JP6620333B2 - Vascular function testing device - Google Patents

Description

  The present invention relates to a blood vessel function testing device.

  It is known that vascular dysfunction precedes serious cardiovascular diseases. Therefore, the vascular function is an index that can grasp the vascular risk earliest, and can be recovered by changing medication or lifestyle before reaching cardiovascular disease. In other words, if a decrease in vascular function can be detected at an early stage, it can be prevented before moving to an irrecoverable disease state.

  Vascular function tests are broadly divided into invasive methods and non-invasive methods. An invasive method is angiography using a catheter. However, this is an in-hospital examination, which is expensive and risky, and a non-invasive method is preferably used. As a non-invasive method, there is (1) a blood flow dependent vasodilator reaction (FMD; Flow-Mediated Dilation) test using an echo image. The echo probe is pressed against the blood vessel by manual operation and the blood vessel diameter is measured, but its reproducibility is low and its clinical application is limited. (2) There is also a peripheral arterial tonometry (PAT) test. The vasodilator response after releasing the brachial cannula is detected as a change in the blood flow rate of the peripheral pulse of the fingertip, but the cost is high because the test probe is disposable. Further, since the upper arm is manually driven using a sphygmomanometer, the burden on the operator is great. Hereinafter, (1) FMD inspection and (2) PAT will be described.

(1) The FMD test is a method in which a blood vessel expands via nitric oxide (NO) synthesized from arginine by signal transmission from an acetylcholine receptor, or a blood vessel undergoes mechanical stimulation or “shear stress”. ) "Is applied in response to the production and expansion of NO from vascular endothelial cells. In recent years, a phenomenon in which a strong shear stress occurs due to an increase in blood flow in the blood vessel after release of the blood pump and then the blood vessel temporarily expands has been clarified, and it was named FMD. That is, FMD is understood as a NO-dependent transient vasodilator response. Vasodilatoryness that reacts to vasodilators such as NO produced from vascular endothelial cells by FMD can be diagnosed. As an inspection method using the FMD, a method of directly measuring a blood vessel diameter change by a blood vessel ultrasonic inspection of the brachial artery is used.

  However, since the device that measures the brachial artery dilatation rate of FMD with ultrasound (BAUS: Brachial Artery Ultrasound) is based on the principle of blood vessel inner diameter determination using ultrasound, the inner diameter rendering is not constant and individual differences are greatly reproduced. Poor nature. In addition, there is a problem that the ultrasonic echo inspection apparatus is expensive (tens of millions of yen), which largely depends on the skill of the ultrasonic echo inspector. Further, there is a problem that the measurement time is relatively long as 15 minutes.

(2) Therefore, recently, with regard to FMD examination, the unstableness of the data of measuring the brachial artery dilatation rate by echo and the vasodilator response after releasing brachial artery blood pressure without using expensive echo equipment are considered to be the pressure of capillary blood vessels at the fingertips. A new FMD measurement method based on PAT technology that captures changes is being developed. For example, Non-Patent Document 1 discloses a method for detecting a blood flow fluctuation at the fingertip as a pressure change with respect to a vasodilator reaction after releasing brachial artery blood transfusion. Further, Patent Documents 1 to 3 exist regarding the PAT technology. There are reports that arteriosclerosis can also be determined by PAT (Masato Mikami, Akifumi Kagiya, Junji Ozawa: Diagnosis of arteriosclerosis by pressurized pulse wave. Japanese Journal of Clinical Physiology 35: 9-18, 2005).

  However, the device that has been commercialized so far by the PAT technology (trade name “Endpad 2000”. “ENDO PAT” is a registered trademark) has a manual blood-feeding part of the upper arm, and pressure is applied. Judgment of whether it is not constant and unstable and is able to drive blood is dependent on the subjective judgment by the examiner's waveform, and is manually applied and repressurized. Since the fingertip blood flow before and after the fingertip pulse pressure is calculated is calculated by the ratio of the pulse pressure (after the blood pressure before / after blood pressure), the rate of change is large. In addition, the fingertip blood pressure measurement probe is highly dependent on the inner membrane of the probe covering the fingertip, and is “one-time use”, and has a problem that the running cost is very high. In addition, the measurement time was 15 minutes, which was not shortened from that of the FMD inspection.

  There were also the following problems. In general, the amplitude of the fingertip pulse wave varies depending on the pressure with which the fingertip is pressed against the sensor. When pressure is applied to the sensor at the optimum pressure, a clear pulse wave with a large amplitude can be sensed. However, if the pressure is too low, the amplitude is small and the noise component is large. Inhibited, the amplitude decreases. Since the optimum pressure varies depending on the thickness of the finger and the hardness of the blood vessel, the pulse wave may not be accurately obtained with a spring-type general probe because the pressure is too weak or too strong. In the spring type probe, since the measurement is continued for 15 minutes and the fingertip is continuously pressed, the amplitude of the pulse wave may be attenuated. The probe that covers the fingertip with the intima also has a slight air leak, so that the amplitude of the pulse wave attenuates with time.

  Furthermore, FMD and PAT have a problem that accuracy and reproducibility of measurement results are low. In the vascular hyperemia reaction principle, as shown in FIG. 1, the shear force P1 due to the flow of blood flow induces NO, which causes expansion of the smooth muscle constituting the blood vessel, whereas vascular wall pressure The change of P2 induces a non-NO-dependent element, and this non-NO-dependent element leads to a change (contraction / expansion) of the smooth muscle constituting the blood vessel. In FMD and PAT, there is a problem that it is difficult to avoid the influence of changes in vascular wall pressure due to non-NO-dependent elements, and the accuracy of measurement results from complex and non-uniform vascular deformation due to shear force P1 and vascular wall pressure P2. In order to increase the reproducibility, a measurement means that is not affected by changes in blood vessel wall pressure due to non-NO dependent elements has been desired. Furthermore, FMD, which is used to measure thick blood vessels, is good at examining vascular endothelial function related to thick blood vessels. On the other hand, PAT, which measures thin blood vessels, is good at examining vascular endothelial function related to thin blood vessels. The versatility of vascular function tests was limited. Therefore, there has been a demand for a measuring means capable of determining the etiology of vascular dysfunction by being able to examine the vascular function of both thick and thin blood vessels and further quantifying the ratio of both by simultaneous observation.

Special Table 2000-515789 Special table 2003-527149 gazette Special table 2004-528052 gazette

Bonetti PO, Pumper GM, Higano ST, et al: Non-invasive Identification ofpatients with early colonary atherosclerosis by assessment of digitasl reacyivehyperemia. J Am Coll cardiol 44: 2137-2141,2004

  The present invention has been made in view of the above problems, and has excellent reproducibility and versatility that can be applied to vascular endothelial function measurement. The fingertip is intended to shorten measurement time and cost required for measurement. And it aims at provision of the pulse wave analysis device of a wrist (rib).

The present invention is grasped by the following composition in order to achieve the above-mentioned object.
(1) A first aspect of the present invention is a blood vessel function test device, which is mounted on the upper arm of the test side, and is mounted on a fingertip or a wrist, and is applied to a pressurizing unit and a fingertip or wrist. A probe for measuring the pulse wave, a control unit for controlling the pressurizing unit and the probe, and a processing unit for giving a command to the control unit and acquiring data relating to the pulse wave from the control unit. The processing unit calculates an average amplitude value and analyzes chaos based on the data relating to the pulse wave, and quantifies the characteristic amount of the pulse wave in order to determine cardiovascular disease and vascular endothelial dysfunction It is characterized by that.

(2) In the configuration of (1) above, the processing unit calculates a chaos attractor indicating blood vessel fluctuations before and after blood transfusion based on the amplitude value of the pulse wave and the rate of change thereof as the chaos analysis, For the calculated chaotic attractor, at least one of the Lyapunov exponent, the outer peripheral area, and the eigenvectors of the minor axis and the major axis may be quantified.

(3) In the configuration of (1) or (2), the probe may measure the pulse wave by a photoelectric method or a pressure method.

(4) In the configuration of (3), the probe is a photoelectric type, and includes an air bag for applying an optimum pressure to the measurement site, a light emitting unit that irradiates light to the measurement site, and the measurement site. And a light receiving portion that receives the reflected light.

(5) In any one of the constitutions (1) to (4), the probe may include a first probe that is attached to the first fingertip on the examination side and measures the pulse wave related to a thin blood vessel. Good.

(6) In the configuration of (5), the probe may further include a second probe that is attached to the first wrist on the examination side and measures the pulse wave related to a thick blood vessel.

(7) In the configuration of (6), the probe is attached to the second fingertip on the control side, and is attached to the third probe for measuring the pulse wave related to a thin blood vessel and the second wrist on the control side. And a fourth probe for measuring the pulse wave related to a thick blood vessel.

(8) In the configuration of the above (7), the processing unit is configured such that the post-transfusion value on the examination side is (A), the pre-transmission value is (B), and the control side is the pulse wave. Assuming that the value after the blood transfusion is (C) and the value before the blood transfusion is (D), the ratio before and after the test side blood drive (A / B), the ratio before and after the control side blood drive (C / D) and the above You may obtain | require the test | inspection side / control side ratio ((A / B) / (C / D)) with respect to the said control side before-and-after driving ratio of the test-side blood-driving ratio.

(9) In any one of the configurations (2) to (8), the storage unit further stores a known chaos attractor group for each of the cardiovascular diseases, and the processing unit includes the calculated chaos. The attractor may be compared with the known chaotic attractor group by pattern matching.

(10) In any one configuration of (1) to (9), a display unit that displays a result processed by the processing unit may be further provided.

(11) A second aspect of the present invention is a blood vessel function test method, wherein the first fingertip and the first wrist on the inspection side and the second fingertip and the second wrist on the control side are preliminarily provided. A first step of applying pressure and measuring each pulse wave; a second step of determining whether the pressure is optimal for the subject; if YES, maintaining the optimal pressure; A third step of calculating an amplitude value based on each previous pulse wave, and calculating a chaos attractor before blood transduction related to the first fingertip, the first wrist, the second fingertip, and the second wrist. And calculating the amplitude value based on each pulse wave after the blood pressure measurement and the fourth step of applying blood pressure to the first fingertip and the first wrist on the examination side for a predetermined time. , The first fingertip, the first wrist, the second fingertip, and the second wrist The fifth step of calculating the attractor, the amplitude value calculated in the fifth step, and the calculated chaotic attractor, the numerical value after the blood pumping on the examination side is (A), and the numerical value before the blood driving is also the same. When (B) and the value after blood pressure on the control side are (C), and the value before blood pressure is also (D), the ratio before and after the test side blood pressure (A / B), before and after the blood pressure on the control side A sixth step of obtaining a test side / control side ratio ((A / B) / (C / D)) of the ratio (C / D) and the test side pre- and post-drive ratio before and after the control-side drive A seventh step for comparing the pre- and post-examination ratio of the test side, the pre- and post-control ratio of the control side and the ratio of the test side / control side with the respective reference values, and the results of the comparison in the seventh step, And an eighth step of determining a functional disorder. .

(12) The configuration of 11) may further include, after the fifth step, a ninth step of comparing the calculated chaotic attractor with a known chaotic attractor group for each cardiovascular disease by pattern matching. Good.

  According to the present invention, pulse wave analysis of fingertips and wrists (ribs) that is excellent in reproducibility and versatility applicable to vascular endothelial function measurement, shortens measurement time, and reduces cost required for measurement. An apparatus can be provided.

It is a figure which shows the hyperemia reaction principle of the blood vessel. It is a figure which shows the structural example of the vascular function test | inspection apparatus which concerns on this embodiment. It is a figure which expands and shows a probe and a cuff among FIG. It is a figure which shows the example of control of the vascular function test | inspection apparatus which concerns on this embodiment. It is a flowchart which shows the procedure of the measurement and analysis by the blood vessel function test | inspection apparatus which concerns on this embodiment. It is a figure which shows the relationship with the amplitude of a pulse wave, the mounting pressure which crimps | bonds a probe to a fingertip or a wrist, and the compliance C of the blood vessel. It is a figure which shows the example of the measurement data (amplitude) of the pulse wave in a test | inspection side and a control | contrast side. It is a figure which shows the example of the chaos attractor before and after blood driving. It is a figure which shows the example of a response | compatibility with the pattern of a chaos attractor, vascular endothelial disorder / deformation, and etiology. It is a 1st figure which shows the method of Turkens about a chaos attractor. It is a 2nd figure which shows the Turkens technique about a chaos attractor. It is a figure which shows a way of thinking about the Lyapunov index of a chaos attractor. It is the figure which displayed the chaos analysis result, Comprising: It is a figure which shows the example of the analysis result of the test subject who has etiology, such as myocardial infarction, cerebral infarction, and coronary arteriosclerosis. It is a figure which displayed the chaos analysis result, Comprising: It is a figure which shows the example of the analysis result of the test subject who has etiology, such as diabetes, a peach source disease, and a peripheral disease. It is a figure which shows the result of the contrast test of this embodiment and end pad 2000. FIG.

<Overall configuration of vascular function testing device 1>
A blood vessel function testing device 1 according to an embodiment of the present invention will be described with reference to the drawings. FIG. 2 shows a configuration example of the present embodiment. A cuff 10 (pressurizing unit) for driving blood is attached to the proximal side of the first upper limb A1, which is the examination side, that is, the upper arm. Four probes 20 for measuring the respective pulse waves are mounted on the distal side of both the first upper limb A1 and the second upper limb A2 that is the control side, that is, both fingertips and wrists. The probe 20 includes a first probe 21 attached to the first fingertip F1 of the first upper limb A1, a second probe 22 attached to the first wrist W1 of the first upper limb A1, and a second of the second upper limb A2. A third probe 23 attached to the fingertip F2 and a fourth probe 24 attached to the second wrist W2 of the second upper limb A2 are included.

  In the following description, the examination side may be referred to as the blood driving side, and the control side may be referred to as the non-blood driving side. In the accompanying drawings, the test side may be displayed as “test” and the control side may be displayed as “control”.

  Each probe is connected to an apparatus main body 30 (control unit) that controls these via the air tubes 21a, 22a, 23a, 24a, and the cuff 10 via the air tube 10a. Is connected to a computer 40 (processing unit) that analyzes and displays the data obtained by the above. Each air tube is provided with wiring for transmitting and receiving signals between connected elements. The computer 40 may be a portable information terminal such as a smart phone or a tablet, and the connection with the apparatus main body 30 may be either wired or wireless. The computer 40 includes a database 41 (storage unit) and a display 42 (display unit), which may be a part of the computer 40 or an external unit.

  FIG. 3 is an enlarged view showing the mounting of the cuff 10 and the mounting of the probe 20, and the connection between the apparatus main body 30 and the computer 40 is omitted. The relationship between the probe 20, the apparatus main body 30, and the computer 40 will be described later with reference to FIG. As shown in FIG. 3, a first probe 21 and a third probe 23 are attached to both finger tips, and a second probe 22 and a fourth probe 24 are attached to both wrists. The first probe 21 and the third probe 23, the second probe 22 and the fourth probe 24 have the same configuration (however, the first probe 21 and the second probe 22 are on the inspection side, and the third probe 23 and the fourth probe 24 are controls). Therefore, the first probe 21 and the second probe 22 will be representatively described below.

  The first probe 21 is attached to the first fingertip F1 on the examination side, the air bag 201 located on the back side, and the LED 202 (light emitting unit) that emits light toward the palm side of the first fingertip F1. The LED 202 includes a light receiving sensor 203 (light receiving unit) that receives the reflected light from the blood vessel. The second probe 22 is attached to the first wrist W1 on the examination side, the air bag 201 located on the palm side of the rib, and the LED 202 (light emitting unit) that emits light toward the palm side of the rib of the first wrist W1. ), And a light receiving sensor 203 (light receiving unit) that receives the reflected light from the blood vessel in parallel with the LED 202.

  Each air bag 201 is pressurized or depressurized by a pressure pump 204 and an exhaust valve 205 provided inside or outside the apparatus main body 30, and the pressure is measured by a pressure sensor 206. The air bag 201 applies an optimum pressure for the subject to the measurement site when measuring the pulse wave, and the pressure pump 204, the exhaust valve 205, and the pressure sensor 206 are controlled by the apparatus main body 30. Details will be described later with reference to FIGS.

  For example, an infrared light emitting diode can be preferably used as each LED 202, and a photodiode or a phototransistor can be preferably used as the light receiving sensor 203. The LED 202 and the light receiving sensor 203 are arranged inside the first probe 21 or the second probe 22 so that their optical axes intersect. Light (infrared light) emitted from the LED 202 is irradiated to the blood vessel through the skin, but a portion of the wavelength band (near infrared light) is absorbed by hemoglobin in the bloodstream, and the amount of reflected light varies with the volume of the blood vessel due to heartbeat. It will change according to (that is, capacitive pulse wave). The light receiving sensor 203 captures this change and outputs it as a voltage change.

  Here, the first probe 21 or the second probe 22 has been described as measuring the capacitive pulse wave by the photoelectric configuration having the LED 202 and the light receiving sensor 203. However, the configuration is not limited to this, and the pressure-type configuration is used. You may make it measure a pressure pulse wave by. In the case of the pressure type, a blood pressure fluctuation is captured by a pressure sensor (pressure element) instead of the LED 202 and the light receiving sensor 203. In the case of the pressure type, it is important to correctly press the pressure sensor directly above the artery for accurate measurement.

  As the cuff 10 for driving blood, one used in a known automatic sphygmomanometer or the like can be used. In addition to the first probe 21 or the second probe 22, the cuff 10 is pressurized by a pressure pump 104 or an exhaust valve 105. The pressure is reduced or the pressure is measured by the pressure sensor 106. The pressure pump 104, the exhaust valve 105, and the pressure sensor 106 are controlled by the apparatus main body 30. Pressurization and release to the cuff 10 are fully automated, and intelligent control of pressurization is performed. The pressurization of the cuff 10 is automatically monitored by the computer 40 and controlled until complete blood driving can be performed, and overpressurization and partial pressurization are avoided.

<Measurement with probe 20>
Next, pulse wave measurement by the probe 20 will be described by using the first probe 21 as a representative while referring to FIGS. 4 and 5. The same applies to the third probe 23. The second probe 22 and the fourth probe are basically the same, but different points will be described later with different measurement sites.

  As shown in FIG. 4, the air bag 201 of the first probe 21 is connected to a pressure pump 204, an exhaust valve 205, and a pressure sensor 206 via an air tube 21a. The pressure of the air bladder 201 is controlled by the control unit 31 controlling the pressure pump 204 and the exhaust valve 205 based on a pressure control command that the computer 40 gives to the control unit 31 of the apparatus body 30 according to the detection result by the pressure sensor 206. Adjusted. The LED 202 is controlled by a pulse wave measurement command given to the control unit 31 by the computer 40, irradiates light to the first fingertip F 1, and reflected light is received by the light receiving sensor 203.

  The apparatus body 30 is provided with an auto gain circuit, a DC component extraction circuit, an A / D (analog / digital) conversion circuit, a USB controller, an analog filter, an amplification circuit, and a differentiation circuit (double differentiation) as the control unit 31. ing. The control unit 31 controls the air bag 201 by a pressure control command received from the computer 40. The pressure control command includes pressurization speed, pressurization start, current pressure maintenance, decompression speed, decompression start, and pressure release. It is. The control unit 31 controls the LED 202 and the light receiving sensor 203 by the pulse wave measurement command received from the computer 40. The pulse wave control command includes measurement start and measurement end.

  The control unit 31 uses the signals acquired by the pressure sensor 206 and the light receiving sensor 203 as pressure time series data, acceleration pulse wave time series digital data, pulse wave DC component time series digital data, and pulse wave time series digital data. Send to. The acceleration pulse wave is obtained by differentiating the capacitive pulse wave, which is the original waveform, twice with a differentiating circuit.

  The computer 40 receiving these digital data performs chaos analysis based on the amplitude value of the pulse wave and the rate of change thereof, and calculates a chaos attractor as a blood vessel fluctuation. Then, the Lyapunov exponent is calculated as the fluctuation index, entropy calculation, peak value (peak value on the upper limit side of amplitude) detection, and heart rate variability analysis (HRV analysis; Heart Rate Variability) by fast Fourier transform (FFT). Do. The chaos analysis will be described later again.

<Measurement and analysis procedures>
Based on the above-described configuration, measurement and analysis are performed according to the procedure shown in FIG. First, before starting full-scale measurement, preliminary measurement is performed in order to obtain the optimum pressure for pressing the light receiving sensor 203 on the palm side of the first fingertip F1 (step S101). For example, the pressurization of the first probe 21 to the air bag 201 is performed for about 1 minute while changing in the range of 20 mmHg to 120 mmHg, and the optimum pressure is found for each subject (step S102).

  Here, as described above, the optimum pressure is that the amplitude of the pulse wave changes depending on the pressure with which the palm side of the first fingertip F1 that is the measurement site is pressed against the light receiving sensor 203, so the pressure is too weak. The pressure is such that the amplitude is small and the noise component is large, and conversely, the pressure is too strong to prevent the blood flow from being inhibited and the amplitude from becoming small. In addition, setting the mounting pressure applied to the fingertip and wrist each time measurement is performed at an optimum pressure absorbs the elements of variation in the measurement results and contributes to excellent reproducibility.

  This is illustrated in FIG. In FIG. 6, the horizontal axis represents time (seconds), the vertical axis represents the pulse wave amplitude (indicated by a one-dot chain line), the mounting pressure of the first probe 21 (indicated by a dotted line), and the blood vessel compliance C (indicated by a broken line). As the mounting pressure rises, the maximum compliance pressure at which the compliance C first takes the extreme point appears, and then the maximum amplitude pressure at which the amplitude of the pulse wave takes the extreme point appears. Therefore, in order to obtain highly reproducible data so that the influence of noise is minimized and the blood flow is not inhibited due to the pressure being too strong, the maximum compliance pressure or amplitude at which this compliance C is maximized is maximized. It is desirable to adopt the maximum amplitude pressure that becomes as the optimum pressure of the probe 20 and maintain it while continuing the full-scale measurement.

  Among these, when the maximum compliance pressure with a relatively low mounting pressure is used, it is easier to change and it is easier to obtain sensitive data changes. For this reason, the maximum compliance pressure is set as the optimum pressure for the first probe 21 (same as the third probe 23) for measuring the pulse wave of the thin blood vessel (peripheral blood vessel) at the fingertip. Is preferred. Here, the compliance C is the extensibility of the blood vessel wall, and is expressed by the change in the volume of the blood vessel / the change in the wall pressure. The mounting pressure at the extreme point of the compliance C (the change in the compliance C is zero) is the optimum pressure. By measuring and maintaining the pulse wave, it is possible to eliminate the influence of non-NO-dependent elements and realize measurement with maximum sensitivity. That is, since it is measured only by the hyperemia reaction by NO (nitrogen monoxide) reflecting the vascular endothelial function, the vascular endothelial function can be evaluated with high accuracy.

  On the other hand, when the maximum amplitude pressure with a relatively high mounting pressure is used, it is easy to obtain data with reduced noise. For this reason, it is preferable that the maximum amplitude pressure be the optimum pressure for the second probe 22 and the fourth probe 24 that measure the pulse wave of the thick blood vessel (radial artery) in the wrist.

  In this way, full-scale measurement is started while maintaining the optimum pressure for each probe 20, and measurement before blood pressure is performed for a predetermined time. The measurement time is approximately 2 minutes. The voltage change measured by the light receiving sensor 203 is amplified by an amplifier circuit, transmitted to the computer 40 after A / D conversion, calculated and stored as an amplitude value, and displayed on the display unit. In addition, the computer 40 calculates a chaos attractor by chaos analysis based on the calculated amplitude value and the rate of change (step S103). The chaos analysis will be described later again.

  Next, the test side is pressurized with the cuff 10 (step S104), and blood is fed for a predetermined time (step S105). The time for driving is approximately 3 minutes. Determine if full blood transfusion has been reached, and if not, continue pressurization until blood transfusion is achieved. As shown in FIG. 3, the cuff 10 is pressurized and released by the pressure pump 104, the pressure reducing valve 105, and the pressure sensor 106. The method for determining whether or not the blood transfusion is complete is to calculate the correlation coefficient of the pulse wave between the first probe 21 and the third probe 23 or between the second probe 22 and the fourth probe 24. When it is smaller than the threshold value, it is determined that blood is being driven. After the blood transfusion is achieved, the set pressure is automatically maintained until a predetermined blood transfusion time elapses while monitoring and controlling the pressure drop.

  Thereafter, the cuff 10 is opened to resume blood flow (step S106), and the measurement after the blood pressure is performed for a predetermined time. The measurement time is approximately 1 minute. As a result, the total measurement time in this embodiment is approximately 5 minutes. The voltage change measured by the light receiving sensor 203 is amplified by an amplifier circuit, transmitted to the computer 40 after A / D conversion, calculated and stored as an amplitude value, and displayed on the display unit. Further, the computer 40 calculates a chaos attractor by chaos analysis based on the calculated amplitude value and the rate of change thereof (step S107). The chaos analysis will be described later again.

  FIG. 7 shows the amplitude of the pulse wave measured by the first probe 21 on the inspection side in the upper stage and the third probe 23 on the control side in the lower stage. The horizontal axis represents time, and the vertical axis represents the amplitude value of the pulse wave. On the inspection side, the pulse wave has disappeared for a certain period of time due to blood pumping. In the figure, A is a measurement interval after blood transfer on the examination side, B is a measurement interval before blood pressure on the examination side, C is a measurement interval after blood pressure on the control side, and D is also before blood pressure on the control side. Represents a measurement interval. The vasodilation rate of the subject is set as follows based on the average amplitude value calculated from the obtained amplitude values before and after the blood transfusion. That is, the mean amplitude value after the blood transfusion on the side of the blood transfusion and the test side is (A), and the average amplitude value before the blood transfusion is also the same as (B). When the average amplitude value is (C) and the average amplitude value before blood transfusion is (D), the ratio before and after blood transfusion (A / B) on the examination side and the ratio before and after blood transfusion (C / D) on the control side The test side / control side ratio ((A / B) / (C / D)) of the former (A / B) with respect to the latter (C / D) is obtained as the vasodilator rate (step S108).

  About this test | inspection side / control | contrast side ratio, it can say as follows in relation to FMD and end pad 2000. That is, the FMD and the end pad 2000 are determined by determining the ratio of before and after blood transfer on the test side and the control side. In this embodiment, however, the FMD and end pad 2000 are expressed abnormally by the ratio of the test side / control side. The result is less. Moreover, about the reproducibility mentioned above, when each subject was measured several times for 3 days by the method of this embodiment, FMD, and end pad 2000, respectively, it was 4.7% in this order as a coefficient of variation. The results of 22% and 18% are obtained. Here, it has been found that the test side / control side ratio has a good inverse correlation with the risk factor (aging, vascular sclerosis), and for aging, the test side / control side ratio = −0. .00194 * age + 2.4019, correlation coefficient r = 0.46, for vascular sclerosis, test side / control ratio = −0.00112 * vascular sclerosis (blood vessel age) +1.8728, correlation coefficient r = 0 .57.

  The above-mentioned ratio before and after the blood transfusion (A / B), the ratio before and after the blood transfusion (C / D) and the ratio of the inspection side / control ((A / B) / (C / D)) Not only the vasodilator ratio obtained from the amplitude value but also the chaotic attractor calculated as vascular fluctuation from the amplitude value and its rate of change by chaos analysis, as explained in the following section, the change in the Lyapunov exponent obtained Even applied as a change in the fluctuation index. Furthermore, the chaos attractor is visualized as a pattern (mode), and is compared with a known chaos attractor group related to cardiovascular disease stored in the database 41 inside and outside the computer 40 by pattern matching. As described above, the state of the vascular function is determined by comparison with the reference value of each ratio (step S109) and / or the pattern matching of the chaos attractor (step S110), and thus the cardiovascular disease is determined.

<Chaos analysis>
In the present embodiment, the vascular function inspection apparatus 1 described above uses a unique chaos analysis technique based on the measured amplitude value of the pulse wave and the rate of change thereof, and a slight change that occurs during vascular fluctuation, that is, vasodilation. Analyze. As shown in FIG. 8, a chaotic attractor obtained by chaotic analysis is grasped as a blood vessel fluctuation, a blood vessel dilation pattern (mode) is shown, and a complex and non-uniform blood vessel due to shear force P1 and blood vessel wall pressure P2 due to blood flow. Deformation can be seen, and it is possible to determine the etiology of vascular dysfunction.

  The upper part of FIG. 8 shows the chaos attractor before blood transfusion (before vasodilation) and after the blood transfusion (after vasodilation) related to the first fingertip F1 on the examination side, and the middle part shows the amplitude of the first fingertip F1. The lower row shows the amplitude of the second fingertip F2 on the control side. Here, as shown in the middle part of FIG. 8, an example is shown in which the amplitude of the pulse wave on the examination side is larger after the blood pumping than before the blood pumping. The chaotic attractor has a larger size (area) than that of the chaotic attractor prior to blood pressure, and has a wider width between the loops. By comparing the chaos tractors before and after blood driving, changes in blood vessel fluctuations can be grasped.

  Furthermore, the pattern of the chaotic attractor after blood transfusion (after vasodilation) is compared with the known chaotic attractor stored in the database 41 corresponding to each cardiovascular disease by pattern matching. The etiology of can be determined. FIG. 9 shows an example of correspondence between chaotic attractor patterns after blood transfusion (after vasodilation), vascular endothelial damage / deformation, and etiology. The upper row shows myocardial infarction and the lower row shows myocardial infarction. Show.

  The chaos analysis will be described in detail below. A chaos attractor is generally a set of a dynamical system that evolves in time. In the dynamical system, when moving from a point close enough to the chaotic attractor, it remains sufficiently close to the chaotic attractor. The trajectory included in the chaotic attractor is not limited other than to remain inside the chaotic attractor, and may be periodic or chaotic. In this embodiment, the horizontal axis is the amplitude value of the pulse wave, and the vertical axis is the set plotted with the change rate (amplitude velocity) of the amplitude value. The shape and size of the chaos attractor can grasp the effective change of vessel group shape and size of the vessel group in a non-linear manner. Quantitatively, the following two matters are grasped.

  First, the Lyapunov exponent is grasped as a fluctuation exponent indicating a shape change. As will be described later, the Lyapunov exponent is a quantity that represents the degree to which a very close trajectory leaves in a dynamic system. The Lyapunov exponent is a numerical value indicating instability (variation). If the value is large, it is unstable and has a lot of variation, and if it is small, the Lyapunov exponent is stable. The term “unstable” here means that when a small force is applied to the dynamic system, it appears as a large change in state.

Second, the outer area of the chaotic attractor is captured as an area indicating the size. The outer peripheral area is an area of a quadrangle when the sides are parallel to the horizontal axis (x axis) and the vertical axis (y axis) so that the entire range in which the chaotic attractor moves can be enclosed. The calculation formula is represented by the following formula.
Env. Area = (max (x) −min (x)) * (max (y) −min (y))

When the first probe 21 of the first fingertip F1 on the examination side and the second probe 22 of the first wrist W1 are targeted, the overall index Index of the vascular endothelial function is calculated as follows using the above two numerical values. Can be expressed as
Index = Cs * {A1 * average amplitude value of the first fingertip (or outer area of the chaotic attractor) + A2 * fluctuation index of the first fingertip} + Cl * {A3 * average amplitude value of the first wrist (or Chaos attractor outer circumference area) + A4 * Fluctuation index of the first wrist}
Here, Cs: contribution to the first fingertip, Cl: contribution to the first wrist, A1 to A4: respective dependency coefficients.

<< Visualization of chaos attractors >>
Next, a method for visualizing a chaos attractor from a biological signal such as a pulse wave will be described. A method of drawing the shape of a chaos attractor from a biological signal of a time series waveform is called a Turkens method, and N state variables such as time series waveforms S _t = {S ₁ , S ₂ ,..., S _N } are used. Consider restoring to d. First, a set P _i of d state variables is created using the delay time τ.
P _i = {S _i , S _{i + τ} , S _{i + 2τ} ,..., S _{i + (d−1) τ} }
If the number of state variables to be restored is 3, the set Pi is as follows.
P _i = {S _i , S _{i + τ} , S _{i + 2τ} }

By repeating this operation in the range of 1 ≦ i <N− (d−1) τ, the structure of the dynamic system can be approximately restored. Further, _Pi can be regarded as d-dimensional state space coordinates, and the motion of the dynamic system can be expressed as a chaos attractor by connecting the coordinates. The image of the Turkens method is shown in FIGS. S _i , S _{i + τ} , and S _{i + 2τ} are regarded as X-axis coordinates, Y-axis coordinates, and Z-axis coordinates, respectively, and (x ₁ , y ₁ , z ₁ ), (x ₂ , y ₂ , z ₂ ), ( x ₃ , y ₃ , z ₃ ) are embedded in a three-dimensional state space having three axes of X, Y, and Z shown in the left diagram of FIG. If this is repeated in the range of 1 ≦ i <N− (d−1) τ, the result is as shown on the right side of FIG. Restoring one state variable to d in this method is called embedding, the delay time τ is the embedding delay time, and the number d of state variables to be restored (this can also be considered as the dimension of the state space) is the embedding dimension. Call it. It is necessary to obtain an optimum value for each parameter using autocorrelation and fractal dimension.

<< Lyapunov index >>
The Lyapunov exponent can be obtained by following the trajectory in a chaos attractor as follows: The states that are similar to each other at the initial time are in similar positions (close distances) in the hypersphere size. As shown in FIG. 12, when this distance is r (0) and this trajectory is developed and the distance at the time t (difference in trajectory, degree of separation) is r (t),
r (t) = r (0) * exp (λt)
This λ is called the Lyapunov exponent. According to the algorithm of Rosenstein (1993), the Lyapunov exponent is estimated as follows. When the initial displacement between adjacent trajectories is D and the displacement after t seconds is d (t), the Lyapunov exponent λ is
d (t) = D * exp (λt)
Logarithm conversion is performed on both sides of the above formula. Log (d (t)) = λt + log (D)
Thus, the Lyapunov exponent λ is estimated as the slope of the linear approximate straight line of the displacement between adjacent trajectories-time function.

<< Pattern matching of chaotic attractors >>
For pattern matching of chaos attractors, pattern similarity is calculated by applying a template matching method used in character recognition. For example, if the chaos attractor of the calculation file and the chaos attractor of the basic data file are each two-dimensional, the number is divided into 100 × 100 cells, and points exist in both chaos attractor cells. Count. In the three-dimensional case, the plane is expanded from a “plane” to a “solid”, divided into 100 × 100 × 100 cells, and the number of points in both chaotic attractor cells is counted.

Here, the similarity between two chaotic attractors is calculated by calculating the number of cells where points exist only in each chaotic attractor as T1, and the number of cells where points exist in common in both chaotic attractors. Is T2, the pattern similarity between the two is expressed by the following equation.
Pattern similarity = (T2 / T1) × 100

<< Other examples showing features of chaotic attractors >>
In addition to the method described above, the method for determining the characteristic amount of the chaos attractor may be as follows, for example. The feature lengths of the minor axis D and the major axis L of each loop of the chaos attractor are calculated, and thereby diagnosis can be performed with high accuracy. The vector is linearly transformed to calculate a vector having the same direction and a different size. D and L are called eigenvectors, and their values (lengths) are called “eigenvalues”. When the eigenvector corresponding to the largest eigenvalue is L and the eigenvector corresponding to the second largest eigenvalue is D,
Q = D / L
For example, if Q = 0.75 or more, a minor failure, if Q = 0.50-0.75, a moderate failure, if Q = 0.50 or less, a severe failure It can be diagnosed.

<< Display of chaos analysis results >>
FIG. 13 and FIG. 14 show an example in which the result obtained by the chaos analysis is displayed on the display 42. In these drawings, from the upper side to the lower side, the amplitude of the pulse wave of the first fingertip F1 on the examination side, the amplitude of the pulse wave of the second fingertip F2 on the control side, and the first wrist W1 on the examination side are shown on the left side. The amplitude of the pulse wave and the amplitude of the pulse wave of the second wrist W2 on the control side are displayed, and the chaos attractors before and after the blood transfusion corresponding to each are displayed in the center. On the upper right side, as analysis results, the average amplitude value, the maximum amplitude value-the minimum amplitude value, the pre- and post-operation ratios on the examination side related to the Lyapunov index, the pre- and post-operation ratios on the control side, and the examination results The side / control side ratio is displayed. On the lower right side, for each fingertip and wrist, the measurement start time before blood transfusion, baseline duration before blood transfusion, measurement start time after blood transfusion, and region of interest (ROI) duration after blood transfusion Is displayed.

  FIG. 13 shows an analysis result of a subject having an etiology such as myocardial infarction, cerebral infarction, coronary arteriosclerosis, and in this case, the analysis result (reduced vascular endothelial function) in a thick blood vessel, that is, the radial artery of the wrist is used effectively. be able to. On the other hand, FIG. 14 shows the analysis result of a subject having an etiology such as diabetes, tonsillar disease, and peripheral disease. In this case, the analysis result (peripheral vascular function decrease) in the peripheral blood vessel of a thin blood vessel, that is, the fingertip is shown. It can be used effectively.

<Comparison with end pad 2000>
Finally, a comparison between this embodiment and the end pad 2000 will be described. In this embodiment, as described above, the probe 20 of both fingertips and both wrists is used only once, whereas the probe of the end pad 2000 is disposable only once. LED / light-receiving sensor type that does not depend on the fingertip is adopted, and the fingertip or wrist is pressed with the optimum pressure. As a result, the running cost is suppressed, an inexpensive probe that can be used semipermanently can be provided, and the cost can be reduced.

  Moreover, when the comparison test with the end pad 2000 and this embodiment was done, the high correlation was confirmed between both test results. Specifically, with a healthy subject as the subject, simultaneous measurement was performed with Endpad 2000 and a prototype device reflecting this embodiment, and the vascular endothelial function evaluation index (RHI; Reactive Hyperemia Index) of both was analyzed. As a result, as shown in FIG. 15, a sufficient correlation with a correlation coefficient R = 0.68 (significance probability P <0.05) and an estimation error of 0.036 was obtained, and significance was recognized. That is, it was confirmed that this prototype device can replace the imported end pad 2000 as a popular device.

<Modification of this embodiment>
In the above-described embodiment, the probe 20 includes the first probe 21 attached to the first fingertip F1 on the examination side, the second probe 22 attached to the first wrist W1 on the examination side, and the second finger on the control side. The case where the third probe 23 attached to the apex F2 and the fourth probe 24 attached to the second wrist W2 on the control side are included, that is, the case of four-point measurement has been described. However, the setting of the probe 20 is not limited to the four-point measurement in which the four probes 20 are mounted, depending on the purpose of the inspection, the condition of the subject, and the like. Even in two-point measurement with two probes 20 attached, the gist of the present invention can be reflected in the configuration and procedure of measurement and analysis.

  For one-point measurement, for example, in the case of a subject who has difficulty with one upper limb, if it is sufficient to measure only thin blood vessels (peripheral blood vessels) with the other upper limb as the examination side, the first finger on the examination side Only the first probe 21 attached to the cusp F1 or only the second probe 22 attached to the first wrist W1 on the examination side is sufficient if it is sufficient to measure only a thick blood vessel (radial artery). There are cases.

  As for the two-point measurement, in the case of a subject who is incapable of having one upper limb, the first probe 21 to be attached to the first fingertip F1 on the inspection side and the first wrist on the inspection side with the other upper limb as the inspection side The case where it is set as the combination of the 2nd probe 22 with which W1 is mounted | worn is mentioned. In the case of a subject whose both upper limbs are free, if it is sufficient to measure only thin blood vessels (peripheral blood vessels), the first probe 21 attached to the first fingertip F1 on the examination side and the second on the control side. A combination of the third probe 23 attached to the fingertip F2 may be used, and if it is sufficient to measure only a thick blood vessel (radial artery), the second probe 22 attached to the first wrist W1 on the examination side. And a combination of the fourth probe 24 attached to the second wrist W2 on the control side.

  In the case of one-point measurement or two-point measurement in which the probe 20 is not attached to the control side, it is not possible to calculate the control side pre-transfusion ratio and the test side / control side ratio for the amplitude value of the pulse wave and the Lyapunov index. Even in such cases, it is possible to compare the ratio before and after the blood transfusion on the examination side, the comparison with the chaos attractor before and after the blood transfusion, and the comparison with the known chaos attractor for each known cardiovascular disease. The gist of can be applied.

<Effect of this embodiment>
The effects of this embodiment are summarized as follows.
(1) The measurement time can be significantly reduced from 15 minutes for FMD and end pad 2000 to approximately 5 minutes.
(2) The cuff wound around the upper arm of the examination side is fully automated for pressurization and release, and intelligent control of pressurization is performed. The cuff pressurization is automatically monitored by a computer and controlled until complete blood can be driven. Pressure and partial pressure can be avoided.
(3) By setting and maintaining the mounting pressure applied to the fingertip and wrist as the optimal pressure at the extreme point of compliance (zero change in compliance) and measuring the pulse wave, The effect can be excluded and measurement with maximum sensitivity is realized. That is, since it is measured only by the hyperemia reaction by NO (nitrogen monoxide) reflecting the vascular endothelial function, the vascular endothelial function can be evaluated with high accuracy.
(4) Compared with FMD and Endpad 2000, vascular endothelial function is represented by a change in amplitude due to hyperemia (ratio on the test side / control side), and abnormal results are reduced.
(5) The mounting pressure applied to the fingertips and wrists every time measurement is performed is set to the optimum pressure, so that elements of variation in measurement results can be absorbed and the reproducibility is excellent.
(6) The inverse correlation obtained between the test side / control side ratio and the risk factor (aging, vascular sclerosis) can be utilized.
(7) Overcoming the drawbacks of FMD and Endpad 2000, providing a probe at low cost, reducing costs, making it easy for anyone to use in fully automatic measurement and analysis, and providing it as a medical device that can be used for general clinical testing.
(8) Since the blood vessel function of both the thick blood vessel and the thin blood vessel can be inspected, and the ratio of both can be quantified by simultaneous observation, it is possible to widely inspect the blood vessel dysfunction.
(9) The pattern (complex state) of vasodilation due to vascular fluctuation can be grasped, and the etiology of a disease caused by vascular dysfunction can be determined.

  As described above, the present invention is not limited to the specific embodiments described above, and includes various modifications, which are described in the scope of the claims for those skilled in the art. It is clear from

  Since the present invention is a method capable of examining a non-invasive direct blood vessel function in a living body, there is a possibility that the present invention can be utilized for a metabolic screening business or the like. In addition to early detection of vascular lesions as a pre-arteriosclerosis diagnosis, it can also contribute to the health management business of residents who have received guidance from the Metaboloc syndrome. In addition, it is possible to determine in vivo drug efficacy of statin drugs and antiplatelet drugs against arteriosclerosis.

DESCRIPTION OF SYMBOLS 1 ... Vascular function test apparatus 10 ... Cuff (pressurization part)
104 ... Pressure pump 105 ... Exhaust valve 106 ... Pressure sensor 20 ... Probe 201 ... Air bag 202 ... LED (light emitting part)
203. Light receiving sensor (light receiving part)
204 ... Pressure pump 205 ... Exhaust valve 206 ... Pressure sensor 21 ... First probe 21a ... Air tube 22 ... Second probe 22a ... Air tube 23 ... Third probe 23a ... Air tube 24 ... Fourth probe 24a ... Air tube 30 ... Device main body 31 ... control unit 40 ... computer (processing unit)
41 ... Database (storage unit)
42 ... Display (display part)

Claims (12)

A vascular function testing device,
A pressurizing part that is mounted on the upper arm of the examination side and performs blood transfer and release;
A probe that is attached to each fingertip on the examination side and the control side , or that is attached to each wrist on the examination side and the control side, and measures pulse waves before and after blood transfusion,
A control unit for controlling the pressurizing unit and the probe;
A processing unit that gives a command to the control unit and acquires data relating to the pulse wave from the control unit;
A numerical value obtained by quantifying a feature amount for the processing unit to calculate an average amplitude value and perform chaos analysis based on data relating to the pulse wave before and after blood transfusion, and to determine cardiovascular disease and vascular endothelial dysfunction To calculate
Based on the quantified numerical value, the processing unit sets the numerical value after the blood pumping on the examination side as (A), the numerical value before the blood pressure driving (B), and the numerical value after the blood pressure driving on the control side (C ), And when the numerical value before blood transfusion is represented by (D), the test side pre- and post-drive ratio (C / D) and the test side pre- and post-drive ratio are A blood vessel function test apparatus characterized by obtaining a test side / control side ratio ((A / B) / (C / D)) with respect to a ratio before and after control side blood transfusion. As the chaos analysis, the processing unit calculates a chaos attractor indicating blood vessel fluctuations before and after blood transfusion based on the amplitude value of the pulse wave and the rate of change thereof, the Lyapunov exponent for the calculated chaos attractor, 2. The blood vessel function testing device according to claim 1, wherein a numerical value obtained by quantifying the feature amount is obtained by quantifying at least one of an outer peripheral area and an eigenvector of a minor axis and a major axis.   The blood vessel function testing device according to claim 1, wherein the probe measures the pulse wave by a photoelectric method or a pressure method.   The probe is photoelectric, and includes an air bag for applying an optimum pressure to the measurement site, a light emitting unit for irradiating the measurement site with light, and a light receiving unit for receiving reflected light from the measurement site. The vascular function testing device according to claim 3.   The blood vessel function according to any one of claims 1 to 4, wherein the probe includes a first probe that is attached to a first fingertip on an examination side and that measures the pulse wave related to a thin blood vessel. Inspection device.   The vascular function testing device according to claim 5, further comprising a second probe that is attached to the first wrist on the examination side and that measures the pulse wave related to a thick blood vessel.   The probe is attached to the second fingertip on the control side and measures the pulse wave related to the thin blood vessel, and the probe is attached to the second wrist on the control side and measures the pulse wave related to the thick blood vessel. The blood vessel function testing device according to claim 6, further comprising a fourth probe. The processing unit is configured to compare the examination-side blood pressure before and after ratio and the control-side blood pressure before and after ratio for both the pulse wave of the fingertip on the examination side and the control side and the pulse wave of the wrist on the examination side and the control side. The blood vessel function testing device according to claim 1, wherein the test side / control side ratio is obtained. A storage unit for storing a group of known chaotic attractors for each of the cardiovascular diseases,
9. The blood vessel function testing device according to claim 2, wherein the processing unit compares the calculated chaotic attractor with the known chaotic attractor group by pattern matching. 10.   The vascular function testing device according to claim 1, further comprising a display unit that displays a result processed by the processing unit. A blood vessel function test method,
A first step of preliminarily applying pressure to the first fingertip and the first wrist on the examination side and the second fingertip and the second wrist on the control side and measuring the respective pulse waves;
Determining whether the pressure is optimal for the subject, and if yes, maintaining a second optimum pressure;
An amplitude value is calculated on the basis of the measured pulse waves before blood transfusion, and a chaotic attractor before blood transfusion related to the first fingertip, the first wrist, the second fingertip, and the second wrist is calculated. A third step of calculating;
A fourth step of applying blood pressure to the first fingertip and the first wrist on the examination side for a predetermined time;
An amplitude value is calculated based on the measured pulse waves after the blood transfusion, and a chaotic attractor after the blood transfusion related to the first fingertip, the first wrist, the second fingertip, and the second wrist is calculated. A fifth step of calculating;
Regarding the amplitude value calculated in the fifth step and the calculated chaos attractor, the numerical value after blood driving on the examination side is (A), the numerical value before blood driving is also (B), and the blood pressure is transferred on the control side. When the subsequent numerical value is (C) and the numerical value before the blood transfusion is (D), the ratio before and after the test side driving (A / B), the ratio before and after the control side driving (C / D), and the test side A sixth step of obtaining a test side / control side ratio ((A / B) / (C / D)) of the pre- and post-transfusion ratio relative to the control-side pre-driving ratio;
A seventh step of comparing the test side pre- and post-drive ratio, the control side pre- and post-drive ratio, and the test / control side ratio with respective reference values;
An eighth step of outputting information relating to cardiovascular disease and vascular endothelial dysfunction based on a result of comparison in the seventh step.   The blood vessel according to claim 11, further comprising a ninth step of comparing the calculated chaotic attractor with a known chaotic attractor group for each cardiovascular disease by pattern matching after the fifth step. Function inspection method.