JP2006141678A - Instrument for measuring blood rheology - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an instrument for measuring blood rheology by which the blood rheology is measured at low costs by enabling anybody other than a specialist to simply measure a blood flow velocity without collecting blood, and by which measurement excellent in correlation property is furthermore carried out also about data between different patients. <P>SOLUTION: The instrument carries out measurement using a blood flow velocity sensor obtained by combining a plurality of ultrasonic sensors each consisting of an ultrasonic transmitter and an ultrasonic receiver, and an optical sensor, and corrects data of the blood flow velocity using data of the optical sensor to reduce variance caused by the individual difference between living bodies. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a technique for measuring a dynamic state of blood flowing in a blood vessel, particularly for evaluation of blood rheology indicating blood fluidity in a living body.

  As one of the examination items for judging the health condition of the human body, blood rheology measurement focusing on blood fluidity has attracted attention. As a means for measuring blood rheology, an apparatus (product name MC-FAN) has been developed that measures the time for a certain amount of blood collected from a subject to pass through a microchannel (microchannel) (see Non-Patent Document 1). .). At present, the MC-FAN apparatus is a standard machine in blood rheology measurement.

  However, in the measurement using the MC-FAN apparatus, blood must be collected as described above, and the measurement can be performed only by medical institutions, and there is a great inconvenience for the purpose of easily checking the health condition of anyone at any time. is there. In addition, blood sampling has a large physical and psychological burden on the subject, and the number of measurement operations per day can only be several times at most, so that there is a problem that continuous data cannot be obtained in time series. is there.

There is a strong correlation between blood rheology and blood flow velocity in vivo. That is, it is considered that when the blood fluidity is low, the blood flow velocity is slow, and when the blood fluidity is high, the blood flow velocity is fast. Therefore, it is possible to know blood rheology indirectly by measuring the blood flow velocity in the living body. Thus, in order to measure blood flow velocity that has a strong correlation with blood rheology, an invention has been proposed in which blood flow velocity is measured from Doppler shift of an ultrasonic wave that propagates in a living body and reflects on blood flow in a blood vessel. (See Patent Document 1).
Japanese Patent Laid-Open No. 2003-159250 “Blood Rheology Measuring Device” Keiji Kikuchi “Measurement of whole blood fluidity using a capillary model” (Food Research Result Information, NO.11, 1999)

  Even in the conventional technique of measuring blood flow velocity from the Doppler shift of ultrasonic waves that propagate in the living body and reflect on the blood flow in the blood vessel, for a specific subject, data that has a high correlation with the measurement data by MC-FAN Could get. However, when measurement is performed on a plurality of subjects, the correlation may be reduced in the comparison of data between different subjects in the conventional technique due to individual differences (individual differences) in the living body.

  Therefore, the present invention does not only collect blood, but anyone other than an expert can easily measure an accurate blood flow velocity, enable not only blood rheology to be measured at low cost, but also data between different subjects. An object of the present invention is to provide a blood rheology measuring apparatus capable of measuring with excellent correlation.

  In order to solve the above problems, in the present invention, measurement is performed using a combination of a blood flow velocity sensor, which is a combination of a plurality of ultrasonic sensors including an ultrasonic transmitter and an ultrasonic receiver, and an optical sensor. . In general, the velocity of the viscous fluid flowing in the pipe is proportional to the pressure and the square of the pipe diameter, and inversely proportional to the viscosity. On the other hand, the flow rate of the fluid is proportional to the pressure and the fourth power of the tube diameter, and inversely proportional to the viscosity. Therefore, the viscosity can be obtained from the speed, flow rate and pressure of the fluid from the above relationship. The velocity of blood flowing in the living body (in the blood vessel) is measured by an ultrasonic sensor. When light of a wavelength that is easily absorbed by blood (blue, green, etc.) is incident on a living body (human body), the remaining reflected or transmitted light of the light absorbed by the blood can be detected according to the blood flow volume. The blood flow rate is detected by an optical sensor that combines a light emitting element and a light receiving element.

  Further, in the optical sensor, the intensity of light emission can be improved and the sensitivity and S / N of the optical sensor can be improved by setting the driving method of the light emitting element to pulse light emission. If the ease of blood flow is the reciprocal of blood viscosity, the blood flow velocity data measured by the ultrasonic sensor is corrected using the flow rate data obtained by the optical sensor, and the data obtained by the ultrasonic sensor alone It is possible to reduce the variation caused by the individual difference of the living body contained in the blood and to determine the ease of blood flow more accurately.

  By using a combination of an ultrasonic sensor and an optical sensor, anyone can easily measure blood rheology without collecting blood from a subject, and the accuracy is further improved. In addition, by using a pulse drive for the light emitting element of the optical sensor, the sensitivity of the optical sensor is improved, and further, only one light receiving element can be provided without providing a plurality of light receiving elements having an expensive multilayer optical filter. Therefore, the increase in the price of the apparatus can be minimized.

(Embodiment 1)
First, the structure of an Example is demonstrated based on drawing. FIG. 1 is a block diagram showing the configuration of the measuring apparatus of the present invention. FIG. 2 shows a blood flow velocity sensor used in the present invention. FIGS. 4 and 5 are schematic views showing the outline of the principle of ultrasonic Doppler signal measurement.

  The blood flow velocity sensor 30 is a combination of two pairs of ultrasonic sensors, that is, an ultrasonic sensor 1a including a transmitting element 2a and a receiving element 3a, and an ultrasonic sensor 1b including a transmitting element 2b and a receiving element 3b. is there. The transmitting elements 2a and 2b and the receiving elements 3a and 3b of the ultrasonic sensors 1a and 1b are all piezoelectric vibrating elements in which an electrode thin film is formed on a piezoelectric ceramic plate. In the present embodiment, the ultrasonic frequency is 15 MHz. In the present invention, two pairs of ultrasonic sensors 1a and 1b are used and arranged on the sensor support substrate 10 so that the directions of directivity of ultrasonic emission and reception are not parallel to each other. The blood flow velocity is measured by bringing the blood flow sensor 30 into contact with a living body 71 (such as a fingertip of a subject) as shown in FIG.

  The ultrasonic wave (transmission wave 13a) emitted from the transmitting element 2a of the ultrasonic sensor 1a propagates through the living tissue and is reflected by the blood flowing through the blood vessel. The reflected wave 14a changes to a signal subjected to Doppler shift according to the blood flow speed. This reflected wave is received by the receiving element 3a. Similarly for the ultrasonic sensor 1b, the ultrasonic wave (transmitted wave 13b) emitted from the transmitting element 2b is reflected by the Doppler shift due to blood flow and detected by the receiving element 3b, but the ultrasonic sensors 1a and 1b Then, the directivity directions in which ultrasonic waves are emitted are different. The blood flow velocity can be calculated from the angle difference α between the ultrasonic sensors 1a and 1b and the Doppler shift frequencies ΔFa and ΔFb obtained from the signals of the ultrasonic sensors 1a and 1b.

  The ultrasonic measurement unit 51 includes a blood flow velocity sensor 30 including two pairs of ultrasonic sensors 1, two detection circuits 23, a filter circuit 24, an amplification circuit 25, and an A / D converter 26. The signals of the receiving elements 3a and 3b that have received the reflected waves 14a and 14b are detected by the detection circuits 23a and 23b, and only the Doppler shift signal component from which the ultrasonic carrier component (base component) is removed is extracted. The frequency components unnecessary for the A / D conversion process are removed by the filter circuits 24a and 24b, and amplified by the amplifier circuits 25a and 25b, respectively. The Doppler shift signal is an analog signal, but is converted into digital data by the A / D converters 26 a and 26 b and temporarily stored in the buffer memory 41. In the present embodiment, the sampling frequency of the A / D converters 25a and 25b is 20 kHz.

  The optical measurement unit 53 is a means for detecting a local blood volume in the living body, and includes an optical sensor 7 including a light emitting element 8 and a light receiving element 9. In the embodiment, the light emitting element 8 is a blue or green light emitting diode, and the light receiving element 9 is a phototransistor. The light emitting element is driven by applying a pulse voltage by a light emitting oscillation circuit and a driving circuit. Since the pulse of a living body is usually about several tens to 100 per minute, it is considered that the light emitting element needs to be driven at a frequency of 100 Hz or more in order to observe the blood flow waveform.

  When the frequency of the driving voltage of the light emitting element is 250 Hz, the duty is 50%, and the sampling frequency of A / D conversion is 1 kHz, the timing shown in FIG. 7 is obtained. When the frequency of the driving voltage of the light emitting element is 250 Hz, the duty is 50%, and the sampling frequency of A / D conversion is 2 kHz, the timing shown in FIG. 8 is obtained. Although it is possible to further increase the sampling frequency of the A / D conversion with respect to the frequency of the driving voltage of the light emitting element, when the sampling timing coincides with the rising and falling timing of the driving voltage of the light emitting element. Discard the data and use the remaining data. In the case of FIG. 7 and FIG. 8, the signal of the light receiving element when the light emitting element is not emitting light is also detected, but the data when not emitting light can be used to eliminate the influence of the background light.

  Incident light 15 emitted from the light emitting element 8 is reflected by the in-vivo tissue to be measured and received by the light receiving element 9. Although incident light 15 also irradiates blood in the living body, since blood has a property of absorbing blue light or green light, the local blood volume included in the irradiation range of incident light 15 and the light receiving range of light receiving element 9 is small. When the amount is large, the reflected light 16 is weak. Conversely, when the local blood volume is small, the reflected light 16 is detected strongly. Therefore, the local blood volume change in the living body accompanying the pulse can be detected by the optical sensor 7. The signal of the optical sensor is amplified by the amplifier circuit 27, and unnecessary high frequency components are removed by the filter circuit 28, and then converted into digital data by the A / D converter 29.

  The arithmetic unit 51 includes buffer memories 41 and 42 and an arithmetic processing unit 43. The buffer memory 41 temporarily stores measurement data from the ultrasonic sensor 30. The buffer memory 42 temporarily holds data from the optical sensor. The data in each buffer memory is sent to the arithmetic processing unit 43 every fixed amount. The arithmetic processing unit 43 receives data from each sensor digitized by each A / D converter via the digital input unit 44, and performs arithmetic processing by the functions of the signal arithmetic processing unit 45 and the general-purpose arithmetic processing unit 46. The blood flow velocity with the noise component removed is calculated. If the arithmetic processing unit 43 operates at a sufficiently high speed with respect to the sampling rate of the measurement data, the buffer memories 41 and 42 can be omitted. The signal arithmetic processing unit 45 is a device that performs signal processing at a high speed with a special hardware configuration. If the processing speed of the general-purpose arithmetic processing unit 46 is high, the signal arithmetic processing unit 45 can be omitted.

  The main storage unit 47 holds measurement data and calculation data used when the calculation processing device 43 executes calculation. Data that needs to be stored, such as measurement data and calculation result data, is stored in the storage 48. The storage 48 is configured by a nonvolatile flash memory device or a hard disk device.

  The input / output device 49 or the like is a device having a user interface function such as a keyboard or a mouse, a device having a screen display function such as a CRT or LCD, or a device having a communication function such as an Ethernet or serial communication bus. Furthermore, as a peripheral device, a blood pressure measuring device is connected, and data can be corrected with a blood pressure value.

  Next, a measurement method using the blood rheology measurement apparatus having the above-described configuration will be described.

  First, before the measurement of the living body, it is placed on the calibration reflector sensor and the reference reflection intensity is measured, and at this time, the optical signal reference value Lr as data is stored in the apparatus. The calibration reflector is an aluminum plate painted in white. As shown in FIG. 4, a blood flow velocity is measured by bringing a blood flow sensor 30 into contact with a living body 71 (such as a fingertip of a subject) that is a measurement target. The ultrasonic wave (transmission wave 13a) emitted from the transmitting element 2a of the ultrasonic sensor 1a propagates through the living tissue and is reflected by blood flowing through the blood vessel. The reflected wave 14a changes to a signal subjected to Doppler shift according to the blood flow velocity. This reflection is received by the receiving element 3a.

  Similarly, for the ultrasonic sensor 1b, the ultrasonic wave (transmitted wave 13b) emitted from the transmitting element 2b is reflected by the Doppler shift due to blood flow and detected by the receiving element 3b, but the ultrasonic wave is emitted. Directional direction is different. The signals of the reflected waves 14a and 14b received by the receiving elements 3a and 3b are detected by the detection circuits 23a and 23b, respectively, and only the Doppler signal component from which the ultrasonic carrier component (base component) is removed is extracted. Further, high frequency components unnecessary for A / D conversion processing are removed by the filter circuits 24a and 24b, and then amplified by the amplification circuits 25a and 26b, respectively. Although this Doppler signal is an analog signal, it is converted into digital data by the A / D converters 26a and 26b, temporarily stored in the buffer memory 42, and then transferred to the main memory 47 through the digital input unit to the arithmetic processing unit 43. And memorized.

  If these measurement data are not immediately analyzed, they are stored in the external storage medium via the network of the storage 48 or the input / output device 49, which is an external storage attached to the device, and the time required for the analysis processing. Just take it out.

  The digital data of the respective Doppler signals of the ultrasonic sensor 1a and the ultrasonic sensor 1b obtained by the above measurement is subjected to Fourier transform (FFT) processing in the signal arithmetic processing unit 45 and the general-purpose arithmetic processing unit 46 of the arithmetic processing unit 43, so that the frequency The data is converted into distribution (spectrum) data, and the frequency distribution data is stored in the main memory 47. Assuming that the sampling frequency of A / D conversion is fs = 20 kHz and the number of FFT processes is Nf = 256, the frequency distribution data every 0.0128 seconds is Nf = 512, and the frequency distribution is every 0.0256 seconds. (However, the number of FFT processing data and the time interval of the FFT processing do not necessarily match. For example, 256 pieces of data can be processed at intervals of 0.01 seconds.) is there).

  If the frequency shift obtained from the data of the ultrasonic sensor 1a by the above method is Fa and the frequency shift obtained from the data of the ultrasonic sensor 1b is Fb, the blood flow velocity Vh can be derived by the following equation.

Vh = cFa / 2Fscosθ
Here, θ = atan ((− cos α−Fb / Fa) / sin α)
α is an angle formed by directivity of emission and reception of ultrasonic waves of the two ultrasonic sensors, c is a sound velocity in the living body, and Fs is a transmission frequency (drive frequency) of the ultrasonic sensors.

  In addition, since the blood is pushed by the blood pressure P of the living body and flows, the blood flow velocity Vh is considered to be affected by the blood pressure of the living body. In order to correct the influence of blood pressure, the blood flow velocity Vh is divided by the blood pressure Ph measured by a blood pressure measuring device. The value of Vh / Ph is referred to as a corrected blood flow velocity Vc for convenience. If this corrected blood flow velocity Vc is large, the blood fluidity in the living body is relatively high, and if Vc is small, the blood fluidity is low. However, if the data of a plurality of individuals (individuals) are simultaneously evaluated, there may be an effect of individual differences in blood vessel diameter, and the variation may increase.

  FIG. 11 shows an example of the output voltage of the optical sensor. The optical signal L80 output from the light receiving element is output with a large signal voltage when the blood flow volume is small, and is affected by the transmittance of the living body. Since the peak value Lp82 of the optical signal L is a signal when the amount of light absorbed by blood is the smallest, the amplitude component of the optical signal is La83, and La is Lq normalized by the ratio of Lp to the optical signal reference value Lr81. It is an index proportional to the blood flow of the living body. That is, Lq = La · (Lr / Lp).

Assuming that the blood vessel diameter is D and the blood viscosity is μ, the blood flow velocity Vh is proportional to the blood pressure P and the square of D, and inversely proportional to μ, from the law of viscous fluid. On the other hand, the blood flow volume is proportional to the fourth power of P and D, and inversely proportional to μ. Therefore, if the index Rh of the ease of blood flow is the reciprocal of the viscosity μ, the ease of flow Rh is Rh∝ (Vh × Vh) / (Lq · P).
That is, the ease of blood flow Rh can be obtained from the blood flow velocity data Vh and the optical blood flow Lq measured by the rheology measurement device of the present invention.

(Embodiment 2)
As another embodiment, a configuration in which a plurality of light emitting elements are provided will be described. 3 and 6, the light emitting element (a) 8a and the light emitting element (b) 8b can emit light having different wavelengths. The voltage of the pulse waveform (a) is applied to the light emitting element (a) 8a by the drive circuit 31, and the voltage of the pulse waveform (b) is applied to the light emitting element (b) 8b. If the frequency of the driving voltage of the light emitting element is 250 Hz, the duty is 25%, and the sampling frequency of A / D conversion is 2 kHz, the timing shown in FIG. 9 is obtained. When the frequency of the driving voltage of the light emitting element is 250 Hz, the duty is 25%, and the sampling frequency of A / D conversion is 4 kHz, the timing shown in FIG. 10 is obtained.

In the case of FIG. 10, the measured value at the time corresponding to the rise and fall of the pulse voltage is not used. The drive circuit 31 includes a program logic circuit and an amplifier circuit that process the duty and phase of a simple rectangular wave voltage of the oscillation circuit and distribute them to each light emitting element. As shown in FIG. 9 and FIG. 10, the pulse waveform (a) and the pulse waveform (b) are not simultaneously overlapped with each other, so that the light emitting element (a) 8a and the light emitting element (b) 8b emit light simultaneously. There is nothing.
By transmitting a signal indicating which light emitting element (a) or (b) is emitting light from the driving circuit to the arithmetic processing device, or by instructing the timing of the pulse voltage from the arithmetic processing device to the driving circuit, The arithmetic processing unit 51 can sort the signal of the light receiving element 9 into a signal when the light emitting element (a) 8a emits light and a signal when the light emitting element (b) 8b emits light. Therefore, it is not necessary to provide optical filters having different transmission wavelengths for each of the plurality of light receiving elements, and blood observation with a plurality of wavelengths can be performed using only one light receiving element without an optical filter.

  With the above configuration, in Embodiment 2, the light emitting element (a) 8a emits blue or green light, and the light emitting element (b) 8b emits red light. By subtracting the direct current component of the signal of the light receiving element 9 when the light emitting element (b) 8b emits light from the signal of the light receiving element 9 when the light emitting element (a) 8a emits light, the influence of venous blood can be corrected and more accurately Blood flow can be measured.

  The present invention is not only capable of measuring blood fluidity (ease of flow) for the purpose of medical care and health maintenance / enhancement, but also the activity state of a living body (human body) and the blood flow state in each part of the living body. It can also be used in measurement to know the correlation.

The block diagram which shows the structure of the measuring apparatus which concerns on this invention The figure which shows the structure of the sensor which concerns on this invention The figure which shows the structure of the sensor which concerns on this invention The figure which shows the structure of the sensor which concerns on this invention The figure which shows the structure of the sensor which concerns on this invention The figure which shows the structure of the sensor which concerns on this invention The figure which shows the drive method of the optical sensor which concerns on this invention The figure which shows the drive method of the optical sensor which concerns on this invention The figure which shows the drive method of the optical sensor which concerns on this invention The figure which shows the drive method of the optical sensor which concerns on this invention The figure which shows the example of the output voltage of the optical sensor which concerns on this invention

Explanation of symbols

1a, 1b Ultrasonic sensor 2a, 2b Transmitting element 3a, 3b Receiving element 7 Optical sensor 8a Light emitting element (a)
8b Light emitting element (b)
DESCRIPTION OF SYMBOLS 9 Light receiving element 10 Sensor support board 13a, 13b Transmitted wave 14a, 14b Reflected wave 15 Incident light 16 Reflected light 21 Transmitter circuit 23a, 23b Detector circuit 24a, 24b Filter circuit 25a, 25b Amplifier circuit 26a, 26b A / D converter 27 Amplification circuit 28 Filter circuit 29 A / D converter 30 Blood flow sensor 31 Drive circuit 32 Oscillation circuit for light emission 41a, 41b Buffer memory 42 Buffer memory 43 Arithmetic processing unit 44 Digital input unit 45 Signal calculation unit 46 General-purpose calculation unit 47 Main memory Unit 48 Storage 49 Input / output device, etc. 50 Ultrasonic measurement unit 51 Calculation unit 52 Blood pressure measurement device 53 Optical measurement unit 54 Peripheral device 60 Drive voltage 61 A / D conversion timing 62 Drive voltage 63 A / D conversion timing 64 Drive voltage (a )
65 Drive voltage (b)
66 A / D conversion timing 67 Drive voltage (a)
68 Drive voltage (b)
69 A / D conversion timing 71 Living body (fingertip)
72 Blood vessel 80 Optical signal L
81 Optical signal reference value Lr
82 Peak value Lp of optical signal
83 Amplitude component La of optical signal

Claims (5)

A blood rheology measuring device for measuring blood rheology indicating fluidity of blood in a living body,
An ultrasonic sensor comprising a transmitting element that makes ultrasonic waves enter the living body, and a receiving element that receives the reflected waves reflected by the incident ultrasonic waves in the living body;
A light sensor comprising a light emitting element that flashes and emits light at a predetermined blinking frequency and enters light into a living body, and a light receiving element that receives light reflected or transmitted through the living body,
A signal sampling means for analog-to-digital conversion of the output signal of the light receiving element in synchronization with the blinking frequency of the blinking light emission at a sampling frequency that is an integer multiple of twice or more the blinking frequency;
Means for calculating the blood rheology of the living body by correcting the information on the blood flow velocity in the living body obtained from the signal of the ultrasonic sensor using the information on the blood flow amount in the living body obtained from the optical signal. And a blood rheology measurement device. A blood rheology measuring device for measuring blood rheology indicating fluidity of blood in a living body,
An ultrasonic sensor comprising a transmitting element that makes ultrasonic waves enter the living body, and a receiving element that receives the reflected waves reflected by the incident ultrasonic waves in the living body;
A plurality of light-emitting elements each having a different emission wavelength, flashing at a predetermined flashing frequency, and flashing at a duty ratio and phase that are not turned on at the same time, and entering light into a living body And a light sensor comprising a light receiving element that receives light reflected or transmitted through the living body,
A signal sampling means for performing analog-to-digital conversion at a sampling frequency obtained by synchronizing the output signal of the light receiving element with the blinking frequency of the blinking emission and multiplying the blinking frequency by an integer multiple greater than the number of light emitting elements;
Means for calculating the blood rheology of the living body by correcting information on the blood flow velocity in the living body obtained from the signal of the ultrasonic sensor using the information on the blood flow in the living body obtained from the optical signal. And a blood rheology measurement device.   The blood rheology measuring apparatus according to claim 1 or 2, wherein at least one of the light emitting elements is a light emitting element that emits light having a wavelength that is easily absorbed by blood in a living body.   3. The blood rheology measurement device according to claim 1, wherein at least one of the light emitting elements is a light emitting element that emits light in a wavelength range corresponding to a center wavelength of blue or green. 4.   A calibration reflector is placed at a certain distance from the optical sensor, and further comprises means for calibrating the signal of the optical sensor when the living body is measured with reference to the intensity of light reflection received by the light receiving element. The blood rheology measuring device according to any one of claims 1 to 4.

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