Methods and System for Image Guided Cell Ablation with Microscopic Resolution

• US 20120150164A1
• Filed: 12/08/2011
• Published: 06/14/2012
• Est. Priority Date: 12/08/2010
• Status: Active Grant

• Current Assignee: Lumicell, Inc.
• Original Assignee: Lumicell Diagnostics, Inc.
• Inventors: Lee, W. D., Stamp, Andrea, Ferrer, Jorge M.
• Granted Patent: US 9,314,304 B2
• Time in Patent Office: Days
• US Class Current: 606/16
• CPC Class Codes: A61B 18/02 by cooling, e.g. cryogenic techniques devices for cooling specific reflex points of the body within cell-life limits A61H39/06
• CPC Class Codes: A61B 18/12 by passing a current through the tissue to be heated, e.g. high-frequency current
• CPC Class Codes: A61B 18/14 Probes or electrodes therefor
• CPC Class Codes: A61B 18/20 using laser
• CPC Class Codes: A61B 18/22 the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
• CPC Class Codes: A61B 18/24 with a catheter A61B18/26, A61B18/28 take precedence
• CPC Class Codes: A61B 2017/00057 Light
• CPC Class Codes: A61B 2017/0011 piezoelectric
• CPC Class Codes: A61B 2018/00029 open
• CPC Class Codes: A61B 2018/00351 Heart
• CPC Class Codes: A61B 2018/00434 Neural system
• CPC Class Codes: A61B 2018/00565 Bone
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61B 2018/00642 with feedback, i.e. closed loop control
• CPC Class Codes: A61B 2018/00886 Duration
• CPC Class Codes: A61B 2018/00904 Automatic detection of target tissue
• CPC Class Codes: A61B 2018/00982 combined with or comprising means for visual or photographic inspections inside the body, e.g. endoscopes
• CPC Class Codes: A61B 2018/20351 Scanning mechanisms
• CPC Class Codes: A61B 2018/20359 by movable mirrors, e.g. galvanometric
• CPC Class Codes: A61B 2018/20361 with redirecting based on sensed condition, e.g. tissue analysis or tissue movement
• CPC Class Codes: A61B 2018/2283 : with pivotable mirrors
• CPC Class Codes: A61B 2503/40 : Animals
• CPC Class Codes: A61B 2562/028 : Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2576/00 : Medical imaging apparatus involving image processing or analysis A61B1/00009, A61B6/52 and A61B8/52 take precedence; image processing per se G06T; details of algorithms for analysing medical images G06T7/0012
• CPC Class Codes: A61B 34/20 : Surgical navigation systems; Devices for tracking or guiding surgical instruments, e.g. for frameless stereotaxis
• CPC Class Codes: A61B 90/30 : Devices for illuminating a surgical field, the devices having an interrelation with other surgical devices or with a surgical procedure
• CPC Class Codes: A61B 90/361 : Image-producing devices, e.g. surgical cameras
• CPC Class Codes: A61B 90/39 : Markers, e.g. radio-opaque or breast lesions markers

Abstract

The invention provides systems and method for the removal of diseased cells during surgery.

Claims

1. An in vivo method of treating abnormal cells comprising:

(a) administering a composition comprising a molecular imaging probe to a tissue of a subject;

(b) obtaining an in situ image of said tissue wherein the image allows for the detection of one or more diseased cells, if present in the tissue;

(c) treating said diseased cell(s) detected in step (b).

2. The method of claim 1, wherein said composition is administered systemically to said subject or applied to the surface of said tissue.

3. The method of claim 2 wherein said surface administration is by spraying or painting.

4. The method of claim 2 wherein said composition is administered on a film or sponge.

5. The method of claim 1, wherein cells are treated with light energy.

6. The method of claim 5, wherein cells are laser ablated.

7. The method of claim 6, wherein the laser ablation comprises of:

(a) locating one or more diseased cells in situ using an imaging system;

(b) transferring the location of the diseased cell to a laser guiding system to move the laser over the target cell for ablation

(c) imaging the actual location of the laser using the imaging system to provide spatial feedback to the laser guiding system

(d) adjusting the location of the laser if necessary based on the aforementioned feedback

(e) ablating detected diseased cell(s).

8. The method of claim 7, comprising an additional feedback algorithm after the ablation of diseased cells to post-image the treatment tissue and verify that the diseased cells have been correctly treated.

9. The method of claim 7, wherein the imaging system is a single-cell resolution imaging system.

10. The method of claim 7, wherein the laser guiding system consists of one or more galvanometer mirrors, MEMS mirrors, acousto-optic deflectors, micromirrors, acousto-optic modulators used as deflectors, piezo-electrial mirrors, electro-optical deflectors, polygonal mirrors, or planar mirrors on a rotating shaft.

11. The method of claim 1 wherein the molecular imaging probe is activated by enzymes.

12. The method of claim 11 wherein the imaging probe comprises one or more fluorochromes and one or more dark quenchers.

13. The method of claim 12, wherein the fluorochrome is selected from the group consisting of Cy3, Cy3.5, Cy5, Alexa 568, Alexa 546, Alexa 610, Alexa 647, ROX, TAMRA, Bodipy 576, Bodipy 581, Bodipy TR, Bodipy 630, VivoTag 645, and Texas Red.

14. The method of claim 12, wherein the dark quencher is selected from the group consisting of a QSY quencher, a dabcyl quencher, an Iowa Black quencher, and a Black Hole quencher.

15. The method of claim 14, wherein the QSY quencher is QSY21, QSY7, QSY9, or QSY35.

16. The method of claim 14, wherein the Iowa Black quencher is Iowa Black FQ or Iowa black RQ.

17. The method of claim 1 wherein the molecular imaging probe comprises a targeting moiety and an imaging moiety.

18. The method of claim 17, wherein said targeting moiety binds specifically to CD20, CD33, carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), CA125, CA19-9, prostate specific antigen (PSA), human chorionic gonadotropin (HCG), acid phosphatase, neuron specific enolase, galacatosyl transferase II, immunoglobulin, CD326, her2NEU, EGFR, PSMA, TTF1, Muc, immature glycoslytaion, an EMT marker, a cathepsin, or an enzyme.

19. The method of claim 17 wherein said imaging moiety is a fluorochrome selected from the group consisting of Cy3, Cy3.5, Cy5, Alexa 568, Alexa 546, Alexa 610, Alexa 647, ROX, TAMRA, Bodipy 576, Bodipy 581, Bodipy TR, Bodipy 630, VivoTag 645, and Texas Red.

20. The method of claim 1, wherein the diseased cell is within 1 cm from the surface.

21. The method of claim 1, wherein the probe is optimally imaged at less than 2 hours after administration.

22. The method of claim 1, wherein the probe is optimally imaged at between 12 and 36 hours after administration.

23. The method of claim 1, wherein the imaging probe is in the visible light spectrum of 350-670 nm.

24. The method of claim 1, wherein the diseased cell is a cancer cell.

25. The method of claim 1, wherein the diseased cell is a central nervous cell, a cardiac cell, a bone cell, a tendon cell, a muscle cell, a tumor associated cell.

26. The method of claim 1, wherein the subject is a mammal.

27. The method of claim 26, wherein the subject is a human.

28. The method of claim 1, wherein the imaging probe consists of a pharmacokinetic modifier.

52. The method of claim 5, wherein the light energy is between 100 nm and 2500 nm.

53. The method of claim 5, wherein the cells are treated with pulsed light energy of pulse duration less than 100 ns.

54. The method of claim 5, wherein the cells are imaged and treated in the entire field of view or subsection of the field of view within 1 s.

55. The method of claim 5, wherein the cells are treated with light energy which imparts delayed cellular death.

56. The method of claim 1, wherein the cells are treated with Radio Frequency ablation.

57. The method of claim 1, wherein the cells are treated with cryo-ablation.

29. A therapeutic medical imaging system comprising:

(a) an excitation source configured to cause an object having a plurality of cells to emit and fluoresce light;

(b) an optical receptor configured to receive the light from the object;

(c) an image processor;

(d) an energy source sufficient for destroying one or more cells; and

(e) a feedback system configured to detect the condition of each cell and apply treatment to detected diseased cells.

30. The system of claim 29, wherein the image processor comprises a field of view (FOV) substantially greater than a diameter of a cell of the object and an analysis resolution substantially matched to the diameter of a cell of the object and configured to receive and analyze the light corresponding to each cell in the FOV.

31. The system of claim 29, wherein the cells are treated using light energy.

32. The system of claim 31, wherein the treatment light energy is delivered by a plurality of lights.

33. The system of claim 31, wherein an optical fiber bundle collects and distributes light to the cells.

34. The system of claim 31, wherein cells are treated using laser ablation.

35. The system of claim 34, wherein the laser for ablation is controlled by a laser guiding system comprising of one or more galvanometer mirrors, MEMS mirrors, acousto-optic deflectors, micromirrors, acousto-optical modulators used as deflectors, piezo-electrial mirrors, electro-optical deflectors, polygonal mirrors, or planar mirrors on a rotating shaft.

36. The system of claim 29, wherein the diseased cell is a cancer cell.

37. The system of claim 29, wherein the diseased cell is a central nervous cell, a cardiac cell, a bone cell, a tendon cell, a muscle cell, a tumor associated cell.

38. The system of claim 29, wherein the diseased cell is a mammal cell.

39. The system of claim 38, wherein the diseased cell is a human cell.

40. The system of claim 29, wherein the feedback system comprises of:

(a) locating the diseased cell in situ using an imaging system;

(b) transferring the location of the diseased cell to a laser guiding system to move the laser over the target cell for ablation

(c) imaging the actual location of the laser using the imaging system to provide spatial feedback to the laser guiding system

(d) adjusting the location of the laser if necessary based on the aforementioned feedback

(e) ablating detected diseased cell(s).

41. The system of claim 40, further comprising an additional feedback algorithm after the ablation of diseased cells to post-image the treatment tissue and verify that the diseased cells have been correctly treated.

42. The system of claim 29, wherein the diseased cell is within 1 cm from the surface.

43. The system of claim 29, wherein the cells emit fluorescence in the visible light spectrum of 350-670 nm.

44. The system of claim 29, further comprising a fluid reservoir which flushes cell area with fluid to remove debris created during ablative process.

45. The system of claim 29, further comprising a fluid reservoir which flushes cell area with fluid to cool tissue as ablative heat destroys abnormal cells, preventing excess treatment to healthy tissue.

46. The system of claim 31, wherein the light energy is between 100 nm and 2500 nm.

47. The system of claim 31, wherein the cells are treated with pulsed light energy of pulse duration less than 100 ns.

48. The system of claim 31, wherein the cells are imaged and treated in the entire field of view or subsection of the field of view within 1 s.

49. The system of claim 31, wherein the cells are treated with light energy which imparts delayed cellular death.

50. The system of claim 29, wherein the cells are treated with Radio Frequency ablation.

51. The system of claim 29, wherein the cells are treated with cryo-ablation.

58. An in vivo method of treating abnormal cells comprising:

(a) obtaining an in situ image of tissue in a subject wherein the image allows for the detection of one or more diseased cells, if present in the tissue;

(b) treating said diseased cell(s) detected in step (a).

59. The method of claim 58, wherein cells are treated with light energy.

60. The method of claim 59, wherein cells are laser ablated.

61. The method of claim 60, wherein the laser ablation comprises of:

(a) locating one or more diseased cells in situ using an imaging system;

(b) transferring the location of the diseased cell to a laser guiding system to move the laser over the target cell for ablation

(c) imaging the actual location of the laser using the imaging system to provide spatial feedback to the laser guiding system

(d) adjusting the location of the laser if necessary based on the aforementioned feedback

(e) ablating detected diseased cell(s).

62. The method of claim 61, comprising an additional feedback algorithm after the ablation of diseased cells to post-image the treatment tissue and verify that the diseased cells have been correctly treated.

63. The method of claim 61, wherein the imaging system is a single-cell resolution imaging system.

64. The method of claim 61, wherein the laser guiding system consists of one or more galvanometer mirrors, MEMS mirrors, acousto-optic deflectors, micromirrors, acousto-optic modulators used as deflectors, piezo-electrial mirrors, electro-optical deflectors, polygonal mirrors, or planar mirrors on a rotating shaft.

65. The method of claim 58, wherein the diseased cell is within 1 cm from the surface.

66. The method of claim 58, wherein the diseased cell is a cancer cell.

67. The method of claim 58, wherein the diseased cell is a central nervous cell, a cardiac cell, a bone cell, a tendon cell, a muscle cell, a tumor associated cell.

68. The method of claim 58, wherein the subject is a mammal.

69. The method of claim 68, wherein the subject is a human.

92. The method of claim 59, wherein the light energy is between 100 nm and 2500 nm.

93. The method of claim 59, wherein the cells are treated with pulsed light energy of pulse duration less than 100 ns.

94. The method of claim 59, wherein the cells are imaged and treated in the entire field of view or subsection of the field of view within 1 s.

95. The method of claim 59, wherein the cells are treated with light energy which imparts delayed cellular death.

96. The method of claim 58, wherein the cells are treated with Radio Frequency ablation.

97. The method of claim 58, wherein the cells are treated with cryo-ablation.

70. A therapeutic medical imaging system comprising:

(a) a light source;

(b) an optical receptor configured to receive the light from the object;

(c) an image processor;

(d) an energy source sufficient for destroying one or more cells; and

(e) a feedback system configured to detect the condition of each cell and apply treatment to detected diseased cells.

71. The system of claim 70, wherein the image processor comprises a field of view (FOV) substantially greater than a diameter of a cell of the object and an analysis resolution substantially matched to the diameter of a cell of the object and configured to receive and analyze the light corresponding to each cell in the FOV.

72. The system of claim 70, wherein the cells are treated using light energy.

73. The system of claim 72, wherein the treatment light energy is delivered by a plurality of lights.

74. The system of claim 72, wherein an optical fiber bundle collects and distributes light to the cells.

75. The system of claim 72, wherein cells are treated using laser ablation.

76. The system of claim 75, wherein the laser for ablation is controlled by a laser guiding system comprising of one or more galvanometer mirrors, MEMS mirrors, acousto-optic deflectors, micromirrors, acousto-optical modulators used as deflectors, piezo-electrial mirrors, electro-optical deflectors, polygonal mirrors, or planar mirrors on a rotating shaft.

77. The system of claim 70, wherein the diseased cell is a cancer cell.

78. The system of claim 70, wherein the diseased cell is a central nervous cell, a cardiac cell, a bone cell, a tendon cell, a muscle cell, a tumor associated cell.

79. The system of claim 70, wherein the diseased cell is a mammal cell.

80. The system of claim 79, wherein the diseased cell is a human cell.

81. The system of claim 70, wherein the feedback system comprises of:

(a) locating the diseased cell in situ using an imaging system;

(b) transferring the location of the diseased cell to a laser guiding system to move the laser over the target cell for ablation

(c) imaging the actual location of the laser using the imaging system to provide spatial feedback to the laser guiding system

(d) adjusting the location of the laser if necessary based on the aforementioned feedback

(e) ablating detected diseased cell(s).

82. The system of claim 81, further comprising an additional feedback algorithm after the ablation of diseased cells to post-image the treatment tissue and verify that the diseased cells have been correctly treated.

83. The system of claim 70, wherein the diseased cell is within 1 cm from the surface.

84. The system of claim 70, further comprising a fluid reservoir which flushes cell area with fluid to remove debris created during ablative process.

85. The system of claim 70, further comprising a fluid reservoir which flushes cell area with fluid to cool tissue as ablative heat destroys abnormal cells, preventing excess treatment to healthy tissue.

86. The system of claim 72, wherein the light energy is between 100 nm and 2500 nm.

87. The system of claim 72, wherein the cells are treated with pulsed light energy of pulse duration less than 100 ns.

88. The system of claim 72, wherein the cells are imaged and treated in the entire field of view or subsection of the field of view within 1 s.

89. The system of claim 72, wherein the cells are treated with light energy which imparts delayed cellular death.

90. The system of claim 70, wherein the cells are treated with Radio Frequency ablation.

91. The system of claim 70, wherein the cells are treated with cryo-ablation.