KR20210031013A - Method of Providing Information for Diagnosing Lymphedema Using ICG Lymphography - Google Patents

Abstract

The present invention relates to an information providing method for diagnosing lymphedema using indocyanine green (ICG) lymphangiography. More specifically, the present invention relates to an information provision method for diagnosing lymphedema using ICG lymphangiography to precisely measure and confirm a skin reflux pattern and location since the protocol of ICG lymphangiography can be established and a camera can be mounted at a desired angle and position and improving the reliability of a follow-up examination for disease such as lymphedema by mounting an imaging marker.

Description

Method of Providing Information for Diagnosing Lymphedema Using ICG Lymphography

The present invention relates to a method for providing information for the diagnosis of lymphedema using ICG (Indocyanine green) lymphography, and more specifically, to establish a protocol for ICG lymphography, and to take pictures with a camera at a desired angle and position. It is possible to accurately measure and confirm the pattern and location of skin reflux, and to provide information for the diagnosis of lymphedema using ICG lymphography, which can improve the reliability of follow-up tests for diseases such as lymphedema by mounting photographic markers. About.

The lymphatic system is composed of lymphatic vessels that carry lymph fluid along with a number of tissues and organs, including lymphoid tissue, which is a special form of reticulated connective tissue containing large amounts of lymphocytes. Although the thymus component of several lymphatic organs is composed of epithelial reticular tissue, the stroma and outer structure of lymphoid tissues are generally composed of complex reticular tissues of reticular fibers (connective tissue forming cells) and reticulocytes (fixed macrophages). It moves interstitial fluid from the stroma of the blood to tissues and blood vessels and plays an important role in maintaining homeostasis, metabolism and immune function. In particular, lymphatic vessels are known to play an important role in the pathophysiological mechanisms of malignant tumors, lymphedema and inflammatory diseases.

Lymphatic vessels are similar in structure to blood vessels, but contain lymphatic capillaries that bind to large lymphatic vessels (lymphatic vessels) with many thin walls and many plates throughout the body and contain lymph nodes in several places throughout the body. The most dense areas of lymph nodes can be found in the face, neck, armpits, chest cavity, intestines and groin, elbows and knees. Usually, the shallow lymphatic vessels in the epidermis extend along the veins, while the deep lymphatic vessels extend along the arteries. Lymphatic vessels supply lymph through the body and function to return proteins to the cardiovascular system when proteins leak out of capillaries. In addition, the lymphatic vessels carry fat from the stomach into the blood. In cancer patients, lymphatic tissue has the function of monitoring and defending heterogeneous cells, bacteria and cancer cells. Certain lymphocytes (T cells) release several substances and destroy these invaders either directly or indirectly. Other lymphocytes (B cells) differentiate into plasma cells that secrete antibodies against foreign substances to help remove these substances. Lymph nodes act as filters for foreign substances carried by the lymph by their reticular fibrous tissue. And macrophages destroy foreign substances through phagocytosis. In addition, lymph nodes produce lymphocytes, some of which are transported from lymph to other parts of the body as part of their immune defense system. The spleen, thymus and tonsils are lymphoid organs that produce B-cells, T-cells, and lymphocytes together with antibodies to complete the immune defense line of the lymphatic system.

As such, lymphatic vessels that drain tissue fluid from tissue stroma play an important role in immunological defense mechanisms, and pathophysiological mechanisms of malignant tumors, lymphedema and inflammatory diseases are known to play an important role in these disorders of lymphatic formation. . Among the dysfunctions of the lymphatic vessels, lymphedema is a condition in which lymphatic fluid is stored under the skin due to the abnormal accumulation of proteins due to damage or blockage of the lymphatic vessels. It is a result of obstruction of lymph drainage of lymphoid tissue area by Penetration of these obstructive tissues by macrophages induces elimination of lymphatic flow through proteolysis of obstructive proteins over a significant period of time. As such, when the lymphatic vessel dysfunction occurs, a problem occurs in the movement of extracellular fluid and macromolecular substances, resulting in tissue swelling, immune dysfunction, and fibrosis of interstitial tissue. Lymphedema occurs due to hereditary or secondary causes, and lymphedema caused by secondary causes often occurs after treatment of malignant tumors accompanied by surgery and radiation therapy. It is reported that acquired edema occurs in more than 45% of breast cancer patients, the number one incidence of female cancer, and occurs in more than 10% of all cancer patients.

For diseases such as lymphedema, since the location of the lymph nodes cannot be accurately located with the naked eye, a nuclear medical imaging method using radioactive isotopes as a tracer, an imaging method using a magnetic fluid having a magnetism, and a bio-dye An optical imaging method using or a method in which a radioactive isotope and a bio-dye are simultaneously combined is used. However, considering that most of the methods place a large burden on the subject in terms of cost, and this is also only a subjective confirmation of the doctor, not a quantified number, there are practically no methods related to this until now.

Accordingly, in order to compensate for the above-described problems, the present inventors recognized that it is urgent to develop a method for diagnosing lymphedema that can quantitatively and visually confirm lymphedema such as lymphedema, and thus completed the present invention.

Korean Patent Publication No. 10-1956291 Korean Patent Publication No. 10-1539180

1.Alitalo K, Tammela T, Petrova TV. Nature 2005;438:946-953

An object of the present invention is to provide a method for diagnosing lymphedema using ICG lymphography, which can accurately measure and confirm the pattern and location of skin reflux by establishing a protocol for ICG lymphography and photographing it through a camera at a desired angle and position.

Another object of the present invention is to provide a method for providing information for diagnosing lymphedema using ICG lymphography, which can improve the reliability of follow-up tests for diseases such as lymphedema by mounting an imaging marker.

The problems of the present invention are not limited to the problems mentioned above, and other problems that are not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the above object, the present invention provides a method for diagnosing lymphedema using ICG lymphography, which can quantitatively and visually identify a lymphatic system disease such as lymphedema.

Hereinafter, the present specification will be described in more detail.

The present invention provides a method for diagnosing lymphedema using CG lymphography comprising the following steps.

(S1) injecting ICG (Indocyanine Green) into the body of the subject and attaching a marker;

(S2) photographing the body of the subject to obtain an image, and image processing the image; And

(S3) analyzing the amount of change in fluorescence intensity over time by setting two-dimensional coordinates on the image-processed image.

In the present invention, in the step (S1), the ICG is injected at a concentration of 0.02 to 0.05 nM, and the marker is a reflective film and is attached to both ends of the body photographing site of the subject.

In the present invention, the step (S2) is characterized by consisting of the following steps.

(S2A) photographing the markers attached to the body of the subject as both ends;

(S2B) image processing the captured image; And

(S2C) horizontally processing the image by recognizing the marker on the processed image.

In the present invention, the image processing is characterized in that the binarization or image processing.

In the present invention, the step (S3) is characterized by consisting of the following steps.

(S3A) converting the image into two-dimensional coordinates;

(S3B) colorizing the coordinated image by setting a brightness range of 0 to 255; And

(S3C) digitizing the amount of change in fluorescence intensity using the colored brightness data.

In the present invention, the steps (S1) to (S3) are performed continuously for 20 minutes to 40 minutes at intervals of 30 seconds to 1 minute.

In the method of providing information for the diagnosis of lymphedema using ICG lymphography of the present invention, since the protocol of ICG lymphography can be established and photographed with a camera at a desired angle and position, the pattern and position of skin reflux can be accurately measured and confirmed. , It is possible to improve the reliability of a follow-up test for diseases such as lymphedema by mounting an imaging marker.

The effects of the present invention are not limited to the above-mentioned effects, and other effects not mentioned will be clearly understood by those skilled in the art from the description of the claims.

1 is a block diagram schematically showing a method of providing information for diagnosing lymphedema using ICG lymphography according to the present invention.
2 is a diagram illustrating step (S2) of the first embodiment in the method of providing information for diagnosing lymphedema using ICG lymphography according to the present invention.
3 is a diagram illustrating step (S2) of the second embodiment in the method of providing information for diagnosing lymphedema using ICG lymphography according to the present invention.
4 is a diagram illustrating step (S3) in the method of providing information for diagnosing lymphedema using ICG lymphography according to the present invention.
FIG. 5 is a diagram of coordinates of an image by performing step (S3A) in the method of providing information for diagnosis of lymphedema using ICG lymphography of the present invention.

Terms used in the present specification have selected general terms that are currently widely used as possible while taking functions of the present invention into consideration, but this may vary according to the intention or precedent of a technician working in the field, the emergence of new technologies, and the like. In addition, in certain cases, there are terms arbitrarily selected by the applicant, and in this case, the meaning of the terms will be described in detail in the description of the corresponding invention. Therefore, the terms used in the present invention should be defined based on the meaning of the term and the overall contents of the present invention, not a simple name of the term.

Unless otherwise defined, all terms used herein including technical or scientific terms have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs. Terms such as those defined in a commonly used dictionary should be interpreted as having a meaning consistent with the meaning in the context of the related technology, and should not be interpreted as an ideal or excessively formal meaning unless explicitly defined in the present application. Does not.

The numerical range includes the numerical values defined in the above range. All maximum numerical limits given throughout this specification include all lower numerical limits as if the lower numerical limits were expressly written. All minimum numerical limits given throughout this specification include all higher numerical limits as if the higher numerical limits were expressly written. All numerical limits given throughout this specification will include all better numerical ranges within the wider numerical range, as if the narrower numerical limits were expressly written.

Hereinafter, examples of the present invention will be described in detail, but it is obvious that the present invention is not limited by the following examples.

Embodiment 1

1 is a block diagram schematically showing a method of providing information for diagnosing lymphedema using ICG lymphography of the present invention. The present invention provides a method for diagnosing lymphedema using ICG lymphography comprising the following steps.

(S1) injecting ICG (Indocyanine Green) into the body of the subject and attaching a marker;

(S2) photographing the body of the subject to obtain an image, and image processing the image; And

(S3) analyzing the amount of change in fluorescence intensity over time by setting two-dimensional coordinates on the image-processed image.

The term “subject” used in the present invention refers to a recipient, and the subject applied to the present invention is a patient with lymphedema or a person suspected of lymphedema using ICG lymphography to diagnose lymphedema. Means the person who does it.

The term "ICG" used in the present invention is a dark green fluorescent dye (reagent) and binds to albumin, a water-soluble protein.

The term "image processing" used in the present invention means any processing technique for changing a set value of an image or moving picture.

The term “two-dimensional coordinates” used in the present invention refers to a coordinate system formed with a coordinate plane composed of X and Y axes, and the two-dimensional coordinates applied to the present invention capture an image processed by photographing the body of the subject. And setting the coordinates on the Y-axis.

In the present invention, the step (S1) may be a step of injecting ICG (Indocyanine Green) into the body of the subject and attaching a marker.

More specifically, in the step (S1), the ICG may be injected at a concentration of 0.02 to 0.05 nM. By injecting the ICG into the subject's body, it is possible to clearly confirm the pattern and location of skin reflux of the subject, and visually confirm changes in the internal lymphatic system according to the expression of lymphedema caused by lymphatic system abnormalities.

The marker may be a marker in the form of a black-based reflective film capable of absorbing light, and may be easily applied as long as it is a black-based marker capable of absorbing light less than or equal to the skin brightness color of the subject.

The markers are attached to both ends of the subject's body photographing portion to find a boundary line between the subject's photographing portion and the marker.

Since the marker can absorb light, it is easy to take an image by irradiation of infrared rays, and thus, coordinates can be set, so that lymphedema can be more accurately diagnosed.

In the present invention, the step (S2) is a step of obtaining an image by photographing the body of the subject, and image processing the image, and may consist of the following steps.

(S2A) photographing the markers attached to the body of the subject as both ends;

(S2B) image processing the captured image; And

(S2C) horizontally processing the image by recognizing the marker on the image-processed image.

FIG. 2 is a diagram illustrating step (S2) of the first embodiment in the method of providing information for diagnosis of lymphedema using ICG lymphography of the present invention, and FIG. 2A corresponds to the step (S2A), and FIG. It corresponds to step (S2B), and FIG. 2C corresponds to step (S2C).

Referring to FIG. 2A, the step (S2A) is a step of photographing the body of the subject. In the step (S1), an infrared ray (IR) is irradiated on the body of the subject into which ICG is injected, and at this time, the ICG It may be a step of photographing infrared rays reflected and emitted in response to and through a camera.

In the step (S2A), infrared rays of 750 to 780 nm are irradiated to the body of the subject injected with the ICG, and at this time, infrared rays in the range of 800 to 820 nm that are reflected and emitted by reacting with the ICG are irradiated with a wavelength of 800 nm or less It can be photographed and imaged through a camera including a filter to be removed.

The camera used in the step (S2A) may be an intensified charge coupled device camera (ICCD camara), and a filter included in the camera may be an IR PASS filter.

The photographing performed in the step (S2A) may be continuously photographed for 20 minutes to 40 minutes at intervals of 30 seconds to 1 minute.

2B and 2C, the step (S2B) is an image processing of the captured image, and the image processing may be binarization and edge processing.

The binarization process may be a technique of imaging the photographed image in black and white based on a threshold value in a brightness range of 0 to 255. The threshold value serving as a reference for the binarization process may be set as an average of the brightness range values of the image captured in the step (S2A).

The edge processing may be a technique of extracting an outer line of the captured image. The edge processing is used to recognize a circle of the marker, and is to obtain an interface between the marker and the subject.

In the (S2B) step, the image processing may be performed only one of the binarization processing and the edge processing, and may be performed simultaneously, preferably, the binarization processing and the edge processing may be performed simultaneously, and most preferably the binarization processing is performed. And edge treatment is preferably performed.

Referring to FIG. 2C, the step (S2C) is a step of horizontally processing the image by recognizing the marker in the image-processed image; more specifically, a marker attached to the body part of the subject in the image-processed image It may be a step of horizontally processing a 2D image with both ends. Due to the horizontal processing, it may be possible to set two-dimensional coordinates in step (S3) to be described later.

In the present invention, the step (S3) is a step of analyzing the amount of change in fluorescence intensity over time by setting two-dimensional coordinates on the image-processed image. It is characterized in that it consists of the following steps.

(S3A) converting the image into two-dimensional coordinates;

(S3B) colorizing the coordinated image by setting a brightness range of 0 to 255; And

(S3C) digitizing the amount of change in fluorescence intensity using the colored brightness data.

FIG. 4 is a diagram illustrating step (S3) in the method for diagnosing lymphedema using ICG lymphography of the present invention, and FIG. 4A corresponds to the step (S3A), and FIGS. 4B and 4C show the ( It corresponds to step S2B). In addition, FIG. 5 is a diagram showing in detail the image coordinateization performed in the step (S3A).

4A and 5, the step (S3A) is a step of converting the horizontally processed image processed in the step (S2) into two-dimensional coordinates, and more specifically, the image processed by photographing the body of the subject. It may be a step of setting the coordinates of the image on the X and Y axes.

More specifically, when the resolution of the image is N × M, the coordinate setting method is as follows. The center of the left marker is set to (X1, Y1) or (N/12, M/(4000/750), and the center of the right marker is set to (X2, Y2). 0) can be set to (X1-(N/12, Y1-(M/(4000/750)))) In this case, the distance (d) between the left and right markers is (X2-X1), The coordinates at the top right of the image may be set to (X1+(N/12, Y1+(M/(4000/750)))) or (d+(N/6), 2M/(4000/750)).

The coordinate setting performed in the step (S3A) may be set using the openCV program.

3B and 3C, the step (S3B) is a step of colorizing the coordinated image by setting a brightness range of 0 to 255, and more specifically, a two-dimensional coordinated image in the step (S3A). Using the openCV program, a brightness range of 0 to 255 pixels, that is, a brightness value of 0 to 255, can be extracted from the image.

In the step (S3B), the image may be colored by assigning a color only to a brightness range of 150 or more in the 0 to 255 brightness range. More specifically, by extracting a brightness value of 150 or more by obtaining an average of the brightness of each pixel corresponding to each color in the image, only pixels corresponding to the brightness range value within the range may be colored.

The step (S3C) is a step of quantifying the amount of change in fluorescence intensity using the colored brightness data, and more specifically, the first photographed and colored random coordinates (X, Y) by the steps (S1) to (S3). ), A1-B1>0 and |A1- If B1|=C, it can be determined that ICG has escaped by C from the arbitrary coordinate point (X, Y).

More specifically, steps (S1) to (S3) may be continuously performed at 30 seconds to 1 minute intervals for 20 to 40 minutes to diagnose lymphedema due to the difference in the amount of change in the ICG of the individually photographed images. For example, the difference between the ICG change amount (A) obtained by first photographing the steps (S1) to (S3) and the ICG change amount (B) obtained by photographing the second step (S1) to (S3) is zero. The closer it is, the more likely it is that ICG is stagnant, so it can be said that lymphedema has occurred. Conversely, as the difference between the amount of change in ICG (A) and the amount of change in the second ICG obtained by the first imaging (B) is larger, the ICG has a linear shape and is regarded as a non-congested form, so that it can be diagnosed instead of lymphedema.

Embodiment 2

The second embodiment of the present invention is the same as the method for diagnosing lymphedema using ICG lymphography of the first embodiment mentioned above, but only the configuration of the step (S2) is different as follows. Step (S2) may consist of the following steps.

(S2A′) photographing the markers attached to the body of the subject as both ends;

(S2B') recognizing and horizontally processing a marker in the captured image; And

(S2C') Image-processing the horizontally processed image.

The step (S2A') is the same as the step (S2A) mentioned above.

The step (S2B') is a step of photographing the markers attached to the body of the subject as both ends, and more specifically, the distance (d) between the markers by recognizing the outer line of the marker attached to the body of the subject and By calculating the angle, the subject's body may be horizontally processed.

The step (S2C') is a step of image processing the horizontally processed image, and the image processing may be a binarization process.

The binarization process may be a technique of imaging the photographed image in black and white based on a threshold value in a brightness range of 0 to 255. The threshold value serving as a reference for the binarization process may be set as an average of the brightness range values of the image captured in the step (S2A).

As described above, it will be understood that the technical configuration of the present invention described above can be implemented in other specific forms without changing the technical spirit or essential features of the present invention by those skilled in the art.

Therefore, the above-described embodiments are to be understood as illustrative and non-limiting in all respects, and the scope of the present invention is indicated by the claims to be described later rather than the detailed description, and the meaning and scope of the claims and the All changes or modifications derived from the equivalent concept should be construed as being included in the scope of the present invention.

Claims (5)

(S1) injecting ICG (Indocyanine Green) into the body of the subject and attaching a marker;
(S2) photographing the body of the subject to obtain an image, and image processing the image; And
(S3) analyzing a change in fluorescence intensity over time by setting two-dimensional coordinates on the image-processed image. The method of claim 1,
In the step (S1),
The ICG is injected at a concentration of 0.02 to 0.05 nM,
The marker is a reflective film, the method for providing information for lymphedema diagnosis, characterized in that attached to both ends of the body photographing portion of the subject. The method of claim 1,
The (S2) step,
(S2A) photographing the markers attached to the body of the subject as both ends;
(S2B) image processing the captured image; And
(S2C) horizontally processing the image by recognizing the marker on the processed image. The method of claim 1,
The (S3) step,
(S3A) converting the image into two-dimensional coordinates;
(S3B) colorizing the coordinated image by setting a brightness range of 0 to 255; And
(S3C) digitizing the amount of change in fluorescence intensity using the colored brightness data. The method of claim 1,
The (S1) to (S3) steps,
Information providing method for the diagnosis of lymphedema, characterized in that performed continuously for 20 to 40 minutes at intervals of 30 seconds to 1 minute.

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