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WO2003030726A1 - Procede de detection automatique, et de traitement ou d'echantillonnage de partie d'objet, du type partie d'objet affectee, et appareil correspondant - Google Patents

Procede de detection automatique, et de traitement ou d'echantillonnage de partie d'objet, du type partie d'objet affectee, et appareil correspondant Download PDF

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Publication number
WO2003030726A1
WO2003030726A1 PCT/JP2002/009906 JP0209906W WO03030726A1 WO 2003030726 A1 WO2003030726 A1 WO 2003030726A1 JP 0209906 W JP0209906 W JP 0209906W WO 03030726 A1 WO03030726 A1 WO 03030726A1
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WIPO (PCT)
Prior art keywords
light
lesion
target site
wavelength
light intensity
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Application number
PCT/JP2002/009906
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English (en)
Japanese (ja)
Inventor
Yoshinaga Kajimoto
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Japan Science and Technology Agency
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Japan Science and Technology Corp
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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

Definitions

  • the present invention is to detect and detect lesions such as tumors, cancers, atherosclerotic lesions, inflammatory lesions, or lesion sites or useful sites in the medical field, with high precision and accuracy, and quantitatively.
  • the present invention relates to a method and a device for treating or collecting lesions based on information such as destruction, removal, excision of the lesions, administration of drugs to the lesions, or collection of a beneficial site.
  • INDUSTRIAL APPLICABILITY The present invention is extremely effective in the fields of surgery and internal medicine, particularly in the fields of neurosurgery, vascular surgery, cardiology, respiratory surgery, urology and the like, and in the fields of gene therapy, gene research, and drug discovery. Background art
  • fluorescent labeling and radioisotope (RI) labeling have been known as methods for identifying and detecting target sites such as lesions and lesions and removing or treating them.
  • excitatory light is irradiated during treatment to a previously labeled lesion, and the lesion site that is qualitatively recognized as a fluorescent region is visually identified, and the affected lesion tissue is resected or removed.
  • the latter isotope labeling is a method of treating lesions that have been detected with a radioactive detection probe while searching for lesions previously labeled with radioisotopes.
  • a remote surgical robotic device and a high-precision operating robot for position determination for example, an artificial joint installation port robot
  • the former method of fluorescence labeling involves detecting tissue during surgery in diagnosing the presence or absence of a lesion to be treated and detecting the boundary between the diseased tissue and normal tissue. Since it was deformed and the quantitative and high-precision evaluation of the lesion was not possible, there was always ambiguity due to visual judgment or qualitative judgment, and no progress could be expected in automated treatment equipment.
  • the latter radioactive In the isotope labeling method the spatial resolution of radiation is extremely low, and errors in determining the presence or absence of a lesion are likely to occur.
  • the place where radioisotopes are used is legally limited and restricted, and the Labeling drugs were also under development and were of little practical use.
  • An optical diagnostic apparatus disclosed in Japanese Patent Application Laid-Open No. 6-165783 has been proposed as a device capable of detecting such a boundary between a deformed and moving lesion tissue and a normal tissue in an operating field. .
  • This optical diagnostic device inserts the distal end of an optical fiber that guides low-coherence light into a suction probe that is inserted inside the head and cuts and removes diseased tissue such as a tumor with a rotating blade.
  • low coherent light generated by the SLD of the light generating section is emitted from the distal end face of this optical fiber, and light reflected from the affected tissue is guided, and the optical path length is changed by the interference light detecting section.
  • This device By interfering with the reference light, reflected light in the depth direction is detected, and the range of the presence of the diseased tissue is determined from the signal of the ratio of the reflected light obtained at the two wavelengths.
  • This device detects the boundary between normal tissue and diseased tissue in living tissue, and enables safe surgery.
  • the optical diagnostic apparatus proposed above emits light with low coherence, causes reflected light from the diseased tissue to interfere with reference light, detects reflected light in the depth direction, and detects the range of the presence of the diseased tissue.
  • the reference light generating means is required.
  • the range of the presence of diseased tissue is determined from the signal of the ratio of the wavelength of the reference light and the wavelength of the reflected light whose optical path length is changed Therefore, the qualitative judgment of the diseased tissue was limited, and the detection performance of the boundary between the normal tissue and the diseased tissue was not sufficient. Further, with the proposed optical diagnostic apparatus, it is only possible to determine the distribution of light in the depth direction, and it has been difficult to detect a characteristic characteristic of a lesion.
  • the problem of the conventional diagnostic apparatus is solved by spectroscopy, and the accuracy and accuracy of the localization of the target site such as a lesion is improved, and the target site such as a lesion having high detection performance is automatically detected. It is an object of the present invention to provide a method for detecting and treating or collecting and a device therefor. Disclosure of the invention
  • a light source irradiates a target site such as a lesion with light, and at least a wavelength range specific to the light source and a wavelength range specific to the target site such as the target lesion in the reflected light emitted from the target site such as the target lesion.
  • two wavelength regions including the maximum light intensity of each of these two are selected to quantitatively measure the relative light intensity of these two, and the quantitative measurement value is output as an electric signal or a magnetic signal to perform digital control or analysis.
  • a method for automatically detecting, treating, or collecting a target site such as a disease which is characterized by detecting and treating or collecting while quantitatively determining a target site, such as a lesion, by performing mouth control.
  • the light source is a laser light, a light emitting diode, a chemiluminescence, a white light. It is characterized in that it is at least one kind of light emitting means selected from a lamp, a mercury lamp, a xenon lamp and a halogen lamp group.
  • the reflected light in the two wavelength ranges that is spectrally selected is one kind of reflected light in a specific wavelength range specific to the light source, and the reflected light is light having a different wavelength from the target part such as a lesion. It is characterized by being light selected from the group consisting of reflected light, light absorption, light emission, fluorescence, and Raman scattering light in a specific wavelength region that is specifically distributed or generated due to the distributed dye.
  • the treatment or the collection operation is performed. It is characterized in that the control means is digitally controlled or analog controlled so as to continue.
  • the present invention is characterized in that a light irradiation is performed on a target portion such as the lesion, and a reflection light from the target portion such as the lesion is received by a probe made of an optical fiber.
  • an ultrasonic destruction device an electric scalpel, a suction device, a laser scalpel, a laser irradiation device, a therapeutic light irradiation device or a biopsy device is incorporated in the probe.
  • the probe is incorporated in a surgical catheter.
  • the present invention is characterized in that light irradiation to a target site such as the lesion and light reception of reflected light from the target site such as the lesion are performed by a lens or a light transmission unit of an interference optical system.
  • the system automatically detects and treats target sites such as the lesions described in 2 to 5.
  • FIG. 1 is a block diagram of a method for automatically detecting and treating or collecting a target site such as a lesion and a systemized block of the apparatus according to the present invention.
  • Fig. 2 In each of the examples of the probe according to the present invention, Fig. 2 (a) shows an example in which an optical fiber is used as a probe, Fig. 2 (b) shows an example in which a lens or an interference optical system is used as a probe, and Figs. (c) is a diagram showing an example of direct irradiation.
  • Fig. 3 Fig. 3 (a) is a photograph of the unlabeled normal brain tissue under irradiation of a blue light-emitting diode, and Fig. 3 (b) is a confirmed photograph of the brain tumor site labeled with fluorescein Na by specific fluorescence.
  • FIG. 3 Fig. 3 (a) shows an example in which an optical fiber is used as a probe
  • Fig. 2 (b) shows an example in which a lens or an interference optical system is used as a probe
  • Figs. (c) is a diagram showing an example of direct irradiation.
  • FIG. 4 is an analysis of the spectral distribution of normal brain tissue backlit under a blue light-emitting diode using a spectrometer
  • Fig. 4 (b) is a brain tumor labeled with fluoride Na.
  • FIG. 5 is an analysis diagram of a spectrum component of a backlit light by a spectrometer.
  • FIG. 1 is a systematic block diagram of a method and apparatus for automatically detecting and treating or collecting a target site such as a lesion according to the present invention.
  • FIG. 2 (a) shows an example in which an optical fiber is used as a probe.
  • Fig. 2 (b) shows an example using a lens or an interference optical system as a probe,
  • Fig. 2 (c) shows an example of direct irradiation,
  • Fig. 3 (a) shows an unlabeled normal brain under irradiation of a blue light-emitting diode. Histological photograph, Fig.
  • FIG. 3 (b) shows the same photomicrograph of the specific fluorescence of the brain tumor site labeled with fluorescide Na
  • Fig. 4 (a) shows the spectrum of normal brain tissue reflected by blue light-emitting diode.
  • FIG. 4 (b) is an analysis diagram of the spectral distribution of a brain tumor site labeled with Fluorescein Na using a spectrometer for back-lighting.
  • light is irradiated from a light source 1 to a target site 3 such as a lesion, and at least a wavelength range specific to the light source and at least a portion of the reflected light emitted from the target site 3 such as an irradiated lesion are irradiated.
  • a target site 3 such as a lesion
  • the target site 3 such as a lesion can be detected and the lesion treatment apparatus 1 can be quantitatively determined. It is characterized by treatment with 0.
  • FIG. T JP02 / 09906 A light source 1 that irradiates a target part 3 such as a lesion through a light source, and a reflected light emitted from the target part 3 such as an illuminated lesion through a light transmitting device 4 and at least two wavelengths by a spectroscopic device 5.
  • the light source 1 at least one kind of light emitting means selected from the group consisting of laser light, light emitting diode, chemiluminescence, white lamp, various lamps, for example, mercury lamp, xenon lamp and halogen lamp is used.
  • a light emitting means selected from the group consisting of laser light, light emitting diode, chemiluminescence, white lamp, various lamps, for example, mercury lamp, xenon lamp and halogen lamp is used.
  • target sites such as lesions or lesions that have not been labeled, stained, or unstained
  • reflected light emitted from the irradiated object is received by the probe, and the received reflected light is optically analyzed.
  • Spectroscopic device 5 such as a dynamic filter, etc., and sharpness is remarkably detected in a strong and clear bright line or a spectral analysis diagram in the spectrum by a spectroscopic measuring means 7 including an optical sensor 1.
  • the detection means and the lesion destruction or collection device are systematized and provided as a treatment or collection device or a robotic operation device.
  • the probe, the optical sensor, and each device constituting the system part can be provided and used as components for the same purpose as the present invention or for another purpose.
  • the above-mentioned systems and components are used for general resection surgery and laser treatment for cancer including brain tumors, and for atherosclerotic lesions and hearts. It can be used as a device for intravascular surgery such as myocardial infarction and for directly applying drugs to affected parts, lesions, diseased tissues, etc., or as a device for collecting useful parts, and is provided for this purpose.
  • the irradiation light light having a wavelength in the range of about 200 Onm to about 400 Onm, that is, ultraviolet light, visible light, infrared light, or the like can be used.
  • the wavelength of the irradiation light is 515 nm.
  • the irradiation target is labeled with a luminescent substance, for example, a fluorescent labeling agent, Fluoride Na, the irradiation target itself emits light and is also referred to as excitation light.
  • light emitted from an object by irradiating the object with light is referred to as back illumination.
  • the irradiated object is dyed in advance with a red dye, the irradiated object absorbs green / yellow wavelength light and reflects red light (so-called ordinary reflected light).
  • the irradiation target is labeled with the above-mentioned fluoroside Na, the irradiation target emits fluorescence having a wavelength of 585 nm under irradiation.
  • reflected light in the present invention, this is referred to as Doppler light
  • the Doppler light is evaluated as a marker for avoiding vascular damage during surgery.
  • the reflected light referred to in the present invention means ordinary reflected light, fluorescence, emission, absorption, Doppler light, Brillouin scattered light and Raman scattered light in a specific wavelength range. Can be used as a target for quantitative measurement.
  • a substance capable of producing, under light irradiation, reflection in the above-mentioned specific wavelength region under light irradiation and capable of specifically labeling or staining tissues such as lesions, lesions, affected parts, and the like, is also provided.
  • Substances that can be specifically distributed or can be distributed to tissues can be used.
  • a spectroscopic device capable of discriminating a target wavelength, that is, a specific wavelength region of the irradiation light wavelength and the back illumination light described above can be appropriately selected and used. That is, according to the purpose described above.
  • a target wavelength that is, a specific wavelength region of the irradiation light wavelength and the back illumination light described above.
  • an optical filter, a spectroscope, an interferometer, etc. can be used.
  • FIG. 2 shows a light transmitting means or an energy transmitting means for destroying or collecting a target site used in the method and apparatus for automatically detecting, treating, or collecting a target site such as a lesion in the present invention.
  • Fig. 2 shows an embodiment of the probe, which mainly irradiates light to a target site such as a lesion and receives the reflected light, and in Fig. 2 (a), light is transmitted by an optical fiber that enables miniaturization. This is an example in which means 4 is configured. Since the miniaturization enables the incorporation into various treatment devices, it is possible to create and provide devices such as new treatment devices.
  • an ultrasonic destruction device or a laser knife may be incorporated in the probe, and the output may be controlled based on a quantitative measurement value, so that a target site such as a lesion can be automatically broken.
  • a laser-irradiation device may be incorporated into the probe to selectively and photodynamically treat a lesion.
  • the probe can be incorporated into a surgical catheter such as a blood vessel to selectively treat atheroma in an atherosclerotic lesion by photodynamic treatment or destruction treatment. Irradiation of the object to be irradiated is performed through one or more optical fibers, a lens optical system, a diffraction grating optical system as shown in FIG. 2 (b), or FIG. 2 (c).
  • the reflected light due to light irradiation is transmitted through one or more optical fibers, a lens optical system, a diffraction grating optical system, or directly incident on a light emitting element.
  • Guide to spectroscopic devices and optical sensors. it can be configured to detect a useful part and efficiently collect it.
  • the concentration of the dye in the target area is measured from the intensity or intensity of the reflected light (normal reflected light, luminescence, fluorescence, Raman scattered light, Doppler light or absorption). However, if absorbance is used, measure from absorbance.
  • the maximum intensity value of the reflected light derived from the dye of the irradiated object is represented by “I ⁇ 0”, and the wavelength thereof is represented by “S0 ⁇ m”.
  • the wavelength; the highest intensity of backlit light originating from a light source other than I 0 PT / JP02 / 09906 Degree value is expressed as “I-s i” and its wavelength is expressed as “ ⁇ i-nm”.
  • the light intensity of the background is expressed as “I b”, which includes the optical sensor and noise associated therewith.
  • the maximum intensity of the light of each wavelength is directly measured for the wavelength of the light emitted from the light source and the back light of the irradiated object.
  • the light intensity is determined based on an evaluation based on a correlation coefficient between a known spectral characteristic of the dye and the light source and the measured spectral characteristic.
  • the dye concentration D of the irradiated object is calculated as the light intensity by the following equations (1), (2) and (3), and the relative light intensity is measured and calculated from the light intensity.
  • the light intensity of the back darland (light intensity in a wavelength range that can be detected outside the wavelength range of the excitation light and reflected light or excitation light non-irradiation) is used. It is desirable to measure the relative light intensity using equation (3) considering “I b”.
  • the control means varies the output by digital control or analog control in accordance with the control, and operates under the control to drive a scalpel or a lesion destruction device, etc., to clearly identify the target site such as a lesion. Can be removed or treated or harvested.
  • the relative light intensity of the two wavelength ranges quantitatively measured under the treatment operation is a threshold value of the light intensity measurement value immediately before the start of the treatment operation, for example, a zero displacement of the continuously measured light intensity.
  • the control means is digitally controlled or analog controlled so as to continue the treatment or sampling operation within a light intensity range selected within 1Z10000 from the point.
  • Medical treatment equipment Existing treatment devices for lesion tissues and lesions, for example, a laser irradiator, a laser scalpel, an ultrasonic destructor, an electric scalpel, an electric scalpel, an electromagnetic irradiator, a shock wave generator, and the like can be used. .
  • Fluorescent labeling agents such as fluorescein Na, which are selectively taken into brain tumor foci and specifically labeled, are injected into the patient's vein in advance, and tumors whose surface has been exposed during surgery for brain tumor excision (Fig. 3 (a )) Was irradiated with excitation light. As a result, only the tumor site showed fluorescence, which could be visually identified (Fig. 3 (b)).
  • the above-mentioned tumor site was locally irradiated with a blue light-emitting diode, reflected light was guided from the irradiated site with an optical fiber, and the spectrum distribution was analyzed with a spectrometer.
  • the fluorescence and the excitation light are decomposed into a wavelength spectrum unique to the excitation light and the fluorescence by the spectroscope or the optical filter, and the respective light intensities are quantified by the optical sensor.
  • the relative concentration of the fluorescent labeling substance in the tissue is quantified, and the quantified relative concentration is converted to a voltage output for output.
  • the sampling device can be controlled. As a result, at the site where the labeling drug is distributed, the site can be destroyed or collected according to the concentration, whereas at sites other than the target site, no destruction or collection is performed. Because of this characteristic, it is possible to realize a highly safe and efficient treatment or sampling device with high target site selectivity.
  • the conversion mode, digital control mode or analog control mode output as an electric signal or a magnetic signal, automatic determination, detection, treatment, and collection of a target site can be appropriately selected.
  • a light source irradiates a target site such as a lesion with light, and at least a wavelength range specific to the light source and a target region of the reflected light emitted from the target site such as a target lesion.
  • Digital output or analog control by outputting as an electrical or magnetic signal to quantify light intensity and detect and treat or collect while quantitatively determining the target site such as a lesion during surgery
  • target site such as a lesion during surgery
  • a part with beneficial properties from the beginning or a part that has obtained valuable properties due to genetic modification etc. is quantitatively determined with high accuracy. And it is possible to collect efficiently.
  • a light source for irradiating the diseased tissue with light a light intensity measuring means for measuring the light intensity of each wavelength by separating reflected light emitted from the irradiated diseased tissue into light of at least two wavelengths, Of the light intensities of the wavelengths, a wavelength range specific to the light source and a wavelength range specific to the target site, such as an irradiated lesion, are selected, and two wavelength ranges including the maximum light intensity of each of these are selected.
  • the light source is selected from at least one kind of light emitting means selected from the group consisting of laser light, light emitting diode, chemiluminescence, white lamp, mercury lamp, xenon lamp, and halogen lamp, thereby making it possible to convert existing or commercially available light.
  • the wavelength of the irradiation light can be within an appropriate range.
  • the reflected light in the two wavelength ranges that are spectrally selected is one kind of reflected light in a specific wavelength region specific to the light source, and the reflected light is light having a different wavelength from the reflected light, and is an object such as a lesion.
  • the light is selected from the group consisting of reflected light, light absorption, luminescence, fluorescence, and Raman scattered light in a specific wavelength region that is specifically distributed due to or distributed in the site, the relative light intensity Bimodal backlighting, whose quantitative measurement value differs greatly between the target site and the other site, is detected, and the target site such as a lesion can be specifically and quantitatively determined.
  • the treatment or the collection operation is continued. If the control means is controlled by digital control or analog control so that it continues to operate, the target site can be detected and diagnosed with high precision and accuracy with high reliability and safety, prompt and accurate operation and treatment. And medication or collection can be continued automatically.
  • the lesion probe is an extremely fine optical fiber. It can be integrated into various devices, and can be applied to a wide range of fields such as minimally invasive surgery such as endoscopic treatment and endovascular treatment and gene-related research. In addition, it is structurally robust with no moving parts, and its production cost is low.
  • the probe when an ultrasonic destruction device, an electric scalpel, a suction device, a laser scalpel, a laser irradiator, a therapeutic light irradiator or a biopsy device is incorporated in the probe, the probe can detect a target site such as a lesion.
  • the structure can be simplified by combining the function with the therapeutic function, the output can be controlled based on the quantitative measurement value, and the lesion tissue can be automatically destroyed. Lesions can be selectively and photodynamically treated.
  • a sampling device such as a biopsy device or a suction device is incorporated in the probe, it is possible to determine with high precision a site that has acquired useful characteristics due to genetic modification or the like, and to collect the sample.
  • Atheroma in an atherosclerotic lesion can be selectively subjected to photodynamic treatment or destructive treatment.
  • the existing inexpensive light is used.
  • the transmission means can be used and the cost is low.
  • the present invention it is possible to provide a method and apparatus for automatically detecting and treating or collecting a target site having high detection performance by improving the accuracy and precision of localization of the target site such as a lesion. .

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  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
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Abstract

L'invention concerne l'application de faisceau lumineux de source lumineuse à une partie d'objet, du type partie affectée. On choisit dans la lumière réfléchie par la partie illuminée au moins deux zones de longueur d'onde, c'est-à-dire la zone spécifique à la source lumineuse et la zone spécifique à la partie considérée. Les deux zones englobent les longueurs d'onde auxquelles l'intensité lumineuse prend des valeurs maximums. On détermine quantitativerment l'intensité lumineuse relative propre aux deux zones, par des moyens de mesure spectroscopique. Les valeurs résultantes sont converties en signaux électriques de contrôle. Il est donc possible d'évaluer quantitativement, de détecter et de traiter ou d'échantillonner une partie d'objet du type partie affectée.
PCT/JP2002/009906 2001-10-01 2002-09-26 Procede de detection automatique, et de traitement ou d'echantillonnage de partie d'objet, du type partie d'objet affectee, et appareil correspondant Ceased WO2003030726A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2001304992A JP2003102672A (ja) 2001-10-01 2001-10-01 病変等の対象部位を自動的に検知かつ治療または採取する方法およびその装置
JP2001/304992 2001-10-01

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WO2003030726A1 true WO2003030726A1 (fr) 2003-04-17

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