Systems and methods for opening a tissue

• US 9,302,124 B2
• Filed: 03/10/2011
• Issued: 04/05/2016
• Est. Priority Date: 09/10/2008
• 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., Borden, Mark A.
• Primary Examiner(s): Le, Long V
• Assistant Examiner(s): BOR, HELENE CATHERINE
• Application Number:
  US13/045,070
• Publication Number:
  US 20110295105A1
• Time in Patent Office: 1,853 Days
• Field of Search: 600/431, 600/433, 600/439, 600/427
• US Class Current: 1/1
• CPC Class Codes: A61B 2090/374 NMR or MRI
• 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 8/481 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 31/005 for contrast media
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61N 2007/0039 using microbubbles
• CPC Class Codes: 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

Abstract

Systems and methods for opening a tissue to a target value are disclosed herein. In an exemplary method, a region of the tissue is targeted for opening, a size range of microbubbles corresponding to the target value is determined, microbubbles of the size range are positioned in proximity to the targeted region, and an ultrasound beam is applied to the targeted region such that the tissue is opened with the assistance of the microbubbles to the target value.

Claims

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

targeting a region of said tissue for opening;

selecting the target value based on a size of a molecule to pass through the tissue and a surface area of the region to be exposed to the molecule;

determining a size range of microbubbles corresponding to said target value;

generating a polydispersed microbubble distribution using acoustic emulsification;

isolating the microbubbles of the size range from the polydispersed microbubble distribution using differential centrifugation;

positioning the microbubbles of said size range in proximity to said targeted region; and

applying an ultrasound beam to said targeted region such that said tissue is opened with the assistance of said microbubbles to said target value.

2. The method of claim 1, further comprising determining a concentration range of microbubbles corresponding to said target value, and wherein positioning said microbubbles further comprises positioning said microbubbles of said concentration range.

3. The method of claim 1, further comprising determining a pressure range for said ultrasound beam corresponding to said target value, and wherein applying said ultrasound beam comprises applying said ultrasound beam at said pressure range.

4. The method of claim 3, wherein said pressure range corresponds to a resonance frequency of said microbubbles proximate to said targeted region.

5. The method of claim 1, wherein said tissue comprises a blood-brain barrier.

6. The method of claim 1, wherein said tissue comprises a vessel.

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

8. The method of claim 1, wherein determining said size range of microbubbles comprises determining a size range corresponding to a size range of vessels of said tissue.

9. The method of claim 1, wherein said size range of microbubbles is 4 to 5 microns.

10. The method of claim 1, wherein said size range of microbubbles is 1 to 2 microns.

11. The method of claim 1, wherein said size range of microbubbles is 9 to 10 microns.

12. The method of claim 1, wherein said size range of microbubbles is 6 to 8 microns.

13. The method of claim 1, wherein said microbubbles are acoustically activated microbubbles.

14. The method of claim 1, wherein said microbubbles are molecule carrying microbubbles.

15. The method of claim 14, wherein said molecule is a medicinal molecule.

16. The method of claim 14, wherein said molecule is a contrast agent.

17. The method of claim 14, wherein said molecule is a biomarker.

18. The method of claim 14, wherein said molecule is a liposome.

19. The method of claim 14, wherein said molecule carrying microbubbles are carrying a medicinal molecule and a contrast agent.

20. The method of claim 1, further comprising positioning medicinal molecules in proximity to said targeted region.

21. The method of claim 1, further comprising positioning a contrast agent in proximity to said targeted region.

22. The method of claim 1, wherein the desired permeability comprises one or more of a size of a molecule to pass through the tissue, an area of the tissue to be opened, and a rate at which molecules pass through the tissue.

23. A method for imaging the opening of a tissue to a target value, comprising:

targeting a region of said tissue for opening;

selecting the target value based on a size of a molecule to pass through the tissue and a surface area of the region to be exposed to the molecule;

determining a size range of microbubbles corresponding to said target value;

generating a polydispersed microbubble distribution using acoustic emulsification;

isolating the microbubbles of the size range from the polydispersed microbubble distribution using differential centrifugation;

positioning the microbubbles of said size range in proximity to said targeted region;

applying an ultrasound beam to said targeted region such that said tissue is opened with the assistance of said microbubbles to said target value; and

collecting image information for said targeted region of said opening tissue.

24. The method of claim 23, wherein imaging said targeted region comprises applying an ultrasound beam to said targeted region.

25. The method of claim 23, wherein imaging said targeted region comprises utilizing a magnetic resonance imaging device to image said targeted region.

26. A system for opening a tissue to a target value, comprising:

a targeting assembly for targeting a region of said tissue;

a processor programmed with logic configured to;

select the target value based on a size of a molecule to pass through the tissue and a surface area of the region to be exposed to the molecule; and

determine a size range of microbubbles corresponding to said target value;

a probe adapted to generate a polydispersed microbubble distribution using acoustic emulsification;

a centrifuge adapted to isolate the microbubbles of the size range from the polydispersed microbubble distribution using differential centrifugation; and

an introducer adapted to deliver a solution including the microbubbles of the size range to a location proximate to said targeted region; and

a transducer, coupled to said targeting assembly, adapted to apply an ultrasound beam to said targeted region to thereby open said tissue with the assistance of said microbubbles to said target value.

27. The system of claim 26, wherein the system comprises an imaging transducer.

28. The system of claim 26, wherein said targeting assembly comprises one or more members for placement on an anatomical landmark of said tissue.

29. The system of claim 26, wherein said solution of size-controlled microbubbles further comprises a microbubble concentration range corresponding to said target value.

30. The system of claim 26, wherein said solution of size-controlled microbubbles further comprise microbubbles of a size range corresponding to a size range of vessels of said tissue.

31. The system of claim 26, wherein said tissue comprises a blood-brain barrier.

32. The system of claim 26, wherein said tissue comprises a vessel.

33. The system of claim 26, wherein said size range of microbubbles is 4 to 5 microns.

34. The system of claim 26, wherein said size range of microbubbles is 1 to 2 microns.

35. The system of claim 26, wherein said size range of microbubbles is 9 to 10 microns.

36. The system of claim 26, wherein said size range of microbubbles is 6 to 8 microns.

37. The system of claim 26, wherein said microbubbles are acoustically activated microbubbles.

38. The system of claim 26, wherein said microbubbles are molecule carrying microbubbles.

39. The system of claim 38, wherein said molecule is a medicinal molecule.

40. The system of claim 38, wherein said molecule is a contrast agent.

41. The system of claim 38, wherein said molecule is a biomarker.

42. The system of claim 38, wherein said molecule is a liposome.

43. The system of claim 38, wherein said molecule carrying microbubbles are carrying a medicinal molecule and a contrast agent.

44. The system of claim 38, wherein said molecule carrying microbubbles are coated with a medicinal molecule and a contrast agent.

45. The system of claim 26, further comprising a solution of medicinal molecules and an introducer for delivering said solution of medicinal molecules to a location proximate to said targeted region.

46. The system of claim 26, further comprising a solution of contrast agent and an introducer for delivering said solution of contrast to a location proximate to said targeted region.

47. A system for imaging the opening of a tissue to a target value, comprising:

a targeting assembly for targeting a region of said tissue;

a data processor programmed with logic configured to;

select the target value based on size of a molecule to pass through the tissue and a surface area of the region to be exposed to the molecule; and

determine a size range of microbubbles corresponding to said target value;

a probe adapted to generate a polydispersed microbubble distribution using acoustic emulsification;

a centrifuge adapted to isolate the microbubbles of the size range from the polydispersed microbubble distribution using differential centrifugation;

an introducer adapted to deliver a solution including the microbubbles of the size range to a location proximate to said targeted region; and

a transducer, coupled to said targeting assembly, adapted to apply an ultrasound beam to said targeted region to thereby open said tissue with the assistance of said microbubbles to said target value;

an imaging device adapted to capture image data of said opened tissue of said targeted region; and

an image processor, operatively coupled to said imaging device, adapted to process said image data to form an image therefrom.

48. The system of claim 47, wherein said imaging device comprises an imaging transducer.

49. The system of claim 47, wherein said imaging device comprises a magnetic resonance imaging device.

50. The system of claim 47, wherein said imaging device comprises an optical imaging device.