Acoustic emission with effusion

Abstract

A combination of ultrasound and effused materials can be used to provide treatment for various conditions. Effused material can interact with ultrasound signal in a complementary fashion, either together or in sequence. A single catheter can be used to provide both treatment modes, as well as complementary treatments such as aspiration.

Description

Attorney Docket No. 19506.0003WOU1ACOUSTIC EMISSION WITH EFFUSIONCROSS-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, sonic treatments are 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 a photoresponsive material that generates ultrasound pulses. Alternatively or additionally, an electrode can be used that causes a spark or cavitation in a carrier fluid around that electrode.SUMMARY

[0005] According to a first aspect, an ultrasound-emitting device is disclosed that includes a catheter extending from a proximal end to a distal end. The catheter defines several lumens therein. A balloon is arranged at the distal end of the catheter, and an interior of the balloon is fluidically coupled to a first one of the lumens. The balloon is inflated by a fluid routed through the connected lumen. An elution material is also arranged at the distal end. An actuation element is arranged in a second one of the lumens. The actuation element extends from the proximal end to the distal end and can generate an ultrasonic signal at the distal end.Attorney Docket No. 19506.0003WOU1

[0006] Optionally, the device can also include a guidewire arranged through another lumen extending from the proximal end and past the distal end. The actuation element can be an optical fiber and the fluid can be a photoresponsive fluid. The elution material can be a pharmaceutical coating arranged on the balloon. The actuation element can be an optical fiber and the balloon can be made of a photoresponsive material. The actuation element can be an optical fiber, and an external shaft of the catheter can be made of a photoresponsive material. The device can also include a tie layer arranged in between the elution material and the balloon, and the tie layer can be a material that is susceptible to disruption by ultrasound. The actuation element can be an electrode. A second balloon can be arranged between the balloon and the proximal end, and an interior of the second balloon can be fluidically coupled to one of the lumens so that the second balloon can be inflated by the fluid routed through that lumen. A second actuation element can be used to generate an ultrasonic signal at the distal end. The device can also include apertures arranged on an outer surface of the catheter between the first balloon and the second balloon. These apertures can be in communication with another one of the lumens. The device can also include an aspiration sleeve circumscribing the catheter. A set of effusion holes can be defined along a length of the catheter between the balloon and the aspiration sleeve.

[0007] According to another aspect, a method for generating ultrasound by an ultrasoundemitting device is disclosed. The method can include positioning an actuation element in a lumen of a catheter such that the actuation element extends from a proximal end of the catheter to a distal and of the catheter. The method can also include inflating a balloon at a distal end of the catheter with a fluid, and eluting an elution material at the distal end. The method includes activating the actuation element at the proximal end of the catheter to generate an ultrasonic acoustic signal at the distal end of the catheter.

[0008] Optionally, the actuation element can be an optical fiber and wherein at least one of the balloon, balloon shaft and / or the fluid comprises a photoresponsive material. The actuation element can be an electrode. The method can include applying the ultrasonic emissions to calcium deposits for calcium debulking. The method can include applying the ultrasonic emissions to an atherosclerotic plaque or other blockage for treatment of arterial occlusion. The elution material can be a coating on the balloon, and eluting the elution material can mean disrupting a tie layer that couples the elution material 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. A set of effusion holes can be defined along a length of the catheter between the balloon and an aspiration sleeve, and eluting theAttorney Docket No. 19506.0003WOU1 elution material can include routing a liquid elution material through the effusion holes. The balloon can be polymer based. The method can include inflating a second balloon located between the balloon and the proximal end, and actuating a second actuation element at the proximal end of the catheter to generate a second ultrasonic acoustic signal at the distal end of the catheter. Eluting the elution material can include routing a liquid elution material through a plurality of effusion holes 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.

[0009] According to a third aspect, an ultrasound-emitting device is disclosed. The device includes a catheter extending from a proximal end to a distal end. The catheter can include any number of lumens therein. A balloon can be arranged at the distal end of the catheter, and an interior of the balloon can be fluidically coupled to one of the lumens. An elution material can be arranged at the distal end of the catheter. An actuation means configured to produce an ultrasound signal is also arranged at the distal end.

[0010] Optionally, the device can include a guidewire arranged through one of the lumens, extending through the catheter from the proximal end and past the distal end thereof. The device can also include a photoresponsive fluid arranged in the balloon and one of the lumens. The balloon can be made of a polymer. The actuation element can be an electrode. The balloon can be made of a photoresponsive material. The device can also include a tie layer disposed between a surface of the balloon and the elution material. The tie layer can be a material that is susceptible to disruption by ultrasound. The device can also include a second balloon arranged between the first balloon and the proximal end, wherein an interior of the second balloon is fluidically coupled to the first one of the plurality of lumens and the second balloon is inflated by the fluid routed through the first one of the plurality of lumens. The device can also include an aspiration sleeve circumscribing the catheter, and effusion holes can be defined along a length of the catheter between the balloon and the aspiration sleeve.

[0011] 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 following detailed description are exemplary and explanatory only and are not restrictive of the broad inventive concepts upon which the embodiments disclosed herein are based.Attorney Docket No. 19506.0003WOU1BRIEF DESCRIPTION OF THE DRAWINGS

[0012] 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:

[0013] FIG. l is a system for catheter-based ultrasonic therapy delivery.

[0014] FIGS. 2A and 2B are cross-sectional views of the catheter of FIG. 1 across line 2 — 2 thereof, according to two different embodiments.

[0015] FIGS. 3A and 3B are partial views of catheters usable in the system of FIG. 1, depicting a distal end thereof, in a photoacoustic ultrasound emission scheme and an electrical ultrasound emission scheme, respectively.

[0016] FIGS. 4A, 4B, and 4C are partial views of a catheter usable in the system of FIG.1 and 3 A, depicting a distal end thereof, the catheter system having a coating for elution.

[0017] FIG. 4D and 4E are partial views of a catheter usable in the system of FIG. 1 and 3B, depicting a distal end thereof, the catheter system having a coating for elution.

[0018] FIG. 5 is a partial view of a catheter system that includes a multi-balloon catheter with elution holes.

[0019] FIG. 6A is a partial view of a catheter system usable in the system of FIGS. 1, 3A, and 4A-4C depicting a distal end thereof, the catheter system incorporating an aspiration catheter.

[0020] FIG. 6B is a partial view of a catheter system usable in the systems of FIGS. 1, 3B, and 4D-4E depicting a distal end thereof, the catheter system incorporating an aspiration catheter.

[0021] FIG. 7 is a flowchart of a method for providing sonic therapy using a catheter of any of FIGS. 1-6.

[0022] 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.

[0023] FIG. 9 is a partial view of a catheter with a microneedle-covered balloon.

[0024] 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.

[0025] FIG. 11 is partial view of a catheter deployed in a vascular system and delivering microbubbles from an outer layer.Attorney Docket No. 19506.0003WOU1

[0026] FIG. 12 is a partial view of a catheter deployed in a vascular system and delivering microbubbles from an interior lumen.

[0027] FIG. 13 is a partial view of a catheter with two balloons delivery microbubbles from an interior lumen.DETAILED DESCRIPTION

[0028] 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.

[0029] Throughout this application, therapies are described that rely upon delivery of sonic signal 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.

[0030] 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.

[0031] 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 and techniques described herein could be used in several cases including chronic total occlusion. Similarly, calcium debulking or removal of other unwanted substances within the vasculatureAttorney Docket No. 19506.0003WOU1 can be accomplished, or similarly differential acoustic absorption characteristics can be used to ablate clots or similar structures.

[0032] 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.

[0033] 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.

[0034] 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.

[0035] 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 is reduced. Similarly, ultrasound can be used to monitor the extent of drug layer that has been disrupted or released from the device.

[0036] 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 size 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,Attorney Docket No. 19506.0003WOU1 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).

[0037] 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.

[0038] 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.

[0039] 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 a photoacoustic effect, and the transducer can receive information for use in imaging or routing based on reflections from the photoacoustic emissions described above that are 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 electricalAttorney Docket No. 19506.0003WOU1 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 transducers can monitor drug release, quantitate photoacoustic 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.

[0040] The photoacoustic effect is a phenomenon in which light is absorbed by a material at specific locations therein. This absorption leads to localized heating, causing a rapid increase in temperature in these regions. This temperature increase is spatially confined to the site of the absorption however because the optical pulse width is shorter than the thermal propagation time and acoustic propagation time. 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 light absorption to create a sound wave. The photoacoustic emission can have a different frequency, intensity, and wavelength response based on the material used, the duration of irradiation, and the solvent / other matrix materials.

[0041] In some treatments, it is desirable to deliver a medication or treatment directly to the vasculature or other part of the anatomy that is adjacent the catheter. As described with respect to several of the drawings herein, effusion of such medications or other substances can be provided in several ways. As used throughout this application, the term “effusion” is used to refer to the delivery of such materials. Effusion can be either a liquid effusion such as liquid emanating from the catheter, or in some circumstances effusion can be delivery of a solid material, such as a coating on the catheter or on a balloon. The solid material can be disrupted to be delivered into the body or the bloodstream, and in some cases can be biocompatible and dissolvable upon delivery.

[0042] Effusion can be combined with ultrasound delivery in a mutually beneficial or reinforcing manner. For example, ultrasound can be used to promote effusion, and the effused material can be used to better provide localized ultrasound treatments, as described in more detail below.Attorney Docket No. 19506.0003WOU1

[0043] In some embodiments described herein, ultrasound is provided using an electrically-powered electrode inside a balloon, which generates cavitation and corresponding acoustic waves. In other embodiments, an optically-driven system can be used to deliver ultrasonic therapy by delivering optical signal to a photoresponsive material at the distal end of the catheter (e.g., the balloon, the liquid in the balloon, or another part of the catheter itself). Optically-driven ultrasound delivery enables the use of catheters having smaller diameter, because the relatively bulky electrode need not be positioned therein. Furthermore, ultrasound can be delivered for a much larger number of pulses, compared to electrodes that rely on cavitation or sparking that results in degradation or ablation of the electrode materials.

[0044] The photoacoustic effect is a phenomenon in which light is absorbed by a material at specific locations therein. This absorption leads to localized heating, causing a rapid increase in temperature in these regions. 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 light absorption to create a sound wave. The photoacoustic emission can have a different frequency, intensity, and wavelength response based on the material used.

[0045] The frequency of that emission is a property of the material and, in some circumstances, the light pulse duration. Typically, each pulse creates a damped oscillation of acoustic waves. See Gao et al, “Photoacoustic elastic oscillation and characterization,” Opt. Express 23, 20617-20628 (2015), though additional light pulses onto the material can be used to create additional bursts of acoustic energy.

[0046] Light signal can be routed to the balloon from the opposite end of the catheter by routing the light guide through a lumen of the catheter. Each pulse of light can be used to generate a burst of photoacoustic emissions from the material that is illuminated.

[0047] 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. 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.Attorney Docket No. 19506.0003WOU1

[0048] No matter whether using electrical or acoustic actuation, a balloon or other catheter structure is provided that delivers the ultrasound, located at a distal end of a catheter using the photoacoustic effect or cavitation from electrical sparking.

[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 with the necessity for systemic delivery of the agent. 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. Actuation 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 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 actuation signal and fluid from actuation 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. Catheter 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 102Attorney Docket No. 19506.0003WOU1 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 FIG. 5). Distal end 106 can also include various ports or aspiration features (as described with respect to FIGS. 5, 6A, and 6B).

[0055] Balloon 108 is an expandable element located at the distal end 106. Balloon 108 can receive actuation energy (e.g., light or electrical power) delivered through catheter 102 from actuation 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 can sit substantially flush with the exterior of the remainder of catheter 102.

[0056] Actuation source 112 can be either a light source or an electrical source, depending on the actuation mechanism of the overall system 100. When providing light, actuation source 112 can include any of a variety of light sources, such as a laser, a diode, or a heat-based illumination source like a globar. In many embodiments, the light provided by illumination source 112 is modulated. In such embodiments, either the source itself can be turned on and off to modulate the light signal, or a modulator can be used in combination with a light source to provide the desired timing of the light. For example, a chopper or other obstruction can be used to modulate light produced by a constant illumination source used as actuation source 112 prior to its introduction to the optical fibers described herein and ultimate delivery to the distal end of the catheter 102 or balloon 108. When actuation signal provided by actuation source 112 is electrical, actuation source 112 can be a voltage supply that is similarly modulated or operable to provide pulses of signal of desired intensity and timing or frequency.

[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.

[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, third lumen 220, and fourth lumen 222. InAttorney Docket No. 19506.0003WOU1 embodiments, each of first lumen 216, second lumen 218, third lumen 220, and fourth lumen 222 can provide passage for an associated apparatus (e.g., guidewires, fibers, transducers, 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 fiber optics to deliver illumination from a source, such as from actuation source 112, to the distal end of the catheter 102. Alternatively, second lumen 218 can provide passage for an electrically conductive element to provide electrical signal from actuation source 112. 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. Fourth lumen 222, located in the center, can provide access for a guidewire. Although the example catheter 102 is shown with four lumens, 216, 218, 220, and 222, 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, three, five, six, etc. lumens to provide for delivery of various components and compounds. In embodiments, a single lumen can be used for multiple functionalities (e.g., both providing fluid and a fiber) or there may be multiple lumens associated with any particular function (e.g., two lumens each dedicated to inflation fluid for the multi-balloon embodiment shown in FIG. 5).

[0059] The lumens (216, 218, 220, 222) shown in FIG. 2 A have roughly equal 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 in the central lumen 222 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 216, 218, 220, and 222 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. The same reference numbers are used to refer to the lumens even though they are oriented differently, in a circumscribed configuration. It should be understood that any number of configurations and orientations for the lumens are usable in different instantiations.Attorney Docket No. 19506.0003WOU1

[0061] FIGS. 3 A and 3B are partial views of two versions of the catheter 302 usable in the system of FIG. 1, and more specifically depicting a distal end 306 thereof. In both versions, balloon 308 is arranged at the distal end 306 of the catheter 302, with some additional length of catheter 302 extending past balloon 308 where, in examples, a guidewire may emerge from the guidewire aperture 326 and provide steering of catheter 302. Figure 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 325 itself may contain driving shafts, distal markers, guide wires, mechanical rotation, or phased arrays. Although only one transducer 325 is shown in FIG. 3, it is understood that multiple transducers may also be used. The transducer 325 shown in FIG. 3 is shown extending from a lumen (e.g., 216, 218, 220, 222 of FIG. 2) inside the catheter 302, but it should be understood that transducer 325 may be arranged in any of the lumens in the catheter and may also emerge from an aperture 324. In some of the lumens the transducer 325 may be located inside of the fluid that is used to inflate the balloon 308. In other instances, it may be in the interior such as lumen as shown and described below with respect to FIG. 5. Multimodal transducers might also be used that offer near-infrared spectroscopy or optical coherence tomography sensing.

[0062] Transducer 325 can receive an ultrasonic signal to produce an image, such as an image of the surrounding anatomy next to the catheter 302, or of an obstruction or other foreign object in the body, a clot, nerves, or the like. Transducer 325 can emit an ultrasonic signal itself, or it can receive a reflected signal that comes back from the body as a reflection due to the ultrasonic acoustic signal generated by another actuation element, such as a balloon or a fluid that is photoacoustically or electrically actuated. The image can be generated by a processor (not shown) that can intake electrical signals from the transducer 325 to generate a corresponding image output. Such an image can be displayed on a screen (not shown) or otherwise handled by the processor to make routing decisions.

[0063] 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 as shown in FIG. 2 A or FIG. 2B. A fluid used to inflate balloon 308 may be selected based on photoacoustic characteristics (in a photo-actuated embodiment), optical absorption characteristics, cavitation characteristics, biocompatibility, 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 photoacoustic response characteristics, which can include frequency and intensity of acoustic emissions in response to received light at a particular wavelength or wavelengths. UltrasoundAttorney Docket No. 19506.0003WOU1 emitted using this photoacoustic response may be enhanced by use of a fluid with specific absorption properties, thermal properties, or cavitation properties, sometimes called a coupling medium. When the transducer used to emit and / or receive ultrasound waves is placed inside of the balloon, the fluid used to fill the balloons serves as a coupling medium.

[0064] FIG. 3A specifically shows a photoacoustic embodiment. The photoacoustic emissions produced by the system of FIG. 3 A 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.

[0065] The deficiencies of some other catheter-based designs can be overcome through imaging the photoacoustic effect. When using many photoacoustic materials, the magnitude of the photoacoustic effect can be controlled by the intensity of the optical pulse. The pulse will move in different directions based on the position of the catheter, the position of the illumination sources, and the local anatomy. The transducer 325 will be able to map and measure the photoacoustic pressure waves as they reflect, refract, and transmit through the body. In that way, the photoacoustic intensity can be increased or decreased based on the realtime feedback provided by the transducer 325. The directionality of the photoacoustic intensity can be changed based on the information / images determined by the transducer. This can be done quickly including video frame rates.

[0066] Some examples of suitable fluids that can be routed into balloon 308 in the photoacoustic embodiment shown in FIG. 3A include perfluorocarbons (PFCs) and liquid metals, like gallium-based alloys, which can be used in certain applications where thermal expansion is a key factor. Absorption of optical signal for thermal expansion can be accomplished through the use of ICG dye, methylene blue, or other similar materials. Additional examples are provided in Han et al., “Contrast Agents for Photoacoustic Imaging: A Review Focusing on the Wavelength Range,” Biosensors 2022, 12, 594 (DOI: 10.3390 / biosl2080594) (see Table 2) and Zackrisson et al., “Light In and Sound Out: Emerging Translational Strategies for Photoacoustic Imaging,” Cancer Research 74(4) (February 15, 2014). Suitable fluids for filling the balloon 308 can include liquids or gases, and can have a combination of optical absorption and thermal expansion that facilitate the use of light to create acoustic signal therefrom.Attorney Docket No. 19506.0003WOU1

[0067] A mixture of fluids could be used where two components or more components are used each with a different absorption spectra. Different optical pulses at different wavelengths could be used to modulate / control the resulting photoacoustic signal. In embodiments, a pulse / echo from the transducer 325 is used to map the anatomy at the site of therapy and obtain more details about the disease site. A therapy is then tailored based on the details about the disease site. This tailoring could include the frequency and amplitude of the photoacoustic effect, the duration of treatment, and the directionality of treatment. The optical pulses could then be selected to guide this treatment (wavelength, pulse width, pulse repetition rate). Using the wavelength of the strong absorber in the mixture would produce high photoacoustic effects. Using the wavelength of the weaker absorber in the mixture would produce weaker photoacoustic effects.

[0068] Optical fibers 322 are admitted to the interior of balloon 308 of FIG. 3 A, 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 optical fibers 322. For example, optical fibers 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. 2A or FIG. 2B. The lumen provides passage for the light guide or optical fiber used to direct optical fibers 322 and light signal.

[0069] One or more optical fibers 322 are deployed into the interior of balloon 308 of FIG. 3A and deliver optical pulses. While balloon 308 is expanded with a fluid, such as saline or fluids containing contrast media, the optical signal that causes photoacoustic pulses to be generated will be delivered to the fluid inside the balloons. As described above, the optical signal delivered at optical fibers 322 can result in photoacoustic response and acoustic emissions within the balloon 308 that can be used for treatments and imaging via the transducer 325.

[0070] Although only one optical fiber 322 is shown in FIG. 3 A, it should be understood that there may be multiple such optical fibers 322 arranged throughout the balloon 308 extending from different ones of the apertures 324. The optical energy is converted into acoustic signal as the optical fiber(s) 322 are illuminated, 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.

[0071] In embodiments, optical fibers 322 are arranged or activated to achieve particular ultrasound directionality. For example, optical fibers 322 may be forwardly- orAttorney Docket No. 19506.0003WOU1 circumferentially-arranged to activate or direct ultrasound toward a forward (or distal) direction relative to an origin or entry point of the catheter 302.

[0072] In embodiments, the optical fibers 322, the fluid filling the balloon 308, and the catheter 302 can be chosen to be compatible.

[0073] The diameter and optical index of a fiber affect which wavelengths are transmitted according to the so-called cutoff wavelength corresponding to the diameter of that fiber. This criterion, along with the sizes of lumens available for the fiber to pass through, determine the cutoff wavelength of a fiber. Core diameters of commonly-used fibers in embodiments can range from about 10 microns to about 1000 microns in some embodiments. A common diameter for a fiber used herein could be about 200 microns. The diameter may vary depending upon whether the light transmitted therein is infrared, near-infrared, visible, or ultraviolet. The fluid responds to incident light as a function of wavelength of that light.

[0074] Many materials are highly absorptive of infrared radiation. Thus, the fluid and the optical fiber may be selected to function well in the infrared regime. However, the catheter can provide a further consideration when choosing the fluid and operating wavelength. As described above, an advantage of the systems described herein is that they are smaller than electrode-based systems and thus able to access more portions of the vasculature. Thus, the fluid, the light source, and the catheter may be chosen such that the core diameter is smaller, such as by using a fluid and light source that operate at a lower wavelength so that the fiber will fit through the apertures in the catheter.

[0075] Thus, the fluid(s), balloon material, fiber diameter, and optical source are chosen so that the optical signal is at a wavelength that passes through the fiber, which is in turn small enough to fit through a corresponding lumen of the catheter, and be delivered to a fluid that is both absorptive at that wavelength as well as exhibiting photoacoustic response at that wavelength to transform the optical signal into acoustic signal at the balloon. As described above, in some embodiments there may be multiple photoacoustic materials, which could either take the form of multiple fluids or, alternatively, a photoacoustic fluid and a photoacoustic balloon skin itself. The multiple photoacoustic materials can be tuned for different photoacoustic emission profiles so that desired types of pulses can be generated with different light emissions delivered thereto.

[0076] FIG. 3B shows an alternative embodiment in which the actuation signal provided to the system is electrical. The main difference between FIGS. 3 A and 3B is that whereas FIG. 3 A shows a fiber 322 that provides light to actuate a photoacoustic material, FIG. 3B insteadAttorney Docket No. 19506.0003WOU1 shows a pair of electrodes 323 that are used to create a spark therebetween and thereby create cavitation in the fluid that fills the balloon 308.

[0077] Referring now to FIGS. 4A, 4B, and 4C, an embodiment of a catheter 402 that uses photoacoustic response to create ultrasound at the distal end 406 thereof is shown, which can be used in the embodiment of FIG. 1 and 3 A, for example. FIG. 4A shows fiber 422 advanced into the balloon 408 that is inflated via holes 424. As described above, a guidewire aperture 426 facilitates passage of a guidewire therethrough.

[0078] The embodiment shown in FIG. 4A looks very similar to the one of FIG. 3 A, and like parts are shown with like reference numbers, iterated by a factor of 100. In contrast to FIG. 3A, however, FIGS. 4A, 4B, and 4C show a multi-layer balloon 408. That is, the skin of the balloon that is inflated via the apertures 424 is made up of multiple layers such that the balloon 408 produces an effect in response to optical stimulation.

[0079] FIGS. 4B and 4C show alternative versions of materials that can be used to form the balloon 408, in detail views. Typically just one type of material would be used in a balloon 408, but either of these, or a combination thereof, or other types of photoresponsive materials, could be used in various embodiments. Some examples are described, for example, in Chen et al., “Multilayered carbon nanotube yam based optoacoustic transducer with high energy conversion efficiency for ultrasound application,” Nano Energy, Volume 46, 2018, Pages 314- 321 (DOI: 10.1016 / j.nanoen.2018.02.006).

[0080] In the example shown in the detailed view of FIG. 4B, nanomaterials 432 are arranged at the interface between a first material 428 and a second material 430. As described in Chen, this arrangement can result in a freestanding optoacoustic transducer using continuous multilayered carbon nanotube yams, gold nanoparticles and elastomeric polymer to create laser-generated ultrasound signal. In this embodiment, the fluid filling the balloon 408 need not have any particular coefficient of thermal expansion, nor would it require any particular absorptivity. Rather, the fluid need only transmit light from the fiber 422 to the balloon 408, which itself generates the acoustic signal.

[0081] Additional types of materials are contemplated, such as those described in Wu et al., “Polydimethylsiloxane / multi-walled carbon nanotube nanocomposite film prepared by ultrasonic-assisted forced impregnation with a superior photoacoustic conversion efficiency of 9.98 x 10'4,” 14 Journal of Nanophysics (October 24, 2020) and Link et al., “Laser-Induced Shape Changes of Colloidal Gold Nanorods Using Femtosecond and Nanosecond Laser Pulses,” J. Phys. Chem. B 6152-6163 (2000) (DOI: 10.102 l / jp000679t).Attorney Docket No. 19506.0003WOU1

[0082] FIG. 4C shows an alternative structure for creating an optoacoustic transducer, in which alternating layers of positively and negatively charged material are interdigitated with one another, in other words creating a layer-by-layer assembly made of a first material 434 and a second material 436. In embodiments, these layers could be poly(allylamine hydrochloride (PAH) and polystyrene sulfonate (PSS). These polymer layers could immobilize optical absorbers (small molecules, nanoparticles) to produce the photoacoustic effect. The charged polymer layers themselves may produce photoacoustic effect: In embodiments, the electrochromic polymers poly(hexyl viologen) (PXV) and poly(3,4- ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:SPS) could be used. These materials have tunable optical properties, including photoacoustic properties in many embodiments that are usable in the systems and methods described herein.

[0083] Depending upon the mode of operation, an ultrasonic signal created either between the optical fibers 422 of FIGS. 4A-4C shining upon the fluid within the balloon 408, or by shining upon the skin of the balloon or other portions that make up the catheter itself as described in FIGS. 4B and 4C, 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 with the delivery of such acoustic signal.

[0084] 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. 4B and 4C. 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 are aclitaxel, sirolimus, heparin, or other anti-inflammatory agents, for example. In embodiments, the coating 438 may have photoacoustic signal that can be detectable by the transducer. The

[0085] change in photoacoustic signal intensity coming from the balloon exterior 408 / 438 can thus report the amount of coating 438 that has been released from the balloon into the surrounding environment. In other embodiments, coating 438 does not produce photoacoustic signal but does have a defined thickness on the ballon exterior as shown in Figure 4B and Figure 4C. This thickness of this layer could be measured with pulse / echo imaging from the transducer. The reduction in the layer thickness could then be correlated to release of coating 438 into the surrounding environment.

[0086] Depending upon the materials involved, the coating may be applied to the balloon 438 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 438Attorney Docket No. 19506.0003WOU1 to the balloon 408. The tie layer can either be a separate layer from the coating 438 or it can be comixed with the coating 438 to provide an acceptable level of bond to the balloon.

[0087] 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); 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).

[0088] FIG. 4D shows the electrodes 423 arranged within the balloon 408, while FIG. 4E shows the coating of eluted material 438 on the outer wall of the balloon 408.

[0089] FIGS. 4A-4E show two different ways to deploy or elute a coating on the outside of a balloon. In some embodiments there can be other components that are not shown in the simplified views used in these drawings. For example, a tie layer can be used to hold the coating 438 to the balloon 408 in either of the versions depicted in FIGS. 4A-4C and 4D-4E. The eluted coating can be distributed as molecules which break off from the balloon, or in larger pieces that break up or are dissolved upon disruption from the balloon 408. There may also be an encapsulant material used on the outside of the coating 438 to prevent early elution.

[0090] In some embodiments, the coating 438 can be made of a medication or other substance that provides a treatment. In other embodiments, ultrasound emitted by the catheter 402 can play a dual role in treatment in the embodiments depicted in FIGS. 4A-4E. UltrasoundAttorney Docket No. 19506.0003WOU1 can be used to disrupt and distribute or elute the coating 438. In addition, ultrasound can be used to provide a treatment using the material that makes up the coating 438 in some embodiments. For example, coating 438 can be made of a material that responds to ultrasound to provide ablation or localized heating.

[0091] FIG. 5 is a partial view of a catheter system 502 depicting a distal end thereof, the catheter system having multiple balloons at the distal end 506. 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 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. The transducer 525 can be positioned inside the proximal or distal balloons or may be located in between the two balloons. 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).

[0092] The balloon catheter 502 described herein incorporates fiber optics 522 that deliver light to the balloons 508, 509 via a lumen as described in FIGS. 2A and 2B. The heating or vibration patterns of the fluid or balloon 508, 509 can be modulated to produce a corresponding frequency of acoustic signal from the balloons 508, 509. In embodiments, catheter 502 will have one more fiber optics 522 that travel through separate lumens to deliver illumination pulses to the interior of balloon 508, 509. Balloons 508, 509 are expanded, such as by saline or fluids containing contrast media, and light pulses will be delivered to the fluid inside the balloons 508, 509.

[0093] 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 is then tailored based on the details about the disease site. This tailoring could include the frequency and amplitude of the photoacoustic effect, the duration of treatment, and the directionality of treatment. The optical pulses could then be selected to guide this treatment (wavelength, pulse width, pulse repetition rate). Using the wavelength of the strong absorber in the mixture would produce high photoacoustic effects. Using the wavelength of the weaker absorber in the mixture would produce weaker photoacoustic effects.

[0094] Though not separately depicted herein, it should be understood that in alternative embodiments electrodes may be used to provide cavitation in the balloons, rather than using photoacoustic response of the fluid within balloons 508, 509 or of the material that makes upAttorney Docket No. 19506.0003WOU1 the balloons 508, 509 themselves. Additionally or alternatively, the material that makes up the catheter 502 itself could be used to provide the ultrasound. It may be particularly beneficial to provide ultrasound along length 540, such as by incorporating photoacoustic material components within the catheter 502 along the length 540 that can be illuminated by a fiber (e.g., 522) that is routed to that position. Similarly, electrodes could be arranged in the length 540 of catheter 502 to create ultrasound from that location.

[0095] In the photoacoustic embodiments, optical energy is converted into heat, with thermoelastic expansion within the fluid or the balloon skin itself resulting in the generation of ultrasound waves and / or shockwaves by causing movement of balloons 508, 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. Similarly, electrodes used in the electronic embodiments create cavitation in a fluid that emits acoustic waves.

[0096] Though the example of FIG. 5 demonstrates the multi-balloon catheter 502 with two balloons 508, 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. 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

[0097] The fiber optics 522 (or electrodes, in electrical equivalent embodiments) in each balloon can be activated or illuminated independently or together with one another in concert. When powered together, the acoustic emissions from each of the balloons 508 and 509 are synchronized, and advantageously it may only be necessary to route light through one or two lumens (see FIGS. 2 A and 2B) within the catheter 502. As 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.

[0098] In other examples, however, the fiber optics 522 may be separately illuminated or separately controlled. The fiber optics 522 can then be used to create acoustic signals from their respective balloons 508, 509 that will constructively or destructively interfere with one another. Additionally or alternatively, one of the balloons 508, 509 can be passive (that is, the fiber optics 522 therein are unpowered) while the other is activated to create acoustic signal. In this way, one balloon (e.g., 509) can be used for anchoring the catheter 502 in place while the other balloon (e.g., 508) provides ultrasonic signal to deliver the desired treatment. WhenAttorney Docket No. 19506.0003WOU1 illumination is provided separately, it may be necessary to route distinct fiber optics through separate lumens of the catheter 502, unless the fiber optics have a small enough cross-section to cohabit a single lumen.

[0099] Similarly, electrodes can be routed to balloons 508, 509 and powered in concert to provide either constructive or destructive interference at different physical locations relative to the catheter 502. In some embodiments, photoacoustic response and electronic response can be used together. For example, electrodes could be included to provide ultrasound (as shown in FIG. 3B), while fiber optics could be used (as shown in FIG. 3 A) to deliver a signal that is used for steering or imaging.

[0100] In use, the embodiment shown in FIG. 5 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. 5, 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 the two balloons 508 and 509. A clot or other structure to be treated can be broken up and, due to the positions of the balloons 508 and 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., FIGS. 6A and 6B). The transducer 525 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.

[0101] The catheter shaft in between the balloons (i.e., the portion of catheter 502 along length 540) may include holes 542 for infusing a drug out into the region adjacent the catheter 502, as indicated by the perforated exterior in that region. 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 include 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.

[0102] 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 hereinAttorney Docket No. 19506.0003WOU1 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.

[0103] The catheter 502 can also house a transducer 525 to record ultrasound pressure waves. This transducer 525 may be a single element transducer or a miniaturized phase array or linear array. The transducer 525 may be positioned at or near the first balloon 508 or the second balloon 509, and may be in the interior of the balloon when accessed through one of the channel s / lum ens in the catheter, similar to its depiction with respect to transducer 325 of FIG. 3 A and FIG. 3B. The transducer 525 shown in FIG. 5 is positioned between the balloons 508 and 509 and, as indicated by arrows, is movable along the length of catheter 502 on the inside thereof, such as through a lumen (e.g., 216, 218, 220, or 222 of FIG. 2A or FIG. 2B). Transducer 525 can be acoustically coupled to the surrounding environment via the fluid used to fill the balloons 508 and 509, or the liquid (e.g., blood) present in the vasculature. The transducer 525 can be moved proximally or distally to record acoustic signals in different areas of the vasculature. The transducer itself may include a second guidewire (not shown) 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 would 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 another design, the transducer 525 would record only. The transducer 525 could record acoustic pressure waves created by a balloon material or by a photoacoustically-active fluid. The acoustic waves produced through a photoacoustic effect might also interact with the surrounding anatomy before being recorded. The transducer 525 could in turn monitor the magnitude and location of the photoacoustic pressure waves. The transducer 525 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 a photoacoustically-active element within the drug.

[0104] FIGS. 6 A and 6B are partial views of a single-balloon catheter usable in the systems described above, including an aspiration sleeve 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 sleeve 650 can aspirate the clots effectively.Attorney Docket No. 19506.0003WOU1

[0105] The aspiration catheter provides for the targeted removal of substances such as blood clots, pus, or other unwanted materials from specific areas within the body. The catheter is equipped with a dedicated lumen or channel through which fluids or materials can be aspirated. Depending on the procedure and application, these catheters may be compatible with various aspiration systems, including manual syringes or automated suction devices. Guidance through imaging modalities, such as fluoroscopy or ultrasonic imaging, ensures precise placement of the catheter for optimal results.

[0106] It should be understood that the aspiration functionality of FIG. 6 can be added to any of the other embodiments described above. In multi-balloon embodiments it may be necessary to deflate at least the relatively more proximal balloon to facilitate aspiration of some regions.

[0107] FIGS. 6 A and 6B further depict elution holes 642 arranged along the length 640 between balloon 608 and the aspiration sleeve 650. As described above, elution holes 642 provide for effusion of materials used for treatments. Additionally, a material that is responsive to ultrasound, such as a material that heats up in the presence of ultrasound, can be eluted through the elution holes 642 and taken up by the body such that the subsequent provision of ultrasound from the balloon 608 will cause targeted treatment (e.g., denervation or ablation) of the region where the eluted material has been taken up in the body.

[0108] The method 700 of FIG. 7 includes positioning an actuation element in a lumen at 702. As described above, in various embodiments light guides (such as fiber optic elements) can be used as the actuation element. These light guides 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 illuminated. Multiple fibers could be used in some embodiments to provide different signals (e.g., different ultrasonic frequency signals) or to create constructive and destructive interference with other signal sources. In some embodiments, a fiber can be advanced within a lumen to a position where it can produce the photoacoustic effect, and retracted as desired. One or multiple fibers can each be advanced to one or more different positions along the catheter during use to produce a photoacoustic effect at specific locations and times.

[0109] In alternative embodiments, the actuation element can be an electrically-powered element, such as an electrode. In those embodiments, the actuation element is not activated by light but rather by provision of electrical signal.

[0110] 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 whereAttorney Docket No. 19506.0003WOU1 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.

[0111] Although FIG. 7 shows the positioning of the catheter at the target location 704 occurring after positioning the actuation element at 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 fiber 702 (or fibers) therein, or the electrode therein, depending upon whether the actuation element is optical or electrical in nature.

[0112] 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.

[0113] The method of FIG. 7 further includes elution at 708. Elution, as shown and described with respect to FIGS. 4A-4E, can include disrupting a material that is on the outside of the catheter. Additionally or alternatively, and as shown with respect to FIGS. 5, 6A, and6B, elution can include providing a material from within the catheter, such as from a lumen that includes the eluted material therein.

[0114] The method of FIG. 7 further includes actuating the actuation element at 710. When referring to optical actuation, illuminating the fiber optic (or other light guide) causes illumination of a photoresponsive material at the distal end of the catheter. That photoresponsive material can make up the balloon skin, the fluid that inflates the balloon, or part of the shaft of the catheter itself. The photoresponsive material, upon exposure to light at its photoacoustic wavelength, emits acoustic signal. In many embodiments, for example, the frequency of the photoacoustic output from the photoresponsive material can be ultrasonic, to provide for an ultrasonic therapy at the target location. When referring to electrical actuation, powering the electrode causes sparking and accompanying cavitation at the distal end of the catheter. The cavitation can be provided at a desired acoustic frequency for a desired number of pulses corresponding to the treatment.

[0115] Although shown occurring in sequence, it should be understood that in some embodiments elution 708 and ultrasound generation 710 occur simultaneously. For example, the elution techniques described at FIGS. 4A-4E use ultrasound to accomplish elution. Therefore these two aspects of method 700 are not necessarily done one before the other. Ultrasound generation 710 may also begin prior to elution 708, such as when the eluted materialAttorney Docket No. 19506.0003WOU1 is a medicament that should be delivered after denervation, thrombus removal, or calcium debulking.

[0116] Optionally, the method of FIG. 7 can include receiving reflected signal for use in imaging. The acoustic signal generated by the ultrasound treatment 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.

[0117] The method 700 may be extended to performing a treatment step. 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 may extend to other procedures and treatments where an ultrasonic catheter is advantageously applied.

[0118] Referring now to FIGS. 8A and 8B, the device depicted in FIGS. 8A and 8B are similar to those of FIGS. 3 and 4A. In contrast to FIGS. 3 A, 3B, 4A, and 4D, however, FIGS. 8A 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 the external surface of the balloon. Internal structures of balloon 808 may be the same or similar to those shown in any of FIGS. 3A, 3B, 4A, and 4D.

[0119] 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.

[0120] 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 theAttorney Docket No. 19506.0003WOU1 circumference of the balloon, and asymmetrically with respect to another dimension, e.g., disposed more toward the distal end.

[0121] 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.

[0122] 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.

[0123] 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.

[0124] 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, when the laser energy is delivered, or when ultrasound is generated. For example, the balloon 808 may 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-4E.

[0125] 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.

[0126] 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-4C. The ultrasound waves generated within or on the balloon at the target location enables treatment at the target location.Attorney Docket No. 19506.0003WOU1

[0127] 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.

[0128] FIG. 9 is a partial view of an example catheter 902 with a microneedle-coated 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. 11. For example, microneedles 1146 may be provided only along a portion of the radial extent of the balloon 1108, similar to the cutting elements of FIGS. 10A and 10B. Additionally, the microneedles 1146 may not be arranged in rows, and can be provided in other arrangements (such as hexagonal packing for increased density) as desired.

[0129] 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 barrier to create a region of permeability to allow delivery of pharmaceutical treatments and other agents.

[0130] 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.

[0131] In addition to solid microneedles for purely mechanical manipulation, the use of coated microneedles, dissolving microneedles, and hollow microneedles is also contemplated.

[0132] 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.Attorney Docket No. 19506.0003WOU1

[0133] 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. 1-6B) that can cause the dissolution of microneedles 946 that have been inserted into the BBB.

[0134] 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.

[0135] 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 in the microneedles 946, while the substance for delivery to the central nervous system is in the bloodstream.

[0136] 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.

[0137] 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.Attorney Docket No. 19506.0003WOU1

[0138] FIG. 12 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 1202b, as indicated by the arrows T.

[0139] 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.

[0140] 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.

[0141] 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.

[0142] 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 locationAttorney Docket No. 19506.0003WOU1 where the ultrasound is generated, such as at a balloon 1108 consistent with any of the embodiments described with respect to FIGS. 1-6B.

[0143] FIG. 12 is a partial view of a catheter 1202 delivering microbubbles 1204 from an interior lumen. Microbubbles 1204 are released 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.

[0144] Notably, in FIG. 12 the microbubbles are not proximate the balloon 1208. As such, ultrasound may be delivered in a manner where ultrasound is focused or directed from a source to a remote location.

[0145] 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 FIG. 5. The use of two balloons provides for contained and therefore more targeted delivery of microbubbles and ultrasound.

[0146] ASPECTS

[0147] 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 balloon is arranged at the distal end, wherein an interior of the balloon is fluidically coupled to a first one of the plurality of lumens and the balloon is inflated by a fluid routed through the first one of the plurality of lumens. An elution material is arranged at the distal end, and an actuation element is arranged in a second one of the plurality of lumens, the actuation element extending from the proximal end to the distal end and configured to generate an ultrasonic signal at the distal end.

[0148] According to a second aspect, the device of the first aspect further comprises a guidewire arranged through a third lumen of the catheter and extending from the proximal end and past the distal end.

[0149] According to a third aspect, the ultrasound-emitting device of the first aspect has the actuation element as an optical fiber and the fluid as a photoresponsive fluid.

[0150] According to a fourth aspect, the ultrasound-emitting device of the third aspect further comprises a tie layer disposed between the elution material and the balloon, and wherein the tie layer comprises a material that is susceptible to disruption by ultrasound.Attorney Docket No. 19506.0003WOU1

[0151] According to a fifth aspect, the ultrasound-emitting device of any one of the first through fourth aspects has the elution material as a pharmaceutical coating arranged on the balloon.

[0152] According to a sixth aspect, the ultrasound-emitting device of the first aspect has the actuation element as an optical fiber and the balloon made of a photoresponsive material.

[0153] According to a seventh aspect, the ultrasound-emitting device of the first or sixth aspects has the actuation element as an optical fiber and an external shaft of the catheter made of a photoresponsive material.

[0154] According to an eighth aspect, the ultrasound-emitting device of the first aspect has the actuation element as an electrode.

[0155] According to a ninth aspect, the ultrasound-emitting device of the first aspect further comprises a second balloon arranged between the balloon and the proximal end, wherein an interior of the second balloon is fluidically coupled to the first one of the plurality of lumens and the second balloon is inflated by the fluid routed through the first one of the plurality of lumens, and a second actuation element configured to generate an ultrasonic signal at the distal end.

[0156] According to a tenth aspect, the ultrasound-emitting device of the ninth aspect further comprises a plurality of apertures arranged on an outer surface of the catheter between the balloon and the second balloon, wherein the plurality of apertures are in communication with a fourth lumen of the plurality of lumens.

[0157] According to an eleventh aspect, the ultrasound-emitting device of any one of the first through tenth aspects further comprises an aspiration sleeve circumscribing the catheter.

[0158] According to a twelfth aspect, the ultrasound-emitting device of the eleventh aspect further comprises a plurality of effusion holes defined along a length of the catheter between the balloon and the aspiration sleeve.

[0159] According to a thirteenth aspect, the ultrasound-emitting device of any one of the first through twelfth aspects further comprises a cutting element arranged on an external surface of the balloon.

[0160] According to a fourteenth aspect, the ultrasound-emitting device of the thirteenth aspect has the cutting element as at least two cutting elements.

[0161] According to a fifteenth aspect, the ultrasound-emitting device of the fourteenth aspect has the at least two cutting elements arranged symmetrically around a circumference of the balloon.Attorney Docket No. 19506.0003WOU1

[0162] According to a sixteenth aspect, the ultrasound-emitting device of the fourteenth or fifteenth aspects has the at least two cutting elements arranged symmetrically along a length of the balloon.

[0163] According to a seventeenth aspect, the ultrasound-emitting device of the fourteenth aspect has the at least two cutting elements arranged asymmetrically around a circumference of the balloon.

[0164] According to an eighteenth aspect, the ultrasound-emitting device of the fourteenth or seventeenth aspects has the at least two cutting elements arranged asymmetrically along a length of the balloon.

[0165] According to a nineteenth aspect, the ultrasound-emitting device of any one of the first through eighteenth aspects further comprises a transducer that can emit and / or receive acoustic waves including recording those waves and convert them to an electrical signal.

[0166] According to a twentieth aspect, the ultrasound-emitting device of the nineteenth aspect further comprises a processor configured to convert the electrical signal to an image.

[0167] According to a twenty -first aspect, a method for generating ultrasound by an ultrasound-emitting device comprises positioning an actuation element in a lumen of a catheter such that the actuation element extends from a proximal end of the catheter to a distal end of the catheter, inflating a balloon at a distal end of the catheter with a fluid, eluting an elution material at the distal end, and activating the actuation element at the proximal end of the catheter to generate an ultrasonic acoustic signal at the distal end of the catheter.

[0168] According to a twenty-second aspect, the method of the twenty-first aspect has the actuation element as an optical fiber and wherein at least one of the balloon, balloon shaft and / or the fluid comprises a photoresponsive material.

[0169] According to a twenty -third aspect, the method of the twenty-first aspect has the actuation element as an electrode.

[0170] According to a twenty-fourth aspect, the method of any one of the twenty-first through twenty-third aspects further comprises denervating an anatomical structure positioned in a region arranged adjacent the balloon.

[0171] According to a twenty-fifth aspect, the method of any one of the twenty-first through twenty-fourth aspects further comprises applying ultrasonic emissions to calcium deposits for calcium debulking.

[0172] According to a twenty-sixth aspect, the method of any one of the twenty-first through twenty-fifth aspects further comprises applying ultrasonic emissions to an atherosclerotic plaque or other blockage for treatment of arterial occlusion.Attorney Docket No. 19506.0003WOU1

[0173] According to a twenty-seventh aspect, the method of the twenty-fifth or twentysixth 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.

[0174] According to a twenty-eighth aspect, the method of any one of the twenty-first through twenty-seventh aspects has the elution material as a coating on the balloon, and wherein eluting the elution material comprises disrupting a tie layer that couples the elution material to the balloon with ultrasonic emissions.

[0175] According to a twenty-ninth aspect, the method of any one of the twenty -first through twenty-eighth aspects further comprises routing the distal end of the catheter to a target location along a guidewire prior to inflating the balloon.

[0176] According to a thirtieth aspect, the method of any one of the twenty-first through twenty-ninth aspects has a plurality of effusion holes defined along a length of the catheter between the balloon and an aspiration sleeve, and eluting the elution material comprises routing a liquid elution material through the effusion holes.

[0177] According to a thirty-first aspect, the method of the thirtieth aspect has activating the actuation element at the proximal end of the catheter to generate an ultrasonic acoustic signal at the distal end of the catheter comprising routing an optical fiber to a region along the length such that the optical fiber is configured to illuminate a region adjacent the length, and illuminating the optical fiber from the proximal end.

[0178] According to a thirty-second aspect, the method of the thirtieth aspect has activating the actuation element at the proximal end of the catheter to generate an ultrasonic acoustic signal at the distal end of the catheter comprising positioning a pair of electrodes in the balloon, and applying an electrical signal to the electrodes from the proximal end.

[0179] According to a thirty -third aspect, the method of the thirtieth, thirty-first, or thirty- second aspects has the balloon as polymer based.

[0180] According to a thirty-fourth aspect, the method of any one of the twenty-first through thirty-third aspects further comprises inflating a second balloon located between the balloon and the proximal end, and actuating a second actuation element at the proximal end of the catheter to generate a second ultrasonic acoustic signal at the distal end of the catheter.

[0181] According to a thirty -fifth aspect, the method of the thirty-fourth aspect has eluting the elution material comprising routing a liquid elution material through a plurality of effusion holes arranged between the balloon and the second balloon and adjacent the catheter.Attorney Docket No. 19506.0003WOU1

[0182] According to a thirty-sixth aspect, the method of any one of the twenty-first through thirty-fifth aspects further comprises receiving an ultrasonic signal at a transducer to produce an image.

[0183] According to a thirty-seventh aspect, the method of the thirty-sixth aspect further comprises emitting an ultrasonic signal by the transducer.

[0184] According to a thirty-eighth aspect, the method of the thirty-sixth or thirty-seventh aspects has the ultrasonic signal received at the transducer including a reflected signal from the ultrasonic acoustic signal generated by the actuation element.

[0185] According to a thirty-ninth 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 balloon arranged at the distal end, wherein an interior of the balloon is fluidically coupled to a first one of the plurality of lumens, an elution material arranged at the distal end, and actuation means configured to produce an ultrasound signal at the distal end.

[0186] According to a fortieth aspect, the ultrasound-emitting device of the thirty-ninth aspect further comprises a guidewire arranged through a second one of the plurality of lumens, extending through the catheter from the proximal end and past the distal end thereof.

[0187] According to a forty-first aspect, the ultrasound-emitting device of the thirty-ninth or fortieth aspects further comprises a photoresponsive fluid arranged in the balloon and the first one of the plurality of lumens.

[0188] According to a forty-second aspect, the ultrasound-emitting device of any one of the thirty-ninth through forty-first aspects has the balloon made of a polymer.

[0189] According to a forty-third aspect, the ultrasound-emitting device of any one of the thirty-ninth through forty-second aspects has the balloon made of a photoresponsive material.

[0190] According to a forty-fourth aspect, the ultrasound-emitting device of any one of the thirty-ninth through forty-third aspects has the actuation means comprising an electrode.

[0191] According to a forty-fifth aspect, the ultrasound-emitting device of any one of the thirty-ninth through forty-fourth aspects further comprises a tie layer disposed between a surface of the balloon and the elution material, wherein the tie layer comprises a material that is susceptible to disruption by ultrasound.

[0192] According to a forty-sixth aspect, the ultrasound-emitting device of any one of the thirty-ninth through forty-fifth aspects further comprises a second balloon arranged between the balloon and the proximal end, wherein an interior of the second balloon is fluidically coupled to the first one of the plurality of lumens and the second balloon is inflated by the fluid routed through the first one of the plurality of lumens.Attorney Docket No. 19506.0003WOU1

[0193] According to a forty-seventh aspect, the ultrasound-emitting device of any one of the thirty-ninth through forty-sixth aspects further comprises an aspiration sleeve circumscribing the catheter.

[0194] According to a forty-eighth aspect, the ultrasound-emitting device of the fortyseventh aspect has the catheter defining a plurality of effusion holes arranged along a length between the balloon and the aspiration sleeve.

[0195] According to a forty-ninth aspect, the ultrasound-emitting device of the fortyeighth aspect further comprises an optical fiber routed to a region along the length such that the optical fiber is configured to illuminate a region adjacent the length.

[0196] According to a fiftieth aspect, the ultrasound-emitting device of the forty-eighth or forty-ninth aspects further comprises a pair of electrodes arranged in the balloon, the electrodes coupled to the proximal end to receive an electrical signal.

[0197] According to a fifty-first aspect, the ultrasound-emitting device of any one of the thirty-ninth through fiftieth aspects further comprises a transducer integrated into the catheter.

[0198] According to a fifty-second aspect, the ultrasound-emitting device of any one of the thirty-ninth through fifty-first aspects further comprises cutting elements arranged on an external surface of the balloon.

[0199] According to a fifty-third aspect, the device of the fifty-second aspect has the cutting elements arranged symmetrically around at least one of a circumference of the balloon and along a length of the balloon.

[0200] According to a fifty-fourth aspect, a method of delivering an agent through the blood-brain 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.

[0201] According to a fifty-fifth aspect, the method of the fifty -fourth aspect has the agent as at least one of a pharmaceutical agent and microbubbles.

[0202] According to a fifty-sixth aspect, the method of the fifty-fourth or fifty-fifth 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.

[0203] The various aspects described herein are designed to be interoperable with one another unless otherwise indicated, allowing for customized device configurations tailored to specific clinical applications. The modular nature of the lumen arrangements, actuation mechanisms, balloon configurations, elution systems, and surface modifications enablesAttorney Docket No. 19506.0003WOU1 practitioners to select optimal combinations of features for particular treatment scenarios while maintaining the fundamental ultrasound generation and delivery capabilities that form the core of the disclosed technology.

[0204] 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. 19506.0003WOU1What 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 balloon arranged at the distal end, wherein an interior of the balloon is fluidically coupled to a first one of the plurality of lumens and the balloon is inflated by a fluid routed through the first one of the plurality of lumens; an elution material arranged at the distal end; and an actuation element arranged in a second one of the plurality of lumens, the actuation element extending from the proximal end to the distal end and configured to generate an ultrasonic signal at the distal end.The device of claim 1, further comprising a guidewire arranged through a third lumen of the catheter and extending from the proximal end and past the distal end.

2. The device of claim 1, further comprising a guidewire arranged through a third lumen of the catheter and extending from the proximal end and past the distal end.

3. The ultrasound-emitting device of claim 1, wherein the actuation element is an optical fiber and the fluid is a photoresponsive fluid.

4. The ultrasound-emitting device of claim 3, further comprising a tie layer disposed between the elution material and the balloon, and wherein the tie layer comprises a material that is susceptible to disruption by ultrasound.

5. The ultrasound-emitting device of any preceding claim, wherein the elution material is a pharmaceutical coating arranged on the balloon.

6. The ultrasound-emitting device of claim 1, wherein the actuation element is an optical fiber and the balloon is made of a photoresponsive material.

7. The ultrasound-emitting device of claim 1 or claim 6, wherein the actuation element is an optical fiber and an external shaft of the catheter is made of a photoresponsive material.Attorney Docket No. 19506.0003WOU18. The ultrasound-emitting device of claim 1, wherein the actuation element is an electrode.

9. The ultrasound-emitting device of claim 1, further comprising: a second balloon arranged between the balloon and the proximal end, wherein an interior of the second balloon is fluidically coupled to the first one of the plurality of lumens and the second balloon is inflated by the fluid routed through the first one of the plurality of lumens, and a second actuation element configured to generate an ultrasonic signal at the distal end.

10. The ultrasound-emitting device of claim 9, further comprising a plurality of apertures arranged on an outer surface of the catheter between the balloon and the second balloon, wherein the plurality of apertures are in communication with a fourth lumen of the plurality of lumens.

11. The ultrasound-emitting device of any preceding claim, further comprising an aspiration sleeve circumscribing the catheter.

12. The ultrasound-emitting device of claim 11, further comprising a plurality of effusion holes defined along a length of the catheter between the balloon and the aspiration sleeve.

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

14. The ultrasound-emitting device of claim 13, wherein the cutting element is at least two cutting elements.

15. The ultrasound-emitting device of claim 14, wherein the at least two cutting elements are arranged symmetrically around a circumference of the balloon.

16. The ultrasound-emitting device of claim 14 or 15, wherein the at least two cutting elements are arranged symmetrically along a length of the balloon.Attorney Docket No. 19506.0003WOU117. The ultrasound-emitting device of claim 14, wherein the at least two cutting elements are arranged asymmetrically around a circumference of the balloon.

18. The ultrasound-emitting device of claim 14 or 17, wherein the at least two cutting elements are arranged asymmetrically along a length of the balloon.

19. The ultrasound-emitting device of any preceding claim, further comprising a transducer that can emit and / or receive acoustic waves including recording those waves and convert them to an electrical signal.

20. The ultrasound-emitting device of claim 19, further comprising a processor configured to convert the electrical signal to an image.

21. A method for generating ultrasound by an ultrasound-emitting device, the method comprising: positioning an actuation element in a lumen of a catheter such that the actuation element extends from a proximal end of the catheter to a distal and of the catheter; inflating a balloon at a distal end of the catheter with a fluid; eluting an elution material at the distal end; and activating the actuation element at the proximal end of the catheter to generate an ultrasonic acoustic signal at the distal end of the catheter.

22. The method of claim 21, wherein the actuation element is an optical fiber and wherein at least one of the balloon, balloon shaft and / or the fluid comprises a photoresponsive material.

23. The method of claim 21, wherein the actuation element is an electrode.

24. The method of claim any of claims 21-23, further comprising denervating an anatomical structure positioned in a region arranged adjacent the balloon.

25. The method of any of claims 21-24, further comprising applying ultrasonic emissions to calcium deposits for calcium debulking.Attorney Docket No. 19506.0003WOU126. The method of any of claims 21-25, further comprising applying ultrasonic emissions to an atherosclerotic plaque or other blockage for treatment of arterial occlusion.

27. The method of claim 25 or 26, 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.

28. The method of any of claims 21-27, wherein the elution material is a coating on the balloon, and wherein eluting the elution material comprises disrupting a tie layer that couples the elution material to the balloon with ultrasonic emissions.

29. The method of any of claims 21-28, further comprising routing the distal end of the catheter to a target location along a guidewire prior to inflating the balloon.

30. The method of any of claims 21-29, wherein a plurality of effusion holes are defined along a length of the catheter between the balloon and an aspiration sleeve, and eluting the elution material comprises routing a liquid elution material through the effusion holes.

31. The method of claim 30, wherein activating the actuation element at the proximal end of the catheter to generate an ultrasonic acoustic signal at the distal end of the catheter comprises: routing an optical fiber to a region along the length such that the optical fiber is configured to illuminate a region adjacent the length; and illuminating the optical fiber from the proximal end.

32. The method of claim 30, wherein activating the actuation element at the proximal end of the catheter to generate an ultrasonic acoustic signal at the distal end of the catheter comprises: positioning a pair of electrodes in the balloon; and applying an electrical signal to the electrodes from the proximal end.

33. The method of claim 30, 31, or 32, wherein the balloon is polymer based.Attorney Docket No. 19506.0003WOU134. The method of any of claims 21-33, further comprising: inflating a second balloon located between the balloon and the proximal end; and actuating a second actuation element at the proximal end of the catheter to generate a second ultrasonic acoustic signal at the distal end of the catheter.

35. The method of claim 34, wherein eluting the elution material comprises routing a liquid elution material through a plurality of effusion holes arranged between the balloon and the second balloon and adjacent the catheter.

36. The method of any of claims 21-35, further comprising receiving an ultrasonic signal at a transducer to produce an image.

37. The method of claim 36, further comprising emitting an ultrasonic signal by the transducer.

38. The method of claim 36 or claim 37, wherein the ultrasonic signal received at the transducer includes a reflected signal from the ultrasonic acoustic signal generated by the actuation element.

39. 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 balloon arranged at the distal end, wherein an interior of the balloon is fluidically coupled to a first one of the plurality of lumens; an elution material arranged at the distal end; and actuation means configured to produce an ultrasound signal at the distal end.

40. The ultrasound-emitting device of claim 39, further comprising a guidewire arranged through a second one of the plurality of lumens, extending through the catheter from the proximal end and past the distal end thereof.

41. The ultrasound-emitting device of claim 39 or 40, further comprising a photoresponsive fluid arranged in the balloon and the first one of the plurality of lumens.Attorney Docket No. 19506.0003WOU142. The ultrasound-emitting device of any of claims 39-41, wherein the balloon is made of a polymer.

43. The ultrasound-emitting device of any of claims 39-42, wherein the balloon is made of a photoresponsive material.

44. The ultrasound-emitting device of any of claims 39-43, wherein the actuation means comprises an electrode.

45. The ultrasound-emitting device of any of claims 39-44, further comprising: a tie layer disposed between a surface of the balloon and the elution material, wherein the tie layer comprises a material that is susceptible to disruption by ultrasound.

46. The ultrasound-emitting device of any of claims 39-45, further comprising a second balloon arranged between the balloon and the proximal end, wherein an interior of the second balloon is fluidically coupled to the first one of the plurality of lumens and the second balloon is inflated by the fluid routed through the first one of the plurality of lumens.

47. The ultrasound-emitting device of any of claims 39-46, further comprising an aspiration sleeve circumscribing the catheter.

48. The ultrasound-emitting device of claim 47, wherein the catheter defines a plurality of effusion holes arranged along a length between the balloon and the aspiration sleeve.

49. The ultrasound-emitting device of claim 48, further comprising an optical fiber routed to a region along the length such that the optical fiber is configured to illuminate a region adjacent the length.

50. The ultrasound-emitting device of claim 48 or 49, further comprising a pair of electrodes arranged in the balloon, the electrodes coupled to the proximal end to receive an electrical signal.

51. The ultrasound-emitting device of any of claims 39-50, further comprising a transducer integrated into the catheter.Attorney Docket No. 19506.0003WOU152. The ultrasound-emitting device of any of claims 39-51, further comprising cutting elements arranged out an external surface of the balloon.

53. The device of claim 52, wherein the cutting elements are arranged symmetrically around at least one of a circumference of the balloon and along a length of the balloon.

54. 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; generating the ultrasonic waves from the catheter; and releasing the agent while the ultrasonic waves are being generated.

55. The method of claim 54, wherein the agent is at least one of a pharmaceutical agent and microbubbles.

56. The method of claim 54 or claim 55, 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.

Images