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    • 专利摘要:
      APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCEMENT AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM, MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS, is an invention, and is an ocular device. an image of a patient's eye, which includes an optical head which includes image optics, light source optics and a camera housing with a perimeter that houses the video camera optics and the light source optics, an slit lamp and chin support device that includes an adjustable headrest, a movable base, a control that adjusts the position of the camera housing in relation to the head support and the housing support that mounts the camcorder, a rubber eyeball that provides a the interface between the chamber housing and the patient's eye protruding from the perimeter and a computer system that analyzes images and data for the presence of amyloid in a retina, and other deposits and provides a diagnosis of macular degeneration, disease Alzheimer's disease, head trauma, multiple concussion lesions, neurodegenerative disorders and other eye diseases.
    公开号:BR112013009910A2
    申请号:R112013009910-0
    申请日:2011-10-24
    公开日:2020-09-01
    发明作者:Steven Verdooner
    申请人:Steven Verdooner；
    IPC主号:
    专利说明:

    "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCEMENT AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM, MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS, AND PROVISIONAL DISEASES OF THE NORMAL REQUIREMENTS" american 61 / 406,551Deposited on 10/25/2010, the complete description of which is incorporated herein by reference.
    The detection of beta-amyloid plaques (including amyloids, beta-amyloid peptides) and other features of pathology and anatomy of the retina or brain is often unattainable, without the use of specialized contrast agents, or autofluorescence techniques. Although druses and amyloid-containing plaques may be visible on the retina with a variety of imaging techniques, specifically beta-amyloid plaques (including plaques in other forms, such as amyloid peptides), located on druses, or other amyloid-containing plaques (or on retina or background in general) are not visible and verifiable as containing amyloid with any retinal imaging modalities with the sole exception of fluorescence / reflection curcumin imaging that was performed in vivo on animals only.
    The device and method can be used to detect amyloid in the retina and brain. This can be achieved only with OCT by identifying an amyloid spectral signature in an OCT data set and or the anatomical location of plaques. Detection can also be achieved by varying the wavelength of the OCT device and analyzing the signal generated to derive an amyloid signal. This can also be achieved through a combination of multi-spectral imaging OCT or the use of multispectral imaging alone or the use of autofluorescence or an OCT contrast agent. In each of the modalities the spectral signature can be obtained by spectral analysis and image processing. Image processing can identify the spectral wavelength and spectral signature identified with amyloid in the retina and brain, using image processing techniques.
    The apparatus and method use a plurality of traditional optical coherence tomography (OCT) and current background imaging techniques for visualizing amyloid in the retina or brain through a combination of optical technology in combination with spectral analysis and image processing . When operating a plurality of OCTs and providing multispectral imaging VOS in a plurality of specific wavelengths a spectral signature of beta-
    Samyloid can be obtained from a data set that uses image processing.
    The apparatus and method use a plurality of different operating modes and configurations, 5 such as a portable instrument or slit lamp, an integrated slit lamp, an integrated bottom chamber, a laser scanning ophthalmoscope, or an optical head ( for example, a bottom chamber) coupled to a separate chin support device.
    The apparatus and method use OCT and / or multi-spectral imaging in combination with proprietary or standard spectral wavelength selection, spectral analysis, and image processing to identify amyloid in the retina (or brain) that makes them visible to a clinical.
    The present invention will be described in exemplary embodiments, but without limitations, illustrated in the accompanying drawings, where as references refer to similar elements, and in which: Figure 1a illustrates a side perspective view of an apparatus for ocular imaging , according to an embodiment of the present invention.
    Figure 1B shows a side perspective view of a camera assembly, according to an embodiment of the present invention.
    Figure 1C shows an upper frontal perspective view of an eyeball, according to an embodiment of the present invention.
    Fig. 1D is an exploded diagram 5 in lateral diagonal perspective of a computer system, according to an embodiment of the present invention.
    Figure 2 illustrates a side perspective view of an ocular imaging apparatus used in combination with a microscope, according to an embodiment of the present invention.
    Figure 3 illustrates a side perspective view of an ocular imaging apparatus that is in motion, according to an embodiment of the present invention.
    Figure 4 is a block diagram of various components that can be used in combination with an ocular imaging apparatus, according to an embodiment of the present invention.
    Figure 5 is a method for diagnosing a disease of the eye in a mammal, according to an embodiment of the present invention.
    Figure 6 is a method for diagnosing an eye disease, in a mammal, according to an embodiment of the present invention.
    Figure 7 is a method for diagnosing an eye disease, in a mammal, according to an embodiment of the present invention.
    Various aspects of illustrative embodiments will be described using terms commonly used by experts in the field, 5 to disclose the substance of their work to other experts in the field. However, it will be apparent to those skilled in the art that the present invention can be practiced with only a few of the aspects described.
    For purposes of explanation, specific numbers, materials and configurations are presented in order to provide a complete understanding of the illustrative embodiments. However, it will be apparent to one skilled in the art that the present invention can be practiced without the specific details. In other examples, well-known features are omitted or simplified, so as not to obscure illustrative embodiments.
    Various operations will be described as multiple discrete operations, in turn, in a way that is most useful for understanding the present invention.
    However, the order of description should not be interpreted as implying that these operations are necessarily dependent on ordering. In particular, these operations do not need to be performed in the order of presentation.
    The expression "in an embodiment" is used repeatedly. The phrase does not generally refer to the same embodiment, however, this is possible. The terms "comprising", "having" and "including" are synonymous, unless the context indicates otherwise.
    Figure 1A illustrates an exploded perspective view of an apparatus 100 for producing an image of an eye, according to an embodiment of the present invention. The image is an image of a beta-amyloid plaque, an amyloid, or a beta-amyloid peptide, or other features of anatomical pathology or in a user's eye or brain. Apparatus 100 detects the beta-amyloid plaque, amyloid or beta-amyloid peptide by a spectral signature. The apparatus 100 performs a projection of maximum and minimum intensity (MIP / MinlP).
    The apparatus for producing an image of an eye 100 includes a video camera 110, optical camera video 112, a camera housing 120 mounted on a slit lamp and an apparatus for supporting the chin 130 and optical light source 140. A video camera 110 is a digital camera, but it can be any type of camera suitable for use with the device to produce an image of an eye 100. The slit lamp and chin support device 130 includes a head support 142, a movable base 144, a control 146, and a support housing 148. The headrest 142 accommodates the patient's chin and forehead in a known fixed position. Head support 142 is provided with a plurality of elevation adjustments to provide a comfortable resting place for the patient's head. The position of the chamber housing 120 in relation to the headrest 5 142 can be adjusted in relatively thick and thin increments using the control 146.
    The apparatus for producing an image of an eye 100 is used in combination with a computer system 150, which is described in more detail in figure 1D. Computer system 150 can be any suitable computer system 150 that can be used in combination with ocular imaging apparatus 100.
    The personal computer 150 forms the center of the apparatus for ocular imaging 100, processing data and controlling the operation of the other components of the apparatus for ocular imaging 100.
    Connected to the personal computer 150 is a video camera
    110. An observation video monitor, which can be the personal computer screen, a slit lamp and chin support device 130, optical light source 140, and the video camera optics 112 are associated with the camera housing 120.
    the personal computer 150 is a relatively compact computer, built-in computer, or tablet computer of relatively high processing power using a standardized operating system and with standardized card slots to interconnect peripheral equipment such as memory cards, video card, printer and a monitor. Personal computer 150 will run custom software, as will be described in more detail below. The monitor or screen of the personal computer will have a high-resolution color graphics capability suitable for displaying images under analysis.
    The scan card accepts a digital file or video input from a 110 video camera and functions as a "capture card", or display. That is, when activated by a signal from the personal computer 150, the digitization card collects the video and / or digital data and images from the camcorder 110 at that instant and stores it in digital data. The digital data produced is stored in memory and made available to the personal computer 150 for analysis.
    Figure 1B shows a side perspective view of a chamber housing 120 of the chin support apparatus 130, according to an embodiment of the present invention. The housing of the camera 120 which contains the video camera 110 optical light source 140 is close to a sectioned eyeball of the EB patient with a C cornea and an R retina.
    The housing 120 can be cylindrical or in any other suitable form. The housing 120 has no forward protruding parts, which prevents accidental direct contact of any part of the imaging apparatus of the eye 100 with the patient's cornea C or facial features during movement of the housing 120 relative to the patient's eyes. This is advantageous since there is no contact with the patient's cornea C to perform the examination and image capture. The outer housing 120 and the lenses are designed to maintain some distance to the C cornea, increasing patient comfort while any test is being performed. A flexible interface such as a rubber cup 180 can be provided at the interface between the box 120 and the patient's EB eyeball.
    The inclusion of the optical light source 140, optical camera 112 and video camera 110 in the camera housing 120 provides a high degree of accessibility. By placing all the elements of the ocular imaging apparatus 100 in a chamber housing 120 it allows an accessible design. In addition, the relatively small design of the ocular imaging device 100 compared to that of a background camera for observation and image capture provides a shorter and more efficient optical path. The compact design and simplicity of the 112, 140 optics reduce production costs and allow greater ease of use for the operator. The design of the ocular imaging apparatus 100 allows images through a smaller pupil compared to a background camera.
    The 110 video camera is relatively compact and incorporates a CCD, color or monochrome CMOS, or multi / hyper-spectral image sensor.
    The patient's focus can also be achieved by focusing 5 internal optical elements of the digital camera. The lens contained inside the camera 100 can be focused automatically or manually by looking at the image displayed on the observation video monitor.
    Alternatively, an electronic auto-focus control system could be provided to automatically adjust the focus of the lens inside the camera
    100. Camcorder 110 may also contain a monochrome or color CCD or CMOS Sensor (not shown).
    Observation optics 112 associated with video camera 110 include lens 170, observation aperture 172, and filter 174. Observation aperture 172 and filter 174 transmit reflected light from retina R to lens 170 and to the video camera
    110. Filter 174 is an infrared enhancement filter (or another filter for other imaging procedures), which improves the contrast of the image seen by the camcorder 110.
    Indo-cyanine green angiography, color background photography, auto fluorescence, or fluorescein angiography, curcumin fluorescence imaging, or other filter sets can be used by the eye imaging device
    100. These filters will be mounted so as to be selectively rotatable inside and outside the axis of vision of the video camera 110 according to the function to be performed. The rotation can be carried out manually or 5 under computer servo control.
    The projection optics 140 of the invention project light onto the R retina, off-axis at an angle to the central axis 176 of lens 170 of video camera 110. Optical projection 140 includes a lamp 141, a group of lens lamp 143, a mirror 145, and a projection aperture 172. A control 1001 is provided to adjust the intensity and position of the lamp 141, either manually or under the control of the computer system.
    150. The control is also used to sequentially control multiple lamps 141, optical shift elements, and motion masks 147, internal LED inversion fixation pointer 1004, and image capture trigger.
    Light from lamp 141 passes through aperture 149 and the lens lamp group assembly 143 which typically has two lenses. The lenses in the lamp lens group 143 concentrate the light output of the lamp 141. The lamp lens group 143 can consist of multiple lenses or a single aspherical lens. The light is then deflected by the mirror 145 which is placed at a critical tilt angle in relation to the video camera 110 and the projection optics 112. The light passes from the mirror 145 past the inversion mask 147 which concentrates the light. The light then passes through a plurality of small pupil masks 1002. The light then passes through the objective lens 1003. The light then passes through cornea C and is projected onto retina R.
    All masks and openings used, such as inversion mask 147 and aperture 149 and 1002, are appropriately sized openings. Although lamp 141 has been described as a generalized LED lamp, it should be noted that lamp 141 can be any source of radiant energy. In one embodiment, lamp 141 is a source of infrared light, and filter specifications 174 are adjusted accordingly to pass the wavelength of lamp 141. Infrared lighting may be particularly desirable for alignment before acquiring images without the problems generated by the lack of pupil dilation. The image can be captured in a relatively dark room with infrared illumination, 2O so that the eye being examined is naturally enlarged. There is also a means for sequentially turning the light source on and off in synchronization with the image capture under each condition, which is a computer system 150, described in figure 1C.
    In another embodiment that addresses the problems caused by the lack of pupil dilation during the examination, the lamp 141 can be fully colored, without reddish color, NIR or other wavelength (based on the desired imaging procedure) during acquisition of the image instead of being kept constantly, thereby preventing the 141 5 lamp energy from narrowing the pupil before the image is captured. Due to the unique design of the 140 projection optics and the image processing capabilities and analysis software used, the useful image data for each image can be collected with minimal pupil dilation. Specifically, the pupils of the eyes being examined can have a diameter of just 2 mm. Projection optics 140 projects light onto the R retina off the axis of the video camera's observation path 110. Another embodiment places an adjustable mask 1002 next to objective lens 1003 that adjusts the patient's pupil to improve the image when the pupil is small.
    Figure 1C shows an upper frontal perspective view of an eyeball 180, according to an embodiment of the present invention.
    Eyeball 180 protrudes out of perimeter 182 at an approximate 10% increase in the approximate degree of 0 ° 184 and 180 ° degrees 186 positions at perimeter 182. More details about eyeball 180 are described in figure 3 and its description.
    Fig. 1D is an exploded diagram in lateral diagonal perspective of a computer system 150, according to an embodiment of the present invention. Said computer system 150 includes a processing unit such as a CPU 151 connected by a bus to a random access memory or RAM 152, a storage device 153, a keyboard 154, a display 155 and a mouse 156. In addition, there is software 157 for data entry that incorporates the device for ocular imaging 100. An example of a computer system 150 can be a Dell computer operated by the Microsoft Windows operating system, or Linux, Macintosh, etc. The invention can also be used on a laptop computer, cell phone, PDA, Apple (™) Mac (™), tablet or other computerized device. The computerized system 150 can also be used in combination with a wireless modem 158 or network interface card 159.
    The various embodiments of the method of the present invention will generally be implemented by a computer by executing a sequence of program instructions to carry out the steps of the method, assuming that all data necessary for processing are accessible to the computer. The sequence of program instructions can be incorporated into a computer program product comprising means that store the program instructions. As will be readily apparent to those skilled in the art, the present invention can be realized in hardware, software, or in a combination of hardware and software. Any type of computer / server system or other device adapted to carry out the methods described here is suitable. A typical combination of hardware and software can be a general purpose computer system with a computer program that, when loaded and executed, performs the method, and variations of the method as described herein.
    Any combination of one or more usable computer or readable computer media may be used. Specific examples of the computer-readable medium may include a hard disk, a random access memory (RAM), a read-only memory (ROM), a programmable read-only memory (EPROM), or flash memory or a portable disk read memory compact (CD-ROM). In the context of this document, a usable or computer-readable computer medium can be any medium that can be used by or in connection with the instruction execution system or apparatus. The code of the computer program to perform the operations of the method in general can be written in any combination of one or more programming languages. The program code can be run entirely on the user's computer, partially on the user's computer, as a software package, partially on the user's computer and partially on a remote computer or entirely on the remote computer or server.
    These computer program instructions can also be stored in a computer-readable medium that can drive a computer or other programmable data-processing device to function in a particular way, such that the instructions stored in the computer-readable medium produce a manufacturing article including means of instructions that implement the function specified in the steps.
    The computer program instruction can also be loaded onto a computer or other programmable data processing device to cause a series of operational steps to be performed on the computer or other programmable device to produce a computer implemented process in such a way that the instructions that run on the computer or other programmable device provide processes to implement the specified functions.
    Figure 2 illustrates a side perspective view of an ocular imaging apparatus 200 used in conjunction with a microscope 260, according to an embodiment of the present invention. Figure 2 illustrates a side perspective view of an ocular imaging apparatus 100 that has all the same components as the ocular imaging apparatus 100 described in figure 1a, except microscope 260 and computer system 150. The apparatus
    .. • 17/29 to produce an image of an eye 200 includes a video camera 210, video camera optics 212, a camera housing 220 mounted on a patient alignment assembly 230 and 5 light source optics 240 The microscope set 230 includes a support 242, a movable base 244, and a housing support
    248. The position of the chamber housing 220 in relation to the headrest 242 can be adjusted in both thin and thick increments using the control 24 6. The microscope 2 60 can be any suitable microscope that can be used in combination with the ocular imaging equipment 200.
    In one embodiment of the apparatus and method, OCT data is presented with the 15 traditional OCT and / or face display modes to produce a plurality of familiar retinal images.
    In an embodiment of the apparatus and method, OCT is performed using a plurality of 20 specific wavelengths that allow visualization of amyloid in the retina and brain. A plurality of OCT data sets are obtained and analysis is performed to identify a plurality of amyloid spectral signature components. These 25 spectral components that correspond to the amyloid are later shown in the OCT data sets that include a face presentation. The spectral characteristics of the signal can be combined with other specific spectral components to provide traditional OCT data sets in combination with the spectral amyloid data set.
    5 In another embodiment of the apparatus and method, a minimum threshold technique in combination with an adaptive spectral window technique is applied to the data sets to provide the visualization of previous features not visible in the OCT data sets. In another embodiment of the device and method, this technique is applied not only for amyloid, but also for other pathologies and also anatomical features of the retina.
    In another embodiment of the apparatus and method, the OCT device is operated at a plurality of different and specific spectral wavelengths to provide the desired signature and information.
    In another embodiment of the apparatus and method, the apparatus and method use multispectral imaging to detect amyloid and other pathology of the retina and features without the use of dyes or contrast agents. In another embodiment of the apparatus and method, this is achieved through multi-spectral optical image and / or autofluorescence techniques in which the specific amyloid signal is identified and displayed.
    In another embodiment of the apparatus and method, curcumin (which binds to amyloid) is used as a contrast agent in combination with OCT to discreetly identify the amyloid. In another embodiment of the apparatus and method, curcumin is used as a contrast agent in combination with optical multispectral imaging and / or autofluorescence to discretely identify amyloid in the retina.
    Another embodiment of the 1O apparatus and method includes a method of diagnosing macular degeneration and other eye diseases in a mammal that administers a fluorescent marker to a mammal to color A [Beta] peptides, obtain the image of the mammalian retina with optical coherence tomography OCT, examining the data sets for colorizing A [Beta] peptides and diagnosing the mammal as having macular degeneration or other eye disease if colored A [Beta] peptides are present.
    Another embodiment of the apparatus and method, in which a fluorescent marker is selected from the group including, but not limited to curcumin, curcumin derivatives, thioflavin S and derivatives, thioflavin T and its derivatives, Congo Red and derivatives, methoxy-X04, Pittsburgh CompoundB (PiB), DDNP, Crisamine-G and their combinations.
    Another embodiment of the apparatus and method, in which the OCT system is used with components including a spectrometer, a fluorescence microscope, a stereoscopic microscope, a mercury arc lamp, a variable wavelength light source, a lamp xenon arc, and an LED, 5 an adjustable light source or scanned source, a closed CCD camera, a color digital camera, a spectral image acquisition system based on tunable acoustic-optical filter, adaptive optics, software image, and their combinations.
    Another embodiment of the device and method, for the prognosis of macular degeneration and other eye disease in a mammal that includes the identification of A [beta] peptides, images of the retina with OCT and / or multi-spectral / autofluorescence imaging, image examination for A [beta] peptides, quantifying the increase / decrease of A [beta] peptides in the retina, compared to a previous diagnosis and providing a prognosis based on the level of A [beta] peptides in the retina, including, but not limited to area, number and volume.
    Another embodiment of the device and method, for the prognosis of macular degeneration and other eye diseases in a mammal, which includes identification of A [beta] peptides, retinal image with OCT and / or multispectral / autofluorescence imaging, examination of images for A [beta] peptides quantifying the increase I decrease of A [beta] peptides in the retina, compared to a previous diagnosis, in combination with a normative database and providing a prognosis based on the level of A [beta] peptides in the retina (including, but not limited to area, number and volume).
    5 Another embodiment of the device and method, for the prognosis of traumatic brain injury and other neurodegenerative diseases in a mammal that includes the identification of A [beta] peptides, retinal image with OCT and / or multi-spectral / autofluorescence imaging, examination of images for Peptides A [beta] quantifying the increase / decrease of A [beta] peptides in the retina, compared to a previous diagnosis, in combination with a normative database and providing a prognosis based on the level of A [beta] peptides on the retina (including, but not limited to area, number and volume).
    Another way of carrying out the apparatus and method is to perform a maximum / minimum intensity projection (MIP / MinIP) and / or in combination with other discrete spectral signatures specific in OCT and / or multi-spectral images for the identification of amyloid in the retina (or brain) and other characteristics of the retina and pathology, including but not limited to choroidal neovascularization. Maximum intensity projection (MIP) and minimum intensity projection (MinIP) are defined as volume execution techniques in which appropriate editing methods are used to define a volume of interest (VOI). The entire set of image data can be used, or the volume can be confined to a region of interest (ROI).
    In an embodiment of the apparatus 5 and method, only the desired characteristics are included or excluded from the VOI and the actual images are generated by projecting the volume of interest in a visualization plan and displaying the maximum verification OCT numbers (for MIP) or the minimum OCT numbers (for MinIP), which are found along the direction of the projection to ensure that an ideal contrast is produced between the low and high contrast structures and the surrounding tissues.
    Figure 3 illustrates a side perspective view of a portable device for ocular imaging 300, according to an embodiment of the present invention. The portable ocular imaging apparatus 300 includes all the same components as the ocular imaging apparatus 100 described in figure 1B and can be used in combination with a microscope 260 (figure 2) or a computer system 150 (figure 1a). The portable ocular imaging device 300 uses a portable housing 310, instead of a camera housing 120 as described in figures 1a and lB, but uses all the same optical and electrical components arranged inside the portable housing
    310.
    The portable apparatus for producing an image of an eye 300 may also use a flexible eyeball 320 which can be attached to the portable apparatus for producing an image of an eye 300, or be used as a disposable, flexible eyeball connecting the end 312 of the apparatus to produce an image of an eye for use in each patient. The flexible eyeball 320 can be made of flexible deflector material 322 such as plastic, rubber, or any other suitable material that gently envelops the patient's eye to create a dark environment and can also be used to keep the eyelids open. patient. The flexible eyeball 320 may have an internal angled spring mechanism 330 that holds the patient's eyelids open. The baffles 322 are flexible to allow adjustable and proper placement around the patient's eye.
    Figure 4 is a block diagram of a plurality of various components 400 that can be used in combination with an ocular imaging apparatus, according to an embodiment of the present invention.
    These components 400 are selected from the group consisting of a spectrometer 405, a fluorescence microscope 410, a stereoscopic microscope 415, a mercury arc lamp 420, a variable wavelength light source 425, a xenon arc lamp 430, an LED light 435, an adjustable light source or scanned source 440, a closed CCD camera 445, a color digital camera 450, a spectral image acquisition system based on tunable acoustic-optical filter 5, a plurality of adaptive optics 460, imaging software 465, and any combinations thereof.
    apparatus 100 is used in combination with one or more contrasting agents that are selected from the group consisting of curcumin, curcumin derivatives, Tioflavin S and derivatives, Tioflavin T and its derivatives, Congo Red and derivatives, methoxy-X04, Pittsburgh CompoundB ( PiB), DDNP, Crisamine-G and their combinations.
    Figure 5 is a method 500 for diagnosing an eye disease in a mammal, according to an embodiment of the present invention.
    Steps in method 500 include administering a contrast agent to a mammal to color one or more Peptides A [beta] 510, obtaining images of the mammalian retina with 520 optical coherence tomography, examining a plurality of data sets of Peptides A [beta] 510 beta] colored 530 and diagnose the mammal as having eye disease if colored Peptides A [beta] are present 540. Administration of a contrast agent to a mammal to color one or more Peptides A [beta] 510 can be performed with one or more contrasting agents selected from the group consisting of curcumin, curcumin derivatives, thioflavin S and derivatives, thioflavin T and derivatives, Congo Red and derivatives, methoxy-X04, Pittsburgh CompoundB (PiB), DDNP, 5 Chrysamine-G and any combinations of these.
    Imaging the mammalian retina with optical coherence tomography 520 can be performed with the apparatus to produce an image of a patient's eye previously described in Figs. lA and lB and their components that include a digital video camera that includes an optical video camera, optical light source and a camera housing with a perimeter that houses the optical video camera and the optical light source, a slit lamp Chinrest and control that includes an adjustable headrest, a movable base, a control that adjusts the position of the camera housing in relation to the head support and the housing support that mounts the camcorder, a rubber eyeball that provides an interface between the chamber housing and the patient's eye that protrudes out of the perimeter and a computer system. The examination of a plurality of data set of colored 530 A [beta] Peptides is typically performed with the computer system previously described in figure 1D. The diagnosis of the mammal as having eye disease if colored Peptides A [beta] are present 540 is frankly a characteristic indication of Peptides A [beta]
    colorful.
    Figure 6 is a method 600 for diagnosing an eye disease in a mammal, according to an embodiment of the present invention.
    5 Method 600 includes administering a fluorescent marker to the mammal to color one or more Peptides A [beta] 610, obtaining images of the mammalian retina with optical coherence tomography 620, examining a plurality of data sets of Peptides A [beta] ] colored 630 and quantify an increase or decrease of Peptides A [beta] in the mammalian retina and provide a prognosis based on a level of Peptides A [beta] 640.
    Administration of a contrast agent to a mammal to color one or more Peptides A [beta] 610 can be performed with one or more contrast agents selected from the group consisting of curcumin, curcumin derivatives, thioflavin S and derivatives, thioflavin T and derivatives, Congo Red and derivatives, methoxy-X04, Pittsburgh CompoundB (PiB), DDNP, Crisamine-G and any combinations thereof. Imaging the mammalian retina with optical coherence tomography 620 can be performed with the apparatus to produce an image of a patient's eye previously described in Figs. lA and lB and their components that include a digital video camera that includes an optical video camera, optical light source and a camera housing with a
    .J 27/29 perimeter that houses the optical video camera and the optical light source, a Chinrest slit lamp and control that includes an adjustable headrest, a movable base, a control that adjusts the position of the camera housing in relation to the head support and the support of the housing that mounts the video camera, a rubber eyeball that provides an interface between the housing of the camera and the patient's eye that protrudes outside the perimeter and a computer system. The examination of a plurality of data set of the colored 630 A [beta] Peptides is typically carried out with the computer system previously described in figure 1D.
    The quantification of an increase or decrease of Peptides A [beta] in the mammalian retina and provide a prognosis based on a level of Peptides A [beta] 640 is typically performed with the computer system previously described in figure lD.
    Figure 7 is a method 700 for diagnosing an eye disease in a mammal, according to an embodiment of the present invention.
    Method 700 comprises administering a fluorescent marker to the mammal to color one or more Peptides A [beta] 710, obtaining retinal images of the mammal with 720 optical coherence tomography, examining a plurality of Peptide A [beta] data sets colored 730 and quantify an increase or
    , '28/29 decrease in Peptides A [beta] in the mammalian retina compared to a previous diagnosis in combination with a normative database and provide a prognosis based on a level of Peptides A [beta] 740.
    5 Administration of a contrast agent to a mammal to color one or more Peptides A [beta] 710 can be performed with one or more contrast agents selected from the group consisting of curcumin, curcumin derivatives, thioflavin S and derivatives, 10 thioflavin T and derivatives, Congo Red and derivatives, methoxy-X04, Pittsburgh CompoundB (PiB), DDNP, Crisamine-G and any combinations thereof. Imaging the mammalian retina with optical coherence tomography 720 can be performed with the apparatus to produce an image of an eye of a patient previously described in Figs. lA and lB and their components, which include a digital video camera that includes an optical video camera, an optical lighting source and a camera housing with a perimeter that houses the optical video camera and the optical lighting source, a Chinrest slot and control that includes an adjustable headrest, a movable base, a control that adjusts the position of the camera housing in relation to the head support and the housing support that mounts the camcorder, a rubber eyeball which provides an interface between the chamber housing and the patient's eye that protrudes out of the perimeter and a computer system. O
    I 29/29 Examination of a plurality of data set of colored Peptides A [beta] 730 is typically performed with the computer system previously described in figure 1D. Quantification of an increase or decrease 5 of Peptides A [beta] in the mammalian retina compared to a previous diagnosis in combination with a normative database and provision of a prognosis based on a level of Peptides A [beta] 740.
    Although the present invention has been related in terms of previous embodiments, those skilled in the art will recognize that the invention is not limited to the described embodiments. The present invention can be practiced with modifications and alterations within the spirit and scope of its 15 claims. Accordingly, the description should be considered as illustrative rather than restrictive in the present invention.
    权利要求:
    Claims (20)
    [1]
    1. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCEMENT AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM, 5 MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS, - characterized by: ocular, characterized by: ocular, and characterized: which includes a digital camera, a plurality of image optics, a plurality of optical illumination sources and a camera housing with a perimeter that houses said optical head and said optical illumination source; - a chin support and control device that includes an adjustable headrest, a movable base, a control that adjusts the position of said camera housing in relation to said headrest and said housing support that mounts said optical head; - a portable set that includes an optical head and manual clamp for operation; - a rubber eyeball that provides an interface between said camera housing and said patient's eye that protrudes out of said perimeter to keep the eyelids open; and - a computer system that includes a real-time viewing window that displays a live video, provides a plurality of alignment devices, processes data, and controls said device that is in communication with said optical head and said video camera and said optical lighting source.
    [2]
    2. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCE AND 5 PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM,
    MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS AND EYE DISEASES ", as claimed in 1, characterized in that said rubber eyeball stands out by approximately 10% increase in an approximate position The degree and an approximate position of 180 degrees to maintain the said eyelids open.
    [3]
    3. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCE AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM,
    MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS, AND EYE DISEASES ", as claimed in 1, characterized in that said computer system is a compact computer, a smart phone, an embedded computer, or a tablet computer.
    [4]
    4. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCE AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM,
    MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS, AND EYE DISEASES ", as claimed in 1, characterized in that said digitalized video card collects a plurality of videos or digital data and images from said video camera and stores said video and said data to be analyzed and processed in one or more plenoptic images, 5 combining a plurality of elements in focus from a plurality of individual images, thus increasing image resolution and quality.
    [5]
    5. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCE AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM,
    MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS, AND EYE DISEASES ", as claimed in 1, characterized in that said device is used in an autofluorescence mode and in combination with one or more contrast agents.
    [6]
    6. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCE AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM,
    MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS, AND EYE DISEASES ", as claimed in 5, characterized in that said contrast agents are selected from the group consisting of curcumin, curcumin derivatives, thio lavine S and derivatives, thioflavin T and its derivatives, CRANAD 3, fluorescein, Indocyanine Green, Congo Red and derivatives, methoxy-X04, Compound Pittsburgh B (PIB), DDNP, Crisamine-G and any combination of these.
    [7]
    7. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCE AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM,
    MACULAR DEGENERATION AND A PLURALITY OF DYSFUNCTIONS 5 NEURODEGENERAT IVAS, AND EYE DISEASES ", as claimed in 1, characterized in that said device is used in combination with one or more components that are selected from the group consisting of a spectrometer, a fluorescence microscope , a stereoscopic, a mercury arc lamp, a variable wavelength light source, a xenon arc lamp, an LED light, an adjustable light source or scanned source, a closed CCD camera, a color digital camera, a spectral image acquisition system of tunable basic acoustic-optical filter, a plurality of adaptive optics, image software and any combination of these.
    [8]
    8. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCEMENT AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM,
    MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS, AND EYE DISEASES ", as claimed in 1, characterized in that said device is used in combination with optical coherence tomography, fluorescein and green indocyanine angiography.
    [9]
    9. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCE AND
    PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM,
    MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERAT IVAS DYSFUNCTIONS AND EYE DISEASES ", as claimed in 1, characterized in that said image 5 shows a beta-amyloid plaque, an amyloid, a druse, an amyloid containing deposit, or a beta-amyloid peptide .
    [10]
    1 O. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCE AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM,
    MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS AND EYE DISEASES ", as claimed in 9, characterized in that said device detects said beta-amyloid plate, said amyloid, said druse, said amyloid containing deposit, or said beta-amyloid peptide by a spectral reflectance signature.
    [11]
    11. "APPARATUS AND METHOD FOR DETECTING AMYLOID IN A RETINA IN A DIAGNOSIS, ADVANCEMENT AND PROGNOSIS OF ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM,
    MACULAR DEGENERATION AND A PLURALITY OF NEURODEGENERATIVE DYSFUNCTIONS, AND EYE DISEASES ", as claimed in 1, characterized in that said device performs a maximum and minimum intensity projection of the optical coherence tomography, auto fluorescence, curcumin imaging, fluorescein and indocyanine angiography , red colorless image and very specific data sets isolate this beta-amyloid plaque, said amyloid, said druse, said amyloid containing deposit, or said beta-amyloid peptide.
    [12]
    12. "A METHOD FOR DIAGNOSISING AN 5 EYE DISEASE IN A MAMMALIAN", characterized by comprising: administering curcumin, curcumin analogues or other fluorescent dye, probe or marker via oral consumption, topical eye drop, or intravenous injection to said mammal to tie and staining one or more Peptides [beta] A; examine said mammalian retina with curcumin fluorescence image, autofluorescence, multi-spectral image, hyperspectral image, fluorescein angiography, ICG angiography and / or optical coherence tomography; examine a plurality of data sets of said [beta] A peptides; and to diagnose said mammal as having said eye disease if said peptides [beta] A spotted, druse, plaques or deposits are present.
    [13]
    13. "A METHOD FOR DIAGNOSING AN EYE DISEASE IN A MAMMALIAN", characterized by comprising: administering curcumin, curcumin analogues or other fluorescent dye, probe or marker via oral consumption, topical eye drops, or intravenous injection to said mammal to tie and stain one or more Peptides [beta] A; examine said mammalian retina with curcumin fluorescence, autofluorescence, multi-spectral image, hyperspectral image, fluorescein angiography, ICG angiography and / or optical coherence tomography; and quantify an increase or decrease of said [beta] A peptides in said mammalian retina compared to a previous diagnosis in combination with a normative disease database and present a prognosis based on a level of said [beta] peptides A, plates, or deposits.
    [14]
    14. "A METHOD TO DIAGNOSE AN ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM, INJURY
    MULTIPLE CONCUSSIVE OR OTHER NEURODEGENERATIVE DISEASE IN A MAMMALIAN ", characterized by comprising: administering curcumin, curcumin analogues or other fluorescent dye, probe or marker via oral consumption, topical eye drop, or intravenous injection to said mammal to tie and spot one or more Peptides [beta] A or deposits, examine said mammalian retina with curcumin fluorescence, autofluorescence, multi-spectral image, hyperspectral image, fluorescein angiography, ICG angiography and / or optical coherence tomography;
    examine a plurality of data sets of said [beta] A peptides; and to diagnose said mammal as having said disease if said peptides [beta] A spotted, 5 druse, plates or deposits are present.
    [15]
    15. "A METHOD TO DIAGNOSE AN ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM, INJURY
    MULTIPLE CONCUSSIVE OR OTHER NEURODEGENERATIVE DISEASE IN A MAMMALIAN ", characterized by comprising: administering curcumin, curcumin analogues or other fluorescent dye, probe or marker via oral consumption, topical eye drop, or intravenous injection to said mammal to tie and spot one or plus Peptides [beta] A or deposits; - examine said mammalian retina with curcumin fluorescence, autofluorescence, multi-spectral imaging, hyperspectral imaging, fluorescein angiography, ICG angiography and / or optical coherence tomography; and quantifying an increase or decrease in said [beta] A peptides in said mammalian retina compared to a previous diagnosis in combination with a disease database in a normative state and presenting a prognosis based on a level of said [beta] A peptides.
    [16]
    16. "A METHOD FOR DIAGNOSING AN ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM, INJURY
    MULTIPLE CONCUSSIVE OR OTHER NEURODEGENERATIVE DISEASE IN A MAMMALIAN ", characterized by understanding: examining this mammalian retina with autofluorescence, multi-spectral image, hyperspectral image, fluorescein angiography, ICG angiography and / or optical coherence tomography; - examine and analyze; a plurality of data sets of said [beta) A peptides, and diagnosing said mammal as having said disease if said [beta] A peptides, plaques or deposits are present.
    [17]
    1 7. "A METHOD FOR DIAGNOSISING AN ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM, INJURY
    MULTIPLE CONCUSSIVE OR OTHER NEURODEGENERATIVE DISEASE IN A MAMMALIAN ", characterized by understanding: examining said mammalian retina with autofluorescence and optical coherence tomography; - examining and analyzing a plurality of data sets of said [beta] A peptides; - analyzing said data of optical coherence tomography to locate within the retina and determine the diagnosis based on the location of amyloid and amyloid containing deposits; quantify the presence of said [beta) A peptides in said mammalian retina as images of autofluorescence and OCT compared to an previous diagnosis in combination with a disease database in a normative state and present a prognosis based on the level of said [beta] A peptides; and diagnose said mammal as having said disease if said [beta] A peptides or 5 deposits are present .
    [18]
    18. "A METHOD FOR DIAGNOSING A DISEASE - FROM ALZHEIMER, CRANIAL TRAUMATISM, INJURY
    MULTIPLE CONCUSSIVE OR ANOTHER NEURODEGENERATIVE DISEASE IN A MAMMALIAN ", characterized by understanding: examining this mammalian retina with autofluorescence; - examining and analyzing a plurality of images and data sets processed to form high resolution plenoptic images of the data sets thus identifying said [beta] A peptides; plaques or deposits; analyzing said autofluorescence data to confirm the diagnosis based on the spectral signature and morphology of amyloid and amyloid containing deposits; quantifying the presence of said [beta] A peptides in said mammalian retina as images with autofluorescence in comparison with a previous diagnosis in combination with a disease database in a normative state and present a prognosis based on a level of said peptides [beta] A; and diagnose said mammal as having said disease if said peptides [ beta] A, plaques or deposits are present.
    [19]
    19. "A METHOD FOR DIAGNOSISING AN ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM, MULTIPLE CONCUSSIVE INJURY OR OTHER NEURODEGENERATIVE DISEASE IN A MAMMALIAN", characterized by understanding: examining this mammal's retina with any combination of image modalities, including image of curcumin, including image curc autofluorescence, OCT, hyperspectral image, multispectral image, fluorescein angiography, ICG angiography, color background image, image without red color; - examine and analyze a plurality of images and data sets, thereby identifying said [beta] A peptides; plates or deposits; - analyze said data to confirm the diagnosis based on the spectral signature and morphology of amyloid and amyloid containing deposits; - examine and analyze a plurality of images and data sets processed to form high resolution plenopic images of the data sets thereby identifying said [beta] A peptides; plates or deposits; quantify the presence of said [beta] A peptides in said mammalian retina as images with autofluorescence compared to a previous diagnosis in combination with a database of
    .J 1 12/13 • disease in normative state and present a prognosis based on a level of said peptides [beta] A; and diagnose the severity of said disease in said mammal based on the generation of an amyloid retina index 5 comprising spectral signature information, background reflectance and fluorescence, intensity, integrated gross density, location on the retina via OCT, geographic location in one or more specific regions of the retina, morphology and 1O regional density.
    [20]
    20. "A METHOD FOR DIAGNOSING AN ALZHEIMER'S DISEASE, CRANIAL TRAUMATISM, INJURY
    MULTIPLE CONCUSSIVE OR OTHER NEURODEGENERATIVE DISEASE IN A MAMMALIAN ", characterized by comprising: 15 examining said mammalian retina with ICG angiography, fluorescein angiography, color background image, and red colorless image; - examining and analyzing a plurality of images and sets of data thus identifying 20 said [beta] A peptides; plates or deposits; - examining and analyzing a plurality of images and data sets processed to form high resolution plenopic images of the data sets thereby identifying said [beta] peptides ] 25 A; plaques or deposits; - analyze said data to confirm the diagnosis based on the spectral signature and morphology of amyloid and amyloid containing deposits;
    quantify the presence of said [beta] A peptides in said mammalian retina as images with ICG angiography compared to a
    5 previous diagnosis in combination with a normative database and present a prognosis based on a level of said peptides [beta] A; and diagnose the severity of said disease in said mammal based on the generation of an index
    10 amyloid retina comprising spectral signature information, background and deposit, intensity,
    integrated gross density, location in the retina via OCT,
    geographic location in a specific region of the retina, morphology and regional density.
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    法律状态:
    2020-10-20| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2020-10-27| B25A| Requested transfer of rights approved|Owner name: NEUROVISION IMAGING LLC (US) |
    2020-11-10| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2020-11-17| B25D| Requested change of name of applicant approved|Owner name: NEUROVISION IMAGING INC. (US) |
    2021-02-23| B11B| Dismissal acc. art. 36, par 1 of ipl - no reply within 90 days to fullfil the necessary requirements|
    2021-11-23| B350| Update of information on the portal [chapter 15.35 patent gazette]|
    优先权:
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    PCT/US2011/057532|WO2012061078A2|2010-10-25|2011-10-24|Apparatus and method for detecting amyloid in a retina in a diagnosis, advancement, and prognosing of alzheimer's disease, traumatic brain injury, macular degeneration and a plurality of neurodegenerative dissorders, and ocular diseases|
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