Methods and apparatus for displaying information relating to delivery and activation of a therapeutic agent using ultrasound energy

• US 6,740,039 B1
• Filed: 05/17/2000
• Issued: 05/25/2004
• Est. Priority Date: 08/20/1999
• Status: Expired due to Term

• Current Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Original Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Inventors: Beiter, Susan E, Rafter, Patrick G
• Primary Examiner(s): Jones, Mary Beth
• Assistant Examiner(s): Jain, Ruby
• Application Number:
  US09/572,268
• Time in Patent Office: 1,469 Days
• Field of Search: 600/439, 601/2, 601/3, 607/97
• US Class Current: 600/439
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 8/463 characterised by displaying multiple images or images and diagnostic data on one display composite display in devices for short-range imaging with acoustic waves G01S7/52074
• 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 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

Abstract

A therapeutic agent is incorporated into microbubbles of a contrast agent, and the microbubbles containing the therapeutic agent are delivered to a region of interest in a patient. An ultrasound image of the region of interest is generated by an ultrasound imaging system, and ultrasound energy for destroying the microbubbles of the contrast agent is transmitted to the region of interest. Parameter data that is representative of activation of the therapeutic agent in the region of interest is acquired, and a parameter display is generated. One or more parameters of the ultrasound energy applied to the region of interest for activating the therapeutic agent may be adjusted, either manually based on the parameter display or automatically based on acquired parameter data. In one embodiment, the parameter display is indicative of a parameter associated with the ultrasound energy transmitted to the region of interest. In another embodiment, the parameter data is acquired by detecting destruction of microbubbles of the contrast agent.

Claims

1. A method for administering a therapeutic agent to a patient, comprising the steps of:

delivering a therapeutic agent to a region of interest in a patient;

generating an ultrasound image of the region of interest at a first ultrasound frequency selected for image quality;

transmitting ultrasound energy at a second ultrasound frequency that is not equal to the first ultrasound frequency,

said second ultrasound frequency being transmitted to the region of interest for activating the therapeutic agent; and

generating a parameter display including an amount of microbubble destruction in the defined region of interest that is indicative of activation of the therapeutic agent in the region of interest and provides feedback control for said activating step; and

automatically adjusting a parameter related to the second ultrasound frequency in accordance with feedback control, wherein said parameter to be adjusted includes one of frequency, power level, beam pattern, or duration of the transmission of the ultrasound energy.

2. A method for administering a therapeutic agent as defined in claim 1 wherein the step of generating a parameter display comprises generating a display that represents a parameter of the ultrasound energy transmitted to the region of interest.

3. A method for administering a therapeutic agent as defined in claim 1 wherein the step of generating a parameter display comprises generating a colorized display in which specified colors are indicative of parameter values or ranges of values associated with activating the therapeutic agent.

4. A method for administering a therapeutic a gent as defined in claim 1 wherein the step of generating a parameter display comprises generating a colorized display in which specified colors are indicative of cumulative dose of the therapeutic agent activated in the region of interest.

5. A method for administering a therapeutic agent as defined in claim 1 wherein the step of generating a parameter display comprises detecting cumulative dose of the therapeutic agent activated in the region of interest and generating a display that is indicative of the cumulative dose.

6. A method for administering a therapeutic agent as defined in claim 1 wherein the step of generating a parameter display comprises generating a graphical representation of a parameter associated with activation of the therapeutic agent.

7. A method for administering a therapeutic agent as defined in claim 1 wherein the step of delivering a therapeutic agent comprises delivering the therapeutic agent incorporated into microbubbles of a contrast agent and wherein the step of transmitting ultrasound energy comprises destroying the microbubbles of the contrast agent for activating the therapeutic agent.

8. A method for administering a therapeutic agent as defined in claim 7 wherein the step of generating a parameter display comprises detecting destruction of microbubbles of the contrast agent and generating a display that is indicative of destruction of microbubbles of the contrast agent.

9. A method for administering a therapeutic agent as defined in claim 8 wherein the step of detecting destruction of microbubbles of the contrast agent comprises detecting loss of correlation between scan lines in said ultrasound image.

10. A method for administering a therapeutic agent as defined in claim 8 wherein the step of detecting destruction of microbubbles of the contrast agent comprises detecting microbubble destruction by acoustic densitometry.

11. A method for administering a therapeutic agent as defined in claim 8 wherein the step of detecting destruction of microbubbles of the contrast agent comprises detecting microbubble destruction by video densitometry.

12. A method for administering a therapeutic agent as defined in claim 8 wherein the step of detecting destruction of microbubbles of the contrast agent comprises detecting microbubble destruction by subtracting successive ultrasound images of the region of interest.

13. A method for administering a therapeutic agent as defined in claim 8 further comprising the step of automatically adjusting one or more parameters of the ultrasound energy transmitted to the region of interest, based on acquired parameter data.

14. A method for administering a therapeutic agent as defined in claim 1 further comprising the step of manually adjusting one or more parameters of the ultrasound energy transmitted to the region of interest, based on said parameter display.

15. A method for administering a therapeutic agent as defined in claim 1 wherein the step of generating a parameter display comprises detecting the spatial distribution of therapeutic agent activated in the region of interest and generating a display that is indicative of the spatial distribution.

16. A method for administering a therapeutic agent to a patient, comprising the steps of:

delivering a therapeutic agent to a region of interest in a patient;

generating an ultrasound image of the region of interest at a first ultrasound frequency selected for image quality;

transmitting ultrasound energy to the region of interest at a second ultrasound frequency that is not equal to the first ultrasound frequency, said second ultrasound frequency being transmitted for activating the therapeutic agent; and

generating a parameter display including an amount of microbubble destruction in the defined region of interest that is indicative of activation of the therapeutic agent in the region of interest and provides feedback control for said transmitting step; and

automatically adjusting a parameter related to the second ultrasound frequency in accordance with feedback control,

wherein said parameter to be adjusted includes one of frequency, power level, beam pattern, or duration of the transmission of the ultrasound energy, and

wherein the step of generating a parameter display comprises generating an area display that overlays said ultrasound image and is indicative of the spatial distribution of a parameter.

17. A method for administering a therapeutic agent as defined in claim 16 wherein the area display comprises contours of constant value of the parameter.

18. A method for administering a therapeutic agent to a patient, comprising the steps of:

delivering a therapeutic agent to a region of interest in a patient;

generating an ultrasound image of the region of interest at a first ultrasound frequency selected for image quality;

transmitting ultrasound energy at a second ultrasound frequency that is not equal to the first ultrasound frequency, said second ultrasound frequency being transmitted to the region of interest for activating the therapeutic agent; and

generating a parameter display including an amount of microbubble destruction in the defined region of interest that is indicative of activation of the therapeutic agent in the region of interest and provides feedback control for said transmitting step; and

automatically adjusting a parameter related to the second ultrasound frequency in accordance with feedback control, wherein said parameter to be adjusted includes one of frequency, power level, beam pattern, or duration of the transmission of the ultrasound energy;

wherein the step of generating a parameter display comprises generating a graphical representation of a parameter associated with activation of the therapeutic agent; and

wherein said graphical representation comprises a graph of cumulative dose of the therapeutic agent as a function of time.

19. Apparatus for facilitating administration of a therapeutic agent to a patient, wherein the therapeutic agent is incorporated into microbubbles of a contrast agent and is delivered with the contrast agent to a region of interest in the patient, comprising:

means for generating an ultrasound image of the region of interest at a first ultrasound frequency selected for image quality;

means for transmitting ultrasound energy to the region of interest at a second ultrasound frequency that is not equal to the first ultrasound frequency and having a different power level, said second ultrasound frequency being transmitted for destroying the microbubbles of the contrast agent;

means for acquiring parameter data that is representative of destruction of the microbubbles of the contrast agent and provides feedback control for said means for transmitting;

means for generating a parameter display of the acquired parameter data, wherein the parameter display includes an amount of microbubble destruction in the region of interest that is indicative of activation of the therapeutic agent in the region of interest; and

means for automatically adjusting a parameter related to the second ultrasound frequency in accordance with feedback control, wherein said parameter to be adjusted includes one of frequency, power level, beam pattern, or duration of the transmission of the ultrasound energy.

20. Apparatus as defined in claim 19 wherein said means for generating a parameter display comprises means for generating a display that represents a parameter of the ultrasound energy transmitted to the region of interest.

21. Apparatus as defined in claim 19 wherein said means for generating a parameter display comprises means for detecting destruction of microbubbles of the contrast agent and generating a parameter display that is indicative of destruction of microbubbles of the contrast agent.

22. Apparatus as defined in claim 19 further comprising means for manually adjusting one or more parameters of the ultrasound energy transmitted to the region of interest, based on said parameter display.

23. Apparatus as defined in claim 19 further comprising means for automatically adjusting one or more parameters of the ultrasound energy transmitted to the region of interest, based on acquired parameter data.

24. Apparatus as defined in claim 19 wherein said means for generating a parameter display comprises means for generating a colorized display in which specified colors are indicative of cumulative dose of the therapeutic agent activated in the region of interest.

25. Apparatus as defined in claim 19 wherein said means for generating a parameter display comprises means for generating a colorized display in which specified colors are indicative of parameter values or ranges of values associated with activating the therapeutic agent.

26. The apparatus as defined in claim 19, wherein said means for generating a parameter display comprises means for generating an area display that overlays said ultrasound image and is indicative of the spatial distribution of a parameter.

27. The apparatus as defined in claim 26, wherein the area display comprises contours of constant values of the parameter.

28. The apparatus as defined in claim 19, wherein said means for generating a parameter display comprises generating a graphical representation of a parameter associated with activation of the therapeutic agent, wherein the graphical representation comprises a graph of the cumulative dose of the therapeutic agent as a function of time.

29. A method for administering a therapeutic agent to a patient, comprising the steps of:

delivering to a region of interest in a patient a therapeutic agent that is incorporated into microbubbles of a contrast agent;

generating an ultrasound image of the region of interest at a first ultrasound frequency selected for image quality;

transmitting ultrasound energy to the region of interest at a second ultrasound frequency that is not equal to the first ultrasound frequency, said second ultrasound frequency being transmitted for destroying the microbubbles of the contrast agent;

acquiring parameter data including an amount of microbubble destruction in the region of interest that is indicative of activation of the therapeutic agent in the region of interest and provides feedback control for said transmitting step; and

automatically adjusting one or more parameters of the ultrasound energy transmitted to the region of interest, based on the feedback control, wherein said parameter to be adjusted includes one of frequency, power level, beam pattern, or duration of the transmission of the ultrasound energy.

30. The method according to claim 29, further comprising display the acquired parameter data in an area display that overlays said ultrasound image and is indicative of the spatial distribution of a parameter of said parameter data.

31. The method according to claim 30, wherein the area display comprises contours of constant value of the parameter.

32. The method according to claim 29, further comprising:

displaying a parameter associated with activation of the therapeutic agent in a graphical representation comprising a graph of a cumulative dose of the therapeutic agent as a function of time.