METHODS OF USING ULTRASOUND WAVES FOR SONODYNAMIC THERAPY
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.
1 . 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 ultrasound waves,
a controller, wherein the controller is coupled to the array of piezoelectric ultrasound transducer elements, 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 a signal to activate the sonosensitizer in the treatment region of the patient,
wherein the signal is configured to minimize a spatial variation of an acoustic intensity in the treatment region,
wherein the signal comprises one or more duty cycles configured to generate the acoustic intensity when activating the sonosensitizer.
2 . The method of claim 1 , wherein the signal comprises one or more frequencies in a range of 20 kHz to 2 MHz.
3 . The method of claim 1 , wherein the signal comprises a modulated wave parameter configured to emit the ultrasound waves to damage the tumor cells in the treatment region.
4 . The method of claim 1 , 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/cm 2 to 50 W/cm 2 .
5 . The method of claim 1 , wherein the signal is modulated by a duty cycle modulated drive signal configured to produce duty cycle modulated acoustic waves.
6 . The method of claim 1 , 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.
7 . The method of claim 1 , wherein the ultrasound waves are planar or defocused.
8 . The method of claim 1 , wherein the signal 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.
9 . The method of claim 1 , wherein the driving the array of piezoelectric ultrasound transducer elements comprises driving multiple elements with multiple signals.
10 . 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 of a patient,
wherein the sonodynamic therapy device comprises:
a patient interface,
an array of piezoelectric ultrasound transducer elements, and
a controller,
wherein each of the piezoelectric ultrasound transducer elements comprises an emitting surface configured to emit a plurality of ultrasound waves,
driving the array of piezoelectric ultrasound transducer elements with a signal to activate the sonosensitizer in the treatment region,
wherein the signal is configured to minimize a spatial variation of an acoustic intensity in the treatment region with a modulated wave parameter configured to emit the plurality of ultrasound waves to activate the sonosensitizer in the treatment region,
wherein the signal is modulated by a duty cycle modulated drive signal comprising a phase configured to drive each of the piezoelectric ultrasound transducer elements to produce a low temporal average acoustic intensity within the treatment region.
11 . The method of claim 10 , wherein the controller drives the array of piezoelectric transducer elements at a plurality of frequencies in a range of 650 kHz to 2 Mhz.
12 . The method of claim 10 , wherein the signal is selected from at least one of the group consisting of: a frequency modulated drive signal and a phase modulated signal.
13 . The method of claim 10 , wherein the signal comprises at least one selected from the group consisting of: a sine wave, a rectangular pulse, and a triangular pulse.
14 . The method of claim 10 , wherein the sonodynamic therapy is configured to minimize a spatial variation of the acoustic intensity in the tumor cells, wherein the signal is selected from the group consisting of: a phase modulated drive signal and a pulse signal.
15 . The method of claim 10 , wherein the sonodynamic therapy is configured to minimize a spatial variation of the acoustic intensity in the tumor cells, wherein the signal is selected from the group consisting of: a duty cycle modulated drive signal and a frequency modulated drive signal.
16 . The method of claim 10 , wherein the patient interface comprises at least one of a cap, a rigid shell, or a flexible shell.
17 . The method of claim 10 , further comprising administering a pro drug to the patient, wherein the pro drug comprises aminolevulinic acid (ALA).
18 . The method of claim 17 , wherein the ALA comprises 5-ALA.
19 . The method of claim 10 , wherein the sonosensitizer comprises a porphyrin.
20 . The method of claim 19 , wherein the porphyrin comprises protoporphyrin IX.