Methods and systems for treating BPH using electroporation

• US 20060293713A1
• Filed: 06/24/2005
• Published: 12/28/2006
• Est. Priority Date: 06/24/2005
• Status: Active Grant

• Current Assignee: AngioDynamics, Inc.
• Original Assignee: AngioDynamics, Inc.
• Inventors: Mikus, Paul, Rubinsky, Boris, Onik, Gary
• Granted Patent: US 8,114,070 B2
• Time in Patent Office: Days
• US Class Current: 607/2
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation
• CPC Class Codes: A61N 1/0412 Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• CPC Class Codes: A61N 1/0476 Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

A system for treating benign prostate hyperplasia (BPH) of a prostate. At least first and second mono-polar electrodes are configured to be introduced at or near a BPH tissue site of the prostate gland of the patient. A voltage pulse generator is coupled to the first and second mono-polar electrodes. The voltage pulse generator is configured to apply sufficient electrical pulses between the first and second mono-polar electrodes to induce electroporation of cells in the BPH tissue site, to create necrosis of cells of the BPH tissue site, but insufficient to create a thermal damaging effect to a majority of the BPH tissue site.

Claims

1. A system for treating benign prostate hyperplasia (BPH) of a prostate, comprising:

at least first and second mono-polar electrodes configured to be introduced at or near a BPH tissue site of the prostate gland of the patient; and

a voltage pulse generator coupled to the first and second mono-polar electrodes and configured to apply sufficient electrical pulses between the first and second mono-polar electrodes to induce electroporation of cells in the BPH tissue site to create necrosis of cells of the BPH tissue site but insufficient to create a thermal damaging effect to a majority of the BPH tissue site.

2. The system of claim 1, further comprising:

a monitoring electrode configured to measure a test voltage delivered to cells in the BPH tissue site.

3. The system of claim 1, wherein the test voltage is insufficient to create irreversible electroporation.

4. The system of claim 1, further comprising:

at least a third mono-polar electrode, the at least first, second and third mono-polar electrodes forming an array of electrodes.

5. The system of claim 4, wherein the array is configured to be positioned in a surrounding relationship relative to the BPH tissue site.

6. The system of claim 1, wherein the electroporation is performed in a controlled manner with real time monitoring.

7. The system of claim 1, wherein the electroporation is performed in a controlled manner to provide for controlled pore formation in cell membrane.

8. The system of claim 1, wherein the electroporation is performed in a controlled manner to create a tissue effect in the cells at the BPH tissue site while preserving surrounding tissue.

9. The system of claim 1, wherein the electroporation is performed in a controlled manner with monitoring of electrical impedance.

10. The system of claim 1, wherein the electroporation is monitored using ultrasound.

11. The system of claim 1, wherein the electroporation is monitored using MRI.

12. The system of claim 1, wherein the electroporation is monitored using a CT scan.

13. The system of claim 1, further comprising:

detecting an onset of electroporation of cells at the BPH tissue site.

14. The system of claim 13, further comprising:

monitoring the effects of electroporation on cell membranes of cells at the BPH tissue site.

15. The system of claim 13, further comprising:

detecting that the effects of electroporation on cell membranes of cells at the BPH tissue site continues.

16. The system of claim 1, wherein the electroporation is performed in a controlled manner with controlled intensity and duration of voltage.

17. The system of claim 1, wherein the electroporation is performed in a controlled manner with real time control.

18. The system of claim 1, wherein the electroporation is performed in a manner to provide for modification and control of mass transfer across cell membranes.

19. The system of claim 1, wherein the electroporation is performed in a controlled manner with a proper selection of voltage magnitude.

20. The system of claim 1, wherein the electroporation is performed in a controlled manner with a proper selection of voltage application time.

21. The system of claim 1, wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 5 microseconds to about 62 seconds.

22. The system of claim 1, wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 90 to 110 microseconds.

23. The system of claim 1, wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 100 microseconds.

24. The system of claim 22, wherein the voltage pulse generator is configured to apply from about 1 to 15 pulses.

25. The system of claim 22, wherein the voltage pulse generator is configured to apply about eight pulses of about 100 microseconds each in duration.

26. The system of claim 1, wherein the voltage pulse generator is configured to provide for pulse application to produce a voltage gradient at the BPH tissue site in a range of from about 50 volt/cm to about 8000 volt/cm.

27. The system of claim 1, wherein a temperature of the BPH tissue site is monitored and the pulses are adjusted to maintain a temperature of 100 degrees C. or less at the BPH tissue site.

28. The system of claim 1, wherein a temperature of the BPH tissue site is monitored and the pulses are adjusted to maintain a temperature of 75 degrees C. or less at the BPH tissue site.

29. The system of claim 1, wherein a temperature of the BPH tissue site is monitored and the pulses are adjusted to maintain a temperature of 60 degrees C. or less at the BPH tissue site.

30. The system of claim 29, wherein the temperature is maintained at 50 degrees C. or less.

31. The system of claim 1, wherein a current-to-voltage ratio is adjusted based on temperature to maintain the BPH tissue site temperature at 100 degrees C. or less.

32. The system of claim 1, wherein a current-to-voltage ratio is adjusted based on temperature to maintain the BPH tissue site temperature at 75 degrees C. or less.

33. The system of claim 1, wherein a current-to-voltage ratio is adjusted based on temperature to maintain the BPH tissue site temperature at 60 degrees C. or less.

34. The system of claim 1, wherein a current-to-voltage ratio is adjusted based on temperature to maintain the BPH tissue site temperature at 50 degrees C. or less.

35. The system of claim 1, wherein the first electrode is placed at about 5 mm to 10 cm from the second electrode.

36. The system of claim 1, wherein the first and second mono-polar electrodes are circular in shape.

37. The system of claim 1, wherein the voltage pulse generator is configured to provide for pulse application of sufficient duration and magnitude to permanently disrupt cell membranes of cells at the BPH tissue site.

38. The system of claim 1, wherein a ratio of electric current through cells at the BPH tissue site to voltage across the cells is detected and a magnitude of applied voltage to the BPH tissue site is adjusted in accordance with changes in the ratio of current to voltage.

40. The system of claim 1, further comprising:

a monitoring electrode configured to measure a test voltage delivered to cells in the BPH tissue site.

41. The system of claim 1, wherein the test voltage is insufficient to create irreversible electroporation.

42. The system of claim 1, further comprising:

at least a second and a third bipolar electrodes, the at least first, second and third bipolar electrodes forming an array of electrodes.

43. The system of claim 42, wherein the array is configured to be positioned in a surrounding relationship relative to the BPH tissue site.

44. The system of claim 1, wherein the electroporation is performed in a controlled manner with real time monitoring.

45. The system of claim 1, wherein the electroporation is performed in a controlled manner to provide for controlled pore formation in cell membranes.

46. The system of claim 1, wherein the electroporation is performed in a controlled manner to create a tissue effect in the cells at the BPH tissue site while preserving surrounding tissue.

47. The system of claim 1, wherein the electroporation is performed in a controlled manner with monitoring of electrical impedance;

48. The system of claim 1, further comprising:

detecting an onset of electroporation of cells at the BPH tissue site.

49. The system of claim 1, wherein the electroporation is performed in a controlled manner with controlled intensity and duration of voltage.

50. The system of claim 1, wherein the electroporation is performed in a controlled manner with real time control.

87. The method of claim 1, wherein the electroporation is performed in a controlled manner with a proper selection of voltage magnitude.

39. A system for treating of benign prostate hyperplasia (BPH) of a prostate, comprising:

a bi-polar electrode configured to be introduced at or near a BPH tissue site of the prostate gland of the patient; and

a voltage pulse generator coupled to the first and second electrodes and configured to apply sufficient electrical pulses to the bi-polar electrode to induce electroporation of cells in the BPH tissue site to create necrosis of cells of the BPH tissue site, but insufficient to create a thermal damaging effect to a majority of the BPH tissue site.

51. The system of claim 39, wherein the electroporation is performed in a manner to for modification and control of mass transfer across cell membranes.

52. The system of claim 39, wherein the electroporation is performed in a controlled manner with a proper selection of voltage magnitude.

53. The system of claim 39, wherein the electroporation is performed in a controlled manner with a proper selection of voltage application time.

54. The system of claim 39, wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 5 microseconds to about 62 seconds.

55. The system of claim 39, wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 90 to 110 microseconds.

56. The system of claim 39, wherein the voltage pulse generator is configured to provide that each pulse is applied for a duration of about 100 microseconds.

57. The system of claim 55, wherein the voltage pulse generator is configured to apply from about 1 to 15 pulses.

58. The system of claim 55, wherein the voltage pulse generator is configured to apply about eight pulses of about 100 microseconds each in duration.

59. The system of claim 39, wherein the voltage pulse generator is configured to provide for pulse application to produce a voltage gradient at the BPH tissue site in a range of from about 50 volt/cm to about 8000 volt/cm.

60. The system of claim 39, wherein a temperature of the BPH tissue site is monitored and the pulses are adjusted to maintain a temperature of 100 degrees C. or less at the BPH tissue site.

61. The system of claim 39, wherein a temperature of the BPH tissue site is monitored and the pulses are adjusted to maintain a temperature of 75 degrees C. or less at the BPH tissue site.

62. The system of claim 39, wherein a temperature of the BPH tissue site is monitored and the pulses are adjusted to maintain a temperature of 60 degrees C. or less at the BPH tissue site.

63. The system of claim 60, wherein the temperature is maintained at 50 degrees C. or less.

64. The system of claim 39, wherein a current-to-voltage ratio is adjusted based on temperature to maintain the BPH tissue site temperature at 100 degrees C. or less.

65. The system of claim 39, wherein a current-to-voltage ratio is adjusted based on temperature to maintain the BPH tissue site temperature at 75 degrees C. or less.

66. The system of claim 39, wherein a current-to-voltage ratio is adjusted based on temperature to maintain the BPH tissue site temperature at 60 degrees C. or less.

67. The system of claim 39, wherein a current-to-voltage ratio is adjusted based on temperature to maintain the BPH tissue site temperature at 50 degrees C. or less.

68. The system of claim 39, wherein the voltage pulse generator is configured to provide for pulse application of sufficient duration and magnitude to permanently disrupt cell membranes of cells at the BPH tissue site.

69. The system of claim 39, wherein a ratio of electric current through cells at the BPH tissue site to voltage across the cells is detected and a magnitude of applied voltage to the BPH tissue site is adjusted in accordance with changes in the ratio of current to voltage.

70. A method for treating of benign prostate hyperplasia (BPH) of a prostate, comprising:

introducing at least first and second mono-polar electrodes to a BPH tissue site of a patient;

positioning the at least first and second mono-polar electrodes at or near the BPH tissue site;

applying an electric field in a controlled manner to the BPH tissue site in an amount sufficient to produce electroporation of cells at the BPH tissue site and below an amount that causes thermal damage to a majority of the BPH tissue site.

71. The method of claim 70, further comprising:

using a monitoring electrode to measure a test voltage delivered to cells in the BPH tissue site.

72. The method of claim 71, wherein the test voltage is insufficient to create irreversible electroporation.

73. The method of claim 70, further comprising:

introducing at least a third mono-polar electrode to the BPH tissue site, the first, second and third mono-polar electrodes forming an array of electrodes.

74. The system of claim 73, wherein the array is positioned in a surrounding relationship relative to the BPH tissue site.

75. The method of claim 70, wherein the at least first and second mono-polar electrodes are introduced through a rectal wall of a patient.

76. The method of claim 70, wherein the at least first and second mono-polar electrodes are introduced through a peritoneum of the patient.

77. The method of claim 70, wherein the at least first and second mono-polar electrodes are introduced through a urethra wall of the patient.

78. The method of claim 70, further comprising:

performing the electroporation in a controlled manner with real time monitoring.

79. The method of claim 70, further comprising:

performing the electroporation in a controlled manner to provide for controlled pore formation in cell membranes.

80. The method of claim 70, further comprising:

performing the electroporation in a controlled manner to create a tissue effect of cells at the BPH tissue site while preserving surrounding tissue.

81. The method of claim 70, further comprising:

performing the electroporation in a controlled manner with monitoring of electrical impedance;

82. The method of claim 70, further comprising:

detecting an onset of electroporation of cells at the BPH tissue site.

83. The method of claim 70, further comprising:

performing the electroporation in a controlled manner with controlled intensity and duration of voltage.

84. The method of claim 70, further comprising:

performing the electroporation in a controlled manner with real time control.

85. The method of claim 70, further comprising:

performing the electroporation in a manner for modification and control of mass transfer across cell membranes.

86. The method of claim 70, further comprising:

performing the electroporation in a controlled manner with a proper selection of voltage magnitude.

88. The method of claim 70, wherein the electroporation is performed in a controlled manner with a proper selection of voltage application time.

89. The method of claim 70, wherein the duration of each pulse is about 5 microseconds to about 62 seconds.

90. The method of claim 70, where the duration of each pulse is about 90 to 110 microseconds.

91. The method of claim 70, wherein the duration of each pulse is about 100 microseconds.

92. The method of claim 90, wherein about 1 to 15 pulses are applied.

93. The method of claim 90, wherein about eight pulses of about 100 microseconds each in duration are applied.

94. The method of claim 70, wherein pulses are applied to produce a voltage gradient at the BPH tissue site in a range of from about 50 volt/cm to about 8000 volt/cm.

95. The method of claim 70, further comprising:

monitoring a temperature of the BPH tissue site; and

adjusting the pulses to maintain a temperature of 100 degrees C. or less at the BPH tissue site.

96. The method of claim 70, further comprising:

monitoring a temperature of the BPH tissue site; and

adjusting the pulses to maintain a temperature of 75 degrees C. or less at the BPH tissue site.

97. The method of claim 70, further comprising:

monitoring a temperature of the BPH tissue site; and

adjusting the pulses to maintain a temperature of 60 degrees C. or less at the BPH tissue site.

98. The method of claim 70, further comprising:

monitoring a temperature of the BPH tissue site; and

adjusting the pulses to maintain a temperature of 50 degrees C. or less at the BPH tissue site.

99. The method of claim 70, further comprising:

adjusting a current-to-voltage ratio based on temperature to maintain the BPH tissue site temperature at 100 degrees C. or less.

100. The method of claim 70, further comprising:

adjusting a current-to-voltage ratio based on temperature to maintain the BPH tissue site temperature at 75 degrees C. or less.

101. The method of claim 70, further comprising:

adjusting a current-to-voltage ratio based on temperature to maintain the BPH tissue site temperature at 60 degrees C. or less.

102. The method of claim 70, further comprising:

adjusting a current-to-voltage ratio based on temperature to maintain the BPH tissue site temperature at 50 degrees C. or less.

103. The method of claim 70, wherein the pulses applied are of sufficient duration and magnitude to permanently disrupt cell membranes of cells at the BPH tissue site.

104. The method of claim 70, wherein a ratio of electric current through cells at the BPH tissue site to voltage across the cells is detected and a magnitude of applied voltage to the BPH tissue site is adjusted in accordance with changes in the ratio of current to voltage.

105. A method for treating of benign prostate hyperplasia (BPH) of a prostate, comprising:

introducing a bi-polar electrode to a BPH tissue site of a patient;

positioning the bi-polar electrode at or near the BPH tissue site;

applying an electric field in a controlled manner to the BPH tissue site in an amount sufficient to produce electroporation of cells at the BPH tissue site and below an amount that causes thermal damage to a majority of the BPH tissue site.

106. The method of claim 105, further comprising:

using a monitoring electrode to measure a test voltage delivered to cells in the BPH tissue site.

107. The method of claim 106, wherein the test voltage is insufficient to create irreversible electroporation.

108. The method of claim 105, further comprising:

introducing at least a second and a third bipolar electrode to the BPH tissue site, the first, second and third bipolar electrodes forming an array of electrodes.

109. The system of claim 108, wherein the array is positioned in a surrounding relationship relative to the BPH tissue site.

110. The method of claim 105, wherein the bipolar electrode is introduced through a rectal wall of a patient.

111. The method of claim 110, wherein a monitoring electrode is provided.

112. The method of claim 111, wherein the monitoring electrode is placed distal or proximal to the bipolar electrode.

113. The method of claim 111, wherein the monitoring electrode is placed at a fixed distance form the bipolar electrode.

114. The method of claim 111, wherein the monitoring electrode is mounted on a sheath through which the bipolar electrode is placed.

115. The method of claim 114, wherein a distance of the monitoring electrode from the bipolar electrode is varied and positioned in response to an imaging of a monitored tissue site.

116. The method of claim 115, wherein the monitored tissue site is a rectal mucosa tissue site.

117. The method of claim 116, wherein the monitoring electrode is positioned at a biopsy guide coupled to the RF electrode.

118. The method of claim 117, wherein the RF electrode is configured to be placed through the biopsy guide.

119. The method of claim 118, wherein the monitoring electrode is placed at a tip of the biopsy guide and rests against the rectal mucosa when the bipolar electrode is placed.

120. The method of claim 105, wherein the bipolar electrode is introduced through a peritoneum of the patient.

121. The method of claim 105, wherein the at least first and second mono-polar electrodes are introduced through a urethra wall of the patient.

122. The method of claim 105, further comprising:

performing the electroporation in a controlled manner with real time monitoring.

123. The method of claim 105, further comprising:

performing the electroporation in a controlled manner to provide for controlled pore formation in cell membranes.

124. The method of claim 105, further comprising:

performing the electroporation in a controlled manner to create a tissue effect of cells at the BPH tissue site while preserving surrounding tissue.

125. The method of claim 105, further comprising:

performing the electroporation in a controlled manner with monitoring of electrical impedance;

126. The method of claim 105, further comprising:

detecting an onset of electroporation of cells at the BPH tissue site.

127. The method of claim 105, further comprising:

performing the electroporation in a controlled manner with controlled intensity and duration of voltage.

128. The method of claim 105, further comprising:

performing the electroporation in a controlled manner with real time control.

129. The method of claim 105, further comprising:

performing the electroporation in a manner for modification and control of mass transfer across cell membranes.

130. The method of claim 105, further comprising:

performing the electroporation in a controlled manner with a proper selection of voltage magnitude.

131. The method of claim 105, wherein the electroporation is performed in a controlled manner with a proper selection of voltage magnitude.

132. The method of claim 105, wherein the electroporation is performed in a controlled manner with a proper selection of voltage application time.

133. The method of claim 105, wherein the duration of each pulse is about 5 microseconds to about 62 seconds.

134. The method of claim 105, wherein the duration of each pulse is about 90 to 110 microseconds.

135. The method of claim 105, wherein the duration of each pulse is about 100 microseconds.

136. The method of claim 134, wherein about 1 to 15 pulses are applied in the about 90 to 110 microseconds.

137. The method of claim 134, wherein about eight pulses of about 100 microseconds each in duration are applied.

138. The method of claim 105, wherein pulses are applied to produce a voltage gradient at the BPH tissue site in a range of from about 50 volt/cm to about 8000 volt/cm.

139. The method of claim 105, further comprising:

monitoring a temperature of the BPH tissue site; and

adjusting the pulses to maintain a temperature of 100 degrees C. or less at the BPH tissue site.

140. The method of claim 105, further comprising:

monitoring a temperature of the BPH tissue site; and

adjusting the pulses to maintain a temperature of 75 degrees C. or less at the BPH tissue site.

141. The method of claim 105, further comprising:

monitoring a temperature of the BPH tissue site; and

adjusting the pulses to maintain a temperature of 60 degrees C. or less at the BPH tissue site.

142. The method of claim 105, further comprising:

monitoring a temperature of the BPH tissue site; and

adjusting the pulses to maintain a temperature of 50 degrees C. or less at the BPH tissue site.

143. The method of claim 105, further comprising:

adjusting a current-to-voltage ratio based on temperature to maintain the BPH tissue site temperature at 100 degrees C. or less.

144. The method of claim 105, further comprising:

adjusting a current-to-voltage ratio based on temperature to maintain the BPH tissue site temperature at 75 degrees C. or less.

145. The method of claim 105, further comprising:

adjusting a current-to-voltage ratio based on temperature to maintain the BPH tissue site temperature at 60 degrees C. or less.

146. The method of claim 105, further comprising:

adjusting a current-to-voltage ratio based on temperature to maintain the BPH tissue site temperature at 50 degrees C. or less.

147. The method of claim 105, wherein the pulses applied are of sufficient duration and magnitude to permanently disrupt cell membranes of cells at the BPH tissue site.

148. The method of claim 105, wherein a ratio of electric current through cells at the BPH tissue site to voltage across the cells is detected and a magnitude of applied voltage to the BPH tissue site is adjusted in accordance with changes in the ratio of current to voltage.