WO2018056574A1 - Pulmonary tumor screening method using near infrared rays - Google Patents

Pulmonary tumor screening method using near infrared rays Download PDF

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WO2018056574A1
WO2018056574A1 PCT/KR2017/008771 KR2017008771W WO2018056574A1 WO 2018056574 A1 WO2018056574 A1 WO 2018056574A1 KR 2017008771 W KR2017008771 W KR 2017008771W WO 2018056574 A1 WO2018056574 A1 WO 2018056574A1
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infrared
chest wall
tumor
infrared rays
screening method
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PCT/KR2017/008771
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French (fr)
Korean (ko)
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안예찬
옥철호
박은기
김성원
이해영
강현욱
유준식
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부경대학교 산학협력단
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/359—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using near infrared light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57423—Specifically defined cancers of lung

Definitions

  • the present invention relates to a lung tumor screening method using near-infrared rays, and more particularly, near-infrared rays or a plurality of near-infrared rays irradiated to a chest wall tumor are projected through a chest wall through the body in vitro, and then near-infrared rays projected from the chest wall tumor To detect the presence or spread of chest wall tumors by detecting with the camera and imaging with shade, or by detecting with camera with the fluorescent dye injected through blood vessels, or by using the spectrophotometer through the difference in absorbance of multiple infrared near-infrared rays.
  • the present invention relates to a lung tumor screening method using near infrared rays.
  • Asbestos classified as a class 1 carcinogen by the World Health Organization's International Cancer Research Institute (WHO / IARC), is one of the leading causes of malignant mesothelioma, a lung tumor occurring in the pleura. Have a 15 to 40 year incubation period
  • the pleura is composed of the parietal pleura and the lateral pleura (visceral pleura), the pleural plaques that occur in the pleura are also generated by asbestos exposure.
  • these pleural plaques are also caused by tuberculosis, there is a lack of evidence for asbestos-related compensation because the high prevalence of tuberculosis and the lack of evidence for clinical symptoms of the pleural plaque have not been identified.
  • malignant mesothelioma has a poor prognosis (less than 1 year of survival after diagnosis) in terms of treatment, and the incidence and mortality rate are continuously increasing. This is because early diagnosis is very difficult.
  • X-ray chest examination is usually confirmed when the size of the cancer is 5 ⁇ 10mm or more to identify the abnormal area, protected by the ribs and because of the nature of the lungs overlapping with the location of the heart, it is blocked by other organs to identify the abnormal site
  • lung tissue is in direct contact with air, and is closely connected to blood vessels, which is highly likely to be malignant. Therefore, X-ray chest examination has a very low utility as an early diagnosis of lung tumors.
  • Korean Patent Publication No. 10-2005-0113442 Korean Registered Patent Publication No. 10-0266831 and the like can be referred to.
  • the present invention has been made to improve the above-mentioned problems, the object of the present invention is to detect the near-infrared rays irradiated to the position of the chest wall tumor of the pleura through the chest wall from the body through the projection, and then detect them and image them with shadows.
  • the present invention provides a lung tumor screening method using near-infrared rays to confirm the presence and spread of chest wall tumors.
  • Another object is to inject fluorescent dyes into blood vessels and deposit them on chest wall tumors, by detecting near-infrared rays irradiated to the chest wall tumor location of the pleura as the fluorescent dyes emit fluorescence in the chest wall tumors, thereby imaging the neovascularization of the chest wall tumors.
  • the present invention provides a lung tumor screening method using near infrared rays to confirm the presence or absence of a chest wall tumor.
  • Another objective is to measure or image the light intensity of multiple near infrared rays at different wavelengths irradiated simultaneously or sequentially to the chest wall tumor location of the pleura, and to determine the presence of chest wall tumors through differences in absorbance. It provides a method for tumor screening.
  • Pulmonary tumor screening method using the near-infrared of the present invention to achieve the object as described above, the near-infrared irradiated to the position of the chest wall tumor invading the body through the chest wall through the body, and detects the chest wall Imaging the shadow of the tumor.
  • the near-infrared ray is irradiated through the optical fiber inserted to the position of the chest wall tumor in the step of incidence of near-infrared radiation, and the step of detecting the near-infrared ray that is incident on the projection is preferably detected by a near-infrared detection camera.
  • the method may further include inserting the guide sheath into the working channel of the bronchoscope to the position of the chest wall tumor after the insertion of the optical fiber and before the step of irradiating the near infrared rays, thereby inserting the optical fiber into the guide sheath.
  • the said near infrared rays are near infrared rays in the 780-2000 nm wavelength range.
  • the step of injecting a fluorescent dye into the blood vessel before the step of irradiating the near infrared the fluorescent dye is leaked from the immature blood vessels around the chest wall tumor and deposited on the chest wall tumor, the fluorescent by the irradiation of the near infrared
  • Another feature is the imaging of neovascularization of the chest wall tumor that emits light.
  • the fluorescent dye is preferably indocyanine green (Indocyanine green (ICG)).
  • a radiation filter disposed in front of the near-infrared detection camera.
  • an excitation filter disposed in front of the near infrared light source.
  • the near-infrared ray is irradiated with near-infrared rays of different wavelengths, by measuring or imaging the intensity of light of each near-infrared ray passing through the chest wall to determine the presence or absence of chest wall tumors through the difference in absorption have.
  • the presence or absence of the chest wall tumor through the difference in absorbance is performed by a spectroscope or a hyperspectral camera.
  • the lung tumor screening method using the near-infrared ray of the present invention it is necessary to regularly screen for a high-risk group with asbestos exposure in order to diagnose malignant carcinoma as a chest wall tumor, and malignant mesothelioma according to the present invention. Early diagnosis of the disease is effective.
  • FIG. 1 is an anatomical image showing a pleura consisting of a parietal pleura and a lateral pleura
  • Figure 2 shows normal results in PET / CT, but PET / CT and endoscopy (Roca E, Laroumagne S, Vandemoortele T, Berdah S, Dutau H, Maldonado F) showing the diagnosis of malignant mesothelioma using thoracoscopy.
  • Astoul P. "18F-fluoro-2-deoxy-d-glucose positron emission tomography / computed tomography fused imaging in malignant mesothelioma patients: looking from outside is not enough"
  • FIG. 3 is a conceptual diagram showing a lung tumor screening method using near infrared rays according to a first embodiment of the present invention
  • FIG. 4 is an enlarged view of a main part of FIG. 3;
  • FIG. 5 is a conceptual diagram showing a lung tumor screening method using near infrared rays according to a second embodiment of the present invention.
  • FIG. 6 is a conceptual diagram showing a lung tumor screening method using near infrared rays according to a third embodiment of the present invention
  • Figure 7 is an example of applying the lung tumor screening method using the near infrared ray in accordance with the present invention in the animal model
  • Figure 8 is an image showing an example showing a normal chest wall by applying the lung tumor screening method using the near infrared ray in accordance with the present invention in an animal model
  • Figure 9 is an image showing an example showing a chest tumor by applying the lung tumor screening method using the near infrared ray in accordance with the present invention in an animal model
  • FIG. 3 is a conceptual diagram illustrating a lung tumor screening method using near infrared rays according to a first embodiment of the present invention
  • FIG. 4 is an enlarged view of a main part of FIG. 3.
  • Lung tumor screening method using near infrared rays according to the first embodiment of the present invention, a method for obtaining an image of the chest wall tumor using a projection using near infrared rays in order to screen and diagnose the chest wall tumor.
  • Near-infrared radiation is an electromagnetic wave with a wavelength in the range of 780-2000 nm, and is widely used for biodiagnosis due to its high transmittance in tissue.
  • NIR source near-infrared
  • the near-infrared ray passing through the chest wall is detected and imaged by a near-infrared detection camera placed outside the body.
  • the shadow of the chest wall tumor is acquired by the near infrared detection camera in the image of the near infrared ray detection, so that the presence or absence and spread of the chest wall tumor can be known.
  • the near-infrared ray is irradiated to the location of the chest wall tumor by the optical fiber, and as shown in FIG. 4, the projection of the portion having the chest wall tumor by inserting a guide sheath into the working channel of the endoscope.
  • the optical fiber is inserted into the guide sheath to irradiate near-infrared rays to the position of the chest wall tumor through the optical fiber, and to enter the body through the chest wall and enter the projection.
  • the near-infrared rays passing through the chest wall confirm the presence and spread of the chest wall tumor as described above.
  • FIG. 5 is a conceptual diagram showing a lung tumor screening method using near infrared rays according to a second embodiment of the present invention.
  • Lung tumor screening method using a near infrared ray according to a second embodiment of the present invention, a method using a fluorescent imaging using indocyanine green (ICG), a fluorescent dye that emits fluorescence by near infrared rays.
  • ICG indocyanine green
  • ICG Indocyanine green
  • ICG is commonly used for vascular imaging by easily binding to plasma proteins, and has the property of maximizing absorption of 780 nm light to emit 820 nm fluorescence.
  • an emission filter of 820 nm is disposed in front of the near-infrared detection camera, and an excitation filter of 780 nm is disposed in front of the near-infrared light source.
  • the near-infrared irradiation is performed by the optical fiber as described above, and the optical fiber is inserted into the guide sheath of the working channel to position the chest wall tumor as described above.
  • FIG. 6 is a conceptual diagram showing a lung tumor screening method using near infrared rays according to a third embodiment of the present invention.
  • the lung tumor screening method using the near infrared rays simultaneously or sequentially records the multi-wavelength NIR sources of two different wavelengths or multiple wavelengths in the near infrared band.
  • a near-infrared spectroscopy method for determining the presence or absence of a tumor through the difference in absorbance by measuring or imaging the intensity of each near-infrared light passing through the chest wall from the body in vitro is presented.
  • the difference in absorbance is measured by measuring or imaging the near-infrared light intensity by a near-infrared detector such as a spectroscope or a hyperspectral camera located outside the body.
  • FIG. 7 is an image showing an example of applying a lung tumor screening method using a near infrared ray to an animal model according to the present invention by injecting near infrared rays through the chest wall into the body in an endoscopic method.
  • the chest wall near-infrared projection method was performed using the lung tumor screening method using the near-infrared ray of Example 1, using a normal New Zealand white rabbit as an animal model.
  • this image it can be seen that a considerable amount of near-infrared rays are projected to the outside through the chest wall in the areas that appear red.
  • FIG. 8 is an image showing near infrared rays projected through the normal chest wall of New Zealand white rabbit
  • FIG. 9 is an image showing near infrared rays projected through the tumor chest wall.
  • the normal chest wall projection image is shaded parallel to the sternum but the tumor chest wall projection image can be seen that the darker as the shadow of the tumor is added.

Abstract

The present invention relates to a pulmonary tumor screening method using near infrared rays, the method being performed by comprising the steps of: projecting near infrared rays such that the near infrared rays incident on even the position of a tumor of the chest wall come from the inside of the body to the outside through the chest wall; and detecting the near infrared rays to image a shadow of the tumor of the chest wall. For early diagnosis of malignant mesothelioma as a tumor of the chest wall, regular screening needs to be carried out on a high-risk group with a history of asbestos exposure, and the diagnosis method of the present invention has an effect of enabling early diagnosis of malignant mesothelioma.

Description

근적외선을 이용한 폐종양 스크리닝 방법Lung Tumor Screening Method Using Near Infrared
본 발명은 근적외선을 이용한 폐종양 스크리닝 방법에 관한 것으로서, 상세히는 흉벽 종양까지 조사되는 근적외선 또는 복수의 근적외선이 체내에서 체외를 통해 흉벽을 통과하여 투영 입사되도록 한 후, 상기 흉벽 종양으로부터 투영 입사되는 근적외선을 카메라로 검출하여 음영으로 영상화하거나, 혈관을 통해 주입된 형광염료와 함께 카메라로 검출하여 영상화하거나, 또는 분광기로 복수 파장의 근적외선의 흡수도의 차이를 통해 영상화하여 흉벽 종양의 유무 및 퍼짐 정도를 확인하도록 한 근적외선을 이용한 폐종양 스크리닝 방법에 관한 것이다.The present invention relates to a lung tumor screening method using near-infrared rays, and more particularly, near-infrared rays or a plurality of near-infrared rays irradiated to a chest wall tumor are projected through a chest wall through the body in vitro, and then near-infrared rays projected from the chest wall tumor To detect the presence or spread of chest wall tumors by detecting with the camera and imaging with shade, or by detecting with camera with the fluorescent dye injected through blood vessels, or by using the spectrophotometer through the difference in absorbance of multiple infrared near-infrared rays. The present invention relates to a lung tumor screening method using near infrared rays.
세계보건기구 산하 국제암연구소(WHO/IARC)에서 1급 발암물질로 분류하고 있는 석면은 흉막에 발생하는 폐종양인 악성중피종의 대표적인 원인물질 중 하나로, 상기 악성중피종은 석면에 처음 노출된 후 약 15∼40년의 잠복기를 가진다.Asbestos, classified as a class 1 carcinogen by the World Health Organization's International Cancer Research Institute (WHO / IARC), is one of the leading causes of malignant mesothelioma, a lung tumor occurring in the pleura. Have a 15 to 40 year incubation period
한편 도 1에서 보는 바와 같이, 흉막은 벽측 흉막(parietal pleura)과 장측 흉막(visceral pleura)으로 구성되며, 상기 흉막에 발생하는 흉막반(pleural plaques)도 석면노출에 의해 발생하고 있다. 그러나 이러한 흉막반은 결핵에 의해서도 발생하므로 국내의 높은 결핵 유병률과 흉막반의 임상적 증상에 대한 근거 부족으로 석면 유래 흉막반과 결핵 유래 흉막반의 차이를 규명하지 못하고 있어 석면관련 보상 근거가 부족하다.On the other hand, as shown in Figure 1, the pleura is composed of the parietal pleura and the lateral pleura (visceral pleura), the pleural plaques that occur in the pleura are also generated by asbestos exposure. However, because these pleural plaques are also caused by tuberculosis, there is a lack of evidence for asbestos-related compensation because the high prevalence of tuberculosis and the lack of evidence for clinical symptoms of the pleural plaque have not been identified.
또한 악성중피종은 치료면에서 예후가 불량(진단 후 생존율 1년 미만)하고, 발생율과 사망률은 지속적 증가하고 있는 상태에 있는데, 이렇게 되는 이유는 조기진단이 매우 어렵기 때문이다.In addition, malignant mesothelioma has a poor prognosis (less than 1 year of survival after diagnosis) in terms of treatment, and the incidence and mortality rate are continuously increasing. This is because early diagnosis is very difficult.
현재 실시되는 X선 흉부검사는 보통 암의 크기가 5∼10mm 이상 되어야 이상 부위를 확인할 수 있으며, 갈비뼈에 의해 보호되고 있고 심장의 위치와 겹쳐있는 폐의 특성상 다른 장기들에 의해 가려져 이상 부위를 확인할 수 없는 경우가 많은 한계점이 있다. 또한 X선 흉부검사에 의해 이상 부위가 확인된다고 하여도 폐 조직은 공기와 직접 접촉하면서 혈관과 밀접하게 연결되어 있어 이미 전이가 이루어지고 있는 등 악성화 되어 있을 가능성이 높다. 따라서 X선 흉부검사는 폐종양의 조기진단법으로서의 효용성이 매우 낮은 상태에 있다.Currently, X-ray chest examination is usually confirmed when the size of the cancer is 5 ~ 10mm or more to identify the abnormal area, protected by the ribs and because of the nature of the lungs overlapping with the location of the heart, it is blocked by other organs to identify the abnormal site There are many limitations. In addition, even if the abnormal site is confirmed by X-ray chest examination, lung tissue is in direct contact with air, and is closely connected to blood vessels, which is highly likely to be malignant. Therefore, X-ray chest examination has a very low utility as an early diagnosis of lung tumors.
특히 얇은 흉막 또는 복막중피에 발생하는 악성중피종의 특성상 도 2에서 보는 바와 같이, 전산단층 촬영이나 PET-CT의 해상도가 충분치 못하여 이들은 조기 진단에 도움이 되지 않고 있다.In particular, due to the characteristics of malignant mesothelioma occurring in the thin pleural or peritoneal mesothelioma, as shown in FIG. 2, the resolution of computed tomography or PET-CT is not good enough for early diagnosis.
한편 조기 진단을 위한 혈액 내의 암 바이오마커에 대한 연구가 있었지만, 비특이도를 극복하기 어려워 진단율의 향상이 잘 이뤄지지 않고 있는 실정에 있다. 최근 도 2에서 보는 바와 같이, 흉강경이나 복강경 기술이 발전함에 따라 이들을 이용한 최소 침습적 악성중피종 검사에 대한 연구가 동물을 대상으로 진행되고 있으나, 이들은 침습적 방법이므로 조기 진단용으로 사용되기에는 한계가 있다.Meanwhile, although there have been studies on cancer biomarkers in the blood for early diagnosis, it is difficult to overcome the non-specificity and thus the diagnosis rate is not improved. As shown in FIG. 2, as the thoracoscopic or laparoscopic technique is developed, studies on the minimally invasive malignant mesothelioma using the same have been conducted in animals, but since they are invasive methods, they are limited to be used for early diagnosis.
관련 선행문헌으로서 한국 공개특허공보 제10-2005-0113442호, 한국 등록특허공보 제10-0266831호 등이 참조될 수 있다.As related prior documents, Korean Patent Publication No. 10-2005-0113442, Korean Registered Patent Publication No. 10-0266831 and the like can be referred to.
본 발명은 상기한 바와 같은 제반 문제점을 개선하기 위해 안출된 것으로서, 그 목적은 흉막의 흉벽 종양의 위치까지 조사되는 근적외선을 체내에서 체외로 흉벽을 통과하여 투영 입사한 후, 이를 검출하여 음영으로 영상화함으로써 흉벽 종양의 유무 및 퍼짐 정도를 확인하도록 한 근적외선을 이용한 폐종양 스크리닝 방법을 제공함에 있다.The present invention has been made to improve the above-mentioned problems, the object of the present invention is to detect the near-infrared rays irradiated to the position of the chest wall tumor of the pleura through the chest wall from the body through the projection, and then detect them and image them with shadows. The present invention provides a lung tumor screening method using near-infrared rays to confirm the presence and spread of chest wall tumors.
다른 목적은 형광염료를 혈관에 주입하여 흉벽 종양에 침착되면, 흉막의 흉벽 종양 위치까지 조사되는 근적외선이 상기 형광염료에 의해 흉벽 종양에서 형광을 방출함에 따라 이를 검출하여 흉벽 종양의 신생 혈관을 영상화함으로써, 흉벽 종양의 유무를 확인하도록 한 근적외선을 이용한 폐종양 스크리닝 방법을 제공함에 있다.Another object is to inject fluorescent dyes into blood vessels and deposit them on chest wall tumors, by detecting near-infrared rays irradiated to the chest wall tumor location of the pleura as the fluorescent dyes emit fluorescence in the chest wall tumors, thereby imaging the neovascularization of the chest wall tumors. In addition, the present invention provides a lung tumor screening method using near infrared rays to confirm the presence or absence of a chest wall tumor.
또 다른 목적은 흉막의 흉벽 종양 위치까지 동시에 또는 순차적으로 조사되는 서로 다른 파장대의 다수의 근적외선의 빛의 세기를 측정하거나 영상화하여 흡수도의 차이를 통해 흉벽 종양의 유무를 확인하도록 한 근적외선을 이용한 폐종양 스크리닝 방법을 제공함에 있다.Another objective is to measure or image the light intensity of multiple near infrared rays at different wavelengths irradiated simultaneously or sequentially to the chest wall tumor location of the pleura, and to determine the presence of chest wall tumors through differences in absorbance. It provides a method for tumor screening.
상기한 바와 같은 목적을 달성하기 위해 본 발명의 근적외선을 이용한 폐종양 스크리닝 방법은, 흉벽 종양의 위치까지 조사되는 근적외선을 체내에서 체외로 상기 흉벽을 통과해서 투영 입사시키는 단계와, 이를 검출하여 상기 흉벽 종양의 음영을 영상화하는 단계를 포함하는 것을 특징으로 하고 있다.Pulmonary tumor screening method using the near-infrared of the present invention to achieve the object as described above, the near-infrared irradiated to the position of the chest wall tumor invading the body through the chest wall through the body, and detects the chest wall Imaging the shadow of the tumor.
또 상기 근적외선의 투영 입사 단계에서 흉벽 종양의 위치까지 삽입되는 광섬유를 통해 상기 근적외선을 조사하고, 투영 입사되는 상기 근적외선을 검출하는 단계에서 근적외선 검출 카메라에 의해 검출하는 것이 바람직하다.In addition, the near-infrared ray is irradiated through the optical fiber inserted to the position of the chest wall tumor in the step of incidence of near-infrared radiation, and the step of detecting the near-infrared ray that is incident on the projection is preferably detected by a near-infrared detection camera.
또 상기 광섬유의 삽입 이후 근적외선의 조사 단계 이전에, 기관지경의 작업채널로 내로 가이드 시스를 흉벽 종양의 위치까지 삽입하는 단계를 더 포함하여, 상기 가이드 시스 내로 광섬유를 삽입하는 것이 바람직하다.The method may further include inserting the guide sheath into the working channel of the bronchoscope to the position of the chest wall tumor after the insertion of the optical fiber and before the step of irradiating the near infrared rays, thereby inserting the optical fiber into the guide sheath.
또 상기 근적외선은 780∼2000nm 영역 파장대의 근적외선인 것이 바람직하다.Moreover, it is preferable that the said near infrared rays are near infrared rays in the 780-2000 nm wavelength range.
또 상기 근적외선의 조사 단계 이전에, 형광염료를 혈관에 주입하는 단계를 더 포함하여, 상기 형광염료가 흉벽 종양 주변의 미성숙 혈관에서 누출되면서 상기 흉벽 종양에 침착되는 것을 통해, 상기 근적외선의 조사로 형광을 방출하는 흉벽 종양의 신생혈관을 영상화하는 것을 다른 특징으로 하고 있다.In addition, the step of injecting a fluorescent dye into the blood vessel before the step of irradiating the near infrared, the fluorescent dye is leaked from the immature blood vessels around the chest wall tumor and deposited on the chest wall tumor, the fluorescent by the irradiation of the near infrared Another feature is the imaging of neovascularization of the chest wall tumor that emits light.
또 상기 형광염료는 인도시아닌 그린(Indocyanine green:ICG)인 것이 바람직하다.In addition, the fluorescent dye is preferably indocyanine green (Indocyanine green (ICG)).
또 상기 근적외선 검출 카메라의 전면에 배치되는 방사 필터를 더 포함하는 것이 바람직하다.In addition, it is preferable to further include a radiation filter disposed in front of the near-infrared detection camera.
또 상기 근적외선 광원 전면에 배치되는 여기 필터를 더 포함하는 것이 바람직하다.In addition, it is preferable to further include an excitation filter disposed in front of the near infrared light source.
또 상기 근적외선은 서로 다른 다수의 파장대의 근적외선으로 조사되어, 흉벽을 통과한 각각의 근적외선의 빛의 세기를 측정하거나 영상화하여 흡수도의 차이를 통해 흉벽 종양의 유무를 확인하는 것을 또 다른 특징으로 하고 있다.In addition, the near-infrared ray is irradiated with near-infrared rays of different wavelengths, by measuring or imaging the intensity of light of each near-infrared ray passing through the chest wall to determine the presence or absence of chest wall tumors through the difference in absorption have.
또 상기한 흡수도의 차이를 통해 흉벽 종양의 유무를 확인하는 것은 분광기나 하이퍼스펙트럼 카메라에 의해 수행되는 것이 바람직하다.In addition, it is preferable that the presence or absence of the chest wall tumor through the difference in absorbance is performed by a spectroscope or a hyperspectral camera.
본 발명의 근적외선을 이용한 폐종양 스크리닝 방법에 의하면, 흉벽 종양으로써 악성종피종을 조기 진단하기 위해서 석면 노출 전력이 있는 고위험군에 대하여 정기적으로 스크리닝을 할 필요가 있는데, 본 발명에 의한 스크리닝 방법으로 악성중피종의 조기 진단이 가능해지는 효과가 있다. According to the lung tumor screening method using the near-infrared ray of the present invention, it is necessary to regularly screen for a high-risk group with asbestos exposure in order to diagnose malignant carcinoma as a chest wall tumor, and malignant mesothelioma according to the present invention. Early diagnosis of the disease is effective.
도 1은 벽측 흉막(parietal pleura)과 장측 흉막(visceral pleura)으로 구성되는 흉막을 보여주는 해부이미지1 is an anatomical image showing a pleura consisting of a parietal pleura and a lateral pleura
도 2는 PET/CT에서는 정상소견 결과를 보였지만 흉강경(thoracoscopy)을 사용해서는 악성중피종임의 확진을 보여주는 PET/CT 사진 및 내시경 사진 (Roca E, Laroumagne S, Vandemoortele T, Berdah S, Dutau H, Maldonado F, Astoul P., "18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography fused imaging in malignant mesothelioma patients: looking from outside is not enough", Lung Cancer. 2013 Feb;79(2):187-90. doi: 10.1016/j.lungcan.2012.10.017. Epub 2012 Dec 1.)Figure 2 shows normal results in PET / CT, but PET / CT and endoscopy (Roca E, Laroumagne S, Vandemoortele T, Berdah S, Dutau H, Maldonado F) showing the diagnosis of malignant mesothelioma using thoracoscopy. , Astoul P., "18F-fluoro-2-deoxy-d-glucose positron emission tomography / computed tomography fused imaging in malignant mesothelioma patients: looking from outside is not enough", Lung Cancer. 2013 Feb; 79 (2): 187 -90.doi: 10.1016 / j.lungcan.2012.10.017.Epub 2012 Dec 1.)
도 3은 본 발명의 제1 실시예에 따른 근적외선을 이용한 폐종양 스크리닝 방법을 보여주는 개념도3 is a conceptual diagram showing a lung tumor screening method using near infrared rays according to a first embodiment of the present invention
도 4는 상기 도 3의 주요부 확대도4 is an enlarged view of a main part of FIG. 3;
도 5는 본 발명의 제2 실시예에 따른 근적외선을 이용한 폐종양 스크리닝 방법을 보여주는 개념도5 is a conceptual diagram showing a lung tumor screening method using near infrared rays according to a second embodiment of the present invention.
도 6은 본 발명의 제3 실시예에 따른 근적외선을 이용한 폐종양 스크리닝 방법을 보여주는 개념도6 is a conceptual diagram showing a lung tumor screening method using near infrared rays according to a third embodiment of the present invention
도 7은 본 발명에 따른 근적외선을 이용한 폐종양 스크리닝 방법을 동물모델에 적용한 예Figure 7 is an example of applying the lung tumor screening method using the near infrared ray in accordance with the present invention in the animal model
도 8은 본 발명에 따른 근적외선을 이용한 폐종양 스크리닝 방법을 동물모델에 적용하여 정상 흉벽을 나타낸 예를 보여주는 이미지Figure 8 is an image showing an example showing a normal chest wall by applying the lung tumor screening method using the near infrared ray in accordance with the present invention in an animal model
도 9는 본 발명에 따른 근적외선을 이용한 폐종양 스크리닝 방법을 동물모델에 적용하여 흉벽 종양을 나타낸 예를 보여주는 이미지Figure 9 is an image showing an example showing a chest tumor by applying the lung tumor screening method using the near infrared ray in accordance with the present invention in an animal model
이하, 본 발명에 따른 근적외선을 이용한 폐종양 스크리닝 방법의 바람직한 실시예를 첨부한 도면을 참조로 하여 상세히 설명한다. 본 발명은 이하에서 개시되는 실시예에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 수 있으며, 단지 본 실시예는 본 발명의 개시가 완전하도록 하며 통상의 지식을 가진 자에게 발명의 범주를 완전하게 알려주기 위하여 제공되는 것이다.Hereinafter, with reference to the accompanying drawings a preferred embodiment of the lung tumor screening method using a near infrared ray according to the present invention will be described in detail. The present invention is not limited to the embodiments disclosed below, but can be implemented in various different forms, only this embodiment to make the disclosure of the present invention complete and to those skilled in the art to fully understand the scope of the invention It is provided to inform you.
도 3은 본 발명의 제1 실시예에 따른 근적외선을 이용한 폐종양 스크리닝 방법을 보여주는 개념도이고, 도 4는 상기 도 3의 주요부 확대도를 도시한 것이다. 3 is a conceptual diagram illustrating a lung tumor screening method using near infrared rays according to a first embodiment of the present invention, and FIG. 4 is an enlarged view of a main part of FIG. 3.
본 발명의 제1 실시예에 따른 근적외선을 이용한 폐종양 스크리닝 방법은, 흉벽 종양을 간단히 스크리닝(screening)하여 진단하기 위해 근적외선을 이용한 투영법을 사용하여 흉벽 종양의 영상을 획득하는 방법을 제시한 것이다. 근적외선은 780∼2000nm 영역의 파장을 가진 전자기파로서 조직 내 투과도가 높아 생체진단용으로 흔히 사용되고 있다. Lung tumor screening method using near infrared rays according to the first embodiment of the present invention, a method for obtaining an image of the chest wall tumor using a projection using near infrared rays in order to screen and diagnose the chest wall tumor. Near-infrared radiation is an electromagnetic wave with a wavelength in the range of 780-2000 nm, and is widely used for biodiagnosis due to its high transmittance in tissue.
이러한 근적외선 투영법에 의한 흉벽 종양의 스크리닝은 도 3에서 보는 바와 같이, 근적외선(NIR source)을 흉벽 종양(tumor)의 위치까지 조사하고, 조사된 근적외선이 체내에서 체외로 흉벽을 통과하여 투영 입사될 때, 이렇게 흉벽을 통과한 근적외선을 체외에 위치시킨 근적외선 검출 카메라(camera)로 검출하여 영상화하도록 한 것이다. 이때 근적외선을 검출한 영상에서 흉벽 종양의 음영이 상기 근적외선 검출 카메라에 의해 획득되어 상기 흉벽 종양의 유무 및 퍼짐 정도를 알 수 있게 된다.Screening of the chest wall tumor by this near-infrared projection method, as shown in Figure 3, irradiates near-infrared (NIR source) to the position of the chest wall tumor (tumor), and when the irradiated near-infrared is projected through the chest wall into the body in vitro In this way, the near-infrared ray passing through the chest wall is detected and imaged by a near-infrared detection camera placed outside the body. In this case, the shadow of the chest wall tumor is acquired by the near infrared detection camera in the image of the near infrared ray detection, so that the presence or absence and spread of the chest wall tumor can be known.
상기 근적외선은 광섬유에 의해 흉벽 종양의 위치에 조사되는데, 도 4에서 보는 바와 같이, 기관지경(endoscope)의 작업 채널(working channel) 내로 가이드 시스(guide sheath)를 삽입하여 흉벽 종양이 있는 부분의 투영하고자 하는 위치를 정한 후, 상기 가이드 시스 내부로 광섬유를 삽입하여 상기 광섬유를 통해 근적외선을 흉벽 종양의 위치에 조사하고 체내에서 체외로 흉벽을 통과해서 투영 입사시키게 된다. 이렇게 흉벽을 통과한 근적외선은 상기한 바와 같은 과정을 거쳐 흉벽 종양의 유무 및 퍼짐정도를 확인하게 된다.The near-infrared ray is irradiated to the location of the chest wall tumor by the optical fiber, and as shown in FIG. 4, the projection of the portion having the chest wall tumor by inserting a guide sheath into the working channel of the endoscope. After determining the desired position, the optical fiber is inserted into the guide sheath to irradiate near-infrared rays to the position of the chest wall tumor through the optical fiber, and to enter the body through the chest wall and enter the projection. In this way, the near-infrared rays passing through the chest wall confirm the presence and spread of the chest wall tumor as described above.
도 5는 본 발명의 제2 실시예에 따른 근적외선을 이용한 폐종양 스크리닝 방법을 보여주는 개념도를 도시한 것이다.5 is a conceptual diagram showing a lung tumor screening method using near infrared rays according to a second embodiment of the present invention.
본 발명의 제2 실시예에 따른 근적외선을 이용한 폐종양 스크리닝 방법은, 근적외선에 의해 형광을 방출하는 형광염료인 인도시아닌 그린(Indocyanine green:ICG)을 이용한 형광 이미징을 이용하는 방법을 제시한 것이다. 인도시아닌 그린(ICG)은 혈장 단백질에 쉽게 결합하여 혈관 이미징에 흔히 사용되고, 780nm의 빛을 최대로 흡수하여 820nm의 형광을 방출하는 특성이 있다.Lung tumor screening method using a near infrared ray according to a second embodiment of the present invention, a method using a fluorescent imaging using indocyanine green (ICG), a fluorescent dye that emits fluorescence by near infrared rays. Indocyanine green (ICG) is commonly used for vascular imaging by easily binding to plasma proteins, and has the property of maximizing absorption of 780 nm light to emit 820 nm fluorescence.
본 발명에서는 도 5에서 보는 바와 같이, 흉벽 종양이 진행되면 종양 주변에 신생혈관이 발생하게 되는데, 이런 경우에 상기 ICG와 같은 형광염료를 혈관으로 주입하여 흉벽 종양 주변의 미성숙 혈관에서 새어나온 형광염료가 상기 흉벽 종양에 침착되는 것을 이용하는 것으로, 상기한 바와 같이 흉벽 종양의 위치로 조사된 후 체내에서 체외로 통과하는 근적외선에 의해 형광을 방출하는 흉벽 종양의 신생혈관을 근적외선 검출 카메라로 영상화하여 상기 흉벽 종양의 유무와 퍼짐정도를 확인하게 된다. 이때 흉벽 종양으로부터 방출하는 형광을 영상화하기 위해 상기 근적외선 검출 카메라의 전면에는 820nm의 방사 필터(emission filter)를 배치하고 근적외선 광원 전면에는 780 nm의 여기 필터(excitation filter)를 배치하도록 한다.In the present invention, as shown in Figure 5, when the chest wall tumor progresses neovascularization is generated around the tumor, in this case by injecting a fluorescent dye, such as the ICG into the blood vessel fluorescent dye leaked from the immature blood vessels around the chest wall tumor Is deposited on the chest wall tumor, and the neovascularization of the chest wall tumor that emits fluorescence by near-infrared radiation that passes through the body after irradiation to the location of the chest wall tumor as described above by imaging with a near-infrared detection camera the chest wall The presence of the tumor and the extent of its spread will be checked. In this case, in order to image the fluorescence emitted from the chest wall tumor, an emission filter of 820 nm is disposed in front of the near-infrared detection camera, and an excitation filter of 780 nm is disposed in front of the near-infrared light source.
본 발명의 제2 실시예에서 근적외선의 조사는 상기한 바와 같은 광섬유에 의해 이루어지며, 상기 광섬유가 작업채널의 가이드 시스 내로 삽입되어 흉벽 종양의 위치를 정하는 것은 상기한 바와 동일하다. In the second embodiment of the present invention, the near-infrared irradiation is performed by the optical fiber as described above, and the optical fiber is inserted into the guide sheath of the working channel to position the chest wall tumor as described above.
도 6은 본 발명의 제3 실시예에 따른 근적외선을 이용한 폐종양 스크리닝 방법을 보여주는 개념도를 도시한 것이다.6 is a conceptual diagram showing a lung tumor screening method using near infrared rays according to a third embodiment of the present invention.
도 6에서 보는 바와 같이, 본 발명의 제3 실시예에 따른 근적외선을 이용한 폐종양 스크리닝 방법은, 근적외선 대의 서로 다른 두 파장 또는 다수의 파장의 근적외선(Multi-wavelength NIR source)을 동시에 또는 순차적으로 상기한 바와 같은 내시경적 방법으로 조사한 후, 체내에서 체외로 흉벽을 통과한 각각의 근적외선 빛의 세기를 측정하거나 영상화하여 흡수도의 차이를 통하여 종양의 유무를 확인하는 근적외선 분광 방법을 제시한 것이다. 이때 상기 근적외선 빛의 세기를 측정하거나 영상화하여 흡수도를 차이를 구하는 것은 체외의 위치하고 있는 분광기(Spectroscope)나 하이퍼스펙트럼 카메라 (Hyperspectral camera)등의 근적외선 검출기에 의해 이루어진다.As shown in FIG. 6, the lung tumor screening method using the near infrared rays according to the third embodiment of the present invention simultaneously or sequentially records the multi-wavelength NIR sources of two different wavelengths or multiple wavelengths in the near infrared band. After investigating by endoscopy as described above, a near-infrared spectroscopy method for determining the presence or absence of a tumor through the difference in absorbance by measuring or imaging the intensity of each near-infrared light passing through the chest wall from the body in vitro is presented. In this case, the difference in absorbance is measured by measuring or imaging the near-infrared light intensity by a near-infrared detector such as a spectroscope or a hyperspectral camera located outside the body.
도 7은 본 발명에 따른 근적외선을 이용한 폐종양 스크리닝 방법을 동물모델에 적용한 것으로 내시경적 방법으로 체내에서 체외로 근적외선을 흉벽을 통과해서 투영 입사시키는 예를 보여주는 이미지이다.FIG. 7 is an image showing an example of applying a lung tumor screening method using a near infrared ray to an animal model according to the present invention by injecting near infrared rays through the chest wall into the body in an endoscopic method.
도 7에서 보는 바와 같이, 동물 모델로 실험 토끼인 정상 뉴질랜드 백색가토를 이용하여 상기한 제1 실시예의 근적외선을 이용한 폐종양 스크리닝 방법으로 흉벽 근적외선 투영법을 실시하여 나타낸 결과 이미지이다. 이 이미지에서 보면 적색으로 보이는 부분에서 상당량의 근적외선이 흉벽을 통과하여 외부로 투영되고 있음을 잘 알 수 있다.As shown in FIG. 7, the chest wall near-infrared projection method was performed using the lung tumor screening method using the near-infrared ray of Example 1, using a normal New Zealand white rabbit as an animal model. In this image, it can be seen that a considerable amount of near-infrared rays are projected to the outside through the chest wall in the areas that appear red.
도 8은 뉴질랜드 백색가토의 정상 흉벽을 통과하여 투영되는 근적외선을 보여주는 이미지이며 도 9는 종양 흉벽을 통과하여 투영되는 근적외선을 보여주는 이미지이다.FIG. 8 is an image showing near infrared rays projected through the normal chest wall of New Zealand white rabbit, and FIG. 9 is an image showing near infrared rays projected through the tumor chest wall.
도 8과 도 9에서 보는 바와 같이, 정상 흉벽 투영이미지는 흉골을 따라 음영이 평행하게 발생하지만 종양 흉벽 투영이미지는 종양의 음영이 추가됨에 따라 어둡게 보이고 있음을 잘 알 수 있다.8 and 9, the normal chest wall projection image is shaded parallel to the sternum but the tumor chest wall projection image can be seen that the darker as the shadow of the tumor is added.
이상과 같이 본 발명에 따른 근적외선을 이용한 폐종양 스크리닝 방법에 대해서 예시한 도면을 참조로 하여 설명하였으나, 본 명세서에 개시된 실시예와 도면에 의해 본 발명이 한정되는 것은 아니며, 본 발명의 기술사상의 범위 내에서 당업자에 의해 다양한 변형이 이루어질 수 있음은 물론이다.As described above with reference to the drawings illustrating a lung tumor screening method using a near infrared ray according to the present invention, the present invention is not limited by the embodiments and drawings disclosed herein, Of course, various modifications may be made by those skilled in the art within the scope.

Claims (9)

  1. 흉벽 종양의 위치까지 조사되는 근적외선을 체내에서 체외로 상기 흉벽을 통과해서 투영 입사시키는 단계와, 이를 검출하여 상기 흉벽 종양의 음영을 영상화하는 단계를 포함하는 것을 특징으로 하는 근적외선을 이용한 폐종양 스크리닝 방법.A method for screening lung tumors using near-infrared radiation, comprising: irradiating near-infrared rays irradiated to the position of chest wall tumors through the chest wall from the body and out of the body, and detecting and imaging the shadows of the chest wall tumors .
  2. 제1항에 있어서,The method of claim 1,
    상기 근적외선의 투영 입사 단계에서 흉벽 종양의 위치까지 삽입되는 광섬유를 통해 상기 근적외선을 조사하고, 투영 입사되는 상기 근적외선을 검출하는 단계에서 근적외선 검출 카메라에 의해 검출하는 것을 특징으로 하는 근적외선을 이용한 폐종양 스크리닝 방법.Lung tumor screening using near-infrared detection camera, characterized in that the near-infrared ray is irradiated through the optical fiber inserted to the position of the chest wall tumor in the near-infrared projection phase, and detected by the near-infrared detection camera in detecting the near-infrared ray incident to the projection. Way.
  3. 제2항에 있어서,The method of claim 2,
    상기 광섬유의 삽입 이후 근적외선의 조사 단계 이전에, 기관지경의 작업채널로 내로 가이드 시스를 흉벽 종양의 위치까지 삽입하는 단계를 더 포함하여, 상기 가이드 시스 내로 광섬유를 삽입하는 것을 특징으로 하는 근적외선을 이용한 폐종양 스크리닝 방법.Inserting the optical fiber into the guide sheath through the insertion of the optical fiber to the position of the chest wall tumor, further comprising the step of inserting the guide sheath into the working channel of the bronchoscope to the position of the chest wall tumor after the insertion of the optical fiber. Lung tumor screening method.
  4. 제1항에 있어서,The method of claim 1,
    상기 근적외선은 780∼2000nm 영역 파장대의 근적외선인 것을 특징으로 하는 근적외선을 이용한 폐종양 스크리닝 방법. The near-infrared lung tumor screening method using near-infrared, characterized in that the near-infrared of the wavelength range of 780 ~ 2000nm.
  5. 제3항 또는 제4항에 있어서,The method according to claim 3 or 4,
    상기 근적외선의 조사 단계 이전에, 형광염료를 혈관에 주입하는 단계를 더 포함하여, 상기 형광염료가 흉벽 종양 주변의 미성숙 혈관에서 누출되면서 상기 흉벽 종양에 침착되는 것을 통해, 상기 근적외선의 조사로 형광을 방출하는 흉벽 종양의 신생혈관을 영상화하는 것을 특징으로 하는 근적외선을 이용한 폐종양 스크리닝 방법.Prior to the irradiation of the near-infrared, further comprising the step of injecting a fluorescent dye into the blood vessel, the fluorescent dye is leaked from the immature blood vessels around the chest wall tumor by depositing on the chest wall tumor, the fluorescence by the near-infrared irradiation A lung tumor screening method using near infrared rays, characterized by imaging neovascularization of the releasing chest wall tumor.
  6. 제5항에 있어서,The method of claim 5,
    상기 형광염료는 인도시아닌 그린(Indocyanine green:ICG)인 것을 특징으로 하는 근적외선을 이용한 폐종양 스크리닝 방법. The fluorescent dye is indocyanine green (Indocyanine green (ICG)), characterized in that lung tumor screening method using near-infrared.
  7. 제5항에 있어서,The method of claim 5,
    상기 근적외선 검출 카메라의 전면에 배치되는 방사 필터와 상기 근적외선 광원 전면에 배치되는 여기 필터를 더 포함하는 것을 특징으로 하는 근적외선을 이용한 폐종양 스크리닝 방법. And a radiation filter disposed in front of the near infrared detection camera and an excitation filter disposed in front of the near infrared light source.
  8. 제1항에 있어서,The method of claim 1,
    상기 근적외선은 서로 다른 다수의 파장대의 근적외선으로 조사되어, 흉벽을 통과한 각각의 근적외선의 빛의 세기를 측정하거나 영상화하여 흡수도의 차이를 통해 흉벽 종양의 유무를 확인하는 것을 특징으로 하는 근적외선을 이용한 폐종양 스크리닝 방법.The near-infrared ray is irradiated with near-infrared rays in different wavelength bands, and by measuring or imaging the intensity of light of each near-infrared ray that has passed through the chest wall, the presence or absence of chest wall tumors is determined by the difference in absorbance. Lung tumor screening method.
  9. 제8항에 있어서,The method of claim 8,
    상기한 흡수도의 차이를 통해 흉벽 종양의 유무를 확인하는 것은 분광기에 의해 수행되는 것을 특징으로 하는 근적외선을 이용한 폐종양 스크리닝 방법.Lung tumor screening method using near-infrared, characterized in that the presence or absence of chest wall tumors through the difference in absorbance is performed by a spectrometer.
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