Method and Apparatus for Treatment of Hypertension Through Percutaneous Ultrasound Renal Denervation

• US 20120232436A1
• Filed: 10/29/2010
• Published: 09/13/2012
• Est. Priority Date: 10/30/2009
• Status: Active Grant

• Current Assignee: Recor Medical, Inc. (Otsuka Holdings Company Limited)
• Original Assignee: Sound Interventions Inc.
• Inventors: Warnking, Reinhard J.
• Granted Patent: US 9,981,108 B2
• Time in Patent Office: Days
• US Class Current: 601/2
• CPC Class Codes: A61B 2017/003 Steerable
• CPC Class Codes: A61B 2017/00323 Cables or rods
• CPC Class Codes: A61B 2017/22021 electric leads passing through the catheter
• CPC Class Codes: A61B 2018/00023 closed, i.e. without wound contact by the fluid
• CPC Class Codes: A61M 2025/1047 having centering means, e.g. balloons having an appropriate shape
• CPC Class Codes: A61M 2025/1068 having means for varying the length or diameter of the deployed balloon, this variations could be caused by excess pressure
• CPC Class Codes: A61M 2025/1086 having a special balloon surface topography, e.g. pores, protuberances, spikes or grooves
• CPC Class Codes: A61M 2025/1093 having particular tip characteristics
• CPC Class Codes: A61M 25/0068 Static characteristics of the catheter tip, e.g. shape, atraumatic tip, curved tip or tip structure
• CPC Class Codes: A61M 25/0082 Catheter tip comprising a tool
• CPC Class Codes: A61M 25/1002 characterised by balloon shape A61M25/1006, A61M25/1009 take precedence
• CPC Class Codes: A61N 2007/0026 Stimulation of nerve tissue
• CPC Class Codes: A61N 2007/0043 intra-cavitary
• CPC Class Codes: A61N 7/00 Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092
• CPC Class Codes: A61N 7/022 intracavitary

Abstract

Apparatus and methods for deactivating renal nerves extending along a renal artery of a mammalian subject to treat hypertension and related conditions. An ultrasonic transducer (30) is inserted into the renal artery (10) as, for example, by advancing the distal end of a catheter (18) bearing the transducer into the renal artery. The ultrasonic transducer emits unfocused ultrasound so as to heat tissues throughout a relatively large impact volume (11) as, for example, at least about 0.5 cm3 encompassing the renal artery to a temperature sufficient to inactivate nerve conduction but insufficient to cause rapid ablation or necrosis of the tissues. The treatment can be performed without locating or focusing on individual renal nerves.

Claims

1. Apparatus for inactivating renal nerve conduction in a mammalian subject comprising:

an ultrasound transducer adapted for insertion into a renal artery of the mammalian subject and for transmitting unfocused ultrasound energy; and

an actuator electrically connected to the transducer, the actuator being adapted to control the ultrasound transducer to transmit unfocused ultrasound energy into an impact volume of at least 0.5 cm³, encompassing the renal artery so that the unfocused ultrasound energy is applied at a therapeutic level sufficient to inactivate conduction of renal nerves throughout the impact volume.

2. The apparatus of claim 1, wherein the actuator is adapted to control the ultrasound transducer so that the unfocused ultrasound is applied throughout the impact volume at a level insufficient to cause rapid necrosis of tissues.

3. The apparatus of claim 2, wherein the impact volume encompasses all of the renal nerves surrounding the renal artery.

4. The apparatus of claim 1, wherein the actuator is adapted to control the ultrasound transducer to transmit unfocused ultrasound energy at an acoustic power level of 10 to 30 watts for 10 to 30 seconds to provide an absorbed dose of 100 to 900 joules in the impact volume.

5. The apparatus of claim 1, wherein the actuator is adapted to control the transducer so as to maintain the temperature of the renal artery wall below 65°

C. while achieving a temperature above 42°

C. throughout the impact volume for several seconds or more.

6. The apparatus of claim 1, wherein the actuator is adapted to control the ultrasound transducer to transmit the unfocused ultrasound energy in a pulsed function.

7. The apparatus of claim 1, wherein the ultrasound transducer is adapted to transmit the ultrasound energy in a pattern having a length of at least approximately 2 mm along the axis of the renal artery.

8. The apparatus of claim 1, wherein the transducer is adapted to apply the ultrasonic energy at the therapeutic level throughout an impact volume having a length of at least approximately 2 mm along the axis of the of the renal artery.

9. The apparatus of claim 5, further comprising a catheter with a distal end and a proximal end, the transducer being mounted to the catheter adjacent the distal end, the catheter and transducer being constructed and arranged to allow a substantial flow of blood through the renal artery while the ultrasound transducer is positioned within the renal artery.

10. The apparatus of claim 9, wherein the catheter is constructed and arranged to hold the transducer out of contact with the wall of the renal artery.

11. The apparatus of claim 9, wherein the transducer has an axis, the catheter is constructed and arranged to hold the axis of the transducer generally parallel to the axis of the renal artery, and the transducer is adapted to transmit the ultrasound energy in a 360°

cylindrical pattern surrounding the axis of the transducer.

12. The apparatus of claim 10, wherein the catheter includes a centering element in proximity to the transducer, the centering element being arranged to hold the transducer substantially centered in the renal artery.

13. The apparatus of claim 12, wherein the centering element includes an expansible element adapted to engage the wall of the renal artery without substantially blocking flow of blood through the renal artery.

14. The apparatus of claim 1, wherein the ultrasound transducer is further adapted to receive ultrasound energy and generate signals representing the received ultrasonic energy and the actuator is further adapted to:

control the ultrasound transducer to transmit measurement ultrasound energy at a level below the therapeutic level, receive echo signals from the transducer representing reflected measurement ultrasonic energy;

analyze the received echo signals; and

determine a size of the renal artery based on the received echo signal.

15. The apparatus of claim 14, wherein the ultrasound system is adapted to control the ultrasound transducer to vary the acoustic power used to transmit the therapeutically effective unfocused ultrasound energy depending on the determined size of the renal artery.

16. A method for inactivating renal nerve conduction in a mammalian subject comprising the steps of:

inserting an ultrasound transducer into a renal artery of the mammalian subject; and

actuating the transducer to transmit a predetermined therapeutically effective dose of unfocused ultrasound energy into an impact volume of at least approximately 0.5 cm³, encompassing the renal artery so that the therapeutically effective dose of unfocused ultrasound energy inactivates conduction of all the renal nerves in the impact volume.

17. The method of claim 16, wherein the ultrasound energy is transmitted at an acoustic power level of approximately 10 to approximately 30 watts for approximately 10 to approximately 30 seconds to provide an absorbed dose of approximately 100 to approximately 900 joules throughout the impact volume.

18. The method of claim 16, wherein the step of transmitting ultrasound energy is performed so as to maintain the temperature of the renal artery wall below 65°

C. while heating the renal nerves in the impact region to above 42°

C.

19. The method of claim 16, wherein the steps of inserting the ultrasound transducer and actuating the transducer to transmit ultrasound energy are performed without determining the actual locations of renal nerves.

20. The method of claim 16, wherein the step of actuating the transducer is performed so that a single application of the ultrasound energy in each renal artery is effective to inactivate conduction of all the renal nerves surrounding that renal artery.

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

repositioning the ultrasound transducer in the renal artery after the step of actuating the transducer; and

then

repeating the step of actuating the transducer.

22. The method of claim 16, wherein the step of actuating the transducer is performed so that the ultrasound energy is transmitted in a pulsed function.

23. The method of claim 16, wherein the step of inserting the ultrasound transducer is performed so as to permit a substantial flow of blood through the renal artery while the transducer is positioned within the renal artery.

24. The method of claim 16, wherein the step of inserting the ultrasound transducer into the renal artery is performed so that the transducer does not contact the wall of the renal artery.

25. The method of claim 16, wherein the therapeutically effective unfocused ultrasound energy is transmitted in a 360°

cylindrical pattern surrounding the transducer.

26. The method of claim 16, wherein the therapeutically effective unfocused ultrasound energy is transmitted in a pattern having a length of at least approximately 2 mm along the axis of the renal artery.

27. The method of claim 16, wherein the therapeutically effective unfocused ultrasound energy inactivates conduction of a length of at least approximately 2 mm of the renal nerves.

28. The method of claim 16, further comprising the step of substantially centering the ultrasound transducer in the renal artery prior to the step of transmitting the therapeutically effective unfocused ultrasound energy.

29. The method of claim 27, wherein the step of substantially centering the transducer is performed so as to allow a substantially undiminished flow of blood through the renal artery.

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

applying non-therapeutic ultrasound energy at a power level less than a power level of the therapeutically effective ultrasonic energy;

receiving reflected non-therapeutic ultrasonic energy and generating echo signals representing the reflected energy; and

determining a size of the renal artery based on the echo signals before the step of actuating the transducer to apply the therapeutically effective ultrasonic energy.

31. The method of claim 30, further comprising the step of adjusting the power applied to the transducer during actuation to emit therapeutically effective unfocused ultrasound energy based at least in part on the size of the renal artery determined in the determining step.

32. A probe for use in renal nerve inactivation, the probe comprising:

an ultrasound transducer adapted for transmitting unfocused ultrasound energy; and

a catheter with a distal end and a proximal end, the transducer being mounted to the catheter adjacent the distal end, the catheter and transducer being constructed and arranged to allow positioning of the distal end and transducer within a renal artery and to allow a substantial flow of blood through the renal artery while the ultrasound transducer is positioned within the renal artery.

33. The probe of claim 32, wherein the catheter is constructed and arranged to hold the transducer out of contact with the wall of the renal artery.

34. The probe of claim 32, wherein the transducer has an axis, the catheter is constructed and arranged to hold the axis of the transducer generally parallel to the axis of the renal artery, and the transducer is adapted to transmit the ultrasound energy in a 360°

cylindrical pattern surrounding the axis of the transducer.

35. The probe of claim 32, wherein the catheter includes a centering element in proximity to the transducer, the centering element being arranged to hold the transducer substantially centered in the renal artery.

36. The probe of claim 35, wherein the centering element includes an expansible element adapted to engage the wall of the renal artery without substantially blocking flow of blood through the renal artery.

37. The probe of claim 32 further comprising an inflatable balloon surrounding the transducer, the balloon having a non-circular portion which, in an inflated condition, has a major diameter adapted to contact the wall of the renal artery and has a minor diameter smaller than the diameter of the renal artery, the catheter having fluid lumens communicating with the balloon, the probe further comprising a circulation device communicating with the balloon through the lumens for circulating a liquid through the balloon.

38. Apparatus for inactivating renal nerve conduction in a mammalian subject comprising:

an ultrasound transducer;

means for positioning the ultrasound transducer in a renal artery of the mammalian subject so that said transducer is spaced all around from a wall of said artery; and

means for actuating the transducer to transmit a predetermined therapeutically effective dose of unfocused ultrasound energy into an impact volume of at least 0.5 cm³, encompassing the renal artery and achieves a temperature above 42°

C. throughout the impact volume for several seconds or more while maintaining the temperature of the renal artery wall below 65°

C. so that the therapeutically effective dose of unfocused ultrasound energy inactivates conduction of all the renal nerves which are disposed in the impact volume without damaging the intima of the renal artery.

39. An apparatus for inactivating renal nerves comprising:

an ultrasound transducer adapted to emit unfocused ultrasound energy radially outwardly at a frequency transmittable through the renal artery to the renal nerves, the ultrasound transducer having;

a shape suitable to produce unfocused ultrasound energy with a length of at least 2 mm,

an axial length suitable for insertion into the renal artery, and

a diameter suitable to allow fluid to flow around the transducer while the transducer is inserted in the renal artery, the fluid providing cooling to the renal artery;

and

an actuator electrically connected to the transducer, the actuator adapted to control the ultrasound transducer to transmit the unfocused ultrasound energy at a power level and duration that generates;

a near field region of ultrasound energy that encompasses the renal artery, and

a therapeutic ultrasound energy level in the near field region that is sufficient to inactivate the renal nerves.

40. The apparatus of claim 39, wherein the actuator is adapted to control the ultrasound transducer to transmit unfocused ultrasound energy at a frequency of 5 MHz to 15 MHz.

41. The apparatus of claim 39, wherein the shape of the transducer is cylindrical and transmits the unfocused ultrasound energy in a 360°

cylindrical pattern.

42. The apparatus of claim 39, wherein the near field region does not encompass other structures of the body.

43. The apparatus of claim 39, wherein the fluid providing cooling to the renal artery is a continuous flow of blood through the renal artery.

44. The apparatus of claim 39, further comprising:

a catheter with a distal end and a proximal end, the ultrasound transducer mounted to the catheter adjacent the distal end;

an expansible element mounted to the catheter in proximity to the ultrasound transducer.

45. The apparatus of claim 44, wherein the expansible element contains cooling fluid to cool the transducer and the renal artery.

46. The apparatus of claim 44, wherein the expansible element is shaped to allow a continuous flow of blood to cool the renal artery.

47. The apparatus of claim 44, wherein the expansible element is a centering element.

48. The apparatus of claim 39, wherein the power level is an acoustic power level of 10 to 30 watts and the duration is 10 to 30 seconds to provide an absorbed dose of 100 to 900 joules in the near field region.

49. The apparatus of claim 39, wherein the therapeutic ultrasound energy level maintains the temperature of the renal artery wall below 65°

C. while achieving a temperature above 42°

C. throughout the near field region for several seconds or more.

50. The apparatus of claim 39, wherein the unfocused ultrasound is applied throughout the near field region at a level insufficient to cause rapid necrosis of tissues.

51. The apparatus of claim 39, wherein the near field region encompasses all of the renal nerves surrounding the renal artery.

52. An apparatus for deactivating renal nerves to treat hypertension, comprising:

an ultrasound transducer device configured to generate a volumetric distribution of ultrasound radiation where intensity of an ultrasound field decreases with distance from the transducer device, said transducer device being so dimensioned as to enable insertion and disposition thereof inside a renal artery;

a support element operatively connected to said transducer device, said support element being configured to support said transducer device so that said transducer device is not in contact with renal artery tissue; and

a control unit operatively connected to said transducer device for energizing same with an ultrasonic electrical signal with frequency, amplitude, and duration parameters selected so that said volumetric distribution of ultrasound radiation encompasses the renal artery and has a therapeutic ultrasound energy level that is sufficient to inactivate renal nerves within said volumetric distribution of ultrasound radiation.

53. The apparatus of claim 52 wherein said ultrasound transducer device has a length of about 2 mm and said volumetric distribution of ultrasound radiation has a length of about 2 mm.

54. The apparatus of claim 52 wherein said ultrasound transducer device is configured to generate a cylindrical distribution of ultrasound radiation.

55. The apparatus of claim 52 wherein said support element is a centering element allowing for blood flow through the renal artery and past said transducer.

56. The apparatus of claim 52 wherein said volumetric distribution of ultrasound radiation encompasses all renal nerves within a predetermined distance of said transducer device.

57. A method for deactivating renal nerves to treat hypertension, comprising:

inserting an ultrasound transducer into a renal artery;

feeding an electrical signal of ultrasonic frequency to said transducer; and

in response to the feeding of said electrical signal, energizing said transducer to generate a volumetric ultrasound field that decreases in intensity with distance from said transducer and that encompasses a long segment of said renal artery, including renal nerves dispersed circumferentially and longitudinally along said renal artery,

wherein said electrical signal has frequency, amplitude, and duration parameters selected to produce a therapeutic ultrasound energy level within said volumetric ultrasound field sufficient to inactivate renal nerves throughout said volumetric ultrasound field.

58. The method of claim 57 wherein said volumetric ultrasound field is axially symmetric about said transducer.

59. The method of claim 58, further comprising positioning said transducer within the renal artery so that said transducer is not in contact with arterial tissue.