Time-based imaging

• US 8,403,862 B2
• Filed: 12/22/2008
• Issued: 03/26/2013
• Est. Priority Date: 12/20/2007
• Status: Active Grant

• Current Assignee: Yeda Research and Development Co. Ltd. (Weizmann Institute of Science)
• Original Assignee: Yeda Research and Development Co. Ltd. (Weizmann Institute of Science)
• Inventors: Grinvald, Amiram, Nelson, Darin, Primack, Harel
• Primary Examiner(s): DOUGHERTY, SEAN PATRICK
• Application Number:
  US12/340,889
• Publication Number:
  US 20090163827A1
• Time in Patent Office: 1,555 Days
• Field of Search: 351/200, 351/206, 351/221, 435/288.7, 600/310, 600/317, 600/318, 600/323, 600/324, 600/476, 600/477, 600/544, 600/558
• US Class Current: 600/558
• CPC Class Codes: A61B 3/1225 using coherent radiation

Abstract

A method includes directing toward a portion of a subject'"'"'s body a first pulse of electromagnetic energy. While the portion is in a functional state due to the first pulse, a second pulse is directed toward the portion. At a second-pulse time, reflected energy due to the second pulse is detected. While the portion is in a functional state due to the first and second pulses, a third pulse is directed toward the portion. At a third-pulse time, energy of the third pulse, reflected from the portion, is detected. In response to detecting the pulses at the second-pulse time and the third-pulse time, a characteristic of the portion is quantified resulting from (a) the functional state due to the first pulse and (b) the functional state due to the first and second pulses. A clinical state of the subject is identified. Other embodiments are described.

Claims

1. A method for diagnosing a clinical state of a portion of a body of a subject, comprising:

(1) causing the portion to enter a functional state, by directing toward the portion a first pulse of electromagnetic energy;

(2) while the portion is in the functional state due to the first pulse of electromagnetic energy, directing toward the portion a second pulse of electromagnetic energy;

(3) detecting with a detecting device, at a second-pulse time, energy of the second pulse of electromagnetic energy that is reflected from the portion;

(4) while the portion is in a functional state due to the first and second pulses of electromagnetic energy, directing toward the portion a third pulse of electromagnetic energy;

(5) detecting with the detecting device, at a third-pulse time, energy of the third pulse of electromagnetic energy that is reflected from the portion;

(6) in response to detecting the energy of the second pulse of electromagnetic energy that is reflected from the portion at the second-pulse time and detecting the energy of the third pulse of electromagnetic energy that is reflected from the portion at the third-pulse time,

quantifying a characteristic of the portion resulting from (a) the functional state due to the first pulse of electromagnetic energy and (b) the functional state due to the first and second pulses of electromagnetic energy; and

(7) identifying a clinical state of the subject in response to quantifying the characteristic of the portion.

2. The method according to claim 1, wherein:

the first pulse of electromagnetic energy includes a first flash of light, and step (1) comprises directing the first flash of light toward the portion;

the second pulse of electromagnetic energy includes a second flash of light, and step (2) comprises, while the portion is in a functional state due to the first flash of light, directing the second flash of light toward the portion;

the second-pulse time includes a second-flash time, and step (3) comprises detecting, at the second-flash time, light of the second flash of light that is reflected from the portion;

the third pulse of electromagnetic energy includes a third flash of light, and step (4) comprises, while the portion is in a functional state due to the first and second flashes of light, directing toward the portion the third flash of light;

the third-pulse time includes a third-flash time, and step (5) comprises detecting, at a third-flash time, light of the third flash of light that is reflected from the portion; and

step (6) comprises,

in response to detecting, at the second-flash time, light of the second flash of light that is reflected from the portion, and detecting, at the third-flash time, light of the third flash of light that is reflected from the portion,

quantifying a characteristic of the portion resulting from (a) the functional state due to the first flash of light and (b) the functional state due to the first and second flashes of light.

3. The method according to claim 2, wherein the portion of the body includes a retina of the subject and wherein directing the first, second, and third flashes of light toward the portion of the body comprises directing the first, second, and third flashes of light toward the subject'"'"'s retina.

4. The method according to claim 3, wherein identifying the clinical state of the subject comprises identifying a clinical state of a part of a body of the subject selected from the group consisting of:

a brain, a cardiovascular system, and a nervous system.

5. The method according to claim 3, wherein detecting the light of the second and third flashes of light reflected from the retina comprises detecting the light of the second and third flashes of light reflected from the retina using a detecting device selected from the group consisting of:

a fundus camera, a CCD, and an ophthalmoscope.

6. The method according to claim 3, further comprising detecting, at a first-flash time, light of the first flash of light that is reflected from the retina while the retina is in a state that is not a functional state due to a flash of light, and wherein quantifying the characteristic of the retina comprises quantifying a characteristic of the retina resulting from (a) the functional state due to the first flash of light, (b) the functional state due to the first and second flashes of light, and (c) the state that is not a functional state due to a flash of light.

7. The method according to claim 3, wherein directing the first, second, and third flashes of light toward the retina comprises directing the first, second, and third flashes of light toward the retina, each of the flashes of light having a duration of less than 1 ms.

8. The method according to claim 3, wherein directing the first, second, and third flashes of light toward the retina comprises directing the first, second, and third flashes of light toward the retina, each of the flashes of light having a duration of 0.1 ms to 10 ms.

9. The method according to claim 3, wherein directing the first, second, and third flashes of light toward the retina comprises directing the first, second, and third flashes of light toward the retina, a time interval between directing the first and the second flashes being equal to a time interval between directing the second and third flashes.

10. The method according to claim 9, wherein directing the first, second, and third flashes of light toward the retina comprises directing the first, second, and third flashes of light toward the retina, a time interval between directing the first and the second flashes being between 10 ms and 300 ms.

11. The method according to claim 9, wherein directing the first, second, and third flashes of light toward the retina comprises directing the first, second, and third flashes of light toward the retina, a time interval between directing the first and the second flashes being between 300 ms and 10 s.

12. The method according to claim 9, wherein directing the first, second, and third flashes of light toward the retina comprises directing the first, second, and third flashes of light toward the retina, a time interval between directing the first and the second flashes being between 1 ms and 20 ms.

13. The method according to claim 12, wherein directing the first, second, and third flashes of light toward the retina comprises directing the first, second, and third flashes of light toward the retina, a time interval between directing the first and the second flashes being between 1 ms and 10 ms.

14. The method according to claim 3, wherein directing the first, second, and third flashes of light toward the retina comprises directing the first, second, and third flashes of light toward the retina, a time interval between directing the first and the second flashes being different from a time interval between directing the second and third flashes.

15. The method according to claim 14, further comprising directing one or more additional flashes of light toward the retina between directing the second and third flashes of light toward the retina.

16. The method according to claim 3, wherein identifying the clinical state of the subject comprises identifying a clinical state of an eye of the subject.

17. The method according to claim 16, wherein identifying the clinical state of the subject comprises identifying glaucoma of a retina of the subject.

18. The method according to claim 16, wherein identifying the clinical state of the subject comprises identifying a clinical state of a retina of the subject selected from the group consisting of:

age related macular degeneration, and diabetic retinopathy.

19. The method according to claim 3, wherein step (3) comprises obtaining a second-flash image of the retina based on the light of the second flash of light that is reflected from the retina, and wherein step (5) comprises obtaining a third-flash image of the retina based on the light of the third flash of light that is reflected from the retina.

20. The method according to claim 19,

wherein step (6) comprises:

processing the second-flash and third-flash images of the retina to obtain a first differential image of the retina;

identifying a region of interest (ROI) of the differential image; and

computing a value that is representative of a darkness of the ROI of the differential image.

21. The method according to claim 20, wherein processing the second-flash and third-flash images of the retina to obtain a first differential image of the retina comprises dividing the third-flash image by the second-flash image.

22. The method according to claim 20, wherein processing the second-flash and third-flash images of the retina to obtain a first differential image of the retina comprises subtracting the second-flash image from the third-flash image.

23. The method according to claim 20, further comprising:

at a first-flash time, detecting light of the first flash of light that is reflected from the retina;

obtaining a first-flash image of the retina based on the light of the first flash of light that is reflected from the retina; and

obtaining a second differential image of the retina by processing the first-flash image of the retina and an image selected from the group consisting of;

the second-flash and third-flash images of the retina.

24. The method according to claim 23, further comprising:

identifying a region of interest (ROI) of the second differential image; and

computing a value that is representative of a darkness of the ROI of the second differential image.

25. The method according to claim 19,

wherein step (6) comprises:

(a) identifying an ROI in the second-flash image;

(b) identifying an outer region of interest (OROI) in the second-flash image;

(c) computing a value (i-in) that is representative of an intensity of the ROI of the second-flash image;

(d) computing a value (i-out) that is representative of an intensity of the OROI of the second-flash image;

(e) computing an extent to which i-in and i-out in the second-flash image are distinct;

(f) identifying an ROI in the third-flash image;

(g) identifying an outer region of interest (OROI) in the third-flash image;

(h) computing a value (i-in) that is representative of an intensity of the ROI of the third-flash image;

(i) computing a value (i-out) that is representative of an intensity of the OROI of the third-flash image;

(j) computing an extent to which i-in and i-out in the third-flash image are distinct; and

(k) quantifying a relationship between (I) the extent to which i-in and i-out in the second-flash image are distinct, and (II) the extent to which i-in and i-out in the third-flash image are distinct.

26. The method according to claim 25, wherein step (e) comprises computing a ratio relating i-in to i-out in the second-flash image, and wherein step (j) comprises computing a ratio relating i-in to i-out in the third-flash image.

27. The method according to claim 25, wherein step (e) comprises computing an arithmetic difference between i-in and i-out in the second-flash image, and wherein step (j) comprises computing an arithmetic difference between i-in and i-out in the third-flash image.

28. The method according to claim 25, wherein step (c) comprises computing a mean intensity of the ROI in the second-flash image, wherein step (d) comprises computing a mean intensity of the OROI in the second-flash image, wherein step (h) comprises computing a mean intensity of the ROI in the third-flash image, and wherein step (i) comprises computing a mean intensity of the OROI in the third-flash image.

29. The method according to claim 25, wherein step (c) comprises computing a median intensity of the ROI in the second-flash image, wherein step (d) comprises computing a median intensity of the OROI in the second-flash image, wherein step (h) comprises computing a median intensity of the ROI in the third-flash image, and wherein step (i) comprises computing a median intensity of the OROI in the third-flash image.

30. The method according to claim 25, wherein identifying the ROI in the second-flash image comprises identifying a portion of the image that corresponds to an optic disk of the subject, and wherein identifying the ROI in the third-flash image comprises identifying a portion of the image that corresponds to an optic disk of the subject.

31. The method according to claim 30, wherein identifying the OROI in the second-flash image comprises identifying a strip that surrounds the ROI of the second-flash image, the strip having an area that is within 50% of an area of the ROI of the second-flash image, and wherein identifying the OROI in the third-flash image comprises identifying a strip that surrounds the ROI of the third-flash image, the strip having an area that is within 50% of an area of the ROI of the third-flash image.

32. The method according to claim 30, wherein identifying the OROI in the second-flash image comprises identifying an outer ring that is separated from the ROI of the second-flash image by an inner ring, and wherein identifying the OROI in the third-flash image comprises identifying an outer ring that is separated from the ROI of the third-flash image by an inner ring.

33. The method according to claim 19,

wherein step (6) comprises:

(a) processing the second-flash and the third-flash images to obtain a differential image;

(b) identifying an ROI of an image selected from the group consisting of;

the second-flash and the third-flash images;

(c) identifying an ROI of the differential image, the ROI of the differential image corresponding to the ROI of the selected image;

(d) computing a value (r-in) that is representative of a darkness of the ROI of the differential image;

(e) computing a value (r-out) that is representative of a darkness of an outer region of interest (OROI) surrounding the ROI of the differential image; and

(f) quantifying a relationship between r-in and r-out.

34. The method according to claim 33, wherein quantifying the relationship between r-in and r-out comprises computing a ratio relating r-in to r-out.

35. The method according to claim 33, wherein quantifying the relationship between r-in and r-out comprises computing an arithmetic difference between r-in and r-out.

36. The method according to claim 33, wherein computing r-in comprises computing a mean darkness of the ROI, and wherein computing r-out comprises computing a mean darkness of the OROI.

37. The method according to claim 33, wherein computing r-in comprises computing a median darkness of the ROI, and wherein computing r-out comprises computing a median darkness of the OROI.

38. The method according to claim 33, wherein step (b) comprises identifying a portion of the selected image that corresponds to an optic disk of the subject.

39. The method according to claim 38, wherein identifying the OROI comprises identifying a strip that surrounds the ROI, the strip having an area that is within 50% of an area of the ROI.

40. The method according to claim 38, wherein identifying the OROI comprises identifying an outer ring that is separated from the ROI by an inner ring.

41. The method according to claim 38, wherein quantifying a relationship between r-in and r-out comprises:

computing a ratio relating r-in to r-out; and

subtracting the ratio from 1 to produce a result.

42. The method according to claim 38, wherein identifying the clinical state of the subject comprises identifying that the subject'"'"'s retina is glaucomatous in response to the relationship between r-in and r-out passing a threshold.

43. The method according to claim 42, further comprising identifying a severity of the glaucoma of the retina in response to the relationship between r-in and r-out.