JP5575293B2 - Subject information acquisition apparatus and subject information acquisition method - Google Patents

Description

  The present invention relates to a subject information acquisition apparatus and a subject information acquisition method.

  Research on an optical imaging apparatus that irradiates light to a living body from a light source such as a laser and images in-vivo information obtained based on incident light has been actively promoted in the medical field.

  As one of the optical imaging, there is a technique called PAT (Photo Acoustic Tomography) called photoacoustic imaging. Photoacoustic imaging is a technique for obtaining an optical characteristic value distribution in a living body with high resolution by utilizing the characteristics of ultrasonic waves that are less scattered in the living body than light (see Patent Document 1 and Non-Patent Document 1). ).

  In this method, pulsed light generated from a light source is irradiated on a living body, and an acoustic wave generated from a living tissue that has absorbed energy of pulsed light that has propagated and diffused in the living body is detected. In other words, using the difference in absorption rate of light energy between the test site such as a tumor and other tissues, the elastic wave generated when the test site absorbs the irradiated light energy and expands instantaneously Is received by the transducer. By analyzing this detection signal, an optical characteristic distribution in the living body, in particular, a light energy absorption density distribution can be obtained.

  On the other hand, as optical imaging other than PAT, there is a technique called DOT (Diffuse Optical Tomography) called diffuse optical imaging. Diffuse light imaging is a technology that irradiates a living body with light from a light source, detects weak light that has propagated and diffused inside the living body with a highly sensitive photodetector, and images the distribution of optical characteristic values in the living body from the detection signal. It is.

  As an imaging technique using light and ultrasonic waves, there is a technique called acousto-optical tomography (AOT). Acousto-optic tomography irradiates light inside a living tissue and irradiates ultrasonic waves focused on a local region, and utilizes the effect of modulating the light by the ultrasonic waves (acousto-optic effect). (Patent Document 2). AOT and PAT are known to have a higher resolution than DOT in order to detect a signal in a local region where light and ultrasonic waves interact.

US Pat. No. 5,843,0023 US Pat. No. 6,957,096

M, Xu, L.M. V. Wang “Photoacoustic imaging in biomedicine”, Review of scientific instruments, 77, 041101 (2006)

PAT can obtain local light absorption information by measuring an acoustic wave generated by being absorbed at a local test site. The pressure p of the acoustic wave generated at the test site is expressed by the following equation (1) using the distance z from the light irradiation point to the test site.
P (z) = Γμ _a (z) Φ (z) (1)
here,
Γ: Gruneisen coefficient (thermal-acoustic conversion efficiency)
μ _a (z): Absorption coefficient at a position at a distance z Φ (z): Light intensity at a position at a distance z. The Grunesen coefficient Γ, which is an elastic characteristic value, is obtained by dividing the product of the square of the volume expansion coefficient β and the speed of sound c by the specific heat Cp.

Since it is known that Γ has a substantially constant value when the biological tissue is determined, the product of μ _a and Φ, that is, the product of μ _a and Φ, that is, by measuring the change of the sound pressure P that is the magnitude of the acoustic wave in a time-sharing manner, A light energy absorption density distribution H can be obtained (see Non-Patent Document 1).

Here, in order to accurately image the distribution of the absorption coefficient μ _a (z) in the living body based on the sound pressure P that is the measurement value, the light intensity Φ (z) at the position of the test site z is accurately determined. It can be seen from equation (1) that it is necessary to estimate well.

As a method for estimating the light intensity Φ (z), Non-Patent Document 1 uses the average light attenuation coefficient μ _eff (r) inside the living body and uses the Lambert-Beer law or the diffusion theory to determine the light intensity Φ (z ) It is described that μ _a (z) is obtained from the sound pressure P (z) using the light intensity Φ (z). Here, the attenuation coefficient μ _eff (r) is expressed by the following equation (2).

Here, μ ′ _s is an equivalent scattering coefficient. However, the expression (2) can be applied when the subject is optically homogeneous, but the light intensity Φ (z) cannot be estimated correctly when the subject is inhomogeneous. For example, the attenuation coefficient μ _eff (r) can be estimated by irradiating the subject with light and measuring the diffused light emitted from the subject. However, the attenuation coefficient μ _eff (r) has a large influence on the optical characteristics near the surface of the subject, and the light intensity reaching the test site relatively deeper than the surface is affected by the non-uniform optical characteristics on the way. Therefore, the light intensity estimated by using μ _eff (r) is greatly deviated. If the light intensity Φ (z) cannot be estimated with high accuracy, the absorption coefficient μ _a (z) of the test site cannot be determined with high accuracy.

  An object of the present invention is to provide a biological information processing apparatus and a biological information processing method capable of estimating an absorption coefficient with high accuracy from a PAT photoacoustic signal by accurately estimating the light intensity at a local test site. Is to provide.

  The subject information acquisition apparatus of the present invention includes a light source for irradiating a subject with each of a plurality of wavelengths of light, an ultrasonic transmitter for irradiating an ultrasonic wave to a local region of the subject, A light detection unit for detecting modulated light in which light from the light source is modulated by the ultrasonic wave in the local region; and for detecting an acoustic wave generated from the local region by receiving light from the light source. And the spectral information of the local region from the acoustic signal output from the acoustic wave detection unit based on the light intensity in the local region acquired from the modulation signal which is the output of the acoustic wave detection unit and the light detection unit And a processing unit for acquiring

  According to the biological information processing apparatus and the biological information processing method of the present invention, by accurately estimating the light intensity at the local test site using the AOT method, the absorption coefficient can be obtained from the PAT photoacoustic signal with high accuracy. Can be estimated. As a result, the absorption coefficient distribution in the living body can be imaged with high resolution.

1 is a schematic diagram illustrating a configuration example of a biological information processing apparatus according to a first embodiment. It is the schematic diagram which showed an example of the positional relationship of the incident position of light, a detection position, and a probe area | region. It is the schematic diagram which showed another example of the positional relationship of the incident position of light, a detection position, and a probe area | region. FIG. 4 is a schematic diagram showing a light propagation path distribution between a light incident / detection position and a probe region in the case of FIG. 3. 3 is a flowchart illustrating an example of a measurement flow when the biological information processing method according to the first embodiment is performed. It is a schematic diagram which shows the other structural example about the measurement part 19 of FIG. It is a schematic diagram which shows the other structural example about the measurement part 19 of FIG. It is a schematic diagram which shows the other structural example about the measurement part 19 of FIG. It is a flowchart which shows an example of the measurement flow in the case of enforcing the biological information processing method of Embodiment 2. FIG. 10 is a schematic diagram illustrating a positional relationship among a light incident position, a detection position, and a plurality of probe regions in the third embodiment. FIG. 10 is a schematic diagram showing a positional relationship between a segmented region inside a living body and a probe region in Embodiment 4.

  Hereinafter, the present invention will be described in more detail with reference to the drawings. In principle, the same components are denoted by the same reference numerals, and description thereof is omitted.

  The biological information processing apparatus of the present invention calculates the absorption characteristics in the local region from the acoustic signal obtained by photoacoustic imaging (PAT) based on the light intensity in the local region calculated from acousto-optic tomography (AOT). It is characterized by doing.

As can be seen from the above equation (1), photoacoustic imaging is performed by irradiating a living body (absorber) in order to obtain _a distribution of absorption coefficient (μ _a ) in the living body from measurement of sound pressure (P) change. It is necessary to obtain the distribution of light quantity (Φ) by some method.

However, in a complicated living body, it is difficult to estimate the amount of light irradiated to the absorber, and only the light energy absorption density distribution (μ _a · Φ) can be imaged only by measuring the sound pressure of a general acoustic wave. Can not. That is, it is difficult to calculate the distribution (Φ) of the amount of light irradiated to the absorber from the measurement of only the acoustic wave, and to accurately separate and image the absorption coefficient distribution (μ _a ) in the living body. As a result, it is not possible to obtain an accurate distribution of the absorption coefficient (μ _a ) only with the PAT, and it is impossible to specify the constituent material of the living tissue and measure the concentration.

Therefore, the absorption coefficient can be obtained from the PAT using the light amount data (Φ) obtained by the AOT. Although details will be described later, the distribution of the light quantity (Φ) that could not be directly measured by the PAT can be determined with higher accuracy. Therefore, the absorption coefficient distribution can be obtained quantitatively and with high resolution by using the light quantity (Φ) obtained by AOT and the light energy absorption density distribution (μ _a · Φ) obtained by PAT. As described above, by combining AOT and PAT, the quantitativeness and resolution of the absorption coefficient distribution can be improved.

(Embodiment 1)
A biological information processing apparatus and a biological information processing method according to Embodiment 1 of the present invention will be described. FIG. 1 is a schematic diagram illustrating a configuration example of the biological information processing apparatus according to the present embodiment.

  The biological information processing apparatus of the present embodiment is a measurement unit 19 that can measure information inside a tissue of a subject 7 that is a living body using both AOT and PAT, and various signals obtained from the measurement unit 19. The signal processing device 9 is an arithmetic unit. Moreover, you may have the display apparatus 14 which displays the image which imaged the information inside the biological body obtained as a result of signal processing.

  The measurement unit 19 has the following configuration. A light source 1 for irradiating light on a subject 7 which is a living body, an ultrasonic transducer 5 which is an ultrasonic transmission unit for irradiating ultrasonic waves to a local region (ultrasonic focusing region 6) of the subject 7, The main configuration is a photodetector 8 which is a light detection unit for detecting modulated light in which light from the light source 1 is modulated by ultrasonic waves in the ultrasonic focusing region 6. Here, the ultrasonic transducer 5 also functions as an acoustic wave detector for detecting an acoustic wave generated from a local region upon receiving light from the light source 1. That is, a single acoustic wave transducer serves to transmit focused ultrasound in AOT and receive acoustic waves in PAT. Further, it has a signal generator 15 for generating a signal such as a sine wave, an incident optical fiber 2, a detection optical fiber 3, and a subject fixing plate 4.

  The light source 1 is used in both AOT measurement and PAT measurement. Further, the ultrasonic transducer 5 transmits an ultrasonic wave in the AOT measurement and receives an acoustic wave in the PAT measurement. The photodetector 8 detects the modulated light in the AOT measurement.

  In the signal processing device 9 that is a calculation unit, the output from the ultrasonic transducer 5 in the PAT measurement is based on the light intensity in the ultrasonic focusing region 6 calculated from the modulation signal that is the output of the photodetector 8 in the AOT measurement. The absorption characteristics in the local region are calculated from the acoustic signal.

  The subject 7 is a living tissue such as a breast and is an absorption scatterer. The subject 7 is in a state of being fixed while being held lightly from two directions by the subject fixing plate 4. The subject fixing plate 4 is optically transparent, and has a relatively close acoustic impedance to the subject 7.

  It is preferable that the light source 1 has a long coherence length (for example, 1 m or more) and can switch between continuous light (CW light: Continuous Wave light) having a constant intensity and pulsed light of several ns inside. The light source 1 can select a plurality of wavelengths according to absorption spectra of water, fat, protein, oxyhemoglobin, deoxyhemoglobin and the like constituting the living tissue. As an example, a suitable range is 600 to 1500 nm, which absorbs water, which is a main component of the internal tissue of the living body, and thus transmits light well and is characterized by the spectra of fat, oxyhemoglobin, and reduced hemoglobin. As a specific example of the light source 1, it may be configured by a semiconductor laser that generates different wavelengths, a wavelength tunable laser, or the like. In the present specification, the “light source” may be two light sources that respectively emit pulsed light irradiated by PAT measurement and CW light irradiated by AOT measurement. Of course, one light source capable of generating pulsed light and CW light may be used. A laser is preferable as the light source, but a light emitting diode or the like may be used instead of the laser. As the laser, various lasers such as a solid laser, a gas laser, a dye laser, and a semiconductor laser can be used.

  The optical fiber 2 guides the light generated from the light source 1 to the subject 7. A condensing optical system that efficiently guides the light from the light source 1 to the end of the optical fiber 2 may be provided in front of the optical fiber 2. The light incident on the inside of the subject 7 propagates inside the subject while repeating absorption and scattering.

[AOT measurement]
First, AOT measurement will be described. The ultrasonic transducer 5 transmits a focused ultrasonic wave to an arbitrary position (ultrasonic focusing region 6) inside the subject 7. For example, the frequency range of the ultrasonic wave is approximately 1 to several tens of MHz. The intensity of ultrasonic waves to be irradiated is adjusted within a range of intensity below a safety standard that can be irradiated to a living body.

  The ultrasonic transducer 5 is composed of, for example, a linear array probe. An ultrasonic focusing region 6 is generated at an arbitrary position inside the subject 7 by electronic focusing using an array probe. Alternatively, the ultrasonic focusing region 6 may be arranged at an arbitrary position by mechanically scanning a circular concave ultrasonic transducer or an acoustic lens. As the acoustic wave transducer, a transducer using a piezoelectric phenomenon, a transducer using optical resonance, a transducer using a change in capacitance, and the like can be used.

  In the ultrasonic focusing region (probe region) 6, a sound field corresponding to the frequency and amplitude of the ultrasonic wave set by the ultrasonic transducer 5 is generated. Inside this region, the density of the medium changes due to the sound pressure, causing a change in the refractive index of the medium and displacement of the scatterer. When the light emitted from the light source 1 enters this region, the phase of the light is modulated by the ultrasonic frequency due to the change in the refractive index of the medium or the displacement of the scatterer. Here, this phenomenon is called an acoustooptic effect. As used herein, “modulated light” means light modulated by an acousto-optic effect caused by ultrasound focused on a local region.

  The modulated light modulated by the acousto-optic effect in the ultrasonic irradiation region 6, the unmodulated light that has not been modulated in the ultrasonic irradiation region 6, and the non-modulated light that has passed through other than the ultrasonic irradiation region 6 are transmitted through the optical fiber 3. It detects by the photodetector 8 via. The photodetector 8 is preferably a single detector such as a PMT (Photomultiplier Tube) or an APD (Avalanche Photodiode). A multi-sensor such as a CCD or CMOS may be used.

  The signal processing device 9 performs processing of analyzing and imaging information related to signal analysis from the photodetector 8 and the ultrasonic transducer 5 and absorption characteristics inside the subject 7, and the signal extraction unit 10 performs computation. A processing unit 11, an image generation unit 12, and a memory 13 are included.

  In the modulated light measurement, the signal extraction unit 10 functions as a filter, and separates modulated light and non-modulated light. For the signal extraction unit 10, a band-pass filter that selectively detects a signal of a specific frequency and a lock-in amplifier that amplifies and detects light of a specific frequency can be applied. The signal extraction unit 10 obtains the light intensity of the modulated light with respect to the signal obtained from the photodetector 8.

  In the present specification, the “modulated signal” refers to an electric signal obtained by converting modulated light modulated by ultrasonic waves by the photoelectric effect of the photodetector 8. The electrical signal is preferably an AC component electrical signal.

[PAT measurement]
Next, PAT measurement will be described. The subject 7 is irradiated with light of several ns pulse from the light source 1, and the acoustic energy generated when the volume of the light energy absorbed in the probe region 6 causes a local temperature rise to expand. In order to measure an acoustic wave from the same probe region 6 as that at the time of AOT measurement, the electronic focus setting used as transmission in AOT is used for reception. When mechanical scanning is performed using a circular concave ultrasonic transducer or an acoustic lens, the same geometric arrangement as that of AOT may be used. The intensity of the photoacoustic signal obtained from the probe region 6 is measured by the signal extraction unit 10.

  In this specification, “acoustic wave” refers to an elastic wave generated from the probe region 6 by the photoacoustic effect. The “acoustic signal” refers to an electric signal obtained by converting an elastic wave generated from the probe region 6 into an electric signal using the ultrasonic transducer 5.

[Other device configurations]
The incident optical fiber 2 and the detection optical fiber 3 have a mechanism capable of two-dimensionally scanning the surface of the subject fixing plate 4 in synchronization. Further, the probe region 6 is set by controlling the ultrasonic transducer 5 in accordance with the positions of the incident optical fiber 2 and the detection optical fiber 3. The probe region 6 is scanned with respect to the subject 7 to perform AOT measurement and PAT measurement, respectively, and obtain a spatial measurement distribution of the subject 7. In addition, in order to acquire the spectral characteristics inside the subject 7, the above measurement can be performed by switching the wavelength of the light source 1.

  The arithmetic processing unit 11 performs signal processing, which will be described later, using the modulation signal in the AOT measurement and the photoacoustic signal in the PAT measurement. Alternatively, the concentration and component ratio of the constituent elements inside the subject 7 are calculated from the spectral characteristics obtained with a plurality of wavelengths. In addition, all the calculated data relating to the spectral characteristics are associated with the position coordinate data of the probe region 6 to create distribution data of the spectral characteristics inside the subject 7.

  The image generation unit 12 forms a three-dimensional tomographic image (image) of the subject 7 from the spectral characteristic distribution data inside the subject 7 created by the arithmetic processing unit 11.

  The memory 13 records the AOT measurement and PAT measurement signal values obtained by the signal extraction unit 10, the data generated by the arithmetic processing unit 11, the image of the spectral characteristics generated by the image generation unit 12, and the like. As the memory 13, a data recording device such as an optical disk, a magnetic disk, a semiconductor memory, or a hard disk can be used.

  The display device 14 displays an image generated by the signal processing device 9, and a display device such as a liquid crystal display, a CRT, or an organic EL can be used.

[Biological information processing method]
Hereinafter, an arithmetic processing method performed by the arithmetic processing unit 11 to obtain the absorption characteristic of the probe region 6 from the photoacoustic signal in the PAT measurement using the modulation signal in the AOT measurement will be described.

In AOT measurement conditions as shown in FIG. 2, as described in Patent Document 2, the light intensity of the modulated light detected by receiving modulation action in the probe region 6 at the position r _p in the subject 7 I _AC (r _p ) can be expressed by the following equation (3).
I _AC (r _p ) = S ₀ Ψ (r _s , r _p ) η Ψ (r _p , r _d ) (3)
Here, Ψ (r _s , r _p ) is a transfer function of light intensity from the light incident position r _s in the subject 7 to the position r _{p in the} probe region 6, and Ψ (r _p , r _d ) is from r _p. It represents the transfer function of the light intensity to the light detection position r _d. S ₀ represents the intensity of light incident on the subject 7, and η represents the efficiency with which the light is modulated in the probe region 6. The transfer function Ψ of the light intensity inside the subject 7 can be modeled by a light diffusion equation, a transport equation, a Monte Carlo simulation, or the like.

  Here, in the present specification, a path through which light irradiated from the incident optical fiber 2 is scattered and propagated until reaching the probe region 6 in the subject is referred to as an incident light propagation region. A path through which light modulated by the probe region 6 is scattered and propagated until reaching the detection optical fiber 3 is called a detection light propagation region.

  As shown in FIG. 3, when the incident optical fiber 2 and the detection optical fiber 3 are placed close to each other,

, (3) can be written as (4).
I _AC (r _p ) = S ₀ Ψ (r _S , r _p ) ² η (4)

Here, as shown in FIG. 4, the position r _p of light to propagation path distribution 18 and the light from the probe region 6 to the light detection position r _d propagation path distribution 18 of the probe region 6 from the light incident position r _s is It will be almost the same. That is, since the incident light propagation region by the light emitted from the light source 1 overlaps the detection light propagation region when detecting the modulated light by the detector 8 and can be regarded as the same, the same propagation path distribution is reciprocally modulated. It is detected as a signal _{I AC.} For this reason, the former transfer function Ψ (r _S , r _p ) and the latter transfer function Ψ (r _p , r _d ) are equal (Ψ (r _S , r _p ) = Ψ (r _p , r _S )). Also, since the transfer function ψ (r) is reversible, equation (4) is obtained.

Therefore, the optical transfer function Ψ from the light incident position r _S to the probe region r _p is expressed by the following equation (4).

It becomes. The transfer function from the light irradiation position r _s up to the local probe region 6, and reflects the optical characteristics of the subject.

Thus, it is preferable to calculate the light intensity I _AC (r _p ) of the modulated light in the local region using the relational expression (4) obtained from the fact that the incident light path and the detection light path are the same. When the incident light path and the detection light path cannot be regarded as the same, the modulation signal obtained by the AOT measurement reflects not only the incident light path but also the optical characteristics inside the subject in the detection light path. On the other hand, in order to obtain the absorption characteristic of the probe region 6 from the photoacoustic signal obtained by the PAT measurement, the attenuation factor of light when propagating through the incident light path, that is, the inside of the subject in which the incident light is in the incident light path As a result, the intensity of light reaching the probe region 6 is required. At this time, as will be described later, under the condition that the incident light path and the detection light path can be regarded as the same, it is only necessary to perform one AOT measurement for one probe region 6 to be measured. However, when the two cannot be regarded as the same, AOT measurement is performed a plurality of times on the probe region 6 to estimate the optical characteristic distribution inside the subject in the incident light path, and the light intensity in the probe region 6 is calculated. It is necessary to calculate. The former is more efficient because the number of AOT measurements is smaller than the latter, and is more accurate because it is not affected by errors due to estimation of the optical distribution in the latter.

On the other hand, in the PAT measurement, consider a case where a photoacoustic signal from the same probe region 6 as in the AOT measurement is detected. If the light incident intensity at the time of PAT measurement is S ′ ₀ , the light intensity Φ (r _p ) in the probe region 6 can be written as follows using the equation (5).
Φ (r _p ) = S ′ ₀ Ψ (r _S , r _p ) (6)

If the expressions (1), (5), and (6) are used, the sound pressure P (r _p ) of the generated acoustic wave can be expressed as the expression (7).

Accordingly, the absorption coefficient μ _a (r _p ) in the probe region 6 is expressed by the following equation.

  If the sound pressure or frequency of the ultrasonic wave irradiated in the AOT measurement is constant, the modulation efficiency η depends on the refractive index, the absorption coefficient, the scattering coefficient, the scattering anisotropy parameter, etc. of the probe region 6. However, in a general soft tissue, when the probe region is sufficiently small (˜mm), the change in modulation efficiency η is small and can be regarded as almost constant. In AOT measurement and PAT measurement, if a constant light intensity is always incident on the living body and the Gruneisen coefficient Γ is substantially constant regardless of the position, the following relational expression can be obtained from the equation (8).

From the equation (9), by measuring the modulated light intensity signal I _AC (r _p ) and the photoacoustic wave P (r _p ) for the same probe region 6 in the AOT measurement and the PAT measurement, the probe region r _p The absorption characteristic μ _a (r _p ) can be obtained.

By measuring by scanning the probe region r _p in 3D space, it is possible to visualize the relative internal distribution of the absorption coefficient of the object 7. The absorption coefficient can also be calculated if the parameters defined as constants in equation (9) are obtained in advance by calibration.

To determine the absorption coefficient mu _a from the photoacoustic signal of the PAT, it is necessary to estimate the light intensity in the development position of the photoacoustic wave. It is a feature of the present invention that this is performed using the modulation signal obtained from the AOT measurement. In the present embodiment, it is preferable to perform AOT measurement by setting the incident optical fiber 2 and the detection optical fiber 3 so that the positions of the incident optical fiber 2 and the detection optical fiber 3 can be regarded as substantially the same position with respect to the probe region 6. In this case, an optical transfer function corresponding to the position of the probe region 6 can be obtained from the modulation signal of AOT measurement. Since the AOT measurement and the PAT measurement are performed with the same probe region arrangement, the light intensity in accordance with the PAT measurement conditions can be estimated as shown in equation (6).

  As described above, when the absorption coefficient of the local region is calculated using the equation (1) for the photoacoustic signal obtained from the PAT measurement, the modulation signal obtained from the AOT measurement is used to obtain the equation (6). Thus, the light intensity can be calculated, and finally the absorption coefficient can be calculated in the form as shown in equation (9).

The above-described conventional method for estimating the light intensity using the average light attenuation coefficient can be applied only to an ideal homogeneous medium with high accuracy. However, the analysis method of the present invention can be applied regardless of whether the inside of the subject 7 is homogeneous or heterogeneous. Even in the case of inhomogeneity, a modulated optical signal I _AC that reciprocates through the inhomogeneous medium is obtained, and a transfer function Ψ reflecting inhomogeneity is obtained using I _AC and the light intensity is estimated using this. Because. That is, the absorption coefficient considering the inhomogeneity of the medium is obtained.

FIG. 5 shows an example of a measurement flow when the biological information processing method of the present embodiment is performed. In S100, the probe region 6 is set. AOT is measured from the next step. In S101, CW light is irradiated, and the probe region 6 is irradiated with pulsed ultrasonic waves. In S102, the light modulated by the probe region 6 is detected by the photodetector 8, and only the optical signal modulated at the ultrasonic frequency is selectively extracted by the signal extraction unit 10 in the signal processing device 9, The modulated optical signal _{IAC is} measured. The measured modulation signal is stored in the memory 13. When the AOT measurement is completed, the CW light and pulse ultrasonic switches are turned off in S103.

  Next, PAT is measured. In step S104, pulse light is irradiated. In S <b> 105, the photoacoustic signal generated in the probe region 6 is detected by the ultrasonic transducer 5. At this time, the ultrasonic wave reception setting is set at the same position as the probe region 6 set in the AOT measurement. The signal extraction unit 10 measures the acoustic wave in the probe region 6 and stores the photoacoustic signal in the memory 13. When the PAT measurement is completed, the pulse light switch is turned off in S106.

In S107, the AOT modulation signal and the PAT photoacoustic signal are read from the memory 13, and the absorption coefficient μ _a (r _p ) of the probe region 6 is calculated using the equation (9).

  The probe region 6 is scanned inside the subject 7 and the flow from S100 to S107 is performed, whereby the absorption distribution of the subject 7 is obtained. If the entire region inside the subject 7 is scanned, the absorption distribution of the entire region inside the subject 7 can be obtained. By mapping the absorption coefficient in correspondence with the position coordinates of each probe region 6 in the image generation unit 12, a three-dimensional spatial distribution of the absorption coefficient is obtained, which is imaged and displayed on the display device 14.

  In addition, the above-described flow is executed by arbitrarily using a plurality of wavelengths of the light source 1, and component ratios of the subject 7, such as component ratios of oxygenated hemoglobin, reduced hemoglobin, water, fat, collagen, oxygen saturation index, etc. Metabolic information can also be obtained by the arithmetic processing unit 11. The function information is mapped in correspondence with the position coordinates of the probe region 6 in the same manner as described above. From this information, a three-dimensional tomographic image can be formed by the image generator 12 and displayed on the display device 14.

  Here, in FIG. 5, the PAT measurement is performed after the AOT measurement. However, the AOT measurement may be performed after the PAT measurement is performed in the reverse order.

[Modification of device configuration]
FIGS. 6-8 is a schematic diagram which shows the other structural example which does not use an optical fiber about the measurement part 19 of FIG. The signal processing device 9 other than the measurement unit 19 has the same configuration as that in FIG.

  In the example of FIG. 6, the beam from the light source 1 is reflected by the beam splitter 20, passes through the illumination / detection optical system 21, and irradiates the subject 7 with light in a relatively large area. At this time, the detection light in the AOT measurement is collected through the same optical system 21 as in the illumination, passes through the beam splitter 20, and the signal light is detected by the photodetector 8. By using the same optical system for light irradiation and light detection and making the aperture area the same, the same geometric condition as in FIG. 3 can be set.

  Alternatively, in a region where the probe region 6 is sufficiently deep with respect to the subject 7 and diffusion approximation is established, the configuration shown in FIG. The same optical system is used on the incident side and the detection side, and the opening with respect to the subject 7 is set in the same region. Light that is incident on the subject 7 from a slight angle is diffused isotropically while being scattered inside the subject, and backscattered light isotropically diffused to detect light emitted from the subject 7. Even in such a configuration, the light irradiation region and the light detection region can be made substantially the same region.

  Alternatively, the configuration is basically the same as that in FIG. 6, but a configuration in which the measurement probe 16 is brought into contact with the subject 7 as shown in FIG. In the measurement probe 16, the photodetector 8, the ultrasonic transducer 5, the beam splitter 20, and the optical system 21 are housed. A matching medium for matching acoustic impedance is filled between the measurement probe 16 and the subject 7. Also in FIG. 8, the light irradiation region and the light detection region can be made substantially the same region.

  Here, the AOT measurement method is a detection method using a single detector such as PMT, parallel detection using a multi-sensor such as a CCD, or hologram detection using a photorefractive element or detection using spectral hole burning. Any of these may be used.

(Embodiment 2)
A biological information processing method according to Embodiment 2 of the present invention will be described. The apparatus configuration of this embodiment is the same as that of the first embodiment. The measurement flow in this embodiment is shown in FIG. First, in S <b> 200, PAT measurement is performed while the incident optical fiber 2 is scanned two-dimensionally with respect to the surface of the subject fixing plate 4, and PAT measurement values are obtained in the entire region of the subject 7. At this time, it is preferable to perform measurement at a plurality of wavelengths and acquire spectral information.

  In S201, for example, a known method disclosed in Non-Patent Document 1 is used to perform image reconstruction using the signal obtained in S201 to obtain a sound pressure distribution inside the subject 7. At this time, the attenuation of the ultrasonic wave propagating through the medium and the system error by the measurement unit 19 and the signal processing unit 9 are removed, and information for reproducing the generated sound pressure distribution at the time of pulse light irradiation is obtained.

  In S202, a region having a local contrast higher than the surrounding is extracted from the obtained reconstructed image. At this time, a threshold value is set in advance. For all measurement regions, it is examined whether the target region exceeds this threshold value than the average signal value in the background.

  In S203, if there is no high contrast region that exceeds the predetermined threshold, the measurement is terminated. If there is a high contrast area, the position coordinates of that area are stored in the memory 13, and the process proceeds to S204.

  In S204, the probe region 6 of the ultrasonic transducer 5 is set in accordance with the position coordinates of the high contrast region, and AOT measurement is performed. AOT measurement is performed on all the high-contrast regions extracted in S202. In addition, it is preferable to similarly perform AOT measurement at an arbitrary position in the background area other than the high contrast area.

  In S205, necessary information such as a PAT measurement result and reconstructed information is appropriately extracted from the memory 13 for the high contrast region, and the sound pressure value is converted into an absorption coefficient value using equation (9). Similarly, the background region is also converted into an absorption coefficient value, and absorption coefficient distribution information is acquired and imaged. The obtained image is displayed on the display device 14. Thereby, the absorption coefficient of the high contrast region with respect to the absorption coefficient of the background region can be evaluated.

  In addition, it is also preferable that the arithmetic processing unit 11 obtains component information such as oxygenated hemoglobin, reduced hemoglobin, water, fat, and collagen, and metabolic information such as an oxygen saturation index from the absorption coefficient image. The function information is imaged and displayed on the display device 14.

  In the present embodiment, PAT identification is performed on an arbitrary local area inside the living body, and an area where the obtained acoustic signal is obtained with a contrast higher than a predetermined threshold is identified. As described above, a region suspected of being abnormal in a biological tissue is specified in advance from PAT measurement, and AOT measurement is performed on the region, whereby measurement time can be shortened and necessary information can be efficiently obtained. In the first embodiment, the AOT measurement and the PAT measurement are continuously performed on the probe region 6, whereas in the present embodiment, the AOT measurement and the PAT measurement are performed completely independently.

  Here, as a structure of a measuring apparatus, the structure shown in FIGS. 6-8 may be sufficient.

(Embodiment 3)
A biological information processing method according to Embodiment 3 of the present invention will be described. The apparatus configuration of this embodiment is the same as that of the first embodiment. However, in Example 1, the positions of the incident optical fiber 2 and the detection optical fiber 3 are arranged so as to be regarded as substantially the same position with respect to the probe region 6, but in the present embodiment, the interval between the two is arbitrarily set. In general, the interval is preferably several centimeters. In the present embodiment, a method for calculating the light intensity of a local region using AOT is different from that in the first embodiment.

  As shown in FIG. 10, a modulated light measurement region 6a for acquiring only an AOT signal is arbitrarily provided from the surface of the subject 7 to the probe region 6 with respect to the probe region 6 for which an absorption coefficient is to be obtained. Measure.

For example, as described in Patent Document 2, the light attenuation coefficient μ _eff (r) at the position r of each modulated light measurement region 6a is set as follows with respect to the modulated light measurement region 6a as described in Patent Document 2. To estimate.

If the propagation of multiple scattered light is expressed using a diffusion equation using the attenuation coefficient μ _eff (r), the following equation (10) is obtained.
(▽ ²⁻ μ ² _eff (r)) U (r) = S (r) (10)

  Here, U (r) represents the intensity of scattered light, and S (r) represents the light intensity of the light source. Further, the modulated light intensity distribution is expressed by using equation (3).

  By using these formulas (3) and (10), Patent Document 2 derives the relationship of the following formula (11).

Here, theta is an angle shown in FIG. 2, the vector from the position r _p of the probe region 6 to the light incident position r _s, the vector from the position r _p of the probe region 6 to the light detection position r _d It is an angle to make.

By using the equation (11), the attenuation coefficient μ _eff (r) can be calculated from the AOT modulation signal. In FIG. 10, the attenuation coefficient μ _eff (r) of the modulated light measurement region 6a is calculated in order from the surface of the subject 7 to the probe region 6, for example, using equation (11). In this case, the results of the attenuation coefficient mu _{eff (r)} was obtained in a more near the surface (10) to reflect the diffusion equation of Formula may be obtained deeper attenuation coefficient of the region mu _{eff (r).}

Using the attenuation coefficient μ _eff obtained spatially discretely as shown in FIG. 10, the area other than the modulated light measurement area 6a is interpolated spatially to obtain the distribution of the attenuation coefficient μ _eff . For the spatial distribution of the obtained attenuation coefficient μ _eff (r), the light intensity Φ (r _p ) in the probe region 6 is obtained by using, for example, Lambert Beer law or diffusion equation, or using Monte Carlo simulation. be able to.

In the PAT measurement, for the photoacoustic signal generated from the probe region 6, the light intensity Φ (r _p ) obtained as described above is substituted into the equation (1), and the absorption coefficient μ in the probe region 6 is calculated from the photoacoustic signal. _a (r _p ) can be obtained.

  Thus, in this embodiment, AOT measurement is performed for a plurality of positions inside the living body, and the spatial distribution of the light attenuation coefficient from the light irradiation position to the probe region is calculated using the modulation signal. The light intensity in the probe region is calculated using the spatial distribution, and the absorption coefficient is obtained using equation (1) based on the light intensity and the acoustic signal obtained by the PAT measurement. In the present embodiment, the absorption characteristics of the probe region in the PAT measurement can be obtained using the modulation signal obtained by the AOT measurement without being restricted by the arrangement of the probes as in the first embodiment.

Here, as shown in the second embodiment, even if the entire region of the subject 7 is measured by PAT and image reconstruction is performed, the present method can be applied only to a region with high contrast. Good. At this time, the entire region inside the subject 7 is divided by the probe region size from the light attenuation coefficient μ _eff (r) at the position r of the modulated light measurement region 6a obtained by a plurality of measurements. Assuming the attenuation coefficient μ _eff (r), the inverse problem estimation as disclosed in Non-Patent Document 1 is performed on the AOT model described in Patent Document 1 and the like, and a more detailed attenuation coefficient μ is obtained. A spatial distribution of _eff (r) may be obtained.

Alternatively, the AOT measurement and the PAT measurement are performed in the entire region of the subject 7 as in the first embodiment, and the AOT measurement is used for all the probe regions 6 measured in the entire region inside the subject using the equation (11). _{Determine the} attenuation coefficient μ _eff . With respect to the spatial distribution of the attenuation coefficient μ _eff obtained here, the light intensity Φ (r _p ) in each probe region 6 is calculated using a diffusion equation or the like, and already obtained by PAT measurement for each probe region. The sound pressure may be converted into an absorption coefficient using light intensity Φ (r _p ) and imaged.

Also in the present embodiment, when the inside of the subject 7 is inhomogeneous, the local light intensity of the probe region 6 can be calculated by _obtaining the spatial distribution of the attenuation coefficient μ _eff by AOT measurement, and the PAT signal Thus, the absorption coefficient can be obtained with high accuracy.

(Embodiment 4)
A biological information processing method according to Embodiment 4 of the present invention will be described. The apparatus configuration of this embodiment is the same as that of the first embodiment. First, before performing AOT measurement or PAT measurement, pulse ultrasonic waves are transmitted using the ultrasonic transducer 5, and ultrasonic echoes that are reflected waves are received by the ultrasonic transducer 5. By measuring the subject 7 while changing the transmission direction of the pulsed ultrasound, the structural information inside the subject 7 is acquired and stored in the memory 13.

  The arithmetic processing unit 11 reads out the structure data inside the subject 7 obtained by ultrasonic echo measurement from the memory 13, and uses the structural features to divide the inside of the subject 7 into regions and store the memory. Save to 13. The structural feature specifies a region where the echo signal obtained by the ultrasonic echo device can obtain a signal with a contrast higher than a preset threshold value. Thus, using the ultrasonic echo signal, a region having a characteristic tissue structure is extracted.

Next, in the AOT measurement, the divided structure information is used. For example, as shown in FIG. 11, the divided structure information is divided into a region A (17a) and a region B (17b) inside the subject and other regions. Since each region is different in terms of organization, optical characteristics such as an absorption coefficient and a scattering coefficient are also different. Therefore, in the AOT measurement, the attenuation coefficient μ _eff is obtained for each region using, for example, the method of the third embodiment.

The attenuation coefficient μ _eff is constant, assuming that each area is almost optically homogeneous, and the light intensity Φ (r _p ) in the probe area 6 is calculated using the distribution of the attenuation coefficient, so that the sound of the PAT measurement is obtained. Based on the signal, the absorption coefficient μ _a (r _p ) of the same region is obtained.

Alternatively, AP Gibson et al, “Recent advancements in diffusion optical imaging”, Phys. Med. Biol. 50 (2005) R1-R43, even if the internal distribution of the attenuation coefficient μ _eff of the subject 7 is reconstructed from a plurality of AOT measurements by solving the inverse problem using structural information. Good. Also in this case, the absorption characteristic can be obtained by calculating the light intensity of the probe region in the PAT measurement using the distribution of the inhomogeneous attenuation coefficient.

  In the present embodiment, the inside of the living body is divided into a plurality of regions based on ultrasonic echoes in advance, and the light intensity of the local region is calculated using the spatial distribution of the light attenuation coefficient calculated for each region. This makes it possible to efficiently extract an optically inhomogeneous region using structural information and selectively perform AOT measurement, thereby shortening the measurement time.

  As mentioned above, although preferable embodiment of this invention was described, this invention is not limited to these, A various deformation | transformation and change are possible within the range of the summary.

1 Light source 5 Ultrasonic transducer 6 Ultrasonic focusing area (probe area)
DESCRIPTION OF SYMBOLS 7 Subject 8 Photodetector 9 Signal processing apparatus 10 Signal extraction part 11 Arithmetic processing part 12 Image generation part 17a, 17b Area | region inside a test object 18 Light propagation path distribution

Claims (20)

A light source for irradiating the subject with each of a plurality of wavelengths of light;
An ultrasonic transmission unit for irradiating ultrasonic waves to a local region of the subject;
A light detection unit for detecting modulated light in which light from the light source is modulated by the ultrasonic wave in the local region;
An acoustic wave detector for detecting an acoustic wave generated from the local region by receiving light from the light source;
A processing unit that acquires spectral information of the local region from an acoustic signal that is an output from the acoustic wave detection unit, based on a light intensity in the local region acquired from a modulation signal that is an output of the light detection unit;
A subject information acquisition apparatus characterized by comprising:   The object information acquiring apparatus according to claim 1, wherein the ultrasonic transmission unit and the acoustic wave detection unit are combined with a single elastic wave transducer.   Incident light propagation region in which light emitted from the light source propagates to the local region in the subject, and detection light propagation in which the modulated light propagates from the local region to the light detection unit in the subject 3. The subject information acquiring apparatus according to claim 1, wherein the incident optical fiber and the detection optical fiber are arranged so that the regions overlap each other. Arranging the incident optical fiber and the detection optical fiber so that the incident light propagation region and the detection light propagation region can be regarded as the same,
The said calculating part calculates the light intensity in the said local area | region using the relational expression obtained from the incident light propagation area | region and the detection light propagation | transmission area | region being the same. Sample information acquisition device.   The processing unit acquires a three-dimensional tomographic image related to spectral information inside the subject by associating the spectral information obtained for the local region with position coordinates of the local region. The subject information acquisition apparatus according to any one of claims 1 to 4.   The light source includes a first light source for irradiating light modulated by the ultrasonic wave, and a second light source different from the first light source for irradiating light generating the acoustic wave. The object information acquiring apparatus according to claim 1, wherein the object information acquiring apparatus is an object information acquiring apparatus.   The object information acquiring apparatus according to claim 1, wherein the spectral information is a component ratio or metabolic information of the object.   The object information acquiring apparatus according to claim 1, wherein the spectral information is an oxygen saturation index. The light source irradiates the subject with first light having a first wavelength and second light having a second wavelength different from the first wavelength;
The processing unit corresponds to the light intensity of the first light in the local region acquired from the modulation signal that is the output of the light detection unit, and the first light that is the output from the acoustic wave detection unit. Obtaining an absorption coefficient corresponding to the first light in the local region based on the acoustic signal
The light intensity of the second light in the local region acquired from the modulation signal that is the output of the light detection unit, and the acoustic signal corresponding to the second light that is the output from the acoustic wave detection unit Based on, obtaining an absorption coefficient corresponding to the second light of the local region,
The spectral information is acquired based on an absorption coefficient corresponding to the first light and an absorption coefficient corresponding to the second light. Subject information acquisition apparatus. The acoustic wave transmitting unit irradiates the subject with pulsed ultrasonic waves,
The acoustic wave detection unit detects an echo of the pulsed ultrasonic wave generated in the subject and outputs an echo signal, and the processing unit adds structural information of the subject obtained from the echo signal. The object information acquiring apparatus according to claim 1, wherein spectral information of the local region is acquired based on the information. Irradiating each of a plurality of wavelengths of light to a local region of a subject and irradiating an ultrasonic wave, and detecting modulated light modulated by the ultrasonic wave in the local region;
Detecting an acoustic wave generated from the local region when the subject is irradiated with light;
Obtaining spectral information of the local region from the acoustic signal obtained from the acoustic wave based on the light intensity in the local region obtained from the modulated signal obtained from the modulated light; and
A method for acquiring subject information, comprising:   An incident light propagation region in which irradiated light propagates to the local region in the subject, and a detection light propagation region when detecting the modulated light propagating from the local region in the subject, The object information acquiring method according to claim 11, wherein light is incident and detected so as to overlap. Performing the incidence and detection of the light so that the incident light propagation region and the detection light propagation region can be regarded as the same,
The object information acquisition according to claim 12, wherein the light intensity in the local region is acquired using a relational expression obtained from the fact that the incident light propagation region and the detection light propagation region are the same. Method. In the step of detecting the acoustic wave, the acoustic wave is detected in an arbitrary local region inside the subject,
Identifying a region within the subject where the acoustic signal is obtained with a contrast higher than a predetermined threshold;
The object information acquiring method according to claim 11, wherein the local region is set with respect to the specified region, and the modulated light is detected. In the step of detecting the modulated light, detecting the modulated light from a plurality of positions inside the subject to obtain a spatial distribution of light attenuation coefficients inside the subject;
The object information acquiring method according to claim 11, further comprising: acquiring the light intensity in the local region using the spatial distribution. Further comprising the step of dividing the interior of the subject into a plurality of regions based on ultrasonic echoes obtained by irradiating the subject with ultrasound;
The object information acquisition method according to claim 15, wherein the light intensity in the local region is acquired using a spatial distribution of the light attenuation coefficient calculated for each region.   12. The three-dimensional tomographic image relating to spectral information inside the subject is acquired by associating the spectral information obtained for the local region with position coordinates of the local region. 17. The subject information acquisition method according to any one of items 1 to 16.   The object information acquisition method according to claim 11, wherein the spectral information is a component ratio or metabolic information of the object.   The object information acquiring method according to claim 11, wherein the spectral information is an oxygen saturation index. Irradiating the subject with pulsed ultrasound;
Detecting an echo of the pulsed ultrasonic wave generated in the subject and outputting an echo signal;
20. The object information acquisition method according to claim 11, wherein spectral information of the local region is acquired based on the structure information of the object obtained from the echo signal.