# US 10,245,098 B2 · Acute blood-brain barrier disruption using electrical energy based therapy

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,245,098 B2
- Document ID: US10245098B2
- Status: Granted
- Kind: B2
- Application number: 14/017,210
- Filed: 2013-09-03
- Published: 2014-02-06
- Granted: 2019-04-02
- Earliest claimed: 2008-04-29
- Applicants: Virginia Tech Intellectual Properties, Inc.
- Inventors: Rafael V. Davalos; John H. Rossmeisl; Paulo A. Garcia
- Web page: https://patentgrep.com/patent/US10245098B2

## CPC

- A61B 18/1206: {Generators therefor}
- A61B 18/14: Probes or electrodes therefor
- A61B 18/1477: {Needle-like probes}
- A61N 1/327: {for enhancing the absorption properties of tissue, e.g. by electroporation}
- C12N 13/00: Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
- A61B 2018/00446: {Brain}
- A61B 2018/00577: {Ablation}
- A61B 2018/00613: {Irreversible electroporation}
- A61B 2034/104: {Modelling the effect of the tool, e.g. the effect of an implanted prosthesis or for predicting the effect of ablation or burring}
- A61N 1/05: for implantation or insertion into the body, e.g. heart electrode (A61N1/06 takes precedence)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A method is provided for ablating brain tissue of a living mammal comprising: placing first and second electrodes in a brain of the living mammal; applying a plurality of electrical pulses through the first and second placed electrodes which are predetermined to: cause irreversible electroporation (IRE) of brain tissue of the mammal within a target ablation zone; and cause a temporary disruption of a blood brain barrier (BBB) within a surrounding zone that surrounds the target ablation zone to allow material in a blood vessel to be transferred to the surrounding zone through the temporarily disrupted BBB. Such methods are useful for delivering large molecule material within a blood vessel of the brain across the BBB, where the large molecule is otherwise blocked by the BBB from passing through the blood vessel into the brain.

## Claims

### Claim 1

An ablation system comprising:
a first and second electrode;
a voltage generator programmed to generate a plurality of electrical pulses between the first and second electrodes placed at a selected separation distance therebetween according to one or more pulse parameters which comprise a voltage-to-distance ratio which is predetermined to:
cause irreversible electroporation (IRE) of tissue of the mammal within a target ablation zone but insufficient to cause irreversible electroporation in a non-target zone adjacent the target ablation zone; and
increase susceptibility of the non-target zone to exogenous agents;
wherein the voltage-to-distance ratio is predetermined to cause temporary disruption of a blood brain barrier (BBB) within the non-target zone;
wherein the system is adapted to provide for a display of an anticipated ablation zone and an anticipated zone of BBB disruption based on an electric field distribution expected by the plurality of electrical pulses.

### Claim 2 (depends on 1)

The system of claim 1, further comprising a detector that detects the occurrence of IRE in the target ablation zone.

### Claim 3 (depends on 1)

The system of claim 1, wherein the voltage generator is programmed to generate each electrical pulse as a direct current pulse having a pulse duration of at least 5 microseconds and provide for a voltage-to-distance ratio of from about 10 V/cm to about 10,000 V/cm.

### Claim 4 (depends on 1)

The system of claim 1, wherein the voltage generator is programmed to generate each electrical pulse as a direct current pulse having a pulse duration of between 5 and 100 microseconds and provide for a voltage-to-distance ratio of from about 10 V/cm to about 10,000 V/cm.

### Claim 5

An ablation system comprising:
a first and second electrode;
a memory;
a processor coupled to the memory; and
a voltage generator programmed to generate a plurality of electrical pulses between the first and second electrodes placed at a selected separation distance therebetween and according to one or more pulse parameters which comprise a voltage-to-distance ratio which is predetermined to be:
sufficiently strong to cause non-thermal irreversible electroporation (NTIRE) of tissue of the mammal within a target ablation zone but insufficient to cause irreversible electroporation in a non-target zone adjacent the target ablation zone; and
increase susceptibility of the non-target zone to exogenous agents;
wherein the voltage-to-distance ratio is predetermined to cause temporary disruption of a blood brain barrier (BBB) within the non-target zone;
wherein the system is adapted to provide for a display of an anticipated ablation zone and an anticipated zone of BBB disruption based on an electric field distribution expected by the plurality of electrical pulses.

### Claim 6 (depends on 5)

The system of claim 5, further comprising a detector that detects the occurrence of IRE in the target ablation zone.

### Claim 7 (depends on 5)

The system of claim 5, wherein the voltage generator is programmed to generate each electrical pulse as a direct current pulse having a pulse duration of at least 5 microseconds and provide for a voltage-to-distance ratio of from about 10 V/cm to about 10,000 V/cm.

### Claim 8 (depends on 5)

The system of claim 5, wherein the voltage generator is programmed to generate each electrical pulse as a direct current pulse having a pulse duration of between 5 and 100 microseconds and provide for a voltage-to-distance ratio of from about 10 V/cm to about 10,000 V/m.

### Claim 9

An ablation system comprising:
a first and second electrode;
a voltage generator programmed to:
generate a plurality of electrical pulses between the first and second electrodes placed at a selected separation distance therebetween and according to one or more pulse parameters which comprise a voltage-to-distance ratio predetermined to:
cause electroporation of brain tissue within a target ablation zone;
cause temporary disruption of a blood brain barrier (BBB) within a non-target zone adjacent the target ablation zone; and
increase susceptibility of the non-target zone to exogenous agents; and
wherein the system is adapted to provide for a display of an anticipated ablation zone and an anticipated zone of BBB disruption based on an electric field distribution expected by e plurality of electrical pulses.

### Claim 10 (depends on 9)

The system of claim 9, wherein the display of the anticipated treatment zone is based on a mathematical model.

### Claim 11 (depends on 9)

The system of claim 9, wherein the display of the anticipated treatment zone is based on a numerical model.

### Claim 12 (depends on 9)

The system of claim 9, wherein the display of the anticipated treatment zone is based on finite element software.

### Claim 13 (depends on 9)

The system of claim 9, further comprising a detector that detects electroporation in the target ablation zone and temporary BBB disruption in the non-target zone.

### Claim 14 (depends on 9)

The system of claim 9, wherein the voltage generator is programmed to generate direct current pulses.

### Claim 15 (depends on 9)

The system of claim 9, wherein the voltage generator is programmed to generate pulses with a duration of at least 5 microseconds.

### Claim 16 (depends on 9)

The system of claim 9, wherein the voltage generator is programmed to generate pulses with a voltage-to-distance ratio of from about 10 V/cm to about 10,000 V/cm.

### Claim 17 (depends on 9)

The system of claim 9, wherein the voltage generator is programmed to generate pulses with a duration of between 5 and 100 microseconds.

### Claim 18 (depends on 17)

The system of claim 17, wherein the voltage generator is programmed to generate pulses with a voltage-to-distance ratio of from about 10 V/cm to about 10,000 V/cm.