Methods and apparatus for pulsed electric field neuromodulation via an intra-to-extravascular approach

• US 7,620,451 B2
• Filed: 02/27/2006
• Issued: 11/17/2009
• Est. Priority Date: 12/29/2005
• Status: Active Grant

• Current Assignee: Medtronic Ardian Luxembourg SARL (Medtronic Plc)
• Original Assignee: Ardian, Inc. (Medtronic Plc)
• Inventors: Thai, Erik, Demarais, Denise, Zadno, Nicolas, Clark, Benjamin J., Gifford, Hanson III
• Primary Examiner(s): Layno; Carl H
• Assistant Examiner(s): MALAMUD, DEBORAH LESLIE
• Application Number:
  US11/363,867
• Publication Number:
  US 20070203549A1
• Time in Patent Office: 1,359 Days
• Field of Search: 607 1- 3, 607/9, 607/72
• US Class Current: 607/3
• CPC Class Codes: A61B 18/1206 Generators therefor
• CPC Class Codes: A61B 18/1477 Needle-like probes
• CPC Class Codes: A61B 2018/0022 Balloons
• CPC Class Codes: A61B 2018/00267 having a basket shaped structure
• CPC Class Codes: A61B 2018/00404 Blood vessels other than those in or around the heart
• CPC Class Codes: A61B 2018/00434 Neural system
• CPC Class Codes: A61B 2018/00505 Urinary tract
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation reversible electroporation A61N1/327
• CPC Class Codes: A61B 2018/126 bipolar
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 5/14 Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
• 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 1/0514 Electrodes for the urinary tract
• CPC Class Codes: A61N 1/0551 Spinal or peripheral nerve electrodes
• CPC Class Codes: A61N 1/321 Electromedical belts
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control

Abstract

Methods and apparatus are provided for pulsed electric field neuromodulation via an intra-to-extravascular approach, e.g., to effectuate irreversible electroporation or electrofusion, necrosis and/or inducement of apoptosis, alteration of gene expression, changes in cytokine upregulation and other conditions in target neural fibers. In some embodiments, the ITEV PEF system comprises an intravascular catheter having one or more electrodes configured for intra-to-extravascular placement across a wall of patient'"'"'s vessel into proximity with target neural fibers. With the electrode(s) passing from an intravascular position to an extravascular position prior to delivery of the PEF, a magnitude of applied voltage or energy delivered via the electrode(s) and necessary to achieve desired neuromodulation may be reduced relative to an intravascular PEF system having one or more electrodes positioned solely intravascularly. The methods and apparatus of the present invention may, for example, be used to modulate one or more target neural fibers that contribute to renal function.

Claims

1. An apparatus for electric field neuromodulation via an intra-to-extravascular approach, the apparatus comprising:

an electric field generator;

a catheter comprising an elongated shaft; and

at least one electrode electrically coupled to the electric field generator and carried by the elongated shaft, the electrode configured for intravascular delivery and extravascular placement via an intra-to-extravascular approach,

wherein the electrode is configured for extravascular delivery of an electric field to induce neuromodulation, and

wherein a distal segment of the elongated shaft is configured to be positioned within a patient, and wherein a proximal segment of the elongated shaft is configured to be external to the patient during neuromodulation.

6. The apparatus of claim 1, wherein the electrode is coupled to an expandable element of the catheter.

2. The apparatus of claim I further comprising a piercing element configured for intravascular delivery, the piercing element configured to pierce a wall of vasculature of a patient from within the vasculature.

3. The apparatus of claim 2, wherein the electrode comprises the piercing element.

4. The apparatus of claim 2, wherein the piercing element comprises a needle or cannula.

5. The apparatus of claim 4, wherein the electrode is configured for extravascular placement through a lumen of the needle.

7. An apparatus for electric field neuromodulation via an intra-to-extravascular approach, the apparatus comprising:

an electric field generator; and

at least one electrode electrically coupled to the electric field generator, the electrode configured for intravascular delivery and extravascular placement via an intra-to-extravascular approach,

wherein the electrode is configured for extravascular delivery of an electric field to induce neuromodulation, and

wherein the electrode comprises at least one bipolar electrode pair having a first electrode and a second electrode, the bipolar electrode pair coupled to the electric field generator.

8. The apparatus of claim 7, wherein the apparatus is configured for extravascular delivery of the electric field across the bipolar electrode pair.

9. The apparatus of claim 7, wherein the first electrode is configured for extravascular placement via an intra-to-extravascular approach, and the second electrode is configured for intravascular placement.

10. The apparatus of claim 9, wherein the first electrode comprises an active electrode and the second electrode comprises a return electrode.

11. The apparatus of claim 7, wherein both the first electrode and the second electrode are configured for extravascular placement via an intra-to-extravascular approach.

12. The apparatus of claim 7, wherein the first electrode and the second electrode are longitudinally spaced apart from one another in a deployed configuration.

13. The apparatus of claim 7, wherein the first electrode and the second electrode are angularly-aligned with one another relative to a circumference of a patient'"'"'s vasculature.

14. An apparatus for electric field neuromodulation via an intra-to-extravascular approach, the apparatus comprising:

an electric field generator;

at least one electrode electrically coupled to the electric field generator, the electrode configured for intravascular delivery and extravascular placement via an intra-to-extravascular approach,

an external ground pad, wherein the electrode is configured for monopolar extravascular delivery of the electric field to induce neuromodulation.

15. An apparatus for electric field neuromodulation via an intra-to-extravascular approach, the apparatus comprising:

an electric field generator; and

at least one electrode electrically coupled to the electric field generator, the electrode configured for intravascular delivery and extravascular placement via an intra-to-extravascular approach,

wherein the electrode is configured for extravascular delivery of an electric field to induce neuromodulation, and

wherein the apparatus is configured for extravascular infusion of agents.

16. The apparatus of claim 15, wherein the apparatus is configured for extravascular infusion of agents that enhance neuromodulation or provide protective effects.

17. A method for electric field neuromodulation via an intra-to-extravascular approach, the method comprising:

intravascularly advancing at least one electrode to a treatment site within vasculature of a patient;

passing a portion of the electrode through at least a portion of a wall of the vasculature to position the electrode at an extravascular location via an intra-to-extravascular approach; and

extravascularly delivering an electric field via the electrode to induce neuromodulation.

18. The method of claim 17, wherein intravascularly advancing at least one electrode to a treatment site within vasculature of a patient further comprises intravascularly moving the electrode to a treatment site within a renal artery of the patient.

19. The method of claim 17, wherein intravascularly advancing at least one electrode to a treatment site within vasculature of a patient further comprises intravascularly moving an intravascular catheter having the electrode to the treatment site within the vasculature of the patient.

20. The method of claim 19, wherein passing a portion of the electrode through at least a portion of a wall of the vasculature to position the electrode at an extravascular location via an intra-to-extravascular approach further comprises expanding an expandable element of the catheter.

21. The method of claim 17, wherein intravascularly advancing at least one electrode to a treatment site within vasculature of a patient further comprises moving the electrode through an intravascular catheter positioned at the treatment site.

22. The method of claim 17, wherein extravascularly delivering an electric field to induce neuromodulation further comprises extravascularly applying the electric field to modulate a neural fiber that contributes to renal function.

23. The method of claim 22, wherein modulating a neural fiber that contributes to renal function further comprises inducing an effect in the neural fiber chosen from the group consisting of irreversible electroporation, electrofusion, necrosis, apoptosis, ablation, gene expression alteration, cytokine upregulation alteration, and combinations thereof.

24. The method of claim 17 wherein passing a portion of the electrode through at least a portion of a wall of the vasculature to position the electrode at an extravascular location via an intra-to-extravascular approach further comprises piercing the wall of the vasculature, and advancing the electrode through the wall piercing.

25. The method of claim 24, wherein piercing the wall of the vasculature further comprises forcing the electrode through the wall of the vasculature.

26. The method of claim 17, wherein advancing at least one electrode to a treatment site further comprises advancing at least one bipolar electrode pair to the treatment site.

27. The method of claim 26, wherein passing a portion of the electrode through at least a portion of a wall of the vasculature to position the electrode at an extravascular location via an intra-to-extravascular approach further comprises moving the bipolar electrode pair extravascularly, and wherein extravascularly delivering an electric field further comprises extravascularly delivering the electric field across the bipolar electrode pair.

28. The method of claim 26, wherein passing a portion of the electrode through at least a portion of a wall of the vasculature to position the electrode at an extravascular location via an intra-to-extravascular approach further comprises positioning a first electrode of the bipolar electrode pair at the extravascular location and positioning a second electrode of the bipolar electrode pair at an intravascular location.

29. The method of claim 17 further comprising infusing an agent to enhance the neuromodulation.

30. The method of claim 17 further comprising infusing an agent to protect non-target tissue.

31. The method of claim 17 wherein extravascularly delivering an electric field via the electrode to induce neuromodulation further comprises extravascularly delivering a pulsed electric field via the electrode to induce neuromodulation.

32. The method of claim 17 wherein extravascularly delivering an electric field via the electrode to induce neuromodulation further comprises extravascularly delivering RE energy via the electrode to induce neuromodulation.

33. The method of claim 17 wherein extravascularly delivering an electric field via the electrode to induce neuromodulation further comprises extravascularly delivering thermal energy via the electrode to induce neuromodulation.

34. The method of claim 33 wherein extravascularly delivering RF energy via the electrode to induce neuromodulation further comprises extravascularly delivering ablative energy via the electrode to induce neuromodulation.