Angiography and tissue elastography device and method

By setting a reference layer on the surface of biological tissue and applying compression excitation, combined with frequency domain optical coherence tomography technology, angiography and tissue elastic imaging are achieved simultaneously, and the vascular network information and tissue elasticity that are carried out separately in the prior art are solved. The lack of characteristics provides more comprehensive diagnostic information.

CN119214602APending Publication Date: 2024-12-31BEIJING INFORMATION SCI & TECH UNIV

Patent Information

Application Number
CN202411593518.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-08
Publication Date
2024-12-31

AI Technical Summary

Technical Problem

The existing optical coherence tomography (OCTA) and optical coherence elastic imaging (OCE) technologies can only provide vascular network information or tissue elastic properties, respectively, and cannot achieve angiography and tissue elastic imaging at the same time.

Method used

A device for angiography and tissue elastic imaging is designed. By setting a reference layer on the surface of biological tissue, using an excitation unit to apply compressive excitation to the reference layer, inducing deformation of the reference layer and biological tissue, and using an imaging unit to perform frequency domain optical coherence. Tomography collects interference intensity signal sequences that vary with wavelength in the reference layer and biological tissue, and uses the upper computer to control the synchronous actions of the excitation unit and the imaging unit to realize angiography, tissue structure imaging and tissue elastic imaging.

Benefits of technology

It is achieved simultaneously obtaining three-dimensional structures and tissue elastic distributions of different layers of epidermal, dermis and subcutaneous tissue, as well as three-dimensional vascular networks or two-dimensional frontal projection maps, providing faster and more complete feature information for the diagnosis of diseases.

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Abstract

The invention relates to the technical field of medical imaging engineering, in particular to an angiography and tissue elastography device and method.The device comprises a reference layer arranged on the surface of biological tissue, and the elasticity modulus of the reference layer is known; the excitation unit is used for applying compression excitation to the surface of the reference layer and inducing the reference layer and the biological tissue to deform through excitation; the imaging unit is used for performing frequency domain optical coherence tomography on the reference layer and the biological tissue and collecting interference intensity signal sequences of the reference layer and the biological tissue along with wavelength change; and the upper computer is used for controlling the excitation unit and the imaging unit to act synchronously, and performing angiography, structural imaging and elastic imaging of the biological tissue according to the Young modulus of the reference layer and the interference signal sequence. Therefore, the problem that in the prior art, angiography and tissue elasticity are carried out separately, and only blood vessel network information or tissue elasticity characteristics can be provided is solved.
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Description

Technical Field

[0001] The present application relates to the technical field of medical imaging engineering, and in particular to a device and method for angiography and tissue elasticity imaging. Background Art

[0002] Most pathological changes in the skin result in changes in the structure, elastic properties and microvascular network of the skin layer. For example, scleroderma shows symptoms of vascular damage in the early stages, manifested as dilated capillaries and a decrease in the number of blood vessels. As scleroderma progresses, the skin thickens and becomes fibrotic, and the Young's modulus of the skin tissue increases. The structure, elasticity and vascular network of the skin can provide key information for the diagnosis of skin diseases. 3 Currently, conventional dermatoscopes can only obtain high-resolution images of the skin surface, while palpation and visual inspection are highly dependent on the doctor's skills and clinical experience. Although biopsy is the gold standard for examining diseased tissue, it cannot be repeated in the short term due to its invasiveness. OCT (Optical Coherence Tomography) is a non-invasive, high-resolution three-dimensional medical imaging technology that has been widely used in clinical and research fields to help diagnose skin diseases. It can observe the structure and function of the skin in real time.

[0003] OCTA (Optical Coherence Tomography Angiography) has been shown to elucidate the relationship between microvascular changes and related pathologies. OCE (Optical Coherence Elastography) has the unique ability to image the mechanical properties of tissues with microscale resolution and depths of several millimeters. OCTA requires three-dimensional volume scanning, while transient OCE is limited to one-dimensional or two-dimensional measurements of the skin. In addition, vascular information is lacking in quasi-static compression OCE experiments that can provide three-dimensional strain elastic maps. Summary of the invention

[0004] The present application provides a device and method for angiography and tissue elasticity imaging to solve the problem in the related art that OCTA and OCE are performed separately and can only provide vascular network information or tissue elasticity characteristics.

[0005] The first aspect of the present application provides a device for angiography and tissue elasticity imaging, including: a reference layer arranged on the surface of biological tissue; an excitation unit, used to apply compression excitation to the surface of the reference layer, and induce deformation of the reference layer by the excitation, thereby inducing deformation of the biological tissue; an imaging unit, used to perform frequency domain optical coherence tomography of the reference layer and the biological tissue, and collect interference intensity signal sequences that vary with wavelength in the reference layer and the biological tissue; a host computer, used to control the synchronous action of the excitation unit and the imaging unit, and perform angiography, tissue structure imaging and tissue elasticity imaging of the biological tissue according to the elastic modulus and interference intensity signal sequence of the reference layer.

[0006] Optionally, the host computer is used to: determine the complex form signal sequence of the target lateral position that varies with depth based on the interference intensity signal sequence of the target lateral position that varies with wavelength; extract amplitude information and phase information from the complex form signal sequence of the target lateral position that varies with depth; perform angiography of the biological tissue based on the amplitude or phase information, perform structural imaging of the reference layer and the biological tissue based on the amplitude information of the complex form signal sequence at different lateral positions, calculate the strain of the reference layer based on the change in the structural thickness of the reference layer, and calculate the strain of the biological tissue based on the amplitude or phase information of the biological tissue; calculate the stress on the surface of the biological tissue based on the elastic modulus of the reference layer and the strain of the reference layer, obtain the elastic modulus of the biological tissue based on the ratio of the stress on the surface of the biological tissue to the strain of the biological tissue, and perform elastic imaging of the biological tissue based on the elastic modulus at different positions of the biological tissue.

[0007] Optionally, the reference layer consists of a flexible translucent or transparent medium.

[0008] Optionally, the excitation unit includes a displacement platform, a transparent plate and a support, wherein the displacement platform applies compression excitation through displacement, the support supports the transparent plate, and the transparent plate is fixedly arranged or separated from the imaging lens of the imaging unit.

[0009] Optionally, if the imaging lens of the imaging unit and the transparent plate are fixedly arranged, when the displacement platform applies the compressive excitation by displacement, the imaging lens and the transparent plate move simultaneously.

[0010] Optionally, if the imaging lens of the imaging unit is disposed separately from the transparent plate, when the displacement platform applies the compressive excitation through displacement, the imaging lens remains stationary and the transparent plate moves.

[0011] Optionally, the imaging unit includes at least one of a swept source optical coherence tomography optical path and a spectral domain optical coherence tomography optical path.

[0012] Optionally, the swept-source optical coherence tomography optical path includes a swept-source light source, a first coupler, a first reference optical path, a first sample optical path and a first photodetector, wherein the first coupler is used for splitting light so that part of the light enters the first reference optical path and part of the light enters the first sample optical path, the light beam of the first reference optical path and the light beam scattered by the first sample optical path interfere with each other in the first coupler, the first photodetector detects the interference light in the first coupler, the swept-source light outputs a single wavelength or narrow-band laser at each moment, and the first photodetector detects the interference intensity of the single wavelength or narrow-band light at each moment, and during the imaging process, the length of the first reference optical path remains unchanged.

[0013] Optionally, the spectral domain optical coherence tomography optical path includes a wide-spectrum light source, a second coupler, a second reference optical path, a second sample optical path, a grating, and a second photodetector, wherein the second coupler is used to split light so that part of the light enters the second reference optical path shown and part of the light enters the second sample optical path. The light beam of the second reference optical path and the light beam scattered by the second sample optical path interfere with each other in the second coupler. The interference light of different wavelengths is spatially separated by the grating and projected to different positions of the second photodetector to achieve simultaneous detection of the intensities of interference light of different wavelengths. During the imaging process, the length of the second reference optical path remains unchanged.

[0014] The second embodiment of the present application provides a method for angiography and tissue elasticity imaging, which uses the angiography and tissue elasticity imaging device of the first aspect for imaging, and includes the following steps: inducing deformation of the reference layer by applying a compressive excitation on the surface of the reference layer, thereby inducing deformation of the biological tissue; performing frequency domain optical coherence tomography on the reference layer and the biological tissue, and collecting interference intensity signal sequences that vary with wavelength in the reference layer and the biological tissue; determining a complex form signal sequence that varies with depth at the lateral position of the target based on the interference intensity signal sequence that varies with wavelength at the lateral position of the target, and extracting the complex form signal sequence The amplitude information and phase information in the image are obtained, and the structural imaging of the reference layer and biological tissue is performed according to the amplitude information of the complex form signal sequence at different lateral positions; the strain of the reference layer is calculated according to the thickness change of the reference layer structure, and the stress on the surface of the biological tissue is calculated according to the elastic modulus of the reference layer and the strain of the reference layer; angiography of the biological tissue is performed according to the amplitude or phase information, the strain of the biological tissue is calculated according to the amplitude or phase information, the elastic modulus of the biological tissue is obtained according to the ratio of the stress on the surface of the biological tissue and the strain of the biological tissue, and elastic imaging of the biological tissue is performed according to the elastic modulus at different positions of the biological tissue. Therefore, the present application includes the following beneficial effects:

[0015] The embodiment of the present application sets a reference layer on the surface of biological tissue, applies compressive excitation to the reference layer surface by using an excitation unit, thereby inducing deformation of the reference layer and biological tissue, uses an imaging unit to perform frequency domain optical coherence tomography on the reference layer and the surface of biological tissue and collects the interference intensity signal sequence that varies with the wavelength in the reference layer and biological tissue, and uses a host computer to control the synchronous action of the excitation unit and the imaging unit, and finally uses the host computer to perform angiography, tissue structure imaging and tissue elasticity imaging of biological tissue according to the elastic modulus and interference intensity signal sequence of the reference layer, so as to achieve simultaneous acquisition of the three-dimensional structure and tissue elasticity distribution of different layers of the epidermis, dermis and subcutaneous tissue, as well as a three-dimensional vascular network or a two-dimensional frontal projection map, providing faster and more complete feature information for the diagnosis of diseases. Thus, the problem that OCTA and OCE in the related art are performed separately and can only provide vascular network information or elastic properties of tissues is solved.

[0016] Additional aspects and advantages of the present application will be given in part in the description below, and in part will become apparent from the description below, or will be learned through the practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The above and / or additional aspects and advantages of the present application will become apparent and easily understood from the following description of the embodiments in conjunction with the accompanying drawings, in which:

[0018] Figure 1 A schematic diagram of the structure of a device for angiography and tissue elasticity imaging provided according to an embodiment of the present application;

[0019] Figure 2 A schematic diagram of a method for angiography and tissue elasticity imaging according to an embodiment of the present application;

[0020] Figure 3 A schematic diagram of a device based on swept source OCT according to an embodiment of the present application;

[0021] Figure 4 A schematic diagram of a device based on spectral domain OCT according to an embodiment of the present application;

[0022] Figure 5 A diagram of a beam scanning scheme for OCT imaging according to an embodiment of the present application;

[0023] Figure 6 An OCT structural image and an OCTA blood flow angiography image provided according to an embodiment of the present application;

[0024] Figure 7 A schematic diagram of tissue deformation before and after compression provided according to an embodiment of the present application;

[0025] Figure 8A schematic diagram of a probe in which a scanning lens is rigidly connected to a compression excitation device according to an embodiment of the present application;

[0026] Fig. 9 A schematic diagram of a probe with a scanning lens and a compression excitation device separated according to an embodiment of the present application;

[0027] Fig.10 A schematic diagram of an imaging system provided according to an embodiment of the present application;

[0028] Fig.11 A diagram of performing angiography and tissue elasticity imaging simultaneously on a model according to one embodiment of the present application;

[0029] Fig.12 The figure is a flow chart of the method of angiography and tissue elasticity imaging provided according to an embodiment of the present application. DETAILED DESCRIPTION

[0030] The embodiments of the present application are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present application, and should not be construed as limiting the present application.

[0031] The following describes the device and method of angiography and tissue elasticity imaging of the embodiment of the present application with reference to the accompanying drawings. In view of the problem that OCTA and OCE in the related art mentioned in the above background technology are performed separately and can only provide vascular network information or elastic properties of tissues, the present application provides a device for angiography and tissue elasticity imaging, which sets a reference layer on the surface of biological tissue, applies compression excitation to the surface of the reference layer by using an excitation unit, thereby inducing deformation of the reference layer and the biological tissue, performs frequency domain optical coherence tomography imaging of the reference layer and the surface of the biological tissue by using an imaging unit, and collects the interference intensity signal sequence that varies with the wavelength in the reference layer and the biological tissue, and uses a host computer to control the synchronous action of the excitation unit and the imaging unit, and finally uses the host computer to perform angiography, tissue structure imaging and tissue elasticity imaging of the biological tissue according to the elastic modulus and interference intensity signal sequence of the reference layer, so as to achieve simultaneous acquisition of the three-dimensional structure and tissue elasticity distribution of different layers of the epidermis, dermis and subcutaneous tissue, as well as a three-dimensional vascular network or a two-dimensional frontal projection map, providing faster and more complete feature information for disease diagnosis.

[0032] Specifically, Figure 1 A schematic diagram of the structure of a device for angiography and tissue elasticity imaging provided in an embodiment of the present application.

[0033] like Figure 1As shown, the device for angiography and tissue elasticity imaging includes: biological tissue 100 , a reference layer 101 , an excitation unit 102 , a host computer 103 and an imaging unit 104 .

[0034] Among them, the reference layer 101 is arranged on the biological tissue surface 100; the excitation unit 102 is used to apply compression excitation to the reference layer 100, so that the reference layer and the biological tissue 101 are deformed; the imaging unit 104 is used to perform frequency domain optical coherence tomography of the reference layer and the biological tissue surface 100, and collect the interference intensity signal sequence that varies with the wavelength in the reference layer and the biological tissue 101; the host computer 103 is used to control the synchronous action of the excitation unit 102 and the imaging unit 104, and perform angiography, tissue structure imaging and tissue elasticity imaging of the biological tissue according to the elastic modulus of the reference layer 101 and the generated deformation and interference intensity signal sequence.

[0035] Among them, the elastic modulus of the reference layer 101 is known, and the elastic modulus is used to describe the degree of deformation of a solid material when subjected to stress; frequency domain optical coherence tomography is a branch of OCT technology, and frequency domain methods can be used to process interference signals to improve imaging speed and signal-to-noise ratio; the interference intensity signal sequence is an interference signal sequence that varies with wavelength over time at a certain position of a biological tissue.

[0036] It can be understood that the embodiment of the present application includes a reference layer 101, an excitation unit 102, a host computer 103 and an imaging unit 104. The reference layer 101 is set on the surface 100 of the biological tissue to be tested, and the excitation unit 102 is used to induce the reference layer 101 and the biological tissue 100 to deform. The host computer 103 controls the excitation unit 102 and the imaging unit 104 to move synchronously. The imaging unit 104 collects the interference intensity signal sequence that varies with the wavelength in the reference layer 101 and the biological tissue 100, and performs frequency domain optical coherence tomography on the reference layer 101 and the biological tissue 100. Finally, the host computer 103 is used to perform angiography, tissue structure imaging and tissue elasticity imaging of the biological tissue based on the known elastic modulus of the reference layer 101 and the generated deformation and the interference intensity signal sequence of the biological tissue 100.

[0037] In an embodiment of the present application, the host computer 103 is used to: determine a complex form signal sequence that varies with depth at the lateral position of the target based on an interference intensity signal sequence that varies with wavelength at the lateral position of the target; extract amplitude information and phase information in the complex form signal sequence; perform angiography of the biological tissue based on the amplitude or phase information, perform structural imaging of the reference layer and the biological tissue based on the amplitude information of the complex form signal sequence at different lateral positions, calculate the strain of the reference layer based on the thickness change of the reference layer structure, calculate the stress on the surface of the biological tissue based on the elastic modulus of the reference layer 100 and the strain of the reference layer, and calculate the strain of the biological tissue 100 based on the amplitude or phase information; obtain the elastic modulus of the biological tissue 100 based on the ratio of the stress on the surface of the biological tissue to the strain of the biological tissue 100, and perform elastic imaging of the biological tissue 100 based on the elastic modulus at different positions of the biological tissue 100.

[0038] The strain is obtained by measuring the change of displacement in the skin tissue with depth, and the calculation formula is: ε is strain, u represents axial displacement, and axial displacement is measured using phase-sensitive detection technology. The calculation formula is: Where λ0 represents the central wavelength of the light source, Δφ represents the phase difference, n represents the refractive index of the sample, and z represents the axis coordinate; the stress is obtained by measuring the reference layer 101, recording the original thickness l0 and the thickness l after compression of the reference layer 101, according to the formula The strain of the reference layer 101 under compressive excitation is calculated, and the elastic modulus E of the reference layer 101 is reference It can be obtained in advance through a compression test machine, and finally calculated to get stress σ=E reference ×ε reference .

[0039] It can be understood that the embodiment of the present application processes the interference signal through the host computer 103, determines the complex form signal sequence of the target lateral position that varies with depth from the interference intensity signal sequence of the target lateral position that varies with wavelength, extracts the amplitude information and phase information of the complex form signal sequence, performs angiography of the biological tissue according to the amplitude or phase information, and performs structural imaging of the biological tissue 100 according to the amplitude information reference layer 101 of the complex form signal sequence at different lateral positions, obtains strain by measuring the variation of displacement in the skin tissue with depth, obtains stress by measuring the reference layer 101, obtains the elastic modulus of the biological tissue 100 according to the ratio of stress to strain, and performs elastic imaging of the biological tissue 100 according to the elastic modulus at different positions of the biological tissue 100.

[0040] In the embodiment of the present application, the reference layer 101 is made of a flexible semi-transparent or transparent medium.

[0041] It can be understood that the reference layer 101 of the embodiment of the present application is composed of a flexible semi-transparent or transparent medium, which can allow the light beam to irradiate the biological tissue surface 100 with minimal loss.

[0042] In the embodiment of the present application, the excitation unit 102 includes a displacement platform, a transparent plate and a support member, wherein the displacement platform applies compression excitation through displacement, the support member supports the transparent plate, and the transparent plate is fixedly arranged or separated from the imaging lens of the imaging unit 104.

[0043] It can be understood that in the embodiment of the present application, the excitation unit 102 is composed of a displacement platform, a transparent plate and a support member. The excitation unit 102 utilizes the displacement platform to displace to form a compressive excitation on the biological tissue 100. The support member supports the transparent plate. The transparent plate and the imaging lens of the imaging unit 104 can be rigidly fixed or separately arranged.

[0044] In the embodiment of the present application, if the imaging lens of the imaging unit 104 and the transparent plate are fixedly arranged, when the displacement platform applies the compressive excitation through displacement, the imaging lens and the transparent plate move simultaneously.

[0045] It is understandable that if the imaging lens of the imaging unit 104 of the embodiment of the present application is fixedly arranged with the transparent plate, when the displacement platform applies compression excitation through displacement, the imaging lens and the transparent plate are rigidly fixed as a whole and move simultaneously to form compression excitation.

[0046] In the embodiment of the present application, if the imaging lens of the imaging unit 104 is separately arranged from the transparent plate, when the displacement platform applies the compressive excitation through displacement, the imaging lens does not move, and the transparent plate moves.

[0047] It can be understood that if the imaging lens of the imaging unit 104 of the embodiment of the present application is set separately from the transparent plate, when the displacement platform applies compression excitation through displacement, the imaging lens and the transparent plate are two separate components, and the compression excitation is applied by moving the transparent plate, while the imaging lens remains stationary.

[0048] In the embodiment of the present application, the imaging unit 104 includes at least one of a swept source optical coherence tomography optical path and a spectral domain optical coherence tomography optical path.

[0049] Among them, swept source optical coherence tomography is a type of OCT, which uses a swept source laser as a light source and can continuously change its emission wavelength in a short time. When the laser is swept, it will emit a series of light of different wavelengths in sequence, and a large amount of depth information can be collected in a short time; spectral domain optical coherence tomography is a type of OCT, which uses a broadband light source to illuminate the sample and a spectrometer to simultaneously measure interference signals of multiple wavelengths. The two will be described in detail below and will not be repeated here.

[0050] It is understandable that the imaging unit 104 includes a swept-source optical coherence tomography optical path or a spectral-domain optical coherence tomography optical path, and both of them can be used to perform frequency-domain optical coherence tomography.

[0051] In an embodiment of the present application, a swept-source optical coherence tomography optical path includes a swept-source light source, a first coupler, a first reference optical path, a first sample optical path and a first photodetector, wherein the first coupler is used to split light so that part of the light enters the first reference optical path and part of the light enters the first sample optical path, and the light beam of the first reference optical path interferes with the light beam scattered by the first sample optical path in the first coupler, and the first photodetector detects the interference light in the first coupler, and the swept-source light outputs a single wavelength or narrow-band laser at each moment, and the first photodetector detects the interference intensity of the single wavelength or narrow-band light at each moment, and during the imaging process, the length of the first reference optical path remains unchanged.

[0052] Among them, the first coupler, also known as a beam splitter, can divide the light from the swept light source into two parts, one part as reference light and the other part as sample light; the first reference light path contains reference light, which does not contact the sample but directly returns to the coupler. The optical path difference between the reference light and the sample light can be controlled by adjusting the length of the reference light path, thereby achieving interference imaging at different depths; the first photodetector is used to detect the interference light coming out of the coupler.

[0053] It can be understood that in the embodiment of the present application, the swept-source optical coherence tomography optical path includes a swept-source light source, a first coupler, a first reference optical path, a first sample optical path, and a first photodetector. The swept-source light source outputs a single wavelength or narrow-band laser at each moment. The light is first divided into two beams by the first coupler, one beam enters the first reference optical path, and the other beam enters the first sample optical path. The light entering the sample optical path irradiates the sample surface, and then is scattered or reflected back to the first coupler by the sample. The light entering the reference optical path also returns to the first coupler. The two beams of light meet at the first coupler and interfere. The first photodetector detects the interference light coming out of the first coupler and records the interference intensity of the detected single wavelength or narrow-band light.

[0054] In an embodiment of the present application, the spectral domain optical coherence tomography optical path includes a wide-spectrum light source, a second coupler, a second reference optical path, a second sample optical path, a grating, and a second photodetector, wherein the second coupler is used to split light so that part of the light enters the second reference optical path shown and part of the light enters the second sample optical path. The light beam of the second reference optical path and the light beam scattered by the second sample optical path interfere with each other in the second coupler. The interference light of different wavelengths is spatially separated by the grating and projected to different positions of the second photodetector to achieve simultaneous detection of the intensities of interference light of different wavelengths. During the imaging process, the length of the second reference optical path remains unchanged.

[0055] It can be understood that in the embodiment of the present application, the optical path of the spectral domain optical coherence tomography includes a wide spectrum light source, a second coupler, a second reference light path, a second sample light path, a grating, and a second photodetector. The spectral light source emits light in a wide spectrum range. The light first passes through the second coupler and is divided into two parts: one part enters the second reference light path, and the other part enters the second sample light path; the light entering the second sample light path irradiates the sample surface, is scattered or reflected back to the second coupler by the sample; the light entering the second reference light path also returns to the second coupler. The two beams of light meet at the second coupler and interfere with each other. The interference light passes through the grating, which separates the light of different wavelengths according to their wavelengths, so that each wavelength of light is imaged at a different position of the detector. The second photodetector can simultaneously detect the intensity distribution of all these interference lights of different wavelengths, and realize the simultaneous detection of the intensity of interference lights of different wavelengths.

[0056] According to the device for angiography and tissue elasticity imaging proposed in the embodiment of the present application, a reference layer is set on the surface of biological tissue, and a compressive excitation is applied to the reference layer by an excitation unit to induce deformation of the reference layer and the biological tissue. The imaging unit is used to perform frequency domain optical coherence tomography on the reference layer and the surface of the biological tissue and collect the interference intensity signal sequence that varies with the wavelength in the reference layer and the biological tissue, and the host computer is used to control the synchronous action of the excitation unit and the imaging unit. Finally, the host computer is used to perform angiography, tissue structure imaging and tissue elasticity imaging of the biological tissue according to the elastic modulus of the reference layer and the generated deformation and interference intensity signal sequence, so as to achieve simultaneous acquisition of the three-dimensional structure and elastic distribution of different layers of the epidermis, dermis and subcutaneous tissue, as well as a three-dimensional vascular network or a two-dimensional frontal projection map, providing faster and more complete feature information for the diagnosis of diseases. Thus, the problem that OCTA and OCE in the related art are performed separately and can only provide vascular network information or elastic properties of tissues is solved.

[0057] The device for angiography and tissue elasticity imaging is further described below through a specific embodiment.

[0058] In this embodiment, the skin imaging device includes a frequency domain optical coherence tomography unit, a compression excitation unit and a flexible semi-transparent reference layer for stress estimation, such as Figure 2As shown. The frequency domain optical coherence tomography unit can realize three-dimensional imaging, two-dimensional cross-sectional imaging and surface topography imaging of skin tissue. The three-dimensional structural data of skin tissue is post-processed, and angiography is performed using angiography algorithm (such as the intensity-based Doppler variance algorithm) to realize the visualization of the skin microvascular network. When the compression excitation unit causes the reference layer and the skin to deform, the frequency domain optical coherence tomography unit combined with Doppler phase analysis can sensitively detect the strain of the skin and the reference layer, and measure the elastic properties of the skin by analyzing their respective deformation properties, such as the strain generated by the skin and the stress generated by the reference layer.

[0059] Optical coherence tomography is a non-invasive, high-resolution, non-labeled three-dimensional medical imaging technology that uses visible light or near-infrared light and the principle of light interference to perform three-dimensional tomographic imaging of tissues and sensitively detect tiny deformations of tissues. Frequency domain optical coherence tomography includes swept source optical coherence tomography and spectral domain optical coherence tomography.

[0060] Swept-source optical coherence tomography uses a swept-source laser light source. The specific imaging optical path can be as follows: Figure 3 As shown. The swept source optical coherence tomography unit mainly includes a swept light source, a coupler, a reference light path, a sample light path and a photodetector. The coupler realizes the splitting effect, so that part of the light enters the reference light path and part of the light enters the sample light path. At the same time, the light beam from the reference light path and the light beam scattered by the sample light path interfere in the first coupler. The interference light is detected by the photodetector. The swept light source outputs a single wavelength (or narrow band) laser at each moment, and the photodetector detects the intensity of the single wavelength (or narrow band) interference light at each moment. During the imaging process, there is no need to time-modulate the length of the reference light path, and the length of the reference light path remains unchanged.

[0061] The spectral domain optical coherence tomography unit uses a wide spectrum light source, and the specific imaging optical path can be as follows: Figure 4 As shown. The spectral domain optical coherence tomography unit mainly includes a wide-spectrum light source, a coupler, a reference optical path, a sample optical path, a grating, a linear array or a planar array photodetector, etc. The coupler realizes the splitting effect, so that part of the light enters the reference optical path and part of the light enters the sample optical path. At the same time, the light beam from the reference optical path and the light beam scattered by the sample optical path interfere in the coupler. Since the wide-spectrum light source emits light beams of different wavelengths at the same time, the interference light has different wavelengths. The interference light of different wavelengths is spatially separated by the grating and projected to different positions of the linear array or planar array camera, thereby realizing the simultaneous detection of the intensity of interference light of different wavelengths. During the imaging process, there is no need to temporally modulate the length of the reference optical path, and the length of the reference optical path remains unchanged.

[0062] The compression excitation unit is composed of a high-precision electric-controlled displacement platform, a transparent plate and corresponding support parts. The imaging lens can be fixed to the transparent plate or separated. If the imaging lens can be fixed to the transparent plate, the imaging lens moves downward together with the transparent plate during compression excitation. The hollow support is connected together by a support rod and a galvanometer to form an integral imaging probe that can directly contact the skin surface. The imaging probe is installed on a high-precision displacement platform, and the displacement platform drives the imaging probe to move downward. The minimum step distance is 1 micron, thereby compressing the skin surface and inducing deformation of the skin. If the imaging lens can be separated from the transparent plate, during compression excitation, the imaging lens does not move and the transparent plate moves downward.

[0063] The reference layer is composed of a flexible translucent or transparent medium, which is responsible for estimating the stress applied to the skin surface. The reference layer can be made of agar powder and fat emulsion. Agar powder determines the elastic properties of the reference layer, and fat emulsion determines the reflection intensity of the reference layer. The reference layer can also be made of silicone and silicon dioxide. Silicone determines the elastic properties of the reference layer, and silicon dioxide determines the reflection intensity of the reference layer. Since the elastic modulus value of the reference layer can be directly obtained by the pressure tester, the deformation of the reference layer under compression excitation can be measured to estimate the stress magnitude of the compression excitation on the skin. In order to minimize the loss of light in the reference layer, the reference layer should be as transparent as possible. However, because the upper and lower boundaries of the reference layer need to be detected, the reference layer should have a certain scattering intensity for identification, so it was finally decided to use a translucent one.

[0064] The interference signal sequence Γ of a certain position (x, y) collected by the optical coherence tomography unit changes with the wavelength λ at time t x,y,t (λ), and Fast Fourier Transform (FFT) is performed to obtain a complex signal that varies with depth z. The complex signal sequence that depends on the imaging depth z can be expressed as F x,y,t (z), including amplitude and phase. Where (x, y) represents the coordinates of the plane perpendicular to the imaging beam, and z represents the coordinates of the imaging beam direction (depth direction), such as Figure 5 As shown. After obtaining the amplitude and phase of the optical coherence tomography signal, the amplitude information is extracted to obtain the structural image of the tissue. During the imaging process, there is no need to modulate the length of the reference optical path in time, and the length of the reference optical path remains unchanged. Depending on the scanning method, the A scan obtains one-dimensional information along the depth direction, the B scan can obtain a two-dimensional cross-sectional image, and the C scan can obtain a three-dimensional structural image.

[0065] Skin angiography relies on the movement of scattering particles (such as red blood cells) to distinguish static tissue from dynamic blood flow. Blood flow imaging is achieved by repeatedly scanning the same position (B scan) and detecting the signal difference over time. The original calculation formula is as follows: where M represents the number of repeated sampling at the same position, F t and F t+1 is the OCT complex signal captured at the same spatial location but at different times, |F t | represents the amplitude of the OCT complex signal. Therefore, the algorithm does not consider the phase component.

[0066]

[0067] like Figure 6 Shown are OCT structural images and OCTA blood flow angiography images. The left image is a two-dimensional cross-sectional structural image acquired by OCT. The position of the blood flow area can be calculated by using the IBDV algorithm, such as the white area pointed to by the yellow arrow in the right image.

[0068] When evaluating the elastic information of soft biological tissues, the elastic modulus (E) is often used to represent it. In compressed optical coherence elastography (OCE), E is numerically equal to the ratio of stress σ to strain ε. Stress σ is obtained by measuring the reference layer, recording the original thickness l0 of the reference layer and the thickness l after compression, according to the formula The strain of the reference layer under compressive excitation is calculated, and the elastic modulus E of the reference layer is reference It can be directly obtained through the pressure tester, and finally the stress σ on the skin surface (reference layer ground) is calculated skin =E reference ×ε reference .like Figure 7 Figure 2 is a schematic diagram of tissue deformation before and after compression.

[0069] The strain ε is obtained by measuring the change of displacement in the skin tissue with depth, and the formula is calculated as Where u represents the axial displacement and z represents the axis coordinate, so the strain can be calculated by the derivative of the axial displacement. The axial displacement is measured using phase-sensitive detection technology, and the calculation formula is: In the formula, λ0 represents the central wavelength of the light source, Δφ represents the phase difference, and n represents the refractive index of the sample. Therefore, as long as the phase of the two OCT images before and after the skin tissue is compressed can be calculated, the displacement generated can be estimated, and then the skin strain ε can be calculated. skin , finally according to the stress σ skin and strain ε skin The ratio of is the skin elastic modulus.

[0070] The strain ε can also be used to perform structural imaging of biological tissues based on the amplitude information of the complex signal sequence at different lateral positions, compare the similarity between the two OCT images before and after compression of the biological tissue, find the position after loading, calculate the displacement through the cross-correlation algorithm, and obtain the strain field through differential operations.

[0071] In this example, it is coupled to the objective lens through a combination of a support rod, a hollow support and a glass sheet. The entire probe is driven axially by a translation stage to form a compressive excitation. The flexible reference layer is placed between the glass sheet and the skin, fitting tightly to the skin surface so that the force is evenly applied to the skin surface. The hollow design and translucent reference layer allow the light beam to irradiate the skin with minimal loss. The OCT signals of the skin before and after the pressure is applied are collected, and through post-processing, the vascular network visualization and elasticity information can be obtained at the same skin location at the same time. Figure 8 The schematic diagram of the probe in which the scanning lens is rigidly connected to the compression excitation device is shown. Fig. 9 Shown is a schematic diagram of the probe with the scanning lens separated from the compression excitation device.

[0072] Taking swept source optical coherence tomography as an example, the schematic diagram of the imaging system is as follows: Fig.10 As shown, it includes an imaging probe and an OCT unit. The OCT unit uses a 1300nm swept frequency light source with an A-line rate of 200kHz. In the imaging probe, a scanning galvanometer probe is fixed on an electric control translation stage to drive the probe for axial displacement. The minimum step size of the translation stage is 1μm. A scanning lens with a working distance of 42.5 mm is installed under the galvanometer. At the same time, a glass window is installed through a support kit. The lower surface of the glass window is located at the normal working distance of the scanning lens, allowing the probe to be close to the sample.

[0073] Images were acquired using the MB scanning protocol. Four B-scan images were acquired at each lateral position, each containing 800 A-lines. A total of 200 lateral positions were scanned. The scanned area was approximately 3.5 × 3.5 mm2, and the resulting volume dataset had dimensions of 2048 × 800 × 800 pixels. During the process, a volume scan was performed when the probe just touched the sample surface. The acquired data were analyzed using the intensity-based Doppler variance algorithm (IBDV) to visualize the vascular network. Subsequently, the probe was pressed down to place the sample in a preloaded state, and another volume scan was performed. Another volume scan was performed after the probe was controlled to move 1 μm in the axial direction. Deformation was analyzed by OCT phase change. To quantify the elastic modulus, a transparent, flexible reference layer made of a 1% agar phantom was placed on the sample surface. The elastic modulus of the layer was 40.25 KPa as measured by the mechanical testing system. The layer adhered to the sample surface, ensuring uniform force transmission. It also helps to quantify the surface stress of the sample, which can be determined by measuring the deformation of the reference layer and using the known elastic modulus.

[0074] This example uses a double-layer agar model to verify the imaging method, as follows:

[0075] The concentration of the upper agar layer was 1%, and the concentration of the lower agar layer was 2%. A tube containing a flowing fat emulsion solution was embedded in the upper agar layer. After verification, measurements were made on the skin of living rats. In the analysis, the OCT signal was expressed as a complex signal, defined as Where A is the amplitude, is the phase. As shown in formula (1), the IBDV method uses the amplitude autocorrelation between adjacent frames to obtain the variance value. The area showing high variance value corresponds to blood flow, indicating that the signal has changed significantly:

[0076]

[0077] Among them, A m andA m+1 is the amplitude of the OCT complex signal captured at the same location but at different times, and M is the number of measurements at the same location, specifically M = 4. In compression OCE, the elastic modulus (E) is defined as the stress (σ zz ) and strain (ε zz ). The stress is estimated from the change in the thickness of the reference layer and the strain is defined as follows: 8

[0078]

[0079] Where λ0 is the central wavelength of the OCT signal, n is the refractive index of the tissue, Δz is the axial pixel spacing, and Δφ is the OCT phase gradient before and after loading. In the vector method, the OCT phase difference φ can be calculated by After The complex signal of the OCT B scan is calculated as follows:

[0080]

[0081] Here, x is the transverse index in the B-scan, z is the axial index, and * represents the conjugate of the complex signal, defining the OCT phase gradient Δφ as:

[0082] c(x,z)=b * (x,z-Δz)·b(x,z)=C(x,z)exp[φ(x,z-Δz)-φ(x,z)]

[0083] =C(x,z)exp(Δφ(x,Δz)),(4)

[0084] By extracting the phase gradient from equation (4) and substituting it into equation (2), the deformation of the sample due to compression can be analyzed.

[0085] Fig.11 Results of simultaneous angiography and elastography on the phantom are shown. Fig.11 (a) OCT 3D image showing a double-layer agar model containing a tube. Fig.11 The strain elasticity diagram of the model B-scan image shown in (b) clearly distinguishes the boundary between the double-layer model and the circular tube. The strain generated by the upper layer of 1% agar is much larger than the strain generated by the lower layer of 2% agar. This observation is consistent with the understanding that the model with a higher agar concentration has a stiffer elasticity. In addition, the area containing the liquid flow shows the largest and most uneven strain values, which affects the area below. This is probably due to the rapid phase changes associated with the flow. Fig.11 (c) shows that after processing using the IBDV method, only the liquid flow area is visible. Fig.11 (d) and (e) are frontal projection images. Here, we demonstrate a method for simultaneous angiography and elastography. At the same imaging position, the IBDV method is used to display the tube representing the simulated blood vessel, while the strain information from the model is displayed by the vector method, thereby qualitatively interpreting the elastic distribution.

[0086] Next, the method of angiography and tissue elasticity imaging according to the embodiment of the present application is described with reference to the accompanying drawings. The method uses the above-mentioned angiography and elasticity imaging device to perform imaging, such as Fig.11As shown, the method of angiography and tissue elasticity imaging comprises the following steps:

[0087] In step S201 , a compression excitation is applied to the reference layer to induce deformation of the reference layer and the biological tissue.

[0088] It can be understood that the embodiment of the present application applies compressive excitation to the reference layer, causing it to deform together with the biological tissue.

[0089] In step S202, frequency domain optical coherence tomography is performed on the reference layer and the biological tissue surface, and interference intensity signal sequences of the reference layer and the biological tissue that vary with wavelength over time are collected.

[0090] It can be understood that the embodiment of the present application performs frequency domain optical coherence tomography on the reference layer and the biological tissue through an imaging unit to collect interference intensity signal sequences of the reference layer and the target lateral position in the biological tissue that vary with wavelength.

[0091] In step S203, a complex form signal sequence of the target lateral position that varies with depth is determined based on the interference intensity signal sequence of the target lateral position that varies with depth, the amplitude information and phase information in the complex form signal sequence of the target lateral position are extracted, and structural imaging of the reference layer and biological tissue is performed based on the amplitude information of the complex form signal sequence at different lateral positions, and the strain of the reference layer is calculated based on the thickness change of the reference layer structure.

[0092] It can be understood that, based on the interference intensity signal sequence of the collected target lateral position that varies with depth, the complex signal sequence at different lateral positions can be determined, and the amplitude and phase information of the complex signal sequence at different lateral positions can be extracted therefrom. The amplitude information of the complex signal sequence at these different lateral positions can be used to perform structural imaging of the reference layer and biological tissue, and the strain of the reference layer can be calculated based on the thickness change of the reference layer caused by excitation.

[0093] In step S204, the stress on the surface of the biological tissue is calculated based on the elastic modulus and strain of the reference layer, angiography of the biological tissue is performed based on the amplitude or phase information, the strain of the biological tissue is calculated based on the amplitude or phase information, the elastic modulus of the biological tissue is obtained based on the ratio of the stress on the surface of the biological tissue to the strain of the biological tissue, and elastic imaging of the biological tissue is performed based on the elastic modulus at different positions of the biological tissue.

[0094] It can be understood that the embodiments of the present application calculate the stress on the surface of the biological tissue through the elastic modulus and the strain of the reference layer, perform angiography of the biological tissue through the extracted amplitude or phase information, calculate the strain of the biological tissue using the amplitude or phase information, determine the elastic modulus of the biological tissue using the ratio of the stress on the surface of the biological tissue to the strain of the biological tissue, and perform elastic imaging of the biological tissue based on the elastic modulus at different positions of the biological tissue.

[0095] It should be noted that the above explanations of the embodiment of the device for angiography and tissue elasticity imaging are also applicable to the method for angiography and tissue elasticity imaging of this embodiment, and will not be repeated here.

[0096] According to the method of angiography and tissue elasticity imaging proposed in the embodiment of the present application, a compressive excitation is applied to the reference layer by an excitation unit, thereby inducing deformation of the reference layer and the biological tissue, performing frequency domain optical coherence tomography on the reference layer and the surface of the biological tissue, and collecting interference intensity signal sequences that vary with wavelength in the reference layer and the biological tissue. Finally, angiography, tissue structure imaging and tissue elasticity imaging of the biological tissue are performed based on the elastic modulus of the reference layer and the strain and interference intensity signal sequences generated. This achieves the simultaneous acquisition of the three-dimensional structure and elasticity distribution of different layers of the epidermis, dermis and subcutaneous tissue, as well as the three-dimensional vascular network or two-dimensional frontal projection image, thereby providing faster and more complete characteristic information for disease diagnosis.

[0097] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms are not necessarily directed to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or N embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0098] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include at least one of the features. In the description of this application, "N" means at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0099] Any process or method description in a flowchart or otherwise described herein may be understood to represent a module, fragment or portion of code comprising one or N executable instructions for implementing the steps of a custom logical function or process, and the scope of the preferred embodiments of the present application includes alternative implementations in which functions may not be performed in the order shown or discussed, including performing functions in a substantially simultaneous manner or in reverse order depending on the functions involved, which should be understood by technicians in the technical field to which the embodiments of the present application belong.

[0100] It should be understood that the various parts of the present application can be implemented in hardware, software, firmware or a combination thereof. In the above-mentioned embodiments, the steps or methods can be implemented in software or firmware stored in a memory and executed by a suitable instruction execution system. For example, if implemented in hardware, as in another embodiment, it can be implemented by any one of the following technologies known in the art or their combination: a discrete logic circuit having a logic gate circuit for implementing a logic function on a data signal, a dedicated integrated circuit having a suitable combination of logic gate circuits, a programmable gate array, a field programmable gate array, etc.

[0101] A person of ordinary skill in the art may understand that all or part of the steps carried by the method for implementing the above-mentioned embodiment may be completed by instructing related hardware through a program, and the above-mentioned program may be stored in a computer-readable storage medium, which, when executed, includes one of the steps of the method embodiment or a combination thereof.

[0102] Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limitations on the present application. Ordinary technicians in this field can change, modify, replace and modify the above embodiments within the scope of the present application.

Claims

1. A device for angiography and tissue elasticity imaging, characterized in that: include: A reference layer disposed on the surface of biological tissue; an excitation unit, used for applying a compressive excitation to the surface of the reference layer, and inducing the reference layer to deform by the excitation, thereby inducing the biological tissue to deform; An imaging unit, used for performing frequency domain optical coherence tomography on the reference layer and the biological tissue, and collecting interference intensity signal sequences in the reference layer and the biological tissue that vary with wavelength; The host computer is used to control the synchronous action of the excitation unit and the imaging unit, and perform angiography, tissue structure imaging and tissue elasticity imaging of biological tissue according to the elastic modulus of the reference layer and the interference intensity signal sequence.

2. The device for angiography and tissue elasticity imaging according to claim 1, characterized in that: The host computer is used for: Determining a complex form signal sequence of the lateral position of the target that varies with depth based on the interference intensity signal sequence of the lateral position of the target that varies with wavelength; Extracting amplitude information and phase information from a complex signal sequence of the target's lateral position that varies with depth; Perform angiography of biological tissue according to the amplitude or phase information, perform structural imaging of the reference layer and the biological tissue according to the amplitude information of the complex signal sequence at different lateral positions, calculate the strain of the reference layer structure according to the thickness change thereof, and calculate the strain of the biological tissue according to the amplitude or phase information of the biological tissue; The stress on the surface of the biological tissue is calculated based on the elastic modulus of the reference layer and the strain of the reference layer, the elastic modulus of the biological tissue is obtained based on the ratio of the stress on the surface of the biological tissue to the strain of the biological tissue, and elastic imaging of the biological tissue is performed based on the elastic modulus at different positions of the biological tissue.

3. The device for angiography and tissue elasticity imaging according to claim 1, characterized in that: The reference layer is made of a flexible semi-transparent or transparent medium.

4. The device for angiography and tissue elasticity imaging according to claim 1, characterized in that: The excitation unit includes a displacement platform, a transparent plate and a support, wherein the displacement platform applies compression excitation through displacement, the support supports the transparent plate, and the transparent plate is fixedly arranged or separated from the imaging lens of the imaging unit.

5. The device for angiography and tissue elasticity imaging according to claim 4, characterized in that: If the imaging lens of the imaging unit and the transparent plate are fixedly arranged, when the displacement platform applies compression excitation by displacement, the imaging lens and the transparent plate move simultaneously.

6. The device for angiography and tissue elasticity imaging according to claim 4, characterized in that: If the imaging lens of the imaging unit is disposed separately from the transparent plate, when the displacement platform applies compression excitation by displacement, the imaging lens remains stationary and the transparent plate moves.

7. The device for angiography and tissue elasticity imaging according to claim 1, characterized in that: The imaging unit includes at least one of a swept source optical coherence tomography optical path and a spectral domain optical coherence tomography optical path.

8. The device for angiography and tissue elasticity imaging according to claim 7, characterized in that: The swept-source optical coherence tomography optical path includes a swept-source light source, a first coupler, a first reference light path, a first sample light path and a first photodetector, wherein the first coupler is used for light splitting so that a portion of the light enters the first reference light path and a portion of the light enters the first sample light path, the light beam of the first reference light path and the light beam scattered by the first sample light path interfere with each other in the first coupler, the first photodetector detects the interference light in the first coupler, the swept-source light source outputs a single wavelength or narrow-band laser at each moment, and the first photodetector detects the interference intensity of the single wavelength or narrow-band light at each moment, and during the imaging process, the length of the first reference light path remains unchanged.

9. The device for angiography and tissue elasticity imaging according to claim 7, characterized in that: The spectral domain optical coherence tomography optical path includes a wide spectrum light source, a second coupler, a second reference optical path, a second sample optical path, a grating, and a second photodetector, wherein the second coupler is used for light splitting so that a portion of the light enters the second reference optical path and a portion of the light enters the second sample optical path, and the light beam of the second reference optical path and the light beam scattered by the second sample optical path interfere with each other in the second coupler, and the interference light of different wavelengths is spatially separated by the grating and projected to different positions of the second photodetector to achieve simultaneous detection of the intensities of interference light of different wavelengths. During the imaging process, the length of the second reference optical path remains unchanged.

10. A method of angiography and tissue elasticity imaging, characterized in that: The method uses the angiography and tissue elasticity imaging device according to any one of claims 1 to 9 to perform imaging, wherein the method comprises the following steps: The reference layer and the biological tissue are induced to deform by compressive excitation applied on the surface of the reference layer; Performing frequency domain optical coherence tomography on the reference layer and the biological tissue, and collecting interference intensity signal sequences of the reference layer and the target lateral position in the biological tissue that vary with wavelength; Determine a complex form signal sequence that varies with depth at the lateral position of the target based on an interference intensity signal sequence that varies with wavelength at the lateral position of the target, extract amplitude information and phase information in the complex form signal sequence, perform structural imaging of a reference layer and biological tissue based on the amplitude information of the complex form signal sequence at different lateral positions, calculate the strain of the reference layer based on a thickness change of the reference layer structure, and calculate the stress on the surface of the biological tissue based on the elastic modulus of the reference layer and the strain of the reference layer; Angiography of the biological tissue is performed based on the amplitude or phase information, the strain of the biological tissue is calculated based on the amplitude or phase information, the elastic modulus of the biological tissue is obtained based on the ratio of the stress on the surface of the biological tissue and the strain of the biological tissue, and elastic imaging of the biological tissue is performed based on the elastic modulus at different positions of the biological tissue.

Citation Information

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