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  Endoscopic, in vivo cellular observation methodsUSPTO Application #: 20070299312Title: Endoscopic, in vivo cellular observation methods Abstract: An endoscope observation system for in vivo cellular observation is disclosed that includes an illumination optical system having a light source for supplying illumination light to an object, an objective optical system that forms a magnified image of the object such that the absolute value of the image scale factor exceeds unity, and an image pickup unit that detects the magnified image. The illumination optical system is provided with a wavelength selection means for dividing, among the blue, green, and red wavelength ranges in the illumination light from the light source, either the blue wavelength range or the red wavelength range into two wavelength bands T1 and T2, with the wavelength band T1 being nearer the green wavelength range than is the wavelength band T2, and light in the wavelength band T1 is prevented from illuminating the object. An in vivo cellular observation method is also disclosed using an endoscope. (end of abstract) Agent: Arnold International - Great Falls, VA, US Inventor: Naoki Hasegawa USPTO Applicaton #: 20070299312 - Class: 600160000 (USPTO) Related Patent Categories: Surgery, Endoscope, Having Imaging And Illumination Means The Patent Description & Claims data below is from USPTO Patent Application 20070299312. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] This application claims the benefit of foreign priority from Japanese Patent Application No. 2003-094028, filed Mar. 31, 2003, the contents of which are hereby incorporated by reference. This is a divisional application of allowed U.S. application Ser. No. 10/808,309 that was filed Mar. 25, 2004. BACKGROUND OF THE INVENTION [0002] Conventional endoscopes have a large field of view that is in the range of about 90.degree. to 140.degree. so that tissues inside a body can be observed without overlooking lesions. They also change the distance to the object in order to obtain either magnified or reduced-sized images of an object to be observed, and thus have a large depth of field for a fixed focus point so that objects at distances between 3 mm and 50 mm can be observed without refocusing. [0003] Conventional endoscopes also have an image scale factor with an absolute value of about 30 to 50 when the image is displayed on a monitor having a 14-inch screen, which is sufficient to observe diseased tissues. Zoom optical systems are used in order to obtain further magnified images, with the absolute value of the image scale factor being approximately 70 when displayed on a monitor having a 14-inch screen. The zoom optical system typically has a built-in, zoom lens driving mechanism. As a result, the endoscope has an insert tip with an outer diameter that is larger than 10 mm and requires complex operations. Such endoscopes have limited applications. [0004] The manner in which living tissues are observed using a conventional endoscope will now be described with reference to FIG. 1. Living tissues to be observed by a conventional endoscope often include a mucous membrane 1, transparent epithelial cells 2 and underlying parenchymal tissues 3 in which blood vessels run. Light illumination emitted at the endoscope tip part 4 must first pass through the mucous membrane and the transparent epithelial cells before reaching the parenchymal tissues. The illumination light which reaches the parenchymal tissues 3 is scattered by the parenchymal tissues 3. Of the light that is scattered by the parenchymal tissues, most re-enters the epithelial cells. The illumination light is also scattered by cell walls 5 and cell nuclei 6 when it is transmitted through the transparent epithelial cells. The light rays B1, B2 that are scattered by the cell nuclei of the epithelial cells are weak and thus the light rays that are scattered by the parenchymal tissues dominate. Consequently, in a conventional endoscope, only the parenchymal tissues are observed through an objective optical system. [0005] When it becomes difficult to provide a diagnosis of an abnormality by observing images of a tissue, such as when a lesion is very small, a suspicious-looking tissue may be excised during the course of an endoscopic examination. The cells of the excised tissue are then examined under a microscope. Whereas an endoscope generally uses incident illumination from an illumination optical system that is positioned around an objective optical system, a microscope instead generally uses an objective optical system and an illumination optical system that are positioned on opposite sides of a sample. The sample is normally pre-processed in order to make it more suitable for observation, such as by removing the parenchymal tissues by slicing the sample thin in order to reduce scattering and/or by staining the sample in order provide better contrast. [0006] The manner in which a sample is observed using a microscope will now be described with reference to FIG. 2. A prepared sample is fixed onto a cover glass 7 and illuminated from below with light from an illumination system 8. Illumination light rays A1', A2' are diffracted by the cell walls and cell nuclei as they transmit through the sample 9. The diffracted light rays B1', B2' interfere with one another both constructively and destructively, producing interference fringes that provide visible contrast. Thus, one can observe the sample by using an objective optical system 10 placed above the sample. [0007] Laser-scanning-type confocal endoscopes which have a resolution sufficient for cellular observation have been proposed that may be inserted within a living body. These typically use a confocal optical system having a pinhole for passing an Airy disk light pattern at a position that is conjugate to the image plane, and the confocal optical system thus acquires diffraction-limited information for each point of an object in the field of view. A laser beam directed from a light emitting optical system scans the object, and information obtained from the reflected light from the object for each point is combined so as to produce an image representing either a two-dimensional or a three-dimensional object. High resolution can thus be realized not only within the image plane, but also in the depth direction. [0008] It takes from several days to several weeks to identify abnormal tissue using conventional procedures wherein living tissues are excised and examined in vitro. Moreover, a cellular sample that is isolated and fixed for observation is only a tiny part of a removed tissue. Thus, although a cellular sample provides information on cellular structures, it is incapable of providing important functional information, such as information concerning fluid circulation within cells. This is because the circumstances between in vitro and in vivo examination are completely different. Thus, there is a need for magnifying endoscopes that will provide real-time, in vivo observation of intact living cells. [0009] In order to form cellular images of a lesion within a living body, a small-sized image pickup unit is necessary that is provided with an objective optical system with an image scale factor having an absolute value that is nearly as high as that of a microscope and which provides high resolution. The objective optical system used in a conventional endoscope does not meet these requirements. As mentioned previously, in a conventional endoscope as shown in FIG. 1, the illumination light is diffracted by the cell walls and cell nuclei as it transmits through the epithelial cells. The diffracted light rays B1, B2 are weak and the light rays A1, A2 that are scattered by the parenchymal tissues are dominant. Consequently, using a convention endoscope, only data from the parenchymal tissues is imaged by the objective optical system. [0010] Although a conventional objective optical system as used in microscopes is satisfactory as far as providing sufficient imaging performance, such an objective optical system is too large for easy insertion into a living body. Laser-scanning-type confocal endoscopes have a problem in that their scanning speeds are still too slow for real-time, in vivo observations. Thus, as described above, an image pickup unit that meets the requirements for in vivo cellular observation has not yet been realized. BRIEF SUMMARY OF THE INVENTION [0011] The present invention relates to a magnifying image pickup unit suitable for in vivo cellular observation, an endoscope for in vivo cellular observation, and an in vivo cellular observation method. BRIEF DESCRIPTION OF THE DRAWINGS [0012] The present invention will become more fully understood from the detailed description given below and the accompanying drawings, which are given by way of illustration only and thus are not limitative of the present invention, wherein: [0013] FIG. 1 is an illustration to explain a principle of living tissue observation using a prior art endoscope; [0014] FIG. 2 is an illustration to explain a principle of excised sample observation using a microscope; [0015] FIG. 3 shows a configuration of a magnifying image pickup unit according to the present invention, along with other components for displaying endoscopic images; [0016] FIG. 4 shows the spectral wavelength distribution of an image detected by an image pickup unit according to the present invention; [0017] FIG. 5 shows a magnified image of cells that have been stained for observation according to an embodiment of the present invention; [0018] FIG. 6 shows the appearance of cells in the background that overlap cells of interest in the foreground; [0019] FIG. 7 shows the spectral transmittance of a wavelength selection filter used in an embodiment of the present invention; [0020] FIG. 8 shows an image in which information from regions other than regions at a desired depth is eliminated; [0021] FIG. 9 shows the spectral transmittance of another wavelength selection filter used in an embodiment of the present invention; Continue reading... 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