Imaging apparatus and method for correcting and restoring images of objects in scattering media using a reflection matrix-based multiple scattering tracking algorithm

Abstract

To provide an imaging device and an imaging method for tracking a multiple scattering locus using a time resolution reflective matrix obtained by using a time resolution light source, then correcting it, and correcting and restoring an internal target image positioned at a deep place of a scattering medium such as a biological tissue.SOLUTION: An imaging device 100 comprises: a light source unit 110 that enters light into a target object; a sensing unit 120 that senses light multiple-scattered from the target object and returned; a reflective matrix measurement unit 130 that measures a time resolution reflective matrix reflecting a multiple scattering locus based on a multiple scattering component on the basis of the returned light; an algorithm processing unit 140 that captures an incident transparent matrix and a reflective transparent matrix by means of a multiple scattering locus algorithm and reflects reverse matrices thereof on the time resolution reflective matrix to capture an object reflective matrix; and an image processing unit 150 that captures an image corrected in multiple scattering distortion on the basis of the captured object reflective matrix.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS] This application claims the benefit of priority based on Korean Patent Application No. 10-2023-0124023, filed on September 18, 2023, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates to an imaging device and method for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm, and more particularly to a technology for tracking multiple scattering trajectories using a time-resolved reflection matrix obtained from an imaging device using a time-resolved light source, and then correcting the trajectories to correct and restore an image of an internal object located deep within a scattering medium such as biological tissue. [Background technology]

[0003] As one goes deeper into biological tissue, the imaging depth is limited by multiple scattering caused by the structure of the tissue.

[0004] To overcome this, reflection matrix microscopy has been developed, which suppresses multiple scattering by measuring the time-resolved reflection matrix.

[0005] In this method, a method of selectively using only ballistic waves that propagate without experiencing multiple scattering among scattered components of light propagating inside a scattering medium can be considered.

[0006] Meanwhile, a CLASS (Closed Loop Accumulation of Single Scattering) method has been developed to measure and correct the aberration of scattering media that distorts ballistic waves.

[0007] A reflection matrix microscope measures the reflection matrix of a scattering medium, and while changing the angle of incidence of light incident on the scattering medium, measures the intensity and phase of the electric field of the reflected light corresponding to each incident beam (light) using the phenomenon of optical interference.

[0008] The measured complex phase image reconstructs the reflectivity matrix of the scattering medium in the form of an output basis matrix relative to the input basis.

[0009] From this reflection matrix, an object image inside the scattering medium is obtained. When the input reference is the position of the incident beam focus, the object image is obtained using the confocal microscope method, and when the incident angle of the incident beam is used as the reference, the object image is reconstructed using the CASS (Collective Accumulation of Single Scattering) microscope method.

[0010] In this process, multiple scattering is suppressed, and only ballistic waves are selectively used.

[0011] The CLASS microscope uses a method to remove the aberrations applied to the ballistic wave by retrieving the aberration information from the reflection matrix and post-correcting it.

[0012] After converting the time-resolved reflection matrix based on the angle of incidence and the angle of reflection, an additional phase delay value is added for each angle of incidence and angle of reflection to maximize the intensity of the final image, thereby correcting the aberration reflected in single scattering.

[0013] If the reference of the incident beam is the position of the focal point, the same operation can be performed by converting it into the reference of the incident angle and the reflection angle through Fourier transformation.

[0014] This technology considers a method of identifying the aberrations that incident light experiences in the process of reaching a target object and the aberrations that light experiences in the process of returning after being reflected by the object, and utilizing these for correction. [Prior art documents] [Patent documents]

[0015] [Patent Document 1] International Publication No. WO2022 / 012927, "SPECTROMETRIC METROLOGY SYSTEMS BASED ON MULTIMODE INTERFERENCE AND LITHOGRAPHIC APPARATUS" [Patent Document 2] Korean Patent Application Publication No. 10-2020-0131908, "Overlay measurement system and method" [Patent Document 3] Korean Patent Application Publication No. 10-2023-0062343, "Microscope system based on adaptive optics of wavefront measurement type for deep depth and ultra-high resolution imaging and its operating method" [Patent Document 4] Korean Patent Application Publication No. 10-2019-0023324, "Image acquisition system capable of acquiring multi-mode images" Summary of the Invention [Problem to be solved by the invention]

[0016] The existing CLASS method only focuses on correcting the angle-dependent phase shift of ballistic waves for image reconstruction, and does not utilize multiply scattered waves. The present invention aims to provide an imaging device and method that tracks and corrects multiply scattered trajectories using a time-resolved reflection matrix obtained from an imaging device that uses a time-resolved light source, thereby correcting and restoring images of internal objects located deep within scattering media such as biological tissue.

[0017] The present invention aims to obtain a time-resolved reflection matrix of a scattering medium, reconstruct the trajectories of multiple scattered waves using a numerical iterative technique based on a Multiple Scattering Tracing (MST) algorithm, and reconstruct and correct a target image corresponding to an image of an object inside the scattering medium using an inverse process of the trajectories of the reconstructed multiple scattered waves.

[0018] The present invention aims to provide an imaging device and method that can be used in a wide range of applications because it acquires images in a label-free manner, does not require additional equipment like existing reflection matrix microscopes, and does not affect the data measurement time itself as a post-processing technique, so it can be used to acquire in-vivo images that require fast measurement, and is expected to be used in research on various disease models or animal experiments, etc., and can be used in a wide range of applications, including as a diagnostic and clinical tool.

[0019] The present invention aims to acquire 3D deep depth images while maintaining the state of the subject in in-vivo imaging as data is acquired and corrected immediately without any prior preparation procedures using a post-correction method that corrects data such as reflection matrix data after acquisition, thereby reducing data measurement time.

[0020] The present invention aims to provide an imaging apparatus and method that can acquire 3D deep depth images while changing the measurement depth as well as reducing data measurement time, and thus has various applications in medical and life science fields.

[0021] The present invention aims to provide an imaging device that can be readily applied to clinical practice because it is an algorithm that applies a reflection matrix obtained through reflection without labeling, and can obtain deep and high-resolution images, and can also be applied to measurement equipment because it can obtain images of the inside of samples such as biological tissues and semiconductors without decomposing the inside of the samples. [Means for solving the problem]

[0022] According to an embodiment of the present invention, an imaging apparatus may include a light source unit that incidents light that has passed through a scattering medium and multiple scattering components in the scattering medium onto an object; a sensor unit that senses the light that has passed through the multiple scattering components from the object after incident and is reflected and returned; a reflection matrix measurement unit that measures a time-resolved reflection matrix reflecting a multiple scattering trajectory based on the multiple scattering components based on the returned light; an algorithm processing unit that numerically iteratively accesses a plurality of phase planes approximated from the scattering medium using a multiple scattering tracking algorithm to obtain an incident transmission matrix and a reflection transmission matrix, and acquires an object reflection matrix by reflecting the inverse matrices of the obtained incident transmission matrix and the obtained reflection transmission matrix on the measured time-resolved reflection matrix; and an image processing unit that acquires an image in which multiple scattering distortion due to the multiple scattering trajectory is corrected based on the obtained object reflection matrix.

[0023] The algorithm processing unit calculates a spatial propagation matrix (P) corresponding to the distance to the k-th phase plane at the input or output end of the time-resolved reflection matrix based on the multiple scattering tracking algorithm. k ) to access each phase plane numerically iteratively, thereby obtaining the k-th incident transmission matrix and the k-th reflected transmission matrix.

[0024] The algorithm processing unit may acquire a difference between phase delay values ​​of the two points by considering a case where light is focused at two different points on a specific phase plane among the plurality of phase planes based on the multiple scattering tracking algorithm, and apply the acquired difference to an incident transmission matrix and a reflected transmission matrix acquired on the specific phase plane.

[0025] Each of the plurality of phase planes may be virtually located within the scattering medium or on the scattering medium by calculating a transmission matrix in association with multiple scattering components within the scattering medium, designing a first phase plane based on the calculated transmission matrix, and designing a second phase plane on the designed first phase plane based on the inverse transmission matrix of the calculated transmission matrix.

[0026] The positions of the plurality of phase planes may be determined as positions where the measured electric field strength is greater than a reference value after measuring the electric field strength by applying the multiple scattering tracking algorithm while changing the distance from the target object.

[0027] The number of the plurality of phase planes may be determined by measuring the electric field strength by applying the multiple scattering tracking algorithm while changing the number of phase planes, and then taking into consideration the calculation time depending on the changed number.

[0028] The reflection matrix measurement unit can measure the time-resolved reflection matrix, where each matrix element is light concentrated at each position on the surface of the target object, and the time-resolved reflection matrix is ​​determined as the intensity and phase values ​​of the electric field measured at each position of a camera placed on a conjugate image plane of the object surface as a result of an input reference, in the reflected light.

[0029] The light source unit can irradiate the light onto the target object as a point illumination, and change the position of the point illumination to change the incident position on the target object.

[0030] The sensing unit may sense a sensing pixel that is changed according to the changed incident position.

[0031] The algorithm processing unit calculates inverse matrices for each of an incident transmission matrix and a reflected transmission matrix associated with the phase values ​​for the plurality of phase planes and the plurality of points constituting each of the plurality of phase planes for the multiple scattering components of the scattering medium using the multiple scattering tracking algorithm, and can acquire an object reflection matrix for the target object by reflecting the calculated inverse matrices in the time-resolved reflection matrix.

[0032] An imaging method according to an embodiment of the present invention may include: a light source unit irradiating light that has passed through a scattering medium and multiple scattering components in the scattering medium onto a target object; a sensing unit detecting the light that has passed through the multiple scattering components from the target object after the incident light and is reflected and returned; a reflection matrix measurement unit measuring a time-resolved reflection matrix reflecting a multiple scattering trajectory based on the multiple scattering components based on the returned light; an algorithm processing unit iteratively accessing a plurality of phase planes approximated from the scattering medium using a multiple scattering tracking algorithm to obtain an incident transmission matrix and a reflection transmission matrix, and applying inverse matrices of the obtained incident transmission matrix and the obtained reflection transmission matrix to the measured time-resolved reflection matrix to obtain an object reflection matrix; and an image processing unit acquiring an image in which multiple scattering distortion due to the multiple scattering trajectory is corrected based on the obtained object reflection matrix.

[0033] The step of acquiring an incident transmission matrix and a reflection transmission matrix by numerically iteratively accessing the plurality of phase planes using the multiple scattering tracking algorithm, and acquiring an object reflection matrix by reflecting the inverse matrices of the acquired incident transmission matrix and the acquired reflection transmission matrix on the measured time-resolved reflection matrix includes: inputting a spatial propagation matrix (P k ) to numerically iteratively access each phase plane to obtain a plurality of incident transmission matrices and a plurality of reflected transmission matrices corresponding to the k-th phase plane.

[0034] The step of numerically iteratively accessing the plurality of phase planes using the multiple scattering tracking algorithm to obtain an incident transmission matrix and a reflection transmission matrix, and acquiring an object reflection matrix by reflecting the inverse matrices of the obtained incident transmission matrix and the obtained reflection transmission matrix on the measured time-resolved reflection matrix may include the step of: considering a case in which light is focused at two different points on a specific phase plane among the plurality of phase planes based on the multiple scattering tracking algorithm, obtaining a difference in phase delay values ​​between the two points, and applying the obtained difference to the incident transmission matrix and the reflection transmission matrix obtained for the specific phase plane.

[0035] Each of the plurality of phase planes may be virtually located within the scattering medium or on the scattering medium by calculating a transmission matrix in association with multiple scattering components within the scattering medium, designing a first phase plane based on the calculated transmission matrix, and designing a second phase plane on the designed first phase plane based on the inverse transmission matrix of the calculated transmission matrix.

[0036] The positions of the plurality of phase planes may be determined as positions where the measured electric field strength is greater than a reference value after measuring the electric field strength by applying the multiple scattering tracking algorithm while changing the distance from the target object, and the number of the plurality of phase planes may be determined by measuring the electric field strength by applying the multiple scattering tracking algorithm while changing the number of phase planes, taking into consideration the calculation time depending on the changed number. [Effects of the Invention]

[0037] The present invention provides an imaging device and method that uses a time-resolved reflection matrix obtained from an imaging device that uses a time-resolved light source to track multiple scattering trajectories, correct the trajectories, and then correct and restore an image of an internal object located deep within a scattering medium such as biological tissue.

[0038] The present invention obtains a time-resolved reflection matrix of a scattering medium, and then reconstructs the trajectories of the multiply scattered waves using a numerical iterative technique based on a Multiple Scattering Tracing (MST) algorithm. Then, it is possible to reconstruct and correct a target image corresponding to an image of an object inside the scattering medium using an inverse process of the trajectories of the reconstructed multiply scattered waves.

[0039] The present invention has a very wide range of applications because it acquires images in a label-free manner, does not require additional equipment compared to existing reflection matrix microscopes, and does not affect the data measurement time itself as a post-processing technique. Therefore, it is expected to be used for in-vivo image acquisition that requires fast measurement, and can be used in research on various disease models or animal experiments, etc., and can provide an imaging device and method whose range of applications can be expanded to include use as a diagnostic and clinical tool.

[0040] The present invention uses a post-correction method in which data such as reflection matrix data is acquired and then corrected, thereby immediately acquiring data without any prior preparation procedures, and as the data measurement time is reduced, it is possible to acquire 3D deep depth images while maintaining the state of the subject through in-vivo imaging.

[0041] The present invention can provide an imaging apparatus and method that can acquire 3D deep depth images while changing the measurement depth as well as reducing data measurement time, and thus can be used in a variety of medical and life science applications.

[0042] The present invention provides an imaging device that can be applied to clinical practice immediately since it is an algorithm that applies a reflection matrix obtained through reflection without labeling, and can obtain a deep and high-resolution image. Furthermore, since it can obtain an image of the inside of a sample such as a biological tissue or a semiconductor without decomposing the inside of the sample, it can also be applied to measurement equipment. [Brief explanation of the drawings]

[0043] [Figure 1]1 illustrates an imaging apparatus for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. [Figure 2a] 1 is a diagram illustrating a multi-layer phase plane approximation structure of a scattering medium in association with a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. FIG. [Figure 2b] 1 is a diagram illustrating a multi-layer phase plane approximation structure of a scattering medium in association with a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. FIG. [Figure 3] 1 is a diagram illustrating a reflection matrix structure according to a multi-layer phase plane approximation model associated with a reflection matrix-based multiple scattering tracking algorithm according to an embodiment of the present invention; [Figure 4] 1A and 1B are diagrams illustrating the schematic structure of transmission matrices in each phase plane associated with a reflection matrix-based multiple scattering tracking algorithm according to an embodiment of the present invention. [Figure 5] 10A and 10B are diagrams illustrating a process of designing multiple phase planes associated with a reflection matrix-based multiple scattering tracking algorithm in an imaging method according to an embodiment of the present invention. [Figure 6] 1 is a diagram illustrating a numerical iteration model structure and a numerical iteration process associated with a reflection matrix-based multiple scattering tracking algorithm according to an embodiment of the present invention; [Figure 7] 1 is a diagram illustrating a numerical iteration model structure and a numerical iteration process associated with a reflection matrix-based multiple scattering tracking algorithm according to an embodiment of the present invention; [Figure 8] 1A and 1B are diagrams illustrating an imaging method for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. [Figure 9] 1A and 1B are diagrams illustrating an imaging method for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. [Figure 10a] FIG. 1 illustrates a numerical simulation of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. [Figure 10b]FIG. 1 illustrates a numerical simulation of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. [Figure 10c] FIG. 1 illustrates a numerical simulation of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. [Figure 11a] FIG. 1 illustrates an experimental demonstration using an onion of a reflection matrix-based multiple scattering tracking algorithm in accordance with one embodiment of the present invention. [Figure 11b] FIG. 1 illustrates an experimental demonstration using an onion of a reflection matrix-based multiple scattering tracking algorithm in accordance with one embodiment of the present invention. [Figure 11c] FIG. 1 illustrates an experimental demonstration using an onion of a reflection matrix-based multiple scattering tracking algorithm in accordance with one embodiment of the present invention. [Figure 12a] 1A-1C illustrate experimental verification of a reflection matrix-based multiple scattering tracking algorithm using biological tissue in accordance with one embodiment of the present invention. [Figure 12b] 1A-1C illustrate experimental verification of a reflection matrix-based multiple scattering tracking algorithm using biological tissue in accordance with one embodiment of the present invention. [Figure 12c] 1A-1C illustrate experimental verification of a reflection matrix-based multiple scattering tracking algorithm using biological tissue in accordance with one embodiment of the present invention. [Figure 12d] 1A-1C illustrate experimental verification of a reflection matrix-based multiple scattering tracking algorithm using biological tissue in accordance with one embodiment of the present invention. [Figure 13a] FIG. 1 illustrates in-vivo imaging results using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. [Figure 13b] FIG. 1 illustrates in-vivo imaging results using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. [Figure 13c] FIG. 1 illustrates in-vivo imaging results using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. [Figure 13d]FIG. 1 illustrates in-vivo imaging results using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention. [Figure 14] 1 is a diagram illustrating the correction and restoration performance of an imaging apparatus that uses a reflection matrix-based multiple scattering tracking algorithm to correct and restore an image of an object in a scattering medium according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0044] For each embodiment in accordance with the inventive concepts disclosed herein, specific structural or functional descriptions are provided merely to illustrate each embodiment in accordance with the inventive concepts, which may be embodied in a variety of forms and are not limited to the embodiments described herein.

[0045] Since each embodiment according to the concept of the present invention can be variously modified and can have various forms, each embodiment is illustrated in the drawings and described in detail herein, but this is not intended to limit each embodiment according to the concept of the present invention to the particular form disclosed, and includes modifications, equivalents, or alternatives within the spirit and technical scope of the present invention.

[0046] Terms such as "first" or "second" may be used to describe various components, but the components should not be limited by the terms. The terms are used only to distinguish one component from another, for example, a first component may be called a second component, and similarly, a second component may be called a first component, without departing from the scope of the inventive concept.

[0047] When a component is said to be "coupled" or "connected" to another component, it should be understood that it may be directly coupled or connected to the other component, but there may also be other components in between. On the other hand, when a component is said to be "directly coupled" or "directly connected" to another component, it should be understood that there are no other components in between. Expressions describing the relationship between components, such as "between," "immediately between," or "directly adjacent to," should be interpreted in the same way.

[0048] The terms used in this specification are merely used to describe specific embodiments and are not intended to limit the present invention. The singular expressions include the plural expressions unless the context clearly dictates otherwise. In this specification, the terms "comprise" or "have" are intended to specify the presence of embodied features, numbers, stages, operations, components, parts, or combinations thereof, and should be understood as not precluding the presence or additional possibility of one or more other features, numbers, stages, operations, components, parts, or combinations thereof.

[0049] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the art to which the present invention belongs. Each commonly used, predefined term should be interpreted as having a meaning consistent with the contextual meaning of the relevant art, and should not be interpreted as an ideal or overly formal meaning unless expressly defined herein.

[0050] FIG. 1 is a diagram illustrating an imaging apparatus for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0051] FIG. 1 illustrates components of an imaging apparatus for correcting and restoring images of objects in scattering media using a reflectance matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0052] Referring to FIG. 1, an imaging device 100 for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention includes a light source unit 110, a sensing unit 120, a reflection matrix measurement unit 130, an algorithm processing unit 140, and an image processing unit 150, and the configuration of the imaging device 100 is controlled based on a control unit 160.

[0053] As an example, the imaging device 100 tracks the trajectories of multiple scattering that occurs within a scattering medium and utilizes this for internal object imaging.

[0054] For example, the imaging device 100 uses a reflection matrix-based multiple scattering tracking algorithm as an algorithm applied in post-processing to reflection matrix data obtained through reflection signals of a target object and a scattering medium without labeling.

[0055] The imaging device 100 can acquire deep and high-resolution images and can be applied to clinical applications. It can also be used as measurement equipment because it can obtain images of the inside of samples such as biological tissues and semiconductors without decomposing the inside of the samples.

[0056] For example, the imaging device 100 can use a reflectance matrix-based multiple scattering tracking algorithm as an algorithm that is applicable to various forms of time-resolved off-axis holographic microscopes or reflectance matrix microscopes.

[0057] According to an embodiment of the present invention, the light source unit 110 may be a source providing unit that provides a pulsed laser.

[0058] For example, the target object is biological tissue, which is a scattering medium, and is most easily applicable to imaging structures where the refractive index changes significantly due to multiple scattering components inside, such as the central nervous system, brain tissue, and blood vessels.

[0059] The deeper one goes into biological tissue, the lower the resolution becomes due to scattering trajectories caused by the structure of the tissue. However, the imaging device 100 can correct for the high-order inverse scattering problem by correcting errors caused by multiple scattering trajectories within the scattering medium, where multiple scattering occurs.

[0060] For example, scattering media can include any medium that contains multiple scattering components within it that can scatter light, such as biological tissue and the skull.

[0061] The sensing unit 120 according to an embodiment of the present invention can sense light that is incident, passes through multiple scattering components from a target object, and is reflected and returned.

[0062] For example, the light source unit 110 can irradiate light onto the target object as a point light and change the position of the point light to change the incident position on the target object.

[0063] Meanwhile, the sensing unit 120 can sense the sensing pixel changed according to the changed incident position.

[0064] According to one embodiment of the present invention, the reflection matrix measurement unit 130 can measure a time-resolved reflection matrix that reflects a multiple scattering trajectory based on multiple scattering components based on light that passes through a scattering medium from a target object and returns.

[0065] As an example, the reflection matrix measurement unit 130 can measure a time-resolved reflection matrix determined as the intensity and phase values ​​of the electric field measured at each position of a camera placed on a conjugate image plane of the object surface as an output reference in the reflected light, with each matrix element being light concentrated at each position on the surface of the target object.

[0066] According to one embodiment of the present invention, the algorithm processing unit 140 numerically iteratively accesses multiple phase planes approximated from the scattering medium using a multiple scattering tracking algorithm to obtain an incident transmission matrix and a reflection transmission matrix, and can obtain an object reflection matrix by reflecting the inverse matrices of the obtained incident transmission matrix and the obtained reflection transmission matrix on the measured time-resolved reflection matrix.

[0067] For example, multiple phase planes can be utilized to approximate a scattering medium to virtual multiple phase planes and find a phase map of the multiple phase planes.

[0068] For example, the multiple scattering tracking algorithm may be an algorithm that approximates the measured reflection matrix to multiple virtual phase planes and finds phase maps in the multiple phase planes that can explain the measured reflection matrix.

[0069] In other words, the multiple scattering tracking algorithm of the present invention can be an algorithm that constructs a reflection matrix by measuring the intensity and phase map of light passing through a scattering medium when different illuminations are incident, then approximates the scattering medium to virtual multiple phase planes, and finds the phase map of the virtual phase plane from the measured reflection matrix.

[0070] For example, the algorithm processing unit 140 may generate a spatial propagation matrix (P k ), each phase plane can be numerically accessed repeatedly to obtain the k-th corresponding multiple incident transmission matrices and multiple reflected transmission matrices.

[0071] For example, the kth may indicate a specific number and may correspond to a natural number.

[0072] For example, if the number of phase planes is five, k may be one of 1 to 5, but is not limited to a particular number and may be changed.

[0073] The algorithm processing unit 140 according to one embodiment of the present invention can obtain the difference in phase delay values ​​between the two points, taking into consideration the case where light is focused at two different points for a specific phase plane among a plurality of phase planes based on a multiple scattering tracking algorithm, and apply the obtained difference to the incident transmission matrix and the reflected transmission matrix obtained for the specific phase plane.

[0074] For example, the algorithm processing unit 140 may calculate inverse matrices for each of the incident transmission matrix and the reflected transmission matrix associated with a plurality of phase planes and phase values ​​for a plurality of points constituting each of the plurality of phase planes for the multiple scattering components of the scattering medium using a multiple scattering tracking algorithm, and may acquire an object reflection matrix for the target object by reflecting the calculated inverse matrices in a time-resolved reflection matrix.

[0075] For example, each of the multiple phase planes can be virtually located inside the scattering medium or on the scattering medium by calculating a transmission matrix in association with multiple scattering components inside the scattering medium, designing a first phase plane based on the calculated transmission matrix, and designing a second phase plane on the designed first phase plane based on the inverse transmission matrix of the calculated transmission matrix.

[0076] The design of multiple phase planes will be further explained with reference to FIG.

[0077] The positions of the multiple phase planes can be determined as positions where the measured electric field strength is greater than a reference value after measuring the electric field strength by applying a multiple scattering tracking algorithm while varying the distance from the target object.

[0078] In connection with determining the position of multiple phase planes, a supplementary explanation will be given with reference to FIG. 12b.

[0079] The number of phase planes can be determined by measuring the electric field strength by applying a multiple scattering tracking algorithm while changing the number of phase planes, and then taking into consideration the calculation time depending on the changed number.

[0080] The determination of the number of phase planes will be further explained with reference to FIG. 12c.

[0081] Therefore, the present invention can provide an imaging device and method that tracks multiple scattering trajectories using a time-resolved reflection matrix obtained from an imaging device that uses a time-resolved light source, corrects the trajectories, and then corrects and restores an image of an internal object located deep within a scattering medium such as biological tissue.

[0082] In addition, the present invention can obtain a time-resolved reflection matrix of a scattering medium, and then reconstruct the trajectories of the multiple scattered waves using a numerical iterative technique based on a Multiple Scattering Tracing (MST) algorithm. Then, the present invention can reconstruct and correct a target image corresponding to an object image inside the scattering medium using an inverse process of the trajectories of the reconstructed multiple scattered waves.

[0083] 2a and 2b are diagrams illustrating a multi-layer phase plane approximation structure of a scattering medium in conjunction with a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0084] FIG. 2a illustrates a multi-layer phase plane approximation structure for solving the scattering distortion problem caused by the multiple scattering form of a scattering medium in connection with a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0085] Referring to FIG. 2a, in a schematic diagram 200 of a structure having a scattering distortion problem due to the multiple scattering form of a conventional scattering medium, light passes through a scattering medium 202 and enters a target object 201 (θ in ) and the process of light being reflected back (θ o ) causes a multiple scattering distortion problem due to the multiple scattering component 203, and the distortion is M in ) and scattered power (θ M o ) is not taken into account.

[0086] To solve such a problem, the scattering medium 202 must be approximated as a set of multi-layered phase planes, and a high-order inverse scattering problem must be solved.

[0087] In the schematic diagram 210 of the multilayer phase plane approximation structure according to one embodiment of the present invention, the process (θ in ) and the process of light being reflected back (θ o ) causes a multiple scattering distortion problem due to the multiple scattering component 203, and the distortion is M in ) and scattered power (θ M o ) for multiple phase planes (Z1 to Z N ), and the higher-order inverse scattering problem is simplified by finding the phase values ​​in each phase plane.

[0088] In other words, the imaging device according to one embodiment of the present invention minimizes scattering due to multiple scattering components 213 at multiple phase planes within scattering medium 212 and reduces the scattering input (θ M in ) and scattered power (θ M o ) distortion correction to the process of light incidence (θ in ) and the process of light being reflected back (θ o ) to correct distortion due to multiple scattering components 213 of the scattering medium 212.

[0089] FIG. 2b illustrates a three-dimensional example of a multi-layer phase plane approximation structure for solving the scattering distortion problem caused by the multiple scattering form of a scattering medium in connection with a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0090] Referring to FIG. 2b, a three-dimensional diagram 220 of a multi-layer phase plane approximation structure according to one embodiment of the present invention may be a structure in which a target object 221 is located inside or below a scattering medium 222 and a multi-layer phase plane 223 is applied.

[0091] The three-dimensional diagram 220 of a multi-layer phase plane approximation structure according to one embodiment of the present invention illustrates a form in which scattering distortion caused by multiple scattering by a scattering medium 222 is corrected through a multi-layer phase plane 223 when an imaging device performs optical imaging on a target object 221.

[0092] For example, the multi-layer phase plane may be a configuration for obtaining a phase value for correcting a virtually designed scattering distortion, or may be an actual phase filter.

[0093] FIG. 3 is a diagram illustrating a reflection matrix structure according to a multi-layer phase plane approximation model related to a reflection matrix-based multiple scattering tracking algorithm according to an embodiment of the present invention.

[0094] FIG. 3 illustrates a reflection matrix structure according to a multi-layer phase plane approximation model associated with a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0095] Referring to FIG. 3, an approximation of the incident transmission matrix, the reflected transmission matrix, and the object reflection matrix is ​​shown in a reflection matrix structure 300 according to one embodiment of the present invention.

[0096] As an example, in the reflection matrix structure 300, for ease of understanding, the object O is located in the center, and the phase planes reflecting the incident and reflected light are located on both sides, but the object O is located inside or below the scattering medium, and multiple phase planes are located inside the scattering medium, so that the incident and reflection occur in the same space.

[0097] In connection with reflection matrix structure 300, the time-resolved reflection matrix R may be approximated as the product of each transmission matrix in each phase plane and an object reflection matrix corresponding to the reflection matrix of the object to be imaged.

[0098] The following Equation 1 can be used to approximate the object reflection matrix.

[0099]

number

[0100] In Equation 1, R can represent the time-resolved reflection matrix, and T in can be denoted as the incident transmission matrix, T T out may denote the reflection / transmission matrix, and O may denote the object reflection matrix.

[0101] The incident transmission matrix can represent the transmission matrix of the object to be imaged on the surface of the scattering medium during the incident process up to a certain depth.

[0102] The reflection / transmission matrix may correspond to the transmission matrix in the process in which light is reflected back.

[0103] FIG. 4 is a diagram illustrating a schematic structure of a transmission matrix in each phase plane associated with a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0104] FIG. 4 illustrates a schematic structure of the transmission matrix for each phase plane associated with a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0105] Referring to FIG. 4, in a transmission matrix schematic structure 400 of each phase plane associated with a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention, k ), phase plane (Z k+1 ) and the phase plane (Z k-1 ) the transmission matrix (T k ) is determined as the product of the internal spatial phase delay value of each plane and the spatial propagation matrix.

[0106] For example, in relation to the spatial propagation matrix, the spatial propagation matrix from the kth phase plane to the k-1th phase plane (P k-1 , k ) can be expressed as

[0107] For example, a transfer function for each phase plane may be utilized in conjunction with a phase delay value.

[0108] FIG. 5 is a diagram illustrating a process of designing multiple phase planes associated with a reflection matrix-based multiple scattering tracking algorithm in an imaging method according to an embodiment of the present invention.

[0109] FIG. 5 illustrates a multiple phase plane design process associated with a reflection matrix-based multiple scattering tracking algorithm in an imaging method according to one embodiment of the present invention.

[0110] Referring to FIG. 5, in step S501, an imaging method according to an embodiment of the present invention determines a target object 500 located inside or below a scattering medium 510.

[0111] The scattering medium 510 contains multiple scattering components 511 therein.

[0112] In step S502, the imaging method according to the embodiment of the present invention constructs a first phase plane 520 within a scattering medium 510 based on a transmission matrix T in association with a plurality of phase plane designs.

[0113] In step S503, the imaging method according to an embodiment of the present invention calculates an inverse transmission matrix (T) in association with a plurality of phase plane designs within the scattering medium 510. -1 ) to construct a second phase plane 521.

[0114] In step S504, when an image of the target object 500 is acquired in the imaging method according to an embodiment of the present invention, an image is acquired in a state where multiple scattering components 511 are removed inside the scattering medium 510.

[0115] According to an embodiment of the present invention, the first phase plane 520 and the second phase plane 521 are combined to form one phase plane.

[0116] 6 and 7 are diagrams illustrating a numerical iteration model structure and a numerical iteration process associated with a reflection matrix-based multiple scattering tracking algorithm according to an embodiment of the present invention.

[0117] FIG. 6 illustrates a numerical iteration model structure and a numerical iteration process associated with a reflection matrix-based multiple scattering tracking algorithm in an imaging method according to one embodiment of the present invention.

[0118] In order to obtain image information of an object inside a scattering medium, the imaging method according to an embodiment of the present invention must solve the inverse scattering problem of Equation 1 to obtain the reflection matrix of the object.

[0119] Therefore, the imaging method is related to a reflection matrix-based multiple scattering tracking algorithm. When the number of phase planes is N, 2N planes are passed through in the incident and reflection process. If a reflection surface is included, Equation 1 can be considered as a (2N+1)th-order high-order inverse scattering problem.

[0120] To solve the above-mentioned problems, a numerical iterative model structure and a numerical iterative process associated with a reflection matrix-based multiple scattering tracking algorithm in an imaging method are exemplified.

[0121] Referring to FIG. 6, in step S601, the imaging method according to an embodiment of the present invention measures an initial time reflection matrix in an input / output structure of the initial reflection matrix.

[0122] As described in step (S601), the imaging method measures a time-resolved reflection matrix R, where each matrix element of the measured time-resolved reflection matrix R can be determined as the intensity and phase values ​​of the electric field measured at each position of a camera placed in a conjugate image plane of the object plane, as an output reference, in the reflected light as a result of an input reference, by applying illumination focused at each position of the object plane.

[0123] In step (S601), the imaging method includes: zo , zo ) to win.

[0124] For example, the time-resolved reflection matrix is o ) to determine the input (incidence) and output (reflection).

[0125] In step S602, the imaging method according to the embodiment of the present invention accesses a phase plane in an input / output structure when a specific phase plane is accessed.

[0126] In addition, the imaging method uses a multiple scattering tracking algorithm to input or output a reflection matrix corresponding to the distance to the k-th phase plane (P k ) to access each of the phase planes.

[0127] The plane (z o ) is determined as the input (incidence), and the phase plane (z3) to be accessed is determined as the output (reflection).

[0128] The resulting matrix can be used to reconstruct the reflected image of an object with illumination (light) focused at each position in a particular phase plane.

[0129] Since the focal plane of the illumination is separated from the object plane, the wavefront of the light illuminating the object may take the form of a spherical wave.

[0130] In step S603, the imaging method according to an embodiment of the present invention acquires and corrects a phase shift in an input / output structure by a method of acquiring a phase map of a corresponding phase plane through correlation.

[0131] In step S603, in the imaging method according to an embodiment of the present invention, when the first and second spherical waves are focused on two different points on a corresponding phase plane, and images of an object illuminated by the first and second spherical waves are reconstructed, these two images may have a correlation due to common object image information in the overlapping region, as shown in the picture.

[0132] At this time, the phase value of the correlation value corresponds to the difference between the phase delay values ​​of two points on the phase plane.

[0133] If this process is repeated for all positions on the phase plane, the phase delay map for the phase plane can be found.

[0134] A space propagation matrix reflecting the difference in phase delay values ​​can be obtained by the following Equation 2.

[0135]

number

[0136] In Equation 2, P may represent a spatial propagation matrix, p may represent a phase value at a specific position on the phase plane, z may represent the phase plane, and i and j may represent natural numbers.

[0137] When this process is numerically repeated for 2N planes in the incident and reflection processes, the transmission matrix (T in ) and the transmission matrix (T out ) can be obtained.

[0138] By multiplying both sides of the reflection matrix by the inverse matrix of the finally obtained transmission matrix, the object reflection matrix can be obtained as shown in the following equation 3.

[0139]

number

[0140] In Equation 2, R can represent the time-resolved reflection matrix, and T in can be denoted as the incident transmission matrix, T T out may denote the reflection / transmission matrix, and O may denote the object reflection matrix.

[0141] According to one embodiment of the present invention, an imaging method can obtain a final image of an object through an acquired reflection matrix of the object.

[0142] FIG. 7 supplements step S603 of FIG. 6 with respect to a numerical iteration model structure and a numerical iteration process associated with a reflection matrix-based multiple scattering tracking algorithm in an imaging method according to an embodiment of the present invention.

[0143] Referring to Figure 7, electric field image function 700 and electric field image function 710 are shown, and object reflection matrix 720 and object reflection matrix 730 are obtained based on a reflection matrix-based multiple scattering tracking algorithm for electric field image function 700 and electric field image function 710, and the phase value of the correlation value between object reflection matrix 720 and object reflection matrix 730 is used to derive the difference 740 in the phase delay values ​​of two points on the phase plane.

[0144] Electric field image function 700 may be associated with a first point in the phase plane, and electric field image function 710 may be associated with a second point in the phase plane.

[0145] The image 701 based on the electric field image function 700 includes the object image and multiple scattering.

[0146] The image 711 based on the electric field image function 710 includes the object image and multiple scattering.

[0147] Image 701 and image 711 show the difference in resolution between the first and second locations.

[0148] The difference in resolution can be seen as the difference in phase delay value between two points on the phase plane.

[0149] By subtracting image 702 from image 701, a target object image 703 is obtained, and by subtracting image 712 from image 711, a target object image 713 is obtained.

[0150] The difference 740 may correspond to the difference reflecting the phase value at each position in the transfer function for the kth phase plane.

[0151] 8 and 9 are diagrams illustrating an imaging method for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0152] FIG. 8 illustrates a procedure for tracking multiple scattering trajectories from a time-resolved reflectance matrix and then correcting them to obtain an image of an object deep inside a scattering medium such as biological tissue, in an imaging method for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0153] For convenience of explanation, the following describes an imaging method for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0154] Referring to FIG. 8, in step S801, the imaging method according to an embodiment of the present invention irradiates light onto an object.

[0155] That is, in the imaging method according to an embodiment of the present invention, light that has passed through a scattering medium and multiple scattering components in the scattering medium is incident on a target object.

[0156] In step S802, the imaging method according to an embodiment of the present invention senses light returning from the target object.

[0157] That is, the imaging method according to an embodiment of the present invention senses light that is incident, passes through multiple scattering components from the target object, and is reflected back.

[0158] In step S803, the imaging method according to an embodiment of the present invention measures a time-resolved reflection matrix.

[0159] That is, the imaging method according to an embodiment of the present invention measures a time-resolved reflection matrix reflecting multiple scattering trajectories based on multiple scattering components based on returning light.

[0160] In step S804, the imaging method according to an embodiment of the present invention obtains an object reflection matrix from the time-resolved reflection matrix.

[0161] That is, an imaging method according to one embodiment of the present invention can obtain an object reflection matrix by numerically iteratively accessing a plurality of phase planes to obtain an incident transmission matrix and a reflected transmission matrix, and then reflecting the inverse matrices of the obtained incident transmission matrix and the obtained reflected transmission matrix on the measured time-resolved reflection matrix.

[0162] In step S805, the imaging method according to an embodiment of the present invention obtains an image in which multiple scattering distortion has been corrected based on the object reflection matrix.

[0163] That is, the imaging method according to an embodiment of the present invention acquires an image of a target object in which multiple scattering distortion due to multiple scattering trajectories is corrected based on the object reflection matrix.

[0164] FIG. 9 illustrates a procedure for performing a multiple scattering tracking algorithm in an imaging method for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0165] For convenience of explanation, the following describes an imaging method for correcting and restoring an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0166] Referring to FIG. 9, in step S901, the imaging method according to an embodiment of the present invention measures a time-resolved reflection matrix.

[0167] That is, the imaging method according to an embodiment of the present invention measures a time-resolved reflection matrix reflecting multiple scattering trajectories based on multiple scattering components based on returning light.

[0168] In step S902, the imaging method according to an embodiment of the present invention obtains a phase function by approaching the ith phase plane and corrects the phase.

[0169] That is, in an imaging method according to an embodiment of the present invention,

[0170] In step S903, the imaging method according to the embodiment of the present invention determines whether convergence has occurred up to the last phase plane.

[0171] That is, the imaging method according to the embodiment of the present invention approaches the last phase plane and proceeds to step S904 when the phase correction is completed, and returns to step S902 when the last phase plane is not reached.

[0172] In step S904, the imaging method according to an embodiment of the present invention obtains an incident transmission matrix, a reflected transmission matrix, and an object reflection matrix.

[0173] That is, an imaging method according to one embodiment of the present invention can obtain an object reflection matrix by numerically iteratively accessing multiple phase planes approximated from a scattering medium, obtaining an incident transmission matrix and a reflection transmission matrix, and reflecting the inverse matrices of the obtained incident transmission matrix and the obtained reflection transmission matrix onto the measured time-resolved reflection matrix.

[0174] In step S905, the imaging method according to the embodiment of the present invention reconstructs an object image based on the object reflection matrix.

[0175] That is, the imaging method according to an embodiment of the present invention reconstructs and acquires an image of a target object using an image in which multiple scattering distortion due to multiple scattering trajectories is corrected based on an object reflection matrix.

[0176] 10a-10c illustrate numerical simulations of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0177] 10a-10c illustrate schematic diagrams and results associated with numerical simulations of a reflection matrix-based multiple scattering tracking algorithm in accordance with one embodiment of the present invention.

[0178] FIG. 10a illustrates a schematic diagram of a simulation model associated with a numerical simulation of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0179] Referring to FIG. 10a, a schematic diagram 1000 shows a resolution target object 1001 placed below a scattering medium 1002, and a reflection matrix based on light that passes through the scattering medium 1002, strikes the target object 1001, and is then reflected is measured.

[0180] An initial scattering medium consisting of four phase planes and a reflection matrix due to the target object are configured through numerical simulation within the scattering medium 1002. Here, the numerical simulation is related to the phase plane design described in FIG.

[0181] FIG. 10b illustrates a phase map and reconstruction results in a phase plane applied to a simulation model in connection with a numerical simulation of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0182] Referring to FIG. 10b, there is shown a simulated phase map 1010 applied to a numerical simulation and a restored phase map 1011 restored from the simulated phase map 1010 using a multiple scattering tracking algorithm.

[0183] Comparing the simulated phase map 1010 with the reconstructed phase map 1011, it can be seen that the shape of the initial phase map can be almost restored by applying a multiple scattering tracking algorithm to the reflection matrix to reconstruct the phase map for each phase plane.

[0184] FIG. 10c illustrates the results of applying the reflection matrix-based multiple scattering tracking algorithm in connection with a numerical simulation of the multiple scattering tracking algorithm according to one embodiment of the present invention.

[0185] Referring to FIG. 10c, image 1020 illustrates an image based on the initial reflection matrix R obtained by numerical simulation, image 1021 illustrates an image of the reflection matrix of the restored target object, image 1022 illustrates a confocal image of the initial object distorted by the initial scattering medium, and image 1023 illustrates an image of the object restored by the multiple scattering tracking algorithm.

[0186] The initial reflection matrix has strong signal intensities distributed in the off-diagonal elements due to the scattering medium.

[0187] However, when the signal is restored using a multiple scattering tracking algorithm, most of the multiple scattering is removed and the signal is distributed only in the diagonal components.

[0188] Also, as shown in image 1022 and image 1023, it can be seen that images distorted by multiple scattering are reliably restored after application of the multiple scattering tracking algorithm.

[0189] 11a-11c illustrate experimental verification using an onion of a reflection matrix based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0190] 11a-11c illustrate schematic diagrams and results associated with an experimental demonstration using an onion of a reflection matrix-based multiple scattering tracking algorithm in accordance with one embodiment of the present invention.

[0191] FIG. 11a illustrates a schematic diagram of a multi-layered onion tissue used as a scattering medium and a resolution target object placed underneath in connection with an experimental demonstration using an onion of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0192] Referring to FIG. 11a, a schematic diagram 1100 shows a resolution target object 1101 placed under a thick onion tissue 1102 having a multi-layer structure, and a reflection matrix based on light incident through an objective lens 1103 and then reflected is measured.

[0193] Schematic diagram 1100 shows an experimental environment for imaging a target object 1101 with a Siemens star pattern in thick onion tissue 1102 .

[0194] In this case, the onion tissue 1102 used as the scattering medium consisted of five cell layers and had a total thickness of about 1 mm.

[0195] FIG. 11b illustrates an image restored by applying the multiple scattering tracking algorithm and a confocal image without applying the multiple scattering tracking algorithm, in connection with experimental verification using an onion of the reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0196] Referring to FIG. 11b, confocal image 1110 may represent a confocal image of an object reconstructed from the reflectance matrix of the sample, without the multiple scattering tracking algorithm applied.

[0197] Meanwhile, a restored image 1111 may represent an image of a target object restored by a multiple scattering tracking algorithm according to an embodiment of the present invention.

[0198] Confocal image 1110 shows that the image of the object is severely distorted by multiple scattering and aberrations in the onion tissue.

[0199] Meanwhile, the reconstructed image 1111 confirms that the image of the target object has been reliably reconstructed based on the multiple scattering tracking algorithm.

[0200] FIG. 11c illustrates an image restored by applying a reflection matrix-based multiple scattering tracking algorithm in connection with experimental verification of the reflection matrix-based multiple scattering tracking algorithm using an onion according to one embodiment of the present invention.

[0201] Referring to FIG. 11c, in order to apply the reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention, it is assumed that there are phase planes at positions 250 μm, 400 μm, 600 μm, 800 μm, and 1000 μm away from the resolution target object, and the phase map of each plane is restored.

[0202] The distance of the first phase plane 1120 is 250 μm, the distance of the second phase plane 1121 is 400 μm, the distance of the third phase plane 1122 is 600 μm, the distance of the fourth phase plane 1123 is 800 μm, and the distance of the fifth phase plane 1124 is 1000 μm.

[0203] Resolution Phase maps of three phase planes near the object provide good images of the onion cells in each layer.

[0204] This proves that the phase plane reconstructed by the multiple scattering tracking algorithm reliably reflects the actual onion tissue structure.

[0205] In the fourth phase plane 1123 and the fifth phase plane 1124, the morphology of the onion cell layer cannot be clearly seen, which may be due to the phase reconstruction resolution of the corresponding layer being insufficient to image the onion cells.

[0206] 12a-12d illustrate experimental verification using biological tissue of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0207] 12a to 12d illustrate schematic diagrams and results related to experimental verification of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention using biological tissue, demonstrating the feasibility of implementing the multiple scattering tracking algorithm in general biological tissue that does not have a multi-layer structure.

[0208] FIG. 12a illustrates a schematic diagram of a mouse skull used as a scattering medium and a resolution target object placed underneath it in connection with an experimental demonstration using biological tissue of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0209] Referring to FIG. 12a, a schematic diagram 1200 shows a resolution target object 1201 placed under a 200 μm thick mouse skull tissue 1202, and a reflection matrix based on light incident through an objective lens 1203 and then reflected is measured.

[0210] In the case of the schematic diagram 1200, unlike the case of the schematic diagram 1100 described in FIG. 11a, since this sample does not have a multi-layer structure, it is necessary to first confirm the position of the phase plane and the number of planes required.

[0211] FIG. 12b illustrates experimental results for determining the position of the phase plane when the sample does not have a multilayer structure in connection with experimental verification using biological tissue of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0212] Referring to FIG. 12b, graph 1210 shows the results depending on the position of the phase plane layer, assuming a single phase plane, and measuring the electric field strength by applying a multiple scattering tracking algorithm while changing the distance (position) of the phase plane from the target object.

[0213] Graph 1210 shows the result of plotting the sum of the image intensity as a function of distance depending on the position of the phase plane layer.

[0214] In the graph 1210, it can be seen that the signal intensity distribution is located in the shaded area, which can indicate that skull tissue is distributed in that location.

[0215] FIG. 12c illustrates experimental results for confirming the number of phase planes when the sample is not a multi-layer structure in connection with experimental verification using biological tissue of a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0216] Referring to FIG. 12c, graph 1220 shows the results of measuring the electric field strength while applying a multiple scattering tracking algorithm based on varying numbers of phase plane layers.

[0217] That is, graph 1220 shows the results of plotting the distribution of signal intensity after assuming 0 to a maximum of 8 phase planes located within the region based on graph 1210 (region of 100 μm to 300 μm) and applying the multiple scattering tracking algorithm.

[0218] Graph 1220 confirms that the signal strength increases as the number of phase planes increases, but the increase in signal strength slows down at around five phase planes.

[0219] This means that the skull tissue in question is well approximated by about five phase planes.

[0220] In addition, the signal strength increases by up to 600 times, which may be a result of utilizing multiple scattering, rather than ballistic waves, for imaging.

[0221] FIG. 12d illustrates confocal and reconstructed images associated with experimental demonstration using biological tissue of a reflectance matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0222] Referring to FIG. 12d, confocal image 1230 may represent a confocal image of an object reconstructed from the reflectance matrix of the sample, without the multiple scattering tracking algorithm applied.

[0223] Meanwhile, a restored image 1231 may represent an image of a target object restored by a multiple scattering tracking algorithm according to an embodiment of the present invention.

[0224] Comparing the confocal image 1230 with the reconstructed image 1231 proves that the image of the target object is reliably reconstructed despite the multiple scattering of the thick skull tissue, which has a non-multilayer structure, demonstrating that the multiple scattering tracking algorithm can be applied to general biological tissues that do not have a multilayer structure.

[0225] 13a-13d are diagrams illustrating in-vivo imaging results using a reflectance matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0226] FIG. 13a illustrates a schematic diagram for imaging the brain cortex through and beyond the skull of a living mouse, in conjunction with in-vivo imaging results using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0227] Referring to FIG. 13a, a schematic diagram 1300 according to one embodiment of the present invention shows that an objective lens 1303 is used to direct light at a specific point on a target object 1301 to image the mouse brain cortex, which corresponds to the target object 1301, through the skull, which corresponds to the scattering medium 1302.

[0228] FIG. 13b illustrates an in-vivo imaging result using a reflectance matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention, illustrating a schematic depth cross-section of a mouse skull and cerebral cortex using a reflectance matrix microscope to which a multiple scattering tracking algorithm is applied.

[0229] Referring to FIG. 13 b, a schematic diagram 1310 illustrates a brain as the target object 1311 and a skull as the scattering medium 1312 .

[0230] A reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention positions multiple phase planes within the scattering medium 1312 to compensate for multiple scattering distortions caused by scattering trajectories due to the multiple scattering components of the scattering medium 1312.

[0231] For example, the multiple phase planes are configured from a first phase plane (z1) to a fifth phase plane (z5) with the target object 1311 as the reference.

[0232] The number of multiple phase planes is proportional to the complexity due to the multiple scattering components of the scattering medium 1312.

[0233] That is, the number of phase planes increases as the complexity increases, and as the number increases, the improvement increases, but the calculation time may also increase, so the number of phase planes can be determined to correspond to maximum efficiency.

[0234] Figure 13c illustrates in-vivo imaging results using a reflectance matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention, illustrating depth cross-section images of a mouse skull and brain cortex using a reflectance matrix microscope before and after application of the multiple scattering tracking algorithm.

[0235] Referring to FIG. 13c, image 1320 shows that the confocal image before the application of the multiple scattering tracking algorithm shows a rapid decrease in signal intensity after 60 μm inside the skull.

[0236] On the other hand, after applying the multiple scattering tracking algorithm, the specific internal morphology is exposed down to a depth of 300 μm.

[0237] Furthermore, the multi-planar image obtained after applying the multiple scattering tracking algorithm reveals that the boundary between the skull and the surface of the cerebral cortex is formed at a depth of approximately 200 μm.

[0238] Figure 13d illustrates a comparison between a confocal image reconstructed from a reflection matrix at each depth and a restored image using the multiple scattering tracking algorithm, relating to in-vivo imaging results using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0239] Referring to FIG. 13d, the depth of the scattering medium is divided into four sections, and a confocal image 1330 in the xy plane is compared with a reconstructed image 1331 according to an embodiment of the present invention.

[0240] The first three rows of images, confocal image 1330 and reconstructed image 1331, show the internal image of the skull, and the last row shows the internal image of the cerebral cortex.

[0241] In the case of the confocal image 1330, at a depth of 80 μm, the specific structures of the cells are already distorted by multiple scattering and cannot be seen clearly.

[0242] On the other hand, restored image 1331 clearly shows the morphology of the osteocytes inside the skull and the canaliculi extending from each cell up to a region of 175 μm at the bottom of the skull.

[0243] In addition, the restored image 1331 clearly shows the nerve bundles in the cortical layer at a depth of 270 μm.

[0244] That is, the present invention can be utilized for in-vivo imaging of living organisms, and it can be seen that the multiple scattering tracking algorithm method can exhibit superior performance compared to existing confocal microscopes.

[0245] Therefore, since the present invention acquires images in a label-free manner, it has a very wide range of applications. It does not require additional equipment as in existing reflection matrix microscopes, and since it does not affect the data measurement time itself as a post-processing technique, it is expected to be used for acquiring in-vivo images that require fast measurement, and can be used in research on various disease models or animal experiments, etc., and it can provide an imaging device and method whose range of applications can be expanded to include use as a diagnostic and clinical tool.

[0246] In addition, the present invention uses a post-correction method in which data such as reflection matrix data is acquired and then corrected, thereby immediately acquiring data without any prior preparation procedures, thereby reducing data measurement time and enabling acquisition of 3D deep depth images while maintaining the state of the subject through in-vivo imaging.

[0247] FIG. 14 is a diagram illustrating the correction and restoration performance of an imaging apparatus that corrects and restores an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention.

[0248] FIG. 14 illustrates the correction and restoration performance of an imaging apparatus that corrects and restores an image of an object in a scattering medium using a reflection matrix-based multiple scattering tracking algorithm according to one embodiment of the present invention, compared to the prior art.

[0249] Referring to FIG. 14, images 1400 to 1430 are shown as examples of performance comparison results for each imaging method of a reflection matrix microscope.

[0250] Image 1400 may represent a confocal microscope image, image 1410 may represent a CLASS microscope image, image 1420 may represent a conjugate-CLASS image, and image 1430 may represent an image corrected and restored using a reflectance matrix-based multiple scattering tracking algorithm.

[0251] Image 1430 may be the corrected and restored image described in FIG.

[0252] When comparing images 1400 to 1430, it can be seen at a glance that the present invention exhibits relatively superior performance.

[0253] This is possible because, while other imaging methods use ballistic waves that decrease exponentially with depth, the present invention is able to utilize multiple scattering as an imaging signal, demonstrating excellent restoration and correction performance.

[0254] Therefore, the present invention can provide an imaging apparatus and method that can acquire a 3D deep image while changing the measurement depth with a reduced data measurement time, and thus can be used in a variety of medical and life science applications.

[0255] Furthermore, the present invention provides an imaging device that can be readily applied to clinical practice because it is an algorithm that applies a reflection matrix obtained through reflection without labeling, and can acquire images with great depth and high resolution. It can also provide an imaging device that can be applied to measurement equipment because it can acquire images of the inside of samples such as biological tissues and semiconductors without decomposing the inside of the samples.

[0256] The devices described above may be implemented using hardware components, software components, and / or a combination of hardware and software components. For example, the devices and components described in each embodiment may be implemented using one or more general-purpose or special-purpose computers, such as a processor, controller, arithmetic logic unit (ALU), digital signal processor, microcomputer, field programmable array (FPA), programmable logic unit (PLU), microprocessor, or any other device capable of executing and responding to instructions. A processing device may execute an operating system (OS) and one or more software applications running on the operating system. A processing device may also access, store, manipulate, process, and generate data in response to the execution of software. For ease of understanding, a single processing device may be described. However, those skilled in the art will recognize that a processing device may include multiple processing elements and / or multiple types of processing elements. For example, a processing device may include multiple processors or one processor and one controller. Other processing configurations are also possible, such as parallel processors.

[0257] Software may include a computer program, code, instructions, or a combination of one or more of these, which may configure a processing device to operate as desired or may instruct the processing device, either individually or collectively. The software and / or data may be permanently or temporarily embodied in any type of machine, component, physical device, virtual device, computer storage medium or device, or transmitted signal wave, for interpretation by the processing device or for providing instructions or data to the processing device. Software may also be distributed across network-coupled computer systems, stored or executed in a distributed manner. The software and data may be stored on one or more computer-readable recording media.

[0258] Although the embodiments have been described above with reference to the drawings, those skilled in the art will appreciate that various modifications and variations may be made to the above description. For example, the techniques described may be performed in a different order than described, and / or the components of the systems, structures, devices, circuits, etc. described may be combined or combined in a different manner than described, or may be substituted or replaced by other components or equivalents, and still achieve suitable results.

[0259] Therefore, other implementations, other embodiments, and equivalents of the claims are also within the scope of the following claims. [Explanation of symbols]

[0260] 100 Imaging Device 110 Light source section 120 Sensing part 130 Reflection matrix measurement section 140 Algorithm processing section 150 Image Processing Unit 160 control section

Claims

1. a light source unit that causes light that has passed through a scattering medium and multiple scattering components in the scattering medium to be incident on a target object; a sensing unit that senses the light that, after being incident, passes through the multiple scattering component from the target object, is reflected, and returns; a reflection matrix measurement unit that measures a time-resolved reflection matrix reflecting a multiple scattering trajectory based on the multiple scattering components based on the returning light; an algorithm processing unit that numerically iteratively accesses a plurality of phase planes approximated from the scattering medium using a multiple scattering tracking algorithm to obtain an incident transmission matrix and a reflection transmission matrix, and obtains an object reflection matrix by reflecting the inverse matrices of the obtained incident transmission matrix and the obtained reflection transmission matrix on the measured time-resolved reflection matrix; and an image processing unit that acquires an image in which multiple scattering distortion due to the multiple scattering trajectory is corrected based on the acquired object reflection matrix; the algorithm processing unit performs numerical iterative access to each phase plane by multiplying an input or output end of the time-resolved reflection matrix by a spatial propagation matrix (P k ) corresponding to a distance to a k-th phase plane based on the multiple scattering tracking algorithm, thereby obtaining a plurality of incident transmission matrices and a plurality of reflection transmission matrices corresponding to the k-th phase plane; An imaging device characterized in that the spatial propagation matrix (P k ) includes an input as an incidence determined with respect to a plane corresponding to the target object and an output as a reflection determined with respect to the kth phase plane to be accessed.

2. 2. The imaging apparatus of claim 1, wherein the algorithm processing unit acquires a difference between phase delay values ​​of two points by considering a case where light is focused at two different points on a specific phase plane among the plurality of phase planes based on the multiple scattering tracking algorithm, and applies the acquired difference to an incident transmission matrix and a reflected transmission matrix acquired on the specific phase plane.

3. 2. The imaging device of claim 1, wherein each of the plurality of phase planes is virtually located within or on the scattering medium by calculating a transmission matrix in association with multiple scattering components within the scattering medium, designing a first phase plane based on the calculated transmission matrix, and designing a second phase plane on the designed first phase plane based on an inverse transmission matrix of the calculated transmission matrix.

4. 2. The imaging apparatus of claim 1, wherein the positions of the plurality of phase planes are determined as positions where the measured electric field strength is greater than a reference value after measuring the electric field strength by applying the multiple scattering tracking algorithm while changing the distance from the target object.

5. 2. The imaging apparatus of claim 1, wherein the number of the plurality of phase planes is determined by measuring an electric field intensity by applying the multiple scattering tracking algorithm while changing the number of phase planes, and then taking into consideration a calculation time depending on the changed number.

6. The imaging device of claim 1, characterized in that the reflection matrix measurement unit measures the time-resolved reflection matrix determined as the intensity and phase values ​​of the electric field measured at each position of a camera placed on a conjugate image plane of the object surface as an output reference in the light reflected as a result of an input reference, with each matrix element being light concentrated at each position on the surface of the target object.

7. the light source unit causes the light to be incident on the target object as a point illumination, and changes the position of the point illumination to change the incident position on the target object; The imaging device of claim 1 , wherein the sensing unit senses a sensing pixel that is changed according to the changed incident position.

8. 2. The imaging apparatus of claim 1, wherein the algorithm processing unit calculates inverse matrices for each of an incident transmission matrix and a reflected transmission matrix associated with the phase values ​​for the multiple scattering components of the scattering medium and the multiple phase planes and the multiple points constituting each of the multiple phase planes using the multiple scattering tracking algorithm, and acquires an object reflection matrix for the target object by reflecting the calculated inverse matrices in the time-resolved reflection matrix.

9. a step of irradiating the light transmitted through the scattering medium and the multiple scattering components in the scattering medium onto the target object in the light source unit; detecting, in a sensing unit, the light that is incident, passes through the multiple scattering component from the target object, and is reflected and returned; measuring, in a reflection matrix measurement unit, a time-resolved reflection matrix in which a multiple scattering trajectory based on the multiple scattering components is reflected based on the returning light; In an algorithm processing unit, a multiple scattering tracking algorithm is used to numerically iteratively access a plurality of phase planes approximated from the scattering medium to obtain an incident transmission matrix and a reflection transmission matrix, and an object reflection matrix is ​​obtained by reflecting the inverse matrices of the obtained incident transmission matrix and the obtained reflection transmission matrix on the measured time-resolved reflection matrix; and acquiring an image in which multiple scattering distortion due to the multiple scattering trajectory is corrected based on the acquired object reflection matrix in an image processing unit; the step of numerically iteratively accessing the plurality of phase planes by the multiple scattering tracking algorithm to obtain an incident transmission matrix and a reflected transmission matrix, and acquiring an object reflection matrix by reflecting the inverse matrices of the obtained incident transmission matrix and the obtained reflected transmission matrix on the measured time-resolved reflection matrix, and performing numerical iterative access to each phase plane by multiplying an input or output end of the time-resolved reflection matrix by a spatial propagation matrix (P k ) corresponding to a distance to the k-th phase plane based on the multiple scattering tracking algorithm, thereby obtaining a plurality of incident transmission matrices and a plurality of reflection transmission matrices corresponding to the k-th phase plane; An imaging method characterized in that the spatial propagation matrix (P k ) includes an input as an incidence determined for a plane corresponding to the target object and an output as a reflection determined for the kth phase plane to be accessed.

10. the step of numerically iteratively accessing the plurality of phase planes by the multiple scattering tracking algorithm to obtain an incident transmission matrix and a reflected transmission matrix, and acquiring an object reflection matrix by reflecting the inverse matrices of the obtained incident transmission matrix and the obtained reflected transmission matrix on the measured time-resolved reflection matrix, 10. The imaging method of claim 9, further comprising: considering a case where light is focused at two different points for a specific phase plane among the plurality of phase planes based on the multiple scattering tracking algorithm, obtaining a difference in phase delay values ​​between the two points, and applying the obtained difference to an incident transmission matrix and a reflected transmission matrix obtained for the specific phase plane.

11. 10. The imaging method of claim 9, wherein each of the plurality of phase planes is virtually located within or on the scattering medium by calculating a transmission matrix in association with multiple scattering components within the scattering medium, designing a first phase plane based on the calculated transmission matrix, and designing a second phase plane on the designed first phase plane based on an inverse transmission matrix of the calculated transmission matrix.

12. the positions of the plurality of phase planes are determined as positions where the measured electric field strength is greater than a reference value after measuring the electric field strength by applying the multiple scattering tracking algorithm while changing the distance from the target object; The imaging method of claim 9, wherein the number of the plurality of phase planes is determined by measuring the electric field strength by applying the multiple scattering tracking algorithm while changing the number of phase planes, and then taking into consideration the calculation time depending on the changed number.

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