WO2010006513A1 - 便携式子***癌前病变诊断装置 - Google Patents

便携式子***癌前病变诊断装置 Download PDF

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Publication number
WO2010006513A1
WO2010006513A1 PCT/CN2009/070098 CN2009070098W WO2010006513A1 WO 2010006513 A1 WO2010006513 A1 WO 2010006513A1 CN 2009070098 W CN2009070098 W CN 2009070098W WO 2010006513 A1 WO2010006513 A1 WO 2010006513A1
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WIPO (PCT)
Prior art keywords
light source
cervical cancer
cervix
light
excitation light
Prior art date
Application number
PCT/CN2009/070098
Other languages
English (en)
French (fr)
Inventor
曾堃
虞震芬
Original Assignee
Zeng Kun
Yu Zhen Fen
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Filing date
Publication date
Priority claimed from CN 200810131630 external-priority patent/CN101322644B/zh
Application filed by Zeng Kun, Yu Zhen Fen filed Critical Zeng Kun
Priority to US13/054,415 priority Critical patent/US20110184272A1/en
Publication of WO2010006513A1 publication Critical patent/WO2010006513A1/zh

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Classifications

    • 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
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/012—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor characterised by internal passages or accessories therefor
    • A61B1/015—Control of fluid supply or evacuation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/04—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
    • A61B1/043—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances for fluorescence imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/06—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements
    • A61B1/0607—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements for annular illumination
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/06—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements
    • A61B1/0638—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements providing two or more wavelengths
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/06—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements
    • A61B1/0661—Endoscope light sources
    • A61B1/0684—Endoscope light sources using light emitting diodes [LED]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/303—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor for the vagina, i.e. vaginoscopes
    • 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
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells

Definitions

  • Portable cervical cancer precancerous lesion diagnosis device
  • the present invention relates to a device for diagnosing precancerous lesions, and more particularly to a diagnostic device for rapid screening or standard detection of precancerous lesions of cervical cancer. Background technique
  • CIN cervical intraepithelial neoplasia
  • the cancer source at the CIN I and CIN II stages occurs in the lower third of the mucosa, and the epithelial (mucosa) surface does not have any The lesions are traced, so the use of gross morphological diagnosis is unable to detect the exact precancerous lesions.
  • the detection of C I N is the basis for the implementation of rational treatment and treatment success, and is the only way to block its progression to cervical cancer.
  • CIN is a cellular and biochemical change in the epithelium (mucosa) that is difficult to display valuable information on the outer layer of the epithelium (mucosa), so colposcopy for preinvasive cancer or intraepithelial cancer It has the value of detection and diagnosis, while the detection rate of CIN is lower.
  • the cervix coated with acetic acid can show metaplastic epithelium and poorly differentiated epithelium, all of which show white plaques. These white plaques may be CIN lesions, but The positive rate of CIN detection is about 40%.
  • the present invention aims to provide a method for efficiently detecting CIN lesions with low detection cost.
  • the portable cervical cancer precancerous lesion diagnosis device is a diagnostic device integrating an intrinsic fluorescence image system and a cervical acetate coloring system.
  • a portable cervical cancer precancerous lesion diagnostic apparatus comprising:
  • the cervical cancer intrinsic fluorescence detecting system comprising a light source and a light source switch for controlling opening and closing of the light source, the light source comprising an excitation light source for providing fluorescence and a cold light source for providing white light, the excitation light source and the cold light source They are all installed in a reflective bowl of a specific focal length, the reflective bowl focuses the light provided by the light source to the cervix;
  • the cervix acetate coloring detection system includes an acetic acid pool, a spray tube connected to the acetic acid pool, a spray tube moving device for moving the position of the spray tube, and a spray switch for controlling opening and closing of the spray tube;
  • the cervical cancer inherent fluorescence detecting system sequentially supplies a white light and an excitation light to illuminate the cervix using a cold light source and an excitation light source;
  • the cervical acetate coloring detection system sprays acetic acid to the cervix. After waiting for a period of time, the cervical cancer intrinsic fluor
  • a portable cervical cancer precancerous lesion diagnostic apparatus includes: a cervical cancer intrinsic fluorescence detecting system, the cervical cancer intrinsic fluorescence detecting system comprising a light source and a light source switch for controlling light source opening and closing,
  • the light source includes an excitation light source for providing fluorescence and a cold light source for providing white light, the excitation light source and the cold light source are both mounted in a reflective bowl of a specific focal length, the reflective bowl focuses the light provided by the light source to the cervix;
  • a coloring detection system the cervical acetic acid coloring detection system comprising an acetic acid pool, a spray tube connected to the acetic acid pool, a spray tube moving device for moving the spray tube position, and a spray switch for controlling the opening and closing of the spray tube;
  • an image acquisition system includes a low light CCD mounted at a center of the reflective bowl to collect light reflected by the cervix; the image acquisition system is coupled to an external image processing system, the external image processing
  • the cervical cancer intrinsic fluorescence detection system sequentially uses the cold light source and the excitation light source to provide white light and excitation light to illuminate the cervix, and the image acquisition system collects the acetic acid spray.
  • a reflected image of the white light and excitation light from the cervix after the fog is provided to the external image processing system. This device can be used for standard inspections.
  • the portable cervical cancer precancerous lesion diagnostic device is fixed to a pistol-type bracket, the pistol-type bracket includes a horizontal portion and a handle portion, and a rear end of the horizontal portion is coupled to an upper end of the handle portion, wherein
  • the reflective bowl is placed at the front end of the horizontal portion, the light sources are arranged in a ring shape on the reflective bowl at equal intervals;
  • the acetic acid pool is placed inside the handle portion, and the spray tube is from the acetic acid The pool begins to extend upwardly inside the handle portion, and continues to extend toward the front end of the horizontal portion along the lower side of the horizontal portion along the lower side of the horizontal portion through a spray tube reversing device;
  • Slidably mounted on the horizontal portion the spray tube moving device extending beyond the horizontal portion and coupled to a spray tube located inside the horizontal portion, the spray tube moving device capable of driving the spray a tube extending from a front end of the horizontal portion;
  • the light source switch being mounted on the handle portion, the light source switch including for controlling ex
  • the excitation light has a wavelength of 360 to 440 nm.
  • the excitation light source includes: a laser that generates 360 to 440 nm light, an LED that generates 360 to 440 nm light, a high pressure mercury lamp that generates 360 to 440 nm light, or a xenon lamp that generates 360 to 440 nm light.
  • the excitation source directs light into the reflective bowl through a quartz fiber, a liquid fiber, or a conventional fiber.
  • the surface of the reflective bowl is plated with a hard or soft ray that reflects ultraviolet rays.
  • the external image processing system includes: an interface circuit connected to a weak light CCD in the image acquisition system; a CPU connected to the interface circuit, and receiving an image acquired by the weak light CCD through the interface circuit; image analysis a device connected to the CPU to analyze an image transmitted by the CPU; an image processing device connected to the image analyzing device to process the analyzed image; a storage device connected to the image processing device, storing the The result of the image and its processing; an output device that outputs the image and the result of its processing.
  • a portable cervical cancer precancerous lesion diagnostic apparatus includes: a cervical cancer intrinsic fluorescence detecting system, the cervical cancer intrinsic fluorescence detecting system comprising a light source and a light source switch for controlling light source opening and closing,
  • the light source includes an excitation light source for providing fluorescence and a cold light source for providing white light, and the excitation light source and the cold light source are both mounted in a reflective bowl of a specific focal length.
  • the reflective bowl focuses the light provided by the light source to the cervix; a cotton quilt or cotton ball for applying acetic acid to the cervix; an image acquisition system, the image acquisition system includes a weak light CCD, and the weak light CCD is mounted on the a central position of the reflective bowl for collecting light reflected by the cervix; the image acquisition system is coupled to an external image processing system, the external image processing system processes the image acquired by the image acquisition system; the cervical cancer inherent fluorescence detection system in turn
  • the cold light source and the excitation light source are used to provide white light and excitation light to illuminate the cervix, and the image acquisition system collects a reflection image of the cervix against white light and excitation light and supplies the image to the external image processing system; the cotton raft or cotton ball smears the acetic acid to Cervical cervix, after waiting for a period of time, the cervical cancer inherent fluorescence detection system sequentially uses a cold light source and an excitation light source to provide white light and ex
  • the excitation light source is an excitation light LED
  • the cold light source is a white light LED
  • the excitation light LED and the white light LED are respectively placed in an isolated dark room in the portable cervical cancer precancerous lesion diagnosis device.
  • the input ends of a bifurcated quartz or liquid optical fiber are respectively connected to the excitation light LED and the white light LED, and the output end of the bifurcated quartz or liquid optical fiber is wrapped by a metal or plastic outer casing.
  • a portable cervical cancer precancerous lesion diagnostic apparatus includes: a cervical cancer intrinsic fluorescence detecting system, the cervical cancer intrinsic fluorescence detecting system comprising a light source and a light source switch for controlling light source opening and closing,
  • the light source includes an excitation light source for providing fluorescence and a cold light source for providing white light, and the excitation light source and the cold light source are connected to an input end of a quartz or liquid optical fiber wrapped with a metal or plastic outer casing, and the output end of the quartz or liquid optical fiber is directly Irradiation of the cervix;
  • Cervical acetic acid staining detection system, the cervical acetate coloring detection system includes an acetic acid tank, a spray tube connected to the acetic acid tank, a spray tube moving device for moving the spray tube position, and a spray for controlling the opening and closing of the spray tube
  • the cervical cancer intrinsic fluorescence detecting system sequentially supplies a white light and an excitation light to illuminate the cervix using a cold light source
  • the invention combines the inherent fluorescence image detection method and the cervical acetic acid coloring detection method, and greatly improves the detection rate of cervical cancer precancerous lesion (CI N ) disease, which can reach about 80%, the present hair Ming's method basically adopts an objective basis, and has little dependence on experience, even if the primary doctor can also detect CI N more accurately.
  • the detection method has the advantages of low cost, high speed, only 2 yuan for detecting the cost of a patient, and the detection time is only about 5 minutes.
  • the portable cervical cancer precancerous lesion diagnosis device of the invention can find more cervical cancer precancerous lesions, and the mature treatment means can block the development of cervical cancer, that is, directly reduce the incidence of uterine cancer. rate.
  • Figure 1 reveals the fluorescence spectra of biomolecules measurable in the epithelium
  • Figure 2 reveals the gradual process of cells in the epithelium
  • Figure 3 reveals the formation and development of cervical cancer
  • Figure 4 reveals the early information about the biochemical environment surrounding the host during the abnormal cell gradual process
  • Figure 5 reveals the principle of fluorescence generation
  • Figure 6 is a view showing the configuration of a first embodiment of the portable cervical cancer precancerous lesion diagnostic apparatus of the present invention.
  • Figure 7 is a block diagram showing the structure of an external image processing system of the present invention.
  • Figure 8 is a view showing the configuration of a second embodiment of the portable cervical cancer precancerous lesion diagnostic apparatus of the present invention.
  • Figures 9a and 9b show a structural view of a third embodiment of the portable cervical cancer precancerous lesion diagnostic apparatus of the present invention.
  • Fig. 10a and Fig. 10b show a structural view of a fourth embodiment of the portable cervical cancer precancerous lesion diagnostic apparatus of the present invention. detailed description
  • cervical cancer lesions also originate in the mucosal epithelial layer.
  • the cervical mucosal epithelium is located between 0.6mm and 1.2mm.
  • the abnormal changes in the epithelium are gradual.
  • Process expressed in biochemical information, not in form The form of learning, so the information of cervical precancerous lesions can not obtain CIN information by physical means such as B-ultrasound, X-ray, CT, MRI, etc.
  • a technique different from morphological detection the detection technique used in the present invention is based on biochemistry, and the spectroscopy technique is applied to early detection of human tumors.
  • a laser induced fluorescence is incorporated by reference to U.S. Patent No. 4,957,114, the disclosure of which is incorporated herein by reference. LIF diagnostic methods and diagnostic criteria have been recognized.
  • the biomimetic fluorescence spectra measured in the epithelium include amino acid collagen, structural proteases and coenzymes, coenzymes related to fat and porphyrin cell metabolism, adenine dinucleotide, flavin adenine dinucleotide (NADH) and flavin alone. Nucleic acids, tryptophan, collagen, anti-dermatitis, elastin, lipipergic pigment, acriflavine, porphyrin, etc. These biomolecules have their own unique emission spectra, as shown in Figure 1, so these biomolecules The changes can all be expressed in the form of a fluorescent spectrum.
  • Virus intrusion caused by unclean sex including HPV16, HPV18, HSV-2, HCMV, etc.;
  • This stage also becomes the primary prevention stage. This phase corresponds to the cells in the "normal epithelial" phase of Figure 2.
  • the second stage is the stage of gene mutation, which is further divided into three sub-stages: gene mutation (CIN1), dysplasia (CIN2) and carcinoma in situ (CIN3), the above three stages.
  • CIN1 gene mutation
  • CIN2 dysplasia
  • CIN3 carcinoma in situ
  • Substantial lesions have occurred in the gene mutation stage, but have not yet developed into cancer. Therefore, if effective diagnosis and treatment can be performed at this stage, it can effectively block the development of invasive cancer. Therefore, a true early diagnosis should be able to effectively diagnose the lesion in the second stage.
  • the mutation stages CI N 1 , CI N2, and CI N3 (in situ carcinoma) all changed in the mucosa, and no obvious morphological features appeared. It is therefore important to detect changes in biochemical information.
  • the second phase also became the secondary prevention phase.
  • the third stage has developed cancer, early invasive carcinoma and invasive carcinoma, corresponding to the "early invasive carcinoma” and “invasive carcinoma” phases in Figure 2. At this time, cancer has formed and treatment has become relatively difficult.
  • the third stage is also called the third stage prevention stage.
  • the excitation light source 502 generates excitation light 504, which is irradiated onto the mucous membrane 508 through the optical fiber 506, and the electrons 510 in the mucous membrane 508 are transitioned to generate corresponding visible light, which is collected by the naked eye or image.
  • Device 512 observes.
  • the fluorescence characteristics of the cervical mucosal epithelium from the cervical mucosal epithelium by light indicate whether the measured cervical mucosal epithelium is normal, benign lesion, cancer or CIN, which can be expressed by fluorescence spectrum curve. , can also be expressed in fluorescent images.
  • the invention expresses in a fluorescent image, and the doctor can visually visualize or visualize the fluorescent color of the cervical mucosa epithelium by visual observation on the display screen, and the detection characteristic of the CI N is high, and the cervical mucosa epithelium can be detected.
  • the deep CI N lesions have low detection cost. The cost per test is only 2 yuan, and the detection speed is fast. It takes only five minutes for each patient to be tested.
  • additional CCD camera through the computer Automated image recognition, storage, etc. This method is suitable for hospital diagnostic applications.
  • Table 1 shows the criteria for image authentication CI N levels.
  • the present invention also introduces acetic acid coloring image diagnosis. Therefore, the core of the present invention integrates the intrinsic fluorescence image diagnosis with the acetic acid colored image diagnosis. The two diagnostic methods were diagnosed separately and their CI N positive detection rate was about 40%.
  • the reason for the fluorescence diagnosis was to identify the biochemical changes in the cervical mucosal epithelium as a basis for diagnosis, while the acetic acid staining image diagnosis (VIA) showed The change of the outer layer (keratinized layer) of the cervical mucosa epithelium is slightly different, and the site of the lesion is half in the mucosal epithelium and the outer layer of the mucosal epithelium, which results in the above method alone. Some lesions could not be detected.
  • the combination of the two diagnostic methods can cover the entire structure of the cervical mucosa epithelium.
  • VIA is responsible for the identification of epithelial diagnosis and fluorescence is responsible for intraepithelial diagnosis.
  • the two diagnostic methods complement each other and can be used for cervical cancer.
  • the detection rate of lesions increased to 70% to 80%.
  • Normal cervical squamous epithelium contains less protein to facilitate the detection of biochemical information in the epithelium.
  • metaplastic epithelium poorly differentiated epithelial membrane, nucleus and cytoplasm contain more collagen and elastin. It is covered by the fluorescence properties of the surface proteins, and it is impossible to display important biochemical information in the epithelium.
  • NADH nicotinamide adenine dinucleotide NADH
  • NADH NADH nicotinamide adenine dinucleotide
  • the fluorescence peak of NADH is around 470 nm, so the value of 470 nm peak can be used as the basis for the possibility of canceration of the tissue.
  • the outer layer of the cervical mucosa epithelium Keratinized layer
  • collagen and elastin it must be measured by fluorescence.
  • the fluorescence data of proteins, and important biochemical substances in the epithelium such as NADH can not be displayed, which is the blind spot of fluorescence diagnosis.
  • VIA can scientifically fill this blind spot.
  • the combined detection of the two methods used the CIN total positive detection rate, and the above-mentioned arguments were confirmed by the data from the CIN screening of large sample populations.
  • the portable cervical cancer precancerous lesion diagnostic apparatus 600 comprises: a cervical cancer intrinsic fluorescence detecting system 602, the cervical cancer intrinsic fluorescence detecting system comprising a light source 620 and a light source switch 622 for controlling light source opening and closing, the light source comprising an excitation light source for providing fluorescence And a cold light source that provides white light, both the excitation source and the cold source are mounted in a reflective bowl 624 of a particular focal length, and the reflective bowl 624 focuses the light provided by the source to the cervix.
  • the wavelength of the excitation light is 360 to 440 nm.
  • the excitation light source can use the following light sources: a laser that produces 360-440 nm light, an LED that produces 360-440 nm light, a high-pressure mercury lamp that produces 360-440 nm light, or a xenon lamp that produces 360-440 nm light.
  • the excitation light source is a laser or a high pressure mercury lamp, because of the large volume of the laser or the high pressure mercury lamp, they are placed outside the portable cervical cancer precancerous lesion diagnostic device 600 and passed through a quartz fiber, a liquid fiber or Ordinary fibers direct light into the reflective bowl 624.
  • Reflective Bowl The surface of the 624 is coated with a hard or soft sputum that reflects UV rays.
  • the focal length of the Reflective Bowl 624 can be around 120mm.
  • the portable cervical cancer precancerous lesion diagnostic apparatus 600 further includes a cervical acetate staining detection system 604 including an acetic acid pool 640, a spray tube 642 connected to the acetic acid pond, and a position for moving the spray tube 642 The spray tube moving device 644 and the spray switch 646 that controls the opening and closing of the spray tube 642.
  • the portable cervical cancer precancerous lesion diagnostic device 600 is attached to a pistol-type bracket that includes a horizontal portion 400 and a handle portion 402, the rear end of the horizontal portion 400 and the handle portion 402. The upper end is connected.
  • the reflective bowl 624 is placed at the front end of the horizontal portion 400, and the light sources 620 are arranged in a ring shape on the reflective bowl 624 at equal intervals.
  • the acetic acid cell 640 is placed inside the handle portion 402.
  • the spray tube 642 extends upwardly from the interior of the handle portion 402 from the acetic acid cell 640. After passing through a spray tube reversing device 404, it continues along the lower side of the horizontal portion 400 within the horizontal portion. Extends to the front end of the horizontal portion.
  • the spray tube reversing device 404 is an annular structure, and the spray tube 642 surrounds the spray tube reversing device 404. Change up to level.
  • the spray tube moving device 644 is slidably mounted on the horizontal portion 400, and the spray tube moving device 644 extends beyond the horizontal portion 400 and is coupled to a spray tube 642 located inside the horizontal portion 400.
  • the spray tube moving device 644 can drive the spray tube 642 extends beyond the front end of the horizontal portion 400.
  • the spray tube 642 can extend a distance of about 5 cm from the front end of the horizontal portion 400.
  • the light source switch 622 is mounted on the handle portion 402.
  • the light source switch 622 includes an excitation light source switch 621 for controlling the opening and closing of the excitation light source and a cold light source switch 623 for controlling the opening and closing of the cold light source.
  • the light source switch 622 is implemented by a bidirectional switch having an upper portion as an excitation light source switch 621 and a lower portion as a cold light source switch 623.
  • a spray switch 646 is also mounted on the handle portion 402.
  • an image acquisition system 606 is further included, the image acquisition system includes a low light CCD 660 mounted at a center of the reflective bowl 624 for collecting light reflected by the cervix; Image acquisition system 606 is coupled to an external image processing system (shown in Figure 7) that processes the images acquired by the image acquisition system.
  • the external image processing system 700 employed in this embodiment includes an interface circuit 702 coupled to a low light CCD 660 in the image acquisition system 606.
  • the CPU 704 is connected to the interface circuit 702 and receives the image acquired by the low light CCD 660 through the interface circuit 702.
  • the image analyzing device 706 is connected to the CPU 704 and analyzes the image transmitted by the CPU 704.
  • the image processing device 708 is connected to the image analyzing device 706 to process the analyzed image.
  • the storage device 710 is coupled to the image processing device 708 to store the images and the results of their processing.
  • Output device 712, the output image and the result of its processing, output device 712 can include display device 71 1 and printing device 713.
  • the working process of the embodiment shown in Fig. 6 is as follows: First, the fluorescence detection, the cervical cancer inherent fluorescence detecting system 602 sequentially supplies the white light and the excitation light to the cervix using the cold light source and the excitation light source, and the image capturing system 606 collects the cervical light to the white light. And a reflected image of the excitation light and provided to the external image processing system 700.
  • the cervical acetate coloring detection system 604 sprays acetic acid to the cervix
  • the cervical cancer inherent fluorescence detection system 602 sequentially uses a cold light source and an excitation light source to provide white light and excitation light to illuminate the cervix, image acquisition system.
  • the operation procedure of the portable cervical cancer precancerous lesion diagnostic apparatus is as follows: After the patient has placed the diffuser, the doctor uses the front end of the portable cervical cancer precancerous lesion diagnostic apparatus to align the front end The port is about 30mm, the cold light source switch is turned on to turn on the white light, the cervix state under white light is identified by the CCD, all the illumination lamps in the diagnosis room (ie, the dark room) are turned off, the excitation light switch is turned on, the excitation light is turned on, and the inherent fluorescence of the cervix is identified by the CCD.
  • the lesion, and the patient's cervical status is discriminated according to the diagnostic criteria of Table 1.
  • Move the spray tube moving device so that the spray tube moves out of the end surface a certain distance (such as 5cm) and aligns with the cervix of the patient being examined.
  • Mg of acetic acid after 2-3 minutes by CCD under the white light source to identify whether the patient has a white acetate acetate.
  • the CCD simultaneously transmits the received signal to the CPU through the interface circuit.
  • a diagnostic report is produced through the display display or the memory or printer. .
  • CCD and its auxiliary equipment require a larger space and are more complicated, so it is more suitable for standard examination in hospitals.
  • Fig. 8 is a view showing the configuration of a second embodiment of the portable cervical cancer precancerous lesion diagnostic apparatus of the present invention.
  • the second embodiment differs in that the cervix acetate coloring detection system is eliminated, and the separated cotton aphid or cotton ball 604 is directly used for the application of acetic acid. In use, it is first irradiated with white light, and then colored with a cotton aphid or a cotton ball, and then irradiated with excitation light.
  • the low light CCD is still used in the embodiment shown in Fig. 8, and is also suitable for use as a standard inspection in hospitals.
  • Fig. 9a and Fig. 9b show a structural view of a third embodiment of the portable cervical cancer precancerous lesion diagnostic apparatus of the present invention.
  • the image capture system is eliminated and the low light CCD is no longer placed at the center of the reflective bowl 924.
  • the condition of the reflected light is observed by the doctor's naked eye.
  • the rest of the structure is consistent with the embodiment shown in FIG. Not using the CCD will slightly reduce the detection accuracy, but it can greatly increase the speed of detection.
  • the size of the entire diagnostic device is greatly reduced, the flexibility is improved, and it is suitable for large-scale liquidity. Quick screening.
  • the excitation source is the excitation light LED 901, cold light
  • the source is a white LED 903, and the excitation LED and the white LED are respectively placed in the isolated darkrooms 902 and 904 in the portable cervical cancer precancerous diagnostic apparatus (refer to Fig. 9b).
  • the input ends of a bifurcated quartz or liquid optical fiber 906 are respectively connected to the excitation light LED 901 and the white LED
  • the output of the bifurcated quartz or liquid fiber 906 is wrapped in a metal or plastic jacket.
  • the case where the CCD is not used is used. It is also possible to apply the above-described light source structure to the first or second embodiment having a CCD.
  • Fig. 10a and Fig. 10b show a structural view of a fourth embodiment of the portable cervical cancer precancerous lesion diagnostic apparatus of the present invention.
  • This fourth embodiment is a further variation of the third embodiment shown in Figures 9a and 9b.
  • the reflective bowl was also cancelled.
  • the excitation light source is the excitation light LED 1001
  • the cold light source is the white light LED 1003
  • the excitation light LED and the white light LED are respectively placed in the isolated darkroom of the portable cervical cancer precancerous lesion diagnostic apparatus.
  • the input ends of a bifurcated quartz or liquid optical fiber 1006 are connected to the excitation light LED 1001 and the white light LED 1003, respectively.
  • the output of the bifurcated quartz or liquid fiber 1006 is wrapped in a metal or plastic jacket.
  • the output of the bifurcated quartz or liquid fiber 1006 extends beyond the front end of the portable cervical cancer precancerous diagnostic device.
  • the output of the bifurcated quartz or liquid fiber 1006 has a thinner diameter, making it easier for doctors. Observed with the naked eye.
  • the embodiment shown in Figures 10a and 10b is more flexible and is equally suitable for large-scale rapid screening of fluidity.
  • the present invention has been described in connection with the above embodiments, it is to be noted that, in practical applications, the intrinsic fluorescent image detecting apparatus and the acetic acid coloring detection do not have to be placed in the same holder, and the separation setting is also possible. Alternatively, the form of the device provided by the present invention is not employed, but other various devices incorporating intrinsic fluorescence image detection and cervical acetate coloring detection are considered to be within the scope of the present invention. It will be apparent to those skilled in the art that the present invention proposes a high-accuracy mucosal cancer detecting means by combining an intrinsic fluorescence image detecting method and a cervical acetate coloring detecting method.
  • the apparatus of the present invention can also be used for the diagnosis of other mucosal precancerous lesions.
  • the invention combines the intrinsic fluorescence image detecting method and the cervical acetic acid coloring detecting method, and greatly improves the detection rate of cervical cancer precancerous lesion (CI N ) disease, which can reach about 80%,
  • the method of the invention basically adopts an objective basis, and has little dependence on experience, even if the primary doctor can also detect CI N more accurately.
  • the detection method has the advantages of low cost, high speed, only 2 yuan for detecting the cost of a patient, and the detection time is only about 5 minutes.
  • the portable cervical cancer precancerous lesion diagnosis device of the invention can find more cervical cancer precancerous lesions, and the mature treatment means can block the development of cervical cancer, that is, directly reduce the incidence of uterine cancer. rate.

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Description

便携式子***癌前病变诊断装置 技术领域
本发明涉及诊断癌前病变的装置， 更具体地说， 涉及用于快速筛查或 标准检测子***癌前病变的诊断装置。 背景技术
全世界癌症死亡率高的主要原因之一， 是诊断学没有重大突破， 尚停 留在大体形态学的诊断方法。 如医生的经验， ***镜、 内窥镜， B超、 CT、 MRI等大体形态学的诊断方法， 此类诊断方法对于小于 0.5cm的微小型癌 尚难以鉴别诊断。 而由于上皮型癌症的病源均发源于上皮 （即粘膜） 内， 因其尚无突破上皮层（粘膜）末形成癌症的所有特征， 故称其为癌前病变。 以子***前病变为例 (简称 CIN , cervical intraepithelial neoplasia ) , 如图 1 所示， 处于 CIN I和 CIN II阶段的癌症病源发生在粘膜内下 1/3部 位， 上皮 （粘膜） 表层无任何病灶痕迹， 故使用大体形态学的诊断是无法 检测到确切癌前病变病灶。 C I N的检测是实施合理治疗和治疗成功的基础， 也是阻断其向子***发展的唯一途径。
目前全世界应用于诊断子***的方法与仪器很多， 广泛使用的是阴 道镜 （Colposcope ) 其原理实际是一种放大镜， 用于观察子宫颈上皮 （粘 膜） 表面色泽轮廓变化， 以及血管的变化。 而 CIN是上皮 （粘膜） 内的细 胞及生物化学的变化， 很难在上皮 （粘膜） 外层表现出有价值信息， 故阴 道镜对于子*** ( preinvasive cancer )或原位癌( intraepithelial cancer ) 具有检测与诊断价值， 而对 CIN的检出率则较低。
醋酸着色后肉眼观察 VIA对检测 CIN有一定价值， 经涂抹醋酸的子宫 颈能显示出化生上皮及分化不良上皮， 它们均呈显出白色斑块， 这些白色 斑块有可能是 CIN病灶， 但其 CIN阳性检出率约 40%左右。
发明内容
本发明旨在提供一种能高效检测 CIN病灶， 又具有较低的检测成本的 便携式子***癌前病变诊断装置， 是集成了固有荧光图像***及子宫颈 醋酸着色***为一体的诊断装置。
根据本发明的一方面，揭示了一种便携式子***癌前病变诊断装置， 包括：
子***固有荧光检测***， 该子***固有荧光检测***包括光源 以及控制光源开闭的光源开关， 所述光源包括提供荧光的激发光源及提供 白光的冷光源， 所述激发光源和冷光源都安装在特定焦距的反光碗内， 所 述反光碗将光源提供的光聚焦到子宫颈； 子宫颈醋酸着色检测***， 该子 宫颈醋酸着色检测***包括醋酸池、 连接到醋酸池的喷雾管、 用于移动喷 雾管位置的喷雾管移动装置、 以及控制喷雾管开闭的喷雾开关； 所述子宫 颈癌固有荧光检测***依次使用冷光源和激发光源提供白光和激发光照射 子宫颈； 所述子宫颈醋酸着色检测***将醋酸喷雾至子宫颈， 等待一段时 间后由所述子***固有荧光检测***依次使用冷光源和激发光源提供白 光和激发光照射子宫颈。 该装置可以用于快速筛查。
根据本发明的另一方面，提供一种便携式子***癌前病变诊断装置， 包括： 子***固有荧光检测***， 该子***固有荧光检测***包括光 源以及控制光源开闭的光源开关， 所述光源包括提供荧光的激发光源及提 供白光的冷光源， 所述激发光源和冷光源都安装在特定焦距的反光碗内， 所述反光碗将光源提供的光聚焦到子宫颈； 子宫颈醋酸着色检测***， 该 子宫颈醋酸着色检测***包括醋酸池、 连接到醋酸池的喷雾管、 用于移动 喷雾管位置的喷雾管移动装置、 以及控制喷雾管开闭的喷雾开关； 图像采 集***， 该图像采集***包括弱光 CCD , 所述弱光 CCD安装在所述反光 碗的中心位置， 采集由子宫颈反射的光； 该图像采集***连接到一外部图 像处理***， 所述外部图像处理***处理该图像采集***采集的图像； 所 述子***固有荧光检测***依次使用冷光源和激发光源提供白光和激发 光照射子宫颈， 图像采集***采集子宫颈对白光和激发光的反射图像并提 供给所述外部图像处理***； 所述子宫颈醋酸着色检测***将醋酸喷雾至 子宫颈， 等待一段时间后由所述子***固有荧光检测***依次使用冷光 源和激发光源提供白光和激发光照射子宫颈， 图像采集***采集经醋酸喷 雾后的子宫颈对白光和激发光的反射图像并提供给所述外部图像处理系 统。 该装置可用于标准检查。
所述便携式子***癌前病变诊断装置固定在一***型支架上， 所述 ***型支架包括一水平部分以及一手柄部分， 所述水平部分的后端与所述 手柄部分的上端连接， 其中， 所述反光碗置于所述水平部分的前端， 所述 光源呈等间隔在所述反光碗上布置成环形； 所述醋酸池置于所述手柄部分 内部， 所述喷雾管从所述醋酸池开始在所述手柄部分的内部向上方延伸， 经过一喷雾管换向装置后继续沿着所述水平部分的下侧在水平部分内部向 所述水平部分的前端延伸； 所述喷雾管移动装置可滑动地安装在所述水平 部分上， 所述喷雾管移动装置延伸到所述水平部分之外并与位于所述水平 部分内部的喷雾管相连接， 所述喷雾管移动装置能带动所述喷雾管伸出所 述水平部分的前端； 所述光源开关安装在所述手柄部分上， 所述光源开关 包括用于控制激发光源开闭的激发光源开关和控制冷光源开闭的冷光源开 关； 所述喷雾开关安装在所述手柄部分上。
所述激发光的波长为 360~440nm。 所述激发光源包括： 产生 360~440nm光的激光器、 产生 360~440nm光的 LED , 产生 360~440nm 光的高压汞灯、 或产生 360~440nm 光的氙灯。 所述激发光源通过石英光 纤、 液体光纤或普通光纤将光引导到所述反光碗内。
所述反光碗表面镀有反射紫外线的硬镆或软镆。
所述外部图像处理***包括： 接口电路， 连接到所述图像采集***中 的弱光 CCD; CPU , 连接到所述接口电路， 通过所述接口电路接收所述弱 光 CCD采集的图像； 图像分析装置， 连接到所述 CPU , 分析所述 CPU传 递的图像； 图像处理装置， 连接到所述图像分析装置， 对分析后的图像进 行处理； 存储装置， 连接到所述图像处理装置， 存储所述图像及其处理的 结果； 输出装置， 输出所述图像及其处理的结果。
根据本发明的另一方面，提供一种便携式子***癌前病变诊断装置， 包括： 子***固有荧光检测***， 该子***固有荧光检测***包括光 源以及控制光源开闭的光源开关， 所述光源包括提供荧光的激发光源及提 供白光的冷光源， 所述激发光源和冷光源都安装在特定焦距的反光碗内， 所述反光碗将光源提供的光聚焦到子宫颈； 用于涂抹醋酸至子宫颈的棉扦 或棉球； 图像采集***， 该图像采集***包括弱光 CCD , 所述弱光 CCD 安装在所述反光碗的中心位置， 采集由子宫颈反射的光； 该图像采集*** 连接到一外部图像处理***， 所述外部图像处理***处理该图像采集*** 采集的图像； 所述子***固有荧光检测***依次使用冷光源和激发光源 提供白光和激发光照射子宫颈， 图像采集***采集子宫颈对白光和激发光 的反射图像并提供给所述外部图像处理***； 所述棉扦或棉球将醋酸涂抹 至子宫颈， 等待一段时间后由所述子***固有荧光检测***依次使用冷 光源和激发光源提供白光和激发光照射子宫颈， 图像采集***采集经醋酸 涂抹后的子宫颈对白光和激发光的反射图像并提供给所述外部图像处理系 统。 该装置可用于标准检查。
所有的装置中，所述激发光源为激发光 LED ,所述冷光源为白光 LED , 所述激发光 LED和白光 LED分别置于所述便携式子***癌前病变诊断 装置内的隔离的暗室内， 一分叉式的石英或者液体光纤的输入端分别连接 所述激发光 LED和白光 LED ,所述分叉式的石英或者液体光纤的输出端采 用金属或者塑料外套包裹。
根据本发明的另一方面，提供一种便携式子***癌前病变诊断装置， 包括： 子***固有荧光检测***， 该子***固有荧光检测***包括光 源以及控制光源开闭的光源开关， 所述光源包括提供荧光的激发光源及提 供白光的冷光源， 所述激发光源和冷光源连到采用金属或塑料外套包裹的 石英或者液体光纤的输入端， 所述石英或者液体光纤的输出端直接照射子 宫颈； 子宫颈醋酸着色检测***， 该子宫颈醋酸着色检测***包括醋酸池、 连接到醋酸池的喷雾管、 用于移动喷雾管位置的喷雾管移动装置、 以及控 制喷雾管开闭的喷雾开关； 所述子***固有荧光检测***依次使用冷光 源和激发光源提供白光和激发光照射子宫颈； 所述子宫颈醋酸着色检测系 统将醋酸喷雾至子宫颈， 等待一段时间后由所述子***固有荧光检测系 统依次使用冷光源和激发光源提供白光和激发光照射子宫颈。
本发明结合了固有荧光图像检测方法及子宫颈醋酸着色检测方法， 大 大提高了子***癌前病变 （CI N ) 病的检出率， 可达到 80%左右， 本发 明的方法基本采用客观依据， 对于经验的依赖少， 即使初级医生同样能比 较准确地检出 CI N。 并且， 该检测方法检测成本低、 速度快、 检测一个病 员成本只需要 2元， 检测时间大约只需要 5分钟。 本发明的便携式子宫颈 癌癌前病变诊断装置可发现更多子***癌前病变病， 经过成熟的治疗手 段即能阻断其向子***方向发展， 也即直接降低了子宫癌的发病率。 附图说明
本发明的上述的以及其他的特征、 性质和优势将通过下面结合附图和 实施例的描述而变得更加明显， 在附图中， 相同的附图标记始终表示相同 的特征， 其中：
图 1揭示了上皮内可测得的生物分子的荧光光谱；
图 2揭示了上皮内细胞的渐变过程；
图 3揭示了子***的形成以及发展过程；
图 4揭示了异常细胞渐变过程宿主周边生物化学环境早期信息； 图 5揭示了荧光产生的原理；
图 6揭示了本发明的便携式子***癌前病变诊断装置的第一实施例 的结构图；
图 7揭示了本发明的外部图像处理***的结构图；
图 8揭示了本发明的便携式子***癌前病变诊断装置的第二实施例 的结构图；
图 9a和 9b揭示了本发明的便携式子***癌前病变诊断装置的第三 实施例的结构图；
图 10a和图 10b揭示了本发明的便携式子***癌前病变诊断装置的 第四实施例的结构图。 具体实施方式
人体肿瘤 85%病灶起源于上皮层内， 而子***病灶同样也是起源于 粘膜上皮层内， 子宫颈粘膜上皮内位于 0.6mm~1 .2mm之间， 上皮内所发 生的异常变化是渐变的过程， 是以生物化学信息予以表达， 而不是以形态 学的形式表达， 故子***前病变的信息无法以物理的手段如 B超、 X线、 CT、MRI等获得 CIN的信息，当然更无法用大体形态学直接观察到 CIN 信 于是， 必须采用一种不同于形态学检测的技术， 本发明采用的检测技 术以生物化学为基础， 将光谱技术应用于人体早期肿瘤检测。 本发明中集 成了 LIF 技术 ( Laser induced fluorescence ) , 参考美国专利 （ US 4,957,114) , 上述美国专利转让给本申请的申请人并通过引用结合于此。 LIF 的诊断方法与诊断标准已得到认可。 上皮内可测得的生物分子荧光光 谱包括氨基酸骨胶原、 结构蛋白酶和辅酶、 脂肪和卟啉细胞代谢相关的辅 酶、 腺嘌呤二核苷酸、 黄素腺嘌呤二核苷酸（NADH) 和黄素单核酸、 色 胺酸、 胶原蛋白、 抗皮炎素、 弹性蛋白、 脂肠色素、 吖啶黄素、 卟啉等， 这些生物分子具有各自独特的发射光谱， 如图 1 所示， 因此这些生物分子 的变化均可以以荧光光谱的形式给于表达。
大部分恶性肿瘤源于上皮内， 并且有逐渐渐变的过程， 当然子*** 也源于粘膜上皮内的渐变。 参考图 2所示， 其示出了上皮内细胞的渐变过 程。 所述的阶段包括基因突变阶段 CIN1、 CIN2、 CIN3 (原位癌） , 早期 ***和***阶段。 图 3示出了子宫癌的形成以及发展的过程。 结合图 2和图 3可见：
***的最初期阶段尚未发生实质性的病变， 仅仅是周边环境中出现 了不良的因素， 这些不良的因素包括：
不洁性生活造成病毒入侵， 这些病毒包括 HPV16、 HPV18、 HSV-2、 HCMV等等；
性生活过早以及良性病灶不治；
遗传、 地理因素。
该阶段并没有出现实质性的病变， 只是这些不良因素可能引起病变， 因此主要是以预防、 消除不良因素为主。 该阶段也成为一级预防阶段。 该 阶段对应图 2中处于 "正常上皮" 阶段的细胞。
第二阶段是基因突变阶段， 进一步分成三个子阶段， 分别是： 基因突 变 （CIN1 ) 、 不典型增生 （CIN2) 和原位癌 （CIN3) , 上述三个阶段的 细胞渐变情况可以参考图 2中的 CI N 1、 CI N2、 CI N3阶段。 基因突变阶段 已经发生了实质性的病变， 但是尚未发展成癌， 因此， 如果能在该阶段进 行有效的诊断和治疗， 能有效地阻断其发展成为***。 因此， 真正的早 期诊断应当能有效地诊断出处于第二阶段的病变。 但是基因突变阶段 CI N 1、 CI N2、 CI N3 (原位癌） 均在粘膜内渐变， 并没有明显的形态特征 出现。 于是检测生物化学信息的变化变得十分重要。 第二阶段也成为二级 预防阶段。
继续参考图 2和图 3， 第三阶段已经形成了癌， 即早期***和浸润 癌， 对应图 2中的 "早期***" 和 "***" 阶段。 此时， 癌已经形成， 治疗变得相对困难。 第三阶段也称三级预防阶段。
通过图 2和图 3的分析可见，很明显的早期诊断的关键在于第二阶段。 在第二阶段的细胞渐变过程中， 虽然形态特征不明显， 但是生物化学特征 的变化是十分明显的。 这些生物化学特征包括异常细胞渐变过程宿主周边 生物化学环境早期信息， 参考图 4所示， 这些信息包括：
血管分布、 荷尔蒙、 核酸碳水化合物代谢、 酶、 蛋白质、 基因突变。 上述的早期信息都具有自己典型的光谱频率， 当某种频率的光照射在 子宫颈粘膜的上皮上， 在一定条件下电子可吸收能量跃迁到较高能级（即 激发态）如果电子直接以激发态幅射方法回到基态， 则是通过发射出相应 光量子来释放能量，这就是荧光的产生（参考图 5所示的荧光产生原理图）。 也是 LIF检测的基本原理， 如图 5所示的， 激发光源 502产生激发光 504 , 通过光纤 506照射到粘膜 508上， 粘膜 508内的电子 510发生跃迁，产生 相应的可见光， 被肉眼或者图像采集装置 512观察到。
基于上述的原理， 用光照从子宫颈粘膜上皮， 从子宫颈粘膜上皮表现 出的荧光特征即代表该被测子宫颈粘膜上皮是否是正常、 良性病变、 癌或 CIN , 它可以以荧光光谱曲线表达， 也可用荧光图像表达。 本发明以荧光 图像表达， 医生用肉眼目视或通过在显示屏观察即能鉴别其子宫颈粘膜上 皮的荧光色泽进行筛查诊断， 其特点 CI N检出率高， 可检出子宫颈粘膜上 皮深层次的 CI N病灶， 检测成本低， 每检测一病员成本仅 2元人民币， 检 测速度快，每检测一病员仅需五分钟。此外如附加 CCD摄像通过计算机可 进行自动进行图像识别， 储存等功能， 此方法适用于医院诊断应用。
表一示出了图像鉴别 CI N级别的标准。
Figure imgf000010_0001
Figure imgf000010_0002
在荧光图像诊断的基础上， 本发明还引入了醋酸着色图像诊断。 因此， 本发明的核心是将固有荧光图像诊断与醋酸着色图像诊断合二为一体。 二 种诊断方法单独实施诊断其 CI N阳性检出率均为 40%左右， 究其原因荧光 诊断为鉴别子宫颈粘膜上皮内的生物化学变化作为诊断依据， 而醋酸着色 图像诊断（VIA )则显示子宫颈粘膜上皮外层（角化层）的变化， 适用的部 位略有不同， 而病变发生的部位在粘膜上皮内和粘膜上皮外层的情况基本 各占一半， 就造成单独采用上述的方法， 无法检出部分的病变。 而将二种 诊断方法相结合， 基本可以覆盖子宫颈粘膜上皮的全部结构， VIA 负责鉴 别上皮外的诊断而荧光则负责上皮内的诊断， 二种诊断方法相互补故可将 子***癌前病变的检出率提高到 70%~80%。 正常子宫颈鳞上皮含较少 蛋白质有利于荧光检测上皮内的生物化学信息， 而当化生上皮， 分化不良 的上皮细胞膜、 核及胞质均含有较多胶原蛋白和弹性蛋白， 此时荧光诊断 被表层蛋白质荧光特性所遮盖，无法将上皮内重要的生物化学信息呈显出， 如 NADH 烟酰胺腺嘌吟二核苷酸 ( Nicotinamide adeninedinucleotide ) NADH被认为是抗氧化剂对自由基能抗氧化保护作用。 它的减少会引起细 胞破坏而有利于癌的形成， 而 NADH 的荧光峰值在 470nm左右， 因此可 以以 470nm峰值的数值作为该组织癌变可能与否的依据。若子宫颈粘膜上 皮外层 （角化层） 均被胶原蛋白与弹性蛋白所覆盖， 那未荧光所测得的必 然是蛋白质的荧光数据， 而上皮内的重要生物化学物质如 NADH等均无法 显示， 这就是荧光诊断的盲点。 而 VIA则能科学的填补了此盲点。 二种方 法联合使用其 CIN总阳性检出率大幅提高，通过大样本人群的 CIN筛选所 得的数据证实了上述的论点。
参考图 6所示， 揭示了本发明的便携式子***癌前病变诊断装置的 第一实施例的结构图。 该便携式子***癌前病变诊断装置 600包括： 子***固有荧光检测*** 602， 该子***固有荧光检测***包括 光源 620以及控制光源开闭的光源开关 622 , 光源包括提供荧光的激发光 源及提供白光的冷光源， 激发光源和冷光源都安装在特定焦距的反光碗 624 内， 反光碗 624 将光源提供的光聚焦到子宫颈。 激发光的波长为 360~440nm。 相应的， 激发光源可以采用下述的光源： 产生 360~440nm 光的激光器、 产生 360~440nm光的 LED, 产生 360~440nm光的高压汞 灯、 或产生 360~440nm 光的氙灯。 其中， 当激发光源为激光器、 高压汞 灯时， 由于激光器或高压汞灯的体积较大， 因此它们被置于便携式子宫颈 癌癌前病变诊断装置 600之外， 并通过石英光纤、 液体光纤或普通光纤将 光引导到反光碗 624内。 反光碗 624表面镀有反射紫外线的硬镆或软镆。 反光碗 624的焦距可为 120mm左右。
该便携式子***癌前病变诊断装置 600还包括子宫颈醋酸着色检测 *** 604 , 该子宫颈醋酸着色检测*** 604包括醋酸池 640、 连接到醋酸 池的喷雾管 642、 用于移动喷雾管 642位置的喷雾管移动装置 644、 以及 控制喷雾管 642开闭的喷雾开关 646。
参考图 7所示的， 该便携式子***癌前病变诊断装置 600固定在一 ***型支架上， ***型支架包括一水平部分 400以及一手柄部分 402， 水 平部分 400的后端与手柄部分 402的上端连接。反光碗 624置于水平部分 400的前端， 光源 620呈等间隔在反光碗 624上布置成环形。 醋酸池 640 置于手柄部分 402 内部， 喷雾管 642从醋酸池 640开始在手柄部分 402 的内部向上方延伸， 经过一喷雾管换向装置 404后继续沿着水平部分 400 的下侧在水平部分内部向水平部分的前端延伸。 喷雾管换向装置 404为一 环形结构， 喷雾管 642围绕该喷雾管换向装置 404—圈后延伸方向由垂直 向上改变为水平。 喷雾管移动装置 644可滑动地安装在水平部分 400上， 喷雾管移动装置 644延伸到水平部分 400之外并与位于水平部分 400内部 的喷雾管 642相连接，喷雾管移动装置 644能带动喷雾管 642伸出水平部 分 400的前端。一般而言， 喷雾管 642可以伸出水平部分 400的前端 5cm 左右的距离。 光源开关 622安装在手柄部分 402上， 光源开关 622包括用 于控制激发光源开闭的激发光源开关 621和控制冷光源开闭的冷光源开关 623。 在图 6所示的实施例中， 光源开关 622采用以双向开关实现， 上部 作为激发光源开关 621 , 下部作为冷光源开关 623。 喷雾开关 646也安装 在手柄部分 402上。
在图 6所示的实施例中， 还包括图像采集*** 606 , 该图像采集*** 包括弱光 CCD 660， 弱光 CCD 660安装在反光碗 624的中心位置， 用于 采集由子宫颈反射的光； 该图像采集*** 606连接到一外部图像处理*** (参考图 7所示） ， 外部图像处理***处理该图像采集***采集的图像。
参考图 7所示， 该实施例中采用的外部图像处理*** 700包括： 接口电路 702， 连接到图像采集*** 606 中的弱光 CCD 660。 CPU 704 , 连接到接口电路 702 , 通过接口电路 702接收弱光 CCD 660采集的 图像。 图像分析装置 706 , 连接到 CPU 704 , 分析 CPU 704传递的图像。 图像处理装置 708， 连接到图像分析装置 706， 对分析后的图像进行处理。 存储装置 710 , 连接到图像处理装置 708 , 存储图像及其处理的结果。 输 出装置 712 , 输出图像及其处理的结果， 输出装置 712可以包括显示装置 71 1和打印装置 713。
图 6所示的实施例的工作过程如下： 首先是荧光检测， 子***固有 荧光检测*** 602依次使用冷光源和激发光源提供白光和激发光照射子宫 颈， 图像采集*** 606采集子宫颈对白光和激发光的反射图像并提供给外 部图像处理*** 700。 之后是醋酸检测， 子宫颈醋酸着色检测*** 604将 醋酸喷雾至子宫颈， 等待一段时间后由子***固有荧光检测*** 602依 次使用冷光源和激发光源提供白光和激发光照射子宫颈， 图像采集*** 606 采集经醋酸喷雾后的子宫颈对白光和激发光的反射图像并提供给外部 图像处理*** 700。 在一具体的实施例中， 该便携式子***癌前病变诊断装置的操作过 程如下： 待病员安置好扩阴器后医生用便携式子***癌前病变诊断装置 水平部分的前端对准扩阴器端口 30mm左右，打开冷光源开关使白光亮启， 通过 CCD鉴别白光下的子宫颈状态， 关闭诊断室所有照明灯（即暗室 )打 开激发光开关使激发光亮启， 通过 CCD鉴别子宫颈固有荧光病灶， 并参照 表一诊断标准判别病人的子宫颈状态。 关闭激发光并开启白光光源， 移动 喷雾管移动装置使得喷雾管向端面外移出一定距离 （比如 5cm ) 并对准被 查病人子宫颈， 按动喷雾开关， 喷雾管向被查病人子宫颈喷涂 0.5ml 的醋 酸， 待 2— 3分钟通过 CCD在白光光源下鉴别诊断患者是否有醋酸白色上 皮。 通过 CCD , 可以直接在显示器上看到子宫颈的状态， CCD 同时将接 收到的信号通过接口电路传输给 CPU , 经过图像分析和图像处理后通过显 示器显示或储存器或打印机制作出一份诊断报告。
采用弱光 CCD的便携式子***癌前病变诊断装置诊断准确率更高， 但是相对而言， CCD及其辅助设备需要较大的空间， 也比较复杂， 因此比 较适合在医院用作标准检查。
图 8揭示了本发明的便携式子***癌前病变诊断装置的第二实施例 的结构图。 与图 6所示的第一实施例相比较， 第二实施例的区别在于子宫 颈醋酸着色检测***被取消 , 直接采用分离的棉扦或棉球 604进行醋酸的 涂抹。 在使用时， 首先采用白光照射， 之后使用棉扦或棉球涂抹醋酸进行 着色， 再以激发光照射。 图 8所示的实施例中仍旧采用弱光 CCD , 也比较 适合在医院用作标准检查。
图 9a和图 9b揭示了本发明的便携式子***癌前病变诊断装置的第 三实施例的结构图。 在该实施例中， 图像采集***被取消， 其反光碗 924 的中心位置不再设置弱光 CCD。 对于反射的光的情况都通过医生的肉眼进 行观察。 其余的结构均与图 6 所示的实施例一致。 不使用 CCD 虽然会使 检测准确度略有下降， 但是可以大大增加检测的速度， 并且， 没有 CCD以 及图像处理设备， 整个诊断装置的体积大大减小， 灵活性提高， 适合于流 动性的大规模快速筛查。
在图 9a和图 9b所示的实施例中， 激发光源为激发光 LED 901 , 冷光 源为白光 LED 903 , 激发光 LED和白光 LED分别置于便携式子***癌 前病变诊断装置内的隔离的暗室 902和 904 内 （参考图 9b ) 。 一分叉式 的石英或者液体光纤 906的输入端分别连接激发光 LED 901 和白光 LED
903。 分叉式的石英或者液体光纤 906 的输出端采用金属或者塑料外套包 裹。 在图 9a和图 9b所示的实示例中， 是不采用 CCD的情况。 将上述的 光源结构应用于具有 CCD的第一或者第二实施例中也是可行的。
图 10a和图 10b揭示了本发明的便携式子***癌前病变诊断装置的 第四实施例的结构图。 该第四实施例是图 9a和图 9b所示的第三实施例的 进一步的变化。 其中， 反光碗也被取消。 图 10a和图 10b所示的实施例中， 激发光源为激发光 LED 1001 , 冷光源为白光 LED 1003 , 激发光 LED和 白光 LED 分别置于便携式子***癌前病变诊断装置内的隔离的暗室 1002和 1004 内 （参考图 10b ) 。 一分叉式的石英或者液体光纤 1006的 输入端分别连接激发光 LED 1001和白光 LED 1003。分叉式的石英或者液 体光纤 1006 的输出端采用金属或者塑料外套包裹。 分叉式的石英或者液 体光纤 1006 的输出端延伸出便携式子***癌前病变诊断装置的前端之 外， 由于分叉式的石英或者液体光纤 1006 的输出端具有较细的直径， 更 加便于医生采用肉眼进行观察。 图 10a和 10b所示的实施例灵活性更高， 同样适合于流动性的大规模快速筛查。
虽然本发明结合上述的实施例进行了描述， 但是需要说明的是， 在 实际应用中， 固有荧光图像检测设备和醋酸着色检测并不一定要放置在同 一个支架内， 分离设置也是完全可以的。 或者， 不采用本发明所提供的装 置的形式， 但是结合应用了固有荧光图像检测及子宫颈醋酸着色检测的其 他各种设备都应被视为是在本发明的范围之内。 对于本领域的技术人员来 说， 很明显的， 本发明提出了通过结合固有荧光图像检测方法及子宫颈醋 酸着色检测方法而获得高准确率的粘膜癌检测手段。
如上面所描述的， 由于大多数粘膜癌的粘膜型病前病变的过程都是接 近的， 因此本发明的设备同样可以被用于其他粘膜型病前病变的诊断。
本发明的结合了固有荧光图像检测方法及子宫颈醋酸着色检测方法， 大大提高了子***癌前病变 （CI N ) 病的检出率， 可达到 80%左右， 本 发明的方法基本采用客观依据， 对于经验的依赖少， 即使初级医生同样能 比较准确地检出 CI N。 并且， 该检测方法检测成本低、 速度快、 检测一个 病员成本只需要 2元， 检测时间大约只需要 5分钟。 本发明的便携式子宫 颈癌癌前病变诊断装置可发现更多子***癌前病变病， 经过成熟的治疗 手段即能阻断其向子***方向发展， 也即直接降低了子宫癌的发病率。
尽管以上描述了本发明的较佳实施例， 但本发明不仅限于此。 本领域 的熟练的技术人员可以在以上描述的基础上进行各种变化和改变。 不脱离 发明精神的各种改变和变化都应落在本发明的保护范围之内。 发明的保护 范围由所附的权利要求书来限定。

Claims

权利要求
1. 一种便携式子***癌前病变诊断装置， 其特征在于， 包括： 子***固有荧光检测***， 该子***固有荧光检测***包括光源 以及控制光源开闭的光源开关， 所述光源包括提供荧光的激发光源及提供 白光的冷光源， 所述激发光源和冷光源都安装在特定焦距的反光碗内， 所 述反光碗将光源提供的光聚焦到子宫颈；
子宫颈醋酸着色检测***， 该子宫颈醋酸着色检测***包括醋酸池、 连接到醋酸池的喷雾管、 用于移动喷雾管位置的喷雾管移动装置、 以及控 制喷雾管开闭的喷雾开关；
所述子***固有荧光检测***依次使用冷光源和激发光源提供白光 和激发光照射子宫颈； 所述子宫颈醋酸着色检测***将醋酸喷雾至子宫颈， 等待一段时间后由所述子***固有荧光检测***依次使用冷光源和激发 光源提供白光和激发光照射子宫颈。
2. —种便携式子***癌前病变诊断装置， 其特征在于， 包括： 子***固有荧光检测***， 该子***固有荧光检测***包括光源 以及控制光源开闭的光源开关， 所述光源包括提供荧光的激发光源及提供 白光的冷光源， 所述激发光源和冷光源都安装在特定焦距的反光碗内， 所 述反光碗将光源提供的光聚焦到子宫颈；
子宫颈醋酸着色检测***， 该子宫颈醋酸着色检测***包括醋酸池、 连接到醋酸池的喷雾管、 用于移动喷雾管位置的喷雾管移动装置、 以及控 制喷雾管开闭的喷雾开关；
图像采集***， 该图像采集***包括弱光 CCD , 所述弱光 CCD安装 在所述反光碗的中心位置， 采集由子宫颈反射的光； 该图像采集***连接 到一外部图像处理***， 所述外部图像处理***处理该图像采集***采集 的图像；
所述子***固有荧光检测***依次使用冷光源和激发光源提供白光 和激发光照射子宫颈， 图像采集***采集子宫颈对白光和激发光的反射图 像并提供给所述外部图像处理***； 所述子宫颈醋酸着色检测***将醋酸 喷雾至子宫颈， 等待一段时间后由所述子***固有荧光检测***依次使 用冷光源和激发光源提供白光和激发光照射子宫颈， 图像采集***采集经 醋酸喷雾后的子宫颈对白光和激发光的反射图像并提供给所述外部图像处 理***。
3. 如权利要求 2所述的便携式子***癌前病变诊断装置，其特征在 于， 所述便携式子***癌前病变诊断装置固定在一***型支架上， 所述 ***型支架包括一水平部分以及一手柄部分， 所述水平部分的后端与所述 手柄部分的上端连接， 其中，
所述反光碗置于所述水平部分的前端， 所述光源呈等间隔在所述反光 碗上布置成环形；
所述醋酸池置于所述手柄部分内部， 所述喷雾管从所述醋酸池开始在 所述手柄部分的内部向上方延伸， 经过一喷雾管换向装置后继续沿着所述 水平部分的下侧在水平部分内部向所述水平部分的前端延伸；
所述喷雾管移动装置可滑动地安装在所述水平部分上， 所述喷雾管移 动装置延伸到所述水平部分之外并与位于所述水平部分内部的喷雾管相连 接， 所述喷雾管移动装置能带动所述喷雾管伸出所述水平部分的前端； 所述光源开关安装在所述手柄部分上， 所述光源开关包括用于控制激 发光源开闭的激发光源开关和控制冷光源开闭的冷光源开关；
所述喷雾开关安装在所述手柄部分上。
4. 如权利要求 2所述的便携式子***癌前病变诊断装置，其特征在 于， 所述激发光的波长为 360~440nm; 所述激发光源包括：
产生 360~440nm 光的激光器、 产生 360~440nm 光的 LED、 产生 360~440nm光的高压汞灯、 或产生 360~440nm光的氙灯。
5. 如权利要求 4所述的便携式子***癌前病变诊断装置，其特征在 于， 所述激发光源通过石英光纤、 液体光纤或普通光纤将光引导到所述反 光碗内。
6. 如权利要求 2所述的便携式子***癌前病变诊断装置，其特征在 于， 所述反光碗表面镀有反射紫外线的硬镆或软镆。
7. 如权利要求 2所述的便携式子***癌前病变诊断装置，其特征在 于， 所述外部图像处理***包括：
接口电路， 连接到所述图像采集***中的弱光 CCD;
CPU , 连接到所述接口电路， 通过所述接口电路接收所述弱光 CCD 采集的图像；
图像分析装置， 连接到所述 CPU , 分析所述 CPU传递的图像； 图像处理装置， 连接到所述图像分析装置， 对分析后的图像进行处理； 存储装置， 连接到所述图像处理装置， 存储所述图像及其处理的结果； 输出装置， 输出所述图像及其处理的结果。
8. 一种便携式子***癌前病变诊断装置， 其特征在于， 包括： 子***固有荧光检测***， 该子***固有荧光检测***包括光源 以及控制光源开闭的光源开关， 所述光源包括提供荧光的激发光源及提供 白光的冷光源， 所述激发光源和冷光源都安装在特定焦距的反光碗内， 所 述反光碗将光源提供的光聚焦到子宫颈；
用于涂抹醋酸至子宫颈的棉扦或棉球；
图像采集***， 该图像采集***包括弱光 CCD , 所述弱光 CCD安装 在所述反光碗的中心位置， 采集由子宫颈反射的光； 该图像采集***连接 到一外部图像处理***， 所述外部图像处理***处理该图像采集***采集 的图像；
所述子***固有荧光检测***依次使用冷光源和激发光源提供白光 和激发光照射子宫颈， 图像采集***采集子宫颈对白光和激发光的反射图 像并提供给所述外部图像处理***；所述棉扦或棉球将醋酸涂抹至子宫颈， 等待一段时间后由所述子***固有荧光检测***依次使用冷光源和激发 光源提供白光和激发光照射子宫颈， 图像采集***采集经醋酸涂抹后的子 宫颈对白光和激发光的反射图像并提供给所述外部图像处理***。
9. 如权利要求 1、 2或 8所述的便携式子***癌前病变诊断装置， 其特征在于，
所述激发光源为激发光 LED ,所述冷光源为白光 LED ,所述激发光 LED 和白光 LED 分别置于所述便携式子***癌前病变诊断装置内的隔离的 暗室内， 一分叉式的石英或者液体光纤的输入端分别连接所述激发光 LED 和白光 LED , 所述分叉式的石英或者液体光纤的输出端采用金属或塑料外 套包裹。
10. 一种便携式子***癌前病变诊断装置， 其特征在于， 包括： 子***固有荧光检测***， 该子***固有荧光检测***包括光源 以及控制光源开闭的光源开关， 所述光源包括提供荧光的激发光源及提供 白光的冷光源， 所述激发光源和冷光源连到采用金属或塑料外套包裹的石 英或者液体光纤的输入端， 所述石英或者液体光纤的输出端直接照射子宫 颈；
子宫颈醋酸着色检测***， 该子宫颈醋酸着色检测***包括醋酸池、 连接到醋酸池的喷雾管、 用于移动喷雾管位置的喷雾管移动装置、 以及控 制喷雾管开闭的喷雾开关；
所述子***固有荧光检测***依次使用冷光源和激发光源提供白光和激 发光照射子宫颈； 所述子宫颈醋酸着色检测***将醋酸喷雾至子宫颈， 等 待一段时间后由所述子***固有荧光检测***依次使用冷光源和激发光 源提供白光和激发光照射子宫颈。
PCT/CN2009/070098 2008-06-13 2009-01-12 便携式子***癌前病变诊断装置 WO2010006513A1 (zh)

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* Cited by examiner, † Cited by third party
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US20080039720A1 (en) * 2006-06-05 2008-02-14 Forth Photonics Ltd. Methods for characterizing cancer and pre-cancer tissues
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US5329938A (en) * 1983-02-17 1994-07-19 The Trylon Corporation Method for endoscopic examination of body cavity using chemilumine-scent light source
CN1302210A (zh) * 1997-10-20 2001-07-04 得克萨斯***大学评议会 荧光分光术中以乙酸用作增强信号对比度试剂
CN1493250A (zh) * 2002-10-31 2004-05-05 ƽ 内窥镜诊断癌前病变的装置
CN1502305A (zh) * 2002-11-22 2004-06-09 上海生标科技有限公司 光活检癌前病变图像诊断仪
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