JP5183406B2 - Biological information processing apparatus and biological information processing method - Google Patents

Description

  The present invention relates to a biological information processing apparatus and a biological information processing 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)

  In DOT, a signal is analyzed mainly from light diffusion theory from data obtained by measuring diffused light in a living body. Then, by performing image reconstruction, it is possible to separate the absorption characteristics and the scattering characteristics inside the living body and estimate the respective internal distributions for imaging. For example, if a living tissue is measured, components such as hemoglobin, water, and fat, which are main measurement targets, can be estimated from the absorption characteristics. In addition, metabolic information such as oxygen saturation in the blood can be estimated. Moreover, the component etc. resulting from a structure can also be specified from a scattering characteristic.

  On the other hand, in AOT, signal contrast can be obtained for both an absorbing object whose absorption coefficient is larger than that of the background medium and a scattering object whose scattering coefficient is larger than that of the background medium. It is done. It is known that AOT can image both an absorbing object and a scattering object with almost the same resolution as the ultrasonic focusing region. That is, the signal obtained by AOT is obtained by combining the absorption coefficient and the scattering coefficient as the contrast. However, a method for separating the absorption coefficient and the scattering coefficient from the signal obtained by AOT is not disclosed. If the absorption and scattering characteristics cannot be separated, the above items that could be estimated by DOT cannot be estimated with high accuracy.

In Patent Document 2, a light diffusion equation is established using an attenuation coefficient expressed by the equation (1) in which an absorption coefficient μ _a and an equivalent scattering coefficient μ ′ _S are combined, and the mathematical model is used to calculate the attenuation coefficient. A spatial distribution can be obtained by image reconstruction.

  In this case, the effects of both absorption and scattering cannot be separated. In a biological tissue in which the scattering coefficient can be considered to be almost uniform spatially, the distribution of the attenuation coefficient is almost equivalent to the distribution of the absorption coefficient. On the other hand, when the scattering distribution is not uniform, Patent Document 2 discloses that absorption and scattering are separated from the attenuation coefficient by further measuring DOT. However, in this method, the spatial resolution of the obtained absorption characteristics and scattering characteristics is determined by DOT. A method for separately measuring the absorption coefficient and the scattering coefficient (equivalent scattering coefficient) with the spatial resolution of AOT determined by the ultrasonic focusing size is not disclosed.

  An object of the present invention is to provide a biological information processing apparatus and a biological information processing method capable of separating each of the local absorption characteristics and the scattering characteristics, which are ultrasonic focusing regions, from AOT signals and calculating each with high accuracy. It is to be.

In view of the above problems, the biological information processing apparatus of the present invention includes a light source for irradiating light to a living body, an ultrasonic transmission unit for irradiating ultrasonic waves to a local region of the living body, and a light source from the light source. A light detecting unit for detecting modulated light and non-modulated light modulated by the ultrasonic wave in the local region; and detecting acoustic waves generated from the local region by receiving light from the light source Acoustic wave detection unit of
A calculation unit that calculates the scattering characteristics of the local region from the output signal of the light detection unit using the absorption characteristics of the local region calculated from the acoustic signal that is the output of the acoustic wave detection unit. Features.

Further, in view of the above problems, the biological information processing method of the present invention provides modulated light that is modulated by the ultrasonic wave in the local region when the local region of the living body is irradiated with light and irradiated with ultrasonic waves. And detecting unmodulated light; detecting acoustic waves generated from the local region when the living body is irradiated with light;
Using the absorption characteristics of the local region calculated from the acoustic signal obtained from the acoustic wave to calculate the scattering characteristics of the local region from the modulated light and the non-modulated light. .

  According to the biological information processing apparatus and the biological information processing method of the present invention, it is possible to separate the local absorption characteristics and the scattering characteristics, which are ultrasonic focusing regions, from the AOT signal and calculate each with high accuracy. . Therefore, it is possible to measure the spectral characteristics and main components inside the living body or the spatial distribution such as metabolic information and scattering power with high resolution.

  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 uses the absorption characteristics of a local region calculated from an acoustic signal obtained by photoacoustic imaging (PAT), and outputs the local region from an output signal obtained by acousto-optic tomography (AOT). It is characterized in that the scattering characteristic at is calculated.

  As an output signal obtained from AOT, for example, there is a modulation degree. Here, the “modulation degree” in this specification refers to the light intensity of modulated light modulated by the acoustooptic effect in the ultrasonic irradiation region, unmodulated light that has not been modulated in the ultrasonic irradiation region, and ultrasonic waves. It is defined as the ratio to the light intensity of the non-modulated light combined with the non-modulated light that has passed through other than the irradiation region. The output signal obtained by the AOT including the modulation degree is based on a parameter in which the absorption coefficient and the scattering coefficient in each local region are combined.

  Therefore, by calculating the absorption coefficient in the local region by PAT, it becomes possible to calculate the scattering characteristics independently of AOT. In this way, by using AOT and PAT in combination, the absorption coefficient distribution and the scattering coefficient distribution in the living body can be obtained with high accuracy without being restricted by the resolution of DOT.

(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 and non-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 signal of the photodetector 8 in the AOT measurement is obtained by using the absorption characteristic of the ultrasonic focusing region 6 calculated from the acoustic signal that is the output of the ultrasonic transducer 5 in the PAT measurement. Thus, the scattering characteristics in the local region are calculated.

  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. Two light sources that emit pulsed light emitted in PAT measurement and CW light emitted in AOT measurement may be provided. 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 non-modulated 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 modulated light and non-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. Further, the “non-modulated signal” refers to an electric signal obtained by converting non-modulated light that has not been modulated by ultrasonic waves by the photoelectric effect of the photodetector 8. The electrical signal is preferably an electrical signal of a direct collection component.

[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. Further, 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 modulated signals and non-modulated signals in AOT measurement and photoacoustic signals in 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 generates 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, a calculation processing technique performed by the calculation processing unit 11 to separate the absorption characteristic and the scattering characteristic in the probe region 6 from the modulation signal in the AOT measurement using the photoacoustic signal in the PAT measurement will be described.

First, an arithmetic processing method for obtaining the absorption characteristic of the probe region 6 from the photoacoustic signal in the PAT measurement will be described. PAT can obtain local light absorption information by measuring a photoacoustic wave generated by being absorbed at a local test site. The pressure P of the elastic wave generated in the probe region 6 is expressed by the following equation (2) using the distance z from the light irradiation point to the probe region.
P (z) = Γμ _a (z) Φ (z) (2)
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.

From the equation (2), it can be seen that the sound pressure proportional to the absorption coefficient μ _a (z) at the position z of the local region to be examined is measured by the generated elastic wave. In order to accurately estimate the absorption coefficient μ _a (z), it is necessary to estimate the light intensity Φ (z) at the position z.

As disclosed in Non-Patent Document 1, if an average light attenuation coefficient μ _eff is obtained, the light intensity Φ (z) can be obtained using a Lambert Beer law or a diffusion equation. Thereby, μ _a (z) can be obtained from the sound pressure P (z).

At the time of PAT measurement, the pulse light irradiated to the subject 7 from the incident optical fiber 2 is diffused inside the subject 7 and the light intensity obtained by the photodetector 8 through the detection optical fiber 3 is monitored by backscattering. . Using the diffusion theory, it is possible to calculate the average attenuation coefficient μ _eff in the region where the pulsed light inside the subject 7 is diffused from the obtained light intensity.

For example, when the Lambert Beer rule is used, the light intensity Φ (z) in the probe region 6 is obtained as in the following equation (3).
Φ (z) = S ₀ exp (−μ _eff z) (3)
Here, S ₀ represents the light intensity incident on the subject 7.

(2) from equation (3), the absorption coefficient in the probe region 6 at the position r _p in the subject 7 mu _{a (z)} can be obtained as follows. The sound pressure P is a measurement value in the PAT measurement.

Next, in the AOT measurement, the intensity ratio between the modulated signal and the non-modulated signal measured by the photodetector 8 is calculated, and this is set as the modulation degree M. The modulation degree M is determined by Sava Sakadzic and Lihong V. Wang, “Ultramodulated of multiple scattered coherent light: Analytical model for anisotropically expressed media 5” as shown in Eq. 2 ₁ (τ) can be Fourier transformed and calculated from the ratio of the 0th order and the 1st order.

  Here, the following equation is established.

Expression (7) is a term indicating the influence due to the interaction by ultrasonic waves, and Expression (8) is a term indicating the influence due to Brownian motion.
here,

τ ₀ can be measured by correlating the signal from the photodetector 8 inside the signal processing device 9. In the equation (7), δ _n and δ _d represent the effects of the refractive index change and the scatterer displacement in the probe region 6, respectively, and are functions relating to the scattering coefficient and the ultrasonic frequency.

  In the equation (5), the absorption coefficient and the scattering coefficient result in variables for the same measurement conditions except for parameters relating to ultrasonic waves. (The scattering coefficient depends on the diffusion coefficient.) Therefore, if the absorption coefficient is obtained from the PAT measurement as described above, it is compared with the measured value of the modulation degree M obtained from the Fourier transform of the equation (5). Thus, the equivalent scattering coefficient can be uniquely obtained.

  In this way, the absorption characteristic of the probe region is calculated from the PAT as shown in the equation (4), and the scattering of the same probe region is calculated from the analysis model of the AOT as shown in the equation (5) using this absorption property. Characteristics can be calculated. That is, the absorption characteristic and the scattering characteristic can be separately measured for the local probe region.

  FIG. 2 shows an example of a measurement flow when the biological information processing method of the present embodiment is performed. In S100, an ultrasonic focusing region (probe region) 6 to be a measurement target is set.

  The PAT measurement described above is performed in S101. The sound pressure is measured from the photoacoustic signal obtained from the ultrasonic transducer 5. At the same time, as described above, the pulse light irradiated to the subject 7 from the incident optical fiber 2 diffuses inside the subject 7 and is obtained by the photodetector 8 through the detection optical fiber 3 by backscattering. Measure.

In S102, the PAT measurement is terminated, and the average attenuation coefficient μ _eff of the subject 7 is calculated from the backscattered light intensity obtained in S101. The light intensity in the probe region 6 is calculated from the obtained attenuation coefficient.

  In S103, based on the equation (4), the absorption coefficient of the probe region 6 is calculated using the sound pressure signal measured in S101 and the light intensity obtained in S102. In this way, in the PAT measurement process, scattered light inside the living body is also detected, and light attenuation characteristics inside the living body are calculated from the detected scattered light. Based on the light intensity in the probe region 6 calculated from the light attenuation property, the absorption property in the probe region 6 can be calculated.

  In S104, the above-described AOT measurement is performed. The modulated light intensity obtained from the light detector 8 and the unmodulated light intensity are measured, and the ratio thereof is calculated to calculate the modulation degree M. At this time, the ultrasonic transmission setting is set at the same position as the probe region 6 which is the ultrasonic reception setting set in the PAT measurement.

  In S105, using the above-described analysis model of the modulation degree M, the equivalent scattering of the probe region 6 using the modulation degree M obtained in S104, the absorption coefficient obtained in S103, and the main measurement conditions for ultrasonic waves. Calculate the coefficient.

  By performing the flow from S100 to S105 while scanning the probe region 6 inside the subject 7, a three-dimensional absorption coefficient distribution and an equivalent scattering coefficient distribution inside the subject 7 are obtained.

  By the method described above, the absorption coefficient and the scattering coefficient of the probe region 6 can be obtained with high accuracy. By scanning the probe region 6 inside the subject 7 and performing it, an absorption distribution and a scattering distribution of the subject 7 are obtained. The image generation unit 12 maps the absorption coefficient and the scattering coefficient inside the living body in correspondence with the position coordinates of each probe region 6 to obtain a three-dimensional spatial distribution related to the absorption coefficient and the scattering coefficient. The three-dimensional tomographic image formed in this way 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. It is also preferable to obtain the metabolic information and the scattering power represented by the following formula (9) by the arithmetic processing unit 11.
μ ′ _S = Bλ− ^sp (9)
Here, B is a constant, λ is the wavelength of light, and SP is the scattering power. The function information can be mapped in correspondence with the position coordinates of the probe region 6 in the same manner as described above, and can be imaged by the image generation unit 12 and displayed on the display device 14.

Here, AP Gibson et al, “Recent advance in diffuse optical imaging”, Phys. Med. Biol. 50 (2005) R1-R43, the sound pressure generated from a medium whose optical characteristics can be regarded as homogeneous is an exponential function according to the distance from the position on the surface of the subject 7 irradiated with light. The energy of light is lost. For this reason, a signal profile is obtained in which the acoustic signal is also attenuated by an exponential function. By obtaining a signal profile corresponding to the distance of the acoustic signal from the background medium and fitting using the equation (3), the attenuation coefficient μ _eff of the background medium can be calculated. Using the attenuation coefficient μ _eff obtained here, the light intensity Φ (z) at an arbitrary depth z from the subject surface is obtained from the equation (3), and the absorption coefficient μ _a (z) is obtained from the acoustic signal. Also good.

Here, when the equivalent scattering coefficient μ ′ _S is calculated from the modulation degree obtained by the AOT measurement using the absorption coefficient μ _a obtained by the PAT measurement, the Sava Sakadzic and not the above-mentioned analytical solution is used. Lihong V. Wang, “Ultramodulated of multiple scattered coherent light: Analytical model for anisotropically calculated T 2” The equivalent scattering coefficient μ ′ _s may be obtained so that the result matches the measurement result.

  The modulation degree M in the AOT measurement is a value determined by parameters of both the absorption coefficient and the scattering coefficient of the probe region 6. It is the essence of the present invention that the absorption coefficient is measured independently from the PAT measurement, and the scattering coefficient is obtained using this value. In the present embodiment, the description has been given using the analytical solution shown in the equation (5), but the present invention is not limited to the analytical solution described above. A model such as a model using a diffusion equation of a correlation function can be changed at any time according to measurement, and the present embodiment can be applied according to an applied calculation model.

  Here, the AOT measurement is performed after performing the PAT measurement as shown in the flow of FIG. 2, but the PAT measurement may be performed after performing the AOT measurement in the reverse order.

  AOT measurement methods include detection methods using a single detector such as PMT, parallel detection using a multi-sensor such as a CCD, hologram detection using a photorefractive element, detection using spectral hole burning, etc. Either may be sufficient. When a multi-sensor such as a CCD is used, for example, Jun Li, Geng Ku and Lihong V. Wang, “Ultrasound-modulated optical tomography of biological tissue of use of laser of laser speckles”, APPLIED OPTICS, Vol. 41, no. 28 (2002), an analytical expression for the degree of modulation 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 higher contrast 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, the average attenuation coefficient μ _eff of the subject 7 is obtained by fitting with the diffusion equation using the intensity of the non-modulated light obtained in the AOT measurement in S204. For the high contrast region, the sound pressure signal of the probe region 6 is read from the memory 13, and the absorption coefficient of the probe region 6 is calculated from the equations (3) and (4) using the above-described attenuation coefficient μ _eff. To do. Further, the scattering coefficient of the probe region 6 is calculated using the method described in the first embodiment by using the modulation degree M obtained by the AOT measurement in S204 and the above-described absorption coefficient.

  Also in the present embodiment, the absorption coefficient distribution and the scattering coefficient distribution obtained for the high contrast region in S205 can be imaged and displayed on the display device 14.

  Further, from the absorption coefficient image, the arithmetic processing unit 11 obtains component information such as oxygenated hemoglobin, reduced hemoglobin, water, fat, and collagen, metabolic information such as an oxygen saturation index, and scattering power information from the scattering 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, the region where the abnormality of the biological tissue is suspected from the PAT measurement is identified in advance, and the AOT measurement is performed on the same region. Can be measured. Since it is not necessary to perform AOT measurement on the entire region of the subject 7, the measurement time can be shortened and necessary information can be obtained efficiently. In Example 1, AOT measurement and PAT measurement are continuously performed on the probe region 6, whereas in the present embodiment, AOT measurement and PAT measurement are performed completely independently.

  In the present embodiment, the light attenuation characteristics inside the living body are calculated from the intensity of the unmodulated light detected by the AOT measurement. Based on the light intensity in the local area calculated from the light attenuation characteristic, the absorption characteristic in the local area is calculated. As a result, unmodulated (steady) light can be measured using COT light for AOT measurement instead of pulse light for PAT measurement, so that the photodetector 8 can be detected with higher accuracy than measuring light intensity with repeated pulse light. Can be measured.

(Embodiment 3)
A biological information processing apparatus and a biological information processing method according to Embodiment 3 of the present invention will be described. The basic apparatus configuration of this embodiment is the same as that of the first embodiment. In the present invention, the absorption characteristic obtained by the PAT measurement is used to calculate the scattering characteristic in the AOT measurement. As is clear from equation (2), in order to obtain the absorption characteristics with high accuracy by PAT, it is necessary to calculate the light intensity Φ (r _p ) in the local region with higher accuracy. In the present embodiment, based on the light intensity Φ (r _p ) calculated from the output signal of the photodetector 8 in AOT measurement, absorption in the local region from the acoustic signal that is the output of the ultrasonic transducer 5 in PAT measurement. Calculate the characteristics.

In AOT measurement conditions as shown in FIG. 4, 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 (10).
I _AC (r _p ) = S ₀ Ψ (r _s , r _p ) ηΨ (r _p , r _d ) (10)
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. represents the transfer function of the light intensity to the light detection position r _d, S ₀ is the light intensity incident on the subject 7, eta represents the efficiency of light is modulated action 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,

, (10) can be written as (11).
I _AC (r _p ) = S ₀ Ψ (r _s , r _p ) ² η (11)
Here, as shown in FIG. 6, 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 and the light detection region when detecting the modulated light by the detector 8 overlap and can be regarded as the same, the modulation signal is reciprocated through the same propagation path distribution. It is detected as 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 _d )). Also, since the transfer function Ψ (r) is reversible, equation (11) is obtained.

Therefore, (11) the optical transfer function Ψ from the light incident position _{r s} to the probe region _{r p} from expression

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 (12).
Φ (r _p ) = S ′ ₀ Ψ (r _s , r _p ) (13)
By using the equations (2), (12), and (13), the sound pressure P (r _p ) of the generated photoacoustic wave can be expressed as the following equation (14).

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 expression (15).

From the equation (16), the probe region r _p is measured 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 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 estimated if the parameters defined as constants in the equation (16) 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 embodiment that this is performed using a modulation signal obtained from AOT measurement. At this time, it is preferable to perform the AOT measurement by setting the positions of the incident optical fiber 2 and the detection optical fiber 3 so as to 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.

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.

  Using the absorption characteristics thus obtained, the scattering characteristics may be calculated from the AOT measurement in the same manner as described in the first embodiment.

(Embodiment 4)
A biological information processing apparatus and a biological information processing method according to Embodiment 4 of the present invention will be described. The basic apparatus configuration of this embodiment is the same as that of the first embodiment.

In the first embodiment, the absorption coefficient and the scattering coefficient are separated from the modulation degree M, which is not separated in the AOT measurement. In this embodiment, the attenuation coefficient μ _eff (r) is calculated as a parameter in which both are not separated in the AOT measurement, and then the scattering coefficient is separated using the absorption coefficient obtained by the PAT measurement.

When the propagation of multiple scattered light is expressed using a diffusion equation using the attenuation coefficient μ _eff (r), the following equation (17) is obtained.
(▽ ²⁻ μ ² _eff (r)) U (r) = S (r) (17)
Here, U (r) represents the intensity of scattered light, and S (r) represents the intensity of the light source. Further, the modulated light intensity distribution is expressed using the equation (10).

  Using these equations (10) and (17), Patent Document 2 derives the relationship of the following equation (18).

Here, theta is the angle shown in Figure 4, a 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.

(18) Using the equation, it is possible to determine the attenuation coefficient of the probe region _{r p} from AOT modulated signals mu _eff (r).

The attenuation coefficient μ _eff (r) is a function of the absorption coefficient μ _a and the equivalent scattering coefficient μ ′ _S as shown in the equation (1). For the attenuation coefficient μ _eff (r) obtained from the AOT modulation signal, the absorption coefficient μ _a obtained from the PAT photoacoustic signal using the expression (16) of Embodiment 3 is used, ), The equivalent scattering coefficient μ ′ _S can be calculated.

  In the present embodiment, preferably, the absorption characteristic of the probe region is first obtained with high accuracy from the PAT acoustic signal using an AOT modulation signal (Embodiment 3). Next, the attenuation coefficient of the probe region is obtained from the AOT modulation signal using the equation (18), and the absorption obtained from the acoustic signal of the PAT using the equation (1) for this attenuation coefficient. The scattering characteristic can be obtained from the characteristic.

  FIG. 7 shows an example of a measurement flow when the biological information processing method of this embodiment is performed. In S300, an ultrasonic focusing area (probe area) 6 to be a measurement target is set.

In S301, AOT measurement is performed. At this time, a modulated optical signal _IAC is obtained. In S302, the attenuation coefficient of the probe region 6 is obtained using equation (18).

  In S303, PAT measurement is performed to obtain a photoacoustic signal. At this time, the ultrasonic reception setting is set to the same position as the probe region 6 which is the ultrasonic transmission setting set in the AOT measurement.

In S304, based on the equation (16), by using the photoacoustic signal obtained by modulated optical signal _{I AC} and S302 obtained in S301, and calculates the absorption coefficient of the probe region 6.

  In S305, the equivalent scattering coefficient of the probe region 6 is calculated based on the equation (1) using the attenuation coefficient obtained in S302 and the absorption coefficient obtained in S304.

  By performing the flow from S300 to S305 while scanning the probe region 6 inside the subject 7, a three-dimensional absorption coefficient distribution and an equivalent scattering coefficient distribution inside the subject 7 are obtained.

  Here, as shown in the second embodiment, the technique shown in the present embodiment may be applied to a region having a high contrast after the PAT measurement and the image reconstruction are executed once.

[Modification of device configuration]
8 to 10 are schematic diagrams illustrating other configuration examples in which the optical fiber is not used for the measurement unit 19 in 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. 8, 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, it is possible to set geometric conditions similar to those in FIG.

  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. 9 may be used. The same optical system is used on the incident side and the detection side, and the opening area with respect to the subject 7 is set to 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. 8, but a configuration in which the measurement probe 16 is brought into contact with the subject 7 as shown in FIG. 10 may be used. 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. 10, the light irradiation region and the light detection region can be made substantially the same region.

(Embodiment 5)
A biological information processing method according to Embodiment 5 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. Further, the structural data is displayed on the display device 14. 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 structure information is divided into structurally specific regions A (17a) and B (17b) inside the subject and other relatively homogeneous regions based on the divided structure information.

  For this structurally specific region A (17a) or region B (17b), for example, using the method described in Embodiment 4, AOT measurement and PAT measurement are performed according to the flow of FIG. Calculate absorption coefficient and scattering coefficient. The distributions of the absorption coefficient and the scattering coefficient are displayed on the display device 14 so as to overlap the structure data.

  In this embodiment, ultrasonic echo measurement is performed in advance, and absorption characteristics and scattering characteristics are calculated for structurally inhomogeneous regions using structure information data. This makes it possible to efficiently extract an optically inhomogeneous region using structural information, selectively perform AOT measurement and PAT measurement, and efficiently perform inhomogeneous tissue inside the subject. In addition, absorption characteristics and scattering characteristics can be measured.

  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 is a schematic diagram illustrating a configuration example of a biological information processing apparatus according to a first embodiment. 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 flowchart which shows an example of the measurement flow in the case of enforcing the biological information processing method of Embodiment 2. 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. 6 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. 5. 12 is a flowchart illustrating an example of a measurement flow when the biological information processing method according to the third 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. FIG. 10 is a schematic diagram showing a positional relationship between a segmented region inside a living body and a probe region in Embodiment 5.

Explanation of symbols

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 (13)

A biological information processing apparatus,
A light source for irradiating the living body with light;
An ultrasonic transmission unit for irradiating the local region of the living body with ultrasonic waves;
A light detection unit for detecting modulated light and non-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;
An arithmetic unit that calculates the scattering characteristics of the local region from the output signal of the light detection unit using the absorption characteristics of the local region calculated from the acoustic signal that is the output of the acoustic wave detection unit;
A biological information processing apparatus characterized by comprising:   The biological information processing apparatus according to claim 1, wherein the ultrasonic transmission unit and the acoustic wave detection unit are combined with one elastic wave transducer.   The biological information processing apparatus according to claim 1, wherein the calculation unit calculates a scattering characteristic of the local region from a modulation degree calculated from an output signal of the light detection unit.   The calculation unit calculates an absorption characteristic of the local region from an acoustic signal that is an output of the acoustic wave detection unit, based on the light intensity of the local region calculated from the output signal of the light detection unit. The biological information processing apparatus according to any one of claims 1 to 3. An incident light propagation region in which light emitted from the light source propagates to the local region in the living body; and a detection light propagation region in which the modulated light propagates from the local region to the light detection unit in the living body; Arrange the incident optical fiber and the detection optical fiber so that they can be regarded as the same,
The living body according to claim 4, wherein the calculation unit calculates the light intensity in the local region using a relational expression obtained from the fact that the incident light propagation region and the detection light propagation region are the same. Information processing device. A biological information processing method,
A step of detecting modulated light and non-modulated light modulated by the ultrasonic wave in the local region when irradiating light to the local region of the living body and irradiating ultrasonic waves;
Detecting an acoustic wave generated from the local region when the living body is irradiated with light;
Using the absorption characteristics of the local area calculated from the acoustic signal obtained from the acoustic wave, calculating the scattering characteristics of the local area from the modulated light and the non-modulated light;
A biological information processing method characterized by comprising:   The biological information processing method according to claim 6, wherein a scattering characteristic of the local region is calculated from a modulation degree calculated from the intensity of the modulated light and the non-modulated light. Detecting the acoustic wave, detecting scattered light inside the living body, and calculating light attenuation characteristics inside the living body from the detected scattered light;
Calculating absorption characteristics in the local region based on light intensity in the local region calculated from the light attenuation characteristics;
The biological information processing method according to claim 6 or 7, characterized by comprising: Calculating a light attenuation characteristic inside the living body from the detected intensity of the non-modulated light,
Calculating absorption characteristics in the local region based on light intensity in the local region calculated from the light attenuation characteristics;
The biological information processing method according to claim 6 or 7, characterized by comprising: Calculating the absorption characteristics of the local region from the acoustic signal obtained from the acoustic wave based on the light intensity in the local region calculated from the modulated signal obtained from the detected modulated light;
The biological information processing method according to claim 6 or 7, comprising: Incidence and detection of the light so that the incident light propagation region in the living body by the irradiated light and the detection light propagation region when detecting the modulated light can be regarded as the same,
The biological information processing method according to claim 10, wherein the light intensity in the local region is calculated using a relational expression obtained from the fact that the incident light path and the detection light path are the same. In the step of detecting the acoustic wave, the acoustic wave is detected in an arbitrary local region inside the living body,
Identifying a region in the living body where the acoustic signal is obtained with a contrast higher than a predetermined threshold,
The biological information processing method according to claim 6, wherein the local region is set with respect to the identified region, and the modulated light and the non-modulated light are detected.   Forming the three-dimensional tomographic image relating to the absorption characteristic or the scattering characteristic inside the living body by associating the absorption characteristic or the scattering characteristic obtained for the local area with the position coordinates of the local area; The biological information processing method according to any one of claims 6 to 12, characterized in that:

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