Systems, methods, and computer readable media for high frequency contrast imaging and image-guided therapeutics

• US 9,532,769 B2
• Filed: 09/07/2010
• Issued: 01/03/2017
• Est. Priority Date: 09/04/2009
• Status: Active Grant

• Current Assignee: Sunnybrook Research Institute
• Original Assignee: Sunnybrook Research Institute, University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Dayton, Paul A., Gessner, Ryan, Lee, Hyunggyun, Lukacs, Marc, Foster, Francis Stuart
• Primary Examiner(s): CHAO, ELMER M
• Application Number:
  US13/393,500
• Publication Number:
  US 20120220869A1
• Time in Patent Office: 2,310 Days
• US Class Current: 1/1
• 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: G01S 7/52039 exploiting the non-linear response of a contrast enhancer, e.g. a contrast agent diagnostic techniques involving the use of contrast agents A61B8/481
• CPC Class Codes: G01S 7/52047 for elimination of side lobes or of grating lobes; for increasing resolving power

Abstract

Systems, methods, and computer readable media for high-frequency contrast imaging and image-guided therapeutics are disclosed. According to one aspect a method for high frequency contrast imaging and image-guided therapeutics includes: providing ultrasound of a first frequency bandwidth, directed toward the volume to be imaged, the volume containing a carrier having non-linear acoustical properties, wherein the ultrasound of the first frequency bandwidth causes the carrier to generate ultrasound of a second frequency bandwidth that is different from the first frequency bandwidth; receiving, from the volume to be imaged, ultrasound of the second frequency bandwidth; and using the received ultrasound of the second frequency bandwidth to generate an image of the volume to be imaged, wherein the components of the second frequency bandwidth that are detected are of a frequency greater than 20 MHz. According to another aspect, ultrasound at a first frequency bandwidth enables imaging of a target, and ultrasound at a second frequency bandwidth mediates drug or gene delivery to a portion of the target, as guided by the image provided by the first frequency.

Claims

1. A method for high-frequency contrast imaging and image-guided therapeutics, the method comprising:

generating and directing ultrasound energy with a transmitter of a first frequency bandwidth toward the volume to be imaged, the volume containing a carrier having non-linear acoustical properties, wherein the ultrasound energy of the first frequency bandwidth causes the carrier to generate ultrasound energy of a second frequency bandwidth that is different from the first frequency bandwidth, wherein the transmitter comprises a first physical component of a multi-frequency ultrasound transducer that is structured to transmit the ultrasound energy of the first frequency bandwidth and wherein the first frequency bandwidth has a center frequency in a range between 0.8 MHz and 10 MHz;

detecting, from the volume to be imaged, the ultrasound energy with a receiver of a second frequency bandwidth, wherein the receiver comprises a second physical component of the multi-frequency ultrasound transducer structured to detect ultrasound energy at frequencies greater than 20 MHz wherein the first frequency bandwidth generated by the transmitter is lower than the second frequency bandwidth detected by the receiver and wherein the first and second physical components of the multi-frequency transducer are structured so that the −

12 dB bandwidths of the transmitter and the receiver do not overlap with each other; and

using the detected ultrasound energy of the second frequency bandwidth to generate an image of the volume to be imaged,

wherein components of the second frequency bandwidth that are detected and used to generate the image are greater than 20 MHz.

2. The method of claim 1 wherein the components of the second frequency bandwidth that are detected are of a frequency greater than 25 MHz.

3. The method of claim 1 wherein the carrier comprises one of:

an acoustically active liposphere;

a liposome;

a gas-filled agent; and

a liquid perfluorocarbon droplet.

4. The method of claim 1 wherein the carrier comprises a contrast agent.

5. The method of claim 1 wherein the carrier comprises a substance having an acoustical property that is different from an acoustical property of biological tissue.

6. The method of claim 5 wherein the acoustical property that is different from an acoustical property of biological tissue comprises acoustic impedance.

7. The method of claim 1 wherein the carrier comprises a therapeutic compound.

8. The method of claim 1 wherein the carrier comprises an outer surface having at least one molecular structure for attaching the carrier to biological structures.

9. The method of claim 1 wherein the carrier comprises an outer surface having at least one molecular structure targeting a cell receptor.

10. The method of claim 1 wherein the ultrasound energy of the first frequency bandwidth is used for at least one of:

affecting a position of the carrier;

affecting a size of the carrier;

affecting a structural integrity of the carrier;

affecting the proximity of the carrier relative to a target portion of the volume to be imaged;

affecting vascular permeability of tissue in the volume to be imaged;

affecting the temperature within the volume to be imaged; and

sonophoresis.

11. The method of claim 1 wherein the volume to be imaged includes at least one of a vein, an artery, a venule, an arteriole, a capillary, and a lymphatic.

12. A system for high-frequency contrast imaging and image-guided therapeutics, the system comprising:

a multi-frequency ultrasound transducer including a transmitter comprising a first physical component structured to generate and transmit ultrasound energy at a first frequency bandwidth has a center frequency in a range between 0.8 MHz and 10 MHz and a receiver comprising a second physical component structured to detect ultrasound at a second frequency bandwidth different from the first frequency bandwidth, the second frequency bandwidth comprising frequencies greater than 20 MHz wherein the first frequency bandwidth generated by the transmitter is lower than the second frequency bandwidth detected by the receiver and wherein first and second physical components are structured such that −

12 dB bandwidths of the transmitter and the receiver do not overlap with each other; and

a control module for controlling the transmitter of the ultrasound transducer to generate and direct the ultrasound energy of the first frequency bandwidth, toward a volume to be imaged, the volume containing a carrier having non-linear acoustical properties, for causing the carrier to generate the ultrasound energy of the second frequency bandwidth, and for controlling the receiver of the ultrasound to detect, from the volume to be imaged, the ultrasound energy of the second frequency bandwidth; and

for using the detected ultrasound energy of the second frequency bandwidth to generate an image of the volume to be imaged,

wherein components of the second frequency bandwidth that are detected and used to generate the image are greater than 20 MHz.

13. The system of claim 12 wherein the components of the second frequency bandwidth that are detected are of a frequency greater than 25 MHz.

14. The system of claim 12 wherein the transducer transmits ultrasound energy at both the first and second frequency bandwidths simultaneously.

15. The system of claim 12 wherein the carrier comprises one of:

an acoustically active liposphere;

a liposome;

a gas-filled agent; and

a liquid perfluorocarbon droplet.

16. The system of claim 12 wherein the carrier comprises a contrast agent.

17. The system of claim 12 wherein the carrier comprises a substance having an acoustical property that is different from an acoustical property of biological tissue.

18. The system of claim 17 wherein the acoustical property that is different from an acoustical property of biological tissue comprises acoustic impedance.

19. The system of claim 12 wherein the carrier comprises a therapeutic compound.

20. The system of claim 12 wherein the carrier comprises an outer surface having at least one molecular structure for attaching the carrier to biological structures.

21. The system of claim 12 wherein the carrier comprises an outer surface having at least one molecular structure targeting a cell receptor.

22. The system of claim 12 wherein the ultrasound energy of the first frequency bandwidth is used for at least one of:

affecting a position of the carrier;

affecting a size of the carrier;

affecting a structural integrity of the carrier;

affecting the proximity of the carrier relative to a target portion of the targeted area;

affecting vascular permeability of tissue in the targeted area;

affecting temperature of a target portion of the targeted area; and

sonophoresis.

23. The system of claim 12 wherein the targeted volume includes at least one of a vein, an artery, a venule, an arteriole, a capillary, and a lymphatic.

24. A non-transitory computer readable medium having stored thereon executable instructions that when executed by the processor of a computer control the computer to perform steps comprising:

generating and directing ultrasound energy with a transmitter of a first frequency bandwidth toward the volume to be imaged, the volume containing a carrier having non-linear acoustical properties, wherein the ultrasound energy of the first frequency bandwidth causes the carrier to generate ultrasound energy of a second frequency bandwidth that is different from the first frequency bandwidth, wherein the transmitter comprises a first physical component of a multi-frequency ultrasound transducer that is structured to transmit the ultrasound energy of the first frequency bandwidth and wherein the first frequency bandwidth has a center frequency in a range between 0.8 and 10 MHz;

detecting, from the volume to be imaged, the ultrasound energy with a receiver of a second frequency bandwidth, wherein the receiver comprises a second physical component of the multi-frequency ultrasound transducer structured to detect ultrasound energy at frequencies greater than 20 MHz wherein the first frequency bandwidth generated by the transmitter is lower than the second frequency bandwidth detected by the receiver and wherein the first and second physical components of the multi-frequency transducer are structured so that the −

12 dB bandwidths of the transmitter and the receiver do not overlap with each other; and

using the detected ultrasound energy of the second frequency bandwidth to generate an image of the volume to be imaged,

wherein components of the second frequency bandwidth that are detected and used to generate the image are greater than 20 MHz.