This is a continuation of International Application PCT/JP2018/035467 which is hereby incorporated by reference herein in its entirety.
The present invention relates to a photoacoustic imaging device.
A photoacoustic imaging device is known in which a specimen is irradiated with pulsed excitation light, and acoustic wave generated in the specimen is detected to thereby acquire an image of the specimen (see PTL 1, for example).
To detect the acoustic wave generated in the specimen without any loss, the device of PTL 1 includes a water tank in which a space between the specimen and an acoustic detector is filled with an acoustic wave propagation medium such as water. The water tank has a form of an open container opened upward, and including, as a bottom surface, a membrane brought into contact closely with an upper surface of the specimen. Furthermore, the acoustic detector is brought into contact closely with water surface of water stored in the container.
Japanese Translation of PCT International Application Publication No. 2011-519281
An aspect of the present invention is a photoacoustic imaging device including an irradiator that irradiates a specimen with excitation light, an acoustic wave detection unit that detects an acoustic wave generated at a position irradiated with the excitation light by the irradiator, an acoustic wave propagation body including a bag-shaped body including a film that deforms in conformity with a surface shape of the specimen, an interior of the bag-shaped body being filled with an acoustic wave propagation medium, and a processor including hardware, the processor being configured to generate an image based on the detected acoustic wave, wherein the acoustic wave propagation body is disposed between the acoustic wave detection unit and the specimen, without interposing any air layers, and moves relative to the specimen along with relative movement of the acoustic wave detection unit and the specimen during image acquisition of the specimen, the acoustic wave detection unit includes an acoustic wave collection optics that collects the acoustic wave, and a converter that converts the acoustic wave collected by the acoustic wave collection optics to an electric signal, the acoustic wave propagation body is attached to the acoustic wave collection optics, and a difference of refractive indexes between the acoustic wave collection optics and the acoustic wave propagation body is smaller than a difference of refractive indexes between the acoustic wave collection optics and air.
Furthermore, another aspect of the present invention is a photoacoustic imaging method including interposing, between a specimen and an acoustic wave detection unit, an acoustic wave propagation body including a bag-shaped body including a film that deforms in conformity with a surface shape, an interior of the bag-shaped body being filled with an acoustic wave propagation medium, without interposing any air layers, irradiating the specimen with excitation light from a light source while moving the light source, the acoustic wave detection unit and the acoustic wave propagation body relative to the specimen, detecting an acoustic wave generated at a position irradiated with the excitation light through the acoustic wave propagation body by the acoustic wave detection unit, and generating an image based on the detected acoustic wave, wherein the acoustic wave detection unit includes an acoustic wave collection optics that collects the acoustic wave, and a converter that converts the acoustic wave collected by the acoustic wave collection optics to an electric signal, the acoustic wave propagation body is attached to the acoustic wave collection optics, and a difference of refractive indexes between the acoustic wave collection optics and the acoustic wave propagation body is smaller than a difference of refractive indexes between the acoustic wave collection optics and air.
Hereinafter, description will be made as to a photoacoustic imaging device 1 and a photoacoustic imaging method according to an embodiment of the present invention with reference to the drawings.
The photoacoustic imaging device 1 according to the present embodiment comprises, as shown in
The stage 2 can move the mounted specimen X in a three-dimensional direction. That is, the stage 2 is moved upward and downward in a vertical direction relative to an objective lens 8 described later, so that a focal position of the objective lens 8 can be moved in a depth direction of the specimen X. Furthermore, the stage 2 is moved in a horizontal direction relative to the objective lens 8, so that a position to be irradiated with the laser light can be adjusted in the horizontal direction.
The excitation light irradiation unit 3 includes the objective lens 8 that condenses the pulsed laser light generated in the light source 7, in a region of interest of the specimen X. In the drawing, reference sign 3a denotes a condenser lens, numeral 9 denotes a mirror, numeral 10 denotes a pinhole, numeral 11 denotes a beam splitter, and numeral 12 denotes an eyepiece lens.
The acoustic wave detection unit 4 includes a branch element (an acoustic wave collection optics) 13 that branches the acoustic wave generated in the specimen X from an optical path of the laser light, and an acoustic wave transducer (a converter) 14 disposed in contact with an upper surface of the branch element 13. The acoustic wave transducer 14 outputs intensity of the detected acoustic wave as an electric signal. In the drawing, numeral 15 denotes an amplifier that amplifies the electric signal outputted from the acoustic wave transducer 14.
As shown in
An inclined surface of the triangular prism 16 and an inclined surface of the parallelogram prism 17 that are arranged adjacent to each other are separated by a liquid disposed between both the surfaces, that is, a nonvolatile liquid with a matched optical refractive index and a low acoustic impedance, such as a thin layer of low molecular weight silicone oil. This layer forms a branch surface 18.
An upper surface of the triangular prism 16 disposed facing and below the tip of objective lens 8 is disposed orthogonally to an optical axis of the objective lens 8.
Consequently, the laser light that exits from the objective lens 8, to enter the triangular prism 16 is transmitted by the branch surface 18 and is emitted from a lower surface of the parallelogram prism 17 to outside the branch element 13. In this case, the laser light is inhibited from being refracted in the upper surface of the triangular prism 16 and the branch surface 18, and the specimen X vertically below the objective lens 8 is straightly irradiated with the laser light emitted from the objective lens.
In the present embodiment, the laser light exits from the lower surface of the parallelogram prism 17, and the acoustic wave enters the lower surface. In this lower surface, a recess (an acoustic lens) 19 that collects the entering acoustic wave is provided. The acoustic wave that enters the branch element 13 from the lower surface of the parallelogram prism 17 is collected in the recess 19 to enter the parallelogram prism 17, reflected by the branch surface 18 and a facing surface parallel to the branch surface 18, in the parallelogram prism 17, and then exits from an upper surface of the parallelogram prism 17 adjacent to the facing surface to outside the branch element 13. On this upper surface, the acoustic wave transducer 14 is disposed, so that the acoustic wave can be detected.
The acoustic wave propagation body 5 is formed of a bag-shaped body 20 having a thin film, an interior of the bag-shaped body being filled with an acoustic wave propagation medium 21 having a refractive index equal to that of the branch element 13 and the bag-shaped body 20, such as water. The bag-shaped body 20 is made of a material that can transmit the laser light and acoustic wave, such as silicone rubber, and has properties of deforming in conformity with a shape of an object in contact, and coming into contact closely with the object without any gaps. Furthermore, the bag-shaped body 20 entirely including the film is illustrated, but the present invention is not limited to this example, and a bag-shaped body in which a part that is not in contact with the object is not a film, may be adopted.
The bag-shaped body 20 is filled with the acoustic wave propagation medium 21 without any air layers formed. The bag-shaped body 20 is attached to the lower surface of the parallelogram prism 17 that is an exit surface of the laser light and an entrance surface of the acoustic wave, and the acoustic wave propagation medium 21 is embedded in the recess 19. The acoustic wave propagation medium 21 having a refractive index equal to that of the parallelogram prism 17 is embedded in the recess 19, and hence, the recess does not have any condensing action to the laser light, and performs a lens function only to the acoustic wave.
The image processing unit 6 generates the image based on the signal amplified by the amplifier 15 and positional information of the stage 2.
Description will be made as to a photoacoustic imaging method in which the photoacoustic imaging device 1 according to the present embodiment including such a configuration as described above is used, with reference to the drawings.
To perform observation of the specimen X by use of the photoacoustic imaging device 1 according to the present embodiment, the specimen X, such as a mouse, is mounted on the stage 2, and as shown in
If the stage 2 is further raised in this state, as shown in
The branch element 13 and the acoustic wave propagation body 5 have an equal refractive index, and the laser light from the objective lens 8 enters the specimen in a direction orthogonal to the surface of the branch element 13. Therefore, the laser light travels straight without being refracted, and is focused in the specimen X.
The laser light that enters the specimen X generates the acoustic wave at the focal position of the objective lens 8. When a part of the generated acoustic wave that returns to an acoustic wave propagation body 5 side is transmitted by the acoustic wave propagation body 5 to enter the branch element 13, the part is collected by the recess 19. Then, the acoustic wave is reflected by the branch surface 18 and the facing surface in the parallelogram prism 17, and detected by the acoustic wave transducer 14 disposed in contact with the parallelogram prism 17 (step S3). The acoustic wave propagation body 5 is in close contact with the surface of the specimen X, and the interior of the bag-shaped body 20 of the acoustic wave propagation body 5 is filled with the acoustic wave propagation medium 21. Therefore, any air layers are not present between the specimen X and the acoustic wave transducer 14, and the acoustic wave can be detected while reducing attenuation of the acoustic wave.
The detected acoustic wave is amplified by the amplifier 15, and is then associated with the positional information of the stage 2, in the image processing unit 6 (step S4). Afterward, it is determined whether or not the acoustic wave is detected at all irradiated positions (step S5). In a case where the detection is not ended, the stage 2 is moved by a predetermined distance in the horizontal direction, to thereby change the irradiated position with the laser light in the horizontal direction (step S6). The steps are repeated from the step S2, so that an image indicating an intensity distribution of the acoustic wave can be generated in the image processing unit 6.
In this case, if the stage 2 is moved, the surface shape of the specimen X in contact with the acoustic wave propagation body 5 changes. However, the acoustic wave propagation body 5 deforms in conformity with the surface shape of the specimen X every time, and a close contact state of the propagation body with the surface of the specimen X is maintained. Consequently, even when the irradiated position with the laser light is changed, the acoustic wave can be detected while reducing the attenuation.
In particular, as shown in
Furthermore, according to the photoacoustic imaging device 1 of the present embodiment, differently from a conventional technology to move the objective lens 8 in a water tank, the acoustic wave propagation body 5 is attached to the acoustic wave detection unit 4. Therefore, it is not necessary to provide a large water tank that covers a relative movement range of the specimen X and the objective lens 8, and there is an advantage that the device can be reduced in size while securing a required imaging range.
Additionally, differently from the water tank in which water surface is formed, the acoustic wave propagation medium 21 is enclosed in the bag-shaped body 20. Consequently, there is also an advantage that generation of a disadvantage such as water scattering due to evaporation of water, mixing of dust and movement of the objective lens 8 can be prevented in advance.
Note that in the present embodiment, the branch element 13 is disposed between the objective lens 8 and the specimen X, and the acoustic wave propagation body 5 is attached to the branch element 13. Alternatively, as shown in
Furthermore, in the present embodiment, the acoustic wave propagation body 5 including the bag-shaped body 20 in which the acoustic wave propagation medium 21 is enclosed is attached to the acoustic wave detection unit 4. Alternatively, as shown in
Additionally, in the present embodiment, the stage 2 on which the specimen X is mounted is moved in a three-dimensional direction, to move the specimen X relative to the acoustic wave detection unit 4. Alternatively, the stage 2 may be fixed, and the acoustic wave detection unit 4 may be moved in a three-dimensional direction.
Water is illustrated as the acoustic wave propagation medium 21, but any other acoustic wave propagation medium 21 may be adopted.
The above-described embodiment also leads to the following aspects.
An aspect of the present invention is a photoacoustic imaging device including an excitation light irradiation unit that irradiates a specimen with excitation light, an acoustic wave detection unit that detects an acoustic wave generated at a position irradiated with the excitation light by the excitation light irradiation unit, an acoustic wave propagation body including a bag-shaped body including a film that deforms in conformity with a surface shape of the specimen, an interior of the bag-shaped body being filled with an acoustic wave propagation medium, and an image generation unit that generates an image based on the detected acoustic wave, wherein the acoustic wave propagation body is disposed between the acoustic wave detection unit and the specimen, without interposing any air layers, and moves relative to the specimen along with relative movement of the acoustic wave detection unit and the specimen during image acquisition of the specimen.
According to the present aspect, upon the irradiation of the specimen with pulsed excitation light, the acoustic wave is generated at the irradiated position of the specimen, and detected via the acoustic wave propagation body in close contact with the specimen and the acoustic wave detection unit, by the acoustic wave detection unit. In the image generation unit, it is possible to measure and arrange a series of amplitudes of the acoustic wave at positions of the specimen to generate an acoustic wave image of the specimen.
In this case, the acoustic wave propagation body moves relative to the specimens along with the relative movement of the acoustic wave detection unit and the specimen. Therefore, even though the acoustic wave propagation body is smaller than an imaging range, the film that forms the bag-shaped body is deformed in conformity with the surface shape of the specimen, at each position of a required imaging range, to fill a space between the acoustic wave detection unit and the specimen. An interposed air layer can therefore be eliminated and loss in acoustic wave can be suppressed. Consequently, the device can be reduced in size while securing the required imaging range, without preparing any large water tanks.
In the above aspect, the acoustic wave propagation body may be attached to the acoustic wave detection unit.
According to this configuration, it is assured that the acoustic wave propagation body can move relative to the specimen along with the relative movement of the acoustic wave detection unit and the specimen.
Furthermore, in the above aspect, the acoustic wave detection unit may include an acoustic wave collection optics that collects the acoustic wave, and a converter that converts the acoustic wave collected by the acoustic wave collection optics to an electric signal, and the acoustic wave propagation body may be attached to the acoustic wave collection optics.
According to this configuration, the acoustic wave generated in the specimen is collected through the acoustic wave propagation body by the acoustic wave collection optics, and converted to the electric signal by the converter.
Additionally, in the above aspect, the acoustic wave detection unit may include a converter that converts the acoustic wave to an electric signal, and the acoustic wave propagation body may be attached to the converter.
According to this configuration, the acoustic wave generated in the specimen directly enters the converter through the acoustic wave propagation body, and is converted to the electric signal in the converter.
Furthermore, another aspect of the present invention is a photoacoustic imaging method including interposing, between a specimen and an acoustic wave detection unit, an acoustic wave propagation body including a bag-shaped body including a film that deforms in conformity with a surface shape, an interior of the bag-shaped body being filled with an acoustic wave propagation medium, without interposing any air layers, irradiating the specimen with excitation light from a light source while moving the light source, the acoustic wave detection unit and the acoustic wave propagation body relative to the specimen, detecting an acoustic wave generated at a position irradiated with the excitation light through the acoustic wave propagation body by the acoustic wave detection unit, and generating an image based on the detected acoustic wave.
Number | Date | Country | |
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Parent | PCT/JP2018/035467 | Sep 2018 | US |
Child | 17207897 | US |