Methods and apparatus for intravascularly-induced neuromodulation

• US 20060142801A1
• Filed: 11/04/2005
• Published: 06/29/2006
• Est. Priority Date: 04/08/2002
• 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.
• Granted Patent: US 7,756,583 B2
• Time in Patent Office: Days
• US Class Current: 607/2
• CPC Class Codes: A61B 17/12136 Balloons
• CPC Class Codes: A61B 18/1492 having a flexible, catheter-like structure, e.g. for heart ablation A61B18/1477 takes precedence
• CPC Class Codes: A61B 2018/00083 low, i.e. electrically insulating
• CPC Class Codes: A61B 2018/00285 Balloons
• CPC Class Codes: A61B 2018/00434 Neural system
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation
• CPC Class Codes: A61M 25/0108 using radio-opaque or ultrasound markers
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• 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
• CPC Class Codes: A61N 1/36121 Production of neurotransmitters; Modulation of genes expression
• CPC Class Codes: A61N 1/36182 Direction of the electrical field, e.g. with sleeve around stimulating electrode
• CPC Class Codes: A61N 1/37205 Microstimulators, e.g. implantable through a cannula
• CPC Class Codes: A61N 1/40 Applying electric fields by inductive or capacitive coupling microwave apparatus A61N5/00; Applying radio-frequency signals

Abstract

Methods and apparatus are provided for intravascularly-induced neuromodulation using a pulsed electric field, e.g., to effectuate irreversible electroporation or electrofusion, necrosis and/or inducement of apoptosis, alteration of gene expression, changes in cytokine upregulation, etc., in target neural fibers. In some embodiments, the intravascular PEF system comprises a catheter having a pair of bipolar electrodes for delivering the PEF, with a first electrode positioned on a first side of an impedance-altering element and a second electrode positioned on an opposing side of the impedance-altering element. A length of the electrodes, as well as a separation distance between the first and second electrodes, may be specified such that, with the impedance-altering element deployed in a manner that locally increases impedance within a patient'"'"'s vessel, e.g., with the impedance-altering element deployed into contact with the vessel wall at a treatment site within the patient'"'"'s vasculature, a magnitude of applied voltage delivered across the bipolar electrodes necessary to achieve desired neuromodulation is reduced relative to an intravascular PEF system having similarly spaced electrodes but no (or an undeployed) impedance-altering element. In a preferred embodiment, the impedance-altering element comprises an inflatable balloon configured to locally increase impedance within a patient'"'"'s vasculature. The methods and apparatus of the present invention may be used to modulate a neural fiber that contributes to renal function.

Claims

1. Apparatus for intravascularly-induced neuromodulation, the apparatus comprising:

a pulsed electric field generator; and

an intravascular catheter comprising an impedance-altering element and a pair of bipolar electrodes positioned on either side of the impedance-altering element, the electrodes being electrically coupled to the pulsed electric field generator, wherein (a) the apparatus is configured for intravascular delivery of a pulsed electric field across the bipolar electrodes, and (b) the impedance-altering element is configured to locally increase impedance within a patient'"'"'s vasculature between the bipolar electrodes during intravascular delivery of the pulsed electric field.

2. The apparatus of claim 1, wherein the impedance-altering element is configured to temporarily occlude blood flow within the patient'"'"'s vasculature.

3. The apparatus of claim 2, wherein the impedance-altering element comprises a balloon element.

4. The apparatus of claim 3, wherein the balloon element comprises a compliant or semi-compliant balloon.

5. The apparatus of claim 3, wherein the balloon element comprises a non-compliant balloon.

6. The apparatus of claim 1, wherein the separation distance between the bipolar electrodes is not greater than about 20 mm.

7. The apparatus of claim 1, wherein each of the bipolar electrodes comprises a length of at least about 1 mm.

8. The apparatus of claim 1 further comprising at least one monitoring electrode.

9. The apparatus of claim 8, wherein the monitoring electrode is configured to monitor electroporation induced in a target neural fiber by the pulsed electric field.

10. The apparatus of claim 8, wherein the electrode is configured to monitor electroporation in non-target tissue exposed to the pulsed electric field.

11. The apparatus of claim 1, wherein the impedance-altering element is configured to substantially center the bipolar electrodes within the patient'"'"'s vasculature.

12. The apparatus of claim 1, wherein the apparatus is configured for intravascular delivery of the pulsed electric field to neural fibers that contribute to renal function in order to modulate the neural fibers.

13. The apparatus of claim 1, wherein the impedance-altering element comprises an insulative covering positioned about a mechanical activation member.

14. The apparatus of claim 1, wherein the impedance altering element is configured to locally increase impedance within the patient'"'"'s vasculature along a segment of the vasculature having a length of less than about 20 mm.

29. The apparatus of claim 1, wherein at least one of the pair of bipolar electrodes comprises a wound coil.

15. A method for intravascularly-induced neuromodulation, the method comprising:

positioning a pair of bipolar electrodes within a patient'"'"'s vasculature, the electrodes being spaced less than about 20 mm apart;

increasing impedance within the vasculature between the bipolar electrodes; and

delivering a pulsed electric field across the bipolar electrodes.

16. The method of claim 15, wherein positioning a pair of bipolar electrodes within a patient'"'"'s vasculature further comprises positioning the pair of bipolar electrodes within the patient'"'"'s renal artery.

17. The method of claim 15, wherein positioning a pair of bipolar electrodes within a patient'"'"'s vasculature further comprises positioning an intravascular catheter having the bipolar electrodes within the patient'"'"'s vasculature.

18. The method of claim 17, wherein positioning an intravascular catheter having the bipolar electrodes further comprises positioning an intravascular catheter having an impedance-altering element positioned between the bipolar electrodes.

19. The method of claim 18, wherein locally increasing impedance further comprises locally increasing impedance with the impedance-altering element.

20. The method of claim 19, wherein locally increasing impedance with the impedance-altering element further comprises occluding blood flow in the vasculature with the impedance-altering element.

21. The method of claim 20, wherein occluding blood flow in the vasculature with the impedance-altering element further comprises inflating a balloon impedance-altering element.

22. The method of claim 15, wherein locally increasing impedance further comprises directing the pulsed electric field across a wall of the patient'"'"'s vasculature between the bipolar electrodes.

23. The method of claim 15, wherein delivering a pulsed electric field further comprises modulating a neural fiber that contributes to renal function.

24. The method of claim 23, 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, gene expression alteration, cytokine upregulation alteration, and combinations thereof.

25. The method of claim 15 further comprising substantially centering the bipolar electrodes within the patient'"'"'s vasculature prior to delivering the pulsed electric field.

26. The method of claim 19, wherein locally increasing impedance with the impedance-altering element further comprises centering the bipolar electrodes within the patient'"'"'s vasculature.

27. The method of claim 15 further comprising monitoring electroporation in tissue exposed to the pulsed electric field.

28. The method of claim 19, wherein locally increasing impedance with the impedance-altering element further comprises expanding an insulative covering into contact with a wall of the vasculature via a mechanical activation member.

30. A method for intravascularly-induced neuromodulation, the method comprising:

positioning a pair of bipolar electrodes within a patient'"'"'s vasculature, the electrodes spaced less than about 20 mm apart;

occluding blood flow within the patient'"'"'s vasculature between the bipolar electrodes; and

delivering a pulsed electric field across the bipolar electrodes.