CN110426373B - In-situ detection method for Brillouin scattering and optical coherence elastography - Google Patents

In-situ detection method for Brillouin scattering and optical coherence elastography Download PDF

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CN110426373B
CN110426373B CN201910638803.2A CN201910638803A CN110426373B CN 110426373 B CN110426373 B CN 110426373B CN 201910638803 A CN201910638803 A CN 201910638803A CN 110426373 B CN110426373 B CN 110426373B
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张余宝
朱羿叡
刘严欢
谢成峰
史久林
何兴道
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Nanchang Hangkong University
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Abstract

The invention provides a method for in-situ detection of Brillouin scattering and optical coherence elastography, which integrates a Brillouin scattering elastography system and an optical coherence elastography system by adopting a wavelength division multiplexing and confocal optical path method, and then can realize imaging detection without mutual influence of the two detection systems through a time sequence control system of a computer, thereby completing in-situ detection of two elastic moduli of a sample body elastic modulus and a shear elastic modulus without moving the position of the sample. The invention has the advantages that: the comparative study of the two elastic moduli can provide technical support for diagnosis and early prevention of a plurality of diseases clinically. The method has important significance and value for diagnosing, treating and preventing various diseases clinically at present, particularly various ophthalmic diseases.

Description

In-situ detection method for Brillouin scattering and optical coherence elastography
Technical Field
The invention relates to an imaging detection method for elastic modulus of biological tissue, in particular to a method capable of realizing in-situ detection of Brillouin scattering and optical coherence elastography.
Background
At present, Brillouin scattering elastography and optical coherence elastography are the latest means for detecting the elastic property of biological tissues, the physical principles of the Brillouin scattering elastography and the optical coherence elastography are different, and the bulk elastic modulus and the shear elastic modulus of the biological tissues can be respectively obtained, so that the Brillouin scattering elastography and the optical coherence elastography have important significance for diagnosis and treatment of some clinical diseases, especially ophthalmic diseases (myopia, keratoconus and the like). However, some technical limitations still exist in the current research on brillouin scattering elastography and optical coherence elastography.
At present, in clinical, some chronic diseases, especially the diseases such as myopia, presbyopia or cataract of ophthalmology, the disease can not be directly judged in the early stage, and the elasticity detection mode can be used for detecting whether the property of the tissue is pathologically changed or not from the biomechanical angle, so the elasticity detection means is needed to obtain the elasticity property of the tissue, but other technical means can not achieve the high precision of the optical means, and the optical means is a nondestructive means. The reason for comparison is that the shear elastic modulus and the bulk elastic modulus are the typical physical quantities which we believe the sample to characterize the elastic property, but because the magnitudes of the two elastic moduli are usually very different, and the comparison cannot be made by using the same system, our patent can realize the problem, which has the advantage that how the elasticity of the tissue changes can be analyzed from the two moduli, or it can be determined that the two elastic moduli are more suitable for clinical detection of the elastic property of the biological tissue, and at present, there is no technical means for simultaneously realizing the detection of the two elastic moduli, and the comparison research of the two elastic moduli cannot be performed.
Disclosure of Invention
The invention aims to provide a method for realizing in-situ detection of Brillouin scattering and optical coherence elastography. Since the pathogenesis of many clinical diseases and the change of the biomechanical properties of the clinical diseases are related at present, a plurality of elastic modulus detection methods are in research, wherein the brillouin scattering elastography technology can detect the bulk elastic modulus of biological tissues, the optical coherence elastography technology can detect the shear elastic modulus of the biological tissues, and the two methods are the most possible technical means for realizing the detection of the elastic modulus of the biological tissues at present. However, because the physical mechanisms of the body elastic modulus and the shear elastic modulus are different in the two technical means, no technical means can realize the common detection and the comparative study of the two elastic moduli at present, mainly because the body elastic modulus and the shear elastic modulus respectively measured by the brillouin scattering elastography and the optical coherence elastography have different elastic modulus magnitudes, and the body modulus is at the Gpa magnitude and the shear modulus is at the kpa magnitude.
The invention realizes the integration of different signal channels of two optical systems by adopting the combination of wavelength division multiplexing and optical path confocal integration, can realize the integration of a Brillouin scattering elastography system and an optical coherence elastography system, and further realizes the in-situ detection and contrast research of the detection body elastic modulus and the shearing elastic modulus. Then, the in-situ asynchronous detection of the two optical systems is realized by a computer time sequence control algorithm.
The invention relates to a method for realizing in-situ detection of Brillouin scattering and optical coherence elastography, which comprises a broadband light source SLD1, an optical isolator 2, an optical coupler 3, a first collimating mirror 4, an optical attenuator 5, a first focusing lens 6, a reflecting mirror 7, a wavelength division multiplexer 8, an optical collimator 9, a scanning galvanometer 10, a focusing objective 11, an annular ultrasonic transducer 12, a second collimating mirror 13, a second focusing lens 14, a diffraction grating 15, a third focusing lens 16, a COMES camera 17, a computer 18, a narrow-linewidth laser 19, an optical circulator 20, a third collimating mirror 21, a first cylindrical mirror 22, a first virtual array spectrometer VIPA23, a second cylindrical mirror 24, a first rectangular diaphragm 25, a fourth focusing lens 26, a second virtual phased array spectrometer VIPA27, a fifth focusing lens 28, a second rectangular diaphragm 29, a sixth focusing lens 30, a seventh focusing lens 31 and an EMCCD 32.
The method of the invention comprises the following specific processes:
(1) the subsystem is as follows: acoustic radiation force optical coherence elastography
The core principle of the system is that shear waves are excited on the surface of biological tissues by ultrasonic excitation generated by an ultrasonic transducer, then the speed of the shear waves transmitted on the surface of a sample is obtained by an optical coherent elastography technology, and the shear modulus and Young modulus of the sample are calculated according to the corresponding relation between the wave speed of the shear waves and the shear modulus of the tissues, and can be calculated by the following formula:
Figure BDA0002131172990000031
where E is the shear modulus, ρ is the sample density, VSIs the shear wave velocity. The specific process of the system is as follows:
1. the broadband light source SLD (1) emits broadband near infrared light with the central wavelength of 850nm, the broadband near infrared light passes through an optical isolator with the central wavelength of 850nm and an optical coupler with the central wavelength of 850nm and is divided into two beams of light with the phase power ratio of 90:10, wherein a reference beam with the power of 10% passes through a first collimating mirror with the central wavelength of 850nm, an optical attenuator and a first focusing lens to enter a reflector, and the reference beam returns to the coupler according to the original path after being reflected by the reflector;
2. another beam of sample light with 90% of power is emitted from the coupler and passes through the wavelength division multiplexer, the optical collimator, the scanning galvanometer and the focusing objective lens, the annular ultrasonic transducer is incident to the sample, the scanning galvanometer is controlled by a driving program of a computer to carry out three-dimensional scanning on the sample, the annular ultrasonic transducer is controlled by the driving program of the computer to generate MHz ultrasonic excitation, elastic waves are generated on the surface of the sample, and then after the sample light and the sample tissue act, the back scattering light of the sample light is focused by the focusing objective lens and returns to the optical coupler along the original path to interfere with the reference light; an interference light signal after the interference of the sample light and the reference light is emitted from the other channel of the optical coupler, passes through the second collimating mirror and the second focusing lens and is focused on the diffraction grating, the interference light is split by the diffraction grating and is focused on the COMES camera by the third focusing lens, the COMES camera is controlled by a computer driving program to collect and process the interference signal, and the detection function of the optical coherent elastography system can be completed at the moment;
(2) and a second subsystem: brillouin scattering elastography
The core principle of the system is that the Brillouin scattering is excited in a sample by laser to generate an acousto-optic effect, the Brillouin frequency shift of the sample is obtained by scanning an F-P interferometer and a photon receiver to further obtain the sound velocity, and the bulk elastic modulus of the sample is calculated by the sound velocity. Can be calculated from the following formula:
Figure BDA0002131172990000041
where K is the shear modulus, ρ is the sample density, VcIs the phonon velocity.
The specific process of the system is as follows:
3. then, a narrow-linewidth laser emits continuous laser with the wavelength of 532nm, the continuous laser passes through an optical circulator, a wavelength division multiplexer, a collimator, a scanning galvanometer, a focusing objective lens and an annular ultrasonic transducer and is focused to a sample, the scanning galvanometer and the annular ultrasonic transducer are controlled by a computer to stop scanning and ultrasonic excitation operation, and a backward Brillouin scattering signal of the sample is focused by the focusing objective lens and returns along an original optical path;
4. the light is emitted from the outlet of the optical circulator, passes through the third collimating lens and the first cylindrical lens, enters the first virtual phased array spectrometer VIPA, passes through the second cylindrical lens and the first rectangular diaphragm, enters the fourth focusing lens to be focused on the second virtual phased array spectrometer VIPA, passes through the frequency selection of the two spectrometers, is focused on the second rectangular diaphragm by the fifth focusing lens, is changed into parallel light by the sixth focusing lens, is focused on the EMCCD by the seventh focusing lens, and is driven and controlled by the computer to collect and process Brillouin scattering spectra by the EMCCD.
Furthermore, the optical paths of the subsystems are all connected by optical fibers, and the focusing lens II, the diffraction grating 15, the focusing lens III 16 and the COMES camera 17 form a grating spectrometer packaging module.
Furthermore, the wavelength division multiplexer, the optical collimator, the narrow linewidth laser, the optical circulator and the collimating mirror are all connected by optical fibers to form a signal excitation light path of the Brillouin scattering elastic imaging system.
The invention has the advantages that: 1. as a biological tissue elastic modulus imaging detection system device, signal optical paths of two different optical systems of Brillouin scattering elastography and optical coherence elastography are integrated mainly in a wavelength division multiplexing and optical path confocal integration mode, and in-situ detection of the two different detection systems is realized through a computer time sequence control system.
2. The Brillouin scattering elastography and optical coherence elastography signal optical paths are integrated, so that in-situ detection of two detection methods can be realized, and the influence of environmental factors in the sample moving process on a test detection result is reduced.
3. The Brillouin scattering elastography and the optical coherence elastography signal optical path are integrated, the in-situ detection of the bulk elastic modulus and the shear elastic modulus can be realized, the influence of other factors on an experimental result in the sample moving process can be effectively avoided, the in-situ detection of two detection modes can be carried out without mutual influence, and the influence of the inherent difference (the property of different sampling points may have difference) of the sample on the experimental result is reduced.
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Fig. 1 is a schematic diagram of the present invention.
FIG. 1 shows: the system comprises a broadband light source SLD1, an optical isolator 2, an optical coupler 3, a first collimating mirror 4, an optical attenuator 5, a first focusing lens 6, a reflecting mirror 7, a wavelength division multiplexer 8, an optical collimator 9, a scanning galvanometer 10, a focusing objective 11, an annular ultrasonic transducer 12, a second collimating mirror 13, a second focusing lens 14, a diffraction grating 15, a third focusing lens 16, a COMES camera 17, a computer 18, a narrow-line-width laser 19, an optical circulator 20, a third collimating mirror 21, a cylindrical mirror 22, a virtual phased array spectrometer VIPA23, a cylindrical mirror 24, a rectangular diaphragm 25, a fourth focusing lens 26, a virtual phased array spectrometer VIPA27, a fifth focusing lens 28, a rectangular diaphragm 29, a sixth focusing lens 30, a seventh focusing lens 31 and an EMCCD 32.
Detailed Description
The invention relates to a method for realizing in-situ detection of Brillouin scattering and optical coherence elastography, which is characterized in that a wavelength division multiplexing and optical path confocal integration method is adopted to integrate two systems of Brillouin scattering elastography and optical coherence elastography together, so that in-situ detection and contrast research of bulk elastic modulus and shear elastic modulus can be realized.
The invention relates to a method capable of realizing in-situ detection of Brillouin scattering and optical coherence elastography, which is characterized by adopting a method of a broadband light source SLD1, an optical isolator 2, an optical coupler 3, a first collimating mirror 4, an optical attenuator 5, a first focusing lens 6, a reflecting mirror 7, a wavelength division multiplexer 8, an optical collimator 9, a scanning galvanometer 10, a focusing objective 11, an annular ultrasonic transducer 12, a second collimating mirror 13, a second focusing lens 14, a diffraction grating 15, a third focusing lens 16, a COMES camera 17, a computer 18, a narrow-line-width laser 19, an optical circulator 20, a third collimating mirror 21, a cylindrical mirror 22, a virtual phased array spectrometer VIPA23, a cylindrical mirror 24, a rectangular diaphragm 25, a fourth focusing lens 26, a virtual array spectrometer VIPA27, a fifth focusing lens 28, a rectangular diaphragm 29, a sixth focusing lens 30, a seventh focusing lens 31 and an EMCCD 32.
(1) The subsystem is as follows: acoustic radiation force optical coherence elastography
The core principle of the system is that shear waves are excited on the surface of biological tissues by ultrasonic excitation generated by an ultrasonic transducer, then the speed of the shear waves transmitted on the surface of a sample is obtained by an optical coherent elastography technology, and the shear modulus and Young modulus of the sample are calculated according to the corresponding relation between the wave speed of the shear waves and the shear modulus of the tissues, and can be calculated by the following formula:
Figure BDA0002131172990000061
where E is the shear modulus, ρ is the sample density, VSIs the shear wave velocity. The specific process of the system is as follows:
1. the broadband light source SLD1 emits broadband near infrared light with the central wavelength of 850nm, the broadband near infrared light passes through an optical isolator 2 with the central wavelength of 850nm and an optical coupler 3 with the central wavelength of 850nm and is divided into two beams of light with the phase power ratio of 90:10, wherein a reference beam with the power of 10% passes through a collimating mirror 4 with the central wavelength of 850nm, an optical attenuator 5 and a focusing lens 6 and is incident to a reflecting mirror 7, and the reference beam returns to the coupler in the original path after being reflected by the reflecting mirror 7;
2. another beam of sample light with 90% of power is emitted from the coupler, passes through the wavelength division multiplexer 8, the optical collimator 9, the scanning galvanometer 10, the focusing objective 11 and the annular ultrasonic transducer 12 and enters the sample, the scanning galvanometer 10 is controlled by a driving program of the computer 18 to carry out three-dimensional scanning on the sample, the annular ultrasonic transducer 12 is controlled by the driving program of the computer 18 to generate MHz ultrasonic excitation, elastic waves are generated on the surface of the sample, and after the sample light and the sample tissue act, the back scattering light of the sample light is focused by the focusing objective 11 and returns to the optical coupler 3 along the original path to interfere with the reference light; interference light signals after interference of the sample light and the reference light are emitted from the other channel of the optical coupler 3, and are focused to the diffraction grating 15 through the second collimating mirror 13 and the second focusing lens 14, the interference light is split through the diffraction grating 15 and is focused to the COMES camera 17 through the third focusing lens 16, the COMES camera 17 is controlled by a computer 18 driving program to collect and process the interference signals, and the detection function of the optical coherence elastography system can be completed at the moment;
(2) and a second subsystem: brillouin scattering elastography
The core principle of the system is that the Brillouin scattering is excited in a sample by laser to generate an acousto-optic effect, the Brillouin frequency shift of the sample is obtained by scanning an F-P interferometer and a photon receiver to further obtain the sound velocity, and the bulk elastic modulus of the sample is calculated by the sound velocity. Can be calculated from the following formula:
Figure BDA0002131172990000071
where K is the shear modulus, ρ is the sample density, VcIs the phonon velocity.
The specific process of the system is as follows:
3. then, a narrow-line-width laser 19 emits continuous laser with the wavelength of 532nm, the continuous laser is focused to a sample through an optical circulator 20, a wavelength division multiplexer 8, a collimator, a scanning galvanometer 10, a focusing objective lens 11 and an annular ultrasonic transducer 12, the scanning galvanometer 10 and the annular ultrasonic transducer 12 are controlled by a computer 18 to stop scanning and ultrasonic excitation operation, and a backward Brillouin scattering signal of the sample is focused by the focusing objective lens 11 and returns along an original optical path;
4. the light is emitted from the outlet of the optical circulator 20, passes through the third collimating mirror 21 and the first cylindrical mirror 22, enters the first virtual phased array spectrometer VIPA23, passes through the second cylindrical mirror 24 and the first rectangular diaphragm 25, enters the fourth focusing lens 26, is focused on the second virtual phased array spectrometer VIPA27, passes through the frequency selection of the two spectrometers, is focused on the second rectangular diaphragm 29 by the fifth focusing lens 28, is converted into parallel light by the sixth focusing lens 30, is focused on the EMCCD32 by the seventh focusing lens 31, and is driven by the computer 18 to control the EMCCD32 to collect and process Brillouin scattering spectra.
Furthermore, the optical paths of the subsystems are all connected by optical fibers, and the focusing lens II 14, the diffraction grating 15, the focusing lens III 16 and the COMES camera 17 form a grating spectrometer packaging module.
Further, the wavelength division multiplexer 8, the optical collimator 9, the narrow linewidth laser 19, the optical circulator 20 and the collimating mirror 21 are all connected by optical fibers, so as to form a signal excitation optical path of the brillouin scattering elastography system.
The invention relates to a method for realizing in-situ detection of Brillouin scattering and optical coherence elastography, which is characterized in that a computer time sequence control system realizes the work of two optical systems without mutual influence, when the optical coherence elastography system works, a computer controls an annular ultrasonic transducer to send out ultrasonic excitation to generate shear waves on the surface of a sample, and then the computer drives a scanning galvanometer to carry out imaging detection. After the optical coherence elastography detection is finished, the computer drives the ring energy ultrasonic transducer and the scanning galvanometer to stop working, and at the moment, the Brillouin scattering elastography system starts to work to finish the Brillouin scattering elastography detection. Therefore, in-situ detection and comparative study of the bulk elastic modulus and the shear elastic modulus can be realized, and the influence of inherent difference of the properties of the sample on the experimental detection result is avoided.
Without being limited thereto, any changes or substitutions that are not thought of through the inventive work should be covered within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope defined by the claims.

Claims (3)

1. A method for in-situ detection of Brillouin scattering and optical coherence elastography is characterized by comprising the following steps:
(1) the subsystem is as follows: acoustic radiation force optical coherence elastography
The core principle of the system is that shear waves are excited on the surface of biological tissues by ultrasonic excitation generated by an ultrasonic transducer, then the speed of the shear waves transmitted on the surface of a sample is obtained by an optical coherent elastography technology, and the shear modulus and Young modulus of the sample are calculated according to the corresponding relation between the wave speed of the shear waves and the shear modulus of the tissues, and can be calculated by the following formula:
Figure FDA0003315412280000011
where E is the shear modulus, ρ is the sample density, VSIs the shear wave velocity; the specific process of the system is as follows:
a. the broadband light source SLD (1) emits broadband near infrared light with the central wavelength of 850nm, the broadband near infrared light passes through an optical isolator (2) with the central wavelength of 850nm and an optical coupler (3) with the central wavelength of 850nm and is divided into two beams of light with the phase-to-power ratio of 90:10, wherein a reference beam with the power of 10% passes through a first collimating mirror (4) with the central wavelength of 850nm, an optical attenuator (5) and a first focusing lens (6) and enters a reflecting mirror (7), and the reference beam returns to the coupler along the original path after being reflected by the reflecting mirror (7);
b. another beam of sample light with 90% of power exits from the coupler, passes through a wavelength division multiplexer (8), a light collimator (9), a scanning galvanometer (10) and a focusing objective lens (11), an annular ultrasonic transducer (12) is incident to a sample, the scanning galvanometer (10) is controlled by a driving program of a computer (18) to carry out three-dimensional scanning on the sample, the annular ultrasonic transducer (12) is controlled by the driving program of the computer (18) to generate MHz ultrasonic excitation, elastic waves are generated on the surface of the sample, and after the sample light and sample tissues act, the back scattered light of the sample light is focused by the focusing objective lens (11) and returns to the optical coupler (3) along an original path to interfere with reference light; interference light signals after interference of the sample light and the reference light are emitted from the other channel of the optical coupler (3), and are focused to the diffraction grating (15) through the second collimating mirror (13) and the second focusing lens (14), the interference light is split through the diffraction grating (15) and is focused to the COMES camera (17) through the third focusing lens (16), the COMES camera (17) is controlled by a computer (18) driving program to collect and process the interference signals, and at the moment, the detection function of the optical coherence elastography system can be completed;
(2) and a second subsystem: brillouin scattering elastography
The core principle of the system is that the Brillouin scattering is excited in a sample by laser to generate an acousto-optic effect, the Brillouin frequency shift of the sample is obtained by scanning an F-P interferometer and a photon receiver to further obtain the sound velocity, and the bulk elastic modulus of the sample is calculated by the sound velocity. Can be calculated from the following formula:
Figure FDA0003315412280000021
where K is the shear modulus, ρ is the sample density, VcIs the phonon velocity;
the specific process of the system is as follows:
c. then, a narrow-linewidth laser (19) emits continuous laser with the wavelength of 532nm, the continuous laser passes through an optical circulator (20), a wavelength division multiplexer (8), a collimator, a scanning galvanometer (10), a focusing objective lens (11) and an annular ultrasonic transducer (12) and is focused to a sample, at the moment, the scanning galvanometer (10) and the annular ultrasonic transducer (12) are controlled by a computer (18) to stop scanning and ultrasonic excitation operation, and a backward Brillouin scattering signal of the sample is focused by the focusing objective lens (11) and returns along an original optical path;
d. the light is emitted from the outlet of the optical circulator (20), enters the first virtual phased array spectrometer VIPA (23) after passing through the third collimating mirror (21) and the first cylindrical mirror (22), then enters the second virtual phased array spectrometer VIPA (23) after passing through the second cylindrical mirror (24) and the first rectangular diaphragm (25), then enters the fourth focusing lens (26) to be focused on the second virtual phased array spectrometer VIPA (27), after frequency selection of the two spectrometers, the emergent light is focused on the second rectangular diaphragm (29) through the fifth focusing lens (28), then is changed into parallel light through the sixth focusing lens (30), then is focused on an EMCCD (32) through the seventh focusing lens (31), and the Brillouin scattering spectrum is collected and processed through the EMCCD (32) under the driving control of the computer (18).
2. The brillouin scattering and optical coherence elastography in-situ detection method according to claim 1, characterized in that the optical paths of the subsystems are all connected by optical fibers, and the focusing lens two (14), the diffraction grating (15), the focusing lens three (16) and the COMES camera (17) constitute a grating spectrometer packaging module.
3. The method for in-situ detection of Brillouin scattering and optical coherence elastography according to claim 1, wherein the wavelength division multiplexer (8), the optical collimator (9), the narrow linewidth laser (19), the optical circulator (20) and the collimating mirror (21) are all connected by optical fibers to form a signal excitation optical path of the Brillouin scattering elastography system.
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