Spectral bio-imaging of the eye

• US 6,556,853 B1
• Filed: 11/20/1998
• Issued: 04/29/2003
• Est. Priority Date: 12/12/1995
• Status: Expired due to Fees

• Current Assignee: Applied Spectral Imaging Ltd.
• Original Assignee: Applied Spectral Imaging Ltd.
• Inventors: Adel, Michael, Horn, Eli, Cabib, Dario, Buckwald, Robert A.
• Primary Examiner(s): Smith, Ruth S.
• Application Number:
  US09/194,196
• Time in Patent Office: 1,621 Days
• Field of Search: 600/407, 600/473, 600/476, 600/477, 600/310, 600/318, 356/345, 356/346, 356/456, 351/211, 351/206, 351/221, 351/246
• US Class Current: 600/407
• CPC Class Codes: A61B 3/10 Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
• CPC Class Codes: A61B 5/14555 specially adapted for the eye fundus
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61B 5/7257 using Fourier transforms
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6841 In situ hybridisation
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: G01J 2003/2866 Markers; Calibrating of scan
• CPC Class Codes: G01J 3/02 Details
• CPC Class Codes: G01J 3/12 Generating the spectrum; Monochromators
• CPC Class Codes: G01J 3/1256 using acousto-optic tunable filter; acousto-optic elements or systems G02F1/11, G02F1/33
• CPC Class Codes: G01J 3/26 using multiple reflection, e.g. Fabry-Perot interferometer, variable interference filters
• CPC Class Codes: G01J 3/2823 Imaging spectrometer
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01J 3/453 by correlation of the amplitudes
• CPC Class Codes: G01J 3/4535 Devices with moving mirror G01J3/4532 takes precedence
• CPC Class Codes: G01N 2021/6417 Spectrofluorimetric devices
• CPC Class Codes: G01N 2021/6423 Spectral mapping, video display
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6456 : Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6458 : Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 33/5005 : involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/56966 : Animal cells
• CPC Class Codes: G01N 33/582 : with fluorescent label
• CPC Class Codes: G06V 10/88 : Image or video recognition using optical means, e.g. reference filters, holographic masks, frequency domain filters or spatial domain filters
• CPC Class Codes: G06V 20/69 : Microscopic objects, e.g. biological cells or cellular parts

Abstract

A spectral bio-imaging method for enhancing pathologic, physiologic, metabolic and health related spectral signatures of an eye tissue, the method comprising the steps of (a) providing an optical device for eye inspection being optically connected to a spectral imager; (b) illuminating the eye tissue with light via the iris, viewing the eye tissue through the optical device and spectral imager and obtaining a spectrum of light for each pixel of the eye tissue; and (c) attributing each of the pixels a color or intensity according to its spectral signature, thereby providing an image enhancing the spectral signatures of the eye tissue.

Claims

1. A method of evaluating a medical condition of a patient comprising the step of enhancing spectral signatures of an eye tissue of the patient by:

(a) providing an optical device for eye inspection being optically connected to a spectral imager;

(b) illuminating the eye tissue of the patient with light via the iris, viewing the eye tissue through said optical device and spectral imager and obtaining a light spectrum for each pixel of the eye tissue;

(c) attributing each of said pixels a color or intensity according to its spectral signature, thereby providing an image enhancing the spectral signatures of the eye tissue; and

(d) using said image to evaluate the medical condition of the patient.

2. The method of claim 1, wherein said medical condition is selected from the group consisting of diabetic retinopathy, ischemia of the eye, glaucoma, macular degeneration, CMV eye infection, retinitis, choroidal ischemia, acute sectorial choroidal ischemia, ischemic optic neuropathy, and corneal and iris problems.

3. An apparatus for providing a display of an image presenting an eye tissue, wherein each pixel in said image is assigned a color or intensity according to a spectral signature of a tissue element from which it is derived, thereby enhancing the spectral signature of the eye tissue comprising:

(a) an optical device for eye inspection being optically connected to a spectral imager;

(b) an illumination source for illuminating the eye tissue with light via the iris; and

(c) an image display device for displaying the image;

wherein the image is realized by viewing the eye tissue through said optical device and spectral imager and obtaining a spectrum of light for each pixel of the eye tissue; and

further by attributing each of said pixels a color or intensity according to its spectral signature, thereby providing the image enhancing the spectral signatures of the eye tissue.

4. A spectral bio-imaging method for obtaining a spectrum of a region of an eye tissue, the method comprising the steps of:

(a) providing an optical device for eye inspection being optically connected to a spectral imager;

(b) illuminating the eye tissue with light via the iris, viewing the eye tissue through said optical device and spectral imager and obtaining a spectrum of light for each pixel of the eye tissue; and

(c) displaying a spectrum associated with said region.

5. A spectral bio-imaging method for enhancing spectral signatures of an eye tissue, the method comprising the steps of:

(a) providing an optical device for eye inspection being optically connected to a high throughput spectral imager;

(b) illuminating the eye tissue with light via the iris, viewing the eye tissue through said optical device and spectral imager and obtaining a spectrum of light for each pixel of the eye tissue; and

(c) attributing each of said pixels a color or intensity according to its spectral signature in a predefined spectral range, thereby providing an image enhancing the spectral signatures of the eye tissue.

6. The method of claim 5, wherein said spectral imager is selected from the group consisting of a wideband filters based spectral imager, decorrelation matched filters based spectral imager, a successively monochromatic illumination based spectral imager and an interferometer based spectral imager.

7. The method of claim 6, wherein step (b) includes:

(i) collecting incident light simultaneously from all pixels of said eye using collimating optics;

(ii) passing said incident collimated light through an interferometer system having a number of elements, so that said light is first split into two coherent beams which travel in different directions inside said interferometer and then said two coherent beams recombine to interfere with each other to form an exiting light beam;

(iii) passing said exiting light beam through a focusing optical system which focuses said exiting light beam on a detector having a two-dimensional array of detector elements;

(iv) rotating or translating one or more of said elements of said interferometer system, so that an optical path difference between said two coherent beams generated by said interferometer system is scanned simultaneously for all said pixels; and

(v) recording signals of each of said detector elements as function of time using a recording device to form a spectral cube of data.

8. The method of claim 7, wherein said two-dimensional array is selected from the group consisting of a video rate CCD, a cooled high dynamic range CCD, an intensified CCD and a time gated intensified CCD.

9. The method of claim 7, further comprising the step of correcting spatial and spectral information for movements of the eye tissue via a spatial registration and spectral correction procedures.

10. The method of claim 5, wherein said optical device is selected from the group consisting of a fundus camera and a funduscope.

11. The method of claim 5, wherein said spectrum of light represents light selected from the group consisting of, light reflected from the eye tissue, light scattered from the eye tissue and light emitted from the eye tissue.

12. The method of claim 11, wherein said light emitted from said eye tissue is selected from the group consisting of administered probe fluorescence, administered probe induced fluorescence and auto-fluorescence.

13. The method of claim 5, wherein said light used for illuminating the eye tissue is selected from the group consisting of coherent light, white light, filtered light, ultraviolet light and a light having a small wavelength range.

14. The method of claim 5, wherein said eye tissue is selected from the group consisting of eye retina, a retinal blood vessel an optic disk, an optic cup, eye macula, fovea, cornea, iris, nerve fiber layer and choroidal layer.

15. The method of claim 5, wherein the eye tissue includes a blood vessel the method is for detecting and mapping the oxygenation level of hemoglobin along the blood vessel.

16. The method of claim 5, wherein step (c) is effected using a mathematical algorithm which computes a Red-Green-Blue color image using predefined wavelength ranges.

17. The method of claim 5, wherein step (c) is effected using a mathematical algorithm which computes a gray scale image using predefined wavelength ranges.

18. The method of claim 5, wherein said spectral signature and, as a result, said color is affected by a substance selected from the group consisting of hemoglobin, cytochromes, oxidases, reductases, flavins, nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, collagen, elastin and melanin.

19. The method of claim 5, wherein enhancing the spectral signatures of the eye tissue includes an enhancement selected from the group consisting of enhancing arteries, enhancing veins, enhancing hemoglobin concentration and enhancing hemoglobin oxygen saturation level.

20. A method of evaluating a medical condition of a patient comprising the step of enhancing spectral signatures of an eye tissue of the patient by:

(a) providing an optical device for eye inspection being optically connected to a high throughput spectral imager;

(b) illuminating the eye tissue of the patient with light via the iris, viewing the eye tissue through said optical device and spectral imager and obtaining a light spectrum for each pixel of the eye tissue;

(c) attributing each of said pixels a color or intensity according to its spectral signature in a predefined spectral range, thereby providing an image enhancing the spectral signatures of the eye tissue; and

(d) using said image to evaluate the medical condition of the patient.

21. The method of claim 20, wherein said medical condition is selected from the group consisting of diabetic retinopathy, ischemia of the eye, glaucoma, macular degeneration, CMV eye infection, retinitis, choroidal ischemia, acute sectorial choroidal ischemia, ischemic optic neuropathy, and corneal and iris problems.

22. An apparatus for providing a display of an image presenting an eye tissue, wherein each pixel in said image is assigned a color or intensity according to a spectral signature of a tissue element from which it is derived, thereby enhancing the spectral signature of the eye tissue comprising:

(a) an optical device for eye inspection being optically connected to a spectral imager;

(b) an illumination source for illuminating the eye tissue with light via the iris; and

(c) an image display device for displaying the image;

wherein the image is realized by viewing the eye tissue through said optical device and spectral imager and obtaining a spectrum of light for each pixel of the eye tissue and further by attributing each of said pixels a color or intensity according to its spectral signature in a predefined spectral range, thereby providing the image enhancing the spectral signatures of the eye tissue.

23. A spectral bio-imaging method for enhancing spectral signatures of at least two eye tissues, each of a different spectral signature, the method comprising the steps of:

(a) providing an optical device for eye inspection being optically connected to a spectral imager;

(b) illuminating the eye tissues with light via the iris, viewing the eye tissues through said optical device and spectral imager and obtaining a spectrum of light for each pixel of the eye tissues; and

(c) selecting spectral ranges highlighting the different spectral signatures of each of the at least two eye tissues; and

(d) generating an image enhancing the different spectral signatures of the at least two eye tissues.