Ultrasound and Microbubbles in Ocular Diagnostics and Therapies

• US 20090030323A1
• Filed: 08/06/2008
• Published: 01/29/2009
• Est. Priority Date: 04/02/2007
• Status: Active Grant

• Current Assignee: Doheny Eye Institute
• Original Assignee: Doheny Eye Institute
• Inventors: Fawzi, Amani, Ameri, Hossein, Humayun, Mark S.
• Granted Patent: US 8,764,658 B2
• Time in Patent Office: Days
• US Class Current: 600/458
• CPC Class Codes: A61B 8/08 Detecting organic movements or changes, e.g. tumours, cysts, swellings A61B8/02 - A61B8/06 take precedence
• CPC Class Codes: A61B 8/10 Eye inspection
• 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: A61B 8/483 involving the acquisition of a 3D volume of data
• CPC Class Codes: A61F 2009/00863 Retina
• CPC Class Codes: A61F 9/008 using laser
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 41/13 by ultrasonic waves
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61M 31/00 Devices for introducing or retaining media, e.g. remedies, in cavities of the body A61M25/00 takes precedence ; introducing or retaining ophthalmic products into the ocular cavities A61F9/0008
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• 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
• CPC Class Codes: G01N 2203/0076 Hardness, compressibility or resistance to crushing
• CPC Class Codes: G01N 2203/0658 using acoustic or ultrasonic detectors

Abstract

The present disclosure described methods, systems, and techniques for applying contrast-enhanced ultrasound to locate areas of blockage within retinal vessels and to break up clots that are causing damage. In addition to identifying the damaged area, the researchers anticipate that the initial image may serve as a baseline for monitoring the effect of treatment on the vessel, which may be achieved in multiple ways. The vibration effect of the ultrasound itself may suffice to dislodge clots. The microbubbles may also be coated or filled with medication, with ultrasonic shock waves activating the coating or causing mini explosions to release the medicine. Loading the microbubbles with a therapeutic agent, visualizing their presence at the diseased site using the ultrasound diagnostic mode, and then activating the microbubbles to release their contents at the targeted lesion could be a powerful and effective way to reverse occlusion without harming other areas of the eye or body.

Claims

1. A method of treating blood vessel blockage, comprising:

applying ultrasound energy to locate one or more areas of blockage within one or more blood vessels;

directing microbubbles to an area of blockage; and

breaking up clots that are causing damage within the one or more areas of blockage.

2. The method of claim 1, wherein the applying ultrasound energy comprises directing ultrasound energy to the eye.

3. The method of claim 1, further comprising using an initial ultrasound image as a baseline for monitoring the effect of treatment on the vessel.

4. The method of claim 1, wherein the vibration effect of the ultrasound dislodges one or more clots in the one or more areas of blockage.

5. The method of claim 1, wherein the microbubbles are coated or filled with medication, with ultrasonic shock waves activating the coating or causing mini explosions to release the medication.

6. The method of claim 1, wherein applying ultrasound energy comprises using an external probe.

7. The method of claim 1, wherein applying ultrasound energy comprises using an intraocular probe.

8. The method of claim 1 wherein the intraocular probe is multifunctional and contains another surgical instrument.

9. The method of claim 8, wherein the intraocular probe is coupled to a laser to deliver optical treatment.

10. The method of claim 8, wherein the intraocular probes include a cautery portion to deliver therapeutic cauterization.

11. The method of claim 8, wherein the multifunctional probe comprises a forceps or manipulating plate at the tip to manipulate intraocular tissue.

12. The method of claim 1 where the microbubbles are delivered intravenously through the systemic circulation.

13. The method of claim 1 where the microbubbles are injected inside the eye, in the intravitreal or the posterior chamber of the eye, in the anterior chamber, or inside the intraocular tissues.

14. The method of claim 13, wherein the intraocular tissues are in the subretinal, subchoroidal, intralenticular, intracorneal, or in the ciliary body.

15. The method of claim 1 where the microbubbles are delivered in the retinal blood vessels by way of a catheter.

16. A system for treating blood vessel blockage, the system comprising:

a source of ultrasound energy;

a probe coupled to the source and configured and arranged to direct ultrasound energy to a desired location; and

one or more microbubbles, configured and arranged to receive the ultrasound energy, wherein the microbubbles are configured and arranged to contain a desired substance and to burst upon receiving the ultrasound energy, releasing the desired substance in the blood vessel.

17. The system of claim 16, wherein the probe is a needle probe comprising a piezoelectric transducer.

18. A method for the delivery of a drug to a tumor, comprising:

using an ultrasound system configured and arranged to produce an ultrasound output; and

supplying ultrasound contrast agents configured and arranged as microbubbles to a tumor wherein the microbubbles are loaded with chemotherapeutic drug that is active against the tumor, and wherein the ultrasound is used to localize the tumor and activate the microbubbles within the tumor to visualize and activate the release of drug within the tumor.

19. The method of claim 18, wherein the tumor is an intraocular choroidal melanoma, and the drug is labeled to attach to the blood vessels of the tumor selectively.

20. The method of claim 18, wherein the tumor is a ciliary body melanoma.

21. The method of claim 18, wherein the tumor is a retinoblastoma.

22. The method of claim 18, wherein the tumor is an iris tumor.

23. The method of claim 18, wherein the microbubbles are loaded with a therapeutic agent active against subretinalneovascularization in the back of the eye.

24. The method of claim 18, wherein the drug is labeled to attach to the blood vessels of newly formed blood vessels, and the ultrasound output is used to activate the microbubbles focally to release the therapeutic agent.

25. The method of claim 24, wherein an optically labeled microbubble, loaded with therapeutic agent is visualized optically, then activated by ultrasound to release the therapeutic agent within the subretinalneovascular complex.

26. The method of claim 24, wherein the microbubbles are loaded with genetic material.

27. The method of claim 24, wherein the disease is retinitis pigmentosa and the genetic material is able to correct the genetic defect.

28. The method of claim 24, wherein the disease is diabetic retinopathy, and the drug or genetic material is able to reverse the vascular defect in abnormal blood vessels of the diseased retina.

29. The method of claim 18, wherein the drug is labeled to attach to the optic nerve, and the ultrasound output is used to activate the microbubbles focally to release the therapeutic agent.

30. The method of claim 29, wherein the therapeutic agent is a nerve growth factor.

31. The method of claim 29, wherein the therapeutic agent is a vascular growth factor.

32. The method of claim 29, wherein the therapeutic agent is an anti-cancer agent against an optic nerve tumor.

33. The methods of claim 29, wherein the ultrasound is applied externally from outside the eye globe.

34. The method of claim 25, wherein the ultrasound is applied internally from inside the eye.

35. The method of claim 18, where the treatment is directed at the cornea, the front most layer of the eye.

36. The method of claim 35, wherein the ultrasound treatment enhances therapy of corneal disease.

37. The method of claim 35, wherein the microbubbles contain a therapeutic agent against a corneal disease or infection.

38. The method of claim 35, wherein the microbubbles are applied to the surface of the eye that are loaded with drugs and whereby the ultrasound treatment facilitates entry of the drugs into the anterior chamber of the eye, delivering therapeutics to the interior of the eye.