JP2007175127A - Blood viscosity measuring device - Google Patents

Abstract

The present invention provides a blood viscosity measuring apparatus capable of more reliably measuring blood viscosity by a non-invasive method than in the past.
SOLUTION: A means for non-invasively irradiating ultrasonic waves along the direction of blood flow in a blood vessel from the surface of the living body, and after the ultrasonic waves are incident on the living body, they are emitted outside the living body via blood. Means B for receiving the ultrasonic wave, means C for measuring the distribution of the frequency difference Δf due to the Doppler effect generated in the ultrasonic wave by blood flow, means D for measuring the temporal change of the difference Δf, and temporal change of the difference Δf. Based on this, the means E for measuring the blood flow velocity distribution in the blood vessel and the means F for measuring the blood viscosity based on the temporal change of the flow velocity distribution constitute a blood viscosity measuring device.
[Selection] Figure 5

Description

  The present invention relates to a blood viscosity measuring apparatus for noninvasively measuring the viscosity of blood flowing in a blood vessel.

  A conventional method for noninvasively measuring the viscosity of blood is proposed in Patent Document 1, for example. In the method described in Patent Document 1, pressure sensors are set in advance at two predetermined distances along the artery, and the blood flow in the artery is changed by the pressure control means that compresses the artery with air pressure. It is characterized by that.

  Specifically, the pressure control means temporarily interrupts the blood flow, and then gradually starts to flow blood by gradually reducing the pressure. At this time, the timing at which the blood has moved under the two sensors is detected by the two pressure sensors. Thereby, the flow rate is measured from the time until blood moves from the pressure sensor 1 to the pressure sensor 2. Since the flow rate is inversely proportional to the viscosity, the viscosity can be finally measured.

  However, in the method described in Patent Document 1, it is necessary to block the blood flow in advance, which imposes a burden on the living body. In addition, it is known that blood is not a Newtonian fluid, and its viscosity changes depending on the flow rate. Therefore, according to the method described in Patent Document 1, it is theoretically difficult to measure the viscosity of blood in a normal blood flow state of a living body.

For example, Non-Patent Document 1 describes the relationship between the blood flow velocity and the viscosity. According to the description of Non-Patent Document 1, the blood flow velocity u (r) at a position a distance a from the blood vessel wall and Between the viscosity μ, the pressures P1 and P2 at two different points, the distance L between the two points, and the diameter r of the blood vessel, the relation: u (r) = (a ² −r ² ) (P ₁ − P ₂ ) / (4 μL) holds.

That is, to determine the viscosity μ, not just the flow velocity u (r), but the distance a from the vessel wall, the pressures P ₁ and P ₂ at two different points, the distance L between the two points, and the vessel The diameter r is essential. Nevertheless, in the method described in Patent Document 1, since the blood vessel is closed and the diameter is changed by the pressure applied from the outside of the living body, accurate measurement becomes difficult in view of the above relational expression. It is.
Japanese Patent No. 3057266 Rheology and blood flow of blood, Motoaki Sugawara, Shinji Maeda, Corona, April 25, 2003, page 80

  Therefore, an object of the present invention is to provide a blood viscosity measuring apparatus that can more reliably measure blood viscosity by a non-invasive method than in the past.

In order to solve the above problems, the present invention provides:
Means A for non-invasively irradiating the first ultrasonic wave along the direction of blood flow in the blood vessel from the surface of the living body (at an angle including the direction of blood flow);
Means B for receiving a second ultrasonic wave emitted from the living body via the blood after the first ultrasonic wave is incident on the living body;
A first frequency of the first ultrasonic wave and a second frequency of the second ultrasonic wave due to the Doppler effect generated between the first ultrasonic wave and the second ultrasonic wave by the blood flow. Means C for measuring the temporal change of the difference Δf from the frequency;
Means D for measuring the temporal change of the difference Δf;
Means E for measuring the flow velocity distribution of the blood in the blood vessel based on the temporal change of the difference Δf;
Means F for measuring the viscosity of the blood based on temporal changes in the flow velocity distribution;
A blood viscosity measuring apparatus comprising:

  According to the above configuration, the temporal change in the flow velocity distribution of the blood flowing in the blood vessel can be measured from the Doppler effect by the addition of ultrasonic waves, and the temporal change in the flow velocity distribution is more reliable than in the past. The viscosity can be measured.

The blood viscosity measuring device is
Means for detecting the pulsation of the pulse;
It is preferable to comprise means for synchronizing the pulsation interval with the temporal change of the flow velocity distribution.
Since blood flow is caused by the heart, the temporal change in flow rate is repeated in response to the beat. Therefore, according to such a configuration, there is an advantage that a more accurate and simple analysis method can be obtained by using acquisition of an average value from repeated data corresponding to pulsation.

Moreover, it is preferable that the said means E has the structure which measures the thickness of the boundary layer in the said blood vessel approximated to the said flow velocity distribution as said flow velocity distribution.
Further, it is preferable that the means F measures the viscosity of the blood based on a temporal change in the thickness of the boundary layer.

  ADVANTAGE OF THE INVENTION According to this invention, the blood viscosity measuring apparatus which can measure the viscosity of blood more reliably compared with the past by a noninvasive method can be provided. Further, according to the blood viscosity measuring apparatus of the present invention, it is not necessary to apply pressure to the living body, and the blood viscosity can be measured while the blood flowing in the blood vessel maintains its normal flow rate.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the drawings. In the following description, the same or corresponding parts are denoted by the same reference numerals, and redundant description is omitted.
First, in order to facilitate understanding of the blood viscosity measuring apparatus of the present invention, a blood flow (blood flow rate) measuring apparatus using the ultrasonic Doppler effect will be described. It is well known that blood flow (blood flow) can be measured by the ultrasonic Doppler effect. FIG. 1 is a diagram showing a configuration of a conventional blood flow measuring device having the simplest configuration using the ultrasonic Doppler effect.

  A conventional blood flow measuring device 100 is configured such that an ultrasonic wave is irradiated and incident at an angle θ with a probe (not shown) including an ultrasonic transmitter 102 and a receiver 104 parallel to the blood vessel 4. have. In FIG. 1, since the blood is irradiated (incident) in the blood flow direction indicated by the arrow P, that is, in the direction of following the blood flow, the ultrasonic wave 104 returned to the receiver 104 is in a direction in which the frequency decreases. Receives the Doppler effect.

  At this time, the difference (change) Δf between the frequency of the incident ultrasonic wave (transmission frequency) and the frequency of the emitted ultrasonic wave (reception frequency) is expressed by Equation (1):

(Where f ₀ is the transmission frequency, C is the speed of sound, U is the blood flow velocity in the blood vessel)
Is required.

  Blood is a viscous fluid. The simplest method for obtaining the flow velocity of a fluid having viscosity is to assume that the Newtonian fluid flows in a laminar flow in the pipe, and formula (2) that holds between the shear velocity ν, shear stress τ, and viscosity μ:

The method using is mentioned. When the fluid flows in the pipe, microscopically, the fluid does not move at the portion in contact with the pipe wall, and the fluid moves at the highest shear rate at the center of the pipe. That is, it is known to exhibit a parabolic behavior.

  However, in reality, the higher the shear rate of blood, the lower the rate, and blood is a non-Newtonian fluid having so-called thixotropic properties. Further, since blood undergoes a temporal change (time transition) due to pulsation, it is difficult to measure the blood flow rate with high accuracy by simply applying the above formulas (1) and (2) to blood. is there.

  On the other hand, as a method for noninvasively measuring the blood flow velocity using the ultrasonic Doppler effect, for example, Non-Patent Document 2 (biological sensor and measuring device, Kenichi Yamakoshi, Tatsuo Togawa, Corona Publishing, 2000 (September 25, pp. 58-103), a method using a continuous wave or a method using an ultrasonic pulse has been proposed. However, the non-Newtonian nature of blood, the temporal change of the flow rate due to pulsation, etc. Due to these factors, it is difficult to measure the average blood flow rate.

The present inventors have actively focused on the above-described factors that hinder accurate measurement of the blood flow rate, and if the Doppler effect is used, the viscosity can be accurately measured as a physical quantity different from the blood flow rate. As a result of intensive studies, the present invention as described above has been completed.
Here, the figure which shows the time change (time transition) by the pulsation of the flow velocity distribution of the blood in the blood vessel is shown in FIG. FIG. 2 is described on page 60 of Non-Patent Document 2 above.

As shown in FIG. 2, the curve indicating the blood flow velocity distribution in the blood vessel has a shape close to a wide trapezoid at the beginning of the pulsation (time t ₁ ), and at the peak of the pulsation (time t _3). ) Shows a shape close to a paraboloid called a Poiseuille flow having a maximum point in the flow direction indicated by the arrow Q. Such behavior is very difficult to handle mathematically, and the above-mentioned Non-Patent Document 1 does not mention detailed analysis.

  Therefore, the present inventors have assumed that the temporal change (time transition) of the blood flow velocity distribution in the blood vessel due to pulsation is a boundary in the region between the tube wall and the fluid when assuming the fluid flowing in the tube. For the first time, attention was paid to the approximation by the layer concept, and it was found that this can be applied to the measurement of blood viscosity, and the present invention has been completed.

  The concept of the boundary layer is described on pages 76 to 78 of Non-Patent Document 1 above. According to this description, a flat plate (wall surface) having an infinitely large area and a viscous fluid having an infinitely large volume are assumed, and when the fluid is moved parallel to the plane of the flat plate, the fluid is separated from the wall surface. The range in which the viscosity affects the flow velocity is zero at the beginning of movement, but increases with time. Finally, between the range (ie, boundary layer thickness) δ, the fluid viscosity μ, the time t, and the fluid density ρ affected by the viscosity of the fluid, Equation (3):

An approximate expression expressed as follows is obtained. In the approximate expression given by equation (3), the boundary layer thickness δ is proportional to the viscosity μ and the square root of time t, and inversely proportional to the density ρ. Further, the thickness δ of the boundary layer increases indefinitely with the passage of time t.

  In view of the above, the blood viscosity measurement device of the present invention has basically the same configuration (for example, a transmitter, a receiver, a mixer, and a calculation device) as the blood flow measurement device 100 using a continuous wave shown in FIG. However, the measurement data analysis algorithm has a different configuration.

When blood in a blood vessel is measured using a mechanism similar to that of the blood flow measuring device 100, at time t (t ₁ , t _2, or t ₃ ), ultrasonic waves incident on the living body due to the Doppler effect (first Frequency (first frequency) and the frequency (second frequency) of the ultrasonic wave (second ultrasonic wave) that is incident on the living body and then exits the living body via blood in the blood vessel. ) Is distributed as shown in FIG. 3, for example.

  FIG. 3 shows the frequency (first frequency) of the ultrasonic wave (first ultrasonic wave) incident on the living body due to the Doppler effect and the blood inside the blood vessel after being incident on the living body to the outside of the living body. It is a figure which shows the data of the time change (time transition) of difference (DELTA) f with the frequency (2nd frequency) of the emitted ultrasonic wave (2nd ultrasonic wave). However, FIG. 3 shows a distribution curve obtained by simplifying the frequency peaks of the respective frequencies by combining them for the subsequent analysis.

As can be seen from FIG. 3, the shape of the distribution curve of Δf changes greatly with the influence of pulsation as time elapses. At time t _1, since it is immediately after ventricular contractions of the heart, small Δf has appeared frequently. This corresponds to time t ₁ in FIG. 2, and blood with a low flow rate (flow rate) is in the radial direction of the blood vessel 4 (ie, in a direction substantially perpendicular to the length direction indicated by the arrow Q in FIG. 2). It shows that it is distributed throughout.

At time t ₃ when the amount of blood discharged from the heart reaches a peak, a large Δf appears at a low frequency as can be seen from FIG. However, a relatively broad peak is observed. This corresponds to the time t ₃ in FIG. 2, and the blood is affected by the viscosity over almost the entire region in the radial direction of the blood vessel 4 and shows that blood having different flow rates (flow rates) is distributed.

Next, in the blood viscosity measuring apparatus of the present invention, in order to quantitatively determine the depth of the boundary layer, further analysis is added to the data shown in FIG. That is, the curve width d1 indicating the half value of the peak value of the distribution intensity is obtained at time t ₁ in FIG. Here, the d value is a quantitative value that relatively indicates the depth of the boundary layer at that time.
Using the constant a,

Then, equation (3) becomes

It becomes.
When the differences d ₂ , d ₃ ... Are obtained in the same manner as described above and plotted against time t, the curve 2 shown in FIG. 4 is obtained. In addition, blood having the same diameter and measurement conditions are used for blood of different viscosities (ie, pseudo blood having different viscosities, the same pseudo blood vessel diameter and the same measurement conditions), and the thickness δ of the boundary layer is obtained with respect to time t. For example, curves 1 and 3 shown in FIG. 4 are obtained. And based on the said Formula (5), the viscosity (micro | micron | mu) of blood can be calculated | required from the inclination of the said curves 1-3. FIG. 4 is a diagram showing the time transition of the d value of blood with different viscosities.

  In the above formulas (3) and (5), it is shown that δ is proportional to the square root of μ. However, in the present invention that is actually applied to blood flow in blood vessels, this approximation is completely. The formula is not true. Specifically, since the above equation (3) assumes a relationship between a flat plate (wall surface) having an infinitely large area and a viscous fluid having an infinitely large volume as described above, δ over time. This is because of the infinite increase.

However, by appropriately selecting the time to be analyzed, the error between the above-described theoretical formula and the actual behavior can be ignored.
FIG. 5 shows the configuration of an embodiment of the blood viscosity measuring apparatus of the present invention completed based on the above-described idea. FIG. 5 is a block diagram conceptually showing the structure of an embodiment of the blood viscosity measurement apparatus of the present invention.

  As shown in FIG. 5, the blood viscosity measuring apparatus 10 of the present invention is a means A for non-invasively irradiating a first ultrasonic wave from the surface (skin) 2 of the living body 1 along the blood flow direction in the blood vessel 4. A transmitter 12 that is, and a receiver 14 that is a means B for receiving the second ultrasonic wave emitted outside the living body 1 via blood after the first ultrasonic wave is incident on the living body 1; It comprises.

  The first frequency of the first ultrasonic wave and the second frequency of the second ultrasonic wave due to the Doppler effect generated between the first ultrasonic wave and the second ultrasonic wave due to blood flow As means C for measuring the temporal change of the difference Δf, a mixer 16 and a spectrum analyzer 18 are provided. The means D for measuring the temporal change of the difference Δf and the above-mentioned in the blood vessel 4 based on the temporal change of the difference Δf. As means E for measuring the blood flow velocity distribution (for example, the thickness of the boundary layer in the blood vessel approximated to the flow velocity distribution), a personal computer (PC) 22 which is an arithmetic unit is provided.

  The PC 22 includes a timer, a memory, and a computing element (CPU), and an algorithm that is a means for measuring the viscosity of blood from the temporal change of the flow velocity distribution (for example, the thickness of the boundary layer) is stored in the memory. Has been.

  According to the blood viscosity measuring apparatus 1 of the present invention, the blood flow velocity distribution is measured using the Doppler effect generated by adding ultrasonic waves, and the blood viscosity is measured from the temporal change. According to this method, it is not necessary to apply pressure to the living body, and the viscosity of blood can be measured while maintaining the normal flow rate of blood in the blood vessel.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in more detail, this invention is not limited to these Examples at all.

In this example, the blood viscosity measuring apparatus 1 of the present invention having the configuration shown in FIG. 5 was used, and the viscosity of blood flowing in the blood vessel of the subject was measured noninvasively.
Transmitter so that an angle (that is, an angle with respect to a blood flow direction indicated by an arrow R in FIG. 5) θ incident on the first ultrasonic wave irradiated from the transmitter 12 including the piezoelectric element is 45 degrees. 12 was fixed on the subject's carotid artery, and an electrical signal of 5,000 kHz was applied to the transmitter 12 from the oscillator 12a to irradiate the first ultrasonic wave.

  A receiver 14 including a piezo element that receives the second ultrasonic wave emitted from the subject via blood after the first ultrasonic wave is incident on the subject. The same specs were used. The receiver 14 was arranged so as to be horizontally symmetric with respect to the transmitter and so that the distance between the transmitter and the receiver was 20 mm.

  The signal from the receiver 14 and the signal from the oscillator 12 were input to the mixer 16, and the control device 24 controlled the input level from the oscillator 12 to remove the 5,000 kHz frequency component in an analog manner. Furthermore, in order to remove the frequency component of 5,000 kHz more strictly, only the frequency component of 4,900 kHz or less was output from the mixer 16 by a low-pass filter built in the main festival. This output was input to a spectrum analyzer, and a frequency distribution (ie, Δf) was obtained as an analog signal.

Further, after the frequency component is converted into a digital signal by the AD converter 20, it is expanded in the memory on the PC 22, plotted in the memory with respect to the time information obtained from the timer in the PC 22, and the memory is obtained by the method described above. The δ value was calculated above. An example of this result is shown in FIG.
In FIG. 6, the plot is represented by equation (6)

The curve approximated by is shown simultaneously.
FIG. 6 shows three discontinuous curves, each corresponding to a beat. That is, FIG. 6 shows a change in d value corresponding to three beats. In this example, a total of 20 beats are measured by adding beats not shown in FIG.

As a result, the average value was 16.4 × 10 ⁴ .
On the other hand, blood was collected from the same subject as described above, and the viscosity of the blood was measured with a viscotic viscometer manufactured by Maruyasu Kogyo Co., Ltd. and found to be 0.048 poise.
As a result, from the above formula (7), the value of α was 74.8 × 10 ⁴ {= 16.4 × 10 ⁴ /(0.048) ⁻² }.

[Evaluation test]
The accuracy of blood viscosity measurement by the blood viscosity measuring apparatus 1 of the present invention was evaluated as follows. That is, the blood viscosity of different subjects measured using the same α value in the same manner as in the above examples was collected from the different subjects measured using a viscotic viscometer manufactured by Maruyasu Kogyo Co., Ltd. Plotted against blood viscosity (in vitro). The results are shown in FIG.

  FIG. 7 is a diagram showing a correlation between blood viscosity measured in the present example and blood viscosity measured by a conventional method. From FIG. 7, it was confirmed that the blood viscosity measured by both methods is well correlated, and that the blood viscosity measuring apparatus of the present invention can accurately measure the blood viscosity even non-invasively.

  In the above-described embodiment, for the sake of explanation, each measurement step is plotted in a diagram and the analysis is performed using the diagram. However, in practice, these measurement steps are all performed by the PC 22 and the control device 24. Can be done automatically.

  Although not shown, the blood viscosity measuring apparatus 1 of the present invention preferably includes a display such as a liquid crystal display, and displays FIGS. 3, 4 and 6 and the measured blood viscosity in each measurement step. Is also possible. However, FIGS. 3, 4, and 6 do not need to be displayed in particular, and it is sufficient that they have a function of displaying at least the measured blood viscosity.

  According to the blood viscosity measuring apparatus of the present invention, blood viscosity can be measured non-invasively, and information on the obtained blood viscosity can be used for, for example, determination of visceral diseases.

It is a figure which shows the structure of the conventional blood-flow measuring apparatus which has the simplest structure using the Doppler effect of an ultrasonic wave. It is a figure which shows the time change (time transition) by the pulsation of the flow velocity distribution of the blood in the blood vessel. Due to the Doppler effect, the frequency (first frequency) of the ultrasonic wave (first ultrasonic wave) incident on the living body and the ultrasonic wave that is emitted to the outside of the living body via blood in the blood vessel after being incident on the living body It is a figure which shows the data of the time change (time transition) of distribution of difference (DELTA) f with the frequency (2nd frequency) of a sound wave (2nd ultrasonic wave). It is a figure which shows the curve obtained by plotting d with respect to time t. It is a block diagram which shows notionally the structure of one Embodiment of the blood viscosity measuring apparatus of this invention. It is a figure which shows the curve obtained by plotting (delta) with respect to time t in the Example of this invention. FIG. 7 is a diagram showing a correlation between blood viscosity measured in the present example and blood viscosity measured by a conventional method.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Living body 2 ... Epidermis 4 ... Blood vessel 10 ... Blood viscosity measuring apparatus 12, 102 ... Transmitter 14, 104 ... Receiver 16, 106 ... Mixer 18 ... Spectrum analyzer 20 ... AD converter 22 ... PC
24... Control device 100... Blood flow measuring device 108.

Claims (4)

Means A for non-invasively irradiating the first ultrasonic wave along the direction of blood flow in the blood vessel from the surface of the living body;
Means B for receiving a second ultrasonic wave emitted from the living body via the blood after the first ultrasonic wave is incident on the living body;
A first frequency of the first ultrasonic wave and a second frequency of the second ultrasonic wave due to the Doppler effect generated between the first ultrasonic wave and the second ultrasonic wave by the blood flow. Means C for measuring the distribution of the difference Δf from the frequency;
Means D for measuring the temporal change of the difference Δf;
Means E for measuring the flow velocity distribution of the blood in the blood vessel based on the temporal change of the difference Δf;
Means F for measuring the viscosity of the blood based on temporal changes in the flow velocity distribution;
A blood viscosity measuring apparatus comprising: Means for detecting the pulsation of the pulse;
Means for synchronizing the beat interval and the temporal change in the flow velocity distribution;
The blood viscosity measuring apparatus according to claim 1 comprising:   The blood viscosity measuring apparatus according to claim 1 or 2, wherein the means E measures a thickness of a boundary layer in the blood vessel approximated to the flow velocity distribution as the flow velocity distribution. The blood viscosity measuring apparatus according to claim 3, wherein the means F measures the viscosity of the blood based on a temporal change in the thickness of the boundary layer.

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