Operator-independent Histotripsy Device

Abstract

Devices and techniques are provided for utilizing ultrasound to fragment blood clots resulting from acute ischemic stroke. [Solution] The histotripsy device 10 may include: a headset 12 configured to be attached circumferentially to the skull of a human or animal; at least one transducer 16A positioned to be positioned in contact with at least one temporal or suboccipital region of the skull and configured to emit focused radiation at an ultrasonic frequency or in an ultrasonic frequency range; at least one processor; and at least one memory having stored therein instructions executable by the at least one processor to cause the at least one processor to activate the at least one transducer to generate at least one pulse of ultrasonic radiation having a pulse duration of 1 millisecond or longer.

Description

Related Applications

[0001]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 064,008, filed August 11, 2020, the disclosure of which is expressly incorporated by reference in its entirety into this specification. [Technical Field]

[0002]

[0002] This disclosure relates generally to devices and techniques that utilize ultrasound to fragment blood clots resulting from acute ischemic stroke. [Background technology]

[0003]

[0003] Acute ischemic stroke (AIS) is the most common type of stroke, and large vessel occlusion (LVO) is one of the most common types of AIS. For LVO, conventional treatments include intravenous thrombolytic therapy (ITM) and / or invasive mechanical thrombectomy. Sonothrombolysis is a conventional therapy that uses focused ultrasound to fragment blood clots or enhance the efficacy of intravenous thrombolytic therapy. Transcranial sonothrombolysis has previously been performed in the form of an operator-independent helmet and combined with ITM. Histotripsy is a subset of sonothrombolysis that employs low-frequency (1 MHz) pulses to fragment soft tissue through controlled cavitation using focused, high-intensity ultrasound pulses. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Provisional Patent Application No. 63 / 064,008 Summary of the Invention [Means for solving the problem]

[0005]

[0004] The present disclosure may include one or more of the features recited in the accompanying claims and / or one or more of the following features and combinations of features: In one aspect, a histotripsy device may include: a headset configured for circumferential attachment to a human or animal skull; at least one transducer attached to the headset, the at least one transducer positioned to be positioned over and in contact with at least one temporal or suboccipital region of the skull when the headset is circumferentially attached to the skull, the at least one transducer configured to emit focused radiation at an ultrasound frequency or in an ultrasound frequency range; at least one processor; and at least one memory having stored therein instructions executable by the at least one processor to cause the at least one processor to activate the at least one transducer to generate at least one pulse of ultrasound radiation having a pulse duration of 1 millisecond or longer.

[0006] In another aspect, a histotripsy device includes a headset configured to be attached to a human or animal skull; at least one transducer array attached to the headset, the at least one transducer array being positioned over and in contact with at least one temporal or suboccipital region of the skull when the headset is attached to the skull, the at least one transducer array including a plurality of transducers or transducer segments each having a focal length of between about 70 and 165 mm and configured to emit focused radiation at an ultrasound frequency or in an ultrasound frequency range; and a control signal input for driving the plurality of transducers or transducer segments to generate pulsed ultrasound radiation. and control circuitry for operating the device. [Brief explanation of the drawings]

[0007] [Figure 1A]FIG. 1 is a right anterior perspective view of an embodiment of an operator-independent Histotripsy device circumferentially attached to a human skull. [Figure 1B] FIG. 1B is a right posterior perspective view of the device of FIG. 1A attached circumferentially to the skull. [Figure 1C] FIG. 1C is a left posterior perspective view of the device of FIGS. 1A and 1B attached to and around the skull. [Figure 2] FIG. 1B is a simplified schematic diagram of an embodiment of the control module illustrated in FIG. 1A. [Figure 3] FIG. 1B is a simplified schematic diagram of an embodiment of one of the transducer arrays illustrated in FIGS. 1A-1C. [Figure 4] 4 is a perspective view of an embodiment of one of the transducers illustrated in FIG. 3. [Figure 5] 5 is a cross-sectional view of the transducer illustrated in FIG. 4 taken along section line 5-5 thereof. DETAILED DESCRIPTION OF THE INVENTION

[0008]

[0013] For the purposes of promoting an understanding of the principles of the present disclosure, reference will now be made to several exemplary embodiments illustrated in the accompanying drawings and specific language will be used to describe the same.

[0009]

[0014] The present disclosure relates to a histotripsy device for fragmenting blood clots resulting from acute ischemic stroke (AIS) and / or blood clots resulting from other events or conditions. The disclosed histotripsy device is portable and operator-independent and illustratively includes a headset carrying at least one transducer array configured to emit and direct high-intensity focused radiation in the ultrasound frequency range into the skull of a human or animal. The device illustratively further includes a control module operably coupled to the headset for controlling operation of the one or more transducer arrays.

[0010]

[0015] 1A-1C, one embodiment of a histotripsy device 10 for fragmenting blood clots resulting from AIS or other events / conditions is shown. In the illustrated embodiment, device 10 includes a head-mounted device or headset 12, illustratively provided in the form of a headband sized and configured for attachment to and around the skull C of a human (as depicted) or animal. In some alternative embodiments, headset 12 may be provided in other forms, including, but not limited to, a helmet, a visor, or the like. In some embodiments, headset 12 may be configured to be attached completely around the skull C, as depicted in FIGS. 1A-1C, in either form, although in alternative embodiments, headset 12 may be configured to only extend partially around the skull C.

[0011]

[0016] In the illustrated embodiment, the headset 12 illustratively includes a front band 12A and a rear band 12B configured to be operably coupled to the front band 12B, the combination of which extends completely around the skull C as illustrated in FIGS. 1A and 1B. The front band 12A is illustratively formed of a polymer, e.g., in the form of a rigid or semi-flexible plastic material, and is sized and configured to extend around the anterior portion of the skull C, e.g., in a generally C-shape, with opposite ends terminating around or adjacent respective ears 20A, 20B on either side of the skull C. In the illustrated embodiment, a pair of temporal transducer arrays 16A, 16B are attached to the inner surface of the front band 12A. The transducer arrays 16A, 16B are positioned relative to the band 12A to be positioned in contact with and localized generally over the right and left temporal regions RT and LT of the head (and brain), respectively, i.e., the regions immediately anterior to the respective ears 20A, 20B. In some embodiments, as shown by way of example in FIGS. 1B and 1C, the transducer arrays 16A, 16B may each include a respective ear alignment or localization member 18A, 18B. Illustratively, the ear localization members 18A, 18B are sized and configured to be positioned adjacent the supra-auricular (or anterior or posterior) portions of the ears 20A, 20B to properly position the transducer arrays 16A, 16B over the temporal regions RT, LT of the patient's head. In some embodiments, the ear positioning members 18A, 18B may be sized and configured to be positioned between portions of the pinnae of the ears 20A, 20B, while in other embodiments, the ear positioning members 18A, 18B may be sized and configured to be positioned adjacent to the pinnae. In some embodiments, the transducer arrays 16A, 16B are fixed in position relative to the front band 12A. In alternative embodiments, either or both of the transducer arrays 16A, 16B may be removably attached to the front band 12A, and in such embodiments, one or more conventional positioning structures may be incorporated into or attached to the front band 12A to provide axial and / or lateral adjustment of the position of the transducer array(s) 16A, 16B relative to the front band 12A.

[0012]

[0017] The posterior band 12B illustratively includes a transducer array carrier 14A and an elastic band 14B operably coupled to the carrier 14A and the ends of the front band 12A. Illustratively, the elastic band 14B is sized to be stretchable to accommodate, i.e., to allow the headband 12 to be fitted around, different sized skulls. In some embodiments, one or more conventional adjustment members may be coupled to the elastic band 14B to lengthen or shorten the elastic band 14B. In either case, the suboccipital transducer array 22 illustratively is attached to the inner surface of the transducer array carrier 14A and is positioned relative to the posterior band 12B so as to be oriented in contact with the suboccipital region SOC of the patient's head generally extending below the occipital region of the skull and above the level of the second cervical vertebra, i.e., overlying the suboccipital triangle. In some embodiments, the transducer array 22 is fixed in position relative to the transducer array carrier 14A (and relative to the rear band 12B). In alternative embodiments, the transducer array 22 may be removably attached to the transducer array carrier 14A and, therefore, the rear band 12B; in such embodiments, one or more conventional position adjustment structures may be incorporated into or attached to the transducer array carrier 22 to provide axial and / or lateral adjustment of the position of the transducer array relative to the transducer array carrier 22 and / or the rear band 12B.

[0013]

[0018] In one embodiment, each transducer array 16A, 16B, 22 illustratively includes an 8-segment spherically focused 1 MHz transducer having a 10 cm aperture, a 7.5 cm focal length, and an F-number greater than 0.9, e.g., an F-number between 1.5 and 1.75. It is understood that in alternative embodiments, one or more or all of transducer arrays 16A, 16B, 22 may be configured to include more or fewer transducer segments, emit radiation at frequencies and / or frequency ranges greater than or less than 1 MHz, have larger or smaller apertures, have larger or smaller focal lengths, and / or have larger or smaller F-numbers. It is further understood that alternative embodiments of device 10 may include any number of temporal and / or suboccipital transducer arrays. It is also understood that in some alternative embodiments, device 10 may include one or both of temporal transducer arrays 16A, 16B. Alternatively, the device 10 may include only the suboccipital transducer array 22, or may include only the suboccipital transducer array 22. It should also be understood that in some alternative embodiments, the device 10 may include one or more transducer arrays appropriately positioned relative to the headset 12 to be positioned over and in contact with any region or regions of the patient's skull (or brain), face, and / or neck.

[0014]

[0019] The headband 12 illustratively further includes an adjustment mechanism for tightening and loosening the headband 12 to and around the patient's skull C. In the illustrated embodiment, the adjustment mechanism is provided in the form of a forehead pad 28 operably coupled to an adjustment wheel 32, both of which may be operably coupled to a portion of the headband 12 positioned adjacent the patient's forehead F. The forehead pad 28 is sized and configured to contact a portion of the patient's forehead F, and the adjustment wheel 32 is configured such that, as the wheel 32 is turned, the forehead pad 28 is advanced toward or retracted from the surface of the forehead F to increase or decrease the distance between the forehead pad 28 and the inner surface of the headband 12, thereby tightening or loosening the headband 12 to and around the patient's skull C. In some embodiments, as shown by way of example in FIG. 1A , the adjustment mechanism may further include a nasal bridge alignment or positioning device 30 coupled to the forehead pad 28 and configured to position the pad 28 over the bridge B of the patient's nose N.

[0015]

[0020] In the illustrated embodiment, the histotripsy device 10 further includes a control module 26 operably coupled to the headband 12 via a cable 25. Illustratively, one end of the cable 25 is mechanically attached, i.e., affixed, to the front band 12A of the headband 12, as shown by way of example in FIGS. 1A and 1B, and the cable 25 further carries electrical conductors, e.g., wires, one or more of which are operably coupled to each of the transducer arrays 16A, 16B, 22. In some embodiments, the cable 25 is secured between the headband 12 and the control module 26, e.g., secured to the housing of the control module 26. In alternative embodiments, the cable 25 and the headband 12 and / or the cable 25 and the control module 26 may be equipped with one or more suitable connectors for electrically connecting the cable 25 to the headband 12 and / or the control module 26.

[0016]

[0021] Referring now to FIG. 2 , a simplified example of one embodiment of the control module 26 is shown. In the illustrated embodiment, the control module 26 includes at least one battery 40 (and / or other electrical power source). In some embodiments, the battery(ies) 40 are rechargeable, and in such embodiments, the module 26 further includes a charging port 42 electrically coupled to the battery(ies) 40 and configured for operative connection to a conventional charging cable connectable to an external power source. In either case, the module 26 illustratively further includes regulator circuitry 44 electrically coupled to the battery(ies) 40. The regulator circuitry 44 is conventional and includes one or more regulator circuits configured to convert the voltage of the battery 44 to one or more voltages suitable for powering the controller circuitry 46 and the transducer arrays 16A, 16B, 22 mounted on the module 26. In this regard, the adjustment circuitry 44 has at least one output section electrically coupled to the control circuitry 46 and at least one output section coupled (or configured to be coupled) to the headband 12 via a cable 25.

[0017]

[0022] In the illustrated embodiment, the controller circuitry 46 includes at least one memory Included is at least one processor or controller 48 operably coupled to (or integrated with) device 50 and to driver circuitry 52. ​​It should be understood that the terms “processor” or “controller,” as used in this disclosure, encompass any computer, processor, microchip processor, integrated circuit, or any other element(s), whether singular or plural, capable of implementing programming to perform the functions specified in the claims and this written description. In this regard, the at least one processor or controller 48 may be a single such element residing on a printed circuit board with other elements of controller circuitry 46, or may be or include two or more elements residing with other elements of controller circuitry 46 and / or residing in one or more locations on headband 12. Memory 50 is similarly conventional and includes instructions stored therein that are executable by processor or controller 48 to implement the various functions of control module 26 described herein. The driver circuitry 52 is conventional and includes one or more driver circuits configured to drive or actuate the transducer arrays 16A, 16B, 22. In this regard, the driver circuitry 52 has at least one output electrically coupled (or configured to be coupled) to the headband 12 via the cable 25.

[0018]

[0023] In some alternative embodiments, headset 12 may carry its own battery and driver circuitry for powering and operating transducer arrays 16A, 16B, 22. In some such embodiments, control module 26 and headband 12 may each include conventional circuitry configured to wirelessly communicate with each other, such that processor(s) or controller 48 may wirelessly control the operation of transducer arrays 16A, 16B, 22 in such embodiments.

[0019]

[0024] As briefly discussed in the Background section above, histotripsy is a subset of sonothrombolysis that employs relatively low frequency pulses to fragment soft tissue through controlled cavitation. Broadly speaking, there are two distinct cavitation mechanisms in histotripsy: (1) shock-scattering and (2) intrinsic threshold (also known as microtripsy). Shock scattering employs short-duration, high-amplitude ultrasound pulses in which multiple positive and negative half-cycles interact to generate a cavitation cloud, sometimes called a "bubble cloud," that mechanically breaks down clot tissue. Intrinsic threshold histotripsy, on the other hand, employs a pulse with a single, large tensile phase to generate a bubble cloud. These two cavitation mechanisms thus utilize different pulse durations and different peak negative pulse pressures.

[0020]

[0025] As briefly described above, memory 50 illustratively includes instructions stored therein that are executable by processor or controller 48 to implement the various functions of control module 26. Illustratively, the instructions stored in memory 50 include instructions for controlling transducers 16A, 16B, and 22 to generate 1 MHz fundamental frequency pulses to nucleate bubble activity through either or both of the intrinsic threshold and impact scattering mechanisms described above. In the former, i.e., intrinsic threshold, embodiment, the instructions stored in memory 50 include instructions executable by processor(s) or controller(s) 48 to cause one or more of transducers 16A, 16B to generate 1 MHz fundamental frequency pulses of 1 millisecond (ms) duration (although frequency pulse durations outside this range are contemplated). In the latter, i.e., impact scattering, embodiment, the instructions stored in memory 50 include instructions executable by processor(s) or controller(s) 48 to cause one or more of transducers 16A, 16B to generate 1 MHz fundamental frequency pulses of 1 ms duration (although frequency pulse durations outside this range are contemplated). The program code includes instructions executable by the processor(s) or controller 48 to cause the roller 48 to control one or more of the transducers 16A, 16B to generate a 1 MHz fundamental frequency pulse of 5 ms (although frequency pulse durations outside this range are contemplated). In either case, a Histotripsy pulse will be generated by the transducers 16A, 16B, 22 with a pulse duration of 1 MHz or longer. The Histotripsy pulse will have a single tensile phase of greater than 35 megapascals (MPa) (e.g., in the range of approximately 35-40 MPa, although pressures outside this range are contemplated), and the peak negative pressure of the pulse will be between approximately 20-30 MPa (although pressures outside this range are contemplated). In one embodiment, at each location, i.e., at each transducer 16A, 16B, 22 location, the transducers 16A, 16B, 22 will be controlled by a processor(s) or controller 48 to generate and apply to each region between 500-1000 pulses at a rate of >40 Hz for a total ultrasound exposure time of between 20-60 seconds, although in alternative embodiments, more or fewer pulses may be applied and / or may be applied at 40 Hz or less for any desired total ultrasound exposure time.

[0021]

[0026] The Histotripsy device 10, operated as described above, can fragment blood clots without the need for adjunctive intravenous thrombolytic therapy (ITM). Advantageously, the device 10 allows for therapy independent of an ITM, allowing patients to avoid the risks and side effects of such medication. However, it should be understood that in alternative embodiments, the Histotripsy device 10 can be used in conjunction with an ITM.

[0022]

[0027] The Histotripsy device 10 is compact, portable, and operator-independent, and therefore can be implemented in a wide variety of clinical settings. For example, it is estimated that approximately 2 million neurons are lost per minute during acute ischemic stroke (AIS), and therefore AIS treatment is highly time-sensitive. In this regard, the fast-acting and easy-to-use nature of the Histotripsy device 10 allows it to be integrated into emergency room environments, potentially significantly shortening time to treatment and thereby improving treatment outcomes. Moreover, because the Histotripsy device 10 is relatively small (e.g., the size of a headband or helmet) and operator-independent, it could further be integrated into local hospitals or mobile stroke units. Use of the Histotripsy device 10 by first responders (e.g., paramedics) or emergency room clinicians at local hospitals could provide treatment to AIS victims, for example, much sooner than they would receive using conventional therapies.

[0023]

[0028] Referring now to Figure 3, a schematic diagram of one embodiment of one of the transducer arrays 16A, 16B, 22 is shown. In one embodiment, the transducer arrays 16A, 16B, 22 are identically configured as illustrated in Figure 3, however, in alternative embodiments, one or more of the transducer arrays 16A, 16B, 22 may be configured differently from the others, for example, by including more or fewer transducers, and / or by having transducers of a different configuration, i.e., having different operating characteristics, and / or by including more, fewer, or different on-board control circuitry. In the embodiment illustrated in Figure 3, the electrical power signal line 251 exiting the control module 26 of Figure 2 is electrically connected to an input of the high voltage power supply circuit 60, The output of the power supply 60 is electrically connected to the input of an energy storage circuit 62. In one embodiment, the energy storage circuit is implemented in the form of a capacitor bank, in which case the power supply 60 may illustratively be designed for capacitor charging, although in alternative embodiments one or more other or additional energy storage circuits may be used. The output of the energy storage circuit 62 is electrically connected to the power supply input of a multi-channel output circuit 64 having M outputs, Each part corresponds to M transducers (or transducer segments) 661-66 M , where M can be any positive integer. In one embodiment, as noted above, M=8, although in alternative embodiments M may be greater or less than 8. In the illustrated embodiment, the multiple output stages of multi-channel output circuit 64 are electrically connected to transducers 661-66. M In either case, the control signal line 252 leaving the control module 26 of FIG. 2 is connected to the multi-channel output circuit. 64 is electrically connected to the control signal input of the line 64.

[0024]

[0029] In the embodiment illustrated in FIG. 2, transducers 661-66 M The operating frequency of the transducers 661-66 is generated by the processor / controller circuitry 48 and driver circuitry 52 of the control module 26, illustratively in the form of a low voltage, or low power, square wave control signal, which is then sent to the transducer arrays 16A, 16B, 22, illustrated by way of example in Figure 3. In the embodiment illustrated in Figure 3, controller circuitry 60, 62, and 64 illustratively transmits the low voltage square wave control signal provided by the control module 26 to the transducers 661-66. M The output circuit 64 is configured as a high voltage switch mode pulse generator that converts the high voltage, i.e., high power, square wave drive signal into a high voltage, i.e., high power, square wave drive signal for driving the transducers 661-66.M The energy for each output pulse provided as an input drive signal to each of the transducers 661-664 is stored in an energy storage circuit 62, which is recharged between pulses by the high voltage supply circuit 60. Based on the low voltage square wave control signal provided by the control module 26 and the high voltage energy stored in the energy storage circuit 62, the multi-channel output circuit 64 drives the transducers 661-664. 66 M A high voltage square wave drive signal is generated and supplied to each of the

[0025]

[0030] In one exemplary embodiment, the control module 26, an example of which is depicted in FIG. 2, and the control circuitry 60, 62, 64 of the transducer arrays 16A, 16B, 22, an example of which is depicted in FIG. 3, cooperate to generate a high voltage square wave drive signal having the following characteristics: a signal frequency of 1.5 MHz + / - 50 kHz, an output voltage of 0 to 500 V. PK The device generates a high voltage square wave drive signal with an output current of 10 A per channel, a pulse repetition frequency of 1-100 Hz, and a burst length of 1-30 cycles. It should be understood that in alternative embodiments, one or more of the above values ​​may be greater or less.

[0026]

[0031] 4 and 5, there is shown one exemplary embodiment of one of the transducers 66 depicted in schematic form in FIG. 3. The transducer 66 illustratively includes a base 70 and a transducer head 72 attached to the base. The ultrasound-emitting surface of the transducer head 72 is illustratively concave. In the illustrated embodiment, the base 70, like the transducer head 72, is generally cylindrical in cross-sectional shape, and the concave ultrasound-emitting surface of the transducer head 72 is therefore a truncated sphere, as best shown in FIG. 5. In alternative embodiments, the base and / or transducer head 72 may have a non-cylindrical cross-sectional shape, and / or the ultrasound-emitting surface of the transducer head 72 may be non-concave, e.g., planar, convex, or other shape.

[0027]

[0032] In the illustrated embodiment, the transducer 66 is self-focusing and configured to generate ultrasonic pulses having a center frequency of approximately 1.5 MHz, although in alternative embodiments, the transducer 66 may not be self-focusing and / or may be configured to generate ultrasonic pulses having a center frequency greater than or less than 1.5 MHz. In one illustrative embodiment, the spherical geometric transducer 66, depicted by way of example in Figures 4 and 5, has the following structural features: It has a diameter of 100 mm, a focal length of 75 mm, and the following ultrasonic pulse signal characteristics: a center frequency of 1.5 MHz + / - 50 kHz, a minimum focal tensile pressure of -35 MPa, a maximum surface pressure amplitude of 300 kPa, and a linear focal gain of 120. It should be understood that in alternative embodiments, one or more of the above values ​​may be greater or less. In some embodiments, transducers 661-66 M may have the above-described geometric shapes and characteristics, whereas transducers 661-66 M (and / or one or more other transducers 661-66 in the transducer array) M ) may have different structural characteristics and / or different pulse signal characteristics, e.g., focal length = 163 mm, minimum focal tension pressure = -25 MPa, maximum surface pressure amplitude = 500 kPa, and linear focal gain = 49. In some alternative embodiments, transducers 661-66 M (and / or one or more of the transducers 661-66 in one or more other transducer arrays) M One or more of the lenses may have a focal length somewhere in the range between approximately 70 and 165 mm.

[0028]

[0033] While the present disclosure has been illustrated and described in detail in the drawings and description, it is understood that they are not to be regarded as illustrative in nature and as limiting, merely showing and describing exemplary embodiments of the invention, and that all changes and modifications that fall within the spirit of the present disclosure are desired to be protected. For example, in some embodiments, one or more of the transducer arrays 16A, 16B, 22, whether movable relative to the headband 12 as described above, can be configured to first determine the exact location of a blood clot(s) and then treat the located blood clot(s) by fragmentation as described above. In such embodiments, the memory 50 would include instructions executable by the processor(s) or controller 48 to cause the processor(s) or controller 48 to make such a determination. [Explanation of symbols]

[0029] 10 Histotripsy Device 12 Head-mounted devices or headsets, headbands 12A front band 12B rear band 14A Transducer array support 14B Elastic Band 16A, 16B Temporal transducer array 18A, 18B Ear alignment or positioning members 20A, 20B ears 22 Suboccipital Transducer Array 25 Cable 251 Electrical power signal line 252 control signal line 26 Control Module 28 Forehead pad 30 Nasal bridge positioning or localization device 32 Adjustment wheel 40 Battery 42 Charging port 44 Adjustment section circuit configuration 46 Control circuit configuration 48 Processor or Controller 50 Memory Devices 52 Drive circuit configuration 60 High voltage power supply circuit 62 Energy storage circuit 64 Multi-channel output circuit 66, 661-66 M Transducer (or transducer segment) 70 base 72 Transducer Head C. Human skull F Frontal area LT left temporal region RT right temporal region SOC suboccipital area N Nose B nose bridge

Claims

1. 1. A histotripsy device, comprising: a headset configured to be attached to a human or animal skull; at least one transducer attached to the headset, the at least one transducer positioned to be positioned over and in contact with at least one temporal or suboccipital region of the skull when the headset is attached to the skull, the at least one transducer configured to emit focused radiation at an ultrasound frequency or in an ultrasound frequency range; at least one processor; at least one memory having stored therein instructions executable by the at least one processor to cause the at least one processor to activate the at least one transducer to generate at least one pulse of ultrasonic radiation having a pulse duration of 1 millisecond (ms) or longer; A histotripsy device comprising:

2. 10. The histotripsy device of claim 1, The at least one transducer is a first transducer operably attached to the headset, the first transducer positioned such that when the headset is attached to the skull, the first transducer is positioned over and in contact with a right temporal region of the skull; a second transducer operably attached to the headset, the second transducer positioned such that when the headset is attached to the skull, the second transducer is positioned over and in contact with a left temporal region of the skull; A histotripsy device, including:

3. The histotripsy device according to claim 1 or 2, the at least one transducer includes a third transducer operably attached to the headset, the third transducer positioned such that the third transducer is positioned over and in contact with the suboccipital region of the skull when the headset is attached to the skull.

4. The histotripsy device according to any one of claims 1 to 3, The histotripsy device, wherein the headset includes a headband configured to be attached to and around the skull.

5. The histotripsy device according to any one of claims 1 to 4, A Histotripsy device, wherein the at least one ultrasound transducer is a spherically focused multi-segment transducer, each segment having an aperture of approximately 10 cm and a focal length of approximately 7.5 cm.

6. 6. The histotripsy device according to claim 1, A histotripsy device, wherein the at least one transducer has an F-number > 0.

9.

7. 7. The histotripsy device according to claim 1, The ultrasonic frequency is approximately 1 MHz.

8. The histotripsy device according to any one of claims 1 to 7, The Histotripsy device, wherein the pulse duration is 1 ms.

9. The histotripsy device according to any one of claims 1 to 7, The Histotripsy device, wherein the pulse duration is 5 ms.

10. 10. The histotripsy device according to claim 1, A histotripsy device, wherein each pulse generated by said at least one transducer produces a single tensile phase pressure in the range of between approximately 35-40 MPa.

11. 11. The histotripsy device according to claim 1, A histotripsy device, wherein each pulse generated by said at least one transducer produces a peak negative pressure in the range of between approximately 20-30 MPa.

12. 12. The histotripsy device according to any one of claims 1 to 11, the instructions stored in the memory further include instructions executable by the at least one processor to cause the at least one processor to activate the at least one transducer to generate between approximately 500 and 1000 pulses.

13. 13. The histotripsy device of claim 12, the instructions stored in the memory further include instructions executable by the at least one processor to cause the at least one processor to activate the at least one transducer to generate the pulses at a rate of >40 Hz.

14. 14. The histotripsy device according to claim 12 or 13, the instructions stored in the memory further include instructions executable by the at least one processor to cause the at least one processor to activate the at least one transducer to generate the pulses for a total insonification time of between approximately 20 and 60 seconds.

15. 1. A histotripsy device, comprising: a headset configured to be attached to a human or animal skull; at least one transducer array attached to the headset, the at least one transducer array being positioned to lie over and in contact with at least one temporal or suboccipital region of the skull when the headset is attached to the skull, the at least one transducer array including a plurality of transducers or transducer segments each having a focal length of between about 70 and 165 mm and configured to emit focused radiation at an ultrasound frequency or in an ultrasound frequency range; controller circuitry for driving the plurality of transducers or transducer segments to generate pulsed ultrasonic irradiation in response to a control signal input; A histotripsy device comprising:

16. 16. The histotripsy device of claim 15, A histotripsy device, wherein the at least one transducer array includes eight transducers or transducer segments.

17. 17. The histotripsy device according to claim 15 or 16, the at least one transducer array a first transducer array including a plurality of transducers or transducer segments attached to the headset such that, when the headset is attached to the skull, the plurality of transducers or transducer segments of the first transducer array are positioned over and in contact with a right temporal region of the skull; a second transducer array including a plurality of transducers or transducer segments attached to the headset such that, when the headset is attached to the skull, the plurality of transducers or transducer segments of the second transducer array are positioned over and in contact with a left temporal region of the skull; A histotripsy device, including:

18. 18. The histotripsy device according to any one of claims 15 to 17, the at least one transducer array a third transducer array including a plurality of transducers or transducer segments attached to the headset such that, when the headset is attached to the skull, the plurality of transducers or transducer segments of the third transducer array are positioned over and in contact with a suboccipital region of the skull; A histotripsy device, including:

19. 19. The histotripsy device according to any one of claims 15 to 18, the controller circuitry comprises a switch-mode pulse generator circuit having an input configured to receive the control signal input and a plurality of outputs each electrically connected to a different one of the plurality of transducers or transducer segments, the switch-mode pulse generator circuit configured to convert the control signal input into a plurality of transducer drive signals provided to the plurality of transducers or transducer segments.

20. 20. The histotripsy device of claim 19, the switch-mode pulse generator circuit includes a high-voltage supply circuit electrically connected to an energy storage circuit, the high-voltage supply circuit configured to charge the energy storage circuit to a high voltage; the input of the switch mode pulse generator circuit having:

21. 21. The histotripsy device according to any one of claims 15 to 20, The histotripsy device, wherein the headset includes a headband configured to be attached to and around the skull.

22. 22. The histotripsy device according to any one of claims 15 to 21, The histotripsy device, wherein the controller circuit is configured to drive the plurality of transducers or transducer segments to generate the pulsed ultrasound irradiation having a pulse duration of 1 millisecond or longer.

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