TISSUE ABLATION WITH IRREVERSIBLE ELECTROPORATION

• US 20120277741A1
• Filed: 07/11/2012
• Published: 11/01/2012
• Est. Priority Date: 12/24/2003
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Rubinsky, Boris, DAVALOS, RAFAEL
• Granted Patent: US 9,005,189 B2
• Time in Patent Office: Days
• US Class Current: 606/41
• 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 18/1233 with circuits for assuring patient safety
• CPC Class Codes: A61B 18/1477 Needle-like probes
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation reversible electroporation A61N1/327
• CPC Class Codes: A61B 2018/00714 Temperature
• CPC Class Codes: A61B 2018/00761 Duration
• CPC Class Codes: A61B 2018/00827 Current
• CPC Class Codes: A61B 2018/1425 Needle
• CPC Class Codes: A61N 1/0412 Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• CPC Class Codes: A61N 1/0472 Structure-related aspects
• CPC Class Codes: A61N 1/05 for implantation or insertion into the body, e.g. heart electrode A61N1/06 takes precedence
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

A new method for the ablation of undesirable tissue such as cells of a cancerous or non-cancerous tumor is disclosed. It involves the placement of electrodes into or near the vicinity of the undesirable tissue through the application of electrical pulses causing irreversible electroporation of the cells throughout the entire area of the undesirable tissue. The electric pulses irreversibly permeate the cell membranes, thereby invoking cell death. The irreversibly permeabilized cells are left in situ and are removed by the body immune system. The amount of tissue ablation achievable through the use of irreversible electroporation without inducing thermal damage is considerable.

Claims

1-33. -33. (canceled)

34. A method of ablating tissue cells by a combination of non-thermal irreversible electroporation and thermal damage, comprising:

identifying a zone of tissue to be ablated;

placing one or more electrodes near the identified tissue zone;

applying electrical pulses through the one or more electrodes in an amount which is;

sufficient to induce irreversible electroporation of cells in a first selected portion of the identified tissue zone, but which is insufficient to induce thermal damage in the first selected portion, and

sufficient to induce thermal damage in a second selected portion of the identified tissue zone,

such that the tissue cells in the identified tissue zone are killed selectively by irreversible electroporation and selectively by thermal damage.

35. The method of claim 34, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to maintain the temperature of the target tissue at 50°

C. or less in the first selected portion.

36. The method of claim 34, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to maintain the temperature of the target tissue at 65°

C. or less in the first selected portion.

37. The method of claim 34, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to be insufficient to induce thermal damage in the first selected portion based on a bioheat equation.

38. The method of claim 34, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to be sufficient to induce irreversible electroporation in the first selected portion based on a transmembrane potential required for irreversible electroporation of the tissue to be ablated.

39. The method of claim 34, wherein the step of applying includes applying each electrical pulse having a pulse length of between 5 microseconds and 110 microseconds.

40. The method of claim 34, further comprising detecting that irreversible electroporation of the tissue to be ablated has occurred.

41. The method of claim 40, wherein the step of detecting includes monitoring the electrical impedance of the tissue to be ablated to detect the occurrence of irreversible electroporation.

42. The method of claim 34, further comprising detecting that irreversible electroporation of the tissue to be ablated has occurred based on electrical impedance tomography.

43. The method of claim 34, further comprising adjusting at least one pulse parameter to maintain the temperature of the identified tissue in the first selected portion at 50°

C. or less.

44. The method of claim 34, further comprising:

continuously detecting an electrical resistance of the identified tissue; and

adjusting at least one pulse parameter to achieve irreversible electroporation of the tissue cells in the first selected portion of the identified tissue zone based on the detected electrical resistance.

45. The method of claim 34, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to be insufficient to induce thermal damage in the first selected portion based on a modified Penne'"'"'s bioheat equation.

46. The method of claim 34, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to be insufficient to induce thermal damage in the first selected portion based on an Arrhenius bioheat equation.

47. The method of claim 34, wherein the step of applying includes applying each electrical pulse having a pulse length of greater than 1 microsecond and less than or equal to 110 microseconds.

48. The method of claim 34, wherein the step of applying includes applying each electrical pulse having a pulse length of between 75 microseconds and 110 microseconds.

49. The method of claim 34, further comprising:

continuously detecting a current flowing through the one or more electrodes; and

adjusting at least one pulse parameter to achieve irreversible electroporation of the identified tissue in the first selected portion based on the detected current flow.

50. A method of ablating tissue cells of a living mammal by a combination of non-thermal irreversible electroporation and thermal damage, comprising:

identifying in the living mammal a zone of tissue to be ablated;

placing one or more electrodes near the identified tissue zone;

applying electrical pulses through the one or more electrodes in an amount which;

has been predetermined to be sufficient to induce irreversible electroporation of cells in a first selected portion of the identified tissue zone, but which has been predetermined to be insufficient to induce thermal damage in the first selected portion, and

has been predetermined to be sufficient to induce thermal damage in a second selected portion of the identified tissue zone,

such that the tissue cells in the identified tissue zone are killed selectively by irreversible electroporation and selectively by thermal damage.

51. The method of claim 50, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to maintain the temperature of the target tissue at 50°

C. or less in the first selected portion.

52. The method of claim 50, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to maintain the temperature of the target tissue at 65°

C. or less in the first selected portion.

53. The method of claim 50, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to be insufficient to induce thermal damage in the first selected portion based on a bioheat equation.

54. The method of claim 50, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to be sufficient to induce irreversible electroporation in the first selected portion based on a transmembrane potential required for irreversible electroporation of the tissue to be ablated.

55. The method of claim 50, wherein the step of applying includes applying each electrical pulse having a pulse length of between 5 microseconds and 110 microseconds.

56. The method of claim 50, further comprising detecting that irreversible electroporation of the tissue to be ablated has occurred.

57. The method of claim 56, wherein the step of detecting includes monitoring the electrical impedance of the tissue to be ablated to detect the occurrence of irreversible electroporation.

58. The method of claim 50, further comprising detecting that irreversible electroporation of the tissue to be ablated has occurred based on electrical impedance tomography.

59. The method of claim 50, further comprising adjusting at least one pulse parameter to maintain the temperature of the identified tissue in the first selected portion at 50°

C. or less.

60. The method of claim 50, further comprising:

continuously detecting an electrical resistance of the identified tissue; and

adjusting at least one pulse parameter to achieve irreversible electroporation of the tissue cells in the first selected portion of the identified tissue zone based on the detected electrical resistance.

61. The method of claim 50, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to be insufficient to induce thermal damage in the first selected portion based on a modified Penne'"'"'s bioheat equation.

62. The method of claim 50, wherein the step of applying includes applying the electrical pulses in an amount which has been predetermined to be insufficient to induce thermal damage in the first selected portion based on an Arrhenius bioheat equation.

63. The method of claim 50, wherein the step of applying includes applying each electrical pulse having a pulse length of greater than 1 microsecond and less than or equal to 110 microseconds.

64. The method of claim 50, wherein the step of applying includes applying each electrical pulse having a pulse length of between 75 microseconds and 110 microseconds.

65. The method of claim 50, further comprising:

continuously detecting a current flowing through the one or more electrodes; and

adjusting at least one pulse parameter to achieve irreversible electroporation of the identified tissue in the first selected portion based on the detected current flow.