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

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.

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.

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 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 produces a standing waveform or focused field, wherein the step of activating the ultrasound transducer produces the standing waveform, and wherein the method includes generating a steady spatial field of nodes and anti-nodes within the target.

An ultrasound transducer cannula assembly (TCA) apparatus comprising:

• a cannula;
• and
• an ultrasound transducer;
• an ultrasound driver wherein the ultrasound driver produces an ultrasound drive signal waveform;
• 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 is operative to monitor a Mechanical Index (MI) of the apparatus during use of the apparatus to direct ultrasound energy to body tissue.

An ultrasound transducer cannula assembly (TCA) apparatus comprising:

• a cannula;
• and
• an ultrasound transducer;
• an ultrasound driver wherein the ultrasound driver produces an ultrasound drive signal waveform;
• 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 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 the directing the ultrasound energy to the body tissue.

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 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 produces a standing waveform or focused field, wherein method includes using the TCA apparatus to produce the standing waveform in the targeted cell tissue or organ so that the standing waveform confines the compound to a desired location in the targeted cell, tissue or organ.

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 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 of the compound, 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 produces a standing waveform or focused field, wherein a compound has a desired location in the tissue or organ, wherein the method includes confining the compound to the desired location in the tissue or organ, wherein the confining includes activating the ultrasound transducer to produce a standing waveform or focused field.

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 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 produces a standing waveform or focused field, wherein the method includes, to infuse the compound into the target, inducing a first standing waveform in the target using the TCA apparatus, and inducing a second standing waveform in the target using the TCA apparatus, the second standing waveform being different than the first standing waveform.