JP6245863B2 - SUBJECT INFORMATION ACQUISITION DEVICE AND METHOD FOR CONTROLLING SUBJECT INFORMATION ACQUISITION DEVICE - Google Patents

Description

  The present invention relates to a subject information acquisition apparatus that measures information inside a subject using light.

Research on optical imaging technology that obtains information in a subject by irradiating the subject with measurement light such as laser light and detecting the measurement light that has propagated through the subject is being actively promoted in the medical field. .
One of the optical imaging techniques is near infrared spectroscopy. Near-infrared spectroscopy obtains light absorption characteristics in the internal tissue of a subject by irradiating the subject with light from a light source and detecting the weak light propagated and diffused in the subject with a photodetector. It is a method to do. Further, by acquiring a change in the detected light intensity, it is possible to obtain information about a change in the light absorption characteristics inside the subject.

It is known that the light absorption characteristics depend on the wavelength of light and the type of absorber. For example, the amount of change in the relative concentrations of oxyhemoglobin and deoxyhemoglobin can be obtained by irradiating the subject with light of two types of wavelengths and measuring the light absorption characteristics of hemoglobin in the blood.
By performing such near-infrared spectroscopy measurement on the head of a living body, changes in oxygen metabolism on the surface of the cerebral cortex (brain activation state) can be measured non-invasively.

  By the way, when measuring the activation state of the brain using near-infrared spectroscopy, it is known that fluctuations in blood flow in the scalp that do not originate from brain activity affect the measurement (Non-Patent Document 1). reference). This is to irradiate the brain with measurement light through the scalp. Tissues that affect measurement, such as the scalp, are called intervening tissues. As described above, when there is an intervening tissue between the light source and the region to be measured, if the blood flow changes in the intervening tissue, the amount of transmitted measurement light changes, so the measurement result changes. .

  As a technique for solving this problem, there is an optical measurement device described in Patent Document 1. In the optical measurement apparatus, the subject is measured by two types of measurement systems in which the interval between the light incident position and the detection position is changed. In the measurement system (first measurement system) in which the interval between the light incident position and the detection position is long, the measurement light reaches the deep part, so that a signal including information on the cerebral cortex and scalp can be obtained. Further, in the measurement system (second measurement system) with a short interval, the measurement light does not reach the deep part, so that a signal including only information on the scalp can be obtained. Therefore, only the information obtained from the cerebral cortex can be extracted by correcting the signal obtained by the first measurement system using the signal obtained by the second measurement system.

JP 2009-148388 A

T. Takahashi “Influence of skin blood flow on near-infrared spectroscopy signals measured on the forehead during a verbal fluency task.”, Neuroimage, Vol.57, (2011) G. Strangman “Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters”, Neuroimage, Vol. 18, (2003)

In the optical measurement device described in Patent Document 1, the influence of the intervening tissue is removed by acquiring the variation in the amount of measurement light transmitted through the intervening tissue and correcting the measurement signal.
In the subject, light propagates along a path connecting the light incident position and the detection position in an arc shape. As described above, when the interval between the light incident position and the detection position is shortened, the light passes through a shallow position in the subject, so that information on a relatively shallow portion can be obtained.

However, although the detected signal reflects local blood flow fluctuations at any position on the arcuate path, it does not necessarily reflect the blood flow fluctuations of the entire intervening tissue. Absent. Further, since the acquired second signal has no resolution in the depth direction, information cannot be extracted by specifying the depth of the intervening tissue.
In other words, the conventional technique has a problem in that it is not always possible to accurately acquire fluctuations in the amount of measurement light transmitted through the intervening tissue.

  In order to avoid this problem, it is conceivable to measure the subject using photoacoustic imaging instead of near-infrared spectroscopy. Photoacoustic imaging is a technique for visualizing a tissue configuration in a subject by analyzing an acoustic wave generated in the subject due to measurement light. Photoacoustic imaging can acquire the optical characteristic distribution in the subject with higher accuracy than near-infrared spectroscopy. However, when photoacoustic imaging is performed on the head of a living body, attenuation and reflection of acoustic waves are generated by the skull, and accurate information cannot be obtained.

  The present invention has been made in view of such problems of the prior art, and provides a technique capable of removing the influence of intervening tissue in a subject information acquisition apparatus using near-infrared spectroscopy. Objective.

The subject information acquisition apparatus according to the present invention includes:
Light irradiating means for irradiating a subject having an intervening tissue on the surface layer, and light detection for detecting the intensity of light transmitted through the intervening tissue and propagating through the subject, and converting it into a first signal Means, an acoustic wave receiving means for detecting an acoustic wave generated in the intervening tissue due to the irradiated light and converting it to a second signal, and the intervening tissue based on the second signal Signal processing means for acquiring optical related information that is information related to the optical characteristics of the optical signal, and correcting the first signal based on the optical related information, and removing the influence of the intervening tissue from the first signal. Signal correction means , wherein the second signal is a signal representing a sound pressure of an acoustic wave generated in the intervening tissue, and the signal processing means is configured to transmit the acoustic wave generated in the intervening tissue. Expressed the relationship between sound pressure and the amount of light transmitted through the intervening tissue Using chromatography data, and acquires the amount of light transmitted through the intervening tissue.

In addition, the control method of the subject information acquisition apparatus according to the present invention includes:
A method for controlling a subject information acquisition apparatus for acquiring internal information of a subject having an intervening tissue on a surface layer, the light irradiation step for generating light to irradiate the subject, and the subject passing through the intervening tissue A light detection step for detecting the intensity of light propagated in the interior and converting it into a first signal; and detecting an acoustic wave generated in the intervening tissue due to the irradiated light; An acoustic wave receiving step for converting, a signal processing step for obtaining optical related information that is information related to optical characteristics of the intervening tissue based on the second signal, and the first based on the optical related information correcting the signal, and a signal correction step of removing the influence of the intervening tissue from said first signal, only contains the second signal represents the sound pressure of the acoustic wave generated within the intervening tissue Signal processing step. In the sound pressure of the acoustic wave generated within the intervening tissue, the intervening tissue using data representing the relationship between the amount of light transmitted through, to get the amount of light transmitted through the intervening tissue Features.

  According to the present invention, the influence of the intervening tissue can be removed in the subject information acquiring apparatus using near infrared spectroscopy.

The figure explaining the structural example of the biological light measuring device which concerns on 1st embodiment. The figure explaining the simulation model in 1st embodiment. The figure explaining the simulation result in 1st embodiment. The figure explaining the simulation result in 1st embodiment. The figure explaining the conversion table in 1st embodiment. The figure explaining the process flowchart in 1st embodiment. The figure explaining the structural example of the biological light measuring device which concerns on 2nd embodiment. The figure explaining the structural example of the biological light measuring device which concerns on 3rd embodiment.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In principle, the same components are denoted by the same reference numerals, and description thereof is omitted. Further, numerical values (thickness, size), materials, and the like used in the description of the embodiments do not limit the scope of the invention.

(First embodiment)
The biological light measurement device according to the first embodiment is a device that visualizes brain functions by acquiring and imaging information on blood flow in the brain of a living body using near infrared spectroscopy. Further, it has a function of acquiring information related to the intervening tissue of the subject using an acoustic wave and removing the influence of the intervening tissue from the measurement result using the acquired information.

<System configuration>
The configuration of the biological light measurement device according to the first embodiment will be described with reference to FIG.
The biological light measurement apparatus according to the first embodiment includes a light source 1, a photodetector 2, an optical waveguide 3, a light projecting probe 4, a light receiving probe 5, an optical waveguide 6, a signal processing unit 7, a pulse light source 8, and an optical waveguide 9. , A second projecting probe 10, an acoustic wave probe 11, and a display unit 12. In addition, the optical measurement device according to the present embodiment includes a light intensity measurement system that measures the first signal and a photoacoustic wave measurement system that measures the second signal in the present invention. The components included in each measurement system will be described in order.

First, the light intensity measurement system will be described.
The light intensity measurement system is a measurement system that detects the intensity of light irradiated from the light source 1 to the subject 100 and propagated through the subject 100 with the photodetector 2 and converts it into a first signal.

The light source 1 is a means for generating light that irradiates the subject 100. The light generated by the light source 1 is preferably light having a specific wavelength that is absorbed by a specific component among the components constituting the subject 100. The wavelength is preferably in the range of 700 nm to 1100 nm with little absorption in the living body. The type of light is any one of continuous light, intensity modulated light, and pulsed light. The light source 1 may be composed of one or a plurality of light sources. Moreover, in order to measure the difference of the optical characteristic value depending on the wavelength, a plurality of light sources having different wavelengths may be used. Hereinafter, the light generated by the light source 1 is referred to as measurement light.
The light source 1 is preferably a laser light source, but a light emitting diode or the like may be used instead of the laser. When a laser light source is used, various types of lasers such as a solid-state laser, a gas laser, a dye laser, and a semiconductor laser can be used.

The optical waveguide 3 is means for guiding measurement light emitted from the light source 1 to the surface of the subject 100. An optical fiber is preferably used for the optical waveguide 3. When there are a plurality of light sources, a plurality of optical fibers corresponding to the respective light sources may be used to guide measurement light to the surface of the subject. Alternatively, measurement light generated by a plurality of light sources may be incident on a single optical fiber and guided to the surface of the subject. On the contrary, a single optical fiber may be branched and a plurality of measurement lights may be guided to the surface of the subject. In addition, when the light source 1 can be arrange | positioned in the vicinity of a subject, the optical waveguide 3 does not necessarily need to be used.

  The light projecting probe 4 is a probe provided at the tip of the optical waveguide 3 and is a means for irradiating the subject with measurement light. The light projecting probe 4 is covered with a housing made of metal, plastic, rubber, or the like, and is provided with an emission surface from which measurement light is emitted. The light projecting probe 4 is arranged on the subject surface by a fixing member (not shown).

  The light receiving probe 5 is means for detecting measurement light propagated in the subject. A light receiving surface on which measurement light is incident is provided at the tip of the light receiving probe 5. The light receiving probe 5 is arranged on the surface of the subject at a position away from the light projecting probe 4 by a predetermined distance by a fixing member (not shown).

Here, the measurement target region and the intervening tissue will be described.
The inside of the subject 100 is roughly divided into a measurement target region 101 that is a target region to be measured by the apparatus and an intervening tissue 102 that is located on the surface layer side of the measurement target region. When the subject is the head of a living body, the measurement target region 101 is a cerebral cortex, and the intervening tissue 102 is an extracerebral tissue such as a scalp or a skull.
The light incident on the subject 100 diffuses inside the subject while being attenuated and scattered, and is emitted from the subject surface. The path 103 of the light emitted from the light projecting probe 4 and incident on the light receiving probe 5 has an arc shape called a banana shape as shown in the figure. The measurement light is divided into three parts: a part emitted from the light projecting probe 4 and transmitted through the intervening tissue 102, a part transmitted through the measurement target region 101, and a part transmitted through the intervening tissue 102 and incident on the light receiving probe 5. It is done.

By adjusting the distance between the light projecting probe 4 and the light receiving probe 5, the depth at which the light reaches can be relatively adjusted. When the subject is an adult head, if the distance between the probes is about 30 mm, the depth of light reaching from the scalp surface can be reduced to about 15 mm to 20 mm. In the case of an adult, since the depth from the scalp surface to the cerebral cortex is about 15 mm, light incident from the scalp surface reaches the cerebral cortex and returns to the scalp surface.
When the light absorption characteristics in the cerebral cortex (measurement target region 101) fluctuate, the amount of measurement light transmitted through the cerebral cortex fluctuates, so that the brain function can be measured by acquiring the fluctuation amount.
However, similarly, when the light absorption characteristic fluctuates in the scalp, the amount of measurement light that reciprocates in the cerebral cortex fluctuates. Factors that change the light absorption characteristics include, for example, changes in the concentration and amount of pigments such as oxyhemoglobin and deoxyhemoglobin in blood. This fluctuates the results of measurements performed on the cerebral cortex.

  The biological light measurement device according to the present embodiment acquires a change in the amount of light that passes through the intervening tissue 102 and corrects the measurement result. Specifically, fluctuations in the measurement result generated when the measurement light reciprocates through the scalp, that is, a portion emitted from the light projecting probe 4 and transmitted through the intervening tissue 102, and transmitted through the intervening tissue 102 to the light receiving probe 5. It corrects fluctuations in the light absorption characteristics caused by the incident part.

Continue to explain the components.
The optical waveguide 6 is a means for guiding the light incident on the light receiving probe 5 to the photodetector 2. It is preferable to use an optical fiber for the optical waveguide 6 as in the optical waveguide 3. In addition, when the photodetector 2 can be disposed in the vicinity of the subject 100, the optical waveguide 6 is not necessarily used.

The photodetector 2 is means for detecting the intensity of light propagated through the subject and converting it into an electrical signal (first signal in the present invention). As the photodetector 2, a photodiode (PD), an avalanche photodiode (APD), a photomultiplier tube (PMT), or the like can be used.
By acquiring the intensity of the light detected by the photodetector 2, it is possible to obtain information about the temporal change in the light absorption characteristics inside the subject. The first signal includes information about a path through which light passes. That is, the first signal includes information on the light absorption characteristics of the measurement target region 101 and the intervening tissue 102 in a mixed manner. The converted signal is sent to the signal processing unit 7.

Next, the photoacoustic wave measurement system will be described.
The photoacoustic wave measurement system irradiates the subject with pulsed light, detects the acoustic wave generated from the light absorber in the subject due to the pulsed light with the acoustic probe 11, and It is a measurement system that converts it into a second signal.

The pulsed light source 8 is means for generating pulsed light that irradiates the subject 100. The wavelength of the pulsed light is preferably substantially the same as the light generated by the light source 1. By matching the light generated by the light source 1 and the wavelength, it is easy to take correspondence with the first signal. The pulse width is preferably on the order of several nanoseconds to several hundred nanoseconds. Hereinafter, the light generated by the pulse light source 8 is simply referred to as pulsed light.
The pulse light source 8 is preferably a laser light source, but a light emitting diode or the like may be used instead of the laser light source. When a laser light source is used, various types of lasers such as a solid-state laser, a gas laser, a dye laser, and a semiconductor laser can be used. Further, in order to increase the irradiation intensity of the light irradiated to the subject, a plurality of light sources that generate light of the same wavelength may be used.

The pulsed light emitted from the pulsed light source 8 is applied to the subject 100 via the optical waveguide 9 and the second light projecting probe 10. The second light projecting probe 10 is disposed in the vicinity of the light projecting probe 4 and the light receiving probe 5.
It is preferable to use an optical fiber for the optical waveguide 9 as in the case of the optical waveguide 3. Further, when there are a plurality of pulse light sources, a plurality of optical fibers corresponding to the respective pulse light sources may be used to guide the pulse light to the surface of the subject 100.
Alternatively, measurement light generated by a plurality of pulsed light sources may be combined by being guided to a single optical fiber and guided to the surface of the subject. Conversely, a plurality of pulsed light beams may be guided to the surface of the subject by branching one optical fiber. If the pulse light source 8 can be disposed in the vicinity of the subject 100, the optical waveguide 9 is not necessarily used.

The acoustic wave probe 11 is a means for converting an acoustic wave generated inside the subject into an electric signal (second signal in the present invention), and is an acoustic wave receiving means in the present invention.
Here, acoustic waves generated inside the subject will be described.
The pulsed light applied to the subject 100 is diffused into the subject 100 while being attenuated by absorption. Then, an acoustic wave is generated when the light absorber absorbs light energy in the subject 100. The initial sound pressure P of the generated acoustic wave can be expressed by Equation 1.
P = Γ × μ _a × φ (Formula 1)
Here, Γ is the Grueneisen constant, μ _a is the light absorption coefficient in the light absorber, and φ is the amount of pulsed light that reaches the light absorber. The sound pressure of the generated acoustic wave is proportional to the absorbed light energy (μ _a × φ). The acoustic wave probe 11 receives the acoustic wave generated in this way.

The acoustic wave probe is also simply called a probe, an acoustic wave probe, or a transducer. The acoustic wave in the present invention is typically an ultrasonic wave, and includes an elastic wave called a sound wave, an ultrasonic wave, a photoacoustic wave, and an optical ultrasonic wave. The acoustic wave probe 11 may be composed of a single acoustic wave probe or a plurality of acoustic wave probes. Further, the second light projecting probe 10 and the acoustic wave probe 11 may be arranged so as to sandwich the light projecting probe 4 (or the light receiving probe 5).
In addition, it is desirable that the acoustic wave probe 11 has high sensitivity and a wide frequency band. Specific examples include PZT (piezoelectric ceramics), PVDF (polyvinylidene fluoride resin), CMUT (capacitive micromachined ultrasonic transducer), and those using a Fabry-Perot interferometer. However, the present invention is not limited to those listed here, and any one may be used as long as it satisfies the function as a probe.

The acoustic wave probe 11 may be one in which a plurality of receiving elements are arranged one-dimensionally or two-dimensionally. When a multidimensional array element is used, acoustic waves can be received at a plurality of locations at the same time, so that the measurement time can be shortened and the influence of vibration of the subject can be reduced. If the probe is smaller than the subject, the probe may be scanned to receive acoustic waves at a plurality of positions.
In addition, when the level of the signal acquired by the acoustic wave probe 11 is small, it is preferable to amplify the signal intensity using an amplifier. An acoustic impedance matching agent (not shown) for suppressing the reflection of sound waves may be disposed between the acoustic probe 11 and the subject 100.
The second signal acquired by the acoustic probe 11 is sent to the signal processing unit 7.

The signal processing unit 7 is a unit that converts the second signal obtained by the acoustic probe 11 into a digital signal and generates (reconstructs) image data. Further, it is a signal correction unit that corrects the first signal using the second signal. A specific correction method will be described later.
The signal processing unit 7 may be realized by a computer, or may be realized by dedicated hardware, FPGA (Field Programmable Gate Array), or the like. Also,
The signal processing unit 7 may include an A / D converter that converts an analog signal into a digital signal, a storage medium that holds information necessary for analysis and an analysis result, and the like.
Examples of the image reconstruction method executed by the signal processing unit 7 include a Fourier transform method, a universal back projection method, a filtered back projection method, a sequential reconstruction method, and the like. It doesn't matter.

  The display unit 12 is a means for displaying the reconstructed image generated by the signal processing unit 7. As the display unit 12, a liquid crystal display, a plasma display, an organic EL display, an FED, or the like can be used.

<How to remove the influence of intervening tissues>
Next, a method for removing the influence of the intervening tissue from the measurement result by correcting the acquired first signal will be specifically described.
First, a method for acquiring the amount of measurement light transmitted through the intervening tissue using the second signal acquired by the acoustic wave probe will be described, and then the measurement signal (first signal) based on the acquired result. ) Will be described.

<< Acquiring the amount of light transmitted through the intervening tissue >>
When the subject is the head of a living body, the intervening tissue is the scalp, and the light absorber in the intervening tissue is melanin or capillaries near the surface of the scalp. The blood flow in these capillaries becomes a variable factor of light absorption characteristics. Information about these light absorbers (optical related information) can be obtained by analyzing acoustic waves generated due to pulsed light.
Since the capillaries are minute relative to the acoustic wave probe 11, the intervening tissue can be regarded as homogeneous. Further, since the amount of light irradiated on the subject surface is constant, the absorbed light energy is substantially proportional to the light absorption coefficient. Therefore, the sound pressure of the acoustic wave generated in the intervening tissue due to the pulsed light is substantially proportional to the absorption coefficient of the intervening tissue.

  Further, the position of the sound source can be specified from the distance between the sound source and the acoustic wave probe and the sound speed. That is, when the distance between the second light projecting probe 10 and the acoustic wave probe 11 and the speed of sound in the intervening tissue are known, the time at which the acoustic wave generated in the intervening tissue is detected can be specified. That is, the sound pressure of the acoustic wave generated in the intervening tissue can be acquired.

  As described above, the absorption coefficient of the intervening tissue has a correlation with the sound pressure of the acoustic wave. That is, if there is data representing this correlation, the amount of measurement light transmitted through the intervening tissue can be obtained from the sound pressure of the received acoustic wave. Here, an example in which the correlation is obtained by performing light propagation analysis and acoustic wave propagation analysis will be described.

The light propagation analysis was performed using the Monte Carlo method which is a known method. For example, Non-Patent Document 2 reports on the optical constants and simulation methods of living organisms.
For the acoustic wave propagation analysis, known analysis software was used. As an analysis software that can handle ultrasound, for example, there is k-wave, which is published at University College London.
In this example, as shown in FIG. 2, a two-dimensional model of 64 millimeters in length and width was simulated to simulate the head. The model has a six-layer structure of air 110, acoustic matching material 111, scalp 112, skull 113, cerebrospinal fluid 114, and cerebral cortex 115. A light irradiation area W having a width of 1 mm is set on the surface of the scalp 112.
By performing light propagation analysis using such a model, the distribution of light absorption energy (μ _a × φ in Equation 1) is obtained, and then the initial sound pressure (in Equation 1 is calculated based on the absorption energy distribution). P) was obtained, and finally acoustic wave propagation analysis was performed. In this example, assuming that the acoustic wave probe 11 is located at a position 5 mm away from the center of the light irradiation region W, the reaching pressure wave was obtained. Table 1 shows the thickness, optical characteristics, and acoustic characteristics of each layer used in the analysis. The parameters used are typical values for each substance.

  FIG. 3 shows the light absorption energy distribution obtained as a result. The vertical axis in FIG. 3 is the vertical direction, and the horizontal axis is the horizontal direction. FIG. 3 is an enlarged view of the region from the scalp 112 to a depth of 30 mm with the light irradiation region as the center in the horizontal direction. Contour lines are displayed in a logarithmic scale with the maximum value normalized to 1. From FIG. 3, it can be seen that in the region within the scalp 112, the light absorption energy is maximized in the region 116 immediately below the light irradiation portion shown in black. Therefore, the maximum initial sound pressure is generated in the region 116 immediately below the light irradiation part. Further, from the light absorption energy distribution, the amount of measurement light irradiated on the surface of the cerebral cortex 115 (that is, the amount of light transmitted through the intervening tissue) is also obtained.

FIG. 4 shows the result of acoustic wave propagation analysis assuming that the light absorption energy distribution is the initial sound pressure distribution. In the figure, the horizontal axis represents time, and the vertical axis represents the sound pressure waveform reaching the acoustic wave probe. The distance (5 mm) between the light irradiation region and the acoustic wave probe and the sound speed (1540 m / s) on the scalp 112
From the relationship of s), it can be seen that the peak appearing at the time of about 3.3 μs in the figure is derived from the acoustic wave generated in the scalp 112. That is, information on the absorbed energy of light in the scalp 112 is obtained from the amplitude A corresponding to the scalp 112 in the figure.

  A similar analysis was performed by changing the absorption coefficient of the scalp 112 from 0.8 to 1.2 times. FIG. 5A shows the relationship between the absorption coefficient and the amplitude A of the acoustic wave generated on the scalp 112. In the figure, the horizontal axis represents the absorption coefficient of the scalp 112, and the vertical axis represents the amplitude of the acoustic wave generated in the scalp 112. Both axes are normalized and displayed with the results calculated under the conditions in Table 1. FIG. 5A shows that there is a proportional relationship between the absorption coefficient of the scalp 112 and the amplitude of the generated acoustic wave.

Next, FIG. 5B shows the relationship between the absorption coefficient of the scalp 112 and the amount of light applied to the surface of the cerebral cortex 115 obtained by light propagation analysis. In the figure, the horizontal axis represents the absorption coefficient of the scalp 112, and the vertical axis represents the amount of light applied to the surface of the cerebral cortex 115. Both axes are normalized and displayed with the results calculated under the conditions in Table 1. FIG. 5B shows that there is a negative correlation between the amount of light applied to the surface of the cerebral cortex 115 and the absorption coefficient of the scalp 112.
FIG. 5C shows the relationship between the amplitude of the acoustic wave generated on the scalp 112 and the amount of light applied to the surface of the cerebral cortex 115, obtained from FIGS. 5A and 5B. FIG. 5C shows that there is a negative correlation between the amount of light applied to the surface of the cerebral cortex 115 and the amplitude of the acoustic wave generated on the scalp 112. If there is such data corresponding to FIG. 5C, it is possible to estimate a change in the amount of measurement light irradiated on the surface of the cerebral cortex 115 from a change in the amplitude of the acoustic wave generated in the scalp 112. .
In addition, as long as the light quantity of the measurement light which permeate | transmits an intervening tissue can be calculated | required from the received acoustic wave, you may use other than an amplitude. For example, the inclination of the waveform of the acoustic wave, the root mean square, the power when the FFT is executed, or the like may be used.

<Measurement signal correction method>
Next, a specific method for correcting the first signal will be described.
First, the “control state” and the “conversion table”, which serve as a reference when measuring the subject, will be described. The control state is a state in which no load is imposed on the subject, or a state in which a standard load that makes the state of the subject constant is imposed (control).
The conversion table is a table that represents the relationship between the amplitude of the acoustic wave generated in the intervening tissue and the amount of light transmitted through the intervening tissue, as shown in FIG. In the present embodiment, using the conversion table, correction is performed in the direction in which the first signal is amplified as the amount of measurement light transmitted through the intervening tissue decreases.
The conversion table can be created in advance by simulation as described above, phantom or animal experiment. Further, only one conversion table corresponding to a standard subject may be used, or a plurality of conversion tables may be prepared according to the subject. For example, the thickness of the intervening tissue varies depending on the measurement site of the subject and the age, sex, and physique of the subject. Therefore, a plurality of conversion tables corresponding to the thickness of the intervening tissue may be prepared in advance, and a conversion table suitable for the target subject may be selected.
The conversion table can be selected using information acquired by magnetic resonance imaging, X-ray tomography, or the like. Further, after measuring the subject a plurality of times, a conversion table that can stably correct the influence of the scalp may be selected afterwards.

The acquisition of the first and second signals is first performed on the subject in the control state (first measurement). Then, the amplitude A ₀ corresponding to the acoustic wave generated in the intervening tissue is acquired from the second signal. The acquisition of the amplitude A ₀ may be performed using a single signal, or may be averaged after performing a plurality of measurements.

Then, while imposing a load on the subject, the first and second signals measured (second measurement of) from the second signal acquired to obtain the amplitude A ₁ corresponding to the acoustic wave of the scalp. Then, using a conversion table change amount of the amplitude _(A 1 _/ A _0), in the first measurement and the second measurement is performed to obtain the amount of change T of the transmitted light intensity. Finally, the first signal acquired in the second measurement is corrected using the reciprocal (1 / T) of the change amount as the correction amount K.
In the present embodiment, the photoacoustic wave measurement system is provided near each of the light projecting probe and the light receiving probe. In such a case, the correction amount K may be acquired for each of the photoacoustic wave measurement systems on the light projecting side and the light receiving side. As shown in Equation 2, a signal in which the change in the absorption coefficient of the intervening tissue is corrected can be obtained by multiplying the first signal by the correction coefficient. Incidentally, I is the first signal, I 'is the corrected signal, K _s is the light projecting probe side of the correction amount, the K _D represents the correction amount of the light receiving probe side.
I ′ = I × (K _s × K _D ) (Formula 2)
In addition, since the said process is for correct | amending the change of the light quantity of the measurement light which arose from the 1st measurement to the 2nd measurement, it is not necessary to correct | amend the signal acquired in the contrast state. Therefore, the first signal acquired in the first measurement is used without correction (I ′ = I).

In addition, the wavelength dependence of the light absorption characteristic can be obtained by measuring the signal I ′ for a plurality of wavelengths. The light absorption characteristics of the measurement target component (for example, oxyhemoglobin or deoxyhemoglobin) in the subject have different wavelength dependencies for each component. Therefore, by measuring the corrected signal I ′ for a plurality of wavelengths, it is possible to calculate the concentration change of the measurement target component in the measurement target region.
For example, when the measurement target component is oxygenated hemoglobin or deoxygenated hemoglobin, two or more wavelengths having wavelengths of 700 nm or more and 1100 nm or less may be used. The light absorption coefficient of oxyhemoglobin and deoxyhemoglobin is reversed in magnitude relation around 800 nm, and therefore, it is preferable to select two or more wavelengths sandwiching at least 800 nm. For example, the relative density change can be measured by using wavelengths of 700 nm and 830 nm.

<Process flowchart>
FIG. 6 shows a flowchart of processing performed by the biological light measurement apparatus according to the present embodiment. It is assumed that the installation of the probe and the like for the subject, the measurement of the control state (first measurement), and the preparation of the conversion table are completed.
First, the subject is irradiated with light of a specific wavelength, and the first signal is measured using a light intensity measurement system (step S1). Next, the subject is irradiated with pulsed light having the same wavelength as in step S1, and the second signal is measured using the photoacoustic measurement system (step S2). Steps S1 and S2 are preferably performed at short intervals.
Next, based on the acoustic waves acquired in the first and second measurements, the amplitude corresponding to the acoustic waves generated in the intervening tissue is acquired, the amount of change in the amplitude is calculated, and the conversion table is used to calculate the amplitude. The correction amount of one signal is calculated (step S3). If there are a plurality of conversion tables, the conversion table most suitable for the condition of the subject is selected and processed.
Next, the first signal acquired in step S1 is corrected using the calculated correction amount (step S4).

Further, it is determined whether measurement has been completed for all wavelengths (step S5). If not completed, the process proceeds to step S1, and measurement is performed again. If measurement has been completed for all wavelengths, the process proceeds to step S6.
Next, using the measurement result for each wavelength, the concentration change of the substance constituting the subject is calculated from the wavelength dependence of the absorption characteristics (step S6).
When measuring the change over time, the processing from step S1 to step S6 is repeated until the predetermined measurement time is over (step S7). When measuring a change over time, the measurement may be repeated at a period having a sufficient time resolution with respect to the change inside the subject. For example, since blood in the cerebral cortex changes in a cycle on the order of one hundred milliseconds to a second, it may be measured in a cycle smaller than the change cycle of the blood flow. Further, by imposing a load on the subject during measurement of changes over time, changes in the internal state relative to the control state can be measured. Examples of the target for measuring a change in the internal state include brain function measurement for measuring an activation region of the brain.

As described above, the biological light measurement apparatus according to the first embodiment can remove the influence of the intervening tissue (scalp) by acquiring the acoustic wave signal generated in the intervening tissue, and the measurement target region ( It is possible to acquire the change of the signal generated in the cerebral cortex more accurately.
As described above, the measurement apparatus according to the prior art cannot accurately acquire the amount of measurement light transmitted through the intervening tissue and cannot accurately acquire the internal information of the subject. On the other hand, in the living body light measurement device according to the present embodiment, since the light absorption characteristics in the intervening tissue can be accurately acquired, the influence of the intervening tissue can be accurately removed, and the measurement accuracy can be improved. .

  Note that the flowchart shown in the present embodiment is an example, and the processing order may be changed as long as an equivalent function can be realized. For example, the order of measurement of the first signal and measurement of the second signal may be reversed. Further, correction and density change calculation may be performed after all predetermined measurements are completed. Further, when the change rate of the second signal can be regarded as moderate with respect to the first signal, the measurement of the second signal may be thinned out.

(Second embodiment)
In the first embodiment, the second light projecting probe 10 and the acoustic wave probe 11 are disposed in the vicinity of the light projecting probe 4 and the light receiving probe 5, respectively. That is, the measurement was performed using a plurality of sets of photoacoustic wave measurement systems. In contrast, the second embodiment is an embodiment in which measurement is performed using a single photoacoustic wave measurement system.
The second embodiment can be applied to the case where the variation amount of the measurement signal caused by the intervening tissue can be regarded as the same regardless of the position.
FIG. 7 is a configuration diagram of the biological light measurement device according to the second embodiment. In the present example, the second light projecting probe 10 and the acoustic wave probe 11 are arranged approximately in the middle between the light projecting probe 4 and the light receiving probe 5. Other configurations are the same as those of the first embodiment. The second light projecting probe 10 and the acoustic wave probe 11 may be arranged anywhere as long as the signal fluctuations caused by the intervening tissues can be regarded as substantially the same.

In this embodiment, the correction coefficient K is acquired as in the first embodiment. However, since there is only one photoacoustic measurement system, the correction coefficient is determined using Equation 3 in the process of step S4. K is a correction amount in the photoacoustic measurement system.
I ′ = I × (K × K) (Formula 3)
When the subject 100 is the head, it is considered that the change in scalp blood flow in the horizontal direction is relatively small compared to the local change in the cerebral cortex. It is considered that no error occurs. Therefore, with the configuration as in this embodiment, the number of photoacoustic wave measurement systems can be reduced and the cost of the apparatus can be reduced.

(Third embodiment)
In the first and second embodiments, different light sources are used for the light intensity measurement system and the photoacoustic measurement system. In contrast, the third embodiment is an embodiment in which measurement is performed using a common pulse light source.
FIG. 8 is a configuration diagram of the biological light measurement device according to the third embodiment. In this example, a pulsed light source 13 which is a common light source is used, and pulsed light is branched by an optical waveguide 14. Other configurations are the same as those of the first embodiment. In the example of FIG. 8, the light projecting probe 15 is also common to the light intensity measurement system and the photoacoustic measurement system, but may be a separate one.

The photodetector 2 detects the pulsed light emitted from the pulsed light source 13 and propagated through the subject as a first signal, and the acoustic probe 11 is detected in the subject by the pulsed light emitted from the pulsed light source 13. The generated acoustic wave is detected as a second signal. The first signal and the second signal may be measured simultaneously or separately. With such a configuration, the number of light sources, optical waveguides, and light projection probes to be used can be reduced, and the cost of the apparatus can be reduced.

(Fourth embodiment)
In the first to third embodiments, the measurement is performed in the control state and in a state where a load is imposed on the subject, and the signal is corrected using the change in the amount of measurement light. On the other hand, the fourth embodiment removes the information of the intervening tissue from the temporal change of the first signal by using the temporal change of the light absorption characteristic of the intervening tissue obtained from the second signal. It is an embodiment. That is, in this embodiment, a plurality of measurements are continuously performed while imposing a load on the subject. The configuration of the biological light measurement device according to the fourth embodiment is the same as that of the first to third embodiments.

In the fourth embodiment, each time measurement is performed, the first signal is collected to generate a time-series signal. Henceforth, the 1st signal in this embodiment shall be a signal showing the time-dependent change of the intensity | strength of the measurement light which permeate | transmitted the test object.
Further, an amplitude corresponding to the acoustic wave generated in the intervening tissue is obtained from the second signal, and a signal representing the amplitude in time series is generated. This is referred to as a third signal. That is, the third signal is a signal that represents a change in the acquired amplitude over time.

  When the signal acquisition is completed, the control state of the subject and the time change with respect to the control state are acquired for the combination of the first signal and the third signal. The time change of the first signal includes information on the light absorption characteristics of the intervening tissue and the measurement target region. In addition, the time change of the third signal includes information on the light absorption characteristics of the intervening tissue. Then, for each time change of the first signal and the third signal, the signal (information component) between the measurement target region and the intervening tissue is separated using a mathematical signal separation method such as independent component analysis, Only the signal (information component) in the measurement target area is extracted.

  In the fourth embodiment, by such a method, random noise components can be removed in the process of separating the signal components, and an effect of improving the signal-to-noise ratio can be obtained.

(Example)
An example corresponding to the first embodiment will be described. The living body light measuring apparatus according to the present embodiment is a measuring apparatus for the purpose of obtaining a change in blood dynamics of a living body's brain.
The light intensity measurement system and the photoacoustic wave measurement system were arranged on the surface of the subject 100 by a holder (not shown). As the light source 1, a light source capable of irradiating semiconductor laser light having wavelengths of 750 nm and 1060 nm was used. The light generated from the light source 1 is modulated light having a modulation frequency of 100 MHz. The pulse light source 8 used was an Nd: YAG laser with a pulse width of 50 nanoseconds, a repetition frequency of 10 Hz, and a wavelength of 1064 nm, and an alexandrite laser with a wavelength of 750 nm.
For the acoustic wave probe 11, a piezo type transducer having a center frequency of 1 MHz was used.

In this embodiment, the light generated by the light source is guided to the light projecting probe 4 via the optical fiber, and is coupled to the light receiving probe 5 on the surface of the subject 100. The interval between the light projecting probe 4 and the light receiving probe 5 was 30 mm. Further, a photomultiplier tube (PMT) was used for the photodetector 2, and measurement was performed in synchronization with the modulation frequency of the light source 1. And the intensity | strength of the light irradiated from the light source 1 and propagated through the subject 100 was acquired by the photodetector 2, and a first signal was obtained.
Further, the subject 100 was irradiated with pulsed light emitted from the pulsed light source 8 from the second projection probe 10 via an optical fiber. Then, an acoustic wave generated in the subject 100 due to the pulsed light was acquired by the acoustic wave probe 11 to obtain a second signal.

The first signal and the second signal were processed by a signal processing unit 7 configured by a computer. The signal processing unit 7 specifies a portion corresponding to the acoustic wave generated in the scalp from the second signal, using the distance between the second light projecting probe 10 and the acoustic probe 11 and the sound speed in the living body. Then, the change of the absorption coefficient in the scalp was obtained. In addition, a correction coefficient was calculated from the change in absorption coefficient, the first signal was corrected, and the change over time in the concentration ratio of oxyhemoglobin and deoxyhemoglobin was obtained. The correction conversion table used in advance was created by simulation and a phantom experiment simulating a living body.
The measurement was performed using a light source having a plurality of wavelengths, and repeated until a predetermined measurement time was completed. The result finally obtained in this way was that the influence of blood flow in the scalp was removed. That is, it was confirmed that the change in the absorption coefficient of the interstitial tissue (scalp) can be accurately obtained, and the blood dynamics of the brain can be obtained after correcting the signal accurately.

(Modification)
The description of each embodiment is an exemplification for explaining the present invention, and the present invention can be implemented with appropriate modifications or combinations without departing from the spirit of the invention. For example, the present invention can also be implemented as a method for controlling a subject information acquisition apparatus including at least a part of the above processing. The above processes and means can be freely combined and implemented as long as no technical contradiction occurs.
For example, a plurality of sets of light intensity measurement systems and photoacoustic wave measurement systems may be provided and arranged one-dimensionally or two-dimensionally on the subject surface. By arranging a plurality of sets of each measurement system, a spatial distribution of measurement results can be obtained. Further, the acquired distribution may be output to the display unit.
Further, in the description of the embodiment, a conversion table representing the correspondence between the amplitude of the acoustic wave and the amount of measurement light transmitted through the intervening tissue is used. That is, the optical related information in the present invention is the amount of measurement light transmitted through the intervening tissue. However, other information may be used as long as the amount of measurement light reaching the cerebral cortex can be obtained. For example, light energy absorbed by the intervening tissue may be used, or an absorption coefficient of light in the intervening tissue may be used.

The present invention can also be implemented by a computer (or a device such as a CPU or MPU) of a system or apparatus that implements the functions of the above-described embodiments by reading and executing a program recorded in a storage device. For example, the present invention can be implemented by a method including steps executed by a computer of a system or apparatus that implements the functions of the above-described embodiments by reading and executing a program recorded in a storage device. .
For this purpose, the program is stored in the computer from, for example, various types of recording media that can serve as the storage device (ie, computer-readable recording media that holds data non-temporarily). Provided to. Therefore, the computer (including devices such as CPU and MPU), the method, the program (including program code and program product), and the computer-readable recording medium that holds the program in a non-temporary manner are all present. It is included in the category of the invention.

  DESCRIPTION OF SYMBOLS 1 ... Light source, 2 ... Photodetector, 3 ... Optical waveguide, 4 ... Projection probe, 5 ... Light reception probe, 7 ... Signal processing part, 8 ... Pulse light source 10 ... second light projecting probe, 11 ... acoustic wave probe

Claims (11)

A light irradiation means for irradiating light to a subject having an intervening tissue on a surface layer;
A light detection means for detecting the intensity of light transmitted through the intervening tissue and propagating through the subject, and converting it into a first signal;
An acoustic wave receiving means for detecting an acoustic wave generated in the intervening tissue due to the irradiated light and converting it to a second signal;
Based on the second signal, signal processing means for acquiring optical related information that is information related to optical characteristics of the intervening tissue;
Signal correcting means for correcting the first signal based on the optical related information and removing the influence of the intervening tissue from the first signal;
Have
The second signal is a signal representing a sound pressure of an acoustic wave generated in the intervening tissue,
The signal processing means uses the data representing the relationship between the sound pressure of the acoustic wave generated in the intervening tissue and the amount of light transmitted through the intervening tissue, to calculate the amount of light transmitted through the intervening tissue. A subject information acquisition apparatus characterized by acquiring. The light detection means performs first and second measurements, obtains the first signal,
The acoustic wave receiving means performs first and second measurements, acquires the second signal,
The signal correction means acquires a fluctuation amount of the amount of light transmitted through the intervening tissue from the second signal obtained by the first and second measurements, and uses the fluctuation amount to obtain the first amount. The object information acquiring apparatus according to claim 1, wherein the first signal obtained by the second measurement is corrected. The data is data acquired in advance by performing light and acoustic wave propagation analysis in the intervening tissue.
The object information acquiring apparatus according to claim 1, wherein the object information acquiring apparatus is an object information acquiring apparatus. The said signal correction means amplifies said 1st signal, so that the light quantity of the light which permeate | transmits the said intervening tissue decreases based on the said optical relevant information, The any one of Claim 1 to 3 characterized by the above-mentioned. 2. The object information acquiring apparatus according to 1. The light irradiation means includes a first light source and a second light source that is a pulse light source,
The light detection means detects the intensity of light generated from the first light source and propagated in the subject,
The object information according to any one of claims 1 to 4 , wherein the acoustic wave receiving means detects an acoustic wave generated due to the pulsed light generated from the second light source. Acquisition device. The object information acquiring apparatus according to claim 5 , wherein the second light source and the acoustic wave receiving unit are disposed in the vicinity of the first light source and the light detecting unit. A method for controlling a subject information acquiring apparatus for acquiring internal information of a subject having an intervening tissue on a surface layer,
A light irradiation step for generating light to irradiate the subject;
A light detection step of detecting the intensity of light transmitted through the intervening tissue and propagating through the subject, and converting the detected light into a first signal;
An acoustic wave receiving step of detecting an acoustic wave generated in the intervening tissue due to the irradiated light and converting it to a second signal;
Based on the second signal, a signal processing step of obtaining optical related information that is information related to optical characteristics of the intervening tissue;
A signal correction step for correcting the first signal based on the optical related information and removing the influence of the intervening tissue from the first signal;
Only including,
The second signal is a signal representing a sound pressure of an acoustic wave generated in the intervening tissue,
In the signal processing step, the amount of light transmitted through the intervening tissue is calculated using data representing the relationship between the sound pressure of the acoustic wave generated in the intervening tissue and the amount of light transmitted through the intervening tissue. A method for controlling an object information acquiring apparatus, comprising: acquiring the object information. In the light detection step, first and second measurements are performed to obtain the first signal,
In the acoustic wave receiving step, first and second measurements are performed, and the second signal is acquired,
In the signal correction step, a fluctuation amount of the amount of light transmitted through the intervening tissue is acquired from the second signal obtained by the first and second measurements, and the fluctuation amount is used to obtain the first The control method of the subject information acquiring apparatus according to claim 7 , wherein the first signal obtained by the second measurement is corrected. The data is data acquired in advance by performing light and acoustic wave propagation analysis in the intervening tissue.
The method for controlling a subject information acquiring apparatus according to claim 7 or 8, wherein The said signal correction step amplifies said 1st signal, so that the light quantity of the light which permeate | transmits the said intervening tissue decreases based on the said optical relevant information, The any one of Claim 7 to 9 characterized by the above-mentioned. 2. A method for controlling the subject information acquiring apparatus according to 1. In the light irradiation step, light irradiation is performed using a first light source and a second light source that is a pulse light source,
In the light detection step, the intensity of light generated from the first light source and propagated in the subject is detected,
The object information according to any one of claims 7 to 10 , wherein in the acoustic wave receiving step, an acoustic wave generated due to pulsed light generated from the second light source is detected. Control method of acquisition device.

Images