Systems and methods for opening of a tissue barrier

• US 9,358,023 B2
• Filed: 03/21/2012
• Issued: 06/07/2016
• 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:
  US13/426,400
• Publication Number:
  US 20130046229A1
• Time in Patent Office: 1,539 Days
• Field of Search: 600/437, 600/439, 601/2
• US Class Current: 1/1
• 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 said tissue to open;

determining at least one acoustic parameter corresponding to said target value, wherein said at least one acoustic parameter is selected to control a magnitude and a type of one or more acoustic cavitation events to open said tissue to said target value, and wherein said target value corresponds to a treatment and/or imaging value to allow passage of certain molecules and/or agents; and

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

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

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

4. The method of claim 2, wherein said 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 said one or more acoustic cavitation events comprises controlling a number of said one or more acoustic cavitation events.

6. The method of claim 1, wherein said 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 said target value.

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

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

10. The method of claim 1, wherein said 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 said microbubbles into vessels of said tissue.

12. The method of claim 1, wherein said 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 2, wherein said microbubbles comprises said molecule-carrying microbubbles, and wherein said 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 said targeted region.

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

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

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

18. The method of claim 1, wherein the target value comprises a measure of increased size of vessels in the tissue.

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

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

21. 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.

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

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

a targeting assembly for targeting a region of said tissue;

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

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

24. The system of claim 23, wherein said targeting assembly comprises at least one of an ultrasound transducer and one or more members for placement on an anatomical landmark of said tissue, and

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

25. The system of claim 23, wherein said solution of microbubbles further comprises a microbubbles concentration range corresponding to said 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 said tissue to open;

determining at least one acoustic parameter corresponding to said target value, wherein said at least one acoustic parameter is selected to control a magnitude and a type of one or more acoustic cavitation events to open said tissue to said target value, and wherein said target value corresponds to a treatment and/or imaging value to allow passage of certain molecules and/or agents;

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

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

27. The method of claim 26, wherein said 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 said tissue to open;

selecting microbubbles having at least one microbubble parameter corresponding to said target duration of time, wherein said at least one microbubble parameter is selected to control a magnitude and a type of one or more acoustic cavitation events to open said tissue for said target duration of time, and wherein said target duration of time corresponds to a treatment and/or imaging value to allow passage of certain molecules and/or agents; and

applying an ultrasound beam to said targeted region such that said tissue is opened with said microbubbles for said 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 29, further comprising selecting at least one acoustic parameter and applying the ultrasound beam at said at least one acoustic parameter, wherein said at least one acoustic parameter is selected to further control the magnitude and the type of the one or more acoustic cavitation events to open said tissue for said target duration of time.