Method of diagnosing impaired blood flow

• US 5,377,681 A
• Filed: 05/13/1994
• Issued: 01/03/1995
• Est. Priority Date: 11/13/1989
• Status: Expired due to Fees

• Current Assignee: University of Florida (State University System of Florida)
• Original Assignee: University of Florida (State University System of Florida)
• Inventors: Drane, Walter E.
• Primary Examiner(s): Stoll, Robert L.
• Assistant Examiner(s): KELLEY, LARA CHAPMAN
• Application Number:
  US08/242,708
• Time in Patent Office: 235 Days
• Field of Search: 424/1.11, 424/4, 424/9, 128/653.4, 128/654
• US Class Current: 600/419
• CPC Class Codes: A61B 6/037 Emission tomography
• CPC Class Codes: A61B 6/507 for determination of haemodynamic parameters, e.g. perfusion CT
• CPC Class Codes: G01T 1/1642 using a scintillation crystal and position sensing photodetector arrays, e.g. ANGER cameras

Abstract

A method of diagnosing impaired blood flow to an organ. The method is especially useful in patients which cannot undergo stress testing due to risk factors.

Claims

1. A method of diagnosing impaired blood flow in an organ of a patient which comprises:

a. administering a diagnostically effective amount of non-inert contrast agent to the patient;

b. generating a first series of generally parallel two-dimensional images, spatially separated along one axis of major blood supply to said organ, of the contrast agent in the organ at a first time after administration sufficient for the contrast agent to be extracted to the organ, said first series of said two-dimensional spatially separated images forming a three-dimensional representation of the contrast agent uptake of said organ as of said first time;

c. adding together, on a pixel by pixel basis, substantially all images from said first series, thereby generating a two-dimensional first composite image from the first series of two-dimensional spatially separated images, such that said first composite image represents an image of total contrast agent uptake as of said first time for the organ of interest, oriented along said one axis;

d. generating a second series of generally parallel two-dimensional images, spatially separated along said one axis, of the contrast agent in the organ at a second time after said first series of images sufficient to allow for a detectable decrease of contrast agent in the organ to occur, said second series of two-dimensional spatially separated images forming a three-dimensional representation of the contrast agent retention by the organ of interest as of said second time;

e. adding together, on a pixel by pixel basis, substantially all images from said second series, thereby generating a two-dimensional second composite image from said second series of two-dimensional spatially separated images, such that said second composite image represents an image of the total contrast agent retention for the organ of interest, as of said second time and oriented along said axis;

f. generating a two-dimensional third composite image by subtracting said two-dimensional second composite image from said two-dimensional first composite image to determine the degree of decrease of contrast agent from the organ, said third composite image representing an image of total contrast agent washout between said first time and said second time, indicating the status of the arterial blood supply along said axis; and

g. displaying the two-dimensional third composite image.

5. The method as in any of claims 1, 2, or 4, wherein the contrast agent is used in a CT instrument.

6. The method of claim 5, wherein the contrast agent is selected from the group consisting of ionic and non-ionic iodinated contrast agents.

7. The method of claim 6, wherein the contrast agent is selected from the group consisting of iothalamate sodium and iopamidol.

8. The method as in any of claims 1, 2, or 4, wherein the contrast agent is used in a PET instrument.

9. The method of claim 8, wherein the contrast agent is selected from the group consisting of ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F.

10. The method as in any of claims 1, 2, or 4, wherein the contrast agent is used in an MRI instrument.

11. The method of claim 10, wherein the contrast agent is selected from the group consisting of ¹⁵⁷ Gd, ⁵⁵ Mn, ¹⁶² Dy, ⁵² Cr, and ⁵⁶ Fe.

12. The method as in any of claims 1, 2, or 4, wherein the contrast agent is used in a SPECT instrument.

13. The method of claim 12, wherein the contrast agent is a boronic acid adduct of technetium dioxime.

14. The method of claim 13, wherein the boronic acid adduct of the technetium dioxime is ^99m Tc-teboroxime.

15. The method as in either of claims 1 or 2, wherein the organ diagnosed is selected from the group consisting of the heart and the brain.

16. The method as in either of claims 1 or 2, wherein the first series of images are generated from about 10 seconds to about 30 minutes after administration of the contrast agent.

17. The method as in either of claims 1 or 2, wherein the first series of images are generated from about 30 seconds to about 20 minutes after administration of the contrast agent.

18. The method as in either of claims 1 or 2, wherein the first series of images are generated from about 1 minute to about 15 minutes after administration of the contrast agent.

19. The method as in either of claims 1 or 2, wherein the second series of images are generated from about 12 minutes to about 200 minutes after administration of the contrast agent.

20. The method as in either of claims 1 or 2, wherein the second series of images are generated from about 15 minutes to about 100 minutes after administration of the contrast agent.

21. The method as in either of claims 1 or 2, wherein the second series of images are generated from about 17 to about 80 minutes after administration of the contrast agent.

22. The method of claim 5, wherein the contrast agent is administered from about 5 to about 100 grams.

23. The method of claim 5, wherein the contrast agent is administered from about 10 to about 80 grams.

24. The method of claim 5, wherein the contrast agent is administered from about 30 to about 60 grams.

25. The method of claim 8, wherein the contrast agent is administered from about 1 to about 300 mCi.

26. The method of claim 8, wherein the contrast agent is administered from about 20 to about 100 mCi.

27. The method of claim 8, wherein the contrast agent is administered from about 30 to about 70 mCi.

28. The method of claim 10, wherein the contrast agent is administered from about 1 to about 60 grams.

29. The method of claim 10, wherein the contrast agent is administered from about 2 to about 30 grams.

30. The method of claim 10, wherein the contrast agent is administered from about 5 to about 10 grams.

31. The method of claim 12, wherein the contrast agent is administered from about 10 to about 100 mCi.

32. The method of claim 12, wherein the contrast agent is administered from about 20 to about 40 mCi.

33. The method of claim 12, wherein the contrast agent is administered from about 30 to about 40 mCi.

34. The method as in any of claims 1, 2, or 4, wherein the first and second images are tomographic images.

35. The method of claims 1, 2, or 4, wherein the contrast agent is administered intravenously.

36. The method as in any of claims 1, 2, or 4, wherein the contrast agent is used in a gamma camera instrument.

2. A method of diagnosing impaired blood flow in an organ of a patient at rest which comprises:

a. administering a diagnostically effective amount of non-inert contrast agent to the at-rest patient;

b. generating a first series of generally parallel two-dimensional images, spatially separated along one axis of major blood supply to said organ, of the contrast agent in the organ at a time after administration sufficient for the contrast agent to be extracted to the organ, said first series of two-dimensional spatially separated images forming a three-dimensional representation of the contrast agent uptake by the organ as of said first time;

c. adding together, on a pixel by pixel basis, substantially all images from said first series, thereby generating a two-dimensional first composite image from said first series of two-dimensional spatially separated images such that said first composite image represents an image of total at-rest contrast agent uptake by said organ as of said first time for said organ and oriented along said one axis;

d. generating a second series of generally parallel two-dimensional images, spatially separated along said one axis, of the contrast agent in the organ at a second time after said first series of images sufficient to allow for a detectable decrease of said contrast agent in the organ to occur, said second series of two-dimensional spatially separated images forming a three-dimensional representation of the contrast agent retention of said organ of interest as of said second time;

e. adding together, on a pixel by pixel basis, substantially all images from said second series, thereby generating a two-dimensional second composite image from said second series of two-dimensional spatially separated images, such that said second composite image represents an image of total contrast agent retention for said organ of interest as of said second time and oriented along said one axis;

f. generating a two-dimensional third composite image by subtracting said two-dimensional second composite image from said two-dimensional first composite image to determine the degree of decrease of contrast agent from the organ, said third composite image representing an image of total contrast agent washout between said first time and said second time, indicating the status of at-rest arterial blood supply of just said organ of interest and oriented along said one axis of major blood supply; and

g. displaying the two-dimensional third composite image.

3. The method of claim 2, further including the steps of:

a. after generating the third composite image, assigning a first of a series of display scale values to the areas of maximum decrease of contrast agent from the organ on the third composite image, with the remaining display scale values being assigned in sequence to the values of any remaining areas of the third composite image, to form a non-normalized composite image; and

b. multiplying each picture element of the non-normalized image by a constant, comprising the quantity of whole organ decrease of contrast agent from the organ, to form a normalized composite image.

4. A method of diagnosing coronary artery disease in a patient at rest which comprises:

a. administering a diagnostically effective amount of non-inert contrast agent to the at-rest patient;

b. generating a first series of generally parallel two-dimensional images, spatially separated along one axis of major blood supply, of the contrast agent in the heart of the at-rest patient at a first time after administration sufficient for the contrast agent to be extracted to the heart, said first series of two-dimensional spatially separated images forming a three-dimensional representation of resting blood flow to the heart of said patient;

c. adding together, on a pixel by pixel basis, substantially all images from said first series, thereby generating a two-dimensional first composite image from said first series of two-dimensional spatially separated images, said first composite image representing an image of total contrast agent retention for just the heart as of said first time and oriented along said one axis of major blood supply;

d. generating a second series of two-dimensional images, spatially separated along said one axis of major blood supply, of the contrast agent in said heart at a time after said first series of images sufficient to allow for a detectable decrease of contrast agent in the heart to occur, said second series of two-dimensional spatially separated images forming a three-dimensional representation of contrast agent retention as of said second time in the heart;

e. adding together, on a pixel by pixel basis, substantially all images from said second series, thereby generating a two-dimensional second composite image from said second series of two-dimensional spatially separated images, said second composite image representing an image of total contrast agent retention for just the heart as of said second time and oriented along said axis of major blood supply;

f. generating a two-dimensional third composite image by subtracting said two-dimensional second composite image from said two-dimensional first composite image to determine the degree of decrease of contrast agent from the heart, said third composite image representing an image of total contrast agent washout, indicating the status of coronary arteries of the heart, oriented along the axis of major blood supply; and

g. displaying the two-dimensional third composite image.

37. A method of diagnosing coronary artery disease in a patient at rest, comprising the steps of

a. administering intravenously a diagnostically effective amount of a contrast agent to said at-rest patient;

b. generating a first series of two-dimensional images of said contrast agent in the myocardium of said patient at a first time after administration sufficient for said contrast agent to be extracted to said myocardium, said images being spatially separated along one axis of major blood supply, said first series of two-dimensional spatially separated images forming a three-dimensional representation of contrast agent uptake in the myocardium as of said first time;

c. adding together, on a pixel by pixel basis, substantially all of said two-dimensional images from said first series, whereby is generated a two-dimensional first composite image from said first series of two-dimensional spatially separated images, said first composite image representing an image of total contrast agent uptake for just the myocardium, as of said first time and oriented along said one axis of major blood flow;

d. generating a second series of two-dimensional images of said myocardium of said patient at a second time after said first series of images sufficient to allow for a detectable decrease of said contrast agent in said myocardium, said second series of images being spatially separated along said one axis, said second series of images forming a three-dimensional representation of the contrast agent retention in the myocardium of said contrast agent as of said second time;

e. adding together, on a pixel by pixel basis, substantially all of said two-dimensional images from said second series, whereby is generated a two-dimensional second composite image from said second series of two-dimensional spatially separated images, said second composite image representing an image of total contrast agent retention for just the myocardium, as of said second time and oriented along said one axis of major blood supply;

f. comparing said first image with said second image to evaluate the degree of decrease of said contrast agent in said myocardium of said patient by generating a two-dimensional third composite image by subtracting said second composite image from said first composite image to determine the degree of decrease of said contrast agent from said myocardium, said third composite image representing an image of total washout of said contrast agent from the myocardium between said first time and said second time, thereby indicating the status of blood flow in the coronary arteries of the heart, oriented along said one axis of major blood supply; and

g. displaying said two-dimensional third composite image.

38. The method of claim 37 further comprising the steps of

a. after generating said third composite image, assigning a first of a series of display scale values to the areas of maximum decrease of said contrast agent from said myocardium on said third composite image, with the remaining said display scale values being assigned in sequence to the values of any remaining areas of said third composite image, to form a non-normalized composite image;

and

b. multiplying each picture element of the non-normalized image by a constant, comprising the quantity of decrease throughout the entire said myocardium of said contrast agent, to form a normalized composite image.

39. The method of claim 37 wherein the images are formed using a computerized tomography instrument.

40. The method of claim 39 wherein the contrast agent is selected from the group consisting of ionic and non-ionic iodinated contrast agents.

41. The method of claim 40 wherein the contrast agent is selected from the group consisting of Conray®

and Isovue®

.

42. The method of claim 37 wherein the image is formed by the use of a PET instrument.

43. The method of claim 42 wherein said contrast agent is selected from the group consisting of ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F.

44. The method of claim 37 wherein the image is formed by the use of an MRI instrument.

45. The method of claim 43 wherein said contrast agent is selected from the group consisting of ¹⁵⁷ Gd, ⁵⁵ Mn, ¹⁶² Dy, ⁵² Cr and ⁵⁶ Fe.

46. The method as in claim 37 wherein the image is formed by the use of a SPECT instrument.

47. The method of claim 46 wherein the contrast agent is a boronic acid adduct of technetium dioxime.

48. The method of claim 47 wherein the boronic acid adduct of the technetium dioxime is ^99m Tc-teboroxime.

49. The method of claim 37 wherein the first series of images are generated from about 10 seconds to about 30 minutes after administration of the contrast agent.

50. The method of claim 37 wherein the first series of images are generated from about 30 seconds to about 20 minutes after administration of the contrast agent.

51. The method of claim 37 wherein the first series of images are generated from about 1 minute to about 15 minutes after administration of the contrast agent.

52. The method of claim 37 wherein the second series of images are generated from about 12 minutes to about 200 minutes after administration of the contrast agent.

53. The method of claim 37 wherein the second series of images are generated from about 15 minutes to about 100 minutes after administration of the contrast agent.

54. The method of claim 37 wherein the second series of images are generated from about 17 to about 80 minutes after administration of the contrast agent.