Methods and systems for non-invasive treatment of tissue using high intensity focused ultrasound therapy

1. A method of non-invasively treating tissue, the method comprising: positioning a focus of an ultrasound source at a target site in tissue, the ultrasound source being configured to emit high intensity focused ultrasound (HIFU) waves; pulsing ultrasound energy from the ultrasound source toward the target site; and generating, from nonlinear propagation of the HIFU waves, shock waves in the tissue, wherein the shock waves are distinct from shock waves resulting from cavitation, wherein the shock waves induce boiling in tissue at the target site, and wherein initiation of boiling in tissue at the target site by the shock waves at least substantially emulsifies the tissue.

2. The method of claim 1 wherein:

pulsing the ultrasound energy further comprises pulsing the ultrasound energy at a pulse repetition frequency between approximately 1 Hz and approximately 1 kHz, wherein individual pulses have a pulse length between approximately 100 μs and approximately 100 μs; and

generating shock waves further comprises generating shock waves at the focus having a peak positive pressure between approximately 30 MPa and approximately 80 MPa.

3. The method of claim 1 wherein pulsing the ultrasound energy comprises raising tissue temperature at the target site due to shock wave heating to at least 100° C. during individual pulses of ultrasound energy.

4. The method of claim 1 wherein pulsing the ultrasound energy further comprises pulsing the ultrasound energy at a pulse length between approximately 1 ms and approximately 40 ms.

5. The method of claim 1 wherein:

pulsing the ultrasound energy further comprises pulsing the ultrasound energy at an ultrasound frequency between approximately 0.5 MHz and approximately 20 MHz and a focal intensity between approximately 1 kW/cm 2 and approximately 25 kW/cm 2 ; and

generating shock waves further comprises generating shock waves having a shock amplitude between approximately 10 MPa and approximately 100 MPa.

6. The method of claim 1 wherein pulsing the ultrasound energy comprises delivering pulses of ultrasound energy having a peak positive pressure at a focus between approximately 30 MPa and approximately 80 MPa, wherein the ultrasound source has a frequency of approximately 2 MHz.

7. The method of claim 1 wherein pulsing the ultrasound energy further comprises pulsing the ultrasound energy at a duty cycle of less than 10%.

8. The method of claim 1 , further comprising cooling the tissue at the target site under 100° C. between individual pulses.

9. The method of claim 1 , further comprising monitoring the boiling of the tissue at the target site in real-time with a monitoring system configured to distinguish boiling bubbles from cavitation bubbles, wherein the monitoring system comprises at least one of an imaging system, a voltage probe, a high-speed camera, and a passive cavitation detection device.

10. The method of claim 1 , further comprising mechanically damaging the tissue at the target site with substantially no thermal damage to tissue at the target site and surrounding the target site.

11. The method of claim 1 : wherein generating shock waves comprises producing boiling bubbles in the tissue at the focus and wherein the produced boiling bubbles have a cross-sectional dimension between approximately 10 μm and approximately 4 mm on the order of the ultrasound source beam-width.

12. The method of claim 1 , further comprising focusing energy deposition of an ultrasound beam from the ultrasound source within approximately 100 microns of the target site.

13. The method of claim 1 , further comprising:

delivering at least one test pulse of ultrasound energy to the tissue;

monitoring the target site during the test pulse in real-time for tissue boiling; and

adjusting at least one of peak positive pressure, shock amplitude, pulse length, pulse repetition frequency, and duty cycle to induce tissue boiling at the target site during individual pulses.

14. The method of claim 1 , further comprising:

applying at least one test pulse to water to obtain the shock amplitude of the pulse at the focus for boiling water within a selected pulse length;

derating pressure amplitude at the ultrasound source to account for absorption of ultrasound energy propagating through the tissue to the focus;

determining a pulse protocol for the ultrasound source, wherein the pulse protocol includes ultrasound source frequency, peak positive pressure, shock amplitude, pulse length, pulse repetition frequency, and duty cycle to induce tissue boiling at the target site during individual pulses; and

delivering the ultrasound energy using the pulse protocol.

15. The method of claim 1 wherein boiling is induced in approximately 10 ms or less from the time the HIFU waves are initiated.

16. A method of treating tissue at a target site, the method comprising:

treating the target site with high intensity focused ultrasound (HIFU), wherein the HIFU is delivered from an ultrasound source, and wherein the HIFU is delivered using a pulsing protocol with individual pulse lengths between approximately 1 ms and approximately 100 ms; and

forming a lesion at the target site in the tissue,

wherein

the lesion is formed by shock waves generated by nonlinear HIFU wave propagation, wherein the generated shock waves are distinct from shock waves resulting from cavitation,

the shock waves are generated proximate to the target site the shock waves induce boiling of the tissue at the target site, and

the target site is proximate to a focal plane of the ultrasound source.

17. The method of claim 16 wherein forming a lesion further comprises generating shock waves having amplitudes between approximately 10 MPa and approximately 100 MPa.

18. The method of claim 16 wherein treating the target site further comprises treating the target site with an ultrasound source having a frequency range between approximately 0.5 MHz and approximately 20 MHz.

19. The method of claim 16 wherein treating the target site further comprises pulsing ultrasound waves with a duty cycle of less than 10%.

20. The method of claim 16 wherein forming a lesion comprises raising tissue temperature at the target site to at least 100° C. during individual pulses of shock waves, the tissue forming boiling bubbles having a cross-sectional dimension between approximately 100 μm and 4 mm.

21. The method of claim 16 , further comprising distinguishing boiling of the tissue at the target site from cavitation with at least one of an imaging system, a voltage probe, a high-speed camera, and a passive cavitation detection device.

22. The method of claim 16 , further comprising:

delivering at least one test pulse of ultrasound energy to the tissue;

monitoring the target site during the test pulse in real-time for tissue boiling; and

adjusting the pulsing protocol to induce tissue boiling at the target site during individual pulses, wherein the pulsing protocol comprises at least one of ultrasound source frequency, peak positive pressure, pulse length, shock wave amplitude, pulse repetition frequency, and duty cycle.

23. The method of claim 16 wherein boiling is induced in approximately 10 ms or less from the time the HIFU is initiated.

24. A method of non-invasively treating tissue, the method comprising: positioning a focus of an ultrasound source at a target site in tissue, the ultrasound source being configured to emit high intensity focused ultrasound (HIFU) waves; pulsing ultrasound energy from the ultrasound source toward the target site; and generating, from nonlinear propagation of the HIFU waves, shock waves in the tissue, wherein the shock waves induce boiling in tissue at the target site, and wherein initiation of boiling in tissue at the target site by the shock waves at least substantially emulsifies the tissue, wherein the induced boiling in tissue at the target site mechanically damages the tissue at the target site with substantially no thermal damage to tissue at the target site.