Ultrasound-assisted convection enhanced delivery of compounds in vivo with a transducer cannula assembly

Patent metadata

Field	Value
Publication number	US-10537725-B2
Application number	US-201113582663-A
Country	US
Kind code	B2
Filing date	Mar 4, 2011
Priority date	Mar 5, 2010
Publication date	Jan 21, 2020
Grant date	Jan 21, 2020

Abstract

A method for convection-enhanced delivery (CED) of compounds and an apparatus for use with the method are provided. The apparatus, an ultrasound transducer cannula assembly (TCA) apparatus, can be used for the delivery of a compound to a target in the body such as a cells, tissue or organ in a healthy or diseased state. The ultrasound TCA apparatus comprises a transducer cannula assembly (TCA) and an ultrasound system to enhance penetration of molecules in the target. The ultrasound system may be portable and pocket-sized. The inclusion of ultrasound in the apparatus improves the distribution volume of material four to six times over a convection-enhanced delivery system without ultrasound. Since the targeting can be more focused, less compound is needed, thus lowering the potential for harmful effects to the host and host cells.

First claim

What is claimed is:

1. An ultrasound transducer cannula assembly (TCA) apparatus comprising:
a cannula;
an ultrasound transducer;
an ultrasound driver wherein the ultrasound driver produces an ultrasound drive signal waveform; and
a connection between the ultrasound driver and the ultrasound transducer;
wherein the apparatus is operative for monitoring acoustic energy produced by the ultrasound transducer, and wherein the apparatus is further operative for one or more of the following consisting of (a) adjusting power produced by the ultrasound transducer, and (b) modulating the ultrasound drive signal waveform; and
wherein activation of the ultrasound transducer creates an acoustic field that is one or more of around, within or through the cannula, wherein the apparatus includes a lens associated to the ultrasound transducer to focus acoustic energy produced by the ultrasound transducer.

2. The apparatus of claim 1 , wherein the cannula comprises the ultrasound transducer.

3. The apparatus of claim 1 , comprising a second cannula for guiding the cannula (hereinafter “guide cannula”).

4. The apparatus of claim 1 , wherein the ultrasound transducer comprises portions defining a hole, canal or groove for positioning of the cannula.

5. The apparatus of claim 4 , wherein the ultrasound transducer comprises portions defining a plurality of holes, canals or grooves for positioning of a plurality of cannulas.

6. The apparatus of claim 1 , comprising a stereotaxic, manual or robotic guide arm.

7. The apparatus of claim 1 , comprising a plurality of ultrasound transducers, wherein a member of the plurality of ultrasound transducers produces a different frequency of ultrasound from another member of the plurality of ultrasound transducers.

8. The apparatus of claim 1 , comprising a plurality of ultrasound transducers, wherein the frequency produced by one member of the plurality of ultrasound transducers and the frequency produced by another member of the plurality of ultrasound transducers have different bioacoustical qualities.

9. The apparatus of claim 1 , wherein the apparatus produces a standing wave or acoustic field.

10. The apparatus of claim 1 , wherein the cannula includes the ultrasound transducer disposed outside the cannula.

11. The apparatus of claim 1 , wherein the cannula includes the ultrasound transducer disposed inside the cannula.

12. The apparatus of claim 1 , wherein the ultrasound transducer is an elongated ultrasound transducer and wherein the cannula includes the ultrasound transducer disposed on the cannula so that the ultrasound transducer is coextensive with the cannula.

13. The apparatus of claim 1 , wherein the cannula includes a plurality of ultrasound transducers spaced apart along a length of the cannula.

14. The apparatus of claim 1 , wherein the apparatus is operative for each of (a) adjusting power produced by the ultrasound transducer, and (b) modulating the ultrasound drive signal waveform.

15. The apparatus of claim 1 , wherein the lens associated to the ultrasound transducer is shaped to focus acoustic energy produced by the ultrasound transducer to produce an acoustic field of a desired arbitrary shape.

16. The apparatus of claim 1 , wherein the lens associated to the ultrasound transducer is shaped to focus acoustic energy produced by the ultrasound transducer to produce an acoustic field of a desired shape, the desired shape being a desired pattern of compound(s) that are infused to target cells, tissues or organs.

17. The apparatus of claim 1 , and wherein the apparatus is further operative for one or more of the following selected from the group consisting of (a) adjusting power produced by the ultrasound transducer, and (b) modulating the ultrasound drive signal waveform.

18. The apparatus of claim 1 wherein the apparatus is operative to monitor a Mechanical Index (MI) of the apparatus during use of the apparatus to direct ultrasound energy to body tissue.

19. The apparatus of claim 1 , wherein the apparatus is operative to monitor a thermal index (TI) of the apparatus during use of the apparatus to direct ultrasound energy to body tissue, the thermal index (TI) indicating a predicted temperature rise of the body tissue attributable to a directing the ultrasound energy to the body tissue.

20. A method for ultrasound-assisted convection-enhanced delivery (UCED) of a compound to a targeted cell, tissue, organ or region of the body (hereinafter “target”) in a subject comprising the steps of:
providing an ultrasound transducer cannula assembly (TCA) apparatus having a cannula and an ultrasound transducer; wherein activation of the ultrasound transducer creates an acoustic field around that is one or more of around, within or through the cannula;
contacting the ultrasound TCA apparatus to the target;
introducing the compound (or a solution thereof) into cannula;
activating the ultrasound transducer, thereby producing an acoustic field; and
releasing the compound from the cannula, whereby the compound contacts the target wherein the step of activating the ultrasound transducer is before the step of releasing the compound, wherein the method includes contacting the ultrasound TCA apparatus to the target and wherein the step of activating includes performing the activating before the contacting the TCA apparatus to the target while the ultrasound TCA apparatus is being guided to the target so that the cannula is vibrating while the ultrasound TCA apparatus is being guided to the target and while the contacting the ultrasound TCA apparatus is being performed.

21. The method of claim 20 , wherein the contacting step comprises stereotactically, manually or robotically guiding the ultrasound TCA apparatus to the target.

22. The method of claim 20 , wherein the introducing step comprises adding stabilized microbubbles to the compound.

23. The method of claim 20 , wherein the step of activating the ultrasound transducer produces a standing waveform or focused field.

24. The method of claim 20 , wherein the step of activating includes performing the activating while the ultrasound TCA apparatus is being guided to the target so that the cannula is vibrating while the ultrasound TCA apparatus is being guided to the target.

25. A method comprising:
providing an ultrasound transducer cannula assembly (TCA) apparatus having a cannula; and a plurality of ultrasound transducers; wherein activation of an ultrasound transducer of the plurality of ultrasound transducers creates an acoustic field that is one or more of around, within or through the cannula, wherein a member of the plurality of ultrasound transducers produces a different frequency of ultrasound from another member of the plurality of ultrasound transducers;
activating a first ultrasound transducer of the plurality of transducers at a first frequency to permeabilize a cell or tissue; and
activating a second ultrasound transducer of the plurality of transducers at a second frequency to push or propel a compound to a desired target.

26. The method of claim 25 , wherein the cannula assembly (TCA) apparatus included a plurality of cannulas, and wherein ultrasound transducers of the plurality of ultrasound transducers are distributed among cannulas of the plurality of cannulas.

27. The method of claim 25 , wherein the method includes permeabilizing the cell or tissue, wherein the permeabilizing the c

Assignees

• Lewis Jr George K
• Olbricht William L
• Univ Cornell

Inventors

• Lewis Jr George K
• Olbricht William L

Classifications

• A61M37/0092 Primary

  using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis · CPC title

• Y10T29/42

  Piezoelectric device making · CPC title

• A61M2210/0693

  Brain, cerebrum · CPC title

• A61B8/0816

  using echo-encephalography · CPC title