Method and Apparatus for Ultrasound Drug Delivery and Thermal Therapy with Phase-Convertible Fluids

• US 20080200845A1
• Filed: 05/25/2006
• Published: 08/21/2008
• Est. Priority Date: 06/07/2005
• Status: Active Grant

• Current Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Original Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Inventors: Bohmer, Marcel Rene, Hall, Christopher Stephen, Sokka, Shunmugavelu
• Granted Patent: US 8,932,239 B2
• Time in Patent Office: Days
• US Class Current: 601/3
• CPC Class Codes: A61B 2017/22008 used or promoted
• CPC Class Codes: A61B 8/12 in body cavities or body tracts, e.g. by using catheters catheters per se A61M25/00
• CPC Class Codes: A61B 8/546 involving monitoring or regulation of device temperature
• CPC Class Codes: A61K 41/0033 Sonodynamic cancer therapy with sonochemically active agents or sonosensitizers, having their cytotoxic effects enhanced through application of ultrasounds ultrasound therapy per se A61N7/00
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• 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: A61N 7/02 Localised ultrasound hyperthermia hyperthermia in general A61F7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

An ultrasound treatment comprises applying ultrasound at a first energy level (32) to a region of interest (20) in a subject for activating a cavitation nucleation agent during a first portion of a treatment cycle (t1-t2). Ultrasound at a second energy level (34) is applied to the region of interest (20) during a second portion of the treatment cycle (t2-t3) for implementing a desired thermal therapy in the presence of the cavitation nucleation agent activated during the first portion of the treatment cycle. The second energy level is at an energy level different from the first energy level.

Claims

1. A method of ultrasound treatment comprising:

applying ultrasound at a first energy level to a region of interest in a subject for activating a cavitation nucleation agent during a first portion of a treatment cycle; and

applying ultrasound at a second energy level to the region of interest during a second portion of the treatment cycle for implementing a desired thermal therapy in the presence of the cavitation nucleation agent activated during the first portion of the treatment cycle, wherein the second energy level is at an energy level different from the first energy level.

2. The method of claim 1, wherein the first portion comprises an ultrasound induced phase conversion portion.

3. The method of claim 2, further wherein the cavitation nucleation agent comprises a phase-convertible fluid and wherein the ultrasound induced phase conversion portion includes phase conversion of the phase-convertible fluid.

4. The method of claim 2, further wherein the phase-convertible fluid includes to a liquid having a boiling point above 37 degrees C. and below 100 degrees C.

5. The method of claim 4, further wherein the liquid contains particles.

6. The method of claim 5, further wherein the particles comprise liquid perfluorocarbon filled particles below 37 degrees C.

7. The method of claim 5, further wherein the particles have a size less than or equal to 5 microns.

8. The method of claim 5, further wherein the particles are encapsulated with a biodegradable polymer shell.

9. The method of claim 2, wherein the first portion further comprises a drug delivery portion.

10. The method of claim 9, further wherein the cavitation nucleation agent comprises a phase-convertible fluid and wherein the ultrasound induced phase conversion portion includes phase conversion of the phase-convertible fluid.

11. The method of claim 2, wherein the second portion comprises an ultrasound thermal treatment portion.

12. The method of claim 11, further wherein the ultrasound thermal treatment portion includes thermal therapy for inducing thermal damage in the region of interest sufficient to produce a desired thermal bioeffect.

13. The method of claim 1, wherein the first energy level comprises an energy level sufficient for enabling ultrasound induced phase conversion of a phase-convertible fluid.

14. The method of claim 13, further wherein the phase-convertible fluid includes to a liquid having a boiling point above 37 degrees C. and below 100 degrees C.

15. The method of claim 14, further wherein the liquid contains particles.

16. The method of claim 15, further wherein the particles comprise liquid perfluorocarbon filled particles.

17. The method of claim 15, further wherein the particles have a size less than or equal to 5 microns.

18. The method of claim 15, further wherein the particles are encapsulated with a biodegradable polymer shell.

19. The method of claim 1, wherein the second energy level comprises an energy level sufficient for implementing a thermal treatment to produce a desired thermal bioeffect in the region of interest.

20. The method of claim 1, wherein the first energy level is sufficient for activating the cavitation nucleation agent and wherein the second energy level is insufficient for activating the cavitation nucleation agent.

21. The method of claim 1, wherein neither of the first energy level or the second energy level is sufficient to induce cavitation for mechanically destroying tissue in the region of interest.

22. The method of claim 11, further wherein ultrasound induced phase conversion and ultrasound thermal treatment occur within the region of interest alone.

23. The method of claim 22, further wherein the ultrasound thermal treatment includes bubble-enhanced heating.

24. The method of claim 1, wherein the ultrasound comprises focused ultrasound and wherein the ultrasound treatment comprises focused ultrasound therapy.

25. The method of claim 24, further wherein the second portion of the treatment cycle comprises focused ultrasound thermal ablation.

26. The method of claim 25, further wherein the second energy level is at or above a level sufficient for thermal ablation, but below a cavitation threshold of tissue in the region of interest.

27. The method of claim 24, further wherein the activated cavitation nucleation agent comprises focused ultrasound generated gas-bubbles.

28. The method of claim 1, wherein the ultrasound comprises focused ultrasound, and further wherein responsive to (i) a presence of a phase-convertible fluid and (ii) the application of focused ultrasound at the first energy level, the phase-convertible fluid and the focused ultrasound generate gas-bubbles in the region of interest.

29. The method of claim 1, further comprising:

delivering a phase-convertible fluid to the region of interest, wherein delivering includes one selected from the group consisting of intravenous delivery distal from the region of interest and injection delivery proximate the region of interest.

30. An ultrasound apparatus comprising:

a control unit;

an ultrasound probe; and

an ultrasound transducer disposed within the ultrasound probe and coupled to the control unit, wherein said control unit is configured for controlling the ultrasound transducer in an ultrasound treatment according to the method of claim 1.

31. A computer program product comprising computer readable media having a set of instructions executable by a computer, wherein the instructions are configured for carrying out an ultrasound treatment according to the method of claim 1.