Medical device for ultrasound-assisted drug delivery

Abstract

Systems and methods for treating a vascular region are disclosed. An example system for treating a vascular region can include an elongate catheter shaft having a distal region. A central lumen can be formed in the elongate catheter shaft. A treatment core can be disposed within the central lumen. The treatment core can include a plurality of ultrasound transducers. A control unit can be coupled to the treatment core. The control unit can be configured to switch between first configurations. A fluid delivery lumen can be defined in the elongate catheter shaft. A pump can be coupled to the elongate catheter shaft. The pump can be configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the control unit is in an inactive state.

Description

Cross-reference to related applications

[0001] This application claims priority to U.S. Provisional Application No. 63 / 547,201, filed November 3, 2023, the entire disclosure of which is hereby incorporated herein by reference. Technical Field

[0002] This disclosure relates to medical devices and methods for manufacturing medical devices. More specifically, this disclosure relates to medical devices for ultrasound-assisted drug delivery. Background Technology

[0003] Various in vivo medical devices have been developed for medical applications, such as intravascular applications. Some of these devices include guidewires, catheters, etc. These devices are manufactured using any of a variety of different manufacturing methods and can be used according to any of these methods. Each of the known medical devices and methods has certain advantages and disadvantages. There is a continued need to provide alternative medical devices and alternative methods for manufacturing and using these devices. Summary of the Invention

[0004] This disclosure provides alternatives for the design, materials, manufacturing methods, and uses of medical devices. A system for treating vascular regions is disclosed. The system includes: an elongated catheter shaft having a distal region; wherein a central lumen is formed within the elongated catheter shaft; a treatment core disposed within the central lumen, the treatment core including a plurality of ultrasonic transducers disposed adjacent to the distal region of the elongated catheter shaft; a control unit coupled to the treatment core, the control unit being configured to switch between the first configuration in which the plurality of ultrasonic transducers are active, and the second configuration in which the plurality of ultrasonic transducers are inactive; a fluid delivery lumen defined within the elongated catheter shaft; and a pump coupled to the elongated catheter shaft, the pump being configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the ultrasonic transducers are in the inactive state.

[0005] As an alternative or additional embodiment to any of the above embodiments, the pump is configured to deliver saline solution through a fluid delivery lumen when the ultrasonic transducer is activated.

[0006] As an alternative or additional embodiment to any of the above embodiments, the pump includes a switch.

[0007] As an alternative or additional embodiment to any of the above embodiments, the switch is configured to switch between a first switch configuration and a second switch configuration, in which the pump delivers microbubbles, nanodroplets, or both to the fluid delivery lumen, and in the second switch configuration, the pump delivers brine to the fluid delivery lumen.

[0008] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first configuration, the plurality of ultrasonic transducers are in an active state for approximately 10 to 60 seconds.

[0009] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first configuration, the plurality of ultrasonic transducers are in an active state for approximately 15 to 45 seconds.

[0010] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first configuration, the plurality of ultrasonic transducers are in an active state for approximately 30 seconds.

[0011] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 10 to 60 seconds.

[0012] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 15 to 45 seconds.

[0013] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 30 seconds.

[0014] As an alternative or additional embodiment to any of the above embodiments, the pump is configured not to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the ultrasonic transducer is activated.

[0015] A system for treating vascular regions is disclosed. The system includes: an elongated catheter shaft; a treatment core disposed within the elongated catheter shaft, the treatment core including a plurality of ultrasonic transducers; a control unit coupled to the treatment core, the control unit being configured to switch between the first state and the second state, in which the plurality of ultrasonic transducers are activated and in the second state, the plurality of ultrasonic transducers are deactivated; a fluid delivery lumen defined within the elongated catheter shaft; and a pump coupled to the elongated catheter shaft, wherein the pump is configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the control unit is in the first state, and wherein the pump is configured not to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the control unit is in the second state.

[0016] As an alternative or additional embodiment to any of the above embodiments, the pump is configured to deliver brine through the fluid delivery lumen when the control unit is in the second state.

[0017] As an alternative or additional embodiment to any of the above embodiments, the pump includes a switch.

[0018] As an alternative or additional embodiment to any of the above embodiments, the switch is configured to switch between a first switch configuration and a second switch configuration, wherein in the first switch configuration, the control unit is in a first state, causing the pump to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen, and in the second switch configuration, the control unit is in a second state, causing the pump to deliver brine to the fluid delivery lumen.

[0019] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first state, the multiple ultrasonic transducers are activated for approximately 10 to 60 seconds.

[0020] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first state, the multiple ultrasonic transducers are activated for approximately 15 to 45 seconds.

[0021] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first state, the multiple ultrasonic transducers are activated for approximately 30 seconds.

[0022] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second state, the multiple ultrasonic transducers are not activated for approximately 10 to 60 seconds.

[0023] A method for delivering drugs to vascular regions has been disclosed. The method includes: advancing a catheter system to a treatment site, the catheter system comprising: an elongated catheter shaft having a distal region, wherein a central lumen is formed in the elongated catheter shaft; a treatment core disposed within the central lumen, the treatment core including a plurality of ultrasonic transducers disposed adjacent to the distal region of the elongated catheter shaft; a control unit coupled to the treatment core, the control unit being configured to switch between a first configuration in which the plurality of ultrasonic transducers are active, and a second configuration in which the plurality of ultrasonic transducers are inactive; a fluid delivery lumen defined in the elongated catheter shaft; and a pump coupled to the elongated catheter shaft, the pump being configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the control unit is inactive; advancing the treatment core through the central lumen such that the plurality of ultrasonic transducers are disposed adjacent to the distal region of the elongated catheter shaft; delivering microbubbles, nanodroplets, or both to the fluid delivery lumen when the control unit is inactive; and activating at least some of the plurality of ultrasonic transducers.

[0024] A system for treating vascular regions is disclosed. The system includes: an elongated catheter shaft having a distal region including a plurality of ultrasonic transducers; a control unit coupled to the ultrasonic transducers, the control unit being configured to switch between the first configuration, in which the plurality of ultrasonic transducers are active, and in the second configuration, the plurality of ultrasonic transducers are inactive; a fluid delivery lumen defined within the elongated catheter shaft; and a pump coupled to the elongated catheter shaft, the pump being configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the ultrasonic transducers are in the inactive state.

[0025] As an alternative or additional embodiment to any of the above embodiments, the pump is configured to deliver saline or another solution through a fluid delivery lumen when the ultrasonic transducer is activated.

[0026] As an alternative or additional embodiment to any of the above embodiments, the pump includes a switch.

[0027] As an alternative or additional embodiment to any of the above embodiments, the switch is configured to switch between a first switch configuration and a second switch configuration, in which the pump delivers microbubbles, nanodroplets, or both to the fluid delivery lumen, and in the second switch configuration, the pump delivers brine or another solution to the fluid delivery lumen.

[0028] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first configuration, the plurality of ultrasonic transducers are in an active state for approximately 10 to 60 seconds.

[0029] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first configuration, the plurality of ultrasonic transducers are in an active state for approximately 15 to 45 seconds.

[0030] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first configuration, the plurality of ultrasonic transducers are in an active state for approximately 30 seconds.

[0031] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 10 to 60 seconds.

[0032] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 15 to 45 seconds.

[0033] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 30 seconds.

[0034] As an alternative or additional embodiment to any of the above embodiments, the pump is configured not to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the ultrasonic transducer is activated.

[0035] A system for treating vascular regions is disclosed. The system includes: an elongated catheter shaft having a distal region including a plurality of ultrasonic transducers; a control unit coupled to the ultrasonic transducers, the control unit being configured to switch between the first state, in which the plurality of ultrasonic transducers are activated, and in the second state, the plurality of ultrasonic transducers are deactivated; a fluid delivery lumen defined within the elongated catheter shaft; and a pump coupled to the elongated catheter shaft, wherein the pump is configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the ultrasonic transducers are in the activated state.

[0036] As an alternative or additional embodiment to any of the above embodiments, the pump is configured to deliver saline or another solution through a fluid delivery lumen when the ultrasonic transducer is inactive.

[0037] As an alternative or additional embodiment to any of the above embodiments, the pump includes a switch.

[0038] As an alternative or additional embodiment to any of the above embodiments, the switch is configured to switch between a first switch configuration and a second switch configuration, in which the pump delivers microbubbles, nanodroplets, or both to the fluid delivery lumen, and in the second switch configuration, the pump delivers brine or another solution to the fluid delivery lumen.

[0039] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first state, the multiple ultrasonic transducers are activated for approximately 10 to 60 seconds.

[0040] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first state, the multiple ultrasonic transducers are activated for approximately 15 to 45 seconds.

[0041] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first state, the multiple ultrasonic transducers are activated for approximately 30 seconds.

[0042] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second state, the multiple ultrasonic transducers are not activated for approximately 10 to 60 seconds.

[0043] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 15 to 45 seconds.

[0044] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 30 seconds.

[0045] As an alternative or additional embodiment to any of the above embodiments, the pump is configured not to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the ultrasonic transducer is inactive.

[0046] A method for delivering drugs to vascular regions has been disclosed. The method includes: advancing a catheter system to a treatment site, the catheter system comprising: an elongated catheter shaft having a distal region, wherein a central lumen is formed in the elongated catheter shaft; a treatment core disposed within the central lumen, the treatment core including a plurality of ultrasonic transducers disposed adjacent to the distal region of the elongated catheter shaft; a control unit coupled to the treatment core, the control unit being configured to switch between a first configuration in which the plurality of ultrasonic transducers are active, and a second configuration in which the plurality of ultrasonic transducers are inactive; a fluid delivery lumen defined in the elongated catheter shaft; and a pump coupled to the elongated catheter shaft, the pump being configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the control unit is inactive; advancing the treatment core through the central lumen such that the plurality of ultrasonic transducers are disposed adjacent to the distal region of the elongated catheter shaft; delivering microbubbles, nanodroplets, or both to the fluid delivery lumen when the control unit is inactive; and activating at least some of the plurality of ultrasonic transducers.

[0047] As an alternative or additional embodiment to any of the above embodiments, the following steps are repeated multiple times during the drug delivery method: delivering microbubbles, nanodroplets or both to a fluid delivery lumen when the control unit is in an inactive state, followed by activating at least some of the multiple ultrasonic transducers.

[0048] A system for treating vascular regions is disclosed. The system includes: an elongated catheter shaft having a distal region comprising a plurality of ultrasonic transducers; a control unit coupled to the ultrasonic transducers, the control unit being configured to switch between the first configuration, in which the plurality of ultrasonic transducers are active for a period of time, and in the second configuration, the plurality of ultrasonic transducers are inactive for a period of time; a fluid delivery lumen defined within the elongated catheter shaft; and a pump coupled to the elongated catheter shaft, the pump being configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen for a period of time, the period of time being controllable and capable of varying from being in phase with the period of activation of the ultrasonic transducers to being out of phase with the period of activation of the ultrasonic transducers.

[0049] As an alternative or additional embodiment to any of the above embodiments, the pump is configured to deliver brine or another solution through the fluid delivery lumen when microbubbles, nanodroplets or both are not delivered to the fluid delivery lumen.

[0050] As an alternative or additional embodiment to any of the above embodiments, the pump includes a switch.

[0051] As an alternative or additional embodiment to any of the above embodiments, the switch is configured to switch between a first switch configuration and a second switch configuration, in which the pump delivers microbubbles, nanodroplets, or both to the fluid delivery lumen, and in the second switch configuration, the pump delivers brine or another solution to the fluid delivery lumen.

[0052] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first configuration, the plurality of ultrasonic transducers are in an active state for approximately 10 to 60 seconds.

[0053] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first configuration, the plurality of ultrasonic transducers are in an active state for approximately 15 to 45 seconds.

[0054] As an alternative or additional solution to any of the above embodiments, when the control unit is in the first configuration, the plurality of ultrasonic transducers are in an active state for approximately 30 seconds.

[0055] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 10 to 60 seconds.

[0056] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 15 to 45 seconds.

[0057] As an alternative or additional solution to any of the above embodiments, when the control unit is in the second configuration, the multiple ultrasonic transducers are inactive for approximately 30 seconds.

[0058] The above overview of some embodiments is not intended to describe every disclosed embodiment or every implementation of this disclosure. The following figures and detailed descriptions illustrate these embodiments in more detail. Attached Figure Description

[0059] A more comprehensive understanding of this disclosure can be achieved by considering the following specific embodiments in conjunction with the accompanying drawings, in which:

[0060] Figure 1 This is a schematic diagram illustrating some features of an exemplary ultrasonic catheter.

[0061] Figure 2 It is along Figure 1 The cross-sectional view taken from line 2-2.

[0062] Figure 3 It is configured to be located in Figure 2 A schematic diagram of an exemplary elongated inner core within the central lumen of the catheter shown.

[0063] Figure 4 It is along Figure 3 The cross-sectional view taken from line 4-4.

[0064] Figure 5 This is a schematic wiring diagram illustrating the technique used to electrically connect five sets of ultrasonic radiating components to form an ultrasonic assembly.

[0065] Figure 6 It demonstrates the use of Figure 5 A schematic wiring diagram of a group of electrical connections in each group.

[0066] Figure 7A yes Figure 5 The ultrasound components are housed in Figure 4 A schematic diagram of the inner core.

[0067] Figure 7B It is along Figure 7A The cross-sectional view taken from line 7B-7B.

[0068] Figure 7C It is along Figure 7A The cross-sectional view taken from line 7C-7C.

[0069] Figure 7D This is a side view of the central filament of an ultrasound assembly twisted into a helical configuration.

[0070] Figure 8 Showing Figure 4 The core's energy delivery segment is located in Figure 1 Within the energy delivery section of the tubular body.

[0071] Figure 9 A portion of the example system is shown.

[0072] Figure 10 The control algorithm used in the example system is illustrated schematically.

[0073] While this disclosure can be modified and alternatively made in various ways, its details have been shown by way of example in the accompanying drawings and will be described in detail. However, it should be understood that this disclosure is not intended to be limited to the specific embodiments described. Rather, it is intended to cover all modifications, equivalents, and alternatives falling within the spirit and scope of this disclosure. Detailed Implementation

[0074] The following definitions of terms shall apply unless otherwise specified in the claims or elsewhere in this specification.

[0075] Whether explicitly stated or not, this document assumes that all numerical values ​​are modified by the term "approximately". The term "approximately" generally refers to a series of numerical values ​​that a person skilled in the art would consider equivalent to the listed values ​​(e.g., having the same function or result). In many cases, the term "approximately" may include numerical values ​​rounded to the nearest significant figure.

[0076] The range of numbers listed by endpoints includes all numbers in that range (for example, 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).

[0077] As used in this specification and the appended claims, unless the context clearly indicates otherwise, the singular forms “a” and “the” include plural references. As used in this specification and the appended claims, unless the content clearly indicates otherwise, the term “or” is generally used in its sense that it includes “and / or”.

[0078] It should be noted that references to "embodiments," "some embodiments," "other embodiments," etc., in the specification indicate that the described embodiments may include one or more specific features, structures, and / or characteristics. However, such descriptions do not necessarily imply that all embodiments include the specific features, structures, and / or characteristics. Furthermore, when a specific feature, structure, and / or characteristic is described in connection with an embodiment, it should be understood that such features, structures, and / or characteristics may also be used in conjunction with other embodiments, whether explicitly described or not, unless expressly stated to the contrary.

[0079] The following detailed description should be read with reference to the accompanying drawings, in which the same elements in different drawings are represented by the same reference numerals. The drawings (not necessarily drawn to scale) depict illustrative embodiments and are not intended to limit the scope of this disclosure.

[0080] As used herein, the term "ultrasonic energy" is used broadly, including in its general sense, and further including mechanical energy transmitted via pressure or compression waves with frequencies greater than about 20 kHz. The frequency of the ultrasonic energy wave is between about 500 kHz and about 20 MHz in one example embodiment, between about 1 MHz and about 3 MHz in another example embodiment, about 3 MHz in yet another example embodiment, and about 2 MHz in yet another example embodiment.

[0081] As used herein, the term “catheter” is used broadly, including its general meaning, and further includes long, flexible tubes configured for insertion into a patient’s body, such as into a body part, cavity, tube, or blood vessel.

[0082] As used herein, the term "therapeutic compound" is used broadly, including in its general sense, and encompasses drugs, pharmaceuticals, dissolved compounds, genetic material, and other substances capable of affecting physiological functions. Mixtures containing such substances are covered within this definition of "therapeutic compound."

[0083] As used herein, the term “end” is used broadly, including its general meaning, and further generally encompasses the region, such that “proximal” includes “proximal region” and “distal” includes “distal region”.

[0084] As illustrated in this article, ultrasound energy can be used to enhance the delivery and / or efficacy of therapeutic compounds. For example, in the context of treating vascular occlusion, ultrasound energy has been shown to increase enzyme-mediated thrombolysis by enhancing the delivery of thrombolytic agents into the thrombus, where these agents dissolve the thrombus by degrading the fibrin that forms it. The thrombolytic activity of the agents is enhanced in the presence of ultrasound energy within the thrombus. In other applications, ultrasound energy has also been shown to enhance the transfection of gene-based drugs into cells and to enhance the transfer of chemotherapeutic drugs into tumor cells. Ultrasound energy delivered from patients has been found to produce non-thermal effects that increase the permeability of biological tissues to therapeutic compounds by up to or greater than an order of magnitude.

[0085] The use of ultrasound catheters to deliver ultrasound energy and therapeutic compounds directly to the treatment site alleviates or overcomes many of the drawbacks associated with systemic drug delivery, such as inefficiency, high utilization rates of therapeutic compounds, and significant side effects due to high doses. Local delivery of therapeutic compounds has been found advantageous in the context of thrombolytic therapy, chemotherapy, radiotherapy, and gene therapy, as well as in applications requiring the delivery of proteins and / or therapeutic humanized antibodies. However, it should be understood that in certain arrangements, ultrasound catheters may also be used in conjunction with systemic drug delivery, rather than local drug delivery or in addition to local drug delivery. Furthermore, local drug delivery can be accomplished using a separate device, such as a catheter.

[0086] As will be described below, an ultrasonic conduit may include one or more ultrasonic radiating elements positioned therein. Such ultrasonic radiating elements may include a transducer (e.g., a PZT transducer) configured to convert electrical energy into ultrasonic energy. In such embodiments, the PZT transducer is excited by specific electrical parameters (referred herein as "power parameters" that cause it to vibrate to generate ultrasonic energy).

[0087] Referring to the illustrated embodiments, Figure 1 An ultrasound catheter 10 configured for use in a patient's vascular system is shown. For example, in some applications, the ultrasound catheter 10 is used to treat long-segment peripheral artery occlusions (such as occlusions in the vascular system of the leg), while in other applications, the ultrasound catheter 10 is used to treat occlusions in small vessels of the neurovascular system or other parts of the body (e.g., other parts of the vascular system). Therefore, the size of the catheter 10 can be adjusted based on the specific application in which it will be used.

[0088] Ultrasonic catheters or catheter systems 10 typically comprise a multi-part, elongated, flexible tubular body or catheter shaft 12 having a proximal region 14 and a distal region 15. The catheter shaft 12 includes a flexible energy delivery segment 18 located in the distal region 15 of the catheter 10. The catheter shaft 12 and other components of the catheter 10 are manufactured according to a variety of technologies. Suitable materials and dimensions are selected based on the natural and anatomical dimensions of the treatment site and the desired percutaneous entry site.

[0089] For example, in one embodiment, the proximal region 14 of the catheter shaft 12 may include a material with sufficient flexibility, kink resistance, stiffness, and structural support to propel the energy delivery segment 18 through the patient's vascular system to the treatment site. Examples of such materials include, but are not limited to, extruded polytetrafluoroethylene (PTFE), polyethylene (PE), polyamide, and other similar materials. In some embodiments, the proximal region 14 of the catheter shaft 12 may be reinforced by braids, mesh, or other constructions to provide increased kink resistance and propulsion. For example, in some embodiments, nickel-titanium or stainless steel wire may be placed along or incorporated into the catheter shaft 12 to reduce kinking.

[0090] In some instances, the energy delivery segment 18 of the conduit shaft 12 may be formed of a material that is (a) thinner than the material forming the proximal region 14 of the conduit shaft 12, or (b) has greater acoustic transparency than the material forming the proximal region 14 of the conduit shaft 12. Thinner materials generally have greater acoustic transparency than thicker materials. Suitable materials for the energy delivery segment 18 include, but are not limited to, high-density or low-density polyethylene, urethane, nylon, etc. In some embodiments, the energy delivery segment 18 is formed of the same material as the proximal region 14 or a material having the same thickness.

[0091] One or more fluid delivery lumens may be incorporated into the catheter shaft 12. For example, in one embodiment, a central lumen extends through the catheter shaft 12. The central lumen extends the length of the catheter shaft 12 and is coupled to a distal outlet port 29 and a proximal inlet port 31. The proximal inlet port 31 forms part of a connector 33 that is attached to the proximal region 14 of the catheter 10. In some cases, connector 33 may include a cooling fluid interface 46 that is hydraulically connected to a lumen within the catheter shaft 12. In some cases, connector 33 may also include a therapeutic compound inlet port 32 that is hydraulically connected to a lumen within the catheter shaft 12. In some cases, the therapeutic compound inlet port 32 may also be hydraulically coupled to a source of therapeutic compound via a connector (such as a Luer connector).

[0092] The conduit 10 is configured to position one or more ultrasonic radiating components therein. For example, in some embodiments, one ultrasonic radiating component may be fixed within the energy delivery section 18 of the tubular body, while in other embodiments, multiple ultrasonic radiating components are fixed to an assembly entering the central lumen. In either case, the one or more ultrasonic radiating components are electrically connected to the control system 100 via cable 45. In one embodiment, the outer surface of the energy delivery section 18 may include a cavitation-enhancing surface configured to enhance / promote cavitation at the treatment site. In some cases, the cavitation-enhancing surface is a textured surface that can retain microcavitation when immersed. Microcavitation can act as a source of microbubbles or nanobubbles, thereby lowering the cavitation threshold in the ultrasonic field. In some cases, the outer surface of the energy delivery section 18 may be coated with a coating comprising components that will lower the cavitation threshold. As an example, the surface may be hydrophobic and textured, such that the textured surface exhibits a lower cavitation threshold than the surrounding large volume of fluid. This can enhance the therapeutic effect of the ultrasound.

[0093] refer to Figures 2 to 8 The diagram illustrates an exemplary arrangement of the energy delivery segment 18 and other portions of the catheter 10 described above. This arrangement may be highly suitable for treating peripheral vascular occlusion.

[0094] Figure 2 Showed along Figure 1 The cross-section of the conduit shaft 12 taken from line 2-2. For example... Figure 2 As shown, three fluid delivery lumens 30 can be incorporated into the catheter shaft 12. In other embodiments, more or fewer fluid delivery lumens can be incorporated into the catheter shaft 12. The catheter shaft 12 may include a hollow central lumen 51 extending through the catheter shaft 12. Figure 2As shown, the cross-section of the catheter shaft 12 can be substantially constant along most of the length of the catheter 10. Therefore, in such embodiments, both the proximal region 14 and the distal region 15 of the catheter 10 have substantially the same cross-section. In some cases, the cross-section may vary within the energy delivery section 18, as will be discussed later.

[0095] In some embodiments, the minimum diameter of the central lumen 51 is greater than about 0.030 inches (about 0.0762 cm). In another embodiment, the minimum diameter of the central lumen 51 is greater than about 0.037 inches (about 0.09398 cm). In one exemplary embodiment, the fluid delivery lumen 30 has dimensions of about 0.026 inches (about 0.06604 cm) wide by about 0.0075 inches (about 0.01905 cm) high, but other dimensions may be used in other applications.

[0096] As described above, the central lumen 51 can extend through the length of the catheter shaft 12. Figure 1 As shown, the central lumen 51 includes a distal outlet port 29 and a proximal inlet port 31. The proximal inlet port 31 forms part of a connector 33 that is attached to the proximal region 14 of the catheter 10. The central lumen 51 can be configured to receive an elongated inner core 34 (e.g., also referred to as a treatment core 34), in Figure 3 An embodiment of the elongated inner core is illustrated. In some cases, the elongated inner core 34 includes a proximal region 36 and a distal region 38. A proximal connector 37 is fitted onto the inner core 34 at one end of the proximal region 36. One or more ultrasonic radiating members 40 (e.g., also referred to as ultrasonic transducers 40) are positioned within an inner core energy delivery section 41 located within the distal region 38. The ultrasonic radiating members 40 form an ultrasonic assembly 42, which will be described in detail below.

[0097] like Figure 4 The shown along Figure 3 As shown in the cross-section taken by line 4-4, the inner core 34 may have a cylindrical shape, the outer diameter of which allows the inner core 34 to be inserted into the central lumen 51 of the conduit shaft 12 via the proximal inlet port 31. Suitable outer diameters of the inner core 34 include, but are not limited to, about 0.010 inches (about 0.0254 cm) to about 0.100 inches (about 0.254 cm). In another embodiment, the outer diameter of the inner core 34 is between about 0.020 inches (about 0.0508 cm) and about 0.080 inches (about 0.2032 cm). In yet another embodiment, the outer diameter of the inner core 34 is about 0.035 inches (about 0.0889 cm).

[0098] Still referencing Figure 4 The inner core 34 may include a cylindrical outer body 35 that houses the ultrasonic component 42. The ultrasonic component 42 includes... Figures 5 to 7D The wiring and ultrasonic radiating components, described in more detail below, enable the ultrasonic assembly 42 to radiate ultrasonic energy from the energy delivery section 41 of the inner core 34. The ultrasonic assembly 42 is electrically connected to a connector 33, wherein the inner core 34 can be connected to the control system 100 via a cable 45. Figure 1 (As shown). In some cases, an electrically insulating potting material 43 fills the inner core 34, thereby surrounding the ultrasonic component 42 and thus preventing movement of the ultrasonic component 42 relative to the outer body 35. In one embodiment, the thickness of the outer body 35 is between about 0.0002 inches (about 0.000508 cm) and 0.010 inches (0.0254 cm). In another embodiment, the thickness of the outer body 35 is between about 0.0002 inches (about 0.000508 cm) and 0.005 inches (0.0127 cm). In yet another embodiment, the thickness of the outer body 35 is about 0.0005 inches (about 0.00127 cm).

[0099] In some embodiments, the ultrasonic component 42 includes a plurality of ultrasonic radiating members 40 grouped into one or more groups. For example, Figures 5 to 6 This is a schematic wiring diagram illustrating the technique used to connect five groups of ultrasonic radiating elements 40 to form an ultrasonic assembly 42. The ultrasonic assembly 42 includes a set of transducer drivers 109, which includes transducer drivers that drive each of the five groups of ultrasonic radiating elements 40 (G1, G2, G3, G4, G5) via electrical connections 110a, 110b, 110c, 110d, and 110e, respectively. The five groups of ultrasonic radiating elements 40 (G1, G2, G3, G4, G5) are also electrically connected to a control system 100. For example, in some cases, a single amplifier is used, where a MUX drives each of the individual groups.

[0100] As used herein, the terms “ultrasonic energy,” “ultrasound,” and “ultrasound” are broad terms with their general meanings and further refer to, but not limited to, mechanical energy transmitted via longitudinal pressure or compression waves. Ultrasonic energy can be emitted as a continuous wave or a pulsed wave, depending on the requirements of a particular application. Additionally, ultrasonic energy can be emitted as waveforms of various shapes, such as sine waves, triangular waves, square waves, or other waveforms. Ultrasonic energy comprises sound waves. In some embodiments, the frequency of the ultrasonic energy is between about 20 kHz and about 20 MHz. For example, in one embodiment, the frequency of these waves is between about 500 kHz and about 20 MHz. In another embodiment, the frequency of these waves is between about 1 MHz and about 3 MHz. In yet another embodiment, the frequency of these waves is about 2 MHz. The average acoustic power of each ultrasonic radiating element 40 is between about 0.01 watts and 300 watts. In some embodiments, the average acoustic power of each ultrasonic radiating element 40 is between about 0.2 watts and about 2.5 watts. In one embodiment, the average acoustic power of each ultrasonic radiating element 40 is about 0.27 watts.

[0101] As used herein, the term "ultrasonic radiating element" refers to any device capable of generating ultrasonic energy. For example, in one embodiment, an ultrasonic radiating element includes an ultrasonic transducer that converts electrical energy into ultrasonic energy. Suitable examples of ultrasonic transducers for generating ultrasonic energy from electrical energy include, but are not limited to, piezoelectric ceramic oscillators. Piezoelectric ceramics may comprise crystalline materials (such as quartz) that change shape when an electric current is applied to the material. This change in shape, caused by an oscillating drive signal, generates ultrasonic waves. In other embodiments, ultrasonic energy may be generated by an ultrasonic transducer located away from the ultrasonic radiating element, and the ultrasonic energy may be transmitted via, for example, a wire coupled to the ultrasonic radiating element.

[0102] Still referencing Figure 5 The control system 100 may include a voltage source 102, etc. The voltage source 102 includes a positive terminal 104 and a negative terminal 106. The negative terminal 106 is connected to a common conductor 108 that connects five sets of G1 to G5 ultrasonic radiating components 40 in series. The positive terminal 104 is connected to multiple leads 110a, 110b, 110c, 110d, and 110e, which are respectively connected to one of the five sets of G1 to G5 ultrasonic radiating components 40. Therefore, in this configuration, each of the five sets of G1 to G5 ( Figure 6One set of wires (shown in the diagram) is connected to the positive terminal 104 via one of leads 110a, 110b, 110c, 110d, and 110e, and to the negative terminal 106 via a common wire 108. The control circuitry system can be configured as part of the control system 100 and can include circuits, control routines, controllers, etc., configured to change one or more power parameters used to drive the ultrasonic radiating member 40.

[0103] Now for reference Figure 6 Each group G1 to G5 includes multiple ultrasonic radiating elements 40. Each of the ultrasonic radiating elements 40 is electrically connected to a common conductor 108 and a lead 110 via one of two positive contact conductors 112. Therefore, when wiring is performed as shown, a constant voltage difference is applied to each ultrasonic radiating element 40 in the group. Although Figure 6 The group shown includes twelve ultrasonic radiating elements 40, but those skilled in the art will recognize that the group may include more or fewer ultrasonic radiating elements 40. Similarly, in Figure 5 The ultrasound assembly 42 shown may include more or fewer than five groups.

[0104] Figure 7A The components for the ultrasound assembly 42 (such as...) are shown. Figure 5 (Symbodily shown) Arranged in the inner core 34 (e.g.) Figure 4 An example technique shown illustratively. Figure 7A Is Figure 5 A cross-sectional view of the ultrasound component 42 taken from group G1, as indicated by the presence of four leads 110. For example, if in Figure 5 If a cross-sectional view of the ultrasound component 42 is taken from group G4, then only one lead 110 will exist (i.e., one lead connecting group G5).

[0105] Still referencing Figure 7A The common conductor 108 comprises an elongated, flat conductive material piece that makes electrical contact with a pair of ultrasonic radiating components 40. Each of the ultrasonic radiating components 40 also makes electrical contact with a positive contact conductor 112. Because the common conductor 108 is connected to the negative terminal 106 and the positive contact conductor 112 is connected to the positive terminal 104, a voltage difference can be generated across each ultrasonic radiating component 40. The lead 110 can be isolated from other components of the ultrasonic assembly 42 to prevent interference with the operation of the ultrasonic radiating components 40 as described above. For example, in one embodiment, the inner core 34 can be filled with an insulating potting material 43 to prevent unwanted electrical contact between the various components of the ultrasonic assembly 42.

[0106] Figures 7B to 7C Showing Figure 7AThe inner core 34 is shown in cross-sectional views taken along lines 7B-7B and 7C-7C, respectively. Figure 7B As shown, the ultrasonic radiating components 40 are mounted in pairs along a common conductor 108. The ultrasonic radiating components 40 are connected by positive contact conductors 112, such that substantially the same voltage is applied to each ultrasonic radiating component 40. Figure 7C As shown, the common conductor 108 may include a wide region 108W on which the ultrasonic radiating components 40 can be mounted, thereby reducing the likelihood of pairs of ultrasonic radiating components 40 shorting together. In some embodiments, outside the wide region 108W, the common conductor 108 may have a more conventional circular conductor shape.

[0107] In an embodiment, for example Figure 7D As shown, the common conductor 108 can be twisted to form a helical shape before being fixed within the inner core 34. In such embodiments, the ultrasonic radiating member 40 is oriented in multiple radial directions, thereby enhancing the radial uniformity of the resulting ultrasonic energy field.

[0108] Those skilled in the art will recognize that the wiring arrangement described above can be modified to allow each group G1, G2, G3, G4, G5 to be powered independently. Specifically, by providing a separate power supply to each group within the control system 100, each group can be individually switched on or off, or each group can be driven with a separate power source. This provides the advantage of allowing the delivery of ultrasound energy to be “turned off” in the treated area of ​​the treatment site, thereby preventing the application of harmful or unnecessary ultrasound energy to the patient.

[0109] The above description and Figure 5 The embodiments shown in Figure 7 illustrate multiple ultrasonic radiating elements grouped in space. That is, in such embodiments, all ultrasonic radiating elements within a group are positioned adjacent to each other, such that when a single group is activated, ultrasonic energy is delivered over a specific length of the ultrasonic assembly. However, in some embodiments, the ultrasonic radiating elements within a group may be spaced apart from each other, such that the ultrasonic radiating elements within a group are not positioned adjacent to each other. In such embodiments, when a single group is activated, ultrasonic energy can be delivered from larger spaced portions of the energy delivery segment. Such modified embodiments may be advantageous in applications where it is desirable to deliver a poorly focused, highly diffuse ultrasonic energy field to a treatment site.

[0110] In some embodiments, the ultrasonic radiating member 40 may include a rectangular lead zirconate titanate (“PZT”) ultrasonic transducer having dimensions of about 0.017 inches (about 0.04318 cm) by about 0.010 inches (about 0.0254 cm) by about 0.080 inches (about 0.2032 cm). In other embodiments, other configurations may be used. For example, in other embodiments, a disc-shaped ultrasonic radiating member 40 may be used. In this embodiment, the common conductor 108 comprises copper and has a thickness of about 0.005 inches (about 0.0127 cm), but in other embodiments, other conductive materials and other sizes may be used. The lead 110 may be, for example, a 36 gauge conductor, while the positive contact conductor 112 may be a 42 gauge conductor. However, those skilled in the art will recognize that in other embodiments, other conductor gauges may be used.

[0111] As described above, suitable frequencies for the ultrasonic radiating element 40 include, but are not limited to, about 20 kHz to about 20 MHz. In one embodiment, the frequency is between about 500 kHz and 20 MHz, and in another embodiment, the frequency is between 1 MHz and 3 MHz. In yet another embodiment, the ultrasonic radiating element 40 operates at a frequency of about 2 MHz.

[0112] Figure 8 The inner core 34, positioned within the catheter shaft 12, is shown. For clarity, details are omitted. Figure 7A Details of the ultrasound component 42 provided herein. As described above, the inner core 34 can slide within the central lumen 51 of the catheter shaft 12, thereby allowing the inner core energy delivery segment 41 (e.g., see...) Figure 3 The core energy delivery section 41, tubular body energy delivery section 18, and potting material 43 are located within the tubular body energy delivery section 18. For example, in an embodiment, the materials comprising the core energy delivery section 41, the tubular body energy delivery section 18, and the potting material 43 can all be materials with similar acoustic impedance, thereby minimizing ultrasonic energy loss at the material interfaces.

[0113] Figure 8 Further illustration shows that the fluid delivery port 58 is positioned within the tubular body energy delivery section 18. As shown, an orifice or slit is formed from the fluid delivery lumen 30 through the conduit shaft 12, thereby allowing fluid to flow from the fluid delivery lumen 30 to the treatment site. Thus, a source of therapeutic compound coupled to the inlet port 32 provides hydraulic pressure, which drives the therapeutic compound through the fluid delivery lumen 30 and out of the fluid delivery port 58.

[0114] By uniformly spacing the fluid delivery lumen 30 around the circumference of the conduit shaft 12 (e.g.) Figure 8As shown, a substantially uniform flow of the therapeutic compound around the circumference of the catheter axis 12 can be achieved. Additionally, the size, location, and geometry of the fluid delivery port 58 can be selected to provide uniform fluid flow from the fluid delivery port 30 to the treatment site. For example, in one embodiment, the diameter of the fluid delivery port 58 closer to the proximal region of the energy delivery segment 18 is smaller than the diameter of the fluid delivery port 58 closer to the distal region of the energy delivery segment 18, thereby allowing uniform fluid delivery across the entire energy delivery segment.

[0115] For example, in one embodiment where the fluid delivery port 58 has a similar size along the length of the catheter axis 12, the diameter of the fluid delivery port 58 is between about 0.0005 inches (about 0.00127 cm) and about 0.0050 inches (about 0.0127 cm). In another embodiment where the size of the fluid delivery port 58 varies along the length of the catheter axis 12, the diameter of the fluid delivery port 58 in the proximal region of the energy delivery segment 18 is between about 0.001 inches (about 0.00254 cm) and about 0.005 inches (about 0.0127 cm) (see, for example, see...). Figure 1 The diameter of the fluid delivery port 58 in the distal region of the energy delivery section 18 is between approximately 0.005 inches (approximately 0.0127 cm) and 0.020 inches (0.0508 cm). The increase in size between adjacent fluid delivery ports 58 depends on the material comprising the catheter shaft 12 and on the size of the fluid delivery lumen 30. The fluid delivery ports 58 can be created in the catheter shaft 12 by punching, drilling, burning or ablation (e.g., using a laser) or by any other suitable method. The flow rate of the therapeutic compound along the length of the catheter shaft 12 can also be increased by increasing the density of the fluid delivery ports 58 toward the distal region 15 of the catheter shaft 12.

[0116] In the delivery of cavitation nuclei, such as microbubbles, nanobubbles, microdroplets, or nanodroplets, it may be advantageous to make the fluid delivery port 58 large enough so that the cavitation nuclei are not subjected to excessive pressure or shear stress as they traverse the fluid delivery lumen 30 and exit the fluid delivery port 58. It should be understood that it may be desirable to provide a non-uniform fluid flow from the fluid delivery port 58 to the treatment site. In such embodiments, the size, location, and geometry of the fluid delivery port 58 can be selected to provide this non-uniform fluid flow.

[0117] Still referencing Figure 8The inner core 34, placed within the conduit shaft 12, further defines a cooling fluid cavity 44. The cooling fluid cavity 44 is formed between the outer surface 39 of the inner core 34 and the inner surface 16 of the conduit shaft 12. In some embodiments, cooling fluid can be introduced through the proximal inlet port 31, such that a cooling fluid flow is generated through the cooling fluid cavity 44 and flows out from the distal outlet port 29 (see [link to documentation]). Figure 1 In some cases, the cooling fluid lumens 44 may be uniformly spaced around the circumference of the catheter axis 12 (i.e., in a three-lumen configuration, spaced in increments of approximately 120°), thereby providing a uniform cooling fluid flow across the inner core 34. This configuration helps remove unwanted heat at the treatment site. The flow rate of the cooling fluid and the power of the ultrasound component 42 can be adjusted to maintain the temperature of the distal region 15 of the catheter 10 within a desired range. In some cases, the desired temperature range may be between 28°C and 52°C. In some cases, the desired temperature range may be between 28°C and 45°C. In some cases, the desired temperature range may be between 28°C and 43°C.

[0118] In this embodiment, the inner core 34 can rotate or move within the catheter shaft 12. Specifically, movement of the inner core 34 can be achieved by manipulating the proximal connector 37 while keeping the connector 33 stationary. The outer body 35 of the inner core is at least partially constructed of a material that provides sufficient structural support to allow movement of the inner core 34 within the catheter shaft 12 without kinking the catheter shaft 12. Additionally, the outer body 35 of the inner core may include a material capable of transmitting torque. Suitable materials for the outer body 35 of the inner core include, but are not limited to, polyimide, polyester, polyurethane, thermoplastic elastomers, and braided polyimide.

[0119] In one embodiment, the fluid delivery lumen 30 and the cooling fluid lumen 44 are open at the distal end of the catheter shaft 12, thereby allowing the therapeutic compound and cooling fluid to enter the patient's vascular system at the distal outlet port. Alternatively, if desired, the fluid delivery lumen 30 may be selectively occluded at the distal end of the catheter shaft 12, thereby providing additional hydraulic pressure to drive the therapeutic compound out of the fluid delivery port 58. In either configuration, the inner core 34 can be prevented from passing through the distal outlet port by making its length less than the length of the tubular body. In other embodiments, a protrusion is formed inside the tubular body in the distal region 15 to prevent the inner core 34 from passing through the distal outlet port.

[0120] In other embodiments, catheter 10 may further include an occlusion device (not shown) positioned at the distal outlet port 29. The occlusion device may have a reduced inner diameter that can accommodate the guidewire but is smaller than the inner diameter of the central lumen 51. This prevents the inner core 34 from extending through the occlusion device and protruding from the distal outlet port 29. Suitable inner diameters of the occlusion device include, but are not limited to, about 0.005 inches (about 0.0127 cm) to about 0.050 inches (about 0.127 cm). In other embodiments, the occlusion device has a closed end, thereby preventing cooling fluid from leaving catheter 10 and instead recirculating it to the proximal region 14 of catheter shaft 12. These and other cooling fluid flow configurations allow the power supplied to the ultrasound assembly 42 to increase proportionally to the cooling fluid flow rate. Additionally, certain cooling fluid flow configurations can reduce patient body exposure to the cooling fluid.

[0121] In some embodiments, such as Figure 8 As shown, the catheter shaft 12 may further include one or more temperature sensors 20, which may be located within the energy delivery section 18. In such embodiments, the proximal region 14 of the catheter shaft 12 includes temperature sensor leads that can be coupled to ( Figure 1 (As shown) in cable 45. Suitable temperature sensors include, but are not limited to, temperature sensing diodes, thermistors, thermocouples, resistance temperature detectors (“RTDs”), and fiber optic temperature sensors using thermochromic liquid crystals. Suitable temperature sensor 20 geometries include, but are not limited to, dots, patches, or strips. Temperature sensor 20 may be located within one or more fluid delivery cavities in fluid delivery cavity 30 (as shown), and / or within one or more fluid delivery cavities in cooling fluid cavity 44.

[0122] The ultrasonic radiation component can operate in pulsed mode. For example, in one embodiment, the time-averaged electrical power supplied to the ultrasonic radiation component 40 is between about 0.001 watts and about 5 watts, and can be between about 0.05 watts and about 3 watts. In some embodiments, the time-averaged electrical power is about 0.45 watts or 1.2 watts over time. The duty cycle is between about 0.01% and about 90%, and can be between about 0.1% and about 50%. In some embodiments, the duty cycle varies between about 7.5%, 15%, or 1% to 30%. The pulse-averaged electrical power of each ultrasonic radiation component 40 can be between about 0.01 watts and about 20 watts, and can be between about 0.1 watts and 20 watts. In some embodiments, the pulse-averaged electrical power is about 4 watts, 8 watts, 16 watts, or varies between 0.5 and 8 watts. As mentioned above, amplitude, pulse width, pulse repetition frequency, peak negative sound pressure level, or any combination of these parameters can be constant or variable during each pulse or over a set of pulses. In nonlinear applications of acoustic parameters, the aforementioned ranges can change significantly. Therefore, the total time-averaged electrical power can remain constant over time, but not the real-time average power.

[0123] In one embodiment, the pulse repetition rate can be between about 1 Hz and about 2 kHz, and can be greater than about 1 Hz and about 50 Hz. In another embodiment, the pulse repetition rate is about 30 Hz, or varies between about 10 Hz and about 40 Hz. The pulse duration or width can be between about 0.5 ms and about 50 ms, and can be between about 0.1 ms and about 25 ms. In some embodiments, the pulse duration is about 2.5 ms, 5 ms, or varies between 1 and 8 ms. Additionally, the peak negative sound pressure level can be between about 0.1 and about 50 MPa, or in another embodiment between about 0.5 and about 2.0 MPa.

[0124] In one embodiment, the transducer operates at an average power of about 0.6 watts, a duty cycle of about 7.5%, a pulse repetition rate of about 30 Hz, an average pulse power of about 8 watts, and a pulse duration of about 2.5 milliseconds.

[0125] The acoustic efficiency of the ultrasonic radiating element used with the electrical parameters described herein can be greater than about 50% and can be greater than about 75%. The ultrasonic radiating element can be formed in various shapes, such as cylindrical (solid or hollow), flat, strip-shaped, triangular, etc. The length of the ultrasonic radiating element can be between about 0.1 cm and about 0.7 cm. The thickness or diameter of the ultrasonic radiating element can be between about 0.02 cm and about 0.5 cm.

[0126] In some embodiments, the therapeutic compound delivered to the treatment site comprises a plurality of bubbles (e.g., microbubbles) having gas formation inside. Exemplary gases that can be used to form microbubbles include, but are not limited to, air, oxygen, carbon dioxide, perfluorocarbon gas, and inert gases.

[0127] In some embodiments, the microbubble therapeutic compound may include approximately 10 per milliliter of liquid. 4 From approximately 10 microbubbles per millimeter of liquid. 10 Each microbubble, or approximately 10 per milliliter of liquid 6 One to about 10 9 Microbubbles. In some embodiments, the diameter of the microbubbles in the microbubble therapeutic compound is between about 0.1 micrometers (μm) and about 30 μm. In some embodiments, the diameter of the microbubbles is about 0.1 to about 10 μm, about 0.2 to about 10 μm, about 0.5 to about 10 μm, about 0.5 to about 5 μm, or about 1 μm. In some embodiments, the diameter of the microbubbles is less than or equal to about 10 μm, about 5 μm, or about 2.5 μm. Other parameters may be used in other embodiments.

[0128] In some embodiments, the efficacy of the therapeutic compound is enhanced by the presence of microbubbles contained therein. In some embodiments, the microbubbles can act as cavitation nuclei, thus allowing cavitation to be induced at lower levels of peak rarefaction sound pressure. Therefore, a reduced amount of peak rarefaction sound pressure can be delivered to the treatment site without diminishing therapeutic efficacy. Reducing the amount of ultrasonic pressure delivered to the treatment site reduces the risk associated with overheating of the treatment site and, in some embodiments, also reduces the time required to treat blood vessels. In some embodiments, cavitation also facilitates more efficient diffusion and penetration of the therapeutic compound into surrounding tissues, such as the vessel walls and / or clotted material. Furthermore, in some embodiments, the mechanical agitation caused by the cavitation of microbubbles is effective in mechanically breaking up clotted material.

[0129] It is understood that the interaction between the fluid (e.g., therapeutic material) and / or microbubbles delivered via a fluid delivery lumen and the ultrasonic energy transmitted by an ultrasonic transmitter can cause the microbubbles to be disrupted and / or otherwise burst. Bursting of microbubbles at or near the target site can help improve the effectiveness / efficacy of the therapeutic material. It is also understood that if the microbubbles burst before the therapeutic material reaches the target site, the benefits of the microbubbles may be reduced or lost. In other words, premature bursting of microbubbles can generally reduce the effectiveness of the fluid / therapeutic material and / or the treatment. This article discloses systems designed to reduce the likelihood of premature bursting of microbubbles delivered via a fluid delivery lumen and / or otherwise maximize the therapeutic benefits of the microbubbles.

[0130] Figure 9An example system 200 is schematically depicted. Typically, system 200 is configured to reduce the likelihood of premature bursting of microbubbles delivered via a fluid delivery lumen and / or otherwise maximize the therapeutic benefits of the microbubbles. System 200 may include an ultrasound catheter 10 (e.g., as disclosed herein, it may also be referred to as catheter 10, catheter shaft 10, etc.) or a similar ultrasound catheter or catheter shaft. Although Figure 9 Not shown, but the catheter shaft 10 may include the structural features disclosed herein, including a treatment core 34, one or more ultrasound transducers 40 coupled to the treatment core 34, one or more fluid delivery lumens 30, etc. In some of these examples and in others, the ultrasound catheter 10 may be the treatment core 34. A control unit 200a and a pump 200b may be coupled to the catheter shaft 10. For example, the control unit 200a may be coupled to the catheter shaft 10 along passage 260. In at least some examples, the control unit 200a may be coupled to the catheter shaft 10 by directly attaching the catheter shaft 10 (e.g., the treatment core 34) to the control unit 200a. Alternatively, one or more connectors and / or conductors may extend between the catheter shaft 10 and the control unit 200a (e.g., along passage 260), such that, for example, the control unit 200a may be used to control the treatment core 34 and / or the ultrasound transducers 40.

[0131] In some instances, pump 200b may be configured to deliver one or more fluids (e.g., saline, therapeutic materials, microbubbles, nanodroplets, and / or combinations thereof) to catheter 10 (e.g., fluid delivery lumen 30). For example, pump 200b may be used to deliver fluid from a first fluid source 264 and / or a second fluid source 266. The first fluid source 264 may include therapeutic materials, thrombolytic materials, microbubbles, nanodroplets, and / or combinations thereof. The second fluid source 266 may include saline, biocompatible fluids, solutions, mixtures, and / or fluids. Other materials are also contemplated. Switch 272 may be used to switch between delivering fluid from the first fluid source 264 and delivering fluid from the second fluid source 266. For example, switch 272 may be used to switch between delivering (a) thrombolytic materials in combination with microbubbles and / or nanodroplets and (b) saline (and / or biocompatible fluids, solutions, mixtures, and / or fluids). The first fluid source 264 may be coupled to switch 272 along passage 268. The second fluid source 266 can be connected to the switch 272 along the passage 270. The switch 272 can be connected to the conduit 10 along the passage 274. In some instances, the control unit 200a can also be connected to the switch 272 along the passage 262.

[0132] As described above, it may be desirable to reduce the likelihood of premature bursting of microbubbles delivered via the fluid delivery lumen and / or otherwise maximize the therapeutic benefits of the microbubbles. System 200 is configured such that control unit 200a and pump 200b can be coordinated (e.g., via a control algorithm) to deliver therapeutic material and microbubble delivery via the fluid delivery lumen when the ultrasound transducer is activated. For example, control unit 200a may be configured to switch between a first configuration or state and a second configuration or state in which the treatment core 34 and / or multiple ultrasound transducers 40 are activated (e.g., activated, energized, etc.) and in which the treatment core 34 and / or multiple ultrasound transducers 40 are deactivated (e.g., unactivated, unenergized, etc.). Pump 200b may be configured to deliver microbubbles, nanodroplets, or both (e.g., along with therapeutic material) to the fluid delivery lumen 30 when control unit 200a is in the second configuration / state (e.g., when the ultrasound transducer 40 is not activated). Pump 200b can also be configured not to deliver microbubbles, nanodroplets, or both (e.g., along with therapeutic materials) to the fluid delivery lumen 30 when control unit 200a is in a first configuration / state (e.g., when ultrasonic transducer 40 is activated). In at least some instances, pump 200b can deliver saline to the fluid delivery lumen 30 when control unit 200a is in the first configuration / state (e.g., when ultrasonic transducer 40 is activated). In some and other instances, pump 200b can be configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen for a controlled period of time, which can vary from being in phase with the period when ultrasonic transducer 40 is activated to being out of phase with the period when ultrasonic transducer 40 is activated. Pump 200b can be configured to deliver saline, biocompatible fluids, solutions, mixtures, and / or fluids, etc., through the fluid delivery lumen 30 when not delivering microbubbles, nanodroplets, or both to the fluid delivery lumen 30.

[0133] Switch 272 can be configured to switch between a first switching configuration and a second switching configuration, in which pump 200b delivers microbubbles, nanodroplets, or both, and therapeutic materials (e.g., from a first fluid source 264) to fluid delivery lumen 30, and in the second switching configuration, pump 200b delivers saline, biocompatible fluid, solution, mixture, and / or fluid (e.g., from a second fluid source 266) to fluid delivery lumen 30. In some instances, control unit 200a can be coupled to switch 272 to control or otherwise activate switch 272. This allows control unit 200a to control whether pump 200b delivers microbubbles, nanodroplets, or both, and therapeutic materials (e.g., from a first fluid source 264) or saline, biocompatible fluid, solution, mixture, and / or fluid (e.g., from a second fluid source 266) to fluid delivery lumen 30.

[0134] Figure 10 A control algorithm for system 200 (and / or other systems disclosed herein) is schematically depicted. In this example, power delivery can be switched between "on" and "off". In this example, "on" power delivery may correspond to control unit 200a being in a first state, in which the treatment core 34 and / or multiple ultrasonic transducers 40 are activated. Power delivery "off" may correspond to control unit 200a being in a second state, in which the treatment core 34 and / or multiple ultrasonic transducers 40 are deactivated. When power delivery is "off" (e.g., control unit 200a is in the second state), pump 200b may be used to deliver / inject thrombolytic materials in combination with microbubbles and / or nanodroplets. When power delivery is "on" (e.g., control unit 200a is in the first state), pump 200b may be used to deliver / inject saline, biocompatible fluids, solutions, mixtures, and / or fluids, etc. Control unit 200a can activate switch 272 to the appropriate fluid sources 264, 266 based on its state / configuration. In some instances, control unit 200a can remain in a first state or a second state, or otherwise activate / deactivate ultrasonic transducers 40 for a period of time. For example, when control unit 200a is in the first state, multiple ultrasonic transducers 40 may be activated or otherwise activated / energized for approximately 10 to 60 seconds, or approximately 15 to 45 seconds, or approximately 30 seconds. When control unit 200a is in the second state, multiple ultrasonic transducers 40 may be deactivated or otherwise inactive for approximately 10 to 60 seconds, or approximately 15 to 45 seconds, or approximately 30 seconds.

[0135] Materials that can be used for various components of the devices described herein may include those commonly associated with medical devices. The devices and components described herein may be made of metals, metal alloys, polymers (some examples of which are disclosed below), metal-polymer composites, ceramics, combinations thereof, or other suitable materials. Examples of suitable polymers may include polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene copolymer (ETFE), fluorinated ethylene propylene copolymer (FEP), polyoxymethylene (POM, e.g., DELRIN® commercially available from DuPont), polyether block esters, polyurethanes (e.g., polyurethane 85A), polypropylene (PP), polyvinyl chloride (PVC), polyether esters (e.g., ARNITEL® commercially available from DSM Engineering Plastics), ether- or ester-based copolymers (e.g., butene / poly(alkylene ether) phthalates and / or other polyester elastomers, such as HYTREL® commercially available from DuPont), and polyamides (e.g., DURETHAN® or Elf commercially available from Bayer). Atochem commercially available CRISTAMID®, elastomer polyamides, block polyamides / ethers, polyether block amides (PEBA, e.g., commercially available under the trade name PEBAX®), ethylene-vinyl acetate copolymer (EVA), silicones, polyethylene (PE), high-density polyethylene, low-density polyethylene, linear low-density polyethylene (e.g., REXELL®), polyesters, polybutylene terephthalate (PBT), polyethylene terephthalate (PET), polypropylene terephthalate, polyethylene naphthalate (PEN), polyetheretherketone (PEEK), polyimide (PI), polyetherimide (PEI), polyphenylene sulfide (PPS), polyphenylene ether (PPO), poly(p-phenylene terephthalamide) (e.g., KEVLAR®), polysulfone, nylon, nylon-12 (e.g., EMS American) Commercially available materials from Grilon include GRILAMID®, perfluoropropyl vinyl ether (PFA), ethylene-vinyl alcohol copolymers, polyolefins, polystyrene, epoxy resins, polyvinylidene chloride (PVdC), poly(styrene-b-isobutylene-b-styrene) (e.g., SIBS and / or SIBS 50A), polycarbonates, ionomers, biocompatible polymers, other suitable materials, or mixtures, combinations, copolymers thereof, polymer / metal composites, etc. In some embodiments, the sheath may be blended with a liquid crystal polymer (LCP). For example, the blend may contain up to about 6% LCP.

[0136] Some examples of suitable metals and metal alloys include stainless steels such as 304V, 304L, and 316LV stainless steels; low-carbon steels; nickel-titanium alloys such as linearly elastic and / or hyperelastic nickel-titanium; other nickel alloys such as nickel-chromium-molybdenum alloys (e.g., UNS: N06625, such as INCONEL® 625; UNS: N06022, such as HASTELLOY® C-22®; UNS: N10276, such as HASTELLOY® C276®; other HASTELLOY® alloys, etc.), nickel-copper alloys (e.g., UNS: N04400, such as MONEL® 400, NICKELVAC® 400, NICORROS® 400, etc.), nickel-cobalt-chromium-molybdenum alloys (e.g., UNS: R30035, such as MP35-N®, etc.), and nickel-molybdenum alloys (e.g., UNS: N10665, such as HASTELLOY® ALLOY). B2®), other nickel-chromium alloys, other nickel-molybdenum alloys, other nickel-cobalt alloys, other nickel-iron alloys, other nickel-copper alloys, other nickel-tungsten or tungsten alloys, etc.; cobalt-chromium alloys; cobalt-chromium-molybdenum alloys (e.g., UNS: R30003, such as ELGILOY®, PHYNOX®, etc.); platinum-rich stainless steel; titanium; combinations thereof; etc.; or any other suitable material.

[0137] In at least some embodiments, the devices described herein may be partially or entirely doped with, made from, or otherwise include radiopaque materials. Radiopaque materials should be understood as materials capable of producing a relatively bright image on a fluorescent screen or other imaging technique during medical procedures. This relatively bright image helps the user of the devices described herein determine their location. Some examples of radiopaque materials may include, but are not limited to, gold, platinum, palladium, tantalum, tungsten alloys, polymeric materials doped with radiopaque fillers, etc. Additionally, other radiopaque marking strips and / or coils may be incorporated into the design of the devices described herein to achieve the same result.

[0138] In some embodiments, the apparatus described herein is endowed with a degree of magnetic resonance imaging (MRI) compatibility. For example, the apparatus or portions thereof described herein may be made of materials that substantially do not distort images and do not produce substantial artifacts (e.g., gaps in the image). For example, certain ferromagnetic materials may not be suitable because they may produce artifacts in MRI images. The apparatus or portions thereof described herein may also be made of materials that an MRI machine can image. Some materials exhibiting these properties include, for example, tungsten, cobalt-chromium-molybdenum alloys (e.g., UNS: R30003, such as ELGILOY®, PHYNOX®, etc.), nickel-cobalt-chromium-molybdenum alloys (e.g., UNS: R30035, such as MP35-N®, etc.), nickel-titanium, and other materials.

[0139] It should be understood that this disclosure is illustrative in many respects only. Changes in detail, particularly in shape, size, and arrangement of steps, may be made without departing from the scope of this disclosure. This may include, to appropriate extent, using any feature of one example embodiment in other embodiments. Of course, the scope of this disclosure is defined by the language of the appended claims.

Claims

1. A system for treating a vascular region, the system comprising: An elongated catheter shaft having a distal region; A central lumen is formed within the elongated conduit shaft; A treatment core is disposed within the central lumen, and the treatment core includes multiple ultrasonic transducers disposed adjacent to the distal region of the elongated catheter shaft. A control unit is connected to the treatment core and is configured to switch between a first configuration and a second configuration, in which the plurality of ultrasonic transducers are in an active state and in the second configuration, the plurality of ultrasonic transducers are in an inactive state. Fluid delivery lumen, the fluid delivery lumen being defined within the elongated conduit shaft; and A pump, connected to the elongated conduit shaft, is configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the ultrasonic transducer is in the inactive state.

2. The system as claimed in claim 1, wherein, The pump is configured to deliver saline solution through the fluid delivery lumen when the ultrasonic transducer is in the activated state.

3. The system as described in any one of claims 1 to 2, wherein, The pump includes a switch.

4. The system as described in claim 3, wherein, The switch is configured to switch between a first switch configuration and a second switch configuration, in which the pump delivers microbubbles, nanodroplets, or both to the fluid delivery lumen, and in the second switch configuration, the pump delivers brine to the fluid delivery lumen.

5. The system as described in any one of claims 1 to 4, wherein, When the control unit is in the first configuration, the plurality of ultrasonic transducers are in the activated state for approximately 10 to 60 seconds.

6. The system as described in any one of claims 1 to 5, wherein, When the control unit is in the first configuration, the plurality of ultrasonic transducers are in the activated state for approximately 15 to 45 seconds.

7. The system as claimed in any one of claims 1 to 6, wherein, When the control unit is in the first configuration, the plurality of ultrasonic transducers are in the activated state for approximately 30 seconds.

8. The system as claimed in any one of claims 1 to 7, wherein, When the control unit is in the second configuration, the plurality of ultrasonic transducers remain in the inactive state for approximately 10 to 60 seconds.

9. The system as claimed in any one of claims 1 to 8, wherein, When the control unit is in the second configuration, the plurality of ultrasonic transducers remain in the inactive state for approximately 15 to 45 seconds.

10. The system as claimed in any one of claims 1 to 9, wherein, When the control unit is in the second configuration, the plurality of ultrasonic transducers remain in the inactive state for approximately 30 seconds.

11. The system as claimed in any one of claims 1 to 10, wherein, The pump is configured not to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the ultrasonic transducer is in the activated state.

12. A system for treating a vascular region, the system comprising: Long duct shaft; A treatment core, wherein the treatment core is disposed within the elongated catheter shaft, and the treatment core includes multiple ultrasonic transducers; A control unit is connected to the treatment core and is configured to switch between a first state and a second state, in which the plurality of ultrasonic transducers are activated and in the second state, the plurality of ultrasonic transducers are deactivated. Fluid delivery lumen, the fluid delivery lumen being defined within the elongated conduit shaft; and A pump coupled to the elongated conduit shaft, wherein the pump is configured to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the control unit is in the first state, and wherein the pump is configured not to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen when the control unit is in the second state.

13. The system of claim 12, wherein, The pump is configured to deliver brine through the fluid delivery lumen when the control unit is in the second state.

14. The system as claimed in any one of claims 12 to 13, wherein, The pump includes a switch.

15. The system of claim 14, wherein, The switch is configured to switch between a first switch configuration and a second switch configuration. In the first switch configuration, the control unit is in the first state, causing the pump to deliver microbubbles, nanodroplets, or both to the fluid delivery lumen. In the second switch configuration, the control unit is in the second state, causing the pump to deliver brine to the fluid delivery lumen.

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