ULTRASOUND ARRAYS FOR ENHANCED SONODYNAMIC THERAPY FOR TREATING CANCER
Ultrasound transducer element arrays using acoustic ensonification drive patterns via a patient interface for sonosensitizer activation in sonodynamic therapy. Incoherent acoustic field generation varying phase, frequencies, and/or amplitude via controlled delivery of low intensity planar acoustic waves. Method includes generating a first and a second signal to generate respective acoustic ensonification drive patterns with phase, frequency, and amplitude and generating at least one relative phase, frequency or amplitude difference to generate a third incoherent acoustic ensonification pattern to activate a sonosensitizer. Calibration and complementary therapy procedures to improve cell susceptibility of cells to sonodynamic therapy are disclosed.
1 . An ultrasound transducer that generates an incoherent acoustic pressure field for activating a sonosensitizer in conjunction with providing sonodynamic therapy, the ultrasound transducer comprising:
a plurality of piezoelectric ultrasonic transducer elements arranged in an array configured to generate an incoherent acoustic pressure field with an energy profile for activating a sonosensitizer located within tissue of a patient,
wherein the incoherent acoustic pressure field comprises one or more of:
a modulated phase across the plurality of piezoelectric ultrasonic transducer elements,
a modulated frequency across the plurality of piezoelectric ultrasonic transducer elements, and
a modulated amplitude across the plurality of piezoelectric ultrasonic transducer elements;
wherein each piezoelectric ultrasonic transducer element in the array of piezoelectric ultrasonic transducer elements comprises a planar emitting surface configured to emit a planar acoustic wave.
2 . The ultrasound transducer of claim 1 ,
further comprising a cooling system configured to remove excess heat from the patient,
wherein the cooling system comprises a flexible cavity for circulation of a cooling fluid, and
wherein the ultrasound is administered non-invasively.
3 . The ultrasound transducer of claim 1 , wherein the energy profile is driven at ultrasonic frequencies in a range of 250 kHz to 3 MHz.
4 . The ultrasound transducer of claim 1 , wherein the incoherent acoustic pressure field comprises a temporal-average intensity output between 1 and 20 W/cm 2 .
5 . The ultrasound transducer of claim 1 , wherein the sonosensitizer is selected from the group consisting of: 5-aminolevulinic acid (5-ALA) and protoporphyrin IX (PpIX).
6 . An ultrasound transducer for activating a sonosensitizer in conjunction with providing sonodynamic therapy, the ultrasound transducer comprising:
a plurality of ultrasonic transducer elements arranged in an array configured to generate an incoherent acoustic pressure field with an energy profile for activating a sonosensitizer located within tissue of a patient.
7 . The ultrasound transducer of claim 6 wherein each of the ultrasonic transducer elements comprises an aperture sized and configured to contour with and / or are close fitting to a body of the patient.
8 . The ultrasound transducer of claim 7 , wherein a size of the aperture is selected to be the same size or larger than a lesion being treated such that an aspect ratio of the aperture to the a lesion size enables initiation of a broad incoherent acoustic pressure field to treat the lesion and surrounding tissue.
9 . The ultrasound transducer of claim 6 , wherein the modulated phase comprises a randomized phase difference.
10 - 15 . (canceled)
16 . The ultrasound transducer of claim 6 , wherein the ultrasonic transducer elements are arranged according to a predetermined element packing technique.
17 - 20 . (canceled)
21 . The ultrasound transducer of claim 1 , wherein the ultrasound transducer defines a rectangular array geometry.
22 . The ultrasound transducer of claim 21 , wherein the rectangular array geometry defines a square.
23 - 27 . (canceled)
28 . The ultrasound transducer of claim 6 , wherein the plurality of ultrasonic transducer elements are arranged in an array disposed on a helmet configured to couple to the a head of the patient.
29 . The ultrasound transducer of claim 6 , wherein the plurality of ultrasonic transducer elements are arranged in an array configured to couple to a head of the patient.
30 - 31 . (canceled)
32 . The ultrasound transducer of claim 6 , wherein the plurality of ultrasonic transducer elements are arranged in a hemispherical array.
33 . The ultrasound transducer of claim 6 , wherein the plurality of ultrasonic transducer elements are arranged in a curved linear array.
34 . (canceled)
35 . The ultrasound transducer of claim 6 , wherein a diameter of the array is in a range of 100 mm - 200 mm.
36 . The ultrasound transducer of claim 6 , wherein a diameter of the array is in a range of 100 to 150 mm.
37 . The ultrasound transducer of claim 6 , wherein a diameter of the array is in a range of 120 to 165 mm.
38 . The ultrasound transducer of claim 6 , wherein a diameter of the ultrasonic transducer element is in a range of 0.5 mm to 20 mm.
39 . The ultrasound transducer of claim 6 , wherein a diameter of the ultrasonic transducer element is in a range of 2 mm to 10 mm.
40 . The ultrasound transducer of claim 6 , configured to activate a sonosensitizer without focusing ultrasound.
41 . The ultrasound transducer of claim 6 configured for treating cancerous tissue in a brain, spine, mouth, in the a lung, breast, colorectal region, prostate or pancreas.
42 . (canceled)
43 . The ultrasound transducer of claim 6 , wherein the sonosensitizer is configured for oral administration to the patient.
44 . (canceled)
45 . The ultrasound transducer of claim 6 , wherein the ultrasound transducer is minimally invasive.
46 . (canceled)
47 . The ultrasound transducer of claim 6 , wherein the plurality of ultrasonic transducer elements is acoustically coupled to the patient via a fluid filled cavity.
48 . (canceled)
49 . The ultrasound transducer of claim 6 ,
wherein the array is driven by a signal to generate the incoherent acoustic pressure field,
wherein each ultrasonic transducer element in the array comprises an emitting surface configured to emit planar or defocused acoustic waves, and
wherein the signal comprises one or more of the group consisting of:
a modulated phase across the plurality of ultrasonic transducer elements,
a modulated frequency across the plurality of ultrasonic transducer elements, and
a modulated amplitude across the plurality of ultrasonic transducer elements.
50 . The ultrasound transducer of claim 6 ,
wherein the plurality of ultrasonic transducer elements is configured to generate the incoherent acoustic pressure field via an aperture sized and configured with an energy profile to saturate a treatment volume to ensure treatment of a targeted lesion of cancer cells and extraneous cancer cells located within the tissue of the patient by activating the sonosensitizer located within the tissue of the patient, and wherein the ultrasound transducer comprises one or more of the following:
wherein each of the ultrasonic transducer elements in the array comprises a dimension in a range of 0.5 mm to 20 mm, and
wherein an aperture size of the aperture is selected to be larger than a lesion size of the targeted lesion of cancer cells, such that an aspect ratio of the aperture size to the lesion size enables initiation of the incoherent acoustic pressure field to treat the targeted lesion of cancer cells and extraneous cancer cells in the tissue.
51 . The ultrasound transducer of claim 6 ,
wherein the array comprises a rectangular subarray geometry,
wherein the plurality of ultrasonic transducer elements comprises between 128 to 1024 ultrasonic transducer elements, and
wherein the plurality of ultrasonic transducer elements are driven at frequencies in a range of 20 kHz to 2 MHz.
52 . The ultrasound transducer of claim 6 , further comprising a cooling system configured to remove excess heat from the patient, wherein the cooling system comprises a flexible cavity for circulation of a cooling fluid, and wherein the incoherent acoustic pressure field is administered non-invasively.