JP4469903B2 - Biological information imaging device - Google Patents

Description

  The present invention relates to a biological information imaging apparatus.

  In general, imaging apparatuses using X-rays, ultrasound, and MRI (nuclear magnetic resonance method) are widely used in the medical field.

  On the other hand, research on optical imaging devices that obtain in-vivo information by propagating light irradiated on a living body from a light source such as a laser into the living body and detecting the propagating light is actively promoted in the medical field. Yes.

  As one of such optical imaging techniques, Photoacoustic Tomography (PAT: Photoacoustic Tomography) has been proposed (Non-patent Document 1).

  Photoacoustic tomography is a technique that irradiates a living body with pulsed light generated from a light source, detects acoustic waves generated from living tissue that absorbs the energy of light propagated and diffused in the living body, and detects the signals at multiple locations. This is a technology for analyzing and visualizing information inside the living body. Thereby, the optical characteristic value distribution in the living body, in particular, the light energy absorption density distribution can be obtained.

According to Non-Patent Document 1, in photoacoustic tomography, the sound pressure (P) of an acoustic wave obtained from an absorber in a living body by light absorption can be expressed by the following equation.
P = Γ · μ _a · Φ
Here, Γ is a Gruneisen coefficient which is an elastic characteristic value, which 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 (C _p ).

μ _a is an absorption coefficient of the absorber, and Φ is a light amount in a local region (amount of light irradiated to the absorber).

Since Γ is known to take a substantially constant value when the structure is determined, the product of μ _a and Φ is obtained by measuring the change in the sound pressure P, which is the magnitude of the acoustic wave, at a plurality of points in a time-sharing manner. That is, a light energy absorption density distribution can be obtained.
M, Xu, L.M. V. Wang ¨ Photoacoustic imaging in biomedicine ¨ Review of scientific instruments, 77, 041101 (2006)

In the photoacoustic tomography in the above-described conventional example, as can be seen from the above equation (1), in order to obtain the absorption coefficient (μ _a ) distribution in the living body from the measurement of the change in the sound pressure (P), It is necessary to obtain the distribution (Φ) of the irradiated light quantity by some method.

However, since the light introduced into the living body diffuses, it is difficult to estimate the amount of light irradiated to the absorber, and the light energy absorption density (μ _a × Φ) distribution can be obtained only by measuring the sound pressure of a normal generated acoustic wave. It can only be imaged.

That is, it is difficult to calculate the distribution (Φ) of the amount of light irradiated to the absorber from the sound pressure measurement of the acoustic wave, and to accurately separate and image the distribution of the absorption coefficient (μ _a ) in the living body. .

As a result, there is a problem that it is difficult to accurately identify constituent substances and measure the concentration of living tissue from the distribution of the absorption coefficient (μ _a ) in the living body.

  The present invention has been made in view of the above problems, and an object of the present invention is to provide a biological information imaging apparatus capable of obtaining a high-resolution in-vivo optical characteristic value distribution, particularly a light absorption coefficient distribution and an average equivalent attenuation coefficient of a living body. And

A biological information imaging apparatus according to the present invention is a biological information imaging apparatus that performs imaging using an acoustic wave generated by irradiating a living body with light, the light source that irradiates light to the living body, and the light source that is irradiated with the light source Obtained by analyzing an acoustic wave detector that detects an acoustic wave generated from a light absorber in the living body that has absorbed a part of the energy of light, and an electrical signal detected by the acoustic wave detector, A signal for calculating an average transmission attenuation coefficient of the living body using a change in relative position information between the light absorber and the light irradiation region of the living body and a sound pressure of an acoustic wave generated from the light absorbing body. And a processing unit.

  According to the present invention, it is possible to obtain a high-resolution in-vivo optical characteristic value distribution, particularly a light absorption coefficient distribution, or an average equivalent attenuation coefficient of a living body, and to accurately image these. A biological information imaging apparatus can be provided.

  Next, embodiments of the present invention will be described with reference to the drawings.

[Embodiment 1]
FIG. 1 illustrates a configuration example of a biological information imaging apparatus according to the present embodiment.

  In FIG. 1A, when the pulse light 13 is irradiated from the first light source 10 to the living body 11, an acoustic wave 14 is generated from the light absorber 12 inside the living body. This acoustic wave 14 is detected by an acoustic wave detector 15 via an electrical signal. The detected electrical signal is analyzed by the signal processing unit 16.

When irradiated with light from the first light source 10, an initial sound pressure P ₁ of the acoustic wave 14 generated from the light absorber 12 in the living body can be expressed by the following equation.

Where Γ is the Gruneisen coefficient of the light absorber, μ _a is the absorption coefficient of the light absorber, Φ is the local light quantity absorbed by the light absorber, μ _eff is the average equivalent attenuation coefficient of the living body, Φ ₀ is the amount of light incident on the living body from the light source.

D ₁ is a distance (first distance) from the region (light irradiation region) irradiated with light from the first light source 10 to the light absorber 12, that is, the depth.
Assuming that the Grenaisen coefficient (Γ) of the light absorber is known because it is almost constant once the tissue is known, the acoustic wave source distribution and the absorption coefficient are obtained by time-resolved measurement of the sound pressure (P) using an acoustic wave detector. The product (light energy absorption density distribution) of (μ _a ) and the light quantity (Φ) can be obtained.

Here, it is assumed that the amount of light Φ ₀ applied to the living body from all light sources is constant, and light is irradiated in a large area with respect to the thickness of the living body, so that the light propagates in the living body like a plane wave. is doing. In addition, in order to make the irradiation light quantity Φ ₀ to the living body constant, the light quantity irradiated from the light source may be made constant.

  In addition, by performing time-resolved measurement of sound pressure (P) change at multiple points, it is possible to estimate the acoustic wave source distribution or light energy absorption density.

  On the other hand, FIG. 1B is a diagram in which the living body 11 is irradiated with the pulsed light 23 from the second light source 20 provided at a position different from the first light source 10. In this case, assuming that the light absorber does not exist at the center in the living body, the distance between the light irradiation region to the living body and the light absorber is different between the first light source 10 and the second light source 20.

By irradiating the pulsed light 23, an acoustic wave 24 is generated from the light absorber 12 inside the living body. The acoustic wave 24 is detected by the acoustic wave detector 26, and the detected electrical signal is processed by the signal processing unit 26.
When the first light source 10 was irradiated with light from the second light source 20 where the distance from the light absorber is different in vivo, the initial sound pressure P ₂ of the acoustic wave 24 generated from the light absorber 12 is next It can be expressed by a formula.

Here, the distance d ₂ from the area where the light from the second light source 20 is irradiated to the living body to the light-absorbing body 12 (second distance), i.e. the depth. As described above, the acoustic wave generation source distribution or the light energy absorption density can be estimated by time-resolved measurement of the sound pressure (P) change.
By the way, taking the logarithm of both sides of the above formula (1), the following formula is obtained.

  Moreover, when the logarithm of both sides of the above formula (2) is taken, the following formula is obtained.

Here, the sound pressure P ₁ and the sound pressure P ₂ can be determined from the measured values. Also, with the first distance d _1, the second distance d ₂ can be determined from the time-resolved measurement of the sound pressure.

  Then, when the distance d between the region irradiated with light and the light absorber is plotted on the horizontal axis, the logarithm of the sound pressure of the acoustic wave is plotted on the vertical axis, and the respective values are plotted as coordinate values, a graph as shown in FIG. Can be created.

If a straight line is specified by the least square method or the like from the coordinate values of FIG. 2, the average equivalent attenuation coefficient (μ _eff ) of the living body can be obtained from the slope of the specified straight line.

Thus, if the average equivalent attenuation coefficient (μ _eff ) of the living body can be obtained, the amount of light Φ irradiated to the light absorber can be obtained as is apparent from the equation (1). Thereby, the distribution of the light energy absorption density, which is the product of the absorption coefficient (μ _a ) and the light quantity (Φ), can be converted into an absorption coefficient distribution. Furthermore, it is possible to accurately identify the constituent material of the living tissue and measure the concentration from the absorption coefficient distribution in the living body, which is difficult with conventional photoacoustic tomography.

The calculation example shown this time is an example, and the essence of the present invention is that the relative position information between the light absorber and the light irradiation region and the sound pressure of the acoustic wave generated from the light absorber are used. The optical characteristic value distribution information is calculated. That is, any calculation method may be used as long as the average equivalent attenuation coefficient (μ _eff ) of the living body can be obtained.

  For example, here, the sound pressure when the irradiation area of the light source is changed, the distance between the irradiation area of the light source and the light absorber is changed is detected, and the logarithm of the detected sound pressure is plotted against the distance. The equivalent attenuation coefficient of the living body was obtained. However, instead of taking the logarithm of the sound pressure, it is also possible to directly obtain the equivalent attenuation coefficient by fitting the change curve with the exponential function of Equation (1) or Equation (2). In this way, the equivalent attenuation coefficient can be obtained by various methods.

  Next, this embodiment will be specifically described.

  The first light source 10 and the second light source 20 irradiate pulsed light having a specific wavelength that is absorbed by the light absorber 12 introduced into the living body. It is desirable to use pulsed light that satisfies the stress confinement condition.

  Lasers are preferable as these light sources, but light emitting diodes or the like can be used instead of lasers. As the laser, various lasers such as a solid laser, a gas laser, a dye laser, and a semiconductor laser can be used.

  In the present embodiment, in order to measure a light absorption coefficient value distribution having wavelength dependence, a light source that can oscillate different wavelengths may be used instead of only light having a single wavelength.

  As the light source at that time, a dye that can convert an oscillating wavelength, a laser using OPO (Optical Parametric Oscillators), or the like can be used.

  Regarding the wavelength of the light source to be used, a region of 700 nm to 1100 nm that absorbs less in the living body is preferable.

  When obtaining the optical characteristic value distribution of the living tissue relatively near the surface of the living body, it is also possible to use a wavelength region having a wider range than the above wavelength region, for example, a wavelength region of 400 nm to 1600 nm.

  In addition, when each light source cannot be arranged near the living body that is the subject, the light irradiation unit can be guided to the living body using an optical transmission path such as an optical fiber.

  In the description using FIG. 1 above, two light sources, the first light source 10 and the second light source 20, are used, but light irradiation is performed from different positions by one light source using an optical path converter such as a mirror. The acoustic wave data may be measured. That is, the first distance obtained by irradiating light from the first position and the second distance obtained by irradiating light from the second position which is different from the first position by the optical path converter. The optical characteristic value distribution information may be calculated from the relative position information obtained using the distance.

  Further, if acoustic wave data is measured using three or more light sources, it is advantageous in that it is possible to obtain coordinate values of a larger number of points and to obtain more probable values.

  The acoustic wave detectors 15 and 25 of the present embodiment detect the acoustic waves 14 and 24 generated from the light absorber in the living body that has absorbed a part of the energy of the light irradiated to the living body from the light source, and convert the detected acoustic waves to the electrical signal. Convert. As these acoustic wave detectors, any acoustic wave detector can be used as long as it can detect acoustic wave signals, such as a transducer using a piezoelectric phenomenon, a transducer using optical resonance, and a transducer using a change in capacitance. A detector may be used.

  In the description using FIG. 1 above, two acoustic wave detectors are provided corresponding to the two light sources, but an acoustic wave obtained by light irradiation from the two light sources is detected by one acoustic wave detector. May be.

  When the electrical signal obtained from the acoustic wave detector is small, it is preferable to amplify the signal intensity using an amplifier.

  In addition, it is desirable to use an acoustic impedance matching agent for suppressing reflection of sound waves between the acoustic wave detector and the biological material to be measured.

  The signal processing units 16 and 26 of the present embodiment can analyze the electrical signal from the acoustic wave detector and thereby obtain the optical characteristic value distribution information of the living body. Specifically, a light energy absorption density distribution, a light absorption characteristic value distribution, an average equivalent attenuation coefficient of a living body, and the like can be obtained.

  Any signal processing unit may be used as long as it stores the intensity of the acoustic wave and its change over time and can convert it into data of the optical characteristic value distribution by the calculation means.

  For example, an oscilloscope and a computer that can analyze data stored in the oscilloscope can be used.

  Further, in FIG. 1 described above, an example in which two signal processing units are provided is shown for convenience of explanation, but optical characteristic value distribution information is calculated by one signal processing unit or three or more signal processing units. Also good.

  In addition, when the light source can generate light of multiple wavelengths and irradiate the living body with light of multiple wavelengths, the living body is configured using the optical characteristic value distribution in the living body that changes depending on each wavelength. It is also possible to image the concentration distribution of the substance to be processed.

  For example, by calculating the absorption coefficient value distribution and comparing these values with the wavelength dependence specific to the substance (glucose, collagen, oxidized / reduced hemoglobin, etc.) constituting the living tissue, the concentration of the substance constituting the living body It is also possible to image the distribution.

  Examples of the light absorber 12 include tumors and blood vessels in the living body, or an object that absorbs light in the living body similar to these. When a molecular probe is used as the light absorber 12, indocyanine green (ICG) or the like is generally selected. However, any material may be used as long as it emits an acoustic wave larger than the surrounding biological material when irradiated with pulsed light.

  By using the biological information imaging apparatus shown in such an embodiment, the optical characteristic distribution of the molecular probe introduced into the living body can be imaged more accurately and easily than in the prior art. .

[Embodiment 2]
In the second embodiment, a configuration example in which an optical characteristic value distribution is calculated from time change information of sound pressure obtained by simultaneously irradiating light from a plurality of light sources will be described.

  FIG. 3 illustrates a configuration example of the biological information imaging apparatus according to this embodiment.

  In FIG. 3, 30 is a light source, 31 is a living body, 32 is a light absorber, 33 is pulsed light, 34 is an acoustic wave, 35 is an acoustic wave detector, and 36 is a signal processing unit (information processing unit).

Here, when the pulsed light is spread and irradiated from n light sources 30 (for example, four in FIG. 3), the sound pressure P _total of the sound wave generated from the light absorber 32 in the living body 31 is expressed by the following equation. It can be shown.

Where Γ is the Gruneisen coefficient of the light absorber, μ _a is the absorption coefficient of the light absorber, Φ is the local light quantity absorbed by the light absorber, μ _eff is the average equivalent attenuation coefficient of the living body, Φ ₀ is the amount of light incident on the living body from the light source.
D _i is the distance from the region irradiated with light from the light source of number i to the light absorber.

Assuming that the Gruneisen coefficient of the absorber is known because it is almost constant once the tissue is known, the first acoustic wave source distribution, absorption coefficient (μ) is obtained by time-resolved measurement of the sound pressure (P) by the acoustic wave detector. _a ) and the product of the light quantity (Φ) (the distribution of the first light energy absorption density) can be obtained.

Here, it is assumed that the irradiation light quantity Φ ₀ from all the light sources is constant, and the light propagates in the living body like a plane wave.

Next, as shown in FIG. 4, when light from the kth light source 30 among the light sources 30 is blocked, pulse light is emitted from n−1 light sources 30. The sound wave P _k generated from the light absorber 32 by this pulsed light can be expressed by the following equation.

Here, d _k is the distance from the region irradiated with light from the kth light source to the light absorber.

  The second acoustic wave generation source distribution and the second light energy absorption density distribution can be obtained by time-resolved measurement of the sound pressure (P) change.

  By the way, the difference between the sound pressure obtained from the n light sources and the sound pressure obtained from the n−1 light sources is obtained by the difference between the equations (5) and (6) and can be expressed by the following equation. .

  Here, when the logarithm of both sides is taken, Expression (7) becomes as follows.

The left side of Equation (8) can be determined from the actual measurement value of sound pressure. Further, the distance d _k between the region irradiated with the light from the blocked k-th light source and the absorber can be determined from the time-resolved measurement of the sound pressure. Accordingly, the distance d between the light irradiation region and the light absorber can be plotted as a reference numeral 37 in FIG. 5 with the horizontal axis as the horizontal axis, the logarithm of the sound pressure of the acoustic wave as the vertical axis, and the respective values as coordinate values. .

Similarly, if the light from the (k−1) th light source is blocked, pulse light is emitted from the n−2 light sources, and the sound wave P _k−1 generated from the light absorber is measured. The difference between the sound wave P _k and the sound wave P _k−1 is obtained, and the distance d _k−1 to the light absorber can be obtained from the region where the light emitted from the blocked (k−1) th light source enters the living body. For example, it can be plotted as indicated by reference numeral 38 in FIG.

  For example, the code is obtained by taking the difference between the light irradiation from the first, second, and third light sources (total three) and the data obtained from the light irradiation from the first and second light sources (total two). It can be plotted as 37. Further, by plotting the difference between the data obtained from the light irradiation from the first and second light sources (two in total) and the light irradiation from the first light source (one), it is plotted as indicated by reference numeral 38. be able to.

  In addition, the difference between the data obtained from the light irradiation from the first and second light sources (two in total) and the light irradiation from the first light source (one) is plotted, and then obtained from the first light source. A second plot may be further performed based on the data. That is, in the configuration of this embodiment, two or more light sources may be provided.

As described above, if a straight line is specified by the least square method or the like from the coordinate values plotted in FIG. 5, the equivalent attenuation coefficient of the living body can be obtained from the slope of the straight line. Thus, if the average equivalent attenuation coefficient (μ _eff ) of the living body can be obtained, the amount of light Φ irradiated to the light absorber can be obtained as is apparent from the equation (1). Thereby, the distribution of the light energy absorption density, which is the product of the absorption coefficient (μ _a ) and the light quantity (Φ), can be converted into an absorption coefficient distribution. Furthermore, it is possible to accurately specify the constituent material of the living tissue and measure the concentration from the absorption coefficient distribution in the living body, which is difficult with conventional photoacoustic tomography.

In addition, the calculation example shown this time is an example, and the essence of the present invention is that the relative position information obtained from the acoustic wave generated from the light absorber and the difference in the sound pressure are used to calculate the optical characteristic value distribution information of the living body. Is to calculate. That is, any calculation method may be used as long as the average equivalent attenuation coefficient (μ _eff ) of the living body can be obtained.

  For example, instead of taking the logarithm of the change sound pressure, it is possible to directly obtain the equivalent attenuation coefficient by fitting the change curve with the exponential function of Expression (7). In this way, the equivalent attenuation coefficient can be obtained by various methods.

  Next, this embodiment will be described more specifically.

  The light source 30 irradiates a living body with pulsed light, and is provided at a plurality of places so that different places of the living body can be irradiated simultaneously. Moreover, it is comprised so that the light from at least 2 or more light sources can be interrupted | blocked. The blocking may be realized by turning on / off the light source, or a light shielding member may be provided between the light source and the living body.

  In addition, as the light source 30, what was demonstrated in Embodiment 1 can be used.

  The light absorber 32 is a tumor, blood vessel, or similar light absorber in the living body. The light absorber 32 absorbs a part of light energy and generates an acoustic wave 34.

  The acoustic wave detector 35 detects the acoustic wave 34 generated by the light absorber 32 that absorbs part of the energy of the light, and converts it into an electrical signal.

  In the present embodiment, a case where a plurality of acoustic wave detectors are arranged in the vicinity of the living body surface is shown. However, the present invention is not limited to this arrangement, and the acoustic waves can be detected at a plurality of locations. Just do it.

  That is, since the same effect can be obtained if acoustic waves can be detected at a plurality of locations, a single sound wave detector may be scanned two-dimensionally on the living body surface.

  Each acoustic wave detector may be an array type in which detectors are arranged in one dimension or two dimensions.

  Note that the amplifier and the acoustic impedance matching agent described in the first embodiment may be used.

  The signal processing unit 36 can analyze the electrical signal from the acoustic wave detector and thereby obtain the optical characteristic value distribution information of the living body. Specifically, a light energy absorption density distribution, a light absorption characteristic value distribution, an average transmission attenuation coefficient of a living body, and the like are obtained.

  As described in the first embodiment, when the light source can generate light having a plurality of wavelengths and irradiates the living body with light having a plurality of wavelengths, the optical characteristic value distribution in the living body for each wavelength It is also possible to image the concentration distribution of substances constituting the living body.

  According to the configuration described in the second embodiment, by simultaneously irradiating light from a plurality of light sources, it is possible to increase the amount of light irradiated to the absorber in the living body, and an acoustic wave signal larger than the conventional one Can be obtained. Further, by using the difference information of the measurement result, it is possible to reduce noise such as the influence of scattering and reflection of acoustic waves in the living body. As a result, the obtained optical characteristic value distribution in the living body is not affected by measurement noise, and accurate analysis is possible.

It is a figure explaining the structural example of the biological information imaging device in Embodiment 1 of this invention. It is a figure explaining an example of the result of having analyzed the signal obtained with the living body information imaging device in Embodiment 1 of the present invention. It is a figure explaining the structural example of the biological information imaging device in Embodiment 2 of this invention. The figure explaining the state which detects the acoustic wave signal which generate | occur | produced from the light absorber, when the light from one or more light sources in Embodiment 2 of this invention is interrupted | blocked, and the biological body is simultaneously irradiated with the other light sources. is there. It is a figure explaining an example of the result of having analyzed the signal obtained with the living body information imaging device in Embodiment 2 of the present invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Light source 11 Living body 12 Light absorber 13 Pulse light 14 Acoustic wave 15 Acoustic wave detector 16 Signal processing part (information processing part)

Claims (8)

A biological information imaging apparatus that performs imaging using acoustic waves generated by irradiating a living body with light,
A light source for irradiating the living body with light;
An acoustic wave detector for detecting an acoustic wave generated from the light absorber in the living body that has absorbed a part of the energy of the light irradiated by the light source;
Relative positional information between the light absorber and the light irradiation area of the living body obtained by analyzing the electrical signal detected by the acoustic wave detector, and the sound pressure of the acoustic wave generated from the light absorber A signal processing unit that calculates an average equivalent attenuation coefficient of the living body using the change of
A biological information imaging apparatus comprising: The signal processing section, the biological information imaging apparatus according to claim 1, characterized in that to calculate the absorption coefficient distribution of the living body from the average equivalent attenuation coefficient of the living body. The said signal processing part calculates the average equivalent attenuation coefficient of the said biological body from the said electrical signal obtained by at least 2 times of light irradiation from a mutually different position, The Claim 1 characterized by the above-mentioned. Biological information imaging device. The light source is composed of two or more light sources,
The signal processing unit was obtained by irradiating light from a first light source and a second light source provided at a position different from the first light source. The biological information imaging apparatus according to claim 1, wherein an average equivalent attenuation coefficient of the living body is calculated using a second distance. An optical path converter that converts an optical path of light emitted from the light source;
The signal processing unit irradiates light from a first position obtained by irradiating light from a first position and from a second position that is different from the first position by the optical path converter. The biological information imaging apparatus according to claim 1, wherein an average equivalent attenuation coefficient of the living body is calculated using the obtained second distance. The light source is composed of two or more light sources,
The signal processing unit uses the difference between the sound pressure obtained by simultaneously irradiating n light sources and the sound pressure obtained by simultaneously irradiating n-1 light sources . The biological information imaging apparatus according to claim 1 , wherein an average equivalent attenuation coefficient is calculated.   The signal processing unit uses an average equivalent attenuation coefficient of the living body using a straight line specified from the relative position information and a coordinate value represented by a logarithm of a sound pressure of an acoustic wave generated from the light absorber. The biological information imaging apparatus according to claim 1, wherein: The biological information imaging apparatus according to claim 7 , wherein the straight line is specified from the coordinate values using a least square method.

Images