Tissue elasticity measuring method and measuring device based on wavelength scanning

Abstract

The invention discloses a tissue elasticity measuring method and device based on wavelength scanning, and the device consists of an excitation part and an imaging function part: an excitation module is used for applying an acting force to a human body tissue, causing the tissue depression, and then causing the propagation of elastic waves on the surface of the tissue; the imaging module is based on a sweep-frequency light source OCT, point scanning of traditional OCT is converted into ultra-fast line scanning detection by adding an optical dispersion assembly (a grating or a prism) and utilizing the fast wavelength scanning function of the sweep-frequency light source, and therefore dynamic tracking and recording of elastic waves on tissues are achieved. And finally, calculating the Young modulus of the tissue by measuring the propagation velocity of elastic waves. Compared with a traditional measurement mode of repeated excitation of OCE and repeated imaging of each site, the method has the technical breakthrough point that one-time measurement can be completed within about 5 ms under single excitation, so that the discomfort caused by repeated excitation and long measurement time during in-vivo measurement of the eye tissue is reduced, and the measurement accuracy is improved. And adverse factors such as eye closing or eye movement caused by the eye closing are avoided.

Description

Technical Field

[0001] The present invention relates to the technical field related to OCT, and in particular to a tissue elasticity measurement method and a measurement device based on wavelength scanning. Background Art

[0002] Clinical significance of measurement of Young's modulus of human tissue Tissue Young's modulus is a key indicator for evaluating biomechanical properties, and plays an important role in histological research and clinical practice. In terms of disease diagnosis, by detecting the differences in Young's modulus of different tissues, it can assist in identifying tumors and assessing cardiovascular disease and the degree of liver fibrosis. During treatment monitoring, based on the changes in Young's modulus during the treatment process, the treatment effects of tumors, cardiovascular diseases, etc. can be judged, and treatment strategies can be adjusted. At the surgical guidance level, it provides a mechanical basis for organ transplant suitability assessment and minimally invasive surgical operations, reducing surgical risks. In terms of prognosis, the risk of disease recurrence can be assessed through its recovery status, the degree of patient recovery can be predicted, and clinical precision medicine can be assisted. It can be seen that the measurement of tissue Young's modulus is of great significance in the management of the entire course of the disease.

[0003] The main methods for measuring tissue Young's modulus in clinical practice Ultrasonic elastography uses a probe to emit ultrasound waves, causing the tissue to vibrate slightly, and then analyzes the deformation of the tissue under the action of elastic force based on the ultrasound signal reflected back by the tissue, thereby calculating the elastic modulus of the tissue, namely Young's modulus. This method can image tissues in real time and non-invasively, and can be used to examine organs such as the breast and thyroid gland, and can assist in determining whether a tumor is benign or malignant.

[0004] Acoustic Radiation Force Impulse Imaging (ARFI) uses an ultrasound probe to emit high-intensity sound pulses to tissues, causing local instantaneous displacement of the tissues. This displacement is then measured using ultrasound imaging technology to calculate the elastic parameters of the tissues, including Young's modulus. It can be used to measure the elasticity of solid organs such as the liver and pancreas, and is helpful in evaluating disease conditions such as the degree of liver fibrosis.

[0005] Magnetic resonance elastography (MRE) applies additional low-frequency mechanical vibration excitation on the basis of traditional magnetic resonance imaging to cause periodic elastic deformation of tissues. Then, the displacement information of tissues is collected through magnetic resonance imaging sequences, and the elastic modulus map of tissues is reconstructed using image analysis technology to obtain the Young's modulus value. MRE has a high resolution for soft tissues and can be used to examine multiple organs such as the brain, liver, and kidneys. It plays an important role in the diagnosis and evaluation of brain diseases, liver lesions, etc.

[0006] Atomic force microscopy (AFM) uses a micro cantilever that is very sensitive to force. One end of the cantilever is fixed and the other end has a tiny needle tip. When the needle tip gently touches the surface of the tissue being measured, the micro cantilever will bend or deflect due to the interaction force between atoms. The force is measured by detecting the deformation of the micro cantilever, and then the Young's modulus of the tissue is calculated based on the mechanical model. AFM can operate and measure biological samples at the nanoscale, and has unique advantages in studying the mechanical properties of biological molecules and cell surfaces, as well as the elasticity of biological membranes, which helps to gain a deeper understanding of the functions of biological molecules, the physiological and pathological processes of cells, etc.

[0007] Optical coherence elastography (OCE) technology Optical coherence elastography is a new imaging technology developed based on optical coherence tomography (OCT). It uses the elastic parameters of soft tissues such as Young's modulus, shear modulus, stress and strain as imaging objects, and evaluates the mechanical properties of tissues by measuring the tiny displacements and deformations of tissues when they are subjected to external or internal stimuli. OCE technology has shown great potential in the field of medical diagnosis with its advantages such as micron-level resolution, real-time image processing and non-invasive imaging. OCE technology has broad application prospects in the field of medical diagnosis. Especially in the diagnosis of cancer, cardiovascular disease and ophthalmic diseases, OCE technology can provide information on the mechanical properties of tissues, which helps doctors to more accurately judge the condition and formulate treatment plans. In addition, OCE technology also has the advantages of being non-invasive and high-resolution, and is suitable for a variety of clinical scenarios.

[0008] Traditional OCE uses the MB scanning mode, that is, after repeated scanning perpendicular to a specific scanning line, a two-dimensional grayscale image of the tissue is constructed based on the optical coherence signal, and then the dynamic response characteristics such as displacement amplitude are obtained by analyzing the interference signal that changes with time along the specific scanning line, thus realizing the comprehensive detection of the elastic properties of the tissue in both time and space dimensions. However, at the same time, the repeated stimulation caused by its scanning will cause discomfort to the subjects. For example, in ophthalmic measurements, it may cause inaccurate measurements caused by eye closure and movement. This limitation has hindered the widespread adoption of this technology in medical clinical applications, especially in the field of ophthalmology. Summary of the invention

[0009] In order to solve the technical defects existing in the prior art, the present invention provides a tissue elasticity measurement method and a measurement device based on wavelength scanning, which can use a single excitation to complete a measurement in milliseconds or about 5ms, thereby reducing the discomfort caused by repeated excitation and long measurement time during in-vivo measurement of eye tissue, and avoiding adverse factors such as eye closure or eye movement caused by this; at the same time, the method can collect images with high resolution and high sensitivity, and through image analysis, objective parameter indicators related to the evaluation of tissue elasticity can be obtained.

[0010] The technical solution adopted by the present invention is: using a tissue elasticity measurement method based on wavelength scanning, comprising the following steps: S1, applying a single instantaneous mechanical excitation to the target tissue through the excitation module to generate elastic waves on the tissue surface; S2, using a swept-source OCT system, the wavelength scanning of the incident light beam is converted into a line scanning mode arranged by wavelength through a dispersion component, and the dynamic deformation interference signal of the tissue after excitation is collected in real time; S3, the imaging module uses continuous acquisition to record the real-time and dynamic changes of tissue morphology under external stimulation; S4. Through image analysis, objective parameter indicators related to evaluating tissue elasticity can be obtained.

[0011] Preferably, the step S4 comprises the following steps: S41, calculating the tissue displacement corresponding to each frame of the interference signal or the corresponding phase change through Fourier transform and other algorithms; S42, calculating the propagation speed of the elastic wave by calculating the time-space distribution signal of the phase or displacement; S43. Calculate the elastic modulus of the target tissue according to the relationship model between elastic wave velocity and Young's modulus.

[0012] Preferably, the line scanning mode in step S2 is implemented by a prism, a reflective or transmissive grating, to form a line field scan covering the target area.

[0013] Preferably, the system can further expand the one-dimensional line field scanning into two-dimensional surface field scanning through a one-dimensional scanning galvanometer.

[0014] Preferably, the excitation module is one of air pulses, piezoelectric transducers or ultrasonic generators, and the excitation application time is precisely aligned with the OCT acquisition start time through a synchronous controller. After OCT starts acquisition, the excitation function module emits a single excitation at the edge of the target position. After the excitation ends, OCT continues to acquire to obtain the tissue structure under tissue compression conditions.

[0015] Preferably, the excitation duration of the excitation module is less than 5 ms.

[0016] Preferably, the grating assembly is a reflective grating with a groove density of 1200 lines / mm.

[0017] A measuring device for realizing a tissue elasticity measurement method, the measuring device comprising an OCT module and an excitation module, the OCT module comprising a light source, the light emitted by the light source entering an imaging probe via an optical coupler, the imaging probe further being provided with a collimator along the optical path direction, the light passing through the collimator is emitted toward a grating, and a tissue sample is scanned in parallel through an objective lens, the measuring device further comprising a reflector in a reference optical path, the OCT detection light is reflected by the tissue, returns via the original optical path, and is coupled into the optical coupler, generating interference with the light returned by the reflector in the reference optical path, and the interference signal is acquired by the detector.

[0018] Preferably, the excitation module is disposed at the front end of the tissue sample to be tested, and exerts force on human tissue to cause tissue depression, thereby causing phase changes at various positions of the tissue.

[0019] Preferably, a synchronization control module is also included, and the synchronization control module is used to coordinate the timing of the acquisition of the OCT module and the excitation application of the excitation module to ensure that the excitation is triggered after the OCT module starts to acquire, and the OCT module continues to acquire at least until the elastic wave attenuation ends.

[0020] The beneficial effect of the present invention is that the present invention provides a method for ultra-fast, non-contact, quantitative measurement of human tissue elasticity. The application objects include but are not limited to tissue structures such as the human cornea, and the cornea is shown in the figure. This wavelength scanning-based tissue elasticity measurement method is based on the swept light source OCT. By adding an optical dispersion element (grating or prism) and utilizing the fast wavelength scanning function of the swept light source, the point scanning of the traditional OCT is converted into an ultra-fast line scanning detection, thereby realizing the dynamic tracking and recording of elastic waves on the tissue, and finally calculating the Young's modulus of the tissue by measuring the propagation speed of the elastic wave. Compared with the measurement mode of repeated excitation and repeated imaging of each site of the traditional OCE, the technical breakthrough of this method is that it can complete a measurement in about 5ms under a single excitation, thereby reducing the discomfort caused by repeated excitation and long measurement time when the eye tissue is measured in vivo, and avoiding the adverse factors such as closing the eyes or eye movement caused by this. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Schematic diagram of the measuring device of the present invention.

[0022] Figure 2It is a schematic diagram of the data processing flow of the present invention; wherein Interference Signal: interference signal; Complex Signal: complex signal; STFT: short-time Fourier transform; PRCD: phase-resolved color Doppler algorithm; Spatial-Temporal Phase Map: spatial-temporal phase distribution map; Spatial-Temporal Displacement Map: spatial-temporal displacement distribution map; Distance-Time Delay Curve: distance-time delay curve; TOF: time-of-flight algorithm; Linear Fitting: linear fitting.

[0023] Among them, 1-OCT module, 2-excitation module, 3-tested eyeball, 4-light source, 5-detector, 6-optical coupler, 7-reflector, 8-collimator, 9-grating, 10-objective lens, 11-cornea, 12-iris, and 13-lens. DETAILED DESCRIPTION

[0024] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0025] A measuring device for realizing a tissue elasticity measurement method, the measuring device comprises an OCT module 1 and an excitation module 2, the OCT module 1 comprises a light source 4, the light emitted by the light source 4 enters an imaging probe through an optical coupler 6, the imaging probe is also provided with a collimator 8 along the optical path direction, the light passes through the collimator 8 and is emitted to a grating 9, and then dispersed according to wavelength to generate a diffraction beam, and the tissue sample is scanned in parallel through an objective lens 10, the measuring device also comprises a reflector 7 in a reference optical path, the OCT detection light is reflected by the tissue, returns through the original optical path, and is coupled into the optical coupler 6, and interferes with the light returned by the reflector 7 in the reference optical path, and the interference signal is obtained by a detector 5. The excitation module 2 is arranged at the front end of the tissue sample to be measured, and exerts a force on the human tissue to cause tissue depression, thereby causing the propagation of elastic waves on the tissue surface. A synchronous control module is also included, and the synchronous control module is used to coordinate the timing of the acquisition of the OCT module 1 and the excitation application of the excitation module 2, to ensure that the excitation is triggered after the OCT module 1 starts to acquire, and the OCT module 1 continues to acquire at least until the elastic wave attenuation ends.

[0026] The external excitation of the excitation module can be in various forms, including but not limited to air, PZT and ultrasound, etc. The air excitation module is used in the example. The main function of this module is to apply a specific form of excitation to biological tissues, so that the tissues produce measurable small deformations. In this way, the elastic property information of the tissue under stress can be obtained, because tissues with different elasticity will produce different degrees and patterns of deformation under the same excitation. The excitation function module provides a basis for obtaining quantitative parameters of tissue elasticity. By precisely controlling the intensity, frequency and other parameters of the excitation, combined with subsequent optical measurement and data analysis, quantitative indicators such as the elastic modulus of the tissue can be calculated, providing a more accurate and objective basis for medical diagnosis and research. The OCT module and the excitation function module need to run synchronously. After OCT starts collecting, the excitation function module emits a single excitation at the edge of the target position. After the excitation ends, OCT continues to collect to obtain the tissue structure under tissue compression conditions.

[0027] Example 1 The system used a swept source laser with a bandwidth of 100 nm and a scanning repetition rate of 100 kHz. After the collimator, a reflection grating with a groove density of 1200 lines / mm was incorporated into the sample arm. Subsequently, the wavelength was scanned using the first-order diffracted beam from the grating. The objective lens with a focal length of 50 mm produced a line focus of 6.285 mm in length and a total power of 1.0 mW on the sample.

[0028] After the system is excited by air pulses, 512 a-lines are repeatedly collected, each containing 1024 points, and a two-dimensional data set of 1024 × 512 points is obtained by scanning the wavelength-dispersed beam in the spatial dimension. At a line scan rate of 100 kHz, a measurement can be completed in about 5 ms.

[0029] Data processing includes the following steps: (1) Set a sliding window with a width of 64 pixels and a step size of 5 pixels, and use the sliding window to perform short-time Fourier transform on the interference signal. Therefore, each a-line data has 193 segments, each containing 32 complex signals; (2) Considering all segments at the same position in the time dimension, a subset of 32 × 512 points is formed. The phase difference Δϕ between the a-lines separated by 5 pixels at each position is calculated using the phase-resolved color Doppler (PRCD) algorithm; (3) After all subsets are processed, the three-dimensional data sets of each phase are projected axially onto the spatiotemporal phase distribution map. Finally, a further displacement map is obtained; (4) The time-of-flight method is used to calculate the displacement delay of each segment. The group velocity can be determined by linearly fitting this distance-time delay curve.

[0030] The results are as follows Figure 2 shown.

[0031] Technical personnel should note that although the present invention has been explained through the above specific implementation methods, the inventive concept of the present invention is not limited thereto. Any improvement or variation based on the inventive concept belongs to the protection scope of this patent right.

[0032] The above is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above embodiments and experimental examples. Any technical solution that follows the concept of the present invention is included in the protection scope of the present invention. It should be emphasized that for ordinary technicians in this technical field, without departing from the purpose and scope of the present invention, any modification or equivalent replacement should be regarded as part of the protection scope of the present invention.

Claims

1. A method for measuring tissue elasticity based on wavelength scanning, characterized in that: The following steps are involved: S1, applying a single instantaneous mechanical excitation to the target tissue through the excitation module to generate elastic waves on the tissue surface; S2, using a swept-source OCT system, the wavelength scanning of the incident light beam is converted into a line scanning mode arranged by wavelength through a dispersion component, and the dynamic deformation interference signal of the tissue after excitation is collected in real time; S3, the imaging module uses continuous acquisition to record the real-time and dynamic changes of tissue morphology under external stimulation; S4. Through image analysis, objective parameter indicators related to evaluating tissue elasticity can be obtained.

2. The method for measuring tissue elasticity based on wavelength scanning according to claim 1, characterized in that: The step S4 comprises the following steps: S41, calculating the tissue displacement corresponding to each frame of the interference signal or the corresponding phase change through Fourier transform and other algorithms; S42, calculating the propagation speed of the elastic wave by calculating the time-space distribution signal of the phase or displacement; S43. Calculate the elastic modulus of the target tissue according to the relationship model between elastic wave velocity and Young's modulus.

3. The method for measuring tissue elasticity based on wavelength scanning according to claim 1, characterized in that: In step S2, the line scanning mode is implemented by a prism, a reflective or transmissive grating, forming a line field scan covering the target area, and the one-dimensional line field scan is expanded into a two-dimensional surface field scan by a one-dimensional scanning galvanometer.

4. The method for measuring tissue elasticity based on wavelength scanning according to claim 3, characterized in that: The excitation module is one of air pulses, piezoelectric transducers or ultrasonic generators. The excitation application time and the start time of OCT acquisition are precisely aligned through a synchronous controller. After OCT starts acquisition, the excitation function module emits a single excitation at the edge of the target position. After the excitation ends, OCT continues to acquire to obtain the propagation state of elastic waves on the tissue.

5. The method for measuring tissue elasticity based on wavelength scanning according to claim 4, characterized in that: The excitation duration of the excitation module is less than 2ms.

6. The method for measuring tissue elasticity based on wavelength scanning according to claim 1, characterized in that: The dispersion component is a grating.

7. A measuring device for implementing the tissue elasticity measuring method according to claim 1, characterized in that: The measuring device comprises an OCT module (1) and an excitation module (2). The OCT module (1) comprises a light source (4). Light emitted by the light source (4) enters an imaging probe via an optical coupler (6). The imaging probe is also provided with a collimator (8) along the optical path. After passing through the collimator (8), the light is emitted toward a grating (9) and scans a tissue sample in parallel via an objective lens (10). The measuring device also comprises a reflector (7) in a reference optical path. After being reflected by the tissue, the OCT detection light returns via the original optical path and is coupled into the optical coupler (6). Interference is generated with the light returned by the reflector (7) in the reference optical path, and an interference signal is acquired by a detector (5).

8. The measuring device of the tissue elasticity measuring method according to claim 7, characterized in that: The excitation module (2) is arranged at the front end of the tissue sample to be tested, and exerts force on human tissue to cause tissue depression, thereby causing the propagation of elastic waves on the tissue surface.

9. The measuring device of the tissue elasticity measuring method according to claim 7, characterized in that: It also includes a synchronization control module, which is used to coordinate the timing of the acquisition of the OCT module (1) and the excitation application of the excitation module (2), ensuring that the excitation is triggered after the OCT module (1) starts to acquire, and that the OCT module (1) continues to acquire at least until the elastic wave attenuation ends.

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