KR20210102794A - Photoacoustic Microscopy System Using Silicone Oil - Google Patents

Abstract

Disclosed is a photoacoustic microscope system using silicone oil. In accordance with one aspect of the present invention, the photoacoustic microscope system for generating a photoacoustic image of a sample by irradiating the sample applied with an acoustic impedance matching material with a laser of a near-infrared wavelength band, comprises: a light source unit for irradiating a laser in a near-infrared wavelength band; an ultrasonic transducer for receiving a photoacoustic signal emitted from a sample to convert the same into an electrical signal; an optical system for transmitting the laser irradiated from the light source unit to the sample, and transmitting the photoacoustic signal emitted from the sample to the ultrasonic transducer; and a control unit for controlling operations of the light source unit and the ultrasound transducer, and analyzing the electrical signal converted by the ultrasound transducer to generate a photoacoustic image of the sample.

Description

Photoacoustic Microscopy System Using Silicone Oil

This embodiment relates to an optoacoustic microscope system using silicone oil as a medium for photoacoustic signals.

The content described in this section merely provides background information for the present embodiment and does not constitute the prior art.

The photoacoustic tomography technique refers to an imaging technique of a method of receiving and imaging a photoacoustic signal generated in a living tissue by an optoacoustic effect with an ultrasound receiver. Here, the photoacoustic effect refers to an effect in which, when a high-power pulsed laser is irradiated to a living tissue, the living tissue absorbs light energy and thermally expands. The photoacoustic tomography technique can use the photoacoustic effect generated in living tissue as described above to examine whether a specific biological tissue exists in a sample including biological tissue or in the body of a subject without incision.

In order for the ultrasound receiver in the optoacoustic imaging system to effectively receive the optoacoustic signal, an acoustic impedance matching material is required. Generally, water is used as an acoustic impedance matching material. Water is the easiest to obtain, has excellent ultrasonic attenuation, and has similar acoustic impedance to living tissue, so that the photoacoustic signal is received by the ultrasonic receiver through the impedance matching material, thereby minimizing the loss due to reflection. In addition, water has been used as an acoustic impedance matching material in almost all optoacoustic systems because there is almost no light absorption at a generally used photoacoustic wavelength of 500 to 900 nm.

However, a specific material in a living tissue, for example, collagen or lipid, must be irradiated with light in a specific wavelength band (long wavelength band after 1200 nm) in order to output a photoacoustic signal. However, water absorbs excessively at long wavelengths after 1200 nm. Accordingly, when water is used as the acoustic impedance matching material, there is a problem in that when the pulse laser in the photoacoustic imaging system is irradiated with a normal intensity, it is impossible to obtain a photoacoustic signal with an intensity sufficient to image completely. In order to acquire an optoacoustic signal with an intensity sufficient to image completely, the intensity of the pulse laser must be increased. If the subject is a human, a pulse laser that is too strong may adversely affect the human body. There is a limit on the intensity of the laser to be irradiated with Accordingly, the conventional photoacoustic imaging system has a problem in that it is not possible to obtain a complete image with respect to a specific material. Therefore, in the related art, only a sample having a large light absorption in visible light can be used as a test object, so the conventional photoacoustic imaging system has a very limited range of use.

In one embodiment of the present invention, by using silicone oil as an acoustic impedance matching material, a high-power laser is delivered to a specific biological tissue by minimizing the loss, and at the same time, the loss is minimized to receive a photoacoustic signal generated in a specific biological tissue. An object of the present invention is to provide an optoacoustic microscope system capable of acquiring an optoacoustic image of a tissue.

According to one aspect of this embodiment, in the photoacoustic microscope system for generating a photoacoustic image of the sample by irradiating a laser of a near-infrared wavelength band to a sample coated with an acoustic impedance matching material, a light source unit irradiating a laser of a near-infrared wavelength band; An ultrasonic transducer that receives the photoacoustic signal emitted from the sample and converts it into an electrical signal, and an optical system that delivers the laser irradiated from the light source to the sample, and transmits the photoacoustic signal emitted from the sample to the ultrasonic transducer and a control unit that controls operations of the light source unit and the ultrasound transducer, and generates a photoacoustic image of the sample by analyzing the electrical signal converted by the ultrasound transducer. .

According to one aspect of this embodiment, the optical system is characterized in that a part or all of it is disposed in contact with the acoustic impedance matching material.

According to one aspect of this embodiment, the acoustic impedance matching material is characterized in that silicone oil.

According to one aspect of this embodiment, in the photoacoustic microscope system for generating a photoacoustic image of the sample by irradiating a laser of a near-infrared wavelength band to a sample coated with an acoustic impedance matching material, the laser of the near-infrared wavelength band is irradiated to the sample a light source unit that receives the photoacoustic signal emitted from the sample and an ultrasonic transducer that converts it into an electrical signal, controls the operation of the light source unit and the ultrasonic transducer, and analyzes the electrical signal converted by the ultrasonic transducer to analyze the sample It provides a photoacoustic microscope system, characterized in that it comprises a control unit for generating a photoacoustic image of.

According to an aspect of this embodiment, the ultrasonic transducer is characterized in that a part or all of it is disposed in contact with the acoustic impedance matching material.

According to one aspect of this embodiment, the acoustic impedance matching material is characterized in that silicone oil.

As described above, according to one aspect of this embodiment, by using silicone oil as an acoustic impedance matching material, a high-power laser is delivered to a specific biological tissue by minimizing the loss, and the photoacoustic generated in a specific biological tissue is minimized at the same time. There is an advantage in that a photoacoustic image of a living tissue can be obtained by receiving a signal.

1 is a graph showing the light absorption (transmission length 10mm) according to the wavelength band of water and silicone oil.
2 is a diagram illustrating the configuration of a photoacoustic microscope system according to an embodiment of the present invention.
3 is a diagram schematically illustrating the intensity of a laser pulse or photoacoustic signal irradiated to living tissue when water and silicone oil are used as acoustic impedance matching materials.
4 to 7 are views illustrating photoacoustic microscope systems according to first to fourth embodiments of the present invention.

Since the present invention can have various changes and can have various embodiments, specific embodiments are illustrated in the drawings and described in detail. However, this is not intended to limit the present invention to specific embodiments, and it should be understood to include all modifications, equivalents and substitutes included in the spirit and scope of the present invention. In describing each figure, like reference numerals have been used for like elements.

Terms such as first, second, A, and B may be used to describe various elements, but the elements should not be limited by the terms. The above terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, a first component may be referred to as a second component, and similarly, a second component may also be referred to as a first component. and/or includes a combination of a plurality of related listed items or any of a plurality of related listed items.

When a component is referred to as being “connected” or “connected” to another component, it is understood that the other component may be directly connected or connected to the other component, but other components may exist in between. it should be On the other hand, when it is said that a certain element is "directly connected" or "directly connected" to another element, it should be understood that no other element is present in the middle.

The terms used in the present application are only used to describe specific embodiments, and are not intended to limit the present invention. The singular expression includes the plural expression unless the context clearly dictates otherwise. It should be understood that terms such as “comprise” or “have” in the present application do not preclude the possibility of addition or existence of features, numbers, steps, operations, components, parts, or combinations thereof described in the specification in advance. .

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related art, and should not be interpreted in an ideal or excessively formal meaning unless explicitly defined in the present application. does not

In addition, each configuration, process, process or method included in each embodiment of the present invention may be shared within a range that does not technically contradict each other.

1 is a graph showing the light absorption (transmission length 10mm) according to the wavelength band of water and silicone oil.

It can be seen that water has a fairly low light absorption in the visible light wavelength band (380 to 750 nm), whereas in the near-infrared wavelength band, especially, in the near-infrared wavelength band (λ ₁ ) of 1200 to 1700 nm, the transmittance length of water is 1.5 level based on 10 mm. Absorbance is shown, where the y-axis light absorbance is on a log scale, showing transmittance of about 3%. Accordingly, if a biological tissue that absorbs light in the wavelength band of visible light, thermally expands, and emits a photoacoustic signal is an object to be tested, water is suitable as an acoustic impedance matching material. On the other hand, if a biological tissue that absorbs light in the near-infrared wavelength band, thermally expands, and emits a photoacoustic signal is an object to be tested, water is not suitable as an acoustic impedance matching material. If water is used as an acoustic impedance matching material for the above-mentioned examination of living tissue, most of the light irradiated to the living tissue is absorbed by the water. Accordingly, a sufficient amount of light to thermally expand the living tissue is not irradiated to the living tissue, so that a sufficient amount of photoacoustic signal is not emitted from the living tissue.

On the other hand, silicone oil shows a fairly high absorption rate in a specific wavelength band, whereas a very low light absorption rate in the _{near-infrared wavelength band (λ 1 ).} Therefore, silicone oil absorbs light in the near-infrared wavelength band (λ ₁ ) and contracts by thermal expansion. is suitable as an acoustic impedance matching material.

On the other hand, even if light is completely irradiated to the living tissue, if most of the photoacoustic signal generated in the living tissue is absorbed by the acoustic impedance matching material, the photoacoustic microscope system cannot completely generate an image of the living tissue. Silicone oil is somewhat larger than water, but has a relatively low level of ultrasonic attenuation. Accordingly, silicone oil is suitable as an acoustic impedance matching material used for image generation of the first living tissue.

2 is a diagram illustrating the configuration of a photoacoustic microscope system according to an embodiment of the present invention.

Referring to FIG. 2 , the photoacoustic microscope system 200 according to an embodiment of the present invention includes a light source unit 210 , an optical system 220 , a control unit 230 , and an ultrasonic transducer 240 . However, according to an embodiment, the photoacoustic microscope system 200 may include only the components other than the optical system 220 .

The photoacoustic microscope system 200 is a system for generating a photoacoustic image of a living tissue using a photoacoustic signal generated from a living tissue, and uses a method different from the conventional method using a fluorescent material that can be confirmed with the naked eye. Inspect (confirm). However, since it is only necessary to irradiate a laser pulse to thermally expand the living tissue, there is no inconvenience such as administering a fluorescent material to the patient or the patient having to take the fluorescent material.

In addition, the photoacoustic microscope system 200 uses, as an acoustic impedance matching material, silicon oil having a significantly low light absorption rate of light in a near-infrared wavelength band and a photoacoustic signal. Accordingly, the photoacoustic microscope system 200 may completely generate a photoacoustic image of the first biological tissue. For example, the first living tissue includes lipids or collagen. Since the photoacoustic microscope system 200 uses silicone oil, it is possible to induce a photoacoustic signal of sufficient intensity even without irradiating a laser pulse to a living tissue with an excessive intensity. 3 shows the results when water in the near-infrared wavelength band is irradiated to living tissue and when water is used as an acoustic impedance matching material and when silicone oil is used.

3 is a diagram schematically illustrating the intensity of a laser pulse or photoacoustic signal irradiated to a living tissue when water and silicone oil are used as acoustic impedance matching materials.

3(a) is a view showing a case in which silicone oil is used as an acoustic impedance matching material. _{When the laser (λ n} ) for thermally expanding the first biological tissue 320 is incident into the silicone oil 310 , absorption in the silicone oil 310 is minimized and most of the lasers are applied to the first biological tissue 320 . ) is investigated. Thereafter, the first living tissue 320 thermally expands and contracts and outputs a photoacoustic signal, and the photoacoustic signal is also emitted to the ultrasonic transducer 240 with minimal attenuation even through silicone oil. Although the photoacoustic signal is emitted in all directions, since a sufficient amount (intensity) of the photoacoustic signal is emitted from the first living tissue 320, a sufficient amount (intensity) to generate a photoacoustic image of the first living tissue 320 is The photoacoustic signal is transmitted to the ultrasonic transducer 240 .

On the other hand, FIG. 3B is a diagram illustrating a case in which water 330 is used as an acoustic impedance matching material. Since most of the laser (λ _n ) is absorbed from the water 330 when irradiated to the first living tissue 320 , only a very small amount of the laser is irradiated to the first living tissue 320 . Accordingly, an insufficient amount (intensity) of the photoacoustic signal is emitted from the first living tissue 320 . In particular, since the photoacoustic signal is irradiated in all directions, a smaller amount (intensity) of the photoacoustic signal is transmitted to the ultrasonic transducer 240 . Accordingly, when water is used as the acoustic impedance matching material, it is difficult for the photoacoustic microscope system to generate a photoacoustic image of the first biological tissue.

Referring back to FIG. 1 , the acoustic impedance matching material in the photoacoustic microscope system 200 satisfies the following equation.

Here, α _s is the ultrasonic attenuation value, ν is the kinematic viscosity of the acoustic impedance matching material, η _B is the bulk viscosity of the acoustic impedance matching material, ρ is the density, and c is the sound wave velocity. means Referring to the above equation, when high-frequency ultrasonic waves are provided, as the kinematic viscosity of the silicone oil increases, the ultrasonic attenuation decreases.

More specifically, when the kinematic viscosity is 1 cSt, the photoacoustic (ultrasound) signal is reduced to 1/10 or less. It is confirmed that when the kinematic viscosity is 500 cSt, the photoacoustic (ultrasound) signal is reduced by about 1/3, and when the kinematic viscosity is 1000 to 3000 cSt, the photoacoustic (ultrasound) signal is reduced by about 1/2. On the other hand, when the kinematic viscosity is 3000 cSt or more, bubbles in the silicone oil are generated. If the silicone oil has a kinematic viscosity of 500 cSt or less, the attenuation of the photoacoustic (ultrasonic) signal is too much, which is not suitable. Therefore, it is preferable that the silicone oil to be used as the acoustic impedance matching material in the photoacoustic microscope system 200 has a kinematic viscosity of 500 to 3000 cSt.

The light source unit 210 irradiates a laser for thermally expanding the first living tissue 320 to the optical system 220 . The light source unit 210 irradiates a laser to the optical system 220 so that the first living tissue 320 thermally expands to output a photoacoustic signal. The laser irradiated to the optical system 220 passes through the optical system 220 and 1 It is irradiated with the living tissue 320 . The light source unit 210 may irradiate a pulse laser having an output of a predetermined intensity or less to the optical system 220 .

The optical system 220 transmits the laser irradiated from the light source unit 210 to the first living tissue 320 and the photoacoustic signal emitted from the first living tissue 320 to the ultrasonic transducer 240 . The optical system 220 includes various optical configurations, and transmits the laser irradiated from the light source unit 210 to the first biological tissue 320 , and simultaneously transmits the photoacoustic signal emitted from the first biological tissue 320 to an ultrasonic transducer. forward to (240). A more detailed configuration will be described later with reference to FIGS. 4 to 7 .

The controller 230 controls the operation of each component in the photoacoustic microscope system 200 , and analyzes the photoacoustic signal received by the ultrasonic transducer 240 to generate a photoacoustic image of the first living tissue 320 . do.

The ultrasonic transducer 240 receives the photoacoustic signal emitted from the first living tissue 320 and converts it into an electrical signal. The ultrasonic transducer 240 converts the photoacoustic signal emitted from the first living tissue 320 into an electrical signal so that the controller 230 can recognize it, and then provides the converted photoacoustic signal to the controller 230 . The controller 230 receives the electrical signal provided by the ultrasound transducer 240 to generate a photoacoustic image of the first biological tissue 320 .

4 is a view showing a photoacoustic microscope system according to a first embodiment of the present invention.

The light source unit 210 irradiates a laser to the optical system 220 .

The optical system 220 includes a mirror unit 410 , a combiner 420 , and a lens 430 .

The mirror unit 410 in the optical system 220 reflects the laser irradiated from the optical system 220 to the combiner 420 .

The combiner 420 reflects the laser reflected from the mirror unit 410 in the direction of the first biological tissue 320 , while the photoacoustic (ultrasonic) signal emitted from the first biological tissue 320 is transmitted by an ultrasonic transducer. (240). The combiner 420 may be implemented as a beam splitter, or may be implemented with a pair of prisms coated with a thin metal thin film coupled thereto.

The lens 430 focuses the laser reflected from the combiner 420 to the first biological tissue 320 , and concentrates the photoacoustic signal emitted from the first biological tissue 320 to the ultrasonic transducer 240 . transmit

Some components in the optical system 220 are in contact with the silicone oil 310, so that the laser emitted from it passes through the silicone oil 310 and is delivered to the first living tissue 320 with minimal attenuation, and the first living body In close proximity to the tissue 320 , the photoacoustic signal emitted from the first living tissue 320 is received as much as possible.

The ultrasonic transducer 240 receives the photoacoustic signal transmitted through the optical system 220 . At this time, the ultrasonic transducer 240 has an optical axis through which the laser irradiated from the light source unit 210 passes through the optical system 220 and is irradiated to the first biological tissue 320 (in FIG. 4 , the y-axis vertically upward of the first biological tissue) ) on the same optical axis. This is because, when the laser irradiated to the first living tissue and the ultrasonic transducer 240 for receiving the photoacoustic signal are disposed on the same optical axis, the best signal-to-noise ratio (SNR) can be secured. Accordingly, since the laser is reflected from the combiner 420 and irradiated to the first living tissue 320 , the ultrasonic transducer 240 is the optical system 220 on the axis in the direction in which the laser is reflected from the combiner 420 . ) is placed in contact with

The ultrasonic transducer 240 is acoustically implemented with characteristics similar to the optical system 220 , in particular, the combiner 420 . Acoustic properties include, for example, hardness. As the acoustic characteristics of the ultrasound transducer 240 and the combiner 420 are similar, the photoacoustic signal emitted from the first living tissue 320 is incident on the ultrasound transducer 240 with minimal loss. .

As it has such an optical structure, the laser is irradiated from the light source unit 210 through the silicone oil 320 to the first biological tissue 320 , and the photoacoustic signal emitted from the first biological tissue 320 is ultrasonic waves. transmitted to the transducer 240 .

5 is a diagram illustrating a photoacoustic microscope system according to a second embodiment of the present invention.

In the photoacoustic microscope system 200 according to the second embodiment of the present invention, the light source unit 210 is disposed on the vertical upper end (+y-axis) of the ultrasonic transducer 240 , avoiding the ultrasonic transducer 240 y The laser is irradiated with a certain angle from the axis. The light source unit 210 may include a plurality of light sources therein, and may irradiate a plurality of lasers at different angles at the same time, or may alternately radiate lasers at different angles. The case may vary depending on the intensity of the laser to be output to the first living tissue 320 .

The optical system 220 includes a reflector 510 . The reflector 510 reflects the laser irradiated from the light source 210 to the first biological tissue 320 without interfering with the path of the ultrasonic transducer 240 . In order to reflect all of the lasers reflected at various angles from the light source unit 210 to the first living tissue 320 , respectively, the reflection unit 510 is disposed in all directions irradiated from the light source unit 210 , or an upper surface and a bottom surface, respectively. With this removed truncated cone shape, it can be disposed in all directions.

After the laser is irradiated to the first living tissue 320 , the photoacoustic signal emitted from the first living tissue 320 is directly incident to the ultrasonic transducer 240 without passing through a separate component.

Even in the photoacoustic microscope system 200 according to the second embodiment, the ultrasonic transducer 240 is positioned on the same axis as the laser irradiated from the light source unit 210 to improve the signal-to-noise ratio of the photoacoustic signal.

6 is a view showing a photoacoustic microscope system according to a third embodiment of the present invention.

The optical system 220 in the photoacoustic microscope system 200 according to the third embodiment of the present invention also includes a reflector 410 , a combiner 420 and a lens 430 like that according to the first embodiment. do. However, the optical system 220 and the ultrasonic transducer 240 in the photoacoustic microscope system 200 according to the third embodiment of the present invention are disposed in the silicone oil 310 .

The laser irradiated from the light source unit 210 is reflected by the combiner 420 , through the lens 430 , is reflected from the reflection unit 410 to the first living tissue 320 . Meanwhile, the photoacoustic signal emitted from the first living tissue 320 is reflected by the reflector 410 and is received by the ultrasonic transducer 240 through the lens 430 and the combiner 420 .

7 is a view showing a photoacoustic microscope system according to a fourth embodiment of the present invention.

The optoacoustic microscope system 200 according to the fourth embodiment of the present invention does not include the optical system 220 separately from the optoacoustic microscope system according to the first to third embodiments. Instead, the photoacoustic microscopy system 200 includes an annular ultrasonic transducer 240 having a hollow. The light source unit 210 irradiates the laser directly to the first living tissue 320 through the hollow of the ultrasonic transducer, and the photoacoustic signal emitted from the first living tissue is directly received by the ultrasonic transducer 240 .

The photoacoustic microscope system 200 does not include a separate optical system 220, so there is an advantage in scale and cost, and the laser or photoacoustic signal does not go through a separate optical configuration, so the loss of light or signal can be minimized. have. In addition, since the ultrasonic transducer 240 may be disposed on the same axis as the laser, the signal-to-noise ratio of the photoacoustic signal may be improved.

The above description is merely illustrative of the technical idea of this embodiment, and various modifications and variations will be possible by those skilled in the art to which this embodiment belongs without departing from the essential characteristics of the present embodiment. Accordingly, the present embodiments are intended to explain rather than limit the technical spirit of the present embodiment, and the scope of the technical spirit of the present embodiment is not limited by these embodiments. The protection scope of this embodiment should be interpreted by the following claims, and all technical ideas within the equivalent range should be interpreted as being included in the scope of the present embodiment.

200: optoacoustic antenna system
210: light source unit
220: optical system
230: control unit
240: ultrasonic transducer
310: silicone oil
320: living tissue
330: water
410, 510: reflector
420: combiner
430: lens

Claims (6)

In the photoacoustic microscope system for generating a photoacoustic image of the sample by irradiating a laser of a near-infrared wavelength band to a sample coated with an acoustic impedance matching material,
a light source unit irradiating a laser of a near-infrared wavelength band;
an ultrasonic transducer that receives the photoacoustic signal emitted from the sample and converts it into an electrical signal;
an optical system that transmits the laser irradiated from the light source to the sample and transmits the photoacoustic signal emitted from the sample to the ultrasonic transducer; and
A control unit that controls operations of the light source unit and the ultrasound transducer, and generates a photoacoustic image of the sample by analyzing an electrical signal converted by the ultrasound transducer
A photoacoustic microscope system comprising a. According to claim 1,
The optical system is
Part or all of the photoacoustic microscope system, characterized in that disposed in contact with the acoustic impedance matching material. According to claim 1,
The acoustic impedance matching material,
A photoacoustic microscope system, characterized in that it is silicone oil. In the photoacoustic microscope system for generating a photoacoustic image of the sample by irradiating a laser of a near-infrared wavelength band to a sample coated with an acoustic impedance matching material,
a light source unit irradiating a laser of a near-infrared wavelength band to the sample;
an ultrasonic transducer that receives the photoacoustic signal emitted from the sample and converts it into an electrical signal;
A control unit that controls operations of the light source unit and the ultrasound transducer, and generates a photoacoustic image of the sample by analyzing the electrical signal converted by the ultrasound transducer
A photoacoustic microscope system comprising a. 5. The method of claim 4,
The ultrasonic transducer is
Part or all of the photoacoustic microscope system, characterized in that disposed in contact with the acoustic impedance matching material. 5. The method of claim 4,
The acoustic impedance matching material,
A photoacoustic microscope system, characterized in that it is silicone oil.

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