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US 12,741,161 B2Granted
Methods of using ultrasound waves for sonodynamic therapy
AssigneeAlpheus Medical, Inc.
InventorsVijay Agarwal, Braden Eliason, Jeremy Ling
Life of this patent
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Abstract
Disclosed are methods of producing ultrasound waves for providing sonodynamic therapy. The method includes coupling a sonodynamic therapy device with an array of piezoelectric transducer elements to a skin surface. A controller is configured to generate an electrical drive signal to produce ultrasound waves to activate a sonosensitizer in a treatment region without damaging healthy cells in the treatment region.
Claims25
A method of producing ultrasound waves for sonodynamic therapy to treat tumor cells harboring a sonosensitizer, comprising:
- coupling a sonodynamic therapy device to a skin surface over a treatment region with the tumor cells of a patient, the sonodynamic therapy device comprising:
- an array of piezoelectric ultrasound transducer elements, wherein each of the piezoelectric ultrasound transducer elements comprises an emitting surface configured to emit an ultrasound wave,
- a controller, wherein the controller is coupled to the array of piezoelectric ultrasound transducer elements and the controller is configured to generate a plurality of signals for driving the piezoelectric ultrasound transducer elements and generating ultrasound waves, and
- a patient interface, wherein the patient interface is configured for conforming to the skin surface of the patient,
- driving the array of piezoelectric ultrasound transducer elements with the plurality of signals to activate the sonosensitizer in the treatment region of the patient,
- wherein the sonosensitizer comprises a porphyrin,
- wherein the plurality of signals comprises one or more frequencies in a range of 20 kHz to 2 MHz,
- wherein the plurality of signals comprises at least one selected from the group consisting of:
- a sine wave, a rectangular pulse, and a triangular pulse,
- wherein individual ones of the plurality of signals are configured to drive individual ones of the piezoelectric ultrasound transducer elements to emit the ultrasound waves to minimize a spatial variation of an acoustic intensity in the treatment region,
- wherein the controller uses an algorithm for the array of piezoelectric ultrasound transducer elements to provide the acoustic intensity in a range of 0.1 W/cm2 to 50 W/cm2,
- wherein the controller is configured to modulate the ultrasound waves with randomized phases, and
- wherein the patient interface comprises a cooling system placed between the array of piezoelectric ultrasound transducer elements and the treatment region, the cooling system comprising one or more cooling loops or channels and a flexible membrane configured to allow circulation of a coolant therein.
10 more elements
A method of producing ultrasound waves for sonodynamic therapy to treat tumor cells harboring a sonosensitizer, the method comprising:
- coupling a sonodynamic therapy device to a skin surface over a treatment region of a patient,
- wherein the sonodynamic therapy device comprises:
- a patient interface comprising a flexible membrane conforming to the skin surface of the patient and one or more cooling loops or channels,
- wherein the patient interface comprises at least one of a cap, a rigid shell, or a flexible shell,
- an array of piezoelectric ultrasound transducer elements, and
- a controller configured to generate a plurality of signals for driving the piezoelectric ultrasound transducer elements,
- wherein the controller drives the array of piezoelectric transducer elements at a plurality of frequencies in a range of 650 kHz to 2 MHz,
- wherein the controller uses an algorithm for the array of piezoelectric ultrasound transducer elements to provide an acoustic intensity in a range of 0.1 W/cm2 to 50 W/cm2,
- wherein the plurality of signals comprises at least one selected from the group consisting of:
- a sine wave, a rectangular pulse, and a triangular pulse,
- wherein each of the piezoelectric ultrasound transducer elements comprises an emitting surface configured to emit an ultrasound wave,
- driving the array of piezoelectric ultrasound transducer elements with the plurality of signals to activate the sonosensitizer in the treatment region,
- wherein the sonosensitizer comprises a porphyrin,
- circulating a coolant via the one or more cooling loops or channels,
- wherein individual ones of the plurality of signals are configured to drive individual ones of the piezoelectric ultrasound transducer elements to emit a plurality of ultrasound waves configured to minimize a spatial variation of the acoustic intensity in the treatment region,
- wherein the plurality of signals comprise a modulated wave parameter configured to modulate the plurality of ultrasound waves with randomized phases thereby promoting broad coverage across the treatment region, and
- wherein the plurality of signals are modulated by a duty cycle modulated drive signal configured to produce a low temporal average acoustic intensity within the treatment region.
14 more elements
A method of producing ultrasound waves for sonodynamic therapy to treat tumor cells harboring a sonosensitizer, comprising:
- coupling a sonodynamic therapy device to a skin surface over a treatment region with the tumor cells of a patient, the sonodynamic therapy device comprising:
- an array of piezoelectric ultrasound transducer elements, wherein each of the piezoelectric ultrasound transducer elements comprises an emitting surface configured to emit an ultrasound wave,
- a controller, wherein the controller is coupled to the array of piezoelectric ultrasound transducer elements and the controller is configured to generate a plurality of signals for driving the piezoelectric ultrasound transducer elements and generating ultrasound waves, and
- a patient interface, wherein the patient interface is configured for conforming to the skin surface of the patient,
- driving the array of piezoelectric ultrasound transducer elements with the plurality of signals to activate the sonosensitizer in the treatment region of the patient,
- wherein the sonosensitizer comprises a porphyrin,
- wherein the plurality of signals comprises one or more frequencies in a range of 20 kHz to 2 MHz,
- wherein individual ones of the plurality of signals are configured to drive individual ones of the piezoelectric ultrasound transducer elements to emit the ultrasound waves to minimize a spatial variation of an acoustic intensity in the treatment region,
- wherein the plurality of signals is configured to drive each of the piezoelectric ultrasound transducer elements to produce high temporal peak acoustic intensities within the treatment region with a low temporal average acoustic intensity when activating the sonosensitizer,
- wherein the controller uses an algorithm for the array of piezoelectric ultrasound transducer elements to provide the acoustic intensity in a range of 0.1 W/cm2 to 50 W/cm2;
- wherein the controller is configured to modulate the ultrasound waves with randomized phases, and
- wherein the patient interface comprises a cooling system placed between the array of piezoelectric ultrasound transducer elements and the treatment region, the cooling system comprising one or more cooling loops or channels and a flexible membrane configured to allow circulation of a coolant therein.
9 more elements
A method of producing ultrasound waves for sonodynamic therapy to treat tumor cells harboring a sonosensitizer, the method comprising:
- coupling a sonodynamic therapy device to a skin surface over a treatment region of a patient,
- wherein the sonodynamic therapy device comprises:
- a patient interface comprising a flexible membrane conforming to the skin surface of the patient and one or more cooling loops or channels,
- wherein the patient interface comprises at least one of a cap, a rigid shell, or a flexible shell,
- an array of piezoelectric ultrasound transducer elements, and
- a controller configured to generate a plurality of signals for driving the piezoelectric ultrasound transducer elements,
- wherein the controller drives the array of piezoelectric transducer elements at a plurality of frequencies in a range of 650 kHz to 2 MHz,
- wherein the controller uses an algorithm for the array of piezoelectric ultrasound transducer elements to provide an acoustic intensity in a range of 0.1 W/cm2 to 50 W/cm2,
- wherein each of the piezoelectric ultrasound transducer elements comprises an emitting surface configured to emit an ultrasound wave,
- driving the array of piezoelectric ultrasound transducer elements with the plurality of signals to activate the sonosensitizer in the treatment region,
- wherein the sonosensitizer comprises a porphyrin,
- circulating a coolant via the one or more cooling loops or channels,
- wherein individual ones of the plurality of signals are configured to drive individual ones of the piezoelectric ultrasound transducer elements to emit a plurality of ultrasound waves configured to minimize a spatial variation of the acoustic intensity in the treatment region,
- wherein the plurality of signals comprise a modulated wave parameter configured to modulate the plurality of ultrasound waves with randomized phases thereby promoting broad coverage across the treatment region, and
- wherein the plurality of signals are modulated by a duty cycle modulated drive signal configured to produce high temporal peak acoustic intensities within the treatment region with a low temporal average acoustic intensity within the treatment region.
12 more elements
A method of producing ultrasound waves for sonodynamic therapy to treat tumor cells harboring a sonosensitizer, comprising:
- coupling a sonodynamic therapy device to a skin surface over a treatment region with the tumor cells of a patient, the sonodynamic therapy device comprising:
- an array of piezoelectric ultrasound transducer elements, wherein each of the piezoelectric ultrasound transducer elements comprises an emitting surface configured to emit an ultrasound wave,
- a controller, wherein the controller is coupled to the array of piezoelectric ultrasound transducer elements and the controller is configured to generate a plurality of signals for driving the piezoelectric ultrasound transducer elements and generating ultrasound waves, and
- a patient interface, wherein the patient interface is configured for conforming to the skin surface of the patient,
- driving the array of piezoelectric ultrasound transducer elements with the plurality of signals to activate the sonosensitizer in the treatment region of the patient,
- wherein the sonosensitizer comprises a porphyrin,
- wherein the plurality of signals comprises one or more frequencies in a range of 20 kHz to 2 MHz,
- wherein individual ones of the plurality of signals are configured to drive individual ones of the piezoelectric ultrasound transducer elements to emit the ultrasound waves to minimize a spatial variation of an acoustic intensity in the treatment region,
- wherein the controller uses an algorithm for the array of piezoelectric ultrasound transducer elements to provide the acoustic intensity in a range of 0.1 W/cm2 to 50 W/cm2;
- wherein the controller uses at least one in situ variable selected from the group consisting of:
- a tissue depth, a tissue volume, a skull thickness, and a temperature, and generates the ultrasound waves based on the at least one in situ variable,
- wherein the controller is configured to modulate the ultrasound waves with randomized phases, and
- wherein the patient interface comprises a cooling system placed between the array of piezoelectric ultrasound transducer elements and the treatment region, the cooling system comprising one or more cooling loops or channels and a flexible membrane configured to allow circulation of a coolant therein.
10 more elements
A method of producing ultrasound waves for sonodynamic therapy to treat tumor cells harboring a sonosensitizer, the method comprising:
- coupling a sonodynamic therapy device to a skin surface over a treatment region of a patient,
- wherein the sonodynamic therapy device comprises:
- a patient interface comprising a flexible membrane conforming to the skin surface of the patient and one or more cooling loops or channels,
- wherein the patient interface comprises at least one of a cap, a rigid shell, or a flexible shell,
- an array of piezoelectric ultrasound transducer elements, and
- a controller configured to generate a plurality of signals for driving the piezoelectric ultrasound transducer elements,
- wherein the controller drives the array of piezoelectric transducer elements at a plurality of frequencies in a range of 650 kHz to 2 MHz,
- wherein the controller uses an algorithm for the array of piezoelectric ultrasound transducer elements to provide an acoustic intensity in a range of 0.1 W/cm2 to 50 W/cm2,
- wherein the controller uses at least one in situ variable selected from the group consisting of:
- a tissue depth, a tissue volume, a skull thickness, and a temperature, and generates the ultrasound waves based on the at least one in situ variable,
- wherein each of the piezoelectric ultrasound transducer elements comprises an emitting surface configured to emit an ultrasound wave,
- driving the array of piezoelectric ultrasound transducer elements with the plurality of signals to activate the sonosensitizer in the treatment region,
- wherein the sonosensitizer comprises a porphyrin,
- circulating a coolant via the one or more cooling loops or channels,
- wherein individual ones of the plurality of signals are configured to drive individual ones of the piezoelectric ultrasound transducer elements to emit a plurality of ultrasound waves configured to minimize a spatial variation of the acoustic intensity in the treatment region,
- wherein the plurality of signals comprise a modulated wave parameter configured to modulate the plurality of ultrasound waves with randomized phases thereby promoting broad coverage across the treatment region, and
- wherein the plurality of signals are modulated by a duty cycle modulated drive signal configured to produce a low temporal average acoustic intensity within the treatment region.
14 more elements
A method of producing ultrasound waves for sonodynamic therapy to treat tumor cells harboring a sonosensitizer, comprising:
- coupling a sonodynamic therapy device to a skin surface over a treatment region with the tumor cells of a patient, the sonodynamic therapy device comprising:
- an array of piezoelectric ultrasound transducer elements, wherein each of the piezoelectric ultrasound transducer elements comprises an emitting surface configured to emit an ultrasound wave,
- a controller, wherein the controller is coupled to the array of piezoelectric ultrasound transducer elements and the controller is configured to generate a plurality of signals for driving the piezoelectric ultrasound transducer elements and generating ultrasound waves, and
- a patient interface, wherein the patient interface is configured for conforming to the skin surface of the patient,
- driving the array of piezoelectric ultrasound transducer elements with the plurality of signals to activate the sonosensitizer in the treatment region of the patient,
- wherein the sonosensitizer comprises a porphyrin,
- wherein the plurality of signals comprises one or more frequencies in a range of 20 kHz to 2 MHz,
- wherein individual ones of the plurality of signals are configured to drive individual ones of the piezoelectric ultrasound transducer elements to emit the ultrasound waves to minimize a spatial variation of an acoustic intensity in the treatment region,
- wherein the controller uses an algorithm for the array of piezoelectric ultrasound transducer elements to provide the acoustic intensity in a range of 0.1 W/cm2 to 50 W/cm2;
- wherein the controller is configured to modulate the ultrasound waves with randomized phases, and
- wherein the patient interface comprises a cooling system placed between the array of piezoelectric ultrasound transducer elements and the treatment region, the cooling system comprising one or more cooling loops or channels and a flexible membrane configured to allow circulation of a coolant therein,
- wherein the driving the array of piezoelectric ultrasound transducer elements occurs with the patient in a seated position on a chair.
9 more elements
A method of producing ultrasound waves for sonodynamic therapy to treat tumor cells harboring a sonosensitizer, the method comprising:
- coupling a sonodynamic therapy device to a skin surface over a treatment region of a patient,
- wherein the sonodynamic therapy device comprises:
- a patient interface comprising a flexible membrane conforming to the skin surface of the patient and one or more cooling loops or channels,
- wherein the patient interface comprises at least one of a cap, a rigid shell, or a flexible shell,
- an array of piezoelectric ultrasound transducer elements, and
- a controller configured to generate a plurality of signals for driving the piezoelectric ultrasound transducer elements,
- wherein the controller drives the array of piezoelectric transducer elements at a plurality of frequencies in a range of 650 kHz to 2 MHz,
- wherein the controller uses an algorithm for the array of piezoelectric ultrasound transducer elements to provide an acoustic intensity in a range of 0.1 W/cm2 to 50 W/cm2,
- wherein each of the piezoelectric ultrasound transducer elements comprises an emitting surface configured to emit an ultrasound wave,
- driving the array of piezoelectric ultrasound transducer elements with the plurality of signals to activate the sonosensitizer in the treatment region,
- wherein the sonosensitizer comprises a porphyrin,
- circulating a coolant via the one or more cooling loops or channels,
- wherein individual ones of the plurality of signals are configured to drive individual ones of the piezoelectric ultrasound transducer elements to emit a plurality of ultrasound waves configured to minimize a spatial variation of the acoustic intensity in the treatment region,
- wherein the plurality of signals comprise a modulated wave parameter configured to modulate the plurality of ultrasound waves with randomized phases thereby promoting broad coverage across the treatment region, and
- wherein the plurality of signals are modulated by a duty cycle modulated drive signal configured to produce a low temporal average acoustic intensity within the treatment region,
- wherein the driving the array of piezoelectric ultrasound transducer elements occurs with the patient in a seated position on a chair.
13 more elements
Dependencies are inferred from the claim text.