Localized production of microbubbles and control of cavitational and heating effects by use of enhanced ultrasound

1. A method of using ultrasound waves focused at a specific location in a medium to cause localized production of microbubbles at said location, to control said production, and to control cavitational and heating effects that take place at said location, the method comprising:

providing multiple ultrasonic transducers;

focusing the transducers at said location;

simultaneously directing ultrasound waves from the transducers at said location; and

selecting a range of parameters of the ultrasound waves being directed from the multiple ultrasonic transducers focused at said location in order to induce cavitation, and to produce from interference of the ultrasound waves at said location a combined waveform:

wherein said combined waveform comprising a spatial and/or temporal combination of two waveforms—one waveform comprising high negative peaks and small positive peaks and the second waveform comprising high positive peaks and only small negative peaks, said combined waveform allowing control of size distribution of the microbubbles and temporal changes of the distribution.

2. The method according to claim 1 , wherein the combined waveform encouraging the production of heat comprises one of:

a waveform comprising high positive peaks and only small negative peaks; and

a sinusoidal waveform.

3. A method according to claim 2 , wherein the combined waveform comprising high positive peaks and small negative peaks encourages reduction of the size of said microbubbles.

4. A method according to claim 1 , wherein a number of the transducers is three.

5. A method according to claim 1 , wherein a radius of the microbubbles is in a range from a fraction of a micron up to 100.

6. The method according to claim 1 , further comprising the step of measuring changes in tissue or microbubble size and accordingly adjusting the waveform to include more negative peaks, more positive peaks, or more equal sized waves.

7. The method according to claim 1 , further comprising the step of measuring temperature of the medium and modifying an output of the transducers according to the measured temperature.

8. The method according to claim 1 , further comprising the step of monitoring generation of the microbubbles at the specific location by using an ultrasound imaging or non-imaging system and controlling the system for one or more of the following purposes:

so that a number of microbubbles will be as planned;

for aiming a focused beam to the targeted location; and

to re-align the beam to a different location.

9. A method according to claim 8 , wherein a response at a half harmonic or at higher harmonics of the transmitted frequencies is used by the ultrasound imaging or non-imaging system to measure one or more of the following:

effect of the heating;

duration of said effect;

number of microbubbles generated within the targeted region; and

spatial distribution of said microbubbles generated within said targeted region.

10. A method according to claim 1 , wherein the multiple ultrasonic transducers are arranged as an array, designed so that their mechanical focus and their own focus combine at a same point in space.

11. A method according to claim 10 , wherein the point in space can be moved by either shifting the whole array, by repositioning of individual transducers, or by phase shift of an excitation pulse.

12. A method according to claim 10 , wherein the ultrasound waves transmitted by the multiple ultrasonic transducers are designed to produce by interference specific waveforms at a focal point, which are not produced at other locations.

13. A method according to claim 12 , wherein the specific waveforms can be modified to produce one of the following effects:

cause cavitation with no significant change in temperature;

increase the temperature with minimal cavitation;

suppress cavitation; and

a combination of these effects.

14. A method according to claim 12 , wherein a region within a focal zone of all the transducers in which the specific waveform develops at significant intensities and amplitudes of the waveforms are less than −3 DB of a maximum amplitude at a distance less than 1 mm away from a point of said maximum amplitude in lateral directions and less than 1.5 mm away in axial directions.

15. A method according to claim 1 , wherein localized production of microbubbles at the location and control of the cavitational and heating effects that take place at said location are for therapeutic purposes.

16. A method according to claim 15 , wherein the therapy is at least one of:

occlusion of varicose veins and telangiectasia;

activation of cellular processes in a body, by either localized pressure forces or shear forces that produce therapeutic responses or damage;

therapy of cancerous tissue by cavitation damage and/or rapid hyperthermia, resulting in apoptosis, tissue ablation or necrosis;

therapy of cancerous tissue by damage and closure of supply and drainage vasculature by cavitation, and/or rapid hyperthermia via coagulation of arteries supplying a tumor;

ablation of ectopic foci or re-entry loops within cardiac walls, mainly within ventricular walls;

thrombolysis of clotted or semi-clotted arteries, lipolysis or other methods of disintegration of fat cells, either by a mechanism of microbubbles collapse and/or by hyperthermia, resulting in apoptosis and drainage of fat deposits;

coagulation of internal bleedings within the body; and

non-invasive surgery of internal tissues and organs, by disintegration of cells along a cut.

17. A method according to claim 16 , wherein activation of cellular processes in the body produces therapeutic responses or damage, including at least one of:

localized drug delivery,

gene therapy, and

angiogenesis.

18. A method according to claim 16 , wherein thrombolysis of clotted or semi-clotted arteries is performed in arteries chosen from at least one of:

coronary arteries,

carotid arteries,

cerebral arteries, and

peripheral arteries.

19. A method according to claim 1 , wherein the transducers are placed extra-corporally, in close proximity to an organ to be treated, with ultrasound gel or water surrounding the ultrasound transducers and space between it and the organ.

20. A method of occlusing varicose veins comprising the steps of:

a) focusing multiple transducers at a same location within a vein;

b) selecting a range of parameters of said multiple transducers to produce a waveform comprising high negative peaks and small positive peaks, said waveform encouraging creation of a cloud of microbubbles;

c) continuing production of the waveform until cavitation causes destruction of cells and initiation of scaring of tissue at said location;

d) focusing said transducers at another location within said vein; and

e) repeating steps (b), (c) and (d) until enough scaring has been initiated to cause occlusion of said vein.

21. A method according to claim 20 , wherein two additional steps are added between steps (c) and (d), said additional steps comprising:

f) changing the range of parameters of the multiple transducers to produce a heating waveforms, said waveform encouraging production of heat at the location; and

g) continuing the production of the waveform until the heating causes destruction of cells and initiation of scaring of the tissue at said location.

22. A system comprising:

at least three arbitrary waveform signal generators;

at least three or more wide-band power amplifiers coupled to the waveform signal generators; wherein

three transducers coupled to the wide-band power amplifiers and configured to focus ultrasound waves at a location in a medium to cause localized production of microbubbles at said location; and

at least one workstation configured to control the production of the microbubbles at said location, and cavitational and heating effects that take place at said location, wherein the workstation selects a range of parameters of the ultrasound waves being directed from the transducers focused at said location in order to induce cavitation, and to produce from interference of the ultrasound waves at said location:

a combined waveform comprising a spatial and/or temporal combination of two waveforms, one waveform comprising high negative peaks and small positive peaks and a second waveform comprising high positive peaks and small negative peaks, said combined waveform allowing control of size distribution of the microbubbles and temporal changes of the distribution.

23. A system according to claim 22 , wherein the three transducers are arranged as an array, designed so that their mechanical focus and their own focus combine at a same point in space.

24. A system according to claim 23 , wherein the point in space can be moved by either shifting the whole array, by repositioning of individual transducers, or by phase shift of an excitation pulse.

25. A system according to claim 23 , wherein the ultrasound waves transmitted by the three transducers are designed to produce by interference specific waveforms at a focal point, which are not produced at other locations.

26. A system according to claim 25 , wherein the specific waveforms can be modified to produce one of the following effects:

cause cavitation with no significant change in temperature;

increase the temperature with minimal cavitation;

suppress cavitation; and

a combination of these effects.

27. A system according to claim 25 , wherein a region within a focal zone of all the transducers in which the specific waveform develops at significant intensities and amplitudes of the waveforms are less than −3 DB of a maximum amplitude at a distance less than 1 mm away from a point of said maximum amplitude in lateral directions and less than 1.5 mm away in axial directions.

28. A system according to claim 23 , adapted for use in a therapeutic procedure;

wherein the array is placed extra-corporally, in close proximity to an organ to be treated, with ultrasound gel or water surrounding the ultrasound transducers and the space between it and the organ.

29. A system according to claim 28 , wherein the therapeutic procedure is at least one of:

occlusion of varicose veins and telangiectasia;

activation of cellular processes in the body, by either localized pressure forces or shear forces that produce therapeutic responses or damage;

therapy of cancerous tissue by cavitation damage and/or rapid hyperthermia, resulting in apoptosis, tissue ablation or necrosis;

therapy of cancerous tissue by damage and closure of the supply and drainage vasculature by cavitation, and/or rapid hyperthermia via coagulation of the arteries supplying the tumor;

ablation of ectopic foci or re-entry loops within the cardiac walls, mainly within the ventricular walls;

thrombolysis of clotted or semi-clotted arteries, lipolysis or other methods of disintegration of fat cells, either by the mechanism of microbubbles collapse and/or by hyperthermia, resulting in apoptosis and drainage of fat deposits;

coagulation of internal bleedings within the body; and

non-invasive surgery of internal tissues and organs, by disintegration of cells along the cut.

30. A system according to claim 22 , further comprising an ultrasound imaging or non-imaging system and a control box.

31. A system according to claim 30 further comprising the ultrasound imaging or non-imaging system configured to view and monitor the region being targeted, monitors generation of the microbubbles at the desired location, and controls the system for one or more of the following purposes:

so that the number of microbubbles will be as planned;

for aiming the focused beam to the targeted location; and

to re-align the beam to a different location.

32. A system according to claim 30 , wherein a response at the half harmonic or at higher harmonics of the transmitted frequencies is used by the ultrasound imaging or non-imaging system to measure one or more of the following:

the effect of the heating;

the duration of said effect;

the number of microbubbles generated within the targeted region; and

the spatial distribution of said microbubbles generated within said targeted region.

33. A system according to claim 30 , wherein the ultrasound imaging or non-imaging system is controlled by the workstation to which it is connected through the control box.

34. A system according to claim 30 , wherein the ultrasound imaging or non-imaging system measures the changes in tissue or the microbubbles size and the control box and workstation accordingly adjust the waveform to include more negative peaks, positive peaks or equal sized waves.

35. A system according to claim 22 , further comprising a temperature measurement system.

36. A system according to claim 35 , wherein the temperature measurement system comprises one or more thermocouples.

37. A system according to claim 35 , wherein the temperature measurement system configured to modify the output of the transducers according to the measured temperature.