Method and apparatus for reflected imaging analysis

• US 6,104,939 A
• Filed: 01/25/1999
• Issued: 08/15/2000
• Est. Priority Date: 10/23/1995
• Status: Expired due to Term

• Current Assignee: Intellectual Property MVM B.V.
• Original Assignee: Cytometrics, Inc.
• Inventors: Groner, Warren, Nadeau, Richard G.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/236,112
• Time in Patent Office: 568 Days
• Field of Search: 600/310, 600/322, 600/473, 600/476, 600/479, 356/39-42, 356/364, 356/369, 356/445, 382/128, 382/130, 382/133, 382/134, 382/274
• US Class Current: 600/322
• CPC Class Codes: A61B 5/0261 using optical means, e.g. infrared light
• CPC Class Codes: A61B 5/14535 for measuring haematocrit
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: G01N 15/05 in blood
• CPC Class Codes: G01N 15/06 Investigating concentration of particle suspensions by weighing G01N5/00; investigating sedimentation of particle suspensions G01N15/04; investigating individual particles G01N15/10
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 2015/016 White blood cells
• CPC Class Codes: G01N 2015/018 Platelets
• CPC Class Codes: G01N 2015/1497 Particle shape

Abstract

Method and apparatus for reflected imaging analysis. Reflected imaging is used to perform non-invasive, in vivo analysis of a subject'"'"'s vascular system. A raw reflected image (110) is normalized with respect to the background to form a corrected reflected image (120). An analysis image (130) is segmented from the corrected reflected image to include a scene of interest for analysis. The method and apparatus can be used to determine such characteristics as the hemoglobin concentration per unit volume of blood, the number of white blood cells per unit volume of blood, a mean cell volume, the number of platelets per unit volume of blood, and the hematocrit. Cross-polarizers can be used to improve visualization of the reflected image.

Claims

1. A method for in vivo analysis of blood, comprising:

(1) imaging blood in reflection to produce a raw image from a depth less than a multiple scattering length;

(2) applying a correction to the raw reflected image to form a corrected image;

(3) segmenting a scene from the corrected image to form an analysis image; and

(4) analyzing the analysis image using Beer'"'"'s Law to determine a concentration characteristic of the blood.

2. The method of claim 1, wherein step (2) comprises:

(a) applying a first wavelength filter to the raw reflected image to form a first filtered image;

(b) applying a second wavelength filter to the raw reflected image to form a second filtered image;

(c) taking the negative logarithm of the quotient obtained by dividing the first filtered image by the second filtered image to form the corrected image.

3. The method of claim 2, wherein the first wavelength filter is centered at a first wavelength located at an isobestic point.

4. The method of claim 2, wherein the first wavelength filter is centered at a first wavelength of 550 nm and the second wavelength filter is centered at a second wavelength of 650 nm.

5. The method of claim 1, wherein step (2) comprises applying a velocity correction so that a moving portion of the raw image is extracted from a stationary portion of the raw image to form the corrected image.

6. The method of claim 2, wherein step (3) comprises:

(a) applying an optical intensity criterion to the corrected image.

7. The method of claim 6, wherein step (3) further comprises:

(b) applying a size criterion to the corrected image.

8. The method of claim 7, wherein the size criterion is used to segment large vessels into the analysis image, wherein large vessels are of sufficient size so that a plurality of red blood cells flow side-by-side through them.

9. The method of claim 7, wherein the size criterion is used to segment small vessels into the analysis image, wherein small vessels are of a size so that red blood cells flow substantially single file through them.

10. The method of claim 7, wherein step (3) further comprises:

(c) applying a shape criterion to the corrected image.

11. The method of claim 1, wherein step (3) comprises using spatial frequency to segment the scene from the corrected image.

12. The method of claim 1, wherein step (4) comprises:

(a) determining a mean reflected light intensity of the analysis image; and

(b) converting the mean reflected light intensity of the analysis image into a hemoglobin concentration per unit volume of blood.

13. The method of claim 1, further comprising the step of:

counting white blood cells in the analysis image to determine a number of white blood cells per unit volume of blood.

14. The method of claim 1, further comprising the step of:

determining a mean cell volume from the analysis image.

15. The method of claim 1, further comprising the step of:

counting platelets in the analysis image to determine a number of platelets per unit volume of blood.

16. The method of claim 1, further comprising the step of:

measuring a volume of cells per unit volume of blood in the analysis image to determine hematocrit.

17. The method of claim 1, wherein step (4) comprises the steps of

(a) determining a mean reflected light intensity of the analysis image;

and

(b) converting the mean reflected light intensity of the analysis image into a hemoglobin concentration per unit volume of blood (Hb); and

wherein said method comprises the further steps of;

(5) measuring a volume of cells per unit volume of blood in the analysis image to determine hematocrit (Hct); and

(6) determining a mean cell volume (MCV) from the analysis image.

18. The method of claim 17 further comprising:

(5) determining a red blood cell count (RBC) from the equation

space="preserve" listing-type="equation">RBC=Hct/MCV.

19. The method of claim 17, further comprising:

(5) determining a mean cell hemoglobin concentration (MCHC) from the analysis image.

20. The method of claim 19, further comprising:

(5) determining a mean cell hemoglobin from the equation

space="preserve" listing-type="equation">MCH=MCV×

MCHC.

21. The method of claim 1, wherein the analysis image is segmented from the corrected image so that the analysis image includes capillary plasma.

22. The method of claim 21, wherein step (4) comprises:

(a) determining a mean reflected light intensity of the analysis image; and

(b) converting the mean reflected light intensity of the analysis image into a bilirubin concentration per unit volume of blood.

23. The method of claim 22, wherein step (2) comprises:

(a) applying a first wavelength filter to the raw image to form a first filtered image;

(b) applying a second wavelength filter to the raw image to form a second filtered image;

(c) taking the negative logarithm of the quotient obtained by dividing the first filtered image by the second filtered image to form the corrected image.

24. The method of claim 23, wherein the first wavelength filter is centered at a first wavelength of 450 nm and the second wavelength filter is centered at a second wavelength of 600 nm.

25. The method of claim 21, wherein step (4) comprises:

(a) detecting optical contrast produced by a marker introduced into the blood.

26. The method of claim 25, wherein the marker is used to detect compounds in the capillary plasma.

27. A method of claim 25, wherein the marker is used to detect compounds that attach to cells in the blood.

28. The method of claim 21, wherein step (4) comprises:

(a) detecting natural constituents of plasma.

29. The method of claim 21, wherein step (4) comprises:

(a) detecting non-natural components of plasma.

30. An apparatus for analyzing blood in vivo, comprising:

means for imaging blood in reflection to produce a raw image from a depth less than a multiple scattering length;

means for applying a correction to the raw reflected image to form a corrected image;

means for segmenting a scene from the corrected image to form an analysis image; and

means for analyzing the analysis image using Beer'"'"'s Law to determine a concentration characteristic of the blood.

31. A method for in vivo analysis of blood, comprising:

(1) imaging blood in reflection to produce a raw image from a depth less than a multiple scattering length;

(2) applying a first wavelength filter to the raw image to form a first filtered image;

(3) applying a second wavelength filter to the raw image to form a second filtered image;

(4) taking the negative logarithm of the quotient obtained by dividing the first filtered image by the second filtered image to form a corrected image;

(5) segmenting a scene from the corrected image to form an analysis image; and

(6) analyzing the analysis image for a characteristic of the blood.

32. An apparatus for in vivo analysis of blood, comprising:

means for imaging blood in reflection to produce a raw image from a depth less than a multiple scattering length;

a first filter for filtering the raw image at a first wavelength to form a first filtered image;

a second filter for filtering the raw image at a second wavelength to form a second filtered image;

means for taking the negative logarithm of the quotient obtained by dividing the first filtered image by the second filtered image to form a corrected image;

means for segmenting a scene from the corrected image to form an analysis image; and

means for analyzing the analysis image for a characteristic of the blood.

33. A method for in vivo analysis of blood, comprising:

(1) imaging blood in reflection to produce a raw image from a depth less than a multiple scattering length;

(2) applying a correction to the raw image to form a corrected image;

(3) segmenting a scene from the corrected image to form an analysis image using spatial frequency to segment the scene from the corrected reflected image; and

(4) analyzing the analysis image for a characteristic of the blood.

34. An apparatus for analyzing blood in vivo, comprising:

means for imaging blood in reflection to produce a raw image from a depth less than a multiple scattering length;

means for applying a correction to the raw image to form a corrected image;

means for segmenting a scene from the corrected image to form an analysis image using spatial frequency; and

means for analyzing the analysis image to determine a characteristic of the blood.

35. A method for in vivo analysis of blood, comprising:

(1) imaging blood in reflection to produce a raw image from a depth less than a multiple scattering length;

(2) applying a correction to the raw image to form a corrected image;

(3) segmenting a scene from the corrected image to form an analysis image that includes capillary plasma;

(4) determining a mean light intensity of the analysis image; and

(5) converting the mean light intensity of the analysis image into a bilirubin concentration per unit volume of blood.

36. An apparatus for analyzing blood in vivo, comprising:

means for imaging blood in reflection to produce a raw image from a depth less than a multiple scattering length;

means for applying a correction to the raw image to form a corrected image;

means for segmenting a scene from the corrected image to form an analysis image that includes capillary plasma;

means for determining a mean light intensity of the analysis image; and

means for converting the mean light intensity of the analysis image into a bilirubin concentration per unit volume of blood.

37. A method for in vivo analysis of blood, comprising:

(1) imaging blood in reflection to produce a raw image from a depth less than a multiple scattering length;

(2) applying a correction to the raw image to form a corrected image;

(3) segmenting a scene from the corrected image to form an analysis image that includes capillary plasma; and

(4) detecting optical contrast produced by a marker introduced into the blood to thereby permit analyzing the analysis image for a characteristic of the blood.

38. A method for in vivo analysis of blood, comprising:

(1) imaging blood in reflection to produce a raw image from a depth less than a multiple scattering length;

(2) applying a correction to the raw image to form a corrected image;

(3) segmenting a scene from the corrected image to form an analysis image that includes capillary plasma; and

(4) detecting non-natural components of plasma to thereby permit analyzing the analysis image for a characteristic of the blood.

39. Apparatus for measuring an absorbing object located within and below the surface of a body, comprising:

a light source for directing light having a first plane of polarization onto and beneath the surface of the body along a first predetermined illumination light path such that the light is reflected from a subsurface region of the body behind the object to be measured;

a detector for detecting the portion of light reflected from the subsurface region of the body;

an analyzer having a second plane of polarization substantially orthogonal to said first plane of polarization, said analyzer being disposed in a second predetermined imaging light path between the object to be imaged and said detector;

wherein the light portion transmitted through said analyzer appears to the detector as emanating from a transmission light source located behind the object to be measured; and

measuring means coupled to an output of said detector for measuring optical characteristics of the detected light as a function of the relationship between the light reflected from the subsurface region of the body behind the object to be measured and that is not absorbed by the object to be measured and the reflected light after absorption by the object to be measured.

40. Apparatus according to claim 39, wherein the body comprises the microvascular system within a living body, and the object to be measured comprises blood cells contained within a vessel of said microvascular system.

41. Apparatus according to claims 40, wherein said measuring means comprises means for measuring said optical characteristics of the detected light as a function of Beer'"'"'s law to determine a concentration characteristic of said blood cells contained within the vessel of said microvascular system.

42. Apparatus according to claim 39, wherein the body comprises the microvascular system within a living body, and the object to be measured comprises blood flowing within a vessel of said microvascular system.