Systems and methods for opening of a tissue barrier

• US 10,166,379 B2
• Filed: 05/26/2016
• Issued: 01/01/2019
• Est. Priority Date: 03/19/2008
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Konofagou, Elisa E., Choi, James J.
• Primary Examiner(s): Bouchelle, Laura
• Application Number:
  US15/165,942
• Publication Number:
  US 20160346526A1
• Time in Patent Office: 950 Days
• CPC Class Codes: A61B 17/225 for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 8/0808 for diagnosis of the brain
• CPC Class Codes: A61B 8/0816 using echo-encephalography
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: A61M 2202/0007 introduced into the body
• CPC Class Codes: A61M 2205/0244 Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
• CPC Class Codes: A61M 2205/058 with ultrasound therapy
• CPC Class Codes: A61M 2210/0693 Brain, cerebrum
• CPC Class Codes: A61M 2210/12 Blood circulatory system
• CPC Class Codes: A61M 2250/00 Specially adapted for animals
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis

Abstract

Systems and methods for opening a tissue to a target value using microbubbles are disclosed herein. In an embodiment of a method for opening a tissue to a target value using microbubbles, a region of the tissue is targeted for opening, an acoustic parameter corresponding to the target value is determined, and an ultrasound beam is applied to the target region at the acoustic parameter such that the tissue at the target region is opened to the target value with the microbubbles. The acoustic parameter can be selected to control an acoustic cavitation event and, in some embodiments, controlling an acoustic cavitation event can include controlling a location, number and/or magnitude of acoustic cavitation events.

Claims

1. A method for opening a tissue to a target value using microbubbles, comprising:

targeting a region of the tissue to open;

determining at least one acoustic parameter corresponding to the target value, the at least one acoustic parameter is selected to control one or more acoustic cavitation events to open the tissue to the target value to thereby allow passage of molecules and/or agents; and

applying an ultrasound beam at the at least one acoustic parameter to the targeted region such that the tissue is opened with the microbubbles to the target value.

2. The method of claim 1, further comprising positioning the microbubbles in proximity to the targeted region, wherein positioning the microbubbles comprises performing at least one injection of the microbubbles such that the microbubbles are positioned proximate to the targeted region.

3. The method of claim 2, further comprising determining at least one of a number of injections of the microbubbles corresponding to the target value and a duration of injection of the microbubbles corresponding to the target value.

4. The method of claim 2, wherein the at least one injection comprises at least one of a systemic injection, a bolus injection and a slow diffusion injection.

5. The method of claim 1, wherein controlling the one or more acoustic cavitation events comprises controlling a magnitude, a type or a number of the one or more acoustic cavitation events.

6. The method of claim 1, wherein the acoustic parameter is selected from at least one of a pulse length, a pulse repetition frequency, a burst length, and a burst repetition frequency.

7. The method of claim 1, wherein determining at least one acoustic parameter further comprises determining at least one of a frequency, a duration and a pressure range corresponding to the target value.

8. The method of claim 7, wherein the at least one acoustic parameter comprises the pressure range, and wherein the pressure range corresponds to a resonance frequency of the microbubbles proximate to the targeted region.

9. The method of claim 1, further comprising determining a concentration range of microbubbles corresponding to the target value prior to the positioning of the microbubbles.

10. The method of claim 1, wherein the tissue comprises at least one of a vessel, a cell and a blood-brain barrier.

11. The method of claim 1, further comprising applying an ultrasound beam to move the microbubbles into vessels of the tissue.

12. The method of claim 1, wherein the microbubbles comprise at least one of acoustically activated microbubbles, molecule carrying microbubbles and microbubbles having a size range between 1 and 10 microns.

13. The method of claim 12, wherein the microbubbles comprises the molecule-carrying microbubbles, and wherein the molecule comprises at least one of a medicinal molecule, a contrast agent, a biomarker and a liposome.

14. The method of claim 1, further comprising positioning at least one of a medicinal molecule and a contrast agent in proximity to the targeted region.

15. The method of claim 1, further comprising imaging the targeted region to form an image of the opened tissue, wherein imaging the targeted region comprises applying an ultrasound beam to the targeted region, utilizing a magnetic resonance imaging device to image the targeted region, or utilizing a fluorescence imaging device to image the targeted region.

16. The method of claim 1, wherein at least a portion of the opened tissue closes, and the method further comprises imaging the targeted region to form an image of the closed tissue.

17. The method of claim 16, further comprising reopening at least a portion of the closed tissue.

18. The method of claim 1, wherein the target value comprises a target size of an opening of the tissue.

19. The method of claim 1, wherein the target value comprises a target rate at which molecules pass through the tissue.

20. The method of claim 1, wherein the at least one acoustic parameter is selected to open the tissue to the target value using the controlled type of the one or more acoustic cavitation events.

21. The method of claim 20, wherein the controlled type of the one or more acoustic cavitation events comprises at least one of stable cavitation and inertial cavitation.

22. A system for opening a tissue to a target value using a solution of microbubbles having size range corresponding to the target value, comprising:

a targeting assembly for targeting a region of the tissue;

an introducer for delivering the solution to a location proximate to the targeted region; and

a transducer, coupled to the targeting assembly, for applying an ultrasound beam to the targeted region at least one acoustic parameter corresponding to the target value thereby opening the tissue with the microbubbles to the target value, wherein the at least one acoustic parameter is selected to control one or more acoustic cavitation events to open the tissue to the target value to thereby allow passage of molecules and/or agents.

23. The system of claim 22, wherein the target value corresponds to an imaging value to allow passage of certain molecules and/or agents.

24. The system of claim 22, wherein the targeting assembly comprises at least one of an ultrasound transducer and one or more members for placement on an anatomical landmark of the tissue, and

wherein the system further comprises an imaging device for capturing image data of the opened tissue of the targeted region, and a processor, operatively coupled to the imaging device, for processing the image data to form an image therefrom.

25. The system of claim 22, wherein the solution of microbubbles further comprises a microbubbles concentration range corresponding to the target value.

26. A method for delivering a drug across a tissue, comprising opening a tissue to a target value using microbubbles, comprising:

targeting a region of the tissue to open;

determining at least one acoustic parameter corresponding to the target value, wherein the at least one acoustic parameter is selected to control one or more acoustic cavitation events to open the tissue to the target value to thereby allow passage of molecules and/or agents;

applying an ultrasound beam at the at least one acoustic parameter to the targeted region such that the tissue is opened with the microbubbles to the target value; and

injecting the drug into the tissue in proximity to the opening.

27. The method of claim 26, wherein the tissue comprises a blood-brain barrier.

28. A method for opening a tissue for a target duration of time using microbubbles, comprising:

targeting a region of the tissue to open;

selecting microbubbles having at least one microbubble parameter corresponding to the target duration of time, wherein the at least one microbubble parameter is selected to control one or more acoustic cavitation events to open the tissue for the target duration of time to thereby allow passage of molecules and/or agents; and

applying an ultrasound beam to the targeted region such that the tissue is opened with the microbubbles for the target duration of time.

29. The method of claim 28, wherein the at least one microbubble parameter comprises a microbubble size.

30. The method of claim 28, further comprising selecting at least one acoustic parameter and applying the ultrasound beam at the at least one acoustic parameter, wherein the at least one acoustic parameter is selected to further control a magnitude, a type, or a number of the one or more acoustic cavitation events to open the tissue for the target duration of time.