Optical coherence tomographic detection of cells and compositions

• US 20070038121A1
• Filed: 05/26/2006
• Published: 02/15/2007
• Est. Priority Date: 05/27/2005
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Feldman, Marc, Oh, Jung-Hwan, Milner, Thomas, Mehmet, Cilingiroglu
• Granted Patent: US 7,983,737 B2
• Time in Patent Office: Days
• US Class Current: 600/476
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• CPC Class Codes: A61B 5/0261 using optical means, e.g. infrared light
• CPC Class Codes: A61B 5/0275 using tracers, e.g. dye dilution
• CPC Class Codes: A61B 5/0515 Magnetic particle imaging
• CPC Class Codes: A61B 5/416 the spleen
• CPC Class Codes: A61B 5/6852 Catheters
• CPC Class Codes: A61B 8/06 Measuring blood flow measuring volume flow in general G01F, e.g. G01F1/66, G01F1/72; measuring speed of fluids in general G01P5/00
• CPC Class Codes: A61B 8/13 Tomography A61B8/10, A61B8/12 take precedence; tomography for radiation diagnosis A61B6/02
• CPC Class Codes: G01N 21/1717 with a modulation of one or more physical properties of the sample during the optical investigation, e.g. electro-reflectance
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B

Abstract

Provided herein are systems and methods for the detection of cells and compositions using optical coherence tomography.

Claims

1. A method for detecting a cell, comprising:

applying a magnetic field to the cell, wherein the cell comprises a cellular membrane and a metallic composition and wherein the magnetic field interacts with the metallic composition to cause a change in the cell; and

detecting the cell by detecting the change in the cell caused by the interaction of the magnetic field with the metallic composition, wherein the change is detected using a phase sensitive optical coherence tomographic imaging modality.

2. The method of claim 1, wherein the change in the cell caused by the interaction of the magnetic field with the metallic composition is selected from the group consisting of:

movement of the cell, movement of the metallic composition, a change in the cellular membrane tension level, and a change in the internal strain field of the cell.

3. The method of claim 1, wherein the phase sensitive optical coherence tomographic imaging modality comprises a probe for transmitting and receiving light energy to and from the cell.

4. The method of claim 3, wherein the probe further comprises a magnetic source for applying the magnetic field to the cell.

5. The method of claim 1, wherein the magnetic field is applied to the cell from a magnetic source located external to the subject.

6. The method of claim 1, wherein the metallic composition is located within the cell.

7. The method of claim 1, wherein the metallic composition is targeted to a location on the cellular membrane of the cell.

8. The method of claim 1, wherein the metallic composition has a non-zero magnetic susceptibility.

9. The method of claim 1, wherein the metallic composition comprises a plurality of metallic nanoparticles.

10. The method of claim 9, wherein the nanoparticles are substantially spherical and have a diameter from about 0.1 nanometers (nm) to about 1000.0 nm.

11. The method of claim 9, wherein the nanoparticles are asymmetrical in shape.

12. The method of claim 11, wherein the largest cross sectional dimension of the nanoparticles is from about 0.1 nanometers (nm) to about 1000.0 nm in length.

13. The method of claim 8, wherein the metallic composition comprises a material selected from the group consisting of iron oxide, iron, cobalt, nickel, and chromium.

14. The method of claim 9, wherein the cell is located within a subject and the metallic composition is administered to the subject.

15. The method of claim 14, wherein the cell is a macrophage and wherein at least one nanoparticle is located within the macrophage.

16. The method of claim 15, wherein the macrophage is located in an atherosclerotic plaque within the subject.

17. The method of claim 15, wherein the macrophage is located within the eye of the subject.

18. The method of claim 14, wherein at least one of the nanoparticles is configured to localize to a target site within the subject.

19. The method of claim 18, wherein the target site is a neoplastic cell.

20. The method of claim 18, wherein the target site is an extracellular domain of a protein.

21. The method of claim 18, wherein in the cell comprises the target site, and wherein the cell is located in the subject at an anatomical location selected from the group consisting of a lung, bronchus, intestine, stomach, colon, eye, heart, blood vessel, cervix, bladder, urethra, skin, muscle, liver, kidney, and blood.

22. The method of claim 18, wherein the cell comprises the target site and wherein the cell is selected from the group consisting of a neoplastic cell, a squameous cell, a transitional cell, a basal cell, a muscle cell, an epithelial cell, and a mucosal cell.

23. The method of claim 18, wherein the nanoparticle comprises an antibody or fragment thereof.

24. The method of claim 23, wherein the antibody or fragment thereof is conjugated to the surface of the nanoparticle.

25. The method of claim 18, wherein the nanoparticle comprises a peptide or a fragment thereof.

26. The method of claim 25, wherein the peptide or fragment thereof is conjugated to the surface of the nanoparticle.

27. The method of claim 1, wherein detecting the change in the cell caused by the interaction of the magnetic field with the metallic composition comprises generating a phase sensitive optical coherence tomographic image, wherein the image comprises one or more lines of phase sensitive light energy data captured using the phase sensitive optical coherence tomography modality, and wherein at least one line is captured during the application of the magnetic field.

28. The method of claim 27, wherein generating one or more data line comprises:

generating light energy;

transmitting at least a first portion of the generated light energy onto a reference reflector wherein at least a portion of the transmitted first portion of light energy is reflected by the reference reflector;

transmitting at least a second portion of the generated light energy to contact the cell wherein at least a portion of the light energy that contacts the cell is reflected by the cell;

receiving the light energy reflected by the reference reflector and by the cell;

combining the received light energy from the cell and reference reflector, wherein the received light energy interferes; and

processing the combined light energy to produce the phase sensitive optical coherence data line.

29. The method of claim 28, wherein movement of the cell caused by the interaction of the magnetic field with the metallic composition is detected.

30. The method of claim 28, wherein a change in the cellular membrane'"'"'s tension level or internal strain field caused by the interaction of the magnetic field with the metallic composition is detected.

31. The method of claim 28, wherein the image produced has a phase sensitive resolution of at least about 30.0 nanometers (nm), 25.0 nm, 15.0 nm, 10.0 nm, 5.0 nm, 4.0 nm, 3.0 nm, or 2.0 nm.

32. The method of claim 27, wherein generating one or more data lines comprises:

generating light energy;

transmitting at least a first portion of the generated light energy onto a reference reflector wherein at least a portion of the transmitted first portion of light energy is reflected by the reference reflector;

transmitting at least a second portion of the generated light energy to contact the metallic composition wherein at least a portion of the light energy that contacts the metallic composition is reflected by the composition;

receiving the light energy reflected by the reference reflector and by the composition;

combining the received light energy, wherein the received light energy interferes; and

processing the combined light energy to produce the phase sensitive optical coherence data line.

33. The method of claim 32, wherein movement of the metallic composition caused by the interaction of the magnetic field with the metallic composition is detected.

34. The method of claim 32, wherein the image produced has a phase sensitive resolution of at least about 30.0 nanometers (nm), 25.0 nm, 15.0 nm, 10.0 nm, 5.0 nm, 4.0 nm, 3.0 nm, or 2.0 nm.

35. The method of claim 27, wherein a plurality of phase sensitive light energy data lines are captured and used to construct the image.

36. The method of claim 35, wherein the plurality of phase sensitive light energy data lines are spatially and temporally distinct and wherein the image comprises a B-mode image frame comprising at least two of the lines.

37. The method of claim 35, wherein the plurality of phase sensitive light energy data lines are temporally distinct and wherein the image comprises a M-mode image comprising at least two of the lines.

38. The method of claim 35, wherein at least a first phase sensitive light energy data line is captured prior to the application of the magnetic field, wherein at least a second phase sensitive light energy data line is captured during application of the magnetic field, and wherein the captured lines are used to create the image.

39. The method of claim 35, further comprising:

capturing at least a first phase sensitive light energy data line during the application of the magnetic field, wherein the magnetic field has a first predetermined strength;

capturing at least a second phase sensitive light energy data line during application of a second magnetic field having a second predetermined strength; and

processing the captured lines to create the image.

40. The method of claim 39, wherein the first predetermined strength is less than the second predetermined strength.

41. A method for detecting a cell, comprising:

applying a first time-varying magnetic field to a cell, wherein the cell comprises a cellular membrane and a metallic composition and wherein the first magnetic field interacts with the metallic composition to induce an electrical eddy current within the metallic composition;

applying a second magnetic field to the cell that interacts with the induced eddy current to cause a change in the cell; and

detecting the cell by detecting the change in the cell caused by the interaction of the magnetic field with eddy current, wherein the change is detected using a phase sensitive optical coherence tomographic imaging modality.

42. The method of claim 41, wherein the change in the cell caused by the interaction of the second magnetic field with the eddy current is selected from the group consisting of:

movement of the cell, movement of the metallic composition, a change in the cellular membrane tension level, and a change in the internal strain field of the cell.

43. The method of claim 41, wherein the metallic composition is non-magnetic.

44. The method of claim 43, wherein the metallic composition comprises gold, sliver, or zinc.

45. The method of claim 41, wherein the metallic composition is magnetic.

46. The method of claim 41, wherein the phase sensitive optical coherence tomographic imaging modality comprises a probe for transmitting and receiving light energy to and from the cell.

47. The method of claim 46, wherein the probe further comprises a magnetic source for applying the magnetic field to the cell.

48. The method of claim 41, wherein the magnetic field is applied to the cell from a magnetic source located external to the subject.

49. The method of claim 41, wherein the metallic composition is located within the cell.

50. The method of claim 41, wherein the metallic composition is targeted to location on the cellular membrane of the cell.

51. The method of claim 41, wherein the metallic composition comprises a plurality of metallic nanoparticles.

52. The method of claim 51, wherein the cell is located within a subject and the metallic composition is administered to the subject.

53. A system for detecting a cell, comprising:

a magnet for applying a magnetic field to a cell; and

a phase sensitive optical coherence tomographic imaging modality for detecting the cell while it is in the presence of the magnetic field.

54. The system of claim 53, wherein the phase sensitive optical coherence tomographic imaging modality comprises an probe for transmitting and receiving light energy to and from the cell.

55. The system of claim 54, wherein the probe further comprises the magnet for applying the magnetic field to the cell.

56. The system of claim 53, wherein the magnet of the system is located external to the subject.

57. The system of claim 53, wherein the phase sensitive optical coherence tomographic imaging modality comprises:

a light source, a light splitter, a probe and a reference reflector, wherein light energy generated by the light source can be transmitted to and split by the splitter for transmission to the reference reflector and to the probe, wherein the probe is configured to transmit at least a portion of the light energy transmitted thereto into a target cell and to receive reflected light energy from the target cell, and wherein the reference reflector is configured to reflect at least a portion of the light energy transmitted thereto; and

a processor for processing reflected light energy from the reference reflector and light energy received by the probe to produce a phase sensitive optical coherence tomography image.

58. The method of claim 57, wherein the probe further comprises a single optical fiber and a rotary reflector in optical communication with the single optical fiber.

59. The system of claim 57, wherein the probe comprises the reference reflector.

60. A method for detecting a composition comprising metal, the method comprising:

applying a magnetic field to the composition, wherein the magnetic field interacts with the composition; and

detecting the composition using a phase sensitive optical coherence tomographic imaging modality.

61. The method of claim 60, wherein the composition is located inside of a cell.

62. The method of claim 60, wherein the composition is connected to the external surface of the cellular membrane of a cell.

63. The method of claim 61, wherein the composition is detected using the phase sensitive optical coherence tomographic imaging modality by detecting a change in the cell.

64. The method of claim 63, wherein the change in the cell that is detected is selected from the group consisting of:

movement of the cell, movement of the metallic composition, a change in the cellular membrane tension level, and a change in the internal strain field of the cell.

65. The method of claim 62, wherein the composition is detected using the phase sensitive optical coherence tomographic imaging modality by detecting a change in the cell.

66. The method of claim 65, wherein the change in the cell that is detected is selected from the group consisting of:

movement of the cell, movement of the metallic composition, a change in the cellular membrane tension level, and a change in the internal strain field of the cell.

67. The method of claim 61, wherein the composition is connected to non-cellular biological matter.

68. The method of claim 67, wherein the non-cellular biological matter is selected from the group consisting of:

a protein, a lipid, a peptide, and a nucleic acid.

69. The method of claim 60, wherein the composition comprises a paramagnetic or magnetic material.

70. A method for detecting a composition, the method comprising:

applying a magnetic field to the composition, wherein the magnetic field interacts with the composition; and

detecting the composition using a phase sensitive optical coherence tomographic imaging modality.

71. The method of claim 70, wherein the composition comprises a magnetic or paramagnetic material.