A corneal elastic modulus measurement device and method based on magnetic nanoparticle excitation

Abstract

A corneal elastic modulus measurement device and method based on magnetic nanoparticle excitation, including a soft magnetic nanoparticle contact lens, an electromagnetic excitation module, an OCT module, and a data processing module. The soft contact lens is wrapped with a sealing film and attached to the corneal surface, and generates a mechanical response under the controllable magnetic field generated by the electromagnetic coil; the OCT module synchronously captures dynamic deformation images before and after excitation, and its optical path is coaxially adapted with the annular electromagnetic structure to ensure synchronization of imaging and excitation. The data processing module extracts displacement information through multi-stage signal processing, combines the magnetic field force and the correction coefficient to compensate for the influence of corneal geometric parameters, and generates a high-resolution two-dimensional elastic modulus map. The system realizes real-time regional measurement of corneal mechanical properties with micron-level resolution, avoids the inadaptability of traditional technology with millimeter-level deformation, significantly improves the detection accuracy, safety and comfort, and is suitable for precise diagnosis and treatment evaluation of clinical corneal diseases.

Description

TECHNICAL FIELD

[0001] The present application relates to corneal mechanical property measurement, in particular to a corneal elastic modulus measurement device and method based on magnetic nanoparticle excitation. BACKGROUND

[0002] The cornea, as an important part of the eye, plays an important role in maintaining the shape of the eyeball, protecting the eye from injury, and participating in the refractive function of the eye, so the research on the cornea is crucial. At present, the research on the cornea mainly focuses on the morphological and pathological aspects, while the research on the mechanical properties of the cornea is still in its infancy.

[0003] Medical research shows that the normal cornea is composed of five layers, from outside to inside, the epithelial cell layer (50 μm), the anterior elastic layer (15 μm), the stroma layer (450 μm), the posterior elastic layer (5 μm) and the endothelial cell layer (5 μm). Each layer is composed of certain collagen fibers, and the orientation and arrangement of these collagen fibers directly affect the mechanical properties of the cornea. Among them, the collagen fibers near the center of the cornea are more dense than the periphery, and the density of the collagen fibers decreases from front to back. The biomechanics of the cornea determines the shape of the cornea, which in turn affects its visual function.

[0004] In view of this, how to accurately, quickly and safely measure the mechanical properties of the corneal stroma layer, and distinguish the differences in mechanical properties of different regions has become a key problem. In addition, the research on the mechanical properties of the cornea can also promote the development of the field of corneal mechanics related diseases. In order to achieve early diagnosis, patient-specific treatment and evaluation of its effectiveness, there is an increasing need for high-resolution screening methods that can assess spatial variations in corneal biomechanics with high sensitivity. At the same time, accurate knowledge of the mechanical properties of the cornea is also crucial for identifying risk factors and preventing serious complications before refractive surgery.

[0005] In recent years, with the development of optical coherence tomography (OCT), it has become possible to observe the characteristics of the cornea using OCT. Compared with atomic force microscopy (AFM), ultrasonic elastography (UE) and other technologies, the relative spatial resolution and penetration depth of OCT are more in line with the observation and detection requirements of the cornea. However, the current OCT device still has a frame rate problem, and under the condition of ensuring clarity, OCT is only suitable for shooting static pictures, and cannot meet the requirements of high frame rate shooting. OCT uses the principle of Michelson interferometer to obtain the depth information of the sample by using the interference information of coherent light. Optical coherence elastography (OCE) uses an excitation device to generate excitation, and then uses OCT to observe.

[0006] The development of a corneal mechanical property measuring instrument is of great significance to the preoperative diagnosis and evaluation of doctors and the planning of postoperative treatment programs. However, there is currently no instrument on the market for directly measuring the mechanical properties of the cornea. The more mature instrument is the non-contact intraocular pressure analyzer (ORA and Corvis ST). At the same time, the hospital currently assesses the mechanical properties of the cornea by detecting the intraocular pressure, but this assessment is not accurate because there is a complex coupling relationship between the intraocular pressure and the mechanical properties of the cornea, and the two cannot be equated.

[0007] The current instrument for evaluating the biomechanics of the cornea is Corvis ST, which introduces the use of a high-speed (4300 frames / second) Scheimpflug camera to capture air-induced (maximum pressure: 25 kpa) corneal deformation. According to the collected multiple frames of images, multiple parameters are obtained, and according to a large amount of medical data, regression analysis is performed to propose a new evaluation index SSI. The SSI index is calculated according to the parameters in the multiple frames of images through a linear equation. The specific regression data is based on the corneal hardness of a 50-year-old healthy sample as an index, defined as SSI = 1, so that the size relationship between SSI and 1 is used to judge the corneal hardness of the patient. The result has a large inaccuracy. Secondly, the SSI index obtained with the help of the Corvis ST device can only evaluate the overall value of the cornea, and cannot evaluate different regions of the cornea or the depth direction of the cornea. Secondly, the Corvis ST needs to use blowing to make the cornea deform by millimeters, and the patient's experience is poor. Therefore, it is necessary to develop a more accurate, real-time, safe and comfortable corneal mechanical property measuring instrument.

[0008] CN110974148A discloses a detection based on air pulse optical coherence elastography technology. Its detection accuracy is still in the millimeter level, and a two-dimensional elastic image of the cornea is not obtained. At the same time, the current corneal mechanics evaluation patents all use a single excitation mode, and with the help of experiments, the influence of intraocular pressure is corrected and eliminated from the results. This method is prone to result errors, which affects the results and causes inaccuracies. In addition, in the existing magnetic nanoparticle optical coherence elastography technology, magnetic nanoparticles are mainly used as contrast agents for imaging. Moreover, the detection accuracy of the current OCT cannot reach the nanometer level, and the displacement of the magnetic nanoparticles cannot be detected. In addition, there is a problem of recycling of magnetic nanoparticles, which involves safety issues to be solved.

[0009] It should be noted that the information disclosed in the above background section is only for understanding the background of the present application, and therefore can include information that does not constitute prior art known to those of ordinary skill in the art. SUMMARY

[0010] The main purpose of the present application is to overcome the defects existing in the background art, provide a corneal elastic modulus measurement device and method based on magnetic nanoparticle excitation, realize high-precision real-time evaluation of spatial distribution of corneal mechanical properties.

[0011] In order to achieve the above purpose, the present application adopts the following technical solutions:

[0012] A corneal elastic modulus measurement device based on magnetic nanoparticle excitation, comprising:

[0013] A soft magnetic nanoparticle contact lens composed of magnetic nanoparticles wrapped by a sealing film, used for attaching to the corneal surface and generating a mechanical response through magnetic field excitation;

[0014] An electromagnetic excitation module containing an electromagnetic coil for generating a controllable magnetic field to drive the magnetic nanoparticles to apply a push-pull force;

[0015] An optical coherence tomography (OCT) module for real-time capture of corneal dynamic deformation images before and after excitation;

[0016] A data processing module for extracting displacement information based on the dynamic deformation images and calculating the real-time elastic modulus distribution of the cornea through an elastic modulus algorithm combined with stress data;

[0017] Wherein, the electromagnetic coil structure of the electromagnetic excitation module is coaxially adapted to the optical path of the OCT module, so that the magnetic field excitation and optical imaging are synchronized, and the data processing module realizes displacement tracking and strain-stress conversion of dynamic deformation signals through multi-stage signal processing, generating a two-dimensional map of corneal elastic modulus.

[0018] Further, the sealing film of the soft magnetic nanoparticle contact lens adopts a double-layer hydrogel structure, which is formed by centrifugal spin coating process, and the magnetic nanoparticles have a pre-set particle size range and paramagnetism to ensure that a measurable stress-strain is generated under magnetic field excitation.

[0019] Further, the electromagnetic excitation module adopts a coreless annular coil design, the inner diameter of the coil matches the imaging light path of the OCT module, and the magnetic field strength and heat dissipation performance are ensured through structure and size selection design to avoid overheating of the electromagnet.

[0020] Further, the high-frame-rate OCT module includes a swept source, a beam splitter, a reference arm and a sample arm lens group, and a balanced detector; the sample arm lens group is conjugate focused with the corneal surface, and the imaging frame rate is improved to more than 200 frames / s by optimizing the light source parameters and scan line number.

[0021] Further, the high frame rate OCT module further comprises a high pass filter for frequency domain filtering of the electrical signal output by the balanced detector to filter out low frequency physiological motion artifacts below 100 Hz; the optical path of the reference arm mirror group and the sample arm mirror group are matched to ensure synchronous capture of corneal deformation signals at different depths.

[0022] Further, the data processing module is configured to perform the following elastic modulus algorithm:

[0023] Time domain averaging is performed on the original image signal to suppress high frequency noise;

[0024] The denoised signal is subjected to frequency domain transformation, and low frequency physiological motion artifacts are separated by high pass filtering;

[0025] The phase change of the laser speckle is tracked to track the deformation of the cornea, the phase difference is extracted by autocorrelation analysis, and the displacement distribution is calculated by integration;

[0026] The local strain is derived from the displacement difference of the two excitations and the corneal thickness, and the stress distribution is calculated in combination with the magnetic field force;

[0027] The elastic modulus of the cornea is generated by the ratio of strain to stress.

[0028] Further, the elastic modulus algorithm further introduces a correction coefficient for compensating for the deviation of the sealing film thickness, corneal curvature and intraocular pressure on the calculation result.

[0029] Further, the electromagnetic excitation module adopts a double excitation timing control, and two magnetic field excitations are applied at intervals to acquire baseline calibration images, so as to eliminate the interference of intraocular pressure on the elastic modulus measurement.

[0030] A real-time measurement method for corneal elastic modulus based on magnetic nanoparticle excitation, comprising the following steps:

[0031] S1, attach a soft magnetic nanoparticle contact lens to the corneal surface, and start the high frame rate OCT module to obtain a baseline corneal image;

[0032] S2, control the electromagnetic excitation module to apply a magnetic field to drive the magnetic nanoparticles to generate push-pull force excitation on the cornea;

[0033] S3, real-time capture of dynamic deformation images before and after excitation by the high frame rate OCT module;

[0034] S4, multi-stage signal processing of the deformation images to extract displacement information and calculate the elastic modulus distribution of the cornea;

[0035] The signal processing includes noise suppression, artifact removal, speckle tracking and strain-stress conversion, and finally generates a corneal elastic modulus map.

[0036] Further, the signal processing in step S4 specifically includes:

[0037] (a) time domain average processing is performed on the original image signal to suppress high frequency noise;

[0038] (b) frequency domain transformation is performed on the denoised signal, and low frequency physiological motion artifacts are separated through high pass filtering;

[0039] (c) corneal deformation is tracked based on phase change of laser speckle, phase difference is extracted through autocorrelation analysis, and displacement distribution is calculated by integration;

[0040] (d) local strain is derived according to displacement difference of two excitations and corneal thickness, stress distribution is calculated by combining magnetic field force and correction coefficient, and the correction coefficient is used to compensate the influence of sealing film thickness, corneal curvature and intraocular pressure;

[0041] (e) corneal elastic modulus two-dimensional atlas is generated through the ratio relationship between strain and stress.

[0042] The present application has the following beneficial effects:

[0043] The present application provides a corneal elastic modulus measurement device and method based on magnetic nanoparticle excitation, which realizes high-precision real-time measurement of corneal elastic modulus by integrating a soft magnetic nanoparticle contact lens, a ring-shaped electromagnetic excitation module and a high-frame-rate optical coherence tomography (OCT) system. The core advantage is that magnetic nanoparticles are used as a mechanical excitation source, combined with a high-frame-rate OCT dynamic imaging technology with micron-level resolution, which can obtain the mechanical properties of different regions of the cornea in one measurement, and optimally eliminate the influence of intraocular pressure based on a double excitation mode. Through a multi-stage signal processing algorithm, corneal deformation is tracked and strain-stress conversion is performed, and finally a two-dimensional elastic modulus atlas is generated. Compared with the prior art, the present scheme avoids the discomfort caused by millimeter-level deformation excitation, significantly improves the detection comfort and safety with non-invasive contact lenses and low-intensity magnetic fields, and solves the limitations of traditional devices that can only evaluate the overall corneal hardness and rely on empirical regression models, providing a more accurate and real-time corneal mechanical evaluation method for clinical use.

[0044] Other beneficial effects of the embodiments of the present application will be further described below. BRIEF DESCRIPTION OF DRAWINGS

[0045] Figure 1 is a schematic diagram of the corneal elastic modulus real-time measurement device of the embodiments of the present application.

[0046] Figure 2 is a hardware schematic diagram of the embodiments of the present application.

[0047] Figure 3A flow chart of the method for real-time measurement of corneal elastic modulus of the present application.

[0048] Figure 4 A flow chart of the data processing of the embodiment of the present application. DETAILED DESCRIPTION

[0049] The embodiments of the present application will be described in detail below. It should be emphasized that the following description is merely exemplary and is not intended to limit the scope of the present application and its applications.

[0050] It should be noted that when an element is referred to as being "fixed" or "attached" to another element, it can be directly on the other element or indirectly on the other element, with one or more intervening elements. When an element is referred to as being "connected" or "coupled" to another element, it can be directly connected or coupled to the other element or indirectly connected or coupled to the other element, with one or more intervening elements. Further, connections can be established for fixed or coupling or communicative purposes.

[0051] It should be understood that the terms "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like, specify relative positions or orientations based on the orientations or positions shown in the drawings, and are used only for convenience in describing the embodiments of the present application and simplifying the description, and thus cannot be understood as indicating or implying that the indicated device or element must have a particular orientation, be constructed and operated in a particular orientation, and thus cannot be understood as limiting the present application.

[0052] In addition, the terms "first", "second", and the like, are used only for descriptive purposes, and cannot be understood as indicating or implying relative importance or an implied indication of the number of the indicated technical features. Thus, the features defined with "first", "second" can explicitly or implicitly include one or more of the features. In the description of the embodiments of the present application, the meaning of "plurality" is two or more, unless otherwise specifically limited.

[0053] Reference is made to Figure 1 and Figure 2The embodiment of the present application provides a corneal elastic modulus measurement device based on magnetic nanoparticle excitation, which comprises: a soft magnetic nanoparticle contact lens composed of a magnetic nanoparticle layer 4 wrapped by a sealing film 3, which is used for attaching to the corneal surface of a human eye 5 and generating a mechanical response through magnetic field excitation; an electromagnetic excitation module 2 containing an electromagnetic coil, preferably annular, which is used for generating a controllable magnetic field to drive the magnetic nanoparticle 41 to apply a push-pull force; an optical coherence tomography module, namely an OCT module 1, which is used for capturing dynamic deformation images of the cornea before and after excitation in real time; a data processing module which is used for extracting displacement information based on the dynamic deformation images and calculating the real-time elastic modulus distribution of the cornea through an elastic modulus algorithm combined with stress data; wherein the electromagnetic coil structure of the electromagnetic excitation module 2 is coaxially adapted to the optical path of the OCT module 1 to ensure that the magnetic field excitation and optical imaging are performed synchronously, and the data processing module realizes displacement tracking of dynamic deformation signals and strain-stress conversion through multi-stage signal processing to generate a two-dimensional atlas of corneal elastic modulus.

[0054] Referring to Figure 2 In the preferred embodiment, the sealing film 3 of the soft magnetic nanoparticle contact lens adopts a double-layer hydrogel structure and is formed through a centrifugal spin coating process, and the magnetic nanoparticle 41 has a preset particle size range and paramagnetism to ensure that a measurable stress and strain are generated under magnetic field excitation.

[0055] In the preferred embodiment, the electromagnetic excitation module 2 adopts a coreless annular coil design, the inner diameter of the coil matches the imaging light path of the OCT module 1, and the magnetic field strength and heat dissipation performance are ensured through the selection and design of the structure and size to avoid overheating of the electromagnet.

[0056] In some embodiments, the OCT module 1 comprises a swept source, a beam splitter, a reference arm and a sample arm mirror group, and a balanced detector; the sample arm mirror group is conjugate focused with the corneal surface, and the imaging frame rate is improved to more than 200 frames / s by optimizing the light source parameters and the number of scanning lines.

[0057] In some embodiments, the OCT module 1 further comprises a high-pass filter for frequency domain filtering of the electrical signal output by the balanced detector to filter out low-frequency physiological motion artifacts below 100 Hz; the optical path of the reference arm mirror group and the sample arm mirror group is matched to ensure synchronous capture of deformation signals at different depths of the cornea.

[0058] In a preferred embodiment, the data processing module is configured to perform an elastic modulus algorithm as follows: time domain averaging of the original image signal to suppress high frequency noise; frequency domain transformation of the de-noised signal and separation of low frequency physiological motion artifacts by high pass filtering; tracking of corneal deformation based on phase change of laser speckle, extracting phase difference by autocorrelation analysis, and integrating to calculate displacement distribution; deriving local strain from displacement difference of two excitations and corneal thickness, and calculating stress distribution in combination with magnetic field force; generating two-dimensional atlas of corneal elastic modulus through the ratio relationship between strain and stress. In a further preferred embodiment, the elastic modulus algorithm further introduces a correction coefficient for compensating for the deviation of the sealing film thickness, corneal curvature and intraocular pressure on the calculation results.

[0059] In a preferred embodiment, the electromagnetic excitation module 2 adopts a double excitation time sequence control, and two magnetic field excitations are applied at intervals to acquire baseline calibration images, so as to eliminate the interference of intraocular pressure on the elastic modulus measurement.

[0060] Referring to Figure 3 and Figure 4 , the embodiment of the present application also provides a real-time measurement method of corneal elastic modulus based on magnetic nanoparticle excitation, comprising the following steps:

[0061] Step S1, attaching a soft magnetic nanoparticle contact lens to the corneal surface, and starting the OCT module 1 to acquire baseline corneal images;

[0062] Step S2, controlling the electromagnetic excitation module 2 to apply a magnetic field to drive the magnetic nanoparticles to produce push-pull force excitation on the cornea;

[0063] Step S3, capturing dynamic deformation images before and after excitation in real time by the OCT module 1;

[0064] Step S4, performing multi-stage signal processing on the deformation images to extract displacement information and calculate the distribution of corneal elastic modulus;

[0065] Wherein, the multi-stage signal processing includes noise suppression, artifact removal, speckle tracking and strain-stress conversion, and finally generates a corneal elastic modulus atlas.

[0066] In the preferred embodiment, the signal processing in step S4 specifically includes: (a) time domain average processing of the original image signal to suppress high frequency noise; (b) frequency domain transformation of the de-noised signal and separation of low frequency physiological motion artifacts through high pass filtering; (c) tracking of corneal deformation based on phase change of laser speckle, extracting phase difference through autocorrelation analysis, and integrating to calculate displacement distribution; (d) deriving local strain according to displacement difference of two excitations and corneal thickness, calculating stress distribution in combination with magnetic field force and correction coefficient, the correction coefficient being used to compensate the influence of sealing film thickness, corneal curvature and intraocular pressure; (e) generating two-dimensional atlas of corneal elastic modulus through the ratio relationship between strain and stress.

[0067] The present application builds an innovative corneal mechanical detection scheme by cooperating the soft magnetic nanoparticle corneal contact lens module, the electromagnetic excitation module and the OCT module, and realizes safe, accurate, efficient and real-time measurement of corneal mechanics. Compared with the prior art, the present application can realize safer and more accurate corneal mechanical measurement, and the introduction of magnetic nanoparticles can improve the comfort, safety and accuracy of corneal mechanical detection to a new height.

[0068] The specific embodiments of the present application are further described below.

[0069] A corneal elastic modulus real-time measurement device mainly includes a soft magnetic nanoparticle corneal contact lens module, an electromagnetic excitation module, an OCT module and a data processing module. The soft magnetic nanoparticle corneal contact lens is composed of two layers of hydrogel sealing film wrapped around magnetic nanoparticles. The hydrogel is made into a thin layer by centrifugal spin coating technology and is demolded by temperature difference. It not only prevents the leakage of magnetic nanoparticles to ensure the safety of measurement, but also improves the measurement sensitivity and reduces the error. The sealing reliability can be tested and verified by soaking and kneading with artificial tears. The magnetic nanoparticles can be selected from biocompatible materials (such as clinically approved iron oxide particles) that meet clinical standards. The magnetic nanoparticles need to meet the specific particle size requirements and have paramagnetism to ensure that enough stress and strain are generated under the action of the magnetic field. The OCT module adopts a high frame rate OCT system.

[0070] The electromagnetic excitation module adopts a non-iron core structure composed of a ring-shaped magnet coil and a wire. This design not only ensures that the light of the high frame rate OCT system can reach the corneal imaging without obstruction, but also optimizes the structure and size to generate sufficient magnetic field strength while avoiding overheating of the device. The high frame rate OCT system optimizes the light source parameters, imaging field of view and acquisition line number to improve the frame rate to 200 frames per second on the premise of ensuring the resolution, and realizes accurate capture of dynamic images with the help of high pass filter and other components.

[0071] When the device is in operation, the contact lens is first attached to the corneal surface, and after being powered on, the electromagnetic excitation module generates a push-pull force on the magnetic nanoparticles, and the high-frame-rate OCT synchronously records the corneal images before and after excitation. In particular, it adopts a double-excitation mode to eliminate the interference of intraocular pressure on the measurement results through two excitations. The corneal elasticity image algorithm is run by the data processing module, which can comprehensively consider factors such as corneal thickness, curvature, internal pressure, and hydration degree, combine the strain information obtained by detection with the stress data provided by the device, and accurately calculate the real-time elastic modulus of the cornea after multi-stage signal processing, and generate a two-dimensional atlas.

[0072] The specific data processing process is shown in Figure 3 and Figure 4 The electrical signal information of corneal movement is obtained through the data acquisition card, which is the original image. The following processing steps are then performed.

[0073] 1) Denoising: The original image will have a lot of high-frequency noise. Therefore, the obtained electrical signal needs to be denoised. The specific operation is to average the signal information of 10 time points as the true information of the point at the previous time period . That is:

[0074]

[0075] wherein, represents the electrical signal intensity (original image signal) at the t time.

[0076] 2) Artifact removal: After processing, the image not only has the original high-frequency noise caused by the system, but also has low-frequency noise caused by factors such as heart skipping, blood vessels, blinking, and involuntary head movement during the detection process. After detection, the frequency of this noise is <100Hz. Different from the excitation frequency of 1200Hz. High-pass filtering is used to remove low-frequency noise. The denoised signal obtained by acquisition is subjected to Fourier transform to obtain a complex signal F(z). That is:

[0077]

[0078] wherein, represents the signal amplitude, represents the signal phase.

[0079] Then, through high-pass filtering, low-frequency signals below 100Hz are removed. The specific formula is:

[0080]

[0081] wherein is the cutoff frequency, R is the set resistance value, and C is the set capacitance value.

[0082] 3) Speckle tracking: Speckle tracking is based on the principle of laser speckle phenomenon. By analyzing the changes of speckle pattern, the movement or deformation of the object can be tracked and measured. When laser irradiates the surface of the object, due to the micro-rough structure of the object surface, the reflected light will interfere with each other to form a speckle pattern. When the object moves or deforms, the speckle pattern will change accordingly. By capturing and analyzing these changes, the movement state or internal stress, displacement, etc. of the object can be inferred.

[0083] 4) Displacement image. The autocorrelation analysis of complex-valued signal can obtain the phase information of the signal. That is:

[0084] ,

[0085] wherein, and represent the complex-valued signals of the first i and the first i sampling, respectively. It can be unified as phase-resolved OCT measurement, and the phase jump can be corrected by known phase unwrapping algorithm (such as adjacent pixel threshold correction).

[0086] Accordingly, by the following formula, the displacement information d of the cornea can be obtained.

[0087] ,

[0088] wherein, represents the center wavelength of the OCT light source, represents the refractive index of the corneal tissue, represents the time interval of signal acquisition, represents the time difference of two samplings.

[0089] 5) Modulus image. According to the displacement information of two excitations, the displacement difference is , and the corneal thickness CCT. The strain can be obtained by the following formula:

[0090] ,

[0091] The stress can be calculated by the following formula:

[0092] ,

[0093] wherein, the force of the magnetic field on the magnetic nanoparticle is , the force on the cornea is , the particle size of the magnetic nanoparticle is r, is a correction coefficient, which corrects the influence of the sealing film thickness, surface curvature, etc. on the actual stress. The magnetic field force The corresponding relationship between the excitation parameters and the corneal Young's modulus can be determined by standard samples (such as PDMS gel) calibration or electromagnetic simulation (such as COMSOL) and the like. The correction coefficient can be divided into sealing film, corneal curvature and the like, and determined by film mechanics measurement, curved surface model or experimental fitting respectively. Finally, the corneal elastic modulus E of a certain point on the cornea is:

[0094] .

[0095] Accordingly, the accurate Young's modulus of the cornea can be obtained under the consideration of the corneal thickness, the corneal surface curvature and the intraocular pressure.

[0096] Examples

[0097] The overall detection route is that, during detection, the person to be detected places his head at a specified position, clicks "start positioning", the detection device finds the corneal position through a positioning algorithm, then the device moves and aims the lens at the cornea and prepares for shooting. After that, a prompt is given and the positioning is completed. Then the device can cover the soft magnetic nano-particle contact lens on the cornea. After preparation, the device shoots the first baseline picture. According to the detection requirements, the excitation mode is set, or the default mode can be directly selected. After selection, "start detection" can be clicked. The excitation device generates the first excitation, the detection device collects the electrical signal for detection, and the first excitation picture is obtained. After an interval of 0.5 seconds, the second excitation is generated, and the second excitation picture is obtained. After an interval of 0.5 seconds, a baseline calibration image is collected. Finally, according to the internal algorithm, the corneal image is reconstructed, the corneal mechanical property parameters are corrected, and the corneal elastic topographic map of the person to be detected is obtained, which is convenient for doctors to judge.

[0098] Overall, the device of the present application not only improves the accuracy and comfort of detection, but also improves the comfort, safety and accuracy of corneal mechanics detection to a new height by introducing magnetic nano-particles. The corneal mechanics measuring instrument of the present application introduces light sources, fiber couplers, balanced detectors, high-pass filters, sample arm lens groups and reference arm lens groups and other key components, constructs a new and accurate detection mechanism by applying magnetic nano-particle excitation, can improve the resolution of detection to the micron level, and significantly improve the detection accuracy and detection efficiency of the measuring instrument. In addition, unlike the resonant frequency magnetic dynamic nano-particle OCT measurement which can only measure single points, the device can measure the corneal hardness at different positions of the entire cornea at one time, and can realize the rapid measurement of the hardness of different regions of the cornea. At the same time, unlike the analysis of static images, with the help of a high-frame-rate optical detection module, the acquisition of dynamic excitation information can be realized, so that the mechanical information of the cornea can be obtained from the dynamic images. Unlike global measurement in traditional detection, the introduction of magnetic nano-particles improves the comfort, safety and accuracy of corneal mechanics detection to a new height.

[0099] In the processing mode, the influence of intraocular pressure on the corneal stiffness measurement is eliminated. In the data processing algorithm, the influence of corneal curvature thickness on the corneal stiffness measurement is corrected. The influence of corneal thickness on the corneal stiffness has been considered from the measurement principle, and thus will not affect the measurement result. In general, the device considers all factors that may affect the corneal stiffness measurement, thereby obtaining more accurate and interpretable corneal stiffness.

[0100] In summary, the multifunctional corneal detector of the present application provides a new detection method and integrated diagnostic function through technical innovation, realizes efficient and accurate corneal mechanical measurement, and provides great convenience for clinical operation.

[0101] The above is a further detailed description of the present application in combination with specific / preferred embodiments, and cannot be regarded as limiting the specific implementation of the present application to these descriptions. For ordinary skilled persons in the technical field to which the present application belongs, they can make several substitutions or modifications to the described embodiments without departing from the concept of the present application, and these substitutions or modifications shall be regarded as falling within the protection scope of the present application. In the description of the present specification, the description of the reference terms "an embodiment", "some embodiments", "preferred embodiment", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in combination with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments or examples. In the case of no mutual contradiction, the skilled person in the art can combine and combine the different embodiments or examples described in the present specification and the features of the different embodiments or examples. Although the embodiments of the present application and their advantages have been described in detail, it should be understood that various changes, substitutions and modifications can be made herein without departing from the scope of protection of the patent application.

Claims

1. A corneal elastic modulus measuring apparatus based on magnetic nanoparticle excitation, characterized by, Comprise: A soft magnetic nanoparticle contact lens composed of magnetic nanoparticles wrapped by a sealing film, used to adhere to the corneal surface and generate a mechanical response by magnetic field excitation; The sealing film of the soft magnetic nanoparticle contact lens adopts a double-layer hydrogel structure, which is formed by centrifugal spin coating process, and the magnetic nanoparticles have a preset particle size range and paramagnetism to ensure that a measurable stress and strain are generated under magnetic field excitation; An electromagnetic excitation module containing an electromagnetic coil for generating a controllable magnetic field to drive the magnetic nanoparticles to exert a push-pull force; The electromagnetic excitation module adopts a double-excitation time sequence control, which applies two magnetic field excitations at intervals and collects baseline calibration images to eliminate the interference of intraocular pressure on the measurement of elastic modulus; An optical coherence tomography (OCT) module for real-time capture of corneal dynamic deformation images before and after excitation; A data processing module for extracting displacement information based on the dynamic deformation images and calculating the real-time elastic modulus distribution of the cornea by an elastic modulus algorithm combined with stress data; Wherein, the electromagnetic coil structure of the electromagnetic excitation module is coaxially adapted to the optical path of the OCT module to synchronize the magnetic field excitation and optical imaging, and the data processing module realizes displacement tracking of dynamic deformation signals and strain-stress conversion through multi-stage signal processing to generate a two-dimensional map of corneal elastic modulus.

2. The apparatus of claim 1, wherein, The electromagnetic excitation module adopts a coreless annular coil design, the inner diameter of the coil matches the imaging light path of the OCT module, and the magnetic field strength and heat dissipation performance are ensured through the selection and design of structure and size to avoid overheating of the electromagnet.

3. The apparatus of any one of claims 1 to 2, wherein, The OCT module includes a swept source, a beam splitter, a reference arm and a sample arm lens group, and a balanced detector; The sample arm lens group is conjugate focused with the corneal surface, and the imaging frame rate is improved to more than 200 frames / s by optimizing the light source parameters and scan line number.

4. The apparatus of claim 3, wherein, The OCT module further includes a high-pass filter for frequency domain filtering of the electrical signal output by the balanced detector to filter out low-frequency physiological motion artifacts below 100Hz; The optical path of the reference arm lens group and the sample arm lens group is matched to ensure synchronous capture of deformation signals at different depths of the cornea.

5. The apparatus of any one of claims 1 to 2, wherein, The data processing module is configured to perform the following elastic modulus algorithm: Time domain average processing of the original image signal to suppress high frequency noise; Frequency domain transformation of the denoised signal and separation of low frequency physiological motion artifacts by high pass filtering; Tracking corneal deformation based on laser speckle phase change, extracting phase difference by autocorrelation analysis, and integrating to calculate displacement distribution; Deduce local strain according to the displacement difference of two excitations and corneal thickness, and calculate stress distribution combined with magnetic field force; Generate a two-dimensional map of corneal elastic modulus through the ratio of strain to stress.

6. The apparatus of claim 5, wherein, The elastic modulus algorithm further introduces a correction coefficient to compensate for the deviation of the sealing film thickness, corneal curvature and intraocular pressure on the calculation results.

7. A method for real-time measurement of corneal elastic modulus based on magnetic nanoparticle excitation, using the measurement device according to any one of claims 1 to 6, characterized in that, Comprise the following steps: S1, adhere the soft magnetic nanoparticle contact lens to the corneal surface, start the OCT module to obtain the baseline corneal image; S2, control the electromagnetic excitation module to apply a magnetic field to drive the magnetic nanoparticles to generate a push-pull force excitation on the cornea; S3, real-time capture of dynamic deformation images before and after excitation by the OCT module; S4, performing multi-stage signal processing on the deformation image to extract displacement information and calculate the corneal elastic modulus distribution; The signal processing includes noise suppression, artifact removal, speckle tracking, and strain-stress conversion, and finally generates a corneal elastic modulus atlas.

8. The method of claim 7, wherein, The signal processing in step S4 specifically includes: (a) performing time domain average processing on the original image signal to suppress high frequency noise; (b) performing frequency domain transformation on the denoised signal, and separating low frequency physiological motion artifacts through high pass filtering; (c) tracking the corneal deformation based on the phase change of laser speckle, extracting the phase difference through autocorrelation analysis, and integrating to calculate the displacement distribution; (d) deriving the local strain according to the displacement difference of two excitations and the corneal thickness, and calculating the stress distribution combined with the magnetic field force and the correction coefficient, the correction coefficient is used to compensate the influence of the sealing film thickness, the corneal curvature and the intraocular pressure; (e) generating a two-dimensional atlas of corneal elastic modulus through the ratio relationship between strain and stress.

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