Spectral bio-imaging of the eye

• US 6,276,798 B1
• Filed: 05/10/1999
• Issued: 08/21/2001
• Est. Priority Date: 09/29/1998
• Status: Expired due to Fees

• Current Assignee: Applied Spectral Imaging Ltd.
• Original Assignee: Applied Spectral Imaging Ltd.
• Inventors: Horn, Eli, Adel, Mike, Gil, Tamir, Cabib, Dario, Buckwald, Robert A.
• Primary Examiner(s): MANUEL, GEORGE C
• Application Number:
  US09/307,569
• Time in Patent Office: 834 Days
• Field of Search: 351/205, 351/206, 351/221, 348/262, 348/263, 348/264, 348/393, 356/345, 356/346
• US Class Current: 351/206
• 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 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• CPC Class Codes: A61B 5/0275 using tracers, e.g. dye dilution
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• 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: G01J 2003/467 Colour computing
• CPC Class Codes: G01J 3/2823 Imaging spectrometer
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01J 3/462 Computing operations in or between colour spaces; Colour management systems
• CPC Class Codes: G01J 3/502 using a dispersive element, e.g. grating, prism
• CPC Class Codes: G01J 3/51 using colour filters

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 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 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, thereby providing an image enhancing the spectral signatures of the eye tissue.

2. The method of claim 1, wherein said spectral imager is selected from the group consisting of a filters based spectral imager, a monochromator based spectral imager and an interferometer based spectral imager.

3. The method of claim 2, 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.

4. The method of claim 3, 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.

5. The method of claim 3, further comprising the step of correcting spatial and spectral information for movements of the eye tissue via a spatial registration and spectral correction procedures.

6. The method of claim 1, wherein said optical device is selected from the group consisting of a fundus camera and a funduscope.

7. The method of claim 1, 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.

8. The method of claim 7, 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.

9. The method of claim 1, wherein said light used for illuminating the eye tissue is selected from the group consisting of coherent light, white light, filtered light, ultraviolet light, infrared light and a light having a small wavelength range.

10. The method of claim 1, 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, lens, nerve fiber layer, choroid, choroidal layer, choroidal blood vessel, pigment epithelium and Bruch'"'"'s membrane.

11. The method of claim 1, wherein the eye tissue includes a blood vessel the method is for detecting and mapping the oxygenation level of hemoglobin along the blood vessel.

12. The method of claim 1, wherein step (c) is effected using a mathematical algorithm which computes a Red-Green-Blue color image using predefined wavelength ranges.

13. The method of claim 1, 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, xanthophyll and melanin.

14. The method of claim 1, 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, enhancing hemoglobin oxygen saturation level, enhancing melanoma lesions and enhancing hemangioma lesions.

15. The method of claim 1, wherein said spectral imager is selected from the group consisting of a filters based spectral imager, a monochromator based spectral imager and an interferometer based spectral imager.

16. The method of claim 15, wherein step (b) includes:

(i) collecting incident light simultaneously from all pixels of said object 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.

17. The method of claim 16, 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.

18. The method of claim 16, further comprising the step of correcting spatial and spectral information for movements of the eye tissue via a spatial registration and spectral correction procedures.

19. 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.

20. The method of claim 19, wherein said medical condition is selected from the group consisting of diabetic retinopathy, ischemia of the eye, glaucoma, macular degeneration, CMV eye infection, melanoma lesions, hemangioma lesions, retinitis, choroidal ischemia, acute sectorial choroidal ischemia, ischemic optic neuropathy, and corneal and iris problems.

21. 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.

22. 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.

23. 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.

24. The method of claim 23, 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.

25. The method of claim 24, 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.

26. The method of claim 25, 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.

27. The method of claim 25, further comprising the step of correcting spatial and spectral information for movements of the eye tissue via a spatial registration and spectral correction procedures.

28. The method of claim 23, wherein said optical device is selected from the group consisting of a fundus camera and a funduscope.

29. The method of claim 23, 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.

30. The method of claim 29, 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.

31. The method of claim 23, 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.

32. The method of claim 23, 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, lens, nerve fiber layer, choroid, choroidal layer, choroidal blood vessel, pigment epithelium and Bruch'"'"'s membrane.

33. The method of claim 23, wherein the eye tissue includes a blood vessel the method is for detecting and mapping the oxygenation level of hemoglobin along the blood vessel.

34. The method of claim 23, wherein step (c) is effected using a mathematical algorithm which computes a Red-Green-Blue color image using predefined wavelength ranges.

35. The method of claim 23, wherein step (c) is effected using a mathematical algorithm which computes a gray scale image using predefined wavelength ranges.

36. The method of claim 23, 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, xanthophyll and melanin.

37. The method of claim 25, 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, enhancing hemoglobin oxygen saturation level, enhancing melanoma lesions and enhancing hemangioma lesions.

38. 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.

39. The method of claim 38, 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.

40. 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.

41. 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;

(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.

42. A spectral bio-imaging method for enhancing blood vessels 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 tissues 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;

(c) employing an algorithm highlighting a spectral signature of blood vessels; and

(d) generating an image enhancing the blood vessels.

43. An apparatus for providing a display of an image presenting an eye tissue in which blood vessels are enhanced by a color or intensity according to a spectral signature specific thereto, the apparatus 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 enhancing the spectral signature of blood vessels in the eye tissue.

44. A spectral bio-imaging method for extracting a spectral signature of a first portion of a layer of an object including at least two layers, each of said at least two layers has different spectral characteristics, the method comprising the steps of:

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

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

(c) using said continuous spectrum of light of each pixel of the object for generating a spectral image of the object in which the first portion is identifiable;

(c) identifying in said spectral image the first portion of the layer and a second portion being adjacent said first portion; and

(d) accounting for spectral characteristics of said second layer, extracting the spectral signature of the first portion.

45. The method of claim 44, wherein said object is an ocular fundus, said at least two layers include a retinal layer and a choroidal layer and said first portion is selected from the group consisting of a retinal blood vessel and a choroidal blood vessel.

46. The method of claim 45, wherein said spectral signature is indicative of an oxygenation state of said first portion.

47. The method of claim 46, further comprising the step of marking a mark indicative of said oxygenation state of said first portion on said spectral image in context of said first portion.

48. The method of claim 47, wherein said mark is a numerical value.

49. The method of claim 44, wherein said spectral signature is indicative of an oxygenation state of said first portion.

50. The method of claim 44, wherein said step of extracting the spectral signature of the first portion includes averaging over a plurality of said pixels.

51. The method of claim 44, wherein said optical device is selected from the group consisting of a fundus camera and a funduscope.

52. The method of claim 44, wherein said continuous spectrum of light represents light selected from the group consisting of, light reflected from the object and light scattered from the object.

53. The method of claim 44, wherein said light used for illuminating the object is selected from the group consisting of coherent light, white light, filtered light, ultraviolet light and a light having a small wavelength range.

54. A method of evaluating a medical condition of a patient comprising the step of extracting a spectral signature of a retinal or choroidal blood vessel of a retina or choroid of an eye by:

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

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

(c) using said continuous spectrum of light of each pixel of the eye for generating a spectral image of the eye in which the retinal or choroidal blood vessel is identifiable;

(c) identifying in said spectral image the retinal or choroidal blood vessel and a tissue being adjacent to the retinal or choroidal blood vessel;

(d) accounting for spectral characteristics of said tissue, extracting the spectral signature of the retinal or choroidal blood vessel; and

(e) using said spectral signature to evaluate the medical condition of the patient.

55. The method of claim 54, wherein said medical condition is selected from the group consisting of diabetic retinopathy, ischemia of the eye, glaucoma, macular degeneration, CMV eye infection, melanoma lesions, hemangioma lesions, retinitis, choroidal ischemia, acute sectorial choroidal ischemia, ischemic optic neuropathy, and corneal and iris problems.

56. An apparatus for providing a display of an image presenting an eye tissue and a marking of an oxygenation state of at least one blood vessel therein, the apparatus 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;

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; and

further by marking in context of the at least one blood vessel the oxygenation state thereof.