# US 10,441,820 B2 · Systems and methods for opening of a tissue barrier in primates

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- Number: US 10,441,820 B2
- Document ID: US10441820B2
- Status: Granted
- Kind: B2
- Application number: 14/091,010
- Filed: 2013-11-26
- Published: 2014-04-24
- Granted: 2019-10-15
- Earliest claimed: 2011-05-26
- Assignees: The Trustees of Columbia University in the City of New York
- Applicants: The Trustees of Columbia University in the Ciy of New York
- Inventors: Elisa E. Konofagou; Fabrice Marquet; Yao-Sheng Tung
- Web page: https://patentgrep.com/patent/US10441820B2

## CPC

- 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})
- A61B 8/0808: {for diagnosis of the brain}
- A61B 8/481: {involving the use of contrast agents, e.g. microbubbles introduced into the bloodstream}
- A61B 17/2258: {integrated in a central portion of the shock wave apparatus}
- A61B 90/10: for stereotaxic surgery, e.g. frame-based stereotaxis
- A61B 2017/00106: {ultrasonic}
- A61B 2017/22008: {used or promoted}
- A61B 2017/22089: {Gas-bubbles}
- A61B 2090/378: {using ultrasound}
- A61B 2503/40: Animals
- A61N 2007/0039: {using microbubbles}
- 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)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

Systems and methods for cavitation-guided opening of a targeted region of tissue within a primate skull are provided. In one example, a method includes delivering one or more microbubbles to proximate the targeted region, applying an ultrasound beam, using a transducer, through the skull of the primate to the targeted region to open the tissue, transcranially acquiring acoustic emissions produced from an interaction between the one or more microbubbles and the tissue, and determining a cavitation spectrum from the acquired acoustic emissions.

## Claims

### Claim 1

A method for cavitation-guided opening of a targeted region of tissue within a primate skull, comprising:
delivering one or more microbubbles to proximate the targeted region;
applying an ultrasound beam using a transducer, through the skull of the primate to the targeted region to open the tissue;
transcranially acquiring acoustic emissions produced from an interaction between the one or more microbubbles and the tissue;
determining a cavitation spectrum from the acquired acoustic emissions;
determining whether a vessel is located between the ultrasound beam and the targeted region or proximate to the targeted region based on the cavitation spectrum; and
determining a cavitation signal-to-noise ratio (SNR) from the acquired acoustic emissions, wherein the cavitation SNR is a ratio of post- to pre-microbubble cavitation doses.

### Claim 2 (depends on 1)

The method of claim 1, wherein the method is performed in vivo.

### Claim 3 (depends on 1)

The method of claim 1, further comprising determining a distance between the skull and the transducer based on the acoustic emissions.

### Claim 4 (depends on 1)

The method of claim 1, further comprising determining a focal depth of the transducer based on the acoustic emissions.

### Claim 5 (depends on 1)

The method of claim 1, further comprising adjusting the targeted region based on the vessel.

### Claim 6 (depends on 1)

The method of claim 1, further comprising adjusting the targeted region based on the vessel, wherein the adjusting comprises avoiding the vessel or shielding by the vessel.

### Claim 7 (depends on 1)

The method of claim 1, further comprising determining a presence of inertial cavitation during opening and adjusting one or more parameters to prevent the inertial cavitation.

### Claim 8 (depends on 7)

The method of claim 7, wherein the one or more parameters is selected from the group consisting of a size of the one or more microbubbles and an acoustic pressure of the ultrasound beam.

### Claim 9 (depends on 8)

The method of claim 8, wherein the one or more microbubbles is adjusted to a size within a range of between 1 to 10 microns.

### Claim 10 (depends on 8)

The method of claim 8, wherein the one or more microbubbles is adjusted to a size within a range of between 4 to 5 microns.

### Claim 11 (depends on 8)

The method of claim 8, wherein the acoustic pressure of the ultrasound beam is adjusted to within a range between 0.3 to 0.45 MPa at the targeted region.

### Claim 12 (depends on 1)

The method of claim 1, wherein the ultrasound beam has a center frequency from 0.5 to 1.5 MHz and a pressure from 0.3 MPa to 0.6 MPa.