Devices incorporating electrically activated elements for ultrasound-based generation and imaging

Abstract

Acoustic responses to electrical signal, such as via cavitation, can be used to generate mechanical responses. Using this phenomenon, ultrasound can be generated even at remote locations by routing electrode to a location where ultrasound is beneficial. As described herein, combinations of structures and materials such as inflation fluids, balloon materials, or catheter shaft materials are used in coordination with electrical signal delivery systems to provide acoustic signal at the functional, distal end of a catheter.

Description

Attorney Docket No. 19506.0002WOU1DEVICES INCORPORATING ELECTRICALLY ACTIVATED ELEMENTS FOR ULTRASOUND-BASED GENERATION AND IMAGINGCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. provisional applications 63 / 682,203, 63 / 682,205, and 63 / 682,207, all filed on August 12, 2024, the disclosures of which are hereby incorporated by reference in their entireties. The contents of the applications filed on even date herewith entitled “Devices Incorporating Photoacoustic Elements and Use of Photoacoustic Effects for Ultrasound-Based Generation and Imaging” and “Devices with Combined Optical and Acoustic Treatment Modes,” are also hereby incorporated by reference in their entirety.BACKGROUND

[0002] Delivery of sonic treatment to the body is useful in a variety of contexts, such as for denervation, calcium debulking, treatment of chronic total occlusion, removal of thrombi or other obstructions, or providing or activating medications and other substances in the body. Often the sonic treatment is in the ultrasound regime.

[0003] In some circumstances, ultrasonic treatment can be provided transcutaneously, by a device outside the body. In other circumstances, precise delivery of sonic treatments is delivered more precisely using a catheter that is routed through the vasculature to a treatment region.

[0004] Catheters used to provide such treatments have attributes that prevent their use in some scenarios. Providing the ultrasonic treatment may use an electrode that causes a spark or cavitation in a carrier fluid around that electrode. These sparks tend to degrade the electrodes. Additionally, in order to reach typical treatment areas, the size of the catheter is inherently limited. Because of the limited initial size and the gradual ablation of the electrode during use, a typical electrode-based ultrasonic treatment delivery system may be limited to no more than a few dozen pulses of ultrasound before burning out and having to be replaced in its entirety. For patients this is expensive and inefficient, and may not provide sufficient ultrasonic treatment to accomplish the full desired treatment.SUMMARY

[0005] Examples presented herein relate to a system for generating targeted ultrasonic waves for the treatment of tissues. The system includes a catheter with a distal end and a proximal end, which defines a plurality of lumens. The catheter also includes a first balloonAttorney Docket No. 19506.0002WOU1 arranged at the distal end and a second balloon arranged more proximally along the shaft. The interior of the first and second balloons is fluidically coupled to a first lumen of the catheter, and they can be inflated by a fluid routed through this lumen.

[0006] According to a first aspect, a device for generating targeted ultrasonic waves for treatment of a tissue is disclosed. The device includes a catheter extending from a proximal end to a distal end, and the catheter defines several lumens. A first balloon is arranged at the distal end and a second balloon arranged more proximally along a shaft of the catheter, wherein an interior of the first and second balloons is fluidically coupled to a first one of the plurality of lumens and the first and second balloons are inflated by a fluid routed through the first one of the lumens. An electrode is arranged in one of the lumens, and extends from the proximal end to the distal end. The electrode is arranged to exert a thermal effect in the fluid at the interior of at least one of the first and second balloons.

[0007] Optionally, a length of the catheter between the first balloon and the second balloon can define holes therein that are usable for drug elution. The catheter can further define a third lumen in communication with the holes. A medication can be delivered to the target region adjacent the length via the third lumen and the plurality of holes. The device can also include a guidewire arranged through one of the lumens and extending from the proximal end and past the distal end. The first balloon and the second balloon can each be made of a polymer. The device can include a tie layer disposed on a surface of at least one of the first balloon and the second balloon, and a pharmaceutical coating coupled to the tie layer. The tie layer can be made of a material that is susceptible to disruption by ultrasound. The device can also include a fiber optic element extending from the proximal end to the distal end, arranged to deliver light from the proximal end to a photoacoustic component at the distal end to produce a photoacoustic effect.

[0008] According to a second aspect, a method for generating ultrasound by an ultrasoundemitting device is disclosed. The method includes positioning an electrode in a first lumen of a catheter such that the electrode extends from a proximal end of the catheter to a distal end of the catheter. The method further includes inflating a balloon of a catheter by delivering a fluid to the balloon via a second lumen of the catheter. The method further includes delivering electrical pulses to the fluid in the balloon via an electrical cable in communication with the electrode arranged within the balloon. The method includes directing ultrasonic waves generated in response to the electrical pulses to a target area to dislodge an adherent mass from the tissue.Attorney Docket No. 19506.0002WOU1

[0009] Optionally, at least one of the balloon, a balloon shaft and / or the fluid comprises a material that can be used to generate an ultrasonic signal. The balloon can be polymer based. The target area can include calcium deposits for calcium debulking, or an atherosclerotic plaque or other blockage for treatment of arterial occlusion, for example. The method can include disrupting a tie layer that couples a pharmaceutical coating to the balloon with the ultrasonic emissions. The method can include routing the distal end of the catheter to a target location along a guidewire prior to inflating the balloon. The method can include inflating a second balloon located between the balloon and the proximal end, and illuminating an electrode at the proximal end of the catheter with the series of electrical pulses, such that the series of electrical pulses travels through the second electrode and is delivered to the second balloon. The method can further include aspirating a region arranged between the balloon and the second balloon and adjacent the catheter. The method can include denervating an anatomical structure positioned in a region arranged adjacent the balloon. The method can further include routing a light through a fiber optic element that extends from the proximal end to the distal end, the fiber optic element arranged to deliver the light to a photoacoustic component at the distal end to produce a photoacoustic response for imaging.

[0010] According to a third aspect, a system for generating targeted ultrasonic waves for treatment of a tissue includes a catheter extending from a proximal end to a distal end, the catheter defining lumens therein. A balloon is arranged at the distal end, and an interior of the balloon is fluidically coupled to a first one of the plurality of lumens. A means of delivering electrical pulses arranged within the balloon is provided, as well as a power supply in connection with the means of delivering electrical pulses via a second one of the plurality of lumens triggering generation of ultrasonic waves in response to the electrical pulses.

[0011] The system further includes a guidewire arranged through one of the lumens, extending through the catheter from the proximal end and past the distal end thereof. The means of delivering electrical pulses can include one or more electrodes. The balloon can include at least a first balloon and a second balloon. The first balloon and the second balloon can be spaced apart such that a target tissue is arranged between the first and the second balloons. The ultrasonic waves can be directed at the target tissue by the first and second balloons. The holes can be arranged between the first and second balloons. The catheter can include a third lumen in communication with the holes, and a medication can be delivered to the target tissue via the third lumen and the plurality of holes. The balloon can be made of a polymer. The system can also include multiple balloons spaced apart to receive a target tissue between them. Holes may be arranged between the balloons for drug delivery, and a guidewire can be included forAttorney Docket No. 19506.0002WOU1 navigation. The balloon, fluid, and / or balloon shaft can be made of thermoacoustic materials or polymers. A fiber optic element can also be included extending from the proximal end to the distal end. The fiber optic element can be arranged to deliver light from the proximal end to a photoacoustic component at the distal end to produce a photoacoustic effect usable for imaging. The system can also include a tie layer disposed on a surface of the balloon and a coating coupled to the balloon by the tie layer. The tie layer can include a material that is susceptible to disruption by ultrasound.

[0012] Various examples of a system and method for generating targeted ultrasonic waves for the treatment of tissues are described in more detail herein. These embodiments include features such as multiple balloons, drug elution holes, thermoacoustic materials, and fiber optic elements to enhance the efficacy of the treatment.

[0013] According to a fourth aspect, a device for generating targeted ultrasonic waves for treatment of a tissue is disclosed. The device includes a catheter extending from a proximal end to a distal end, the catheter defining a plurality of lumens therein. A balloon is arranged at the distal end. An interior of the balloon is fluidically coupled to a first one of the plurality of lumens such that the balloon can be inflated by a fluid routed through the first one of the plurality of lumens. An electrode is arranged in a second one of the plurality of lumens, the electrode extending from the proximal end to the distal end and arranged to exert a thermal effect in the fluid at the interior of the balloon.

[0014] Optionally, a length of the catheter more proximate than the distal balloon defines a plurality of holes therein that are usable for drug elution. The catheter can also include a third lumen in communication with the plurality of holes. A medication can be delivered to the target region adjacent the length via the third lumen and the plurality of holes. The device can also include a guidewire arranged through a fourth lumen of the plurality of lumens and extending from the proximal end and past the distal end. The device can also include a tie layer disposed on a surface of the balloon, and a pharmaceutical coating coupled to the tie layer. The tie layer can be made of a material that is susceptible to disruption by ultrasound. The device can also include a fiber optic element extending from the proximal end to the distal end. The fiber optic element can be arranged to deliver light from the proximal end to a photoacoustic component at the distal end to produce a photoacoustic effect.

[0015] A variety of additional inventive aspects will be set forth in the description that follows. The inventive aspects can relate to individual features and to combinations of features. It is to be understood that both the forgoing general description and the followingAttorney Docket No. 19506.0002WOU1 detailed description are exemplary and explanatory only and are not restrictive of the broad inventive concepts upon which the embodiments disclosed herein are based.BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The accompanying drawings, which are incorporated in and constitute a part of the description, illustrate several aspects of the present disclosure. A brief description of the drawings is as follows:

[0017] FIG. l is a system for catheter-based ultrasonic therapy delivery.

[0018] FIGS. 2A and 2B are cross-sectional views of the catheter of FIG. 1 across line 2 — 2 thereof, according to two different embodiments.

[0019] FIG. 3 is a partial view of a catheter usable in the system of FIG. 1, depicting a distal end thereof.

[0020] FIG. 4A is a partial view of a catheter usable in the system of FIG. 1, depicting a distal end thereof, the catheter system having a drug coating.

[0021] FIGS. 4B is a detailed cross-sectional views of the skin of the balloon of the catheter system of FIG. 4 A.

[0022] FIG. 5A is a partial view of a catheter system usable in the system of FIG. 1, depicting a distal end thereof, the catheter system having multiple balloons at the distal end.

[0023] FIG. 5B is a partial view of a catheter system usable in the system of FIG. 1, depicting a distal end thereof, the catheter system having multiple balloons at the distal end and drug eluting apertures in the length between the two balloon.

[0024] FIG. 5C is a partial view of the catheter system of FIGS. 5 A and 5B, depicting an imaging system arranged therein.

[0025] FIG. 6 is a partial view of a single-balloon catheter usable in the system of FIG. 1, as well as an aspiration subsystem coupled thereto.

[0026] FIG. 7 is a flowchart of a method for providing sonic therapy using a catheter.

[0027] FIGS. 8 A and 8B are partial views of a catheter system usable in the system of FIG. 1, depicting a distal end thereof, the catheter system having a balloon with a cutting element at the distal end.

[0028] FIG. 9 is a partial view of a catheter with a microneedle-coated balloon.

[0029] FIG. 10 is a partial view of a pair of catheters deployed in a vascular system, with a first upstream catheter delivering microbubbles and a second downstream catheter delivering ultrasound.Attorney Docket No. 19506.0002WOU1

[0030] FIG. 11 is partial view of a catheter deployed in a vascular system and delivering microbubbles from an outer layer.

[0031] FIG. 12 is a partial view of a catheter deployed in a vascular system and delivering microbubbles from an interior lumen.

[0032] FIG. 13 is a partial view of a catheter with two balloons delivery microbubbles from an interior lumen.DETAILED DESCRIPTION

[0033] Reference will now be made in detail to exemplary aspects of the present disclosure that are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts. Furthermore, when two similar embodiments are shown in different figures that have similar parts, those similar parts may be referred to using reference numbers iterated by a factor of 100. In such instances, the full description of those components may not be repeated, and it should be understood that they apply equally to the similar instances with similar reference numbers.

[0034] Throughout this application, therapies are described that rely upon delivery of sonic energy or ultrasonic pressure waves to the body. In many situations, the desired frequency of the treatment is ultrasonic (i.e., above about 20 kHz, and in some embodiments several MHz). As a matter of convenience, therefore, this application refers to delivery of ultrasonic treatments. However, it should be understood that in some situations delivery of therapies outside of this specific range may be desired. The systems and methods described herein are capable of providing therapies at any desired frequency, and can be configured to deliver either lower or higher frequency treatments as desired.

[0035] Catheters and components thereof described herein can be used for thrombectomy, or for denervation, or for a variety of other uses. In general, the devices and methods described herein relate to the delivery of ultrasonic signal from a source located within the body. This ultrasound can be delivered alone, or it can be delivered in combination with chemical or mechanical treatments including drug delivery, aspiration, and the like.

[0036] One example of a use for the devices and methods described herein is in thrombectomy. Thrombectomy catheters are medical devices designed to remove blood clots from blood vessels, particularly in the context of treating conditions like stroke or deep vein thrombosis. Clot removal is necessary in many cases to restore blood flow and prevent further complications associated with clot obstruction. Thrombectomy procedures are often employed when anticoagulant medications alone prove insufficient in resolving the clot. The devices andAttorney Docket No. 19506.0002WOU1 techniques described herein could be used in several cases including chronic total occlusion. Similarly, calcium debulking or removal of other unwanted substances within the vasculature can be accomplished, or similarly differential acoustic absorption characteristics can be used to ablate clots or similar structures.

[0037] Various technologies are employed in thrombectomy catheters, including aspiration, mechanical thrombectomy, and ultrasound to break up or remove the clot or its component parts. Aspiration involves using suction to draw the clot into the catheter, while mechanical thrombectomy devices often use rotating or pulsating components to fragment and remove the clot. The choice of thrombectomy catheter depends on the specific characteristics of the clot and the patient's condition. Thrombectomy procedures are often performed by interventional radiologists or neurointerventionalists using imaging guidance, ensuring precise placement of the catheter and accurate removal of the clot.

[0038] Mechanical thrombectomy is often chosen for the removal of blood clots from arteries or veins with the help of a catheter that utilizes mechanical means such as a clot retriever or aspiration. A limiting factor with currently available thrombectomy catheter devices is the inability to treat wall-adherent and organized thrombus sufficiently. The flushing or sucking technique in aspiration thrombectomy does not effectively break the thrombus away from the wall of the vessel.

[0039] Disclosed herein is a thrombectomy catheter to remove, for example, wall adherent or otherwise organized clots more effectively by making novel use of ultrasonic waves generated by electrical shockwave to dislodge the clots from the walls of the arteries or veins as well as to provide real time imaging.

[0040] Ultrasonic therapy delivered in this way can be used in a variety of contexts, beyond thrombectomy. In one example, renal denervation can be used as a treatment for uncontrolled hypertension. Similar approaches could be used to perform denervation to treat atrial fibrillation. A catheter can be used to deliver ultrasonic therapy to denervate overactive nerves in the renal arteries without damaging the renal arteries themselves. In another example, atherosclerosis can be treated by drug-eluting balloons. Ultrasound can be used to disrupt a drug coating or a tie layer holding the drug to the exterior of the balloon. In this way, loss of drug during transfer efficacy is reduced. Similarly, ultrasound can be used to monitor the extent of drug layer that has been disrupted or released from the device.

[0041] In another example, ultrasound can be used to assist in delivery of active agents through the blood-brain barrier (BBB). Currently, drugs, biologies, and other active agents which need to be delivered to the brain to effect treatment are designed with a molecular sizeAttorney Docket No. 19506.0002WOU1 small enough to cross through this barrier and are delivered systemically. However, many drugs cannot be effectively delivered in this way or modified for this delivery mode. Recently, external focused ultrasound (FUS) has been used with some success. FUS is still limited by the need for systemic delivery of an agent (e.g., microbubbles) and the size of molecules which can be passed through the BBB (< 150kDa). See, for example, “Ultrasound-mediated bloodbrain barrier opening: An effective drug delivery system for theranostics of brain diseases” by Jieqiong Wang, et.al. Advanced Drug Delivery Reviews, Volume 190, November 2022 (DOI: 10.1016 / j.addr.2022.114539).

[0042] As disclosed herein and discussed in further detail below, an endovascular catheter and / or a balloon catheter that can provide ultrasonic waves, such as embodiments of the photoacoustic balloon catheter disclosed herein, can be used to locally and temporarily open the BBB. In embodiments, the ultrasonic waves may be generated using various methods and energy sources, drug delivery may be incorporated via, e.g., the catheter or a coating on the catheter, and the balloon and / or catheter may incorporate various physical attributes to modify or improve the opening of the BBB. For example, a catheter configured for delivering a treatment across the BBB may incorporate features which effect the amount of time the BBB is open and / or the size or number of openings.

[0043] Described herein is a novel application of local ultrasound delivery in conjunction with microbubble infusion and targeted drug administration for precise modulation of the blood-brain barrier. By combining these techniques, the disclosure aims to achieve localized and temporary opening of the epithelial cell lining, allowing for enhanced drug delivery while minimizing the potential infiltration of undesirable substances. In comparison to conventional methods that may leave the epithelial cell lining open for prolonged periods, up to four hours in some cases, this innovative approach promotes rapid closure of the barrier, ensuring efficient drug delivery with reduced risk of unwanted compounds breaching the barrier. Through the coordinated use of ultrasound, microbubbles, and carefully selected therapeutic agents, this disclosure offers a novel strategy for delivering drugs directly to specific sites within the body while preserving the integrity of the blood-brain barrier.

[0044] Ultrasound can be used for imaging as well, using arrangements of sensors called transducers that emit and / or receive acoustic pressure to map the region around the catheter. These acoustic waves can be echoes from acoustic pressure waves emitted by the transducer. The acoustic waves could also be generated through use of electrodes to cause cavitation or otherwise generate acoustic waves, and the transducer can receive information for use in imaging or routing based on reflections from the acoustic emissions described above that areAttorney Docket No. 19506.0002WOU1 used for treatment. A source external to the body could also be used to generate ultrasound pressure waves that are detected by the transducer. Regardless, the transducer(s) can covert acoustic pressure waves into an electrical signal and the magnitude of the signal can be converted into image intensity. The time at which the acoustic pressure wave arrives at the transducer can be used to estimate the distance from the transducer at which the signal originated via the speed of sound in tissue in a time-of-flight analysis or the like. Ultrasound imaging with one or more transducer can monitor drug release, quantitate acoustic pressure waves, and make maps of anatomy (including diseases like calcification and thrombosis) in the vasculature. Importantly, the imaging can be done longitudinally to understand how disease changes as a function of time or therapy from the device. These transducers can be miniaturized and routed through the very small lumens of the catheter. The transducer can rotate across 360 degrees to map all sides of the vasculature. Similarly, the transducer may be stationary relative to the catheter, and the entire catheter may rotate in the vasculature. These and other implementations are described in more detail below with respect to the drawings.

[0045] In embodiments, a balloon is provided that delivers the ultrasound, located at a distal end of a catheter using, for example, cavitation. Cavitation is fundamentally based on the generation of acoustic waves due to local heating or sparking within a material across a spark gap, or rapid heating or phase change in that region. Alternatively, passing an electric current through a conductive material can result in resistive heating, causing localized temperature increases and triggering the generation of acoustic signal.

[0046] Either the balloon material itself or a fluid that fills the balloon has a nonzero coefficient of thermal expansion (CTE). In embodiments, an electrode or other resistive heating element provides heat to the inside of the balloon. The fluid material should also be able to absorb the heat to generate further thermal energy and an accompanying acoustic emission. In some embodiments, rather than having the fluid itself absorb and expand or contract in response to heating, a balloon or catheter shaft can absorb the thermal or electrical stimulation, be activated to produce an acoustic effect by the incoming thermal signal, and therefore generate the acoustic (e.g., ultrasound) signal.

[0047] Generating cavitation or other acoustic signal generation from electrical pulses causes absorption or heat or other energy, which in turn leads to localized heating, causing a rapid increase in temperature and potentially phase change in these regions, which thus may also be activated by supplying thermal energy directly. As the temperature rises, the molecules undergo thermal expansion and create a localized pressure gradient within the material. This pressure gradient propagates outward from the region of thermal activation to create a soundAttorney Docket No. 19506.0002WOU1 wave. The acoustic emission can have a different frequency, intensity, and wavelength response based on the material used.

[0048] Heat sources can be routed to the balloon from the opposite end of the catheter by routing an electrode through a lumen of the catheter. Each pulse of the electrode can be used to generate a burst of acoustic emissions from the material that is heated. The acoustic signal can be generated as an output from cavitation from rapid heating or sparking in saline, for example.

[0049] Ultrasonic therapy delivered in this way can be used in a variety of contexts. In one example, renal denervation can be used as a treatment for uncontrolled hypertension. A catheter can be used to deliver ultrasonic therapy to denervate overactive nerves in the renal arteries without damaging the renal arteries themselves. In another example, atherosclerosis can be treated by drug-eluting balloons. Ultrasound can be used to disrupt a drug coating or a tie layer holding the drug to the exterior of the balloon. In this way, loss of drug during transfer efficacy is reduced. An ultrasonic drug-delivery catheter can be used to deliver drugs and other agents across the BBB without needing to deliver the agent systemically. Ultrasound can be used for imaging as well, using arrangements of sensors that receive reflected ultrasonic waves to map the region around the catheter. These and other implementations are described in more detail below with respect to the drawings.

[0050] FIG. 1 shows a system for catheter-based ultrasound delivery. As shown in FIG. 1, an ultrasound-emitting system 100 includes a catheter 102 having a proximal end 104 and a distal end 106. A balloon 108 is arranged at the distal end 106, and a guidewire 110 optionally extends beyond the distal end 106 for routing the catheter 102 to a desired location. Power source 112 and fluid source 114 are arranged at the proximal end 104 of the catheter 102.

[0051] Ultrasound-emitting system 100 is one example of a system that can deliver ultrasonic therapy as described above and is shown in a simplified form in FIG. 1. More complex arrangements are shown and described in the subsequent figures. The version of ultrasound-emitting system 100 shown in FIG. 1 depicts just one simple combination of components that can be used to provide ultrasonic therapy.

[0052] Catheter 102 is a multi-lumen catheter that can be used to couple proximal end 104 to distal end 106. The lumens of catheter 102, which are shown in more detail with respect to FIG. 2, provide for delivery of power and fluid from power source 112 and fluid source 114, for example, as well as providing an aperture for guidewire 110. Other lumens can be used to provide access for an imaging transducer, as described in more detail with respect to FIG. 5C.Attorney Docket No. 19506.0002WOU1Catheter 102 is also shown in a simplified form, and can include various other elements not depicted in FIG. 1, such as imaging sensors.

[0053] Proximal end 104 is a portion of catheter 102 that can be controlled, accessed, and manipulated throughout a procedure, as it remains outside of the patient. The term “proximal end,” as used throughout this application, refers to more than just the very end of the catheter 102. In some examples the proximal end 104 can extend for some length along catheter 102 from the far end thereof, to include any region of catheter 102 where access is provided to the lumens defined therein, or the region of the catheter 102 that is manipulated as it is directed into the patient.

[0054] Distal end 106, similarly, includes more than just the end face of catheter 102. Distal end 106 includes the region extending from the terminus of catheter 102 through the balloon 108 (or multiple balloons, as described with respect to FIGS. 6 and 8). Distal end 106 can also include various ports or aspiration features (as described with respect to FIGS. 7A-7C and 8).

[0055] Balloon 108 is an expandable element located at the distal end 106. Balloon 108 can receive power delivered through catheter 102 from power source 112. The interior of the balloon 108 can further be fluidically coupled to one of the lumens of catheter 102 so that the balloon 108 can be inflated or deflated by fluid source 114. FIG. 1 shows balloon 108 in an inflated form. That is, in the view shown in FIG. 1, balloon 108 is filled with fluid provided from fluid source 114. In a deflated form, balloon 108 sits substantially flush with the exterior of the remainder of catheter 102.

[0056] Power source 112 can include any of a variety of sources of electrical power, such as an AC or DC power supply, a battery, a generator, a rectifier, or an inverter. In many embodiments, the electricity provided by power source 112 is modulated. In such embodiments, either the source itself can be turned on and off to modulate the electrical signal, or a modulator can be used in combination with a power source to provide the desired timing of the power. For example, a chopper or other obstruction can be used to modulate power produced by a constant power source 112 prior to its introduction to the electrodes described herein and ultimate delivery to the distal end of the catheter 102 or balloon 108.

[0057] Digital acquisition system (DAQ) 113 can control the time of acoustic pulsing in the transducer. This system can also contain a motor drive unit and a console to display images. It can cause the transducer to emit pressure waves at desired intervals. It can also record acoustic pressure waves in the transducers and convert the pressure intensity into electrical signals for conversion to an image.Attorney Docket No. 19506.0002WOU1

[0058] FIG. 2A is a cross-sectional view of the catheter 102 of FIG. 1 across line 2 — 2 thereof as depicted in FIG. 1. Catheter 102 is a multi-lumen catheter including, in the depicted example, first lumen 216, second lumen 218, and third lumen 220. In embodiments, each of first lumen 216, second lumen 218, and third lumen 220 can provide passage for an associated apparatus (e.g., guidewires, electrical wires or cables, or the like) or fluids used with the catheter. In examples, first lumen 216 is used to provide a fluid through the catheter 102, such as for inflating balloon 108, and second lumen 218 provides passage for electrical cables to supply power, such as from power source 112, to the distal end of the catheter 102. In embodiments, third lumen 220 provides for drug delivery of one or more drugs. In other embodiments, third lumen 220 provides access for an intravascular ultrasound transducer. Although the example catheter 102 is shown with three lumens, 216, 218, and 220, it is to be understood that other numbers of lumens are contemplated and may be implemented depending on the application and other considerations of various implementations. In embodiments, catheter 102 may have one, two, four, five, six, etc. lumens to provide for delivery of various components and compounds.

[0059] The lumens (216, 218, 220, 222) shown in FIG. 2 A have identical sizes, but it should be understood that in alternative embodiments they may have different sizes commensurate to different uses. For example, it will often be the case that a larger or central lumen can be used for a guidewire. Some systems housed in the lumens may have a second guidewire.

[0060] FIG. 2B shows a front view of an alternative embodiment with a central guidewire lumen. As shown with the cross-hatching in the view of FIG. 2B, the lumens are separated by walls and form radially inner and outer passageways for fluid, light guides such as fiber optics, or electrical wiring to pass. It should be understood that the walls (hatched portions) and the lumens (216, 218, 220, 222) are not necessarily to scale. That is, the radial extent of each of the lumens 216, 218, 220, 222 as well as the wall (hatched) portions between them can vary as needed to route solid structures (e.g., transducers, optical fibers, guidewire) or liquids (e.g., inflation fluid) therein.

[0061] FIG. 3 is a partial view of a catheter 302 usable in the system of FIG. 1, depicting a distal end 306 thereof. Balloon 308 is arranged at the distal end 306 of the catheter 302, with some additional length of catheter 302 extending past balloon 308 and out of guidewire aperture 326 to extend where, in examples, a guidewire may emerge and provide steering of catheter 302. FIG. 3 shows transducer 325. Transducer 325 can be moved more proximal or distal within the balloon to change the area being imaged including via a guidewire. The transducer 325Attorney Docket No. 19506.0002WOU1 itself may contain driving shafts, distal markers, guide wires, mechanical rotation, or phased arrays, though these are not shown in detail in FIG. 3. Transducer 325 can be a separate movable component from the catheter 302 as shown in FIG. 3, or alternatively the transducer 325 can be arranged in one of the plurality of lumens (FIG. 2; 216, 218, 220, or 222) or integrated into the catheter (FIG. 2; 102). Images obtained using the transducer 325 can be used to make a decision, such as to continue or stop treatment, move the catheter 302, or change various other treatment parameters.

[0062] Balloon 308 can either contain a fluid that can be used to cause cavitation, such as saline, or alternatively a mechanical structures such as the shaft of catheter 302 or the balloon 308 itself may exhibit a response to electrical or thermal signal that causes acoustic emission.

[0063] Although only one transducer is shown in FIG. 3, multiple transducers may also be used in alternative embodiments. The transducer 325 shown in FIG. 3 is shown extending from a lumen inside the catheter, but it should be understood that it may be in any of the lumens in the catheter and may also emerge from an aperture such as 324. In some embodiments, the transducer 325 may be located inside of the fluid that is used to inflate the balloon. In other instances, it may be in the interior such as lumen 520 in Figure 5C. Multimodal transducers might also be used that offer near-infrared spectroscopy or optical coherence tomography sensing. The details of these have been published extensively, e.g., Peng et al., Recent Advances in Transducers for Intravascular Ultrasound (IVUS) Imaging, Sensors EISSN 1424-8220 (19 May 2021) and Wang et al., Capacitive Micromachined Ultrasound Transducers for Intravascular Ultrasound Imaging, Microsystems & Nanoengineering (2020)6:73, and Yock & Fitzgerald, Intravascular Ultrasound: State of the Art and Future Directions, 81 The American Journal of Cardiology 7, supplement 1 (9 April 1998).

[0064] Fluid is delivered to balloon 308 through apertures 324 to inflate balloon 308. One or more of the apertures 324 may be in communication with, for example, first lumen 216 of FIG. 2 A. A fluid used to inflate balloon 308 may be selected based on acoustic output characteristics, thermal absorption or cavitation characteristics, or other considerations depending on a specific implementation. In one example, the fluid used to inflate balloon 308 can be saline. In other examples, the fluid used to inflate the balloon 308 can be chosen based on its acoustic output response characteristics, which can include frequency and intensity of acoustic emissions in response to received heat, cavitation, or electrical input at a particular frequency or frequencies. Ultrasound emitted in this way may be enhanced by use of a fluid with specific thermal or cavitation properties, sometimes called a coupling medium.Attorney Docket No. 19506.0002WOU1

[0065] The acoustic (e.g., ultrasonic) emissions produced by such a system reflect, refract, and transmit through the body in ways that make imaging or therapy of the body around the catheter possible. This property is useful in applications where controlled ultrasonic treatment, heating, and / or imaging are desired, as they can be used for positioning and targeting relative to a feature of interest for treatment. For example, targeted local ultrasound from a catheter positioned within a vessel of the brain can disrupt the BBB for effective delivery of therapeutic agents without the limitations of external FUS.

[0066] When using some types of electrode 322 arrangements, the magnitude of the acoustic signal emitted can be controlled by the intensity of the electrical input signal. The pulse will move in different directions based on the position of the electrodes 322 within the catheter 302 or extending therefrom into the balloon 308. As noted above, the electrodes 322 can be independently moved within lumens (e.g., 216, 218, 220, 222), such that the distance therebetween can be adjusted in some cases. A transducer 325 positioned at the distal end 306 will be able to map and measure the acoustic pressure waves as they reflect, refract, and transmit through the body. In that way, the acoustic intensity can be increased or decreased (e.g., by moving the locations of the electrodes 322 relative to one another) based on the realtime feedback provided by the transducer. The directionality of the acoustic intensity can be changed based on the information / images determined by the transducer. This can be done quickly including video frame rates.

[0067] In various embodiments, the device includes a transducer 325 (or alternative transducers as shown in the accompanying drawings) to record ultrasound pressure waves. This transducer 325 may be a single element transducer 325 or a miniaturized phase array or linear array, for example. The transducer 325 may be positioned at or near the balloon 308 or may be in the interior of the balloon 308 when accessed through one of the channel s / lum ens in the catheter 302. The transducer 325 can be acoustic coupled to the surrounding environment via the fluid used to fill the balloon 308 or the liquid (e.g., blood) present in the vasculature. In embodiments, the transducer 325 can be moved proximally or distally to record acoustic signals in different areas of the vasculature, either with the remainder of the catheter 302 or separately from the catheter 302, such as back and forth within a lumen of the catheter 302.

[0068] The transducer 325 itself may include a second guidewire to adjust position and angling, and this would be known to persons skilled in the state of the art as intravascular ultrasound (IVUS). The transducer 325 can be used to emit and / or receive pressure waves. In one design, the transducer 325 will both emit and receive pressure waves. These waves emitted from the transducer 325 interact with surrounding tissue and some would return to theAttorney Docket No. 19506.0002WOU1 transducer 325. These waves could be used to make images that monitor changes to the surrounding physical environment, such as tissues.

[0069] In another design, the transducer 325 would only record pressure waves. The transducer 325 could record acoustic pressure waves created by the balloon 308 material or the fluid. The acoustic waves produced by the electrodes 322 might also interact with the surrounding anatomy before being record. The transducer 325 could in turn monitor the magnitude and location of the pressure waves. The transducer could also monitor release of drug from the catheter due to changes in acoustic properties of the drug-carrying layer or through the presence of an active element within the drug.

[0070] Some examples of suitable fluids that can be routed into balloon 308 include saline, or alternatively perfluorocarbons (PFCs) and liquid metals, like gallium-based alloys, which can be used in certain applications where thermal expansion is a key factor. Suitable fluids for filling the balloon 308 can include liquids or gases, and can have a combination of thermal absorption and thermal expansion that facilitate the use of electrodes to create acoustic signal therefrom.

[0071] Cavitation-generated ultrasound waves can be used for various purposes, such as enhancing the contrast in imaging or facilitating targeted drug delivery in medical applications. For medical imaging purposes, contrast agents are often introduced into the body to improve the visibility of certain structures or organs. These agents can be microbubbles, for example microbubbles containing inert gases such as xenon or sulfur hexafluoride, or nanoparticles, such a lipid-based nanoparticles, suspended in a fluid such as water or another carrier fluid chosen for its compatibility with the body and ability to support cavitation. Other examples of fluid which may be chosen for their cavitation properties includes certain polymeric solutions which, when properly formulated, can exhibit cavitation effects.

[0072] Electrodes 322 are admitted to the interior of balloon 308, such as through apertures 324. Apertures 324 may be connected to one or more of lumens, 216, 218, 220, and 222 of FIG. 2 and provide access to the interior of balloon 308 for various media and devices, such as fluid for inflation or electrodes 322. For example, electrode 322 may be delivered to the interior of balloon 308 via an aperture 324 connected to a lumen, such as second lumen 218 of FIG. 2. The lumen provides passage for the electrical cable used to direct electrode 322 and supply power.

[0073] One or more electrodes 322 are deployed into the interior of balloon 308 and deliver electrical pulses. While balloon 308 is expanded with a fluid, such as saline or fluids containing contrast media, the electrical signal that causes acoustic pulses to be generated willAttorney Docket No. 19506.0002WOU1 be delivered to the fluid inside the balloons. As described above, the electrical signal delivered at electrodes 322 can result in acoustic response and acoustic emissions within the balloon 308 that can be used for treatments and imaging via the transducer 325.

[0074] Although two electrodes 322 is shown in FIG. 3, it should be understood that there may be any number of such electrodes 322 arranged throughout the balloon 308 extending from different ones of the apertures 324. The electrical energy is converted into acoustic signal as the electrode(s) 322 are powered, either simultaneously or sequentially. The ultrasonic waves created in this way may be used to dislodge wall-adherent and organized thrombus, for example, or provide denervation at a nearby anatomical structure.

[0075] In embodiments, electrodes 322 are arranged or activated to achieve particular ultrasound directionality. For example, electrodes 322 may be forwardly- or circumferentially- arranged to activate or direct ultrasound toward a forward (or distal) direction relative to an origin or entry point of the catheter 302.

[0076] In embodiments, the electrodes 322, the fluid filling the balloon 308, and the catheter 302 can be chosen to be compatible.

[0077]

[0067] FIGS. 4A and 4B show a multi-layer balloon with a coating 438.

[0078] FIG. 4A shows a balloon 408 inflated along a catheter 402, at a distal end 406 thereof. As described with respect to the similar embodiments above, a guidewire 426 extends from the furthest distal portion of the distal end 406, and a series of apertures 424 are arranged along the catheter 402 inside of the balloon 408. Some of the apertures 424 are usable to route fluid through the catheter 402 to the interior of the balloon 408 and cause inflation or deflation thereof. Others of the apertures 424 are used to provide access to the interior of the balloon 408 for electrodes 422 that can create localized and timed acoustic emissions in any desired pattern, such as by driving the electrodes 422 at a corresponding power level and frequency from the proximal end of the catheter 402.

[0079] Depending upon the mode of operation, an ultrasonic signal created either between the electrodes 422 producing heat within the fluid within the balloon 408, or by heating upon the skin of the balloon, is transferred outward from the balloon 408 to surrounding structures. In each of the modes of operation described herein the outer layer or skin of the balloon 408 vibrates to deliver of such acoustic signal to the surrounding vasculature or other structures.

[0080] Taking advantage of this vibration, it may be beneficial to provide a layer of a coating 438 along the balloon 408 as shown in FIGS. 4 A and 4B. The coating 438 can be, for example, a medication, a coagulant or embolic material, or an anticoagulant, or a dye or tagging material. Specific example materials that could be used as a coating 438 on the balloon 408 areAttorney Docket No. 19506.0002WOU1 aclitaxel, sirolimus, heparin, or other anti-inflammatory agents, for example. These coatings 438 can be retained by the balloon, even during inflation and deflation, using a tie layer as described below that is only disrupted by appropriate levels or frequencies of acoustic signal.

[0071] In embodiments, the coating 438 may produce some signal that can be detectable by the transducer (e.g., 325 of FIG. 3). The change in signal intensity coming from the balloon

[0081] In other embodiments, coating 438 does not produce its own signal but does have a defined thickness on the ballon exterior as shown in Figure 4A and Figure 4B. This thickness of this layer of coating 438 could be measured with pulse / echo imaging from the transducer (e.g., 325). The reduction in the thickness of coating 438 could then be correlated to release of coating 438 into the surrounding environment.

[0082] Depending upon the materials involved, the coating may be applied to the balloon 408 directly. In other examples, the coating 438 and the balloon 408 are either not compatible and will not stick to one another, or they may stick to one another too well to be disrupted by ultrasonic signal. Therefore it may be preferably to use a tie layer that couples the coating 438 to the balloon 408. The tie layer can either be a separate layer from the coating 538 or it can be comixed with the coating 438 to provide an acceptable level of bond to the balloon.

[0083] The tie layer material, when used, can be selected from materials that will not be disrupted by the expansion of the balloon alone, but will be disrupted by the application of ultrasonic signal. The selection of an appropriate tie material is dependent upon both the balloon 408, the coating 438, and the expected levels of expansion of the balloon 408 and exposure to acoustic signal. The efficiency of these ties can be influenced by a variety of factors that are not described in detail herein, but are discussed, for example, in Cao et al., “The factors influencing the efficiency of drug-coated balloons,” Frontiers in Cardiovascular Medicine, 12 October 2022 (DOI: 10.3389 / fcvm / 2022.94776); Huan et al., “Acoustically active liposomes for drug encapsulation and ultrasound-triggered release,” 1665 Biochimica et Biophy sica Acta (BBA) - Biomembranes 1-2, pp. 134-141 (11 October 2004); Damien V. B. Batchelor et al., “Nested Nanobubbles for Ultrasound-Triggered Drug Release,” ACS Applied Materials & Interfaces 2020 12 (26), 29085-29093 (DOI: 10.1021 / acsami.0c07022); Klibanov et al., “Ultrasound-triggered release of materials entrapped in microbubble-liposome constructs: a tool for targeted drug delivery,” J Control Release. 2010 November 20; 148(1): 13-17. doi: 10.1016 / j.jconrel.2010.07.115; Delaney et al., “Making waves: how ultrasound-targeted drug delivery is changing pharmaceutical approaches,” Mater. Adv., 2022, 3, 3023 (DOI: 10.1039 / dlma01197a); Wilson et al., “Effective ultrasound-triggered drug release from stable nanocarriers,” bioRxiv 2021.12.14.471689 (DOI: https: / / doi.org / 10.1101 / 2021.12.14.471689);Attorney Docket No. 19506.0002WOU1 and Sirsi et al., “State-of-the-art materials for ultrasound-triggered drug delivery,” Advanced Drug Delivery Reviews, Vol. 72 pp. 3-14 (2014) (DOI: 10.1016 / j.addr.2013.12.010).

[0084] In embodiments, the electrodes incorporate materials chosen with consideration to conductivity, corrosion resistance, and mechanical strength. Examples include graphene-based composites, carbon nanotubes, and conductive polymers. Electrodes may be configured as planar electrodes, three-dimensional structures providing increased surface area for improved electrochemical reactions, or flexible electrodes, as some examples. Some embodiments may feature hybrid electrode configurations, combining the advantages of different materials to optimize specific properties. For instance, a hybrid electrode may combine a conductive metal base with a thin layer of graphene for enhanced conductivity and flexibility. Electrodes may be coated with functional layers to enhance their performance in specific applications. Examples include catalytic coatings for improved electrocatalysis, anti-fouling coatings for biomedical applications, and protective layers for extended durability.

[0085] FIG. 5 A is a partial view of a catheter system 502 usable in the system of FIG. 1, depicting a distal end thereof, the catheter system having multiple balloons at the distal end. The first balloon 508 and the second balloon 509 are separated, in embodiments, by a length 540 of the catheter. In some implementations, a target region, such as a thrombus, is aligned with the length 540 of the catheter 502 such that the target region is isolated when the first and second balloons 508, 509 are inflated. This alignment aides in isolation and directed treatment of the thrombus or other target. Transducer 525 can be positioned inside the proximal or distal balloons or may be located in between the two balloons, and is shown in phantom in FIG. 5A. The transducer can be used to create images that guide balloon deployment and expansion as described in Mudra et al., Ultrasound Guidance of Palmaz-Schatz Intracoronary Stenting With a Combined Intravascular Ultrasound Balloon Catheter, 90 Circulation 3 (September 1994).

[0086] The balloon catheter 502 described herein incorporates electrodes 522 and electrical cables, provided within a lumen, that deliver electrical pulses to the inside of the balloons 508, 509 via a lumen as described in FIGS. 2A and 2B. As in previously described embodiments, the catheter 502 can be routed by a guidewire extending from an aperture 526 at the far extreme of a distal end 506 of the catheter. Balloon 508 and balloon 509 can be inflated with fluid through apertures 524 therein.

[0087] The heating or vibration patterns of the fluid or balloon 508 or balloon 509 can be modulated to produce a corresponding frequency of acoustic signal from the balloon 508 and 509. In embodiments, catheter 502 will have one more electrodes 522 and multiple cables that travel through separate lumens to deliver electrical pulses to the interior of balloon 508 and / orAttorney Docket No. 19506.0002WOU1 balloon 509. Balloon 508 and balloon 509 are expanded, such as by saline or fluids containing contrast media, and electrical pulses will be delivered to the fluid inside the balloons 508, 509.

[0088] The electrical energy is converted into heat, with thermoelastic expansion and / or cavitation within the fluid or the balloon skin itself resulting in the generation of ultrasound waves and / or shockwaves by causing movement of balloon 508 and / or balloon 509 as described with respect to the other embodiments above. The ultrasound waves and / or shockwaves are directed to the isolated target area, e.g., consisting of thrombus. In embodiments, a pulse / echo from the transducer is used to map the anatomy at the site of therapy and obtain more details about the disease site. A therapy can then be tailored based on the details about the disease site. This tailoring could include characteristics of the acoustic effect, the duration of treatment, and the directionality of treatment. In FIG. 5A, where multiple balloons are used, a different fluid or fluid mixture could be routed to each balloon through an associated catheter.

[0089] Though the example of FIG. 5 A demonstrates the multi -balloon catheter 502 with two balloons (balloon 508 and balloon 509), those of skill in the art will understand that the multi-balloon catheter 502 may be configured with any number of balloons. For example, catheter 502 may be configured with three, four, six, eight etc. balloons to simultaneously, sequentially, or selectively target one or more areas along the length of the catheter 502. The balloons (e.g., balloon 508 and balloon 509) can have different sizes, shapes, and inflation fluids from one another, as needed to accomplish a desired outcome. For example, two or three or more balloons may be inflated and ultrasonically activated to target a particular area. In some implementations, a different two of the three or more balloons may be inflated and ultrasonically activated to target another area. In examples, multiple balloons may be inflated and ultrasonically activated to affect a large clot formation. The transducer described above can be used in pulse / echo mode here to image the formation or deformation of a clot, dispersion of medication, or perform other mapping or monitoring functions.

[0090] In some embodiments, a multi-balloon arrangement can be used to stop blood loss. For example, the most distal balloon used to fill the vasculature, while a second balloon is used to induce a clot through acoustic or thermal emissions. This can be used as an alternative to cauterization in some procedures.

[0091] The electrodes 522 in each of the balloons can be activated independently or together with one another in concert. When powered together, the acoustic emissions from each of the balloon 508 and balloon 509 are synchronized, and advantageously it may only be necessary to route power through one or two lumens (see FIG. 2) within the catheter 502. AsAttorney Docket No. 19506.0002WOU1 such, that catheter 502 may have a relatively small cross-sectional area and can be routed to areas of the vasculature where a larger catheter would not be able to reach.

[0092] In other examples, however, the electrodes 522 may be separately powered or separately controlled. The electrodes 522 can then be used to create acoustic signals from their respective balloons (e.g., balloon 508 and balloon 509) that will constructively or destructively interfere with one another. Additionally or alternatively, one of balloon 508 and / or balloon 509 can be passive (that is, the electrodes 522 therein are unpowered) while the other is activated to create acoustic signal. In this way, one of the balloons (e.g., balloon 509) can be used for anchoring the catheter 502 in place while the other (e.g., balloon 508) provides ultrasonic signal to deliver the desired treatment. When power is provided separately, it may be necessary to route distinct electrodes through separate lumens of the catheter 502, unless the electrodes have a small enough cross-section to cohabit a single lumen.

[0093] In use, the embodiment shown in FIG. 5A can be delivered around a target to be ablated. That is, the target to be ablated may be in the region labeled length 540 in FIG. 5A, arranged between the first balloon 508 and the second balloon 509. Acoustic pulses such as ultrasound can be delivered from one or both sides using balloon 508 and balloon 509. A clot or other structure to be treated can be broken up and, due to the positions of the balloon 508 and balloon 509, the constituent parts that are dislodged are not able to travel away but are instead trapped therebetween. Subsequently, balloon 508 can be deflated and aspiration can be used to remove those parts (see, e.g., FIG. 6). In some cases, transducer 525 can be used to create images of a dislodged material to confirm aspiration prior to or after deflating balloon 508.

[0094] FIG. 5B is a partial view of a catheter system 502 usable in the system of FIG. 1, depicting a distal end 506 thereof, the catheter system having multiple balloons (e.g., balloon 508 and balloon 509) at the distal end and drug eluting apertures 542 in the length 540 between balloon 508 and balloon 509.

[0095] The catheter shaft in between the balloons (i.e., the portion of catheter 502 along length 540) may include holes for infusing a drug out into the region adjacent the catheter 502, as indicated by the perforated exterior in that region in FIG. 5B. The catheter 502 can include one or more additional lumens to deliver medications infused to the thrombus in the area isolated by the balloons 508 and 509 along the catheter shaft. Upon infusing the medication and activating the ultrasound or shockwave, the drugs can be effectively directed into the thrombus to destroy the thrombus. This targeted treatment is particularly useful when the clot is located in a specific vessel or organ. Examples of drugs employed in this procedure includeAttorney Docket No. 19506.0002WOU1 tissue plasminogen activator (tPA), such as alteplase, which is a thrombolytic agent that breaks down fibrin clots, and anticoagulants like heparin, which prevents further clot formation.

[0096] In addition to drug therapy, catheter-based procedures may involve the delivery of thrombin inhibitors and fibrinolytic agents like bivalirudin and urokinase, respectively. These drugs are delivered directly to the thrombus through the catheter, enabling a higher concentration at the clot site and reducing systemic effects. Moreover, as disclosed herein catheter-directed thrombolysis may incorporate the application of ultrasound to drive the drugs into the thrombus and effect breakup of the thrombus from the ultrasonic effects. This approach offers the advantage of localized treatment, minimizing the risk of bleeding complications associated with systemic drug administration.

[0097] Additionally, FIG. 5B depicts, in phantom, a transducer 525 that can be used for imaging. Transducer 525 can be positioned inside the proximal balloon 508 or the distal balloon 509, or may be located in between balloon 508 and balloon 509 along the length of catheter 502 as is shown in phantom in FIG. 5B. The transducer can be used in pulse / echo mode here to monitor the destruction of the thrombus. The images can be used to confirm that constituent parts that are dislodged around aspirated and not allowed to circulate in the vasculature.

[0098] In embodiments, the catheter devices disclosed herein are used for the delivery of microbubbles, such as in the context of penetrating the BBB to affect a treatment on the brain. While the examples of FIGS. 5A and 5C depict two balloons adjacent to one another along the shaft of the catheter, other arrangements of multiple balloons are envisioned. For example, two or more balloons is arranged with an inner balloon within an outer balloon. The outer balloon may be inflated to oppose the walls of a vessel where the catheter is positioned, while the inner balloon is configured to provide ultrasonic waves and / or drug delivery as disclosed herein.

[0099] FIG. 5C shows a cutaway perspective view, similar to that of FIG. 2A, in which a transducer 525 is shown. The transducer 525 is depicted emanating a region 550 of ultrasonic signal. The region 550 can be shaped and targeted based upon the geometry of the transducer 525 and how it is operated. The region 550 is not a physical substance but rather a series of acoustic waves at a desired frequency to produce a desired treatment, to create imaging signal, or both.

[0100] Like FIG. 2A, FIG. 5C includes four lumens, 516, 518, 520, and 522. Transducer 525 is in the first of these, lumen 516. It should be understood that, like in the other embodiments described herein, there could be more or fewer lumens than are shown in FIG. 5C. Lumens can be put to common purposes, such as by routing fluid through a lumen that also routes the transducer 525 or other physical components like electrodes (not shown in FIG. 5C).Attorney Docket No. 19506.0002WOU1In embodiments, there may be a separate guidewire that is used to route the transducer 525, in addition to a guidewire that is used to route the catheter 502 more generally.

[0101] Transducer 525 is arranged on an outer lumen, so that it is capable of producing acoustic signal that will pass through the catheter 502 to an adjacent structure. It may be desirable in some embodiments to route transducers relatively close to the outer edge of the catheters they are positioned in, so that they can easily be exposed at a surface thereof, or (as shown in FIG. 5C) so that they can provide acoustic signal through the wall thereof without significant acoustic impedance.

[0102] In embodiments, a pulse / echo from the transducer 525 is used to map the anatomy at the site of therapy and obtain more details about the disease site. A therapy can then be tailored based on the details about the disease site. This tailoring could include the frequency and amplitude of the ultrasound emitted, the duration of treatment, and the directionality of treatment. The electrical pulses delivered to the electrodes 522 could be selected to guide this treatment by tuning the amplitude, frequency, voltage, or other attributes of the electrically delivered signal, or the relative locations of the electrodes 522 to one another and to the balloon 508 and / or balloon 509 could be modified. For example, a larger distance between electrodes 522 with a higher voltage delivered would tend to cause a larger spark and cavitation, and therefore a stronger acoustic signal.

[0103] FIG. 6 is a partial view of a single-balloon catheter 602 usable in the system of FIG. 1, as well as an aspiration subsystem 650 coupled thereto. In this example, the balloon catheter 602 (and in particular the balloon 608) will also act as a distal protection during clot dislodgement and can improve aspiration efficiency. Once the clot is dislodged, the aspiration catheter 650 can aspirate the clots effectively, or the device as a whole can be retracted to remove the dislodged material.

[0104] The aspiration catheter 650 provides for the targeted removal of substances such as blood clots, pus, or other unwanted materials from specific areas within the body. The catheter 602 is equipped with a dedicated lumen or channel through which fluids or materials can be aspirated. Depending on the procedure and application, these lumens or channels may be compatible with various aspiration systems, including manual syringes or automated suction devices. Guidance through imaging modalities, such as fluoroscopy or ultrasonic imaging, including IVUS provided from the catheter 602, ensures precise placement of the catheter.

[0105] It should be understood that the aspiration functionality of FIG. 6 can be added to any of the other embodiments shown in FIG. 3, 4A, 4B, 5A, 5B, or 5C as well. The electrode 622 and electrode 623 can operate similarly to those electrodes described with respect to theseAttorney Docket No. 19506.0002WOU1 other figures to generate ultrasound signal and produce a treatment in the area surrounding the balloon 608. In multi -balloon embodiments it may be necessary to deflate at least the relatively more proximal balloon to facilitate aspiration.

[0106] FIG. 7 is an example of a method 700 of using any of the catheters of FIGS. 1-6.

[0107] The method 700 of FIG. 7 includes positioning an electrode in a lumen at 702. As described above, in various embodiments electrical wires or cables can be arranged in one or more lumens, depending upon the number of balloons or, in some cases, the number of areas within each balloon to be powered. Multiple electrodes could be used in some embodiments to provide different signals (e.g., different amplitude or frequency signals) or to create constructive and destructive interference with other signal sources. In some embodiments, an electrode can be advanced within a lumen to a position where it can produce acoustic emissions by sparking or heating the coupling medium, and retracted as desired. One or multiple electrodes can each be advanced to one or more different positions along the catheter during use to produce acoustic signal (e.g., ultrasound) at specific locations and times.

[0108] The method 700 of FIG. 7 further includes routing the catheter to a target location at 704. For example, the catheter could be routed to a location of a clot, an artery where denervation should be performed, or another such target for a medical procedure. In some embodiments, such as those depicted above, a guidewire may be used to advance the catheter.

[0109] Although FIG. 7 shows the positioning of the catheter at the target location 704 occurring after positioning the electrode 702, in some embodiments these could be reordered. In other words, it is possible to route the catheter to a target location 704 prior to positioning the electrode 702 (or electrodes) therein.

[0110] The method of FIG. 7 further includes inflating a balloon at 706. The catheter can include a balloon that is inflatable toward the distal end thereof. Inflating the balloon can be done temporarily, to prevent migration of materials (such as disrupted clot materials). In some embodiments, the balloon can also be part of a system that performs aspiration to remove such materials.[OHl] The method of FIG. 7 further includes powering the electrode at 708. Powering the electrode causes heating of a coupling medium or other material at the distal end of the catheter to generate ultrasound. That material is typically arranged between two or more electrodes, so that sparking or heating between the electrodes will cause cavitation or rapid heating. The coupling medium or other material between the electrodes, upon exposure to thermal effects from the output of the electrode, emits acoustic signal. In many embodiments, for example, theAttorney Docket No. 19506.0002WOU1 frequency of the acoustic output from the coupling medium or other material can be ultrasonic, to provide for an ultrasonic therapy at the target location.

[0112] Optionally, the method of FIG. 7 can include using a transducer to emit or receive reflected or refractive signal such as echoes for use in imaging at 710. The acoustic signal generated by the coupling medium or other material may reflect off of some surfaces, and can be used in echolocation or imaging to locate and identify objects in the vicinity of the distal end of the catheter through the transducer described above. The transducer could be used to emit and / or receive pressure waves. In one design, the device will emit and receive pressure waves. These waves emitted from the transducer would interact with surrounding tissue and some would return to the transducer. These waves could be used to make images that monitor tissue. In a second design, the transducer would record only. The transducer could record acoustic pressure waves created by the balloon material or the fluid therein. The acoustic waves produced by the devices or systems described herein might also interact with the surrounding anatomy before being record. The transducer could in turn monitor the magnitude and location of the acoustic waves. In a third design, the transducer could also monitor release of drug from the catheter due to changes in acoustic properties of the drug-carrying layer or through the presence of an acoustically-active or reflective element within the drug. Thus, it is understood that while step 710 (imaging) is shown to be between steps 708 and 712, the imaging could be done at multiple points to position the catheter, position the items in the lumens, monitor balloon inflation, stratify the disease at the site, monitor acoustic reflection or echoes, monitor destruction of tissue, and monitor release of material from the balloon.

[0113] The method 700 also includes performing a treatment at step 712. Several examples of treatments which may be performed using the catheter devices of the present disclosure are discussed throughout. For instance, performing a treatment may include using ultrasonic waves generated by the catheter to break up calcium deposits or other occlusions, to denervate a targeted region for pain management or therapy for motor disorders, or to create a temporary opening in the BBB to allow a drug or other active agent to reach the brain. These examples are non-limiting, and performing a treatment at step 712 may extend to other procedures and treatments where an ultrasonic catheter is advantageously applied.

[0114] Referring now to FIGS. 8A and 8B, the device depicted in FIGS. 8A and 8B are similar to those of FIGS. 3 and 4 A. In contrast to FIGS. 3 and 4 A, however, FIGS. 8 A and 8B show a balloon 808 with a cutting element 846. In FIGS. 8A and 8B, structures lying within balloon 808 are obscured in order to more clearly depict cutting element 846 affixed to theAttorney Docket No. 19506.0002WOU1 external surface of the balloon. Internal structures of balloon 808 may be the same or similar to those shown in any of FIGS. 3 and 4 A.

[0115] The generated ultrasound and the cutting elements working together provide increased efficiency for breaking calcium deposits or other occlusions that restrict flow within a vein or other body lumen. The examples shown in FIGS. 8 A and 8B each depict three cutting elements 846, but any number of cutting elements may be used. For instance, one, two, three, four, five, six, ten, fifteen, twenty, etc. cutting elements may be affixed to the balloon, depending, for example, on the size of the cutting elements, the size of the balloon, the arrangement of the cutting elements, etc. Cutting element 846 may be arranged symmetrically around balloon 808, as shown in FIG. 8 A, or asymmetrically as shown in FIG. 8B.

[0116] Symmetrical arrangement may be preferable for treatment of concentric calcium deposits and other concentric occlusions. Cutting elements may be arranged symmetrically about a circumference of the balloon, as shown in the example of FIG. 8A, or arranged symmetrically along a length of the balloon, e.g., from a proximal end to a distal end, or both. Cutting elements 846 may be arranged symmetrically in one dimension, e.g., about the circumference of the balloon, and asymmetrically with respect to another dimension, e.g., disposed more toward the distal end.

[0117] Asymmetrical arrangement may be preferable for treatment of eccentric calcium deposits and occlusions. Cutting elements 846 may be arranged asymmetrically about a circumference of the balloon. For example, FIG. 8B depicts an embodiment with the cutting elements arranged together in one area 848a of the balloon’s circumference with another area 848b, relatively opposite to the area 848a, has no cutting elements.

[0118] Catheters with asymmetric cutting elements may incorporate other design features to enable a user to rotate the catheter or balloon so that the cutting element can be directed to the vascular structures that need to be cut or modified. For example, manual or mechanical steering may be used with a guidewire provided through a lumen in catheter 802 and used to steer the cutting elements toward a target occlusion. Other possible manual steering configurations include pull wires, pre-shaped tips, and torque transmission.

[0119] In embodiments, cutting elements 846 are attached to an external surface of the balloon using an attachment layer of polymer or adhesive. Some non-limiting examples of an attachment layer include UV-curable adhesives, silicone adhesives, polyurethane adhesives, and polyimide.

[0120] In embodiments, an additional tie layer and / or a drug coating may also be applied to this balloon surface, which may be released, for example, when the balloon is expanded,Attorney Docket No. 19506.0002WOU1 when the laser energy is delivered, or when ultrasound is generated. For example, the balloon 808may also have a coating on the surface that elutes a drug (e.g., Paclitaxel) to treat the target lesion. The drug coating may also utilize a tie layer that could be activated using the ultrasound generated or the laser energy supplied. The additional layer may be applied with similar considerations to those discussed with reference to the coating 438 in FIGS. 4A-4B.

[0121] In embodiments, an additional tie layer and / or a drug coating may be applied to the cutting elements 846 themselves, with similar considerations as those considered to application to the balloon. Applying the drug coating to the cutting elements 846 may be advantageous, for example, for targeted delivery of the drug or other agent.

[0122] The balloon catheter 802 may include an electrode to induce cavitation inside of the balloon or into the inside of the balloon shaft. Balloon catheter 802 may have one more lumen to incorporate one or more electrodes inside of the balloon or to the inside of the balloon shaft as well as to inject the fluid to inflate the balloon. Ballon 808 may be a multi-layer balloon as shown in FIGS. 4A-4B. The ultrasound waves generated within or on the balloon at the target location enables treatment at the target location.

[0123] Alternatively or in addition, the ultrasound waves can allow imaging of the target location. For imaging application, the catheter may incorporate sensors that can detect the ultrasound signals generated as well as that of its response from the surrounding tissues thereby enabling photoacoustic imaging of the surrounding tissues while delivering the therapeutic treatment.

[0124] FIG. 9 is a partial view of an example catheter 902 with a microneedle-covered balloon 908. The example catheter 902 has a balloon 908 with rows of microneedles 946 disposed across the surface of the balloon 908. It should be understood that in alternative embodiments, the microneedles may not be arranged in rows, and may not cover the same portion of the balloon as shown in FIG. 9. For example, microneedles 946 may be provided only along a portion of the radial extent of the balloon 908, similar to the cutting elements of FIGS. 8 A and 8B. Additionally, the microneedles 946 may not be arranged in rows, and can be provided in other arrangements (such as hexagonal packing for increased density) as desired.

[0125] In embodiments, microneedles 946 support targeted drug delivery. For example, the microneedles 946 may be used for drug delivery, such as with a single or small number of rows arranged for targeted drug delivery at a precise location. In embodiments, the microneedles may be applied to mechanically provide access to a targeted delivery location. For example, the catheter 902 may be disposed in a ventricle or vessel of the brain and, once the balloon 908 is inflated, the microneedles 946 are massaged against the blood-brain barrierAttorney Docket No. 19506.0002WOU1 to create a region of permeability to allow delivery of pharmaceutical treatments and other agents.

[0126] Microneedles 946 can be used without any drug or medicament thereon. It has been observed that the mechanical stimulation provided by microneedles 946 can be sufficient to open the BBB. Accordingly, for some embodiments the microneedles 946 are simple mechanical structures configured to provide this mechanical stimulation.

[0127] In addition to solid microneedles for purely mechanical manipulation, the use of coated microneedles, dissolving microneedles, and hollow microneedles is also contemplated.

[0128] In a coated microneedle embodiment, microneedles 946 can be coated with a substance that is used to open the BBB. The substance can be, for example, a drug or other medicament that is sufficient to open the BBB, such as osmotic agents, including mannitol and the like. These agents, either alone or in combination with the physical manipulation of the BBB described above, can be used to temporarily open the BBB for delivery of desired therapeutics.

[0129] In a dissolving microneedle embodiment, microneedles 946 can be made of a material that will biodegrade upon interaction with the BBB. The degradation of the dissolving microneedles 946 can be caused, in some embodiments, by the application of ultrasound. That is, the balloon 908 may emit or transmit an ultrasound signal (as described above with respect to FIGS. 1-5C) that can cause the dissolution of microneedles 946 that have been inserted into the BBB.

[0130] In a hollow microneedle embodiment, the substance used to open the BBB can be contained inside microneedles 946. Microneedles 946 can inject the substance used to open the BBB in response to being inserted into the BBB, or in response to stimulus such as ultrasound, as described with respect to the dissolving microneedle embodiment.

[0131] Typically the BBB is opened with the intent to provide some material to the other side, such as a medication. Opening the BBB permits material from the blood side (where the catheter 902 is located) into the central nervous system. It should be understood that while microneedles 946 can be used to provide the substance that opens the BBB, they can equally be used to provide the medication or other substance for delivery to the central nervous system. In some embodiments, microneedles 946 can provide both a substance to open the BBB as well as a substance to be delivered to the central nervous system. In other embodiments, the substance that opens the BBB can be routed through the bloodstream, while the microneedles 946 merely open the BBB. In other embodiments, the substance that opens the BBB can be inAttorney Docket No. 19506.0002WOU1 the microneedles 946, while the substance for delivery to the central nervous system is in the bloodstream.

[0132] FIG. 10 is a partial view of a pair of catheters 1002a, 1002b deployed in a vascular system, with a first upstream catheter 1002a delivering microbubbles 1004 and a second downstream catheter 1002b delivering ultrasound 1006. Microbubbles 1004 are released into the vascular system at an upstream 1008 location and travel downstream 1010. Travel T demonstrates microbubbles 1004 flowing downstream. Ultrasound 1006 is emitted by a downstream catheter 1002b. When the microbubbles 1004 reach the location of the ultrasound 1006 emission, the microbubbles circulating in nearby blood vessels to oscillate in response to the pressure waves. This stable cavitation exerts mechanical forces on the endothelial cells of the BBB, temporarily disrupting the tight junctions between the cells of the BBB and increasing its permeability at the targeted site. As a result, drugs or other therapeutic agents that would ordinarily be blocked are able pass into the brain tissue. Importantly, this effect is both localized and transient, allowing the barrier to quickly reseal and preserve its protective function.

[0133] FIG. 10 shows both catheters 1002a and 1002b in close proximity, for ease of illustration. It should be understood that in many embodiments, catheter 1002a and catheter 1002b may be located distant from one another, so long as catheter 1002a is ‘upstream’ of catheter 1002b, in the sense that the microbubbles released by catheter 1002a are still in the bloodstream when it reaches the point where ultrasound is created by the second catheter 1002b, as indicated by the arrows T.

[0134] Catheters 1002a and 1002b are also simplified for purposes of illustration, and do not show the various balloons, cutters, or microneedles described above with respect to FIGS. 1-9. It should be understood that any of the ultrasound generation techniques and structures described in those embodiments could equally be used to create ultrasound in the embodiment shown in FIG. 10.

[0135] Various embodiments are envisioned for the release of the microbubbles. In some embodiments, microbubbles are generated within the catheter itself just prior to release. This may be accomplished by the controlled introduction of gas and a stabilizing liquid, e.g., a lipid or surfactant solution, through microfluidic or flow-focusing mechanisms inside the catheter. These systems allow for real-time production of uniformly sized microbubbles, which can then be released, sometimes immediately, into the bloodstream or ventricular system. In-catheter generation may promote bubble stability and precise control over their physical characteristics at the point of delivery.Attorney Docket No. 19506.0002WOU1

[0136] FIG. 11 is partial view of an example catheter 1102 delivering microbubbles 1104 from an outer sheath or layer 1114. In embodiments, the microbubbles may be pre-formed in suspension or stored in a pressurized reservoir. When catheter 1102 reaches a target site, the outer sheath 1114 retracts or deploys through small openings, allowing microbubbles 1104 to disperse radially into the surrounding fluid. This approach may be particularly advantageous when a more diffuse distribution of microbubbles is desired, such as in the ventricular system, where wide coverage may promote effective ultrasound interaction.

[0137] While FIG. 11 shows an emulsion of microbubbles in the outer sleeve of the catheter 1102, it should be understood that in alternative embodiments there may be a gas provided through a lumen (e.g., via outer sheath 1112) which is then bubbled into the bloodstream at the distal end 1114 thereof. In such embodiments, rather than the flared end shown in FIG. 11, there may be a pinhole aperture or other similar structure that will accomplish the transformation of the gas stream provided into bubbles. In any event, the bubbles are created and travel downstream (as indicated by the arrow T) towards the location where the ultrasound is generated, such as at a balloon 1108 consistent with any of the embodiments described with respect to FIGS. 1-5C.

[0138] FIG. 12 is a partial view of a catheter 1202 delivering microbubbles 1204 from an interior lumen. Microbubbles 1204 are release from apertures 1216. Acoustic emission devices 1214, such as electrodes, may also be positioned within an interior lumen of catheter 1202 with apertures 1216 to allow positioning of the acoustic emission device 1214 for targeted ultrasound. In embodiments, either pre-formed or freshly generated microbubbles are injected directly into the target area using, for example, low-pressure infusion. In examples, this method and similar methods may allow for more directional control and precise timing.

[0139] Notably, in FIG. 12 the microbubbles are not proximate the balloon 1208. As such, ultrasound may be delivered in the manner described with respect to FIG. 5C, for example (in which the ultrasound is emitted from the shaft of the catheter 1202 itself, towards the distal end 1206).

[0140] FIG. 13 is a partial view ofa catheter 1302 with two balloons 1308, 1309 delivering microbubbles 1304 from an interior lumen. Microbubbles 1304 are released from apertures 1316. The catheter 1302 may be used with similar considerations to those discussed with reference to the dual ballon design in FIGS. 5 A and 5B. The use of two balloons provides for contained and therefore more targeted delivery of microbubbles and ultrasound.

[0141] ASPECTSAttorney Docket No. 19506.0002WOU1

[0142] According to a first aspect, an ultrasound-emitting device comprises a catheter extending from a proximal end to a distal end, the catheter defining a plurality of lumens therein, a first balloon arranged at the distal end and a second balloon arranged more proximally along a shaft of the catheter, wherein an interior of the first balloon is fluidically coupled to a first one of the plurality of lumens, and wherein the first balloon is fluidically coupled to the proximal end via the first one of the plurality of lumens to be inflatable by a fluid routed through the first one of the plurality of lumens, and an electrode arranged in a second one of the plurality of lumens, the electrode extending from the proximal end to the distal end and arranged to exert a thermal effect in the fluid at the interior of at least one of the first and second balloons.

[0143] According to a second aspect, the ultrasound-emitting device of the first aspect has an interior of the second balloon fluidically coupled to a second one of the plurality of lumens, and wherein the second balloon is fluidically coupled to the proximal end via the second one of the plurality of lumens to be inflatable by a fluid routed through the second one of the plurality of lumens.

[0144] According to a third aspect, the ultrasound-emitting device of any one of the first or second aspects has the first one of the plurality of lumens the same as the second one of the plurality of lumens.

[0145] According to a fourth aspect, the ultrasound-emitting device of any one of the first through third aspects further comprises a transducer that can emit and / or receive acoustic waves including recording these waves, converting them to an electrical signal, using those signals to create an image, and using that image to direct a decision.

[0146] According to a fifth aspect, the ultrasound-emitting device of the fourth aspect has the transducer arranged in one of the plurality of lumens or integrated into the catheter.

[0147] According to a sixth aspect, the ultrasound-emitting device of any one of the first through fifth aspects has a length of the catheter between the first balloon and the second balloon defining a plurality of holes therein that are usable for drug elution.

[0148] According to a seventh aspect, the ultrasound-emitting device of the sixth aspect has the catheter further comprising a third lumen in communication with the plurality of holes, wherein a medication is delivered to a target region adjacent the length via the third lumen and the plurality of holes.

[0149] According to an eighth aspect, the ultrasound-emitting device of any one of the first through seventh aspects further comprises a guidewire arranged through a fourth lumen of the plurality of lumens and extending from the proximal end and past the distal end.Attorney Docket No. 19506.0002WOU1

[0150] According to a ninth aspect, the ultrasound-emitting device of any one of the first through eighth aspects has the first balloon and the second balloon each made of a polymer.

[0151] According to a tenth aspect, the ultrasound-emitting device of any one of the first through ninth aspects further comprises a tie layer disposed on a surface of at least one of the first balloon and the second balloon, and a pharmaceutical coating coupled to the balloon by the tie layer, wherein the tie layer comprises a material that is susceptible to disruption by ultrasound.

[0152] According to an eleventh aspect, the ultrasound-emitting device of any one of the first through tenth aspects further comprises a fiber optic element extending from the proximal end to the distal end, wherein the fiber optic element is arranged to deliver light from the proximal end to a photoacoustic component at the distal end to produce a photoacoustic effect.

[0153] According to a twelfth aspect, the ultrasound-emitting device of any one of the first through eleventh aspects further comprises a cutting element arranged on an external surface of the balloon.

[0154] According to a thirteenth aspect, the ultrasound-emitting device of the twelfth aspect has the cutting element as at least two cutting elements.

[0155] According to a fourteenth aspect, the ultrasound-emitting device of any one of the twelfth or thirteenth aspects has the at least two cutting elements arranged symmetrically around a circumference of the balloon.

[0156] According to a fifteenth aspect, the ultrasound-emitting device of any one of the twelfth through fourteenth aspects has the at least two cutting elements arranged symmetrically along a length of the balloon.

[0157] According to a sixteenth aspect, the ultrasound-emitting device of any one of the twelfth or thirteenth aspects has the at least two cutting elements arranged asymmetrically around a circumference of the balloon.

[0158] According to a seventeenth aspect, the ultrasound-emitting device of any one of the twelfth, thirteenth, or sixteenth aspects has the at least two cutting elements arranged asymmetrically along a length of the balloon.

[0159] According to an eighteenth aspect, a method for generating ultrasound by an ultrasound-emitting device comprises positioning an electrode in a first lumen of a catheter such that the electrode extends from a proximal end of the catheter to a distal end of the catheter, inflating a first balloon of the catheter by delivering a fluid to the first balloon via a second lumen of the catheter, inflating a second balloon of the catheter by delivering the fluid to the second balloon via a third lumen of the catheter, delivering electrical pulses to the fluid in theAttorney Docket No. 19506.0002WOU1 first balloon via an electrical cable in communication with the electrode arranged within the first balloon, and directing ultrasonic waves generated in response to the electrical pulses to a target area to dislodge an adherent mass from the tissue.

[0160] According to a nineteenth aspect, the method of the eighteenth aspect has at least one of the first balloon, a balloon shaft and / or the fluid comprising a material that can be used to generate an ultrasonic signal.

[0161] According to a twentieth aspect, the method of any one of the eighteenth or nineteenth aspects has the first balloon polymer based.

[0162] According to a twenty-first aspect, the method of any one of the eighteenth through twentieth aspects has the target area comprising calcium deposits for calcium debulking.

[0163] According to a twenty-second aspect, the method of any one of the eighteenth through twentieth aspects has the target area comprising an atherosclerotic plaque or other blockage for treatment of arterial occlusion.

[0164] According to a twenty -third aspect, the method of any one of the twenty-first or twenty-second aspects further comprises arranging one of the first balloon and the second balloon such that a cutting element on an external surface of the balloon is positioned against at least one of the calcium deposits, the atherosclerotic plaque, or the other blockage.

[0165] According to a twenty-fourth aspect, the method of any one of the eighteenth through twenty-third aspects further comprises disrupting a tie layer that couples a pharmaceutical coating to the first balloon with the ultrasonic waves.

[0166] According to a twenty -fifth aspect, the method of any one of the eighteenth through twenty-fourth aspects further comprises routing the distal end of the catheter to a target location along a guidewire prior to inflating the first balloon.

[0167] According to a twenty-sixth aspect, the method of any one of the eighteenth through twenty -fifth aspects further comprises inflating the second balloon located between the first balloon and the proximal end, and powering an electrode from the proximal end of the catheter with the electrical pulses, such that the electrical pulses travel to a second electrode located within the second balloon.

[0168] According to a twenty-seventh aspect, the method of the twenty-sixth aspect further comprises aspirating a region arranged proximal to the first balloon.

[0169] According to a twenty-eighth aspect, the method of the twenty-seventh aspect further comprises creating images of a dislodged material to confirm aspiration.Attorney Docket No. 19506.0002WOU1

[0170] According to a twenty-ninth aspect, the method of any one of the twenty-seventh or twenty-eighth aspects has the region proximal to the first balloon arranged between the first balloon and the second balloon and adjacent the catheter.

[0171] According to a thirtieth aspect, the method of any one of the eighteenth through twenty-ninth aspects further comprises denervating an anatomical structure positioned in a region arranged adjacent the first balloon or the second balloon.

[0172] According to a thirty-first aspect, the method of any one of the eighteenth through thirtieth aspects further comprises routing a light through a fiber optic element that extends from the proximal end to the distal end, the fiber optic element arranged to deliver the light to a photoacoustic component at the distal end to produce a photoacoustic response for imaging.

[0173] According to a thirty-second aspect, the method of any one of the eighteenth through thirty-first aspects further comprises recording a location and a magnitude of an acoustic pressure wave reflecting or echoing from an adjacent structure at a transducer.

[0174] According to a thirty-third aspect, the method of the thirty-second aspect further comprises positioning the catheter based upon the location and the magnitude of the acoustic pressure wave recorded by the transducer.

[0175] According to a thirty-fourth aspect, the method of any one of the thirty-second or thirty-third aspects further comprises creating pulse / echo images of a plaque, blockage, calcium deposits, and the like by the transducer to evaluate an extent of therapy.

[0176] According to a thirty-fifth aspect, the method of any one of the thirty-second through thirty-fourth aspects further comprises creating images of a dislodged material to confirm aspiration.

[0177] According to a thirty-sixth aspect, a system for generating targeted ultrasonic waves for treatment of a tissue comprises a catheter extending from a proximal end to a distal end, the catheter defining a plurality of lumens therein, a balloon arranged at the distal end, wherein an interior of the balloon is fluidically coupled to a first one of the plurality of lumens, a means of delivering electrical pulses arranged within the balloon, and a power supply in connection with the means of delivering electrical pulses via a second one of the plurality of lumens triggering generation of ultrasonic waves in response to the electrical pulses.

[0178] According to a thirty-seventh aspect, the system of the thirty-sixth aspect further comprises a guidewire arranged through a third one of the plurality of lumens, extending through the catheter from the proximal end and past the distal end thereof.Attorney Docket No. 19506.0002WOU1

[0179] According to a thirty-eighth aspect, the system of any one of the thirty-sixth or thirty-seventh aspects has the means of delivering electrical pulses comprising one or more electrodes.

[0180] According to a thirty -ninth aspect, the system of any one of the thirty-sixth through thirty-eighth aspects has the balloon comprising at least a first balloon and a second balloon.

[0181] According to a fortieth aspect, the system of the thirty-ninth aspect has the first balloon and the second balloon spaced apart such that a target tissue is arranged between the first and the second balloons.

[0182] According to a forty-first aspect, the system of any one of the thirty -ninth or fortieth aspects has the ultrasonic waves directed at the target tissue by the first and second balloons.

[0183] According to a forty-second aspect, the system of any one of the thirty-ninth through forty-first aspects has a plurality of holes arranged between the first balloon and the second balloon.

[0184] According to a forty-third aspect, the system of the forty-second aspect has the catheter further comprising a fourth lumen in communication with the plurality of holes, wherein a medication is delivered to the target tissue via the fourth lumen and the plurality of holes.

[0185] According to a forty -fourth aspect, the system of any one of the thirty-sixth through forty -third aspects has the balloon made of a polymer.

[0186] According to a forty-fifth aspect, the system of any one of the thirty-sixth through forty-fourth aspects further comprises a fiber optic element extending from the proximal end to the distal end, wherein the fiber optic element is arranged to deliver light from the proximal end to a photoacoustic component at the distal end to produce a photoacoustic effect usable for imaging.

[0187] According to a forty-sixth aspect, the system of the forty-fifth aspect has the photoacoustic component as one of the balloon and the catheter.

[0188] According to a forty-seventh aspect, the system of any one of the thirty-sixth through forty-sixth aspects further comprises a tie layer disposed on a surface of the balloon and a coating coupled to the balloon by the tie layer, wherein the tie layer comprises a material that is susceptible to disruption by ultrasound.

[0189] According to a forty-eighth aspect, the system of any one of the thirty-sixth through forty-seventh aspects further comprises a cutting element arranged on an external surface of the balloon.Attorney Docket No. 19506.0002WOU1

[0190] According to a forty-ninth aspect, the system of the forty-eighth aspect has the cutting element as at least two cutting elements.

[0191] According to a fiftieth aspect, the system of any one of the forty-eighth or fortyninth aspects has the at least two cutting elements arranged symmetrically around at least one of a circumference of the balloon and along a length of the balloon.

[0192] According to a fifty-first aspect, the system of any one of the forty-eighth through fiftieth aspects has the at least two cutting elements arranged asymmetrically around at least one of a circumference of the balloon and along a length of the balloon.

[0193] According to a fifty-second aspect, a device for generating targeted ultrasonic waves for treatment of a tissue comprises a catheter extending from a proximal end to a distal end, the catheter defining a plurality of lumens therein, a balloon arranged at the distal end, wherein an interior of the balloon is fluidically coupled to a first one of the plurality of lumens such that the balloon can be inflated by a fluid routed through the first one of the plurality of lumens, and an electrode arranged in a second one of the plurality of lumens, the electrode extending from the proximal end to the distal end and arranged to exert a thermal effect in the fluid at the interior of the balloon.

[0194] According to a fifty-third aspect, the device of the fifty-second aspect has a length of the catheter more proximate than the balloon defining a plurality of holes therein that are usable for drug elution.

[0195] According to a fifty-fourth aspect, the device of the fifty-third aspect has the catheter further comprising a third lumen in communication with the plurality of holes, wherein a medication is delivered to a target region adjacent the length via the third lumen and the plurality of holes.

[0196] According to a fifty-fifth aspect, the device of any one of the fifty-second through fifty-fourth aspects further comprises a guidewire arranged through a fourth lumen of the plurality of lumens and extending from the proximal end and past the distal end.

[0197] According to a fifty-sixth aspect, the device of any one of the fifty-second through fifty-fifth aspects further comprises a tie layer disposed on a surface of the first balloon and a pharmaceutical coating coupled to the first balloon via the tie layer, wherein the tie layer comprises a material that is susceptible to disruption by ultrasound.

[0198] According to a fifty-seventh aspect, the device of any one of the fifty-second through fifty-sixth aspects further comprises a fiber optic element extending from the proximal end to the distal end, wherein the fiber optic element is arranged to deliver light from the proximal end to a photoacoustic component at the distal end to produce a photoacoustic effect.Attorney Docket No. 19506.0002WOU1

[0199] According to a fifty-eighth aspect, the device of any one of the fifty-second through fifty-seventh aspects further comprises cutting elements arranged on an external surface of the balloon.

[0200] According to a fifty-ninth aspect, the device of the fifty-eighth aspect has the cutting elements arranged symmetrically around at least one of a circumference of the balloon and along a length of the balloon.

[0201] According to a sixtieth aspect, a method of delivering an agent through the bloodbrain barrier of a patient comprises positioning a catheter within a vessel in the patient's brain, the catheter configured for local delivery of both ultrasonic waves and the agent, generating the ultrasonic waves from the catheter, and releasing the agent while the ultrasonic waves are being generated.

[0202] According to a sixty-first aspect, the method of the sixtieth aspect has the agent as at least one of a pharmaceutical agent and microbubbles.

[0203] According to a sixty-second aspect, the method of any one of the sixtieth or sixty- first aspects has the agent released by the ultrasonic waves wherein the agent is affixed to the catheter by a tie-layer and the tie-layer is configured to release in response to the ultrasonic waves.

[0204] The various aspects described herein can be combined and interchanged with one another to create additional embodiments not explicitly described. The features, elements, and characteristics of any particular aspect are not limited to that aspect alone and can be incorporated into other aspects where technically feasible and beneficial. For example, the balloon configurations, electrode arrangements, cutting elements, microneedles, drug delivery systems, imaging capabilities, and microbubble delivery mechanisms described in different aspects can be combined in various permutations to optimize performance for specific medical applications. The modular nature of these components allows for customization based on the particular therapeutic or diagnostic requirements of a given procedure.

[0205] Having described the preferred aspects and implementations of the present disclosure, modifications and equivalents of the disclosed concepts may readily occur to one skilled in the art. However, it is intended that such modifications and equivalents be included within the scope of the claims which are appended hereto.

Claims

Attorney Docket No. 19506.0002WOU1What is claimed is:

1. An ultrasound-emitting device comprising: a catheter extending from a proximal end to a distal end, the catheter defining a plurality of lumens therein; a first balloon arranged at the distal end and a second balloon arranged more proximally along a shaft of the catheter, wherein an interior of the first balloon is fluidically coupled to a first one of the plurality of lumens, and wherein the first balloon is fluidically coupled to the proximal end via the first one of the plurality of lumens to be inflatable by a fluid routed through the first one of the plurality of lumens; and an electrode arranged in a second one of the plurality of lumens, the electrode extending from the proximal end to the distal end and arranged to exert a thermal effect in the fluid at the interior of at least one of the first and second balloons.

2. The ultrasound-emitting device of claim 1, wherein an interior of the second balloon is fluidically coupled to a second one of the plurality of lumens, and wherein the second balloon is fluidically coupled to the proximal end via the second one of the plurality of lumens to be inflatable by a fluid routed through the second one of the plurality of lumens.

3. The ultrasound-emitting device of claim 1 or 2, wherein the first one of the plurality of lumens is the same as the second one of the plurality of lumens.

4. The ultrasound-emitting device of any of claims 1-3, further comprising a transducer that can emit and / or receive acoustic waves including recording these waves, converting them to an electrical signal, using those signals to create an image, and using that image to direct a decision.

5. The ultrasound-emitting device of claim 4 wherein the transducer is arranged in one of the plurality of lumens or integrated into the catheter.Attorney Docket No. 19506.0002WOU16. The ultrasound-emitting device of any of claims 1-5, wherein a length of the catheter between the first balloon and the second balloon defines a plurality of holes therein that are usable for drug elution.

7. The ultrasound-emitting device of claim 6, wherein the catheter further comprises a third lumen in communication with the plurality of holes, wherein a medication is delivered to a target region adjacent the length via the third lumen and the plurality of holes.

8. The ultrasound-emitting device of any of claims 1-7, further comprising a guidewire arranged through a fourth lumen of the plurality of lumens and extending from the proximal end and past the distal end.

9. The ultrasound-emitting device of any of claims 1-8, wherein the first balloon and the second balloon are each made of a polymer.

10. The ultrasound-emitting device of any of claims 1-9, further comprising: a tie layer disposed on a surface of at least one of the first balloon and the second balloon; and a pharmaceutical coating coupled to the balloon by the tie layer, wherein the tie layer comprises a material that is susceptible to disruption by ultrasound.

11. The ultrasound-emitting device of any of claims 1-10, further comprising a fiber optic element extending from the proximal end to the distal end, wherein the fiber optic element is arranged to deliver light from the proximal end to a photoacoustic component at the distal end to produce a photoacoustic effect.

12. The ultrasound-emitting device of any one of claims 1-11, further comprising a cutting element arranged on an external surface of the balloon.

13. The ultrasound-emitting device of claim 12, wherein the cutting element is at least two cutting elements.Attorney Docket No. 19506.0002WOU114. The ultrasound-emitting device of claim 12 or 13, wherein the at least two cutting elements are arranged symmetrically around a circumference of the balloon.

15. The ultrasound-emitting device of any of claims 12-14, wherein the at least two cutting elements are arranged symmetrically along a length of the balloon.

16. The ultrasound-emitting device of claim 12 or claim 13, wherein the at least two cutting elements are arranged asymmetrically around a circumference of the balloon.

17. The ultrasound-emitting device of claim 12, 13, or 16, wherein the at least two cutting elements are arranged asymmetrically along a length of the balloon.

18. A method for generating ultrasound by an ultrasound-emitting device, the method comprising: positioning an electrode in a first lumen of a catheter such that the electrode extends from a proximal end of the catheter to a distal end of the catheter; inflating a first balloon of the catheter by delivering a fluid to the first balloon via a second lumen of the catheter; inflating a second balloon of the catheter by delivering the fluid to the second balloon via a third lumen of the catheter; delivering electrical pulses to the fluid in the first balloon via an electrical cable in communication with the electrode arranged within the first balloon; and directing ultrasonic waves generated in response to the electrical pulses to a target area to dislodge an adherent mass from the tissue.

19. The method of claim 18, wherein at least one of the first balloon, a balloon shaft and / or the fluid comprises a material that can be used to generate an ultrasonic signal.

20. The method of claim 18 or claim 19, wherein the first balloon is polymer based.Attorney Docket No. 19506.0002WOU121. The method of any of claims 18-20, wherein the target area comprises calcium deposits for calcium debulking.

22. The method of any of claims 18-20, wherein the target area comprises an atherosclerotic plaque or other blockage for treatment of arterial occlusion.

23. The method of claim 21 or 22, further comprising arranging one of the first balloon and the second balloon such that a cutting element on an external surface of the balloon is positioned against at least one of the calcium deposits, the atherosclerotic plaque, or the other blockage.

24. The method of any of claims 18-23, further comprising disrupting a tie layer that couples a pharmaceutical coating to the first balloon with the ultrasonic waves.

25. The method of any of claims 18-24, further comprising routing the distal end of the catheter to a target location along a guidewire prior to inflating the first balloon.

26. The method of any of claims 18-25, further comprising: inflating the second balloon located between the first balloon and the proximal end; and powering an electrode from the proximal end of the catheter with the electrical pulses, such that the electrical pulses travel to a second electrode located within the second balloon.

27. The method of claim 26, further comprising aspirating a region arranged proximal to the first balloon.

28. The method of claim 27, further comprising creating images of a dislodged material to confirm aspiration.

29. The method of claim 27 or claim 28, wherein the region proximal to the first balloon is arranged between the first balloon and the second balloon and adjacent the catheter.Attorney Docket No. 19506.0002WOU130. The method of any of claims 18-29, further comprising denervating an anatomical structure positioned in a region arranged adjacent the first balloon or the second balloon.

31. The method of any of claims 18-30, further comprising routing a light through a fiber optic element that extends from the proximal end to the distal end, the fiber optic element arranged to deliver the light to a photoacoustic component at the distal end to produce a photoacoustic response for imaging.

32. The method of any of claims 18-31, further comprising recording a location and a magnitude of an acoustic pressure wave reflecting or echoing from an adjacent structure at a transducer.

33. The method of claim 32, positioning the catheter based upon the location and the magnitude of the acoustic pressure wave recorded by the transducer.

34. The method of claim 32 or claim 33, further comprising creating pulse / echo images of a plaque, blockage, calcium deposits, and the like by the transducer to evaluate an extent of therapy.

35. The method of any of claims 32-34, further comprising creating images of a dislodged material to confirm aspiration.

36. A system for generating targeted ultrasonic waves for treatment of a tissue, the system comprising: a catheter extending from a proximal end to a distal end, the catheter defining a plurality of lumens therein; a balloon arranged at the distal end, wherein an interior of the balloon is fluidically coupled to a first one of the plurality of lumens; a means of delivering electrical pulses arranged within the balloon; and a power supply in connection with the means of delivering electrical pulses via a second one of the plurality of lumens triggering generation of ultrasonic waves in response to the electrical pulses.Attorney Docket No. 19506.0002WOU137. The system of claim 36, further comprising a guidewire arranged through a third one of the plurality of lumens, extending through the catheter from the proximal end and past the distal end thereof.

38. The system of claim 36 or claim 37, wherein the means of delivering electrical pulses comprises one or more electrodes.

39. The system of any of claims 36-38, wherein the balloon comprises at least a first balloon and a second balloon.

40. The system of claim 39, wherein the first balloon and the second balloon are spaced apart such that a target tissue is arranged between the first and the second balloons.

41. The system of claim 39 of 40, wherein the ultrasonic waves are directed at the target tissue by the first and second balloons.

42. The system of any of claims 39-41, wherein a plurality of holes are arranged between the first balloon and the second balloon.

43. The system of claim 42, wherein the catheter further comprises a fourth lumen in communication with the plurality of holes, wherein a medication is delivered to the target tissue via the fourth lumen and the plurality of holes.

44. The system of any of claims 36-43, wherein the balloon is made of a polymer.

45. The system of any of claims 36-44, further comprising a fiber optic element extending from the proximal end to the distal end, wherein the fiber optic element is arranged to deliver light from the proximal end to a photoacoustic component at the distal end to produce a photoacoustic effect usable for imaging.Attorney Docket No. 19506.0002WOU146. The system of claim 45, wherein the photoacoustic component is one of the balloon and the catheter.

47. The system of any of claims 36-46, further comprising: a tie layer disposed on a surface of the balloon; and a coating coupled to the balloon by the tie layer, wherein the tie layer comprises a material that is susceptible to disruption by ultrasound.

48. The system of any one of claims 36-47, further comprising a cutting element arranged on an external surface of the balloon.

49. The system of claim 48, wherein the cutting element is at least two cutting elements.

50. The system of claim 48 or claim 49, wherein the at least two cutting elements are arranged symmetrically around at least one of a circumference of the balloon and along a length of the balloon.

51. The system of any of claims 48-50, wherein the at least two cutting elements are arranged asymmetrically around at least one of a circumference of the balloon and along a length of the balloon.

52. A device for generating targeted ultrasonic waves for treatment of a tissue, the device comprising: a catheter extending from a proximal end to a distal end, the catheter defining a plurality of lumens therein; a balloon arranged at the distal end, wherein an interior of the balloon is fluidically coupled to a first one of the plurality of lumens such that the balloon can be inflated by a fluid routed through the first one of the plurality of lumens; and an electrode arranged in a second one of the plurality of lumens, the electrode extending from the proximal end to the distal end and arranged to exert a thermal effect in the fluid at the interior of the balloon.Attorney Docket No. 19506.0002WOU153. The device of claim 52, wherein a length of the catheter more proximate than the balloon defines a plurality of holes therein that are usable for drug elution.

54. The device of claim 53, wherein the catheter further comprises a third lumen in communication with the plurality of holes, wherein a medication is delivered to a target region adjacent the length via the third lumen and the plurality of holes.

55. The device of any of claims 52-54, further comprising a guidewire arranged through a fourth lumen of the plurality of lumens and extending from the proximal end and past the distal end.

56. The device of any of claims 52-55, further comprising: a tie layer disposed on a surface of the first balloon; and a pharmaceutical coating coupled to the first balloon via the tie layer, wherein the tie layer comprises a material that is susceptible to disruption by ultrasound.

57. The device of any of claims 52-56, further comprising a fiber optic element extending from the proximal end to the distal end, wherein the fiber optic element is arranged to deliver light from the proximal end to a photoacoustic component at the distal end to produce a photoacoustic effect.

58. The device of any of claims 52-57, further comprising cutting elements arranged on an external surface of the balloon.

59. The device of claim 58, wherein the cutting elements are arranged symmetrically around at least one of a circumference of the balloon and along a length of the balloon.

60. A method of delivering an agent through the blood-brain barrier of a patient, the method comprising: positioning a catheter within a vessel in the patient’s brain, the catheter configured for local delivery of both ultrasonic waves and the agent;Attorney Docket No. 19506.0002WOU1 generating the ultrasonic waves from the catheter; and releasing the agent while the ultrasonic waves are being generated.

61. The method of claim 60, wherein the agent is at least one of a pharmaceutical agent and microbubbles.

62. The method of claim 60 or claim 61, wherein the agent is released by the ultrasonic waves wherein the agent is affixed to the catheter by a tie-layer and the tie-layer is configured to release in response to the ultrasonic waves.

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