Systems and methods for imaging a sample

• US 6,980,299 B1
• Filed: 10/16/2002
• Issued: 12/27/2005
• Est. Priority Date: 10/16/2001
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: de Boer, Johannes Fitzgerald
• Primary Examiner(s): Toatley, Jr., Gregory J.
• Assistant Examiner(s): Lyons, Michael A.
• Application Number:
  US10/272,171
• Time in Patent Office: 1,168 Days
• Field of Search: 356/479, 356/497
• US Class Current: 356/497
• CPC Class Codes: G01B 9/02083 characterised by particular signal processing and presentation
• CPC Class Codes: G01B 9/02091 Tomographic interferometers, e.g. based on optical coherence

Abstract

A system and method for imaging a sample are provided. In particular, a first combination of light and a second combination of light are received, in which a first cross correlation function is associated with the first combination and a second cross correlation function is associated with the second combination. Each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination. In an exemplary embodiment of the present invention, the first cross correlation function is transformed into a first complex cross spectral density and the second cross correlation function is transformed into a second complex cross spectral density. Moreover, a third complex cross spectral density can be determined which is approximately an average of the first complex cross spectral density and the second complex cross spectral density.

Claims

1. A method for obtaining information regarding a sample, comprising the steps of:

receiving a first combination of light and a second combination of light, wherein a first cross spectral density is associated with the first combination and a second cross spectral density is associated with the second combination, wherein each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and wherein a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination; and

determining a third cross spectral density which is at least approximately an average of the first cross spectral density and the second cross spectral density for imaging the sample.

2. The method of claim 1, further comprising the step of determining a particular width of a Gaussian spectra of a source of associated with the first combination and the second combination based on the third cross spectral density.

3. The method of claim 2, wherein the determining step comprises the substeps of:

determining an area of the third cross spectral density;

determining an average amplitude of the third cross spectral density; and

determining a width of the third cross spectral density, wherein the particular width is based on the area, the average amplitude, and the width of the third cross spectral density.

4. The method of claim 2, further comprising the steps of

determining a correction curve based on a ratio between the Gaussian spectra and the third cross spectral density;

modifying the first cross spectral density as a function of the correction curve; and

modifying the second cross spectral density as a function of the correction curve.

5. The method of claim 4, wherein the step of modifying the first cross spectral density comprises the substep of multiplying the first cross spectral density by the correction curve to obtain a first modified cross spectral density, and wherein the step of modifying the second complex cross spectral density comprises the substep of multiplying the second cross spectral density by the correction curve to obtain a second modified complex cross spectral density.

6. The method of claim 5, further comprising the steps of:

transforming the first modified cross spectral density into a first modified cross correlation function;

transforming the second modified cross spectral density into a second modified cross correlation function; and

determining a coherence function envelope of the sample based on the first modified cross correlation function and the second modified cross correlation function.

7. The method of claim 1, wherein the first cross spectral density is transformed from a first cross correlation function, and the second cross spectral density is transformed from a second cross correlation function.

8. The method of claim 1, wherein at least one of the first cross spectral density and the second cross spectral density is complex.

9. A method for obtaining information regarding a sample, comprising the steps of:

receiving a first combination of light and a second combination of light, wherein a first cross spectral density is associated with the first combination and a second cross spectral density is associated with the second combination, wherein each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and wherein a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination; and

determining a particular width of a Gaussian spectra of a source associated with the first combination and the second combination based on a third cross spectral density which is at least partially based on the first cross spectral density and the second cross spectral density, wherein the particular width is used for imaging the sample.

10. A method for obtaining information regarding a sample, comprising the steps of:

receiving a first combination of light and a second combination of light, wherein a first cross spectral density is associated with the first combination and a second cross spectral density is associated with the second combination, wherein each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and wherein a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination; and

modifying the first cross spectral density to implement a phase shift of the first cross spectral density.

11. The method of claim 10, further comprising the step of modifying the second cross spectral density to implement a phase shift of the second cross spectral density.

12. The method of claim 10, further comprising the step of generating an image of the sample based on the first cross spectral density and the second cross spectral density.

13. The method of claim 12, further comprising the step of determining an average variance associated with the image.

14. The method of claim 13, wherein the step of modifying the first cross spectral density comprises the substep of multiplying the first cross spectral density by a predetermined factor to obtain a first modified cross spectral density, and wherein the predetermined factor includes a particular quadratic phase shifting term.

15. The method of claim 14, further comprising the steps of:

generating a modified image of the sample based on at least the first modified cross spectral density; and

determining an average variance associated with the modified image.

16. The method of claim 15, further comprising the steps of:

modifying the particular quadratic phase shifting term to obtain a modified predetermined factor;

multiplying the first cross spectral density by the modified predetermined factor to obtain a second modified cross spectral density;

generating a further modified image of the sample based on at least the second modified cross spectral density; and

determining an average variance associated with the further modified image.

17. A method for obtaining information regarding a sample, comprising the steps of:

receiving a first combination of light and a second combination of light, wherein a first cross correlation function is associated with the first combination and a second cross correlation function is associated with the second combination, wherein each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and wherein a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination;

modifying the first cross correlation function to obtain a modified cross correlation function;

determining an average of the modified cross correlation function over a first electronic receiver frequency range which is different than a second electronic receiver frequency range of the first cross correlation function; and

transforming the first modified cross correlation function into a first cross spectral density.

18. The method of claim 17, further comprising the steps of:

modifying the second cross correlation function to obtain a further modified cross correlation function;

determining an average of the further cross correlation function over the first frequency range; and

transforming the further cross correlation function into a second cross spectral density.

19. The method of claim 18, further comprising the step of determining a third complex cross spectral density which is at least approximately an average of the first cross spectral density and the second cross spectral density.

20. The method of claim 19, further comprising the step of determining a particular width of a Gaussian spectra of a source associated with the first combination and the second combination based on the third cross spectral density.

21. The method of claim 20, wherein the determining step comprises the substeps of:

determining an area of the third cross spectral density;

determining an average amplitude of the third cross spectral density; and

determining a width of the third cross spectral density, wherein the particular width is based on the area, the average amplitude, and the width of the third cross spectral density.

22. The method of claim 20, further comprising the steps of

determining a correction curve based on a ratio between the Gaussian spectra and the third cross spectral density;

modifying the first cross spectral density as a function of the correction curve; and

modifying the second cross spectral density as a function of the correction curve.

23. The method of claim 22, wherein the step of modifying the first cross spectral density comprises the substep of multiplying the first cross spectral density by the correction curve to obtain a first modified cross spectral density, and wherein the step of modifying the second cross spectral density comprises the substep of multiplying the second cross spectral density by the correction curve to obtain a second modified cross spectral density.

24. The method of claim 23, further comprising the steps of:

transforming the first modified cross spectral density into a third modified cross correlation function;

transforming the second modified cross spectral density into a fourth modified cross correlation function; and

determining a coherence function envelope of the sample based on the third modified cross correlation function and the fourth modified cross correlation function.

25. The method of claim 18, further comprising the step of modifying the first cross spectral density to implement a phase shift of the first cross spectral density.

26. The method of claim 25, further comprising the step of modifying the second cross spectral density to implement a phase shift of the second cross spectral density.

27. The method of claim 25, further comprising the step of generating an image of the sample based on the modified cross correlation function and the further modified cross correlation function.

28. The method of claim 27, further comprising the step of determining an average variance associated with the image, wherein the average variance associated with the image is used to determine an optimum phase correction.

29. The method of claim 28, wherein the modifying step comprises the substep of multiplying the first cross spectral density by a predetermined factor to obtain a first modified cross spectral density, wherein the predetermined factor includes a particular quadratic phase shifting term.

30. The method of claim 29, further comprising the steps of:

transforming the first modified cross spectral density into a third cross correlation function;

generating a modified image of the sample based on at least the third cross correlation function; and

determining an average variance associated with the modified image, wherein the average variance associated with the modified image is used to determine the optimum phase correction.

31. The method of claim 30, further comprising the steps of:

modifying the particular quadratic phase shifting term to obtain a modified predetermined factor;

multiplying the first cross spectral density by the modified predetermined factor to obtain a second modified cross spectral density;

transforming the second modified cross spectral density into a fourth cross correlation function;

generating a further modified image of the sample based on at least the fourth cross correlation function; and

determining an average variance associated with the further modified image, wherein the average variance associated with the further modified image is used to determine the optimum phase correction.

32. A method for obtaining information regarding a sample, comprising the steps of:

receiving a first combination of light and a second combination of light, wherein a first cross spectral density is associated with the first combination and a second cross spectral density is associated with the second combination, wherein each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and wherein a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination; and

modifying an electrical receiver frequency range of the first cross spectral density from a first frequency range to a second frequency range.

33. The method of claim 32, further comprising the steps of:

modifying a frequency range of the second cross spectral density from the first frequency range to the second frequency range.

34. The method of claim 33, wherein the first frequency range is between about 600 Hz and about 1 kHz, and wherein the second frequency range is between about −

200 Hz and about 200 Hz.

35. An system for obtaining information regarding a sample, comprising:

a computer arrangement, which when executing a software program, is configured to;

receive a first combination of light and a second combination of light, wherein a first cross spectral density is associated with the first combination and a second cross spectral density is associated with the second combination, wherein each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and wherein a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination; and

determine a third cross spectral density which is at least approximately an average of the first cross spectral density and the second cross spectral density.

36. The system of claim 35, wherein the computer arrangement is further configured to determine a particular width of a Gaussian spectra of a source of the first combination and the second combination based on the third cross spectral density.

37. The system of claim 36, wherein the computer arrangement is further configured to:

determine an area of the third cross spectral density,

determine an average amplitude of the third cross spectral density, and

determine a width of the third cross spectral density, wherein the computer arrangement determines the particular width based on the area, the average amplitude, and the width of the third cross spectral density.

38. The system of claim 36, wherein the computer arrangement is further configured to:

determine a correction curve based on a ratio between the Gaussian spectra and the third cross spectral density,

modify the first cross spectral density as a function of the correction curve, and

modify the second cross spectral density as a function of the correction curve.

39. The system of claim 38, wherein, in order to modify the first cross spectral density comprises, the computer arrangement is configured to multiply the first cross spectral density by the correction curve to obtain a first modified cross spectral density, and wherein, in order to modify the second cross spectral density, the computer arrangement is configured to multiply the second cross spectral density by the correction curve to obtain a second modified cross spectral density.

40. The system of claim 39, wherein the computer arrangement is further configured to:

transform the first modified cross spectral density into a first modified cross correlation function,

transform the second modified cross spectral density into a second modified cross correlation function, and

determine a coherence function envelope of the sample based on the first modified cross correlation function and the second modified cross correlation function.

41. The system of claim 35, wherein the first cross spectral density is transformed from a first cross correlation function, and the second cross spectral density is transformed from a second cross correlation function.

42. The system of claim 35, wherein at least one of the first cross spectral density and the second cross spectral density is complex.

43. A system for obtaining information regarding a sample, comprising the steps of:

a computer arrangement, which when executing a software program, is configured to;

receive a first combination of light and a second combination of light, wherein a first cross spectral density is associated with the first combination and a second cross spectral density is associated with the second combination, wherein each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and wherein a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination; and

determine a particular width of a Gaussian spectra of a source associated with the first combination and the second combination based on a third cross spectral density which is at least partially based on the first cross spectral density and the second cross spectral density, wherein the particular width is used for imaging the sample.

44. A system for obtaining information regarding a sample, comprising:

a computer arrangement, which when executing a software program, is configured to;

receive a first combination of light and a second combination of light, wherein a first cross spectral density is associated with the first combination and a second cross spectral density is associated with the second combination, wherein each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and wherein a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination, and

modify the first cross spectral density to implement a phase shift of the first cross spectral density.

45. The system of claim 44, wherein the computer arrangement is further configured to modify the second cross spectral density to implement a phase shift of the second cross spectral density.

46. The system of claim 44, wherein the computer arrangement is further configured to generate an image of the sample based on the first cross correlation function and the second cross correlation function.

47. The system of claim 46, wherein the computer arrangement is further configured to determine an average variance associated with the image, wherein the average variance associated with the image is used to determine an optimum phase correction.

48. The system of claim 47, wherein the computer arrangement is configured to modify by multiplying the first cross spectral density by a predetermined factor to obtain a first modified cross spectral density, wherein the predetermined factor includes a particular quadratic phase shifting term.

49. The system of claim 48, wherein the computer arrangement is further configured to:

transform the first modified cross spectral density into a third cross correlation function,

generate a modified image of the sample based on at least the third cross correlation function, and

determine an average variance associated with the modified image, wherein the average variance associated with the modified image is used to determine the optimum phase correction.

50. The system of claim 49, wherein the computer arrangement is further configured to:

modify the particular quadratic phase shifting term to obtain a modified predetermined factor,

multiply the first cross spectral density by the modified predetermined factor to obtain a second modified cross spectral density,

transform the second modified cross spectral density into a fourth cross correlation function,

generate a further modified image of the sample based on at least the fourth cross correlation function, and

determine an average variance associated with the further modified image, wherein the average variance associated with the further modified image is used to determine the optimum phase correction.

51. A system for obtaining information regarding a sample, comprising:

a computer arrangement, which when executing a software program, is configured to;

receive a first combination of light and a second combination of light, wherein a first cross correlation function is associated with the first combination and a second cross correlation function is associated with the second combination, wherein each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and wherein a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination,

modify the first cross correlation function to obtain a modified cross correlation function,

determine an average of the modified cross correlation function over a first electronic receiver frequency range which is different than a second electronic receiver frequency range of the first cross correlation function, and

transform the modified cross correlation function into a cross spectral density.

52. The system of claim 51, wherein the computer arrangement is further configured to:

modify the second cross correlation function to obtain a further modified cross correlation function,

determine an average of the further modified cross correlation function over the first frequency range, and

transform the further modified cross correlation function into a further cross spectral density.

53. The system of claim 52, wherein the computer arrangement is further configured to determine a third cross spectral density which is at least approximately an average of the cross spectral density and the further cross spectral density.

54. The system of claim 53, wherein the computer arrangement is further configured to determine a particular width of a Gaussian spectra of a source of the first combination and the second combination based on the third cross spectral density.

55. The system of claim 54, wherein the computer arrangement is further configured to:

determine an area of the third cross spectral density,

determine an average amplitude of the third cross spectral density, and

determine a width of the third cross spectral density, wherein the particular width is based on the area, the average amplitude, and the width of the third cross spectral density.

56. The system of claim 54, wherein the computer arrangement is further configured to:

determine a correction curve based on a ratio between the Gaussian spectra and the third cross spectral density,

modify the cross spectral density as a function of the correction curve, and

modify the further cross spectral density as a function of the correction curve.

57. The system of claim 56, wherein the computer arrangement is configured to modify the cross spectral density by multiplying the cross spectral density by the correction curve to obtain modified cross spectral density, and wherein the computer arrangement is configured to modify the cross spectral density by multiplying the further cross spectral density by the correction curve to obtain a further modified cross spectral density.

58. The system of claim 57, wherein the computer arrangement is further configured to:

transform the modified cross spectral density into a third modified cross correlation function,

transform the further modified cross spectral density into a fourth modified cross correlation function, and

determine a coherence function envelope of the sample based on the third modified cross correlation function and the fourth modified cross correlation function.

59. The system of claim 52, wherein the computer arrangement is further configured to modify the first cross spectral density to implement a phase shift of the cross spectral density.

60. The system of claim 59, wherein the computer arrangement is further configured to modify the further cross spectral density to implement a phase shift of the further cross spectral density.

61. The system of claim 59, wherein the computer arrangement is further configured to generate an image of the sample based on the modified cross correlation function and the further modified cross correlation function.

62. The system of claim 61, wherein the computer arrangement is further configured to determine an average variance associated with the image, wherein the average variance associated with the image is used to determine an optimum phase correction.

63. The system of claim 62, wherein the computer arrangement is further configured to modify by multiplying the cross spectral density by a predetermined factor to obtain a modified cross spectral density, wherein the predetermined factor includes a particular quadratic phase shifting term.

64. The system of claim 63, wherein the computer arrangement is further configured to:

transform the modified cross spectral density into a third cross correlation function,

generate a modified image of the sample based on at least the third cross correlation function, and

determine an average variance associated with the modified image, wherein the average variance associated with the image is used to determine the optimum phase correction.

65. The system of claim 64, wherein the computer arrangement is further configured to:

modify the particular quadratic phase shifting term to obtain a modified predetermined factor,

multiply the first cross spectral density by the modified predetermined factor to obtain the further modified cross spectral density,

transform the further modified cross spectral density into a fourth cross correlation function,

generate a further modified image of the sample based on at least the fourth cross correlation function, and

determine an average variance associated with the further modified image, wherein the average variance associated with the further modified image is used to determine the optimum phase correction.

66. A system for obtaining information regarding a sample, comprising:

a computer arrangement, which when executing a software program, is configured to;

receive a first combination of light and a second combination of light, wherein a first cross spectral density is associated with the first combination and a second cross spectral density is associated with the second combination, wherein each of the first and the second combinations includes a first portion of light which is received from a reference arrangement and a second portion of light which is received from the sample, and wherein a first relative position of the sample associated with the first combination is different than a second relative position of the sample associated with the second combination, and

modify an electrical receiver frequency range of the first cross spectral density from a first frequency range to a second frequency range.

67. The system of claim 66, wherein the computer arrangement is further adapted to:

modify a frequency range of the second cross spectral density from the first frequency range to the second frequency range.

68. The system of claim 67, wherein the first frequency range is between about 600 Hz and about 1 kHz, and wherein the second frequency range is between about −

200 Hz and about 200 Hz.

69. A method for determining data associated with at least one portion of a sample, comprising:

a) obtaining at least one spectral density associated with at least one first section of light from the at least one portion of the sample and at least one second section of light from a reference;

b) modifying the at least one spectral density using a particular criteria or function which is at least one of predetermined and determinable; and

c) generating an image for the at least one portion of the sample based on the at least one modified spectral density.

70. The method according to claim 69, wherein the particular criteria or function is a spectral correction function which is intended to be used to modify an amplitude of the at least one spectral density.

71. The method according to claim 69, wherein the particular criteria or function is a phase function intended to implement a variable phase shift of the at least one spectral density as a function of at least one of a wavelength and a wave vector, and wherein the phase function is intended to be used to modify only a phase of the at least one spectral density, without modifying the amplitude thereof.

72. The method according to claim 71, further comprising:

d) iteratively modifying the phase function so as to increase a variance of the image.

73. The method according to claim 69, wherein the at least one spectral density is a plurality of spectral densities, and wherein the at least one modified spectral density is a plurality of modified spectral densities.

74. An imaging system for imaging a sample, comprising:

a computer arrangement, which when executing a software program, is configured to;

a) obtain at least one spectral density associated with at least one first section of light from the at least one portion of the sample and at least one second section of light from a reference,

b) modify the at least one spectral density using a particular criteria or function which is at least one of predetermined and determinable, and

c) generate an image for the at least one portion of the sample based on the at least one modified spectral density.

75. The system according to claim 74, wherein the particular criteria or function is a spectral correction function which is intended to be used to modify an amplitude of the at least one spectral density.

76. The system according to claim 74, wherein the particular criteria or function is a phase function intended to implement a variable phase shift of the at least one spectral density as a function of at least one of a wavelength and a wave vector, and wherein the phase function is intended to be used to modify only a phase of the at least one spectral density, without modifying the amplitude thereof.

77. The system according to claim 76, wherein the computer arrangement is further configured to:

d) iteratively modifying the phase function so as to increase a variance of the image.

78. The system according to claim 74, wherein the at least one spectral density is a plurality of spectral densities, and wherein the at least one modified spectral density is a plurality of modified spectral densities.

79. The system according to claim 78, wherein the particular criteria or function is approximately an average of the plurality of spectral densities.