METHODS OF USING FOCUSED ACOUSTIC WAVES FOR NON-INVASIVE SONODYNAMIC THERAPY
Disclosed are methods of using focused acoustic waves for providing non-invasive sonodynamic therapy. The method includes acoustically coupling an array of piezoelectric transducers to a patient. A controller is configured to generate an electrical drive signal at a frequency selected from a range of frequencies, modulate the drive signal, and drive the transducer with the modulated drive signal at the frequency to produce modulated acoustic waves to produce an average acoustic intensity sufficient to activate a sonosensitizer in a treatment region without damaging healthy cells in the treatment region.
1 . A method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising:
acoustically coupling a patient interface to a skin surface of a head of a patient with a brain with tumor cells, the patient interface comprising: an ultrasound transducer array and a cooling system,
wherein the ultrasound transducer array comprises a plurality of ultrasound transducer elements,
wherein the ultrasound transducer array is configured to emit focused acoustic waves through the skull,
wherein the patient interface is configured to acoustically couple the ultrasound transducer array of to the skin surface,
wherein the patient interface is configured for conforming to the skin surface;
driving the ultrasound transducer array with a signal,
wherein the signal is configured to deliver the focused acoustic waves at a frequency with an acoustic intensity in the brain at the tumor cells of the patient; and
circulating a fluid through the cooling system to reduce heat at the head of the patient at the patient interface.
2 . The method of claim 1 , further comprising moving the patient interface with respect to the head of the patient.
3 . The method of claim 1 , wherein the patient interface comprises at least one of a cap, a rigid shell, and a flexible shell.
4 . The method of claim 1 , wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour.
5 . The method of claim 1 , further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain,
wherein the sonosensitizer is a porphyrin compound,
wherein the focused acoustic waves are configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
6 . The method of claim 1 , further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the ultrasound transducer array comprises a grid of elements,
wherein the sonosensitizer is a porphyrin compound, wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the acoustic intensity is in a range of 0.1 W/cm 2 to 50 W/cm 2 to activate the sonosensitizer.
7 . A method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising:
acoustically coupling a non-invasive sonodynamic therapy system to a skin surface of a head of a patient with a brain with tumor cells,
wherein the non-invasive sonodynamic therapy system comprises:
a patient interface, and
an array of ultrasound transducer elements wherein each of the ultrasound transducer elements is configured to emit focused acoustic waves through the skull;
driving the array of ultrasound transducer elements with a signal,
wherein the signal is configured to deliver the focused acoustic waves at a frequency with an acoustic intensity in the brain at the tumor cells of the patient,
wherein the patient interface is configured to acoustically couple the array of ultrasound transducer elements to the skin surface of the head.
8 . The method of claim 7 , wherein the patient interface comprises at least one of a cap, a rigid shell and a flexible shell.
9 . The method of claim 7 , wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour.
10 . The method of claim 7 , wherein the signal is a pulse signal to pulse the focused acoustic waves to affect a spatial variation of the acoustic intensity in the brain at the tumor cells of the patient.
11 . The method of claim 7 , wherein the focused acoustic waves deliver the non-invasive sonodynamic therapy at the frequency in a range of 20 kHz to 2 MHz to the tumor cells in the brain of the patient to activate the sonosensitizer,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the sonosensitizer is a porphyrin compound.
12 . The method of claim 7 , further comprising administering aminolevulinic acid (ALA) to the patient, wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain.
13 . A method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising:
acoustically coupling a patient interface to a skin surface of a head of a patient with a brain with tumor cells, wherein the patient interface comprises an array of ultrasound transducer elements,
wherein each of the ultrasound transducer elements is configured to emit focused acoustic waves through the skull;
driving the array of ultrasound transducer elements with a signal,
wherein the signal is configured to deliver an acoustic intensity in the brain at the tumor cells of the patient.
14 . The method of claim 13 , wherein the focused acoustic waves comprise a frequency of 1 MHz.
15 . The method of claim 13 , wherein the patient interface comprises at least one of a cap, a rigid shell and a flexible shell.
16 . The method of claim 13 , wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour.
17 . The method of claim 13 ,
wherein the focused acoustic waves comprises a frequency in a range of 20 kHz to 2 MHz,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the sonosensitizer is a porphyrin compound,
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
18 . The method of claim 14 , further comprising administering microbubbles to the tumor cells,
wherein the sonosensitizer is a porphyrin compound,
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
19 . The method of claim 13 ,
wherein the signal comprises at least one selected from the group consisting of:
a sine wave, a rectangular pulse, and a triangular pulse; and
wherein the sonosensitizer is a porphyrin compound.
20 . The method of claim 13 , further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the sonosensitizer is a porphyrin compound,
wherein the focused acoustic waves is configured to activate the porphyrin compound to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells.