Histotripsy for thrombolysis

• US 10,219,815 B2
• Filed: 01/23/2009
• Issued: 03/05/2019
• Est. Priority Date: 09/22/2005
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Maxwell, Adam, Xu, Zhen, Gurm, Hitinder S., Cain, Charles A.
• Primary Examiner(s): Nguyen, Hien
• Application Number:
  US12/358,549
• Publication Number:
  US 20090177085A1
• Time in Patent Office: 3,693 Days
• Field of Search: 600439
• CPC Class Codes: A61B 17/22004 using mechanical vibrations, e.g. ultrasonic shock waves A61B17/225 takes precedence
• CPC Class Codes: A61B 17/2258 integrated in a central portion of the shock wave apparatus
• CPC Class Codes: A61B 2017/00154 pulsed
• CPC Class Codes: A61B 2017/00172 Pulse trains, bursts, intermittent continuous operation
• CPC Class Codes: A61B 2017/00778 Operations on blood vessels A61B2017/22097, A61B2017/320741 take precedence
• CPC Class Codes: A61B 2017/22001 Angioplasty, e.g. PCTA
• CPC Class Codes: A61B 2017/22008 used or promoted
• CPC Class Codes: A61B 2017/22088 ultrasound absorbing, drug activated by ultrasound
• CPC Class Codes: A61B 2017/22089 Gas-bubbles
• CPC Class Codes: A61B 2090/378 using ultrasound
• CPC Class Codes: A61B 5/0536 Impedance imaging, e.g. by tomography
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 8/00 Diagnosis using ultrasonic, sonic or infrasonic waves imaging of objects using sonar G01S15/00
• CPC Class Codes: A61B 8/08 Detecting organic movements or changes, e.g. tumours, cysts, swellings A61B8/02 - A61B8/06 take precedence
• CPC Class Codes: A61B 8/485 involving measuring strain or elastic properties
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis

Abstract

Methods for performing non-invasive thrombolysis with ultrasound using, in some embodiments, one or more ultrasound transducers to focus or place a high intensity ultrasound beam onto a blood clot (thrombus) or other vascular inclusion or occlusion (e.g., clot in the dialysis graft, deep vein thrombosis, superficial vein thrombosis, arterial embolus, bypass graft thrombosis or embolization, pulmonary embolus) which would be ablated (eroded, mechanically fractionated, liquefied, or dissolved) by ultrasound energy. The process can employ one or more mechanisms, such as of cavitational, sonochemical, mechanical fractionation, or thermal processes depending on the acoustic parameters selected. This general process, including the examples of application set forth herein, is henceforth referred to as “Thrombolysis.”

Claims

1. A method for controlled mechanical fractionation of a thrombus, said method comprising:

outputting an initiation ultrasound pulse sequence from a therapy transducer resulting in cavitation forming a targeting bubble cloud;

detecting a location of said targeting bubble cloud to define a treatment region; and

aligning said therapy transducer such that said treatment region is aligned with the thrombus.

2. The method according to claim 1, further comprising:

outputting said initiation ultrasound pulse sequence from a therapy transducer resulting in cavitation forming a therapy bubble cloud within said treatment region;

detecting formation of said therapy bubble cloud generally aligned with at least a portion of the thrombus;

outputting a bubble cloud sustaining ultrasound pulse sequence; and

outputting a therapy ultrasound pulse sequence which interacts with said therapy bubble cloud to produce at least partial fractionation of the thrombus.

3. The method according to claim 2, further comprising:

detecting fractionation of the thrombus.

4. The method according to claim 3 wherein said detecting fractionation of the thrombus comprises detecting reduced echogenicity on a B-Mode ultrasound image.

5. The method according to claim 3 wherein said detecting fractionation of the thrombus comprises detecting changes in ultrasound Doppler color flow downstream of said treatment region on an ultrasound image.

6. The method according to claim 2 wherein said detecting formation of said therapy bubble cloud comprises detecting formation of said therapy bubble cloud using feedback techniques.

7. The method according to claim 6 wherein said feedback techniques are chosen from the group consisting essentially of acoustic backscatter detection, ultrasound imaging, and combinations thereof.

8. The method according to claim 2, wherein said initiation ultrasound pulse sequence, said bubble cloud sustaining ultrasound pulse sequence, and said therapy ultrasound pulse sequence are not identical.

9. The method according to claim 1, wherein said detecting a location of said targeting bubble cloud to define a treatment region comprises detecting a location of said targeting bubble cloud on an ultrasound image.

10. The method according to claim 1, wherein detecting a location of said targeting bubble cloud to define a treatment region comprises detecting a hyperechoic zone on a real-time B-mode ultrasound image to define said treatment region.

13. The method of claim 1 wherein the an initiation ultrasound pulse sequence comprises a peak negative pressure of >

=6 MPa, a peak positive pressure of >

=8 MPa, a pulse length shorter than 50 cycles, and a duty cycle between approximately 0.1% and 5%.

11. A method for acoustic manipulation of at least a fragment of a thrombus, said method comprising:

outputting an initiation ultrasound pulse sequence from a transducer resulting in cavitation forming a bubble cloud within a predetermined volume;

detecting a location of the bubble cloud; and

actuating said transducer such that the fragment of the thrombus is spatially positioned within said predetermined volume in response to the location of said bubble cloud.

12. The method according to claim 11, further comprising:

outputting a bubble cloud sustaining ultrasound pulse sequence; and

outputting an ultrasound pulse sequence which interacts with said bubble cloud to produce at least partial fractionation of the fragment of the thrombus.

14. The method of claim 11 wherein the an initiation ultrasound pulse sequence comprises a peak negative pressure of >

=6 MPa, a peak positive pressure of >

=8 MPa, a pulse length shorter than 50 cycles, and a duty cycle between approximately 0.1% and 5%.