# US 7,756,583 B2 · Methods and apparatus for intravascularly-induced neuromodulation

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- Number: US 7,756,583 B2
- Document ID: US7756583B2
- Status: Granted
- Kind: B2
- Application number: 11/266,993
- Filed: 2005-11-04
- Published: 2006-06-29
- Granted: 2010-07-13
- Earliest claimed: 2002-04-08
- Assignees: Ardian, Inc.
- Inventors: Denise Demarais; Nicolas Zadno; Benjamin J. Clark; Erik Thai
- Web page: https://patentgrep.com/patent/US7756583B2

## CPC

- A61B 18/1492: {having a flexible, catheter-like structure, e.g. for heart ablation (A61B18/1477 takes precedence)}
- A61B 17/12136: {Balloons}
- 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})
- A61N 1/327: {for enhancing the absorption properties of tissue, e.g. by electroporation}
- A61N 1/36121: {Production of neurotransmitters; Modulation of genes expression}
- A61N 1/36182: {Direction of the electrical field, e.g. with sleeve around stimulating electrode}
- A61N 1/40: Applying electric fields by inductive or capacitive coupling (microwave apparatus A61N5/00); {Applying radio-frequency signals}
- A61B 2018/00083: {low, i.e. electrically insulating}
- A61B 2018/00285: {Balloons}
- A61B 2018/00434: {Neural system}
- A61B 2018/00613: {Irreversible electroporation}
- A61M 25/0108: {using radio-opaque or ultrasound markers}
- A61N 1/36007: {of urogenital or gastrointestinal organs, e.g. for incontinence control}
- A61N 1/37205: {Microstimulators, e.g. implantable through a cannula}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)

## 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

### Claim 1

An apparatus for intravascularly-induced neuromodulation, the apparatus comprising:
an electric field generator; and
an intravascular catheter comprising a shaft, an impedance-altering element, and a pair of bipolar electrodes positioned on the shaft on opposite sides of the impedance-altering element, wherein the impedance-altering element comprises an expandable, vessel occluding member;
a first lead connected between one of the electrodes and a first terminal on the electric field generator;
a second lead connected between the other one of the electrodes and a second terminal of opposite polarity on the electric field generator;
at least one monitoring electrode carried by the impedance-altering element; and
a current supply connected to said monitoring electrode for supplying current for monitoring a tissue property,
wherein (a) the apparatus is configured for intravascular delivery of an 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 electric field.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 2)

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

### Claim 4 (depends on 3)

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

### Claim 5 (depends on 3)

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 1)

The apparatus of claim 1 wherein the at least one monitoring electrode is carried by an external surface of the impedance-altering element and is positioned to contact a vessel wall.

### Claim 9 (depends on 8)

The apparatus of claim 8, wherein the monitoring electrode is configured to monitor a treatment effect in tissue exposed to the electric field.

### Claim 10 (depends on 8)

The apparatus of claim 8, wherein the monitoring electrode is configured to monitor impedance of tissue proximate to the monitoring electrode.

### Claim 11 (depends on 1)

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

### Claim 12 (depends on 1)

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

### Claim 13 (depends on 1)

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

### Claim 14 (depends on 1)

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.

### Claim 15 (depends on 1)

The apparatus of claim 1, wherein the electric field generator is configured to deliver a pulsed electric field via the electrode.

### Claim 16 (depends on 15)

The apparatus of claim 15 wherein the at least one monitoring electrode is carried by an external surface of the impedance-altering element and is positioned to contact a vessel wall.

### Claim 17 (depends on 16)

The apparatus of claim 16, wherein the monitoring electrode is configured to monitor electroporation induced in a target tissue by the pulsed electric field.

### Claim 18 (depends on 16)

The apparatus of claim 16, wherein the monitoring electrode is configured to monitor electroporation induced in a non-target tissue by the pulsed electric field.

### Claim 19 (depends on 1)

The apparatus of claim 1, wherein the electric field generator is configured to deliver energy to a target tissue via the electrode, and wherein the energy is sufficient to denervate the target tissue.