JP2017012485A - Biomarker and subject information acquisition apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a biomarker capable of reducing interferences and artifacts caused when a subject is imaged by a modality excluding a photoacoustic apparatus.SOLUTION: Used is a biomarker in which the absolute value of a difference between a luminance value based on the light absorption coefficient of the biomarker among the luminance values constituting image data formed by a photoacoustic apparatus capturing an image of a subject and a luminance value based on the light absorption coefficient of the tissue which is located about the biomarker and constitutes the subject, is greater than the absolute value of a difference between a luminance value based on the output from a modality excluding the photoacoustic apparatus to the biomarker among the luminance values constituting image data formed by the modality excluding the photoacoustic apparatus capturing an image of the subject and a luminance value based on the output from the modality excluding the photoacoustic apparatus to the tissue which is located about the biomarker and constitutes the subject.SELECTED DRAWING: Figure 1

Description

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

  Research on photoacoustic devices that image in-vivo information by irradiating a living body with laser light or the like and receiving ultrasonic waves generated from the inside of the living body due to the irradiation has been actively promoted in the medical field. Yes. When the living body is irradiated with irradiation light on the subject such as pulsed laser light, an acoustic wave is generated when the irradiation light on the subject is absorbed by the living tissue in the living body. By receiving and analyzing this acoustic wave (typically, an ultrasonic wave), information related to the optical characteristics inside the living body can be imaged. Such a technique is called photoacoustic tomography (PAT). Patent Document 1 discloses a configuration having a puncture function in a biological information imaging apparatus using photoacoustics. Patent Document 2 discloses a biomarker that can be imaged with most modalities in an apparatus for marking a living body for therapeutic or diagnostic treatment.

Japanese Patent No. 5349839 Japanese National Patent Publication No. 10-508504

  In the apparatus configuration of Patent Document 1, when the biomarker described in Patent Document 2 is used, a marking function appears in an image captured using a photoacoustic apparatus. However, when imaging is performed using other modalities, an image in which an unintentionally emphasized portion appears is formed. Thereby, the image resulting from the biomarker may give a sense of interference during image diagnosis or may be an artifact. For this reason, the problem which should be improved further remains.

  In view of the above problems, an object of the present invention is to provide a biomarker that can reduce a sense of obstruction and artifacts when a subject is imaged with a modality other than a photoacoustic apparatus.

In order to achieve the above object, the present invention is located around a luminance value based on its own light absorption coefficient among luminance values constituting image data formed by a photoacoustic apparatus imaging a subject. The absolute value of the difference from the luminance value based on the light absorption coefficient of the tissue constituting the subject constitutes image data formed by a modality other than the photoacoustic apparatus imaging the subject. Among the luminance values to be generated, the luminance value based on the output from the modality other than the photoacoustic device to itself and the modality other than the photoacoustic device to the tissue constituting the subject that is located around the luminance value A biomarker that is larger than the absolute value of the difference from the luminance value based on the output of is provided.
According to another feature of the invention, the absolute value of the difference between the light absorption coefficient of the subject and the light absorption coefficient of the subject is the acoustic impedance of the subject, the X-ray transmittance of the subject, or the MRI. The absolute value of the difference between the application result when the magnetic field and radio wave are applied to the subject and the acoustic impedance, X-ray transmittance, or the application result when the MRI applies the magnetic field and radio wave to the subject. Larger biomarkers are provided.

  As described above, according to the present invention, there is provided a biomarker that can reduce a sense of interference and artifacts when a subject is imaged with a modality other than the photoacoustic apparatus.

1 is a block diagram showing Example 1 of an object information acquiring apparatus according to the present invention. The flowchart which shows the arrangement | positioning method of the biomarker in Example 1. The schematic diagram which shows the structure of the arrangement | positioning part in Example 1. FIG. FIG. 3 is a block diagram showing a second embodiment of the subject information acquiring apparatus of the present invention. The flowchart which shows the arrangement | positioning method of the biomarker in Example 2.

  Embodiments of the present invention will be described in detail below with reference to the drawings. In principle, the same components are denoted by the same reference numerals, and description thereof is omitted. However, the detailed calculation formulas, calculation procedures, and the like described below should be appropriately changed according to the configuration and various conditions of the invention, and the scope of the invention is limited to the following description. Is not.

  The object information acquisition apparatus in the description receives an acoustic wave generated in the object by irradiating the object (including phantom) with light (electromagnetic waves) such as near infrared rays, and images the object information. Includes devices that use photoacoustic effects acquired as data. The object information acquiring apparatus in the description includes, for example, a photoacoustic wave diagnostic apparatus. In the case of an apparatus using the photoacoustic effect, the acquired object information is the source distribution of acoustic waves generated by light irradiation, the initial sound pressure distribution in the object, or the optical energy derived from the initial sound pressure distribution Absorption density distribution, absorption coefficient distribution, and concentration distribution of substances constituting the tissue are shown. The concentration distribution of the substance is, for example, an oxygen saturation distribution, a total hemoglobin concentration distribution, an oxidized / reduced hemoglobin concentration distribution, or the like. Further, characteristic information that is object information at a plurality of positions may be acquired as a two-dimensional or three-dimensional characteristic distribution. The characteristic distribution can be generated as image data indicating characteristic information in the subject. The acoustic wave in the description is typically an ultrasonic wave, and includes an acoustic wave called a sound wave and an ultrasonic wave. An acoustic wave generated by the photoacoustic effect is called a photoacoustic wave or an optical ultrasonic wave. An acoustic detector (for example, a probe) receives acoustic waves generated or reflected in the subject.

  The techniques compared with the present invention include the following. That is, an apparatus using ultrasonic echo technology (US: ultrasonographic) that transmits ultrasonic waves to a subject, receives reflected waves (echo waves) reflected inside the subject, and acquires subject information as image data Is included. Furthermore, magnetic resonance imaging (MRI) that includes imaging by outputting a magnetic field to the subject is included. Furthermore, mammography (abbreviated as “MMG”, excluding those using the photoacoustic effect in the present specification) that is imaged by irradiating the subject with X-rays is included. Furthermore, CT (Computed Tomography) is included. The subject information acquired by the apparatus using the ultrasonic echo technique is information reflecting the difference in acoustic impedance of the tissue inside the subject.

<Example 1>
FIG. 1 is a block diagram showing Example 1 of an object information acquiring apparatus 100 (hereinafter, simply referred to as “apparatus 100”) according to an embodiment of the present invention. The apparatus 100 according to the first embodiment is configured based on a light source 13, a probe 14, a signal processing unit 15, a display unit 16, and an arrangement control unit 20. The arrangement control unit 20 is a mechanism for arranging the biomarker 11 (hereinafter abbreviated as “marker 11”) inside the subject 17. However, the present invention is not limited to this, and the arrangement may be made such that a doctor who is a user of the apparatus 100 arranges the marker 11 inside the subject 17 by his / her hand without providing the arrangement control unit 20. The marker 11 serves as a positional reference for evaluating an image formed by being picked up by the apparatus 100, and is displayed so as to have a luminance value larger than that of other parts. However, the present invention is not limited to this, and the luminance value may be smaller than that of other parts. This is because the portion where the marker 11 is displayed is darker than the other portions, and as a result, the darkly displayed portion can serve as a positional reference for the entire image.

≪Marker 11≫
The marker 11 (corresponding to itself) is used together with the apparatus 100 and marks a part in the subject (for example, a living body) 17. The material of the marker 11 is preferably a material having optical characteristics (for example, a light absorption coefficient). This material may be a non-metallic material, and for example, a polyol, a polyol in which a compound having a light absorption property is dispersed, or a mixture in which ink is mixed with an aqueous solution in which agar is dissolved can be applied. In addition, when this material uses a polyol, a polyether polyol is preferable. This is because the marker 11 can be configured to approximate the acoustic characteristics of the tissue of the subject 17 and the marker 11 can be configured so as not to inhibit the propagation of the photoacoustic wave. The compound having light absorption characteristics is, for example, a compound having a certain light absorption coefficient. This acoustic characteristic is, for example, an acoustic propagation characteristic indicating the ease of propagation (or difficulty of propagation) of acoustic waves, and an acoustic characteristic of ease of attenuation (or difficulty of attenuation) of acoustic waves. Attenuation characteristics are included.

  The compound having the light absorption property is used, for example, to reproduce the light absorption property of the subject tissue. Specifically, a pigment can be used, and carbon black or the like can be preferably used. It is preferable to use it dispersed in a material such as polyol. Other pigments and dispersants can be used as the pigment. In this example, in order to approximate the optical characteristics of human tissue, particularly hemoglobin, a carbon black pigment and a mixture of a polyether dispersant having an affinity with the pigment were added to the polyether as a compound having light absorption characteristics. . The polyol used was a polyether polyol copolymer (number average molecular weight 6000) having a molar ratio of ethylene oxide to propylene oxide of 1: 1. Since the polyol used in this example is usually a liquid, it was cured using hexamethylene diisocyanate (HDI) as a curing agent. The light absorption coefficient of the marker 11 is 0.098 / mm at a wavelength of 797 nm. The size of the marker 11 is not particularly limited. However, in view of the arrangement in a subject such as a breast in a human body, a size as small as possible is preferable, and a size that can be visually recognized in a photoacoustic image (an image obtained as a result of imaging with a photoacoustic apparatus) is appropriately selected. Selected.

  Further, the light absorption coefficient of the tissue of the subject 17 in the vicinity of the marker 11 arranged in the subject (for example, living body) 17 is 0.013 / mm regardless of the wavelength (for example, 756 nm and 797 nm). Thereby, in the formation of image data (image reconstruction), the image based on the marker 11 of the present example was confirmed as an image having a luminance (luminance value) of about 7 times at a wavelength of 797 nm compared to the surroundings. On the other hand, since the acoustic impedance of the marker 11 of this example and the subject 17 tissue in the vicinity thereof are both 1.4 MRayls, they have substantially the same luminance value in the ultrasonic echo image. As a result, the contrast, which is the difference between the luminance values based on the marker 11 and the subject 17 tissue in the vicinity thereof, becomes substantially zero. Thereby, in the ultrasonic echo image, the marker 11 and the subject 17 tissue in the vicinity thereof cannot be distinguished and visually recognized. Accordingly, a doctor or the like can suitably perform an image diagnosis using any of the images formed by using the photoacoustic apparatus and the ultrasonic echo apparatus.

However, the present invention is not limited to this, and the subject 17 tissue in the vicinity may be confirmed as an image having a luminance (luminance value) approximately twice that of the marker 11 of the present embodiment. Thereby, the luminance value based on the marker 11 is smaller than the luminance value based on the nearby subject 17 tissue, and only the image portion corresponding to the marker 11 is displayed darkly. This is because the marker 11 can be visually distinguished from the nearby subject 17 tissue on the image. That is, the absolute value of the difference between the luminance value based on the nearby subject 17 tissue and the luminance value based on the marker 11 may be equal to or larger than a value that can be visually recognized on the image. In addition, the light absorption coefficient value of the marker 11 may be set to a light absorption coefficient value equivalent to that of blood, for example. Thereby, the marker can be visually recognized in the photoacoustic image without a sense of incongruity.

  Further, the X-ray transmittance of the marker 11 of this embodiment and the living body (subject 17) in the vicinity thereof may be substantially the same. As a result, in the images captured by CT and MMG, which are devices that capture images by applying X-rays to the subject 17, the marker 11 and the living body (subject 17) tissue in the vicinity thereof have substantially the same luminance value. . As a result, the contrast, which is the difference in luminance value, becomes substantially zero, and the marker 11 and the living body (subject 17) tissue in the vicinity thereof cannot be distinguished and visually recognized. Thereby, in the image formed by CT and MMG, the marker 11 is not displayed as an unnecessary artifact. That is, the marker 11 and the living body (subject 17) tissue in the vicinity thereof cannot be distinguished and visually recognized. Thereby, a doctor or the like can preferably perform an image diagnosis using any one of images formed by using the photoacoustic apparatus, CT, and MMG.

  In this embodiment, the application result when the MRI applies a magnetic field and radio waves to the marker 11 and the application result when the MRI applies the magnetic field and radio waves to a living body (subject 17) tissue in the vicinity of the marker 11 May be substantially the same. Thereby, in the image formed by MRI, the marker 11 and the living body (subject 17) tissue in the vicinity thereof have substantially the same luminance value. As a result, the contrast, which is the difference in luminance value, becomes substantially zero, and the marker 11 and the living body (subject 17) tissue in the vicinity thereof cannot be distinguished and visually recognized. Thereby, in the image formed by MRI, the marker 11 is not reflected as an unnecessary artifact. That is, the marker 11 and the living body (subject 17) tissue in the vicinity thereof cannot be distinguished and visually recognized. Thereby, a doctor or the like can preferably perform an image diagnosis using any of the images captured using the photoacoustic apparatus and the MRI. This application result includes a nuclear magnetic resonance (NMR) which is an MRI imaging principle.

  In addition, it is not restricted to this, You may make it combine the said property of the marker 11 suitably. For example, a doctor or the like preferably uses any of images formed by imaging the marker 11 arranged in the subject 17 separately using a photoacoustic apparatus, US, CT, MMG, and MRI. A diagnosis may be performed. This is because artifacts due to the marker 11 are reduced in images formed by separately capturing images using US, CT, MMG, and MRI, and the marker 11 is clearly displayed in an image captured by the photoacoustic apparatus. is there.

≪Arrangement unit 12≫
The placement unit 12 moves the marker 11 from the outside to the inside of the subject 17 and places it at a desired position. The placement unit 12 may be configured by a known tube such as a needle, a cannula, a trocar, or the like. The placement unit 12 is guided to the selected site in the subject 17 by the placement control unit 20. The selected portion is a portion arbitrarily set by the user of the apparatus 100, and may be a region that the user wants to see in the subject 17 for example. The region to be viewed is a region where a lesion site such as cancer may exist, for example. However, the present invention is not limited to this, and the selected site need not be set. The arrangement control unit 20 may control the arrangement unit 12 based on an operation from the display unit 16 by the user.

<< Light source 13 >>
The light source 13 is a device that generates pulsed light that irradiates the subject 17. The light source 13 is preferably a laser light source in order to obtain a large output, but a light emitting diode, a flash lamp, or the like can be used instead of the laser. Lasers applicable to the light source 13 are solid lasers, gas lasers, dye lasers, semiconductor lasers, and the like. The irradiation timing, waveform, intensity, and the like of the light (pulse light) emitted from the light source 13 are controlled by a light source control unit (not shown). The light source control unit may be integrated with the light source 13. Further, the wavelength of the pulsed light emitted from the light source 13 is absorbed by a specific component among the components constituting the subject 17 and may be a wavelength at which light propagates to the inside of the subject 17. preferable. Specifically, it is preferably 650 nm or more and 1100 nm or less. The light source 13 also emits light in a sufficiently short time according to the thermal characteristics of the subject 17 in order to effectively generate photoacoustic waves. The pulse width of the pulsed light generated from the light source 13 is preferably about 10 to 50 nanoseconds in the case of the subject 17. The light from the light source 13 may be irradiated to the subject 17 so as to be guided to the subject 17 by the bundle fiber. Alternatively, the subject 17 may be directly irradiated with light from the light source 13. Alternatively, an arbitrary optical system such as a diffusion plate may be provided for the light from the light source 13 to guide the pulsed light to the subject 17. Alternatively, the configuration may be such that pulse light emitted from the light source 13 is guided to the subject 17 and irradiated to the subject 17 by using a combination of mirrors provided in the light shielding cylinder without using the bundle fiber. The apparatus 100 may be provided between the light source 13 and the subject 17 as an irradiation unit that guides light from the light source 13 to the subject 17 and irradiates the subject 17.

≪Probe 14≫
The probe 14 receives an acoustic wave generated due to pulsed light (hereinafter abbreviated as “irradiation light”) irradiated to the subject 17 and converts the received acoustic wave into an analog electric signal. , Send it to the subsequent stage. The probe 14 is also called a transducer. Moreover, the probe 14 may be comprised from a single acoustic detector, and may be comprised by arranging several acoustic detectors. This acoustic detector may be composed of a piezo element or the like. As the form of the probe 14, an ultrasonic probe type for an endoscope, a hand-held probe type, a transmission type probe for mammography, and the like are appropriately selected and applied. The probe 14 preferably has high sensitivity and a wide frequency band. Specific examples of the probe 14 include PZT (piezoelectric ceramics), PVDF (polyvinylidene fluoride resin), CMUT (capacitive micromachined ultrasonic transducer), and a Fabry-Perot interferometer. However, the present invention is not limited to those listed here, and any one may be used as long as it satisfies the function as a probe.
<< Signal processing unit 15 >>
The signal processing unit 15 amplifies the analog electric signal output from the probe 14 and converts it into a digital signal, and sends the digital signal to the subsequent stage. The signal processing unit 15 typically includes an amplifier, an analog / digital converter (ADC), an FPGA (Field Programmable Gate Array) chip, and the like. When there are a plurality of electrical signals sent from the probe 14, the signal processing unit 15 is preferably capable of simultaneously processing the plurality of signals simultaneously. However, the present invention is not limited to this, and the amplifier may be built in the probe 14. The signal processing unit 15 also reconstructs an image of this digital signal to generate image data and sends it to the subsequent stage. As this image reconstruction method, various methods such as a Fourier transform method, a universal back projection method, a filtered back projection method, and a sequential reconstruction method can be applied. The signal processing unit 15 may be a computer having a CPU, a main storage device, and an auxiliary storage device, or may be hardware designed exclusively.

≪Display unit 16≫
The display unit 16 displays the image data sent from the signal processing unit 15 as a visible image. As the display unit 16, a liquid crystal display, a plasma display, an organic EL display, an FED (Field Emission Display), or the like can be applied.

(Arrangement method of the marker 11)
FIG. 2 is a flowchart showing a method for arranging the markers 11 of the apparatus 100 according to the first embodiment of the present invention. The flow starts when the apparatus 100 is supplied with power and the subject 17 is held in the holding unit of the apparatus 100. In addition, this holding part may be a cup-shaped member that can insert and hold the subject 17 as long as the probe 14 has a hemispherical shape. Alternatively, the holding unit may be the pair of plates as long as the holding unit holds the breast as the subject 17 with the pair of plates interposed therebetween.

  In step S21, the pulsed light emitted from the light source 13 is directly irradiated onto the subject 17 through a bundle fiber or the like, and the process proceeds to step S22. In this case, when a part of the energy of the light propagating through the subject 17 is absorbed by the light absorber such as blood, an acoustic wave is generated from the light absorber due to thermal expansion. When cancer is present inside the subject 17, light is specifically absorbed by the new blood vessels (light absorber) of the cancer in the same manner as other normal blood, and an acoustic wave is generated.

  In step S <b> 22, the acoustic wave generated from the subject 17 is received by the probe 14. Then, the received acoustic wave is converted into an analog electric signal by an acoustic wave detecting element (piezo element or the like) included in the probe 14 and sent to the signal processing unit 15. Then, analog / digital conversion and amplification are performed by the ADC in the signal processing unit 15 to generate a digital signal. Then, the digital signal is stored in the memory in the signal processing unit 15, and the process proceeds to step S23.

  In step S23, the stored digital signal is read, and image data is generated by performing image reconstruction processing on the read signal. Then, it is stored in the memory in the signal processor 15, and the process proceeds to step S24. In this image data, for example, characteristic information (for example, initial sound pressure distribution and light absorption coefficient distribution) inside the subject 17 is reflected as the luminance value. In step S <b> 24, image data is read from the memory in the signal processing unit 15 and sent to the display unit 16. Then, the display unit 16 displays the image data as a visible image, and the process proceeds to step S25. This image may be, for example, a three-dimensional image or a two-dimensional image.

  In step S25, an operator such as a doctor determines a selected site on the image of the display unit 16, and the process proceeds to step S26. This selected region may be, for example, a region on the image corresponding to the internal region of the specific subject 17 that the doctor particularly wants to see. For example, when a doctor predicts a place where cancer is likely to exist within a certain range in the subject 17, the rough range may be selected on the display screen. And you may comprise so that the selected area | region may be set to the apparatus 100 through operation in the display part 16 as a selection part.

  In step S <b> 26, the arrangement control unit 20 moves the tip of the arrangement unit 12 to the area in the subject 17 corresponding to the selected site on the screen. In this case, a selection signal corresponding to the selection of the selected portion on the display unit 16 may be sent to the arrangement control unit 20, and the arrangement unit 12 may be automatically moved based on this selection signal. The placement unit 12 may be configured from a puncture needle. This facilitates insertion into the subject 17 and facilitates placement of the marker 11. After the placement unit 12 is moved as described above, the process proceeds to step S27.

In step S <b> 27, the marker 11 is placed in the subject 17 by the placement unit 12. In this case, the marker 11 may be arranged by the arrangement control unit 20, or the arrangement of the marker 11 may be performed by operating the arrangement unit 12 by a procedure such as a doctor. In addition, when the placement unit 12 completes the placement of the marker 11, a completion signal may be sent from the placement unit 12 to the placement control unit 20, and the placement completion may be displayed on the display unit 16 based on the transmission. Then, after the display, a command for pulling out the placement unit 12 from the subject 17 is sent to the placement control unit 20 by an operation on the display unit 16 by the user. Based on this command, the placement control unit 20 pulls out the placement unit 12 from the subject 17 and ends the flow. In the present embodiment, an example in which, after the imaging is completed, the selected region is determined by the operator on the image formed by the imaging, and the marker 11 is arranged inside the subject 17 is described. However, the present invention is not limited to this, and the marker 11 may be arranged while the subject 17 is imaged in a timely manner and an image that changes in real time based on the imaging is confirmed by the user.

(Check result)
After arranging the marker 11 according to the above processing, the subject 17 was imaged by the apparatus 100. Thereby, the display based on the marker 11 was able to be visually recognized on the image displayed on the display part 16. FIG. Moreover, it imaged with modality (US, MMG, MRI, CT) other than a photoacoustic apparatus. This imaging result is such that the marker 11 cannot be visually recognized on each modality image, or is indistinguishable from the tissue image of the subject 17 (the marker 11 and its surrounding tissue are indistinguishable on the image). . Note that modality refers to imaging means for medical images, such as X-rays, ultrasound, and MRI.

  FIG. 3 is a schematic diagram illustrating the structure of the arrangement portion 12 in the first embodiment. The placement unit 12 is inserted into the subject 17 so as to reach the vicinity of a portion in the subject 17 where there is a possibility that, for example, cancer exists. The arrangement part 12 has a structure similar to a puncture needle in this embodiment. The main body portion 32 has a hollow structure, and an opening portion 33 through which a wire 34 with the marker 11 provided at the tip thereof can be taken in and out is provided in a part thereof. The wire 34 is passed through the cylindrical interior of the main body 32, the marker 11 is provided at one end, and the wire operation ring 35 is provided at the other end. The wire operation ring 35 can be operated by a doctor or the like. The marker 11 at the tip of the wire 34 is placed at a desired location on the subject 17 based on this operation. The distal end portion 36 has a sharp shape so that it can be smoothly inserted into the subject 17.

  The operation method of the arrangement | positioning part 12 is as follows, for example. That is, first, the placement unit 12 is inserted from the outside to the inside of the subject 17. And it inserts until the opening part 33 reaches | attains near site | parts, such as cancer. When the opening 33 reaches that portion, the wire operation ring 35 is operated by a doctor or the like, whereby the wire 34 is pushed out from the opening 33 in the direction of the arrow. And the marker 11 is arrange | positioned in the vicinity of the site | part. Then, the wire 34 is stored inside the main body portion 32 by operating the wire operation ring 35. And the main-body part 32 is extracted from the subject 17, and arrangement | positioning operation is complete | finished.

  However, the present invention is not limited to this, and the arrangement control unit 20 may automatically perform the above operation based on a user instruction.

<Example 2>
FIG. 4 is a block diagram showing Example 2 of the subject information acquiring apparatus according to the embodiment of the present invention, and the same components as those in Example 1 are denoted by the same reference numerals and description thereof is omitted. In addition, regarding the configuration similar to that of the first embodiment, numbers in the 400s are attached, common numbers are given to the tenth place and the first place, and the description is omitted unless necessary. The object information acquisition apparatus 400 (hereinafter simply referred to as “apparatus 400”) of the second embodiment is also configured based on the light sources 413 and 18, the probe 14, the signal processing unit 15, and the display unit 16. The apparatus 400 is different from the apparatus 100 in that the apparatus 400 includes light sources 413 and 18 that generate light having different wavelengths. The light sources 413 and 18 may be laser light sources similar to the light source 13 in the apparatus 100. The apparatus 400 irradiates the subject 17 with light having different wavelengths from the light sources 413 and 18, thereby obtaining a concentration distribution of a substance that is functional information in the subject 17 based on each acoustic wave generated from the subject 17. It can be acquired.

  The apparatus 400 displays an image made up of luminance values corresponding to the value of oxygen saturation in the subject 17 on the display unit 16. This image can be used, for example, so that a biomarker 411 (hereinafter abbreviated as “marker 411”) is placed in the subject 17 while a doctor or the like looks at the image. That is, for example, since cancer requires a lot of oxygen, the oxygen saturation around it decreases. As a result, on the image, there is a high possibility that cancer or the like is present at a location where the luminance value is significantly reduced. By arranging the marker 411 at such a location, it becomes a mark when performing an image diagnosis of cancer or the like, which is useful.

  The irradiation light to the subject 17 generated from the light sources 413 and 18 may be near infrared light. This near-infrared light easily penetrates water constituting most of the subject 17 and is easily absorbed by hemoglobin in blood, so that a blood vessel image can be imaged. The signal processing unit 15 may calculate the oxygen saturation in the blood, which is functional information, by comparing blood vessel images with irradiation light that is pulsed light with different wavelengths. The light of different wavelengths may be light of two wavelengths, for example. One of the two wavelengths may be more easily absorbed by oxyhemoglobin than reduced hemoglobin, and the other may be more easily absorbed by reduced hemoglobin than oxyhemoglobin. As described above, the wavelength of light generated from the light source 413 is more easily absorbed by oxyhemoglobin than reduced hemoglobin, and the wavelength of light generated from the light source 18 is more easily absorbed by reduced hemoglobin than oxyhemoglobin. And

The calculation processing of the oxygen saturation in the signal processing unit 15 is as follows, for example. That is, the absorption coefficient μ _a (λ) is calculated by photoacoustic measurement performed by irradiating the subject 17 with light having the wavelength λ of the light radiated to the subject 17 from the light source of the apparatus 400. . The absorption coefficient μ _a (λ) is expressed by the following formula (1) when the main light absorbers are oxygenated hemoglobin and reduced hemoglobin.

μ _a (λ) = ε _ox (λ) · C _ox + ε _de (λ) · C _de
... (1)
Formula (1) is the sum of the product of the absorption coefficient ε _ox (λ) of oxyhemoglobin and the abundance ratio C _ox of oxyhemoglobin, and the product of the absorption coefficient ε _de (λ) of deoxyhemoglobin and the abundance ratio C _de of reduced hemoglobin. It consists of ε _ox (λ) and ε _de (λ) are constant values and are measured in advance by other methods. Thus, the unknowns in equation (1) _is a C _ox, two _{C de.}

Therefore, first, photoacoustic measurement is performed by irradiating the subject 17 with light of different wavelengths generated from the light sources 413 and 18. In this case, it is performed at least once for one wavelength. Based on this, simultaneous equations for the abundance ratio C _ox of oxyhemoglobin and the abundance ratio C _de of reduced hemoglobin are solved by the signal processing unit 15 to calculate C _ox and C _de . In this case, when photoacoustic measurement is performed at a larger number of wavelengths or times, the signal processing unit 15 performs fitting by the method of least squares. Thereby, C _ox and C _de may be calculated. This is because the calculation accuracy of C _ox and C _de can be improved. Note that the photoacoustic measurement refers to at least a period from receiving an acoustic wave generated by irradiating the subject 17 with light and acquiring image data formed based on the reception.

The oxygen saturation level SO ₂ is a ratio of oxyhemoglobin in the total hemoglobin, and is calculated from the equation (2).
SO ₂ = C _ox / (C _ox + C _de )
... (2)
When measurement is performed at two types of wavelengths λ ₁ and λ ₂ , C _ox and C _de obtained by solving the simultaneous equations of Equation (1) by the signal processing unit 15 are substituted into Equation (2). . Thus, SO ₂ can be expressed as the following formula (3).

SO ₂ = {− μ _a (λ ₁ ) ε _de (λ ₂ ) + μ _a (λ ₂ ) ε _de (λ ₁ )} / [− μ _a (λ ₁ ) {ε _de (λ ₂ ) −ε _ox ( λ ₂ )} + μ _a (λ ₂ ) {ε _de (λ ₁ ) −ε _ox (λ ₁ )]
... (3)
Formula (3) can be further transformed into the following formula (4).
SO ₂ = [− {μ _a (λ ₁ ) / μ _a (λ ₂ )} ε _de (λ ₂ ) + ε _de (λ ₁ )] / [− {μ _a (λ ₁ ) / μ _a (λ ₂ ) } {Ε _de (λ ₂ ) −ε _ox (λ ₂ )} + {ε _de (λ ₁ ) −ε _ox (λ ₁ )}]
... (4)

The oxygen saturation SO ₂ is calculated by the ratio of the measured value μ _a (λ ₁ ) to the measured value μ _a (λ ₂ ) as can be seen from the equation (4). Thus, if the measured value μ _a (λ ₁ ) and the measured value μ _a (λ ₂ ) are acquired, the oxygen saturation SO ₂ is calculated regardless of the magnitude of the value.

(About the configuration of the device 400)
The marker 411 is used together with the device 400 and does not necessarily constitute the device 400, but will be described here for convenience of description. The material constituting the marker 411 preferably has different light absorption characteristics (absorption coefficients) for two or more wavelengths. This material is composed of phthalocyanine compounds having different maximum absorption wavelengths and different absorption coefficients at a wavelength of 756 nm (λ ₁ ) and absorption coefficients at a wavelength of 797 nm (λ ₂ ). In this material, the dispersion amount of the phthalocyanine compound is adjusted and added to the polyether. The phthalocyanine compound is composed of copper phthalocyanine (maximum absorption wavelength 825 nm) and a phthalocyanine vanadium complex (maximum absorption wavelength 750 nm). However, the present invention is not limited to this, and various phthalocyanine compounds can be applied. The light absorption coefficient of the marker 411 is 0.033 / mm at a wavelength of 756 nm and 0.026 / mm at a wavelength of 797 nm.

  The light source of the apparatus 400 includes a light source 413 and a light source 18 that can emit light having a first wavelength and a second wavelength different from the first wavelength, respectively. The absorption coefficients of oxyhemoglobin and reduced hemoglobin of the subject 17 are preferably greatly different between the wavelength of light generated from the light source 413 and the wavelength of light generated from the light source 18. This is because the calculation accuracy of oxygen saturation can be improved. The light irradiation timings of the light source 413 and the light source 18 are preferably different from each other. This is because it is necessary to individually acquire image data based on the absorption coefficient of the subject 17 for each wavelength. The light sources 413 and 18 are composed of a titanium sapphire laser. The wavelength of the irradiation light of the light source 413 is 756 nm, and the wavelength of the irradiation light of the light source 18 is 797 nm. However, the present invention is not limited to this, and more light sources having different wavelengths of irradiation light may be provided, or a single light source may be configured to be capable of irradiating light by switching a plurality of wavelengths.

(Arrangement method of marker 411)
FIG. 5 is a flowchart showing a method for arranging the markers 411 in the second embodiment of the present invention. In addition, about the process common to the process in the flowchart of FIG. 2, a common referential mark is attached | subjected and description is abbreviate | omitted unless there is particular need. The flow starts when power supply to the apparatus 400 is started and the subject 17 is held at a predetermined position of the apparatus 400.

In step S50, the subject 17 is irradiated with light having a wavelength of 756 nm, and the process proceeds to step S22. In step S52, it is determined whether or not the object 17 is irradiated with light of all wavelengths and an acoustic wave is received based on the irradiation. When no acoustic wave is received for all wavelengths, the process proceeds to step S50. In step S50, light having a wavelength of 797 nm, which is another wavelength, is irradiated, and the process proceeds to step S52 via step S22. In the case of the present embodiment, the apparatus 400 irradiates only the above two wavelengths. In this case, the total wavelength is the two wavelengths. On the other hand, when it is determined in step S52 that acoustic waves have been received for all wavelengths, the process proceeds to step S54.

  In step S54, digital data based on the irradiation light is subjected to image reconstruction processing for each wavelength. Thereby, image data reflecting the absorption coefficient distribution for each wavelength is reconstructed and acquired, and stored in a built-in memory. Then, the image data reflecting the absorption coefficient distribution of the two wavelengths is subjected to processing based on the magnitude relationship, so that image data reflecting the oxygen saturation distribution is formed. This image data needs to be formed by processing after the image data of a plurality of absorption coefficient distributions are prepared. For this reason, the image data reflecting the absorption coefficient distribution of the wavelength processed previously is stored in a memory (main storage device) built in the signal processing unit 15. In this case, as described above, the processing based on the magnitude relationship is performed by substituting the absorption coefficient distribution obtained in Equation (3), and the oxygen saturation distribution is calculated by the processing based on the magnitude relationship. . In this embodiment, the oxygen saturation of the marker 411 is 55%. Further, the process based on the magnitude relationship may be a comparison process that is a difference operation or a process that takes a ratio. The process of substituting the absorption coefficient distribution obtained in Expression (3) is a process of performing computation by substituting the matrix having each of the absorption coefficients obtained in Expression (3) as an absorption coefficient distribution. Also good.

  In step S56, image data reflecting the generated oxygen saturation distribution is input to the display unit 16, and an image reflecting the oxygen saturation distribution is displayed on the screen based on this input. The display unit 16 can display an image in a color corresponding to the numerical value of the oxygen saturation by setting a color look-up table (CLUT). Thereafter, the same processing as in the first embodiment is performed, and the flow is terminated.

<Confirmation result>
After placing the marker 411 on the subject 17 based on the above flow, the subject 17 was imaged by the apparatus 400. As a result, the marker 411 could be visually recognized on the image reflecting the oxygen saturation distribution. Further, when imaging is performed with other modalities (US, MMG, MRI, CT), the marker 411 cannot be visually recognized on the image formed by imaging using those modalities, or an image of the surrounding tissue of the subject 17 The result was indistinguishable.

<Other examples>
The present invention supplies a program that realizes one or more functions of the above-described embodiments to a system or apparatus via a network or a storage medium, and one or more processors in the computer of the system or apparatus read and execute the program This process can be realized. It can also be realized by a circuit (for example, ASIC) that realizes one or more functions.

  The implementation of various features of the present invention is not limited to the embodiments described above. For example, the devices 100 and 400 may automatically control the placement unit 12 to place the biomarker. In this case, various modes such as wireless communication, communication using circuit wiring, communication using light by a photocoupler, and the like can be applied to the transmission / reception format of signals between the devices 100 and 400 and the placement unit 12. Alternatively, the placement unit 12 may be displayed on the screen of the display unit 16 in real time by photoacoustic measurement, and a biomarker may be placed by manipulating the placement unit 12 with a technique while a doctor or the like looks at it. . In this case, the biomarker may be configured to generate an acoustic wave by irradiating light so as to have a light absorption property and appear in an image.

  11 Biomarker

Claims (10)

  Among the luminance values constituting the image data formed by the photoacoustic apparatus imaging the subject, the luminance value based on its own light absorption coefficient and the tissue that is located around the subject and constitutes the subject The absolute value of the difference from the luminance value based on the light absorption coefficient is the photoacoustic value to itself among the luminance values constituting the image data formed by the modality other than the photoacoustic apparatus imaging the subject. Absolute difference between a luminance value based on an output from a modality other than the apparatus and a luminance value located around itself and based on an output from a modality other than the photoacoustic apparatus to the tissue constituting the subject A biomarker greater than the value.   The biomarker according to claim 1, wherein the subject is a human body.   The biomarker according to claim 2, wherein its own acoustic propagation characteristic is substantially the same as the acoustic propagation characteristic of human body tissue.   The biomarker according to any one of claims 1 to 3, wherein the biomarker is formed of a non-metallic material.   The biomarker according to any one of claims 1 to 4, wherein the biomarker is formed of a material that absorbs light of a predetermined wavelength.   The biomarker according to claim 5, wherein the material that absorbs light of the predetermined wavelength is carbon black.   The value of the own light absorption coefficient for the light of the first wavelength is different from the value of the own light absorption coefficient for the light of the second wavelength different from the first wavelength. Biomarker.   The modality other than the photoacoustic apparatus is configured to image the subject by outputting at least one of an ultrasonic wave, an X-ray, a magnetic field, and a radio wave to the subject. The biomarker according to item.   When the absolute value of the difference between the light absorption coefficient of the subject and the light absorption coefficient of the subject is the acoustic impedance of the subject, the X-ray transmittance of the subject, or MRI applies a magnetic field and radio waves to the subject A biomarker having an acoustic impedance, an X-ray transmittance, or an MRI greater than the absolute value of the difference between the application result when the magnetic field and the radio wave are applied to the subject. An irradiation unit for irradiating the subject with light; and
A probe that receives an acoustic wave generated from the subject based on light irradiated by the irradiation unit and outputs an electrical signal;
A signal processing unit for acquiring characteristic information of the subject based on an electrical signal output by the probe;
When the irradiation unit irradiates the light, an arrangement unit that arranges the biological marker according to any one of claims 1 to 9 in the subject;
A subject information acquisition apparatus having:

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