Method and apparatus combining diagnostic ultrasound with therapeutic ultrasound to enhance thrombolysis

• US 6,635,017 B1
• Filed: 02/09/2000
• Issued: 10/21/2003
• Est. Priority Date: 02/09/2000
• Status: Expired due to Term

• Current Assignee: Spentech Incorporated
• Original Assignee: Spentech Incorporated
• Inventors: Voie, Arne H., Spencer, Merrill P., Moehring, Mark A.
• Primary Examiner(s): Smith, Ruth S.
• Application Number:
  US09/500,708
• Time in Patent Office: 1,350 Days
• Field of Search: 600/439, 600/459, 600/454, 600/441, 601/2, 604/21, 604/22
• US Class Current: 600/439
• CPC Class Codes: A61B 17/22004 using mechanical vibrations, e.g. ultrasonic shock waves A61B17/225 takes precedence
• CPC Class Codes: A61B 17/2256 with means for locating or checking the concrement, e.g. X-ray apparatus, imaging means A61B17/2255 takes precedence
• CPC Class Codes: A61B 2090/378 using ultrasound
• CPC Class Codes: A61B 8/06 Measuring blood flow measuring volume flow in general G01F, e.g. G01F1/66, G01F1/72; measuring speed of fluids in general G01P5/00
• CPC Class Codes: A61B 8/0808 for diagnosis of the brain
• CPC Class Codes: A61B 8/0816 using echo-encephalography
• CPC Class Codes: A61B 8/0833 involving detecting or locating foreign bodies or organic structures
• 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: 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 method and apparatus for combining therapeutic pulsed or continuous-wave ultrasound with diagnostic pulsed ultrasound are described. In both a therapeutic mode and in a diagnostic mode, the ultrasound is administered from a single probe to a patient suffering from thrombosis. The ultrasound can have the same or different frequency ranges in the diagnostic and therapeutic modes. The pulsed or continuous-wave ultrasound in the therapeutic mode enhances a lysing effect of a thrombolytic agent. The pulsed ultrasound in the diagnostic mode allows monitoring of blood flow to locate a thrombus, to determine an optimal window to administer the therapeutic pulsed ultrasound, and to detect when recanalization has occurred. If an operator attends the device, a graphical display operates during the diagnostic mode to display an image representative of the blood flow.

Claims

1. A method of treating a patient suffering from thrombosis, the method comprising:

positioning a single ultrasound probe external to a body of the patient;

in a diagnostic mode, administering pulsed ultrasound from the single probe to the patient at a first frequency for a first period of time to locate a target region within the body of the patient along a diagnostic beam axis, the diagnostic beam originating from a diagnostic ultrasound source and along which the pulsed ultrasound propagates; and

in a therapeutic mode, administering ultrasound from the single probe substantially along the diagnostic beam axis to the target region at a second frequency for a second period of time to enhance a thrombolytic action of a thrombolytic agent.

2. The method of claim 1, further comprising externally administering the thrombolytic agent into the patient prior to administering the ultrasound in the therapeutic mode.

3. The method of claim 1, further comprising externally administering the thrombolytic agent, the thrombolytic agent comprising tissue plasminogen activator (t-PA), recombinant t-PA (rt-PA), TNK tPA, urokinase, or streptokinase.

4. The method of claim 1 wherein the thrombolytic agent comprises a naturally occurring agent in the patient.

5. The method of claim 1 wherein the ultrasound administered in the therapeutic mode comprises pulsed or continuous-wave ultrasound.

6. The method of claim 1 wherein the first frequency is different from the second frequency.

7. The method of claim 1 wherein the first and second frequencies comprise a substantially 2 MHz frequency.

8. The method of claim 1 wherein the first frequency comprises a substantially 2 MHz frequency, and the second frequency comprises a frequency substantially between 1 MHz and 3 MHz.

9. The method of claim 1 wherein the second frequency comprises a frequency below 200 kHz.

10. The method of claim 1 wherein administering ultrasound in the diagnostic and therapeutic modes is controlled by a computer.

11. The method of claim 1 wherein administering ultrasound in the diagnostic and therapeutic modes occurs simultaneously.

12. The method of claim 1 wherein the second period of time is greater than the first period of time.

13. The method of claim 1 wherein administering ultrasound in the diagnostic and therapeutic modes comprises applying ultrasound to a cranial region of the patient.

14. The method of claim 1 wherein administering ultrasound in the diagnostic and therapeutic modes comprises applying ultrasound to a region of the leg of the patient.

15. The method of claim 1 wherein administering ultrasound in the diagnostic and therapeutic modes comprises applying ultrasound to the heart of the patient.

16. The method of claim 1 wherein administering ultrasound in the diagnostic and therapeutic modes comprises applying ultrasound to the pulmonary artery of the patient.

17. The method of claim 1 wherein the ultrasound is administered from the single probe in the diagnostic mode having a derated spatial peak temporal average intensity less than 720 mW/cm² in water.

18. The method of claim 1 where in administering ultrasound in the therapeutic mode comprises administering ultrasound having an spatial peak temporal average intensity less than 50 mW/cm² at a middle cerebral artery.

19. The method of claim 1 wherein administering ultrasound comprises intermittently transmitting a signal having a substantially sinusoidal waveform.

20. The method of claim 1 wherein ultrasound in the diagnostic and therapeutic modes is administered intermittently.

21. The method of claim 1, further comprising administering a ultrasound in the therapeutic mode with a wider beam profile than the pulsed ultrasound administered in the diagnostic mode.

22. The method of claim 1, further comprising repeating administration of the ultrasound in the diagnostic and therapeutic modes until thrombosis is substantially eliminated.

23. The method of claim 1, further comprising:

selecting a region on a body surface of the patient;

defining a plurality of areas within the region;

administering the pulsed ultrasound to a first one of the areas during the diagnostic mode and evaluating a window through that first area;

if the window through the first area is not an optimum window, administering the pulsed ultrasound to a second one of the areas in the diagnostic mode and evaluating a window through the second area, at least a portion of the second area including at least a portion of the one area; and

repeating the administering the pulsed ultrasound to another area in the diagnostic mode if prior areas administered with pulsed ultrasound do not substantially include the optimum window, until an area having substantially the optimum window is located.

24. The method of claim 23 wherein defining a plurality of areas comprises placing on the body surface an ultrasound probe having a plurality of transducer elements arranged in an array, the array defining an area corresponding to the region.

25. The method of claim 23 wherein administering ultrasound and repeating the administering are controlled by a computer.

26. The method of claim 1, further comprising:

selecting a region on a body surface of the patient;

defining a plurality of areas within the region;

administering the pulsed ultrasound to a first one of the areas during the diagnostic mode and evaluating a window through that first area;

if the window through the first area is not an optimum window, administering the pulsed ultrasound to a second one of the areas in the diagnostic mode and evaluating a window through the second area, at least a portion of the second area including at least a portion of the first area;

repeating administering the pulsed ultrasound to another area in the diagnostic mode if prior areas administered with pulsed ultrasound do not substantially include the optimum window, until an area having substantially the optimum window is located; and

administering ultrasound in the therapeutic mode through the area having substantially the optimum window.

27. The method of claim 26 wherein defining a plurality of areas comprises placing on the body surface an ultrasound probe having a plurality of transducer elements arranged in an array, the array defining an area corresponding to the region.

28. The method of claim 26 wherein administering the pulsed ultrasound in the diagnostic mode, repeating the administering, and administering ultrasound in the therapeutic mode are controlled by a computer.

29. The method of claim 1, further comprising determining blood flow at a plurality of locations along a beam axis of the pulsed ultrasound during the diagnostic mode.

30. A method of treating a patient suffering from thrombosis, the method comprising:

positioning a single ultrasound probe external to the body of the patient, the single probe having a diagnostic mode and a therapeutic mode;

in the diagnostic mode, administering a diagnostic ultrasound from the single probe to the patient at a first frequency, the diagnostic ultrasound originating from a diagnostic ultrasound beam source and directed from the diagnostic ultrasound beam source along a first beam axis; and

in the therapeutic mode, administering therapeutic ultrasound from the single probe to the patient at a second frequency to enhance a thrombolytic action of a thrombolytic agent, the therapeutic ultrasound originating from a therapeutic ultrasound beam source and directed from the therapeutic ultrasound beam source along a second beam axis, the diagnostic and therapeutic ultrasound administered from overlapping ultrasound beam sources.

31. The method of claim 30 wherein the diagnostic and therapeutic ultrasound are administered simultaneously.

32. The method of claim 30 wherein the therapeutic ultrasound is administered for a period of time greater than the diagnostic ultrasound.

33. The method of claim 30 wherein administering the diagnostic and therapeutic are intermittently repeated.

34. The method of claim 30 wherein positioning the single ultrasound probe comprises:

mounting the single ultrasound probe on to a headframe device, the headframe device having a movable mount structured to allow the single ultrasound probe to be positioned at a plurality of different orientations with respect to the body surface of the patient; and

attaching the headframe on to a cranial region of the patient.

35. The method of claim 30 wherein the single ultrasound probe comprises a first crystal superimposed over a second crystal and wherein the first frequency is administered from the first crystal in the diagnostic mode and the second frequency is administered from the second crystal in the therapeutic mode.

36. The method of claim 30 wherein the single ultrasound probe comprises an outer element annularly arranged around an inner element and wherein the second frequency is administered from the inner element in the therapeutic mode and the first frequency is administered from the inner and outer elements in the diagnostic mode.

37. The method of claim 30, further comprising providing information to a user concerning blood flow by displaying graphical information depicting blood flow at a plurality of locations along a beam axis of the pulsed ultrasound.

38. The method of claim 30, further comprising providing information to a user concerning blood flow by:

displaying first graphical information depicting blood flow at a plurality of locations along a beam axis of the pulsed ultrasound; and

displaying second graphical information depicting blood flow velocities at a selected one of the locations, the first and second graphical information being displayed simultaneously.

39. The method of claim 30, further comprising determining blood flow at a plurality of locations along a beam axis of the diagnostic ultrasound during the diagnostic mode.

40. The method of claim 30 wherein the first and second beam axes are coincident.

41. An apparatus to treat a patient suffering from thrombosis, the apparatus comprising:

a single ultrasound probe structured for positioning proximate to a region of a body of the patient to transmit pulsed ultrasound in a diagnostic mode and ultrasound in a therapeutic mode, the ultrasound having a characteristic in the therapeutic mode that is different from a characteristic of the pulsed ultrasound in the diagnostic mode, the single ultrasound probe having a diagnostic ultrasound beam source and a therapeutic ultrasound beam source from which the ultrasound in the respective modes originates, the diagnostic and therapeutic ultrasound beam sources arranged to produce an ultrasound beam in each mode that overlaps the other at the respective beam source; and

a controller structured to switch the single ultrasound probe between the diagnostic and therapeutic modes and to process ultrasound Doppler signals returned by the single ultrasound probe during the diagnostic mode.

42. The method of claim 41, further comprising a headframe device structured to be worn on the head of a patient and having a movable mount onto which the single ultrasound probe is mounted, the movable mount structured to allow the single ultrasound probe to be positioned at a plurality of different orientations with respect to the body surface of the patient.

43. The apparatus of claim 41, wherein the single ultrasound probe comprises two transducer elements.

44. The apparatus of claim 43 wherein the two transducer elements comprise a first crystal and a second crystal, respectively, the first crystal superimposed on the second crystal, and the single ultrasound probe structured to transmit a first frequency from the first crystal in the diagnostic mode and to transmit a second frequency different from the first frequency from the second crystal in the therapeutic mode.

45. The apparatus of claim 43 wherein the two transducer elements comprise an outer element and an inner element, the outer element annularly arranged over the inner element, and the single ultrasound probe structured to transmit ultrasound from the inner element in the therapeutic mode and to transmit the pulsed ultrasound from the inner and outer elements in the diagnostic mode.

46. The apparatus of claim 41 wherein the single ultrasound probe comprises plurality of transducer elements arranged in an array, the array defining an area.

47. The apparatus of claim 46 wherein each of the transducer elements is triangular shaped, and the area is hexagonal shaped.

48. The apparatus of claim 46 wherein each of the transducer elements is rectangular shaped, and the area is polygonal.

49. The apparatus of claim 46, wherein the plurality of transducer elements comprises 128 transducer elements.

50. The apparatus of claim 41, further comprising a graphical display responsive to the controller and coupled to the single ultrasound probe, the graphical display having a blood locator display structured to depict a plurality of locations along an ultrasound beam axis at which blood flow is detected, the blood locator display responsive to the controller to depict the plurality of locations during the diagnostic mode based on the Doppler signals.

51. The apparatus of claim 50 wherein the graphical display further comprises:

a location indicator to identify a selected one of the plurality of locations; and

a spectogram to depict detected blood flow velocities as a function of time at the selected location.

52. The apparatus of claim 41, wherein the controller is structured to drive the single ultrasound probe to transmit a pulsed ultrasound in both the therapeutic and diagnostic modes at a substantially 2 MHz frequency.

53. The apparatus of claim 41 wherein the controller is structured to drive the single ultrasound probe to transmit a pulsed or continuous-wave ultrasound in the therapeutic mode.

54. The apparatus of claim 41 wherein the controller is structured to drive the single ultrasound probe to transmit a pulsed or continuous-wave ultrasound in the therapeutic mode for a period of time greater than a period of time to transmit the pulsed ultrasound in the diagnostic mode.

55. The apparatus of claim 41 wherein the controller is structured to drive the single ultrasound probe to transmit ultrasound in the therapeutic and diagnostic modes simultaneously.

56. The apparatus of claim 41 wherein the single ultrasound probe is structured to transmit a pulsed or continuous-wave ultrasound in the therapeutic mode with a beam profile wider than a beam profile of the pulsed ultrasound in the diagnostic mode.

57. The apparatus of claim 41 wherein the controller processes ultrasound Doppler signals returned by the single ultrasound probe during the diagnostic mode to determine blood flow at a plurality of locations along a beam axis of the pulsed ultrasound.

58. An apparatus to treat a patient suffering from thrombosis, the apparatus comprising:

a single ultrasound probe structured to transmit pulsed ultrasound in a diagnostic mode along a diagnostic beam axis, the diagnostic beam axis originating at an ultrasound source and along which the pulsed ultrasound propagates and to transmit ultrasound in a therapeutic mode along the diagnostic beam axis, the ultrasound having a characteristic in the therapeutic mode that is different from a characteristic of the pulsed ultrasound in the diagnostic mode; and

a controller structured to switch the single ultrasound probe between the diagnostic and therapeutic modes and to process ultrasound Doppler signals returned by the single ultrasound probe during the diagnostic mode.