JP4739878B2 - Cerebral blood flow measuring device - Google Patents

Description

  The present invention relates to a cerebral circulatory blood flow measuring apparatus for measuring a state of a living body, particularly cerebral circulatory blood flow, using near infrared rays and ultrasonic waves.

Circulating blood flow to the brain occupies about 20% of the total blood flow flowing through the living body, and the cerebral circulating blood flow is an effective index for evaluating the state of the living body.

  Transcranial ultrasound Doppler (TCD) has become widespread since its development as a means for viewing the circulating blood flow of the brain within the skull. However, since the acoustic impedance of the bone is much larger than that of the soft tissue part, the ultrasonic wave that passes through the skull and enters the inside is about 20% at most, although there are individual differences. Therefore, the reflected wave amplitude of the ultrasonic wave reflected from the inside of the skull and emitted to the outside of the skull is about 4% of the amplitude of the incident ultrasonic wave even if the internal reflectance is 100%, for example. However, in the actual brain tissue, it has an extremely small reflectivity determined depending on the slight difference in acoustic impedance at the tissue interface between the red blood cell membrane and plasma. The ultrasonic wave emitted to the is extremely weak. Therefore, in order to improve the S / N, it is generally performed to increase the incident energy of the ultrasonic wave, but it is known that the temperature of the irradiation unit is increased. Moreover, the possibility of gene damage due to long-time irradiation of high-intensity ultrasonic waves has been pointed out, and it is not preferable to irradiate ultrasonic waves continuously for a long time from the viewpoint of biological safety.

  In addition, positron emission tomography (PET) and magnetic resonance imaging (MRI) have been widely used as non-invasive methods for probing changes in cerebral blood flow associated with brain function. Is extremely large.

  Also, near infrared light has good biological permeability, and it is well known as near infrared light spectroscopy (NIRS) that information on hemoglobin in a living body can be obtained using near infrared light. A widely used application is a pulse oximeter that measures oxygen saturation in peripheral arterial blood. It is also possible to measure cerebral blood flow by measuring the near-infrared light transmission characteristics of the head, and the development of an optical functional imaging method called optical CT using near-infrared light has also been attempted. . In general, it is difficult to obtain local information with high accuracy due to light scattering. However, in optical CT, a large number of optical probes are usually attached to the head and scattered in the living body. Even with light, it is possible to determine the spatial distribution as optical brain topography by applying complex signal processing.

  As described above, the conventional method used to know the cerebral blood flow is generally a very large device, and the subject goes to the place where the device is installed and is examined. Can not be used. Moreover, since it becomes a very expensive apparatus, it cannot always be used.

  In view of these circumstances, a single optical probe based on NIRS measures the blood flow state of the brain easily and non-invasively, converts the measurement result into sound, and a doctor can always carry a stethoscope An instrument that can receive information with an ear and can respond to an emergency has been devised (see, for example, Patent Document 1).

Japanese Patent Laying-Open No. 2001-95767 (page 2-4, FIG. 1)

  However, when light is incident on the living body from the outside, the scalp and the skull have a thickness of about 7 to 9 mm. With the optical probe, the measurement target site cannot be narrowed down locally, making accurate measurement difficult.

(Object of invention)
An object of the present invention is to provide a device that can accurately and locally measure the state of cerebral blood flow while being a device that can be always carried by a general doctor such as a stethoscope. .

The cerebral circulatory blood flow measuring apparatus according to the present invention includes an ultrasonic wave incident means for making an ultrasonic wave incident on a living body head, an irradiation means for irradiating near infrared light, and a near infrared light by dividing the near infrared light. Is divided into a living body and the other near-infrared light is used as reference light, and a detecting means for detecting a beat signal generated by interference between the near-infrared light incident on and reflected from the head of the living body and the reference light And an optical / ultrasonic unit having
The light / ultrasound combination unit is non-invasively contacted with the living body head, and one near infrared light is incident on the living body head together with the ultrasonic wave. It is characterized in that a change in blood volume is calculated from a change in intensity of a beat signal caused by interference between one near infrared light reflected from a living body head that has caused a Doppler shift and a reference light.

  In addition, the optical / ultrasonic unit has a pressure sensor.

    Also, the pressing force when the optical / ultrasonic unit is brought into contact with the living body head is detected by a pressure sensor, the depth from the living body surface is specified by the pressing force, and the cerebral circulation of the specified depth is detected. An informing means for informing the blood flow is provided.

  As described above, according to the present invention, the apparatus is small and portable and inexpensive, and can be used for diagnosis at any time in general clinical practice. In addition, information on the inside of the skull can be obtained with low-energy ultrasonic incidence, so that safety to the living body is remarkably improved. In addition, since the straightness of ultrasonic waves is used, local measurement is possible, the measurement position accuracy can be improved, and the position of the measurement site can be specified.

  A cerebral circulation blood flow measurement apparatus according to an embodiment of the present invention will be described with reference to the drawings. FIG. 2 is a diagram for explaining an optimal embodiment of the present invention. As shown in FIG. 2, the cerebral circulatory blood flow measuring device according to the present embodiment includes an ultrasonic transducer 3 as an ultrasonic wave incident means for making an ultrasonic wave incident on the head of the living body 1, and an irradiating means for irradiating near infrared light. A laser diode 4 as a light beam splitter 6 as a splitting means for splitting near-infrared light into two light beams of incident light and reference light on a living body, reference light and near-infrared light emitted from the living body And an optical / ultrasonic decoding unit 30 having a photodiode 5 as detection means for interfering the two combined lights and converting them into electrical signals. The ultrasonic wave incident means causes an ultrasonic wave packet to be incident from the head, which is the living body 1, in order to cause movement in the living tissue inside the skull of the living body 1. This movement of the living tissue causes a Doppler shift corresponding to the movement speed of the light reflected from the living body 1.

FIG. 1 shows an overall block diagram of a cerebral blood flow measuring apparatus according to this embodiment. The living body 1 is in contact with an optical / ultrasonic decoding unit 30 including a pressure sensor 2, an ultrasonic transducer 3, an optical beam spiriter 6, an optical beam mixer 7, a laser diode 4, and a photodiode 5. The transmission unit 8 controlled by the CPU 9 generates an electric pulse and sends it to the ultrasonic transducer 3. The ultrasonic signal reflected from the living body 1 is converted into an electric signal by the ultrasonic transducer 3, amplified by the preamplifier 12, unnecessary signals are removed through the filter 14, amplified by the amplifier 16, detected by the detector 19, It is converted into a digital signal by the AD converter 18 and stored in a memory in the CPU 9. The electric signal from the photodiode 5 is amplified by the preamplifier 13, unnecessary signals are removed through the filter 15, amplified by the amplifier 17, converted into a digital signal by the AD converter 18, and stored in the memory in the CPU 9. The CPU 9 calculates the stored digital signal and displays the calculation result on the display unit 10. Further, the calculation result is input to the sound source device 11 and notified as a sound.

  The operation of the intracerebral blood flow measuring device according to the present invention will be described below with reference to FIG. First, the transmission unit 8 generates an electrical pulse having a pulse width of 100 ns and a transmission frequency of 10 kHz, that is, a transmission interval of 100 μs, and sends the electrical pulse to the ultrasonic transducer 3 to generate an ultrasonic pulse train having a very short width. .

  The resonance frequency of the ultrasonic transducer 3 is preferably 10 MHz. In this way, an ultrasonic pulse having a pulse width of 100 ns is generated from the ultrasonic transducer 3. The generated ultrasonic wave enters the brain 52 as a wave packet via the scalp 50 and the skull 51.

  Simultaneously with the incidence of the ultrasonic wave, the light of the frequency f generated by the laser diode 4 is divided into two by the light beam spiriter 6, one is made incident into the brain 52, and the other is the reference light, which is a photo detector. The light is guided to the diode 5 via the light beam mixer 7.

  In the region where the ultrasonic wave exists inside the brain 52, the living tissue, particularly the red blood cell, moves at a velocity V (z, t) due to the sound pressure of the ultrasonic wave. z represents coordinates in the ultrasonic traveling direction, and t represents time. Therefore, light whose frequency has shifted by Δ (z, t) according to the motion of the living tissue is reflected by the Doppler interaction of light and sound waves.

  As shown in FIG. 4, this deviation of Δ (z, t) occurs as the ultrasonic wave advances to the inside and changes with time t. However, since the ultrasonic wave has a half-value width of 100 ns, the ultrasonic wave is localized in an area of about 0.16 mm. Therefore, Δ (Z, t) becomes a function Δ (t) only for time t as shown in FIG. 5 in the coordinate system on the ultrasonic wave packet.

  As a result, the two coherent reference lights having different frequencies and the reflected light from the living tissue optically interfere with each other on the photodiode 5, and are detected as a high-frequency electric signal having the frequency Δ (t) by the photodiode 5. Is done. As described above, since the frequency of reflected light is changed with time by Δ (t), a component of Δ (t) is detected when the detected high frequency is detected.

  Since the speed of the ultrasonic wave is known, the amount of red blood cells in the cerebral blood vessel, that is, the blood volume, can be determined by obtaining an increase / decrease in the detection output at time t when the ultrasonic wave reaches the position of the brain 52. In simple near-infrared spectroscopy, it is difficult to obtain local information due to light diffusivity, but the ultrasonic wave packet can be converged arbitrarily, so local information can be obtained by using ultrasonic waves. Can be obtained. Therefore, since the intensity of the detection output depends on the blood of the brain 52, particularly the amount of red blood cells, it is possible to know a local change in the cerebral blood flow.

Therefore, in the above cerebral circulation blood flow measurement method, near-infrared light is divided, one is made incident on the head of the living body, the other is used as reference light, and ultrasonic waves that are simultaneously incident on the head of the living body are used for living tissue. The beat signal generated by the interference between the near-infrared light reflected from the living tissue that has caused the Doppler shift by the induced motion and the reference light can be detected, and the cerebral circulation blood flow can be easily and accurately measured.

  Specific examples of the cerebral circulation blood flow measuring apparatus and the measuring method described above will be described in detail with reference to FIGS. 1, 2, and 6. FIG. 6 is a view showing the structure of the optical / ultrasonic composite unit 30.

  In the ultrasonic echo method used in the cerebral circulatory blood flow measuring apparatus according to this embodiment, as shown in FIGS. The electric pulse is sent to the ultrasonic transducer 3 to generate an ultrasonic pulse train having a pulse width of 100 ns as a main component from the ultrasonic transducer 3. The ultrasonic waves are incident on the brain 52 as a wave packet via the scalp 50 and the skull 51. The resonance frequency of the ultrasonic transducer 3 is preferably 10 MHz.

  As shown in FIG. 6, the ultrasonic transducer 3 in the optical / ultrasonic composite unit 30 includes a base 110, a backing material 120, a piezoelectric body 130, and a protective film 140. A base body 110 is fixed in a cylindrical casing 100 via a sealing resin 102, and a piezoelectric body 130 is provided on the front surface of the base body 110 via a backing material 120 made of a copper plate having a thickness of 200 μm. The front surface is covered with a protective film 140. The base 110 is a fixed substrate for the backing material 120 and the piezoelectric body 130, and is fixed only around the backing material 120 so that the backing material 120 vibrates under suitable conditions. A bonding gel member 200 is inserted between the ultrasonic transducer 3 and the living body 1. The casing 100 is coupled to the pressure sensor 2 fixed to the pressure sensor base 84 via the pressure transmission member 80. The pressure sensor 2 includes a pressure receiving gel 81, a silicon chip 82, and a package 83.

  As the piezoelectric body 130, for example, a polymer piezoelectric material such as PVDF (polyvinylidene fluoride), or a composite of these polymer piezoelectric materials and an inorganic piezoelectric material such as lead zirconate titanate (PZT) is used. . In addition, front and back electrodes (not shown) are formed on both surfaces of the piezoelectric body 130. One end of a lead wire (not shown) is electrically connected to each of the front electrode and the back electrode. In order to achieve a resonance frequency of 10 MHz with respect to an electric pulse width of 100 ns, the thickness of the PVDF thin film is preferably 20 μm to 30 μm. Also, the backing material 120 reflects ultrasonic waves to the back side to the front side, so that ultrasonic pulses with a short pulse width are efficiently generated. The diameter of the piezoelectric body 130 is preferably 4 to 5 mm for ultrasonic incidence to the head.

  In this state, a pulse voltage of about 10 V is applied between the lead wires to generate ultrasonic waves from the piezoelectric body 130 in a pulsed manner. The incident energy is approximately 1 mW, and it may be considered that there is no influence on the living body. The ultrasonic pulses obtained in this way are transmitted through the examination object, and the ultrasonic waves are largely reflected on the outer surface and the inner surface of the skull whose acoustic impedance is much larger than that of living soft tissue.

  The reflected wave of the ultrasonic wave from the inside of the body is received by the piezoelectric body 130, and a voltage signal is generated between the lead wires. By detecting this voltage signal, the depth and properties of the tissue interface can be known. For example, as shown in FIG. 3, ultrasonic reflected waves 301, 302, and 303 appear on the surface of the scalp 50, the interface between the scalp 50 and the skull 51, and the inner surface of the skull 51, respectively.

Since the acoustic impedance of the living body 1 is about the same as that of the PVDF thin film of the ultrasonic transducer 3, even if the living body 1 is in direct contact with the living body 1, the ultrasonic energy is efficiently incident into the living body. And the like cause unnecessary multiple reflection, and the S / N is lowered. In the present invention, in order to perform acoustic impedance matching for the coupling between the piezoelectric body 130 and the living body 1, a polyolefin-based coupling gel member 200 having a thickness of 12 mm, which is close to the skin tissue, is inserted, and the section is substantially 12 mm. A transparent and non-reflective area is obtained. In addition, since the gel member has moderate adhesiveness, it eliminates the scattering of ultrasonic waves due to the unevenness of the skin surface and improves the S / N, and at the same time does not require a normally used liquid gel member. Convenience improved significantly.

  Next, means for irradiating near infrared light will be described. A laser diode 4 is used as a near infrared light source. The center emission wavelength of the laser diode 4 is 850 to 950 nm, which has good sensitivity characteristics with respect to changes in blood volume. The frequency of light of the laser diode 4 at that time is assumed to be f. The laser diode to be used is preferably a DFB laser diode having a gorge band spectrum in order to enhance coherence.

  The light emitted from the laser diode 4 is divided into two light beams by a light beam spiriter 6 having a reflectance of about 5% and a transmittance of about 95%. The reflected light from the light beam spiriter 6 is used as reference light and guided to the photodiode 5 via the light beam mixer 7.

  The other transmitted light beam transmitted through the light beam splitter 6 is incident on the living body 1 and then scattered and reflected at various locations in the living tissue. To cause interference with the reference beam.

Now, when the ultrasonic wave packet is incident by the ultrasonic wave incident unit simultaneously with the irradiation of the near infrared light by the irradiation unit, the ultrasonic wave packet travels inside the living body 1 and causes movement in the living tissue by the sound pressure. The frequency of the light reflected from the moving biological tissue is shifted by the frequency f _D corresponding to the Doppler shift from the optical frequency f in accordance with the speed of the moving biological tissue. Suppose that red blood cells move at a velocity of V in the region where the ultrasonic wave packet exists. When the maximum amplitude of the piezoelectric body 130 is 0.1 μm, the maximum velocity V is 6 m / sec for an ultrasonic wave packet of 100 ns. The corresponding Doppler shift of light is 8 MHz. Therefore, light having a frequency transition of a maximum of 8 MHz according to the movement of the living tissue is scattered and reflected from the tissue of the living body 1 by the Doppler interaction of light and sound waves.

The weakly scattered light scattered and reflected from the blood vessels on the surface of the brain 52, in particular, the reference light having the original frequency f is mixed and synthesized by the light beam mixer 7 in the same direction. cause interference is detected as a high frequency of f _D. The light beam mixer 7 also has a reflectance of 5% and a transmittance of about 57%. Eventually, about 0.25% of the reference light is incident on the photodiode 5, and when the reflection efficiency from the living body 1 is about 0.2%, the intensity ratio becomes substantially equal, and a large interference signal can be obtained.

Since the ultrasonic wave travels as a plane wave inside, the motion caused by the ultrasonic wave of the tissue body of the living body 1 is constant inside the living body 1 in the continuous tissue body. Therefore, the shift of the frequency f _D is attenuated by the reflection loss at the interface of the tissue having different acoustic impedance as the ultrasonic wave packet advances to the inside, but is constant in the continuous tissue body. On the other hand, light scattering decreases as the distance from the light emitting / receiving element increases as it travels inward. That is, when the frequency f _D optical beat signal is detected, the intensity becomes a function I _D (t) of time t as shown by a curve 400 in FIG. Since the optical beat signal intensity is dependent on the blood volume i.e. red cell mass of the brain 52, if the local change appears in cerebral blood flow, localized shown in FIG. 5 to the function I _D (t) shown in curve 400 It can be detected as a curve 405 on which the change 407 is superimposed.

The distance between the laser diode 4 and the photodiode 5 is about 1 cm because the bonding gel member 200 is interposed therebetween. The output from the photodiode 5 is amplified to an appropriate voltage range by the high-frequency preamplifier 12, and only the appropriate frequency region is passed by the filter 14 having the band pass characteristic, and only the signal component detected by the detector 19 is output. The amplifier 16 amplifies the voltage range suitable for digital processing.

  The signal component is digitized by the AD converter 18 and stored in the memory from the time obtained by delaying the coupled gel member 200 by the time required for the reciprocation of the ultrasonic wave with respect to the trigger signal synchronized with the transmission timing of the ultrasonic pulse. The sampling frequency of the AD converter 18 is 100 MHz (sampling interval 10 ns). One sampling is set to 20 μs, and a total of 2000 data is acquired. Since the speed of the ultrasonic wave is approximately 1600 (m / sec), information from the surface of the living body 1 to the inside of approximately 16 mm in the depth direction is acquired.

  After the sampling is completed, the CPU 9 sequentially reads out the numerical values recorded in the memory and calculates the detected component with respect to the traveling direction of the ultrasonic wave. Since the detected signal intensity is proportional to the red blood cell concentration, the depth from the surface of the living body 1 is used as a parameter, and the intensity of the detected component there is displayed on the display unit 10 or converted into sound by the sound source device 11 and the pitch of the sound. Informs the erythrocyte concentration as a change in.

  The optical / ultrasound composite unit 30 in this embodiment includes a pressure sensor 2. A pressure transmission gel 80 is interposed in the optical / ultrasonic composite unit 30, and the pressing force is detected by the pressure sensor 2. This purpose will be described below. The user (physician) pays attention to a specific depth region such as the surface of the brain. The specification of the depth can be changed by the force of pressing the optical / ultrasonic composite unit 30. That is, when the optical / ultrasonic composite unit is brought into contact with the living body 1 and measurement is performed, the pressure sensor 2 simultaneously detects the pressing force. The depth is determined using this pressing force as a parameter. The pressing force is converted into a depth based on the depth at the timing of the ultrasonic reflected wave 303 from the inside of the skull of the living body head shown in FIG. 3, and a signal having a desired depth is obtained from the digital signal stored in the CPU 9. And the magnitude of the cerebral blood flow in the depth direction of the living body head is reported as a function of the pressing force, that is, a function of the depth. For example, the intensity of the detected component at that depth is displayed on the display unit 10 as a curve 405 shown in FIG. More preferably, the sound source device 11 converts the sound into sound. The conversion to sound is preferably represented by a change in pitch according to the detected component intensity proportional to the red blood cell concentration. In this way, the doctor decides the depth of his / her attention by freely controlling the pressing force using only his / her hand holding the sensor, and listens to the change in the local red blood cell concentration at the site with his / her ear. Can be heard as the pitch of. This is extremely suitable for the doctor because the operation for instructing the depth can be obtained by a method equivalent to the use of a conventional stethoscope without using vision.

  As described above, according to the intracerebral blood flow measuring device of the present invention, the device is portable in the clinical field, the accuracy of the measurement position is improved, and the state of local cerebral blood flow is determined. Is possible, and the benefits are extremely large.

It is a block diagram which shows the structure of the cerebral blood flow measuring device which concerns on this embodiment of this invention. It is a figure which shows the cerebral blood flow measuring device in the Example of this invention. It is a figure which shows the received signal of the ultrasonic echo for demonstrating the principle of the cerebral blood-flow measuring apparatus in the Example of this invention. It is a figure which shows the interference signal of the received light for demonstrating the principle of the cerebral blood flow measuring device in the Example of this invention. It is a figure which shows the change of the received signal by the blood flow change of the cerebral blood flow measuring device in the Example of this invention. It is a figure which shows the structure of the optical and ultrasonic composite unit in the Example of this invention.

Explanation of symbols

1 Living body 2 Pressure sensor
3 Ultrasonic transducer 4 Laser diode 5 Photo diode 6 Optical beam splitter
7 Light Beam Mixer 8 Transmitter 9 CPU
DESCRIPTION OF SYMBOLS 10 Display part 11 Sound source device 18 AD converter 30 Light / ultrasonic composite unit 50 Scalp 51 Skull 52 Brain 80 Pressure transmission gel

Claims (3)

Ultrasonic incident means for making ultrasonic waves incident on the living body head, irradiation means for irradiating near infrared light, and splitting the near infrared light so that one near infrared light is incident on the living body and the other near red Light / ultrasonic wave having splitting means that uses external light as reference light, and detection means that detects a beat signal generated by interference between the near-infrared light incident and reflected on the living body head and the reference light With a recovery unit,
Non-invasively contacting the light / ultrasound combination unit with the living body head, the one near infrared light is incident on the living body head together with the ultrasonic wave, and the ultrasonic waves are applied to the tissue of the living body head. A change in blood volume is calculated from a change in the intensity of a beat signal caused by interference between the near-infrared light reflected from the living body head that has caused a Doppler shift due to the induced motion and the reference light. Cerebral circulation blood flow measurement device.   The cerebral blood flow measurement apparatus according to claim 1, wherein the optical / ultrasonic combination unit includes a pressure sensor.   The pressure sensor detects the pressing force when the optical / ultrasonic unit is brought into contact with the living body head, the depth from the living body surface is specified by the pressing force, and the brain of the specified depth The cerebral circulatory blood flow measuring device according to claim 2, further comprising an informing means for informing the circulatory blood flow.

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