 performs frequency analysis on the transmitted wave transmitted from the ultrasonic sensor 22 and the received wave received by the ultrasonic sensor 22 by FFT analysis and performs maximum analysis. The blood flow velocity u _max has been calculated. For example, the transmission wave and the reception wave are directly obtained by calculating the blood flow velocity distribution of each segment in the cross section of the blood vessel using a well-known complex autocorrelator. The average value of the blood flow velocity of the segment may be set as the maximum blood flow velocity u _max .

  Although not illustrated one by one, the present invention can be implemented in variously modified and improved modes based on the knowledge of those skilled in the art.

10: Vascular endothelial function testing device (biological artery endothelial function measuring device)
A: Increase rate (constant)
AUC: Integrated value of shear rate (arterial endothelial stimulation)
B: change curve B1: apex B2: base M1: brachial artery M7: arterial wall H: change rate of blood vessel diameter (index value)
G1: Ascending line G2: Decay curve u: Blood flow velocity μ: Shear velocity (arterial endothelial stimulation value)
τ: Time constant (attenuation constant, constant)

Claims (5)

The shape change of the artery due to the expansion of the artery caused by the blood flow resumed at the time of releasing the blood transfusion to the artery of the living body is measured, and an index value for evaluating the arterial endothelial function is calculated based on the shape change On the other hand, the blood flow velocity in the artery that rapidly increases at the time of releasing the blood transfusion and then decays is sequentially measured, the arterial endothelial stimulation amount is calculated based on the blood flow velocity, and the index is calculated based on the arterial endothelial stimulation amount A device for measuring arterial endothelial function of a living body that normalizes and outputs a value,
A constant indicating a change in a predetermined base is obtained from a change curve indicating the blood flow velocity that rapidly increases at the time of releasing the blood transfusion and then decays or a change curve indicating the arterial endothelial stimulation value calculated from the blood flow velocity. An apparatus for measuring an arterial endothelial function in a living body, wherein the apex of the change curve is estimated based on the constant, and the arterial endothelial stimulation amount is calculated based on at least the estimated apex. The base and top of the change curve are included in the descending section of the change curve,
The top of the descending section has the same attenuation constant as the decay curve indicated by the base of the descending section, and is calculated as an attenuation curve from the descending start point of the change curve. Arterial endothelial function measuring device. The base and the top of the change curve are included in the rising section of the change curve,
The top of the ascending section has the same rate of increase as that indicated by the base of the ascending section, and is calculated as an ascending line that continues until the descent start point of the change curve. Biological arterial endothelial function measuring device. The arterial endothelial stimulation value is the shear rate of the inner wall of the artery calculated based on the blood flow velocity,
4. The living body arterial endothelium according to any one of claims 1 to 3, wherein the arterial endothelial stimulation amount is an integral value of a predetermined section from the time of the blood transfusion release of a change curve indicating a change in the shear rate after the blood transfusion is released. Functional measuring device.   The living body arterial endothelial function measuring apparatus according to claim 1, wherein the normalization is a ratio of the index value to the arterial endothelial stimulation amount.

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