Systems and methods for intravascular treatment

Abstract

An endovascular apparatus for performing an intravascular treatment, such as disrupting a lesion of calcified plaque by intravascular lithotripsy. The apparatus comprises an angioplasty balloon mounted on a catheter. The balloon has an inflatable chamber and a membrane that is expandable radially by inflation of the chamber. An ultrasonic waveguide extending along a waveguide lumen of the catheter is disposed radially inward of the membrane. The catheter-mounted balloon is navigated to a treatment site in a blood vessel. The chamber of the balloon is then inflated to expand the membrane toward a wall of the vessel. Ultrasonically activating the waveguide generates cavitation shockwaves in liquid surrounding the waveguide. Energy of those shockwaves is transmitted to the membrane to vibrate the membrane and is thereby transmitted onwards from the membrane to the wall of the vessel or to a lesion in the vessel.

Description

[0001] Systems and methods for intravascular treatment

[0002] This invention relates to systems and methods for performing intravascular treatment using ultrasonic energy, an example being intravascular lithotripsy (IVL) performed to fracture or fragment calcified lesions or to disrupt plaque in a blood vessel.

[0003] More generally, the invention can be used to effect dilation of blood vessels, to treat resistant lesions for management of haemodialysis access, to improve vessel compliance, and to improve the effectiveness of drug-coated balloons used for drug delivery. An aspect of the invention involves sonoporation, using ultrasound to improve the uptake or absorption of drugs or other molecules through cell membranes.

[0004] Our PCT applications, including those published as WO 2020 / 094747, WO 2021 / 089859, WO 2021 / 224357, WO 2022 / 129623 and WO 2023 / 111361 , disclose various systems and methods for treating lesions in the vasculature using ultrasonic energy. Those systems comprise a controller that generates, processes and controls electrical signals, and an actuator that receives an ultrasonic signal from the controller. The actuator contains a transducer driven by the ultrasonic signal and a coupling to couple ultrasonic energy from the transducer into an active waveguide exemplified by a super-elastic wire. The coupling can couple the ultrasonic energy from the transducer into the wire at any of various locations along the length of the wire.

[0005] The invention relates particularly to the deployment of an ultrasonically-activated waveguide - such as a wire, wand, probe, mandrel, sonotrode or other member or elongate element - within an angioplasty balloon as a means for performing intravascular treatment. For brevity, this specification will exemplify such a waveguide as a wire.

[0006] A balloon catheter comprises an elongate tubular body or sheath and an angioplasty balloon positioned distally along the body. The catheter is configured to deliver a liquid medium that inflates the balloon when in situ within the patient’s vasculature. By expansion, an external surface of the balloon wall or membrane approaches or contacts the internal lumen of a surrounding blood vessel, for example diseased sections at which atherosclerotic plaque is calcified. The catheter also contains a wire to be activated ultrasonically when the balloon has been inflated. The balloon is longitudinally aligned with, and surrounds, one or more sections of the wire.Ultrasonic energy imparted to a proximal section of the wire is experienced differently in a narrower distal section of the wire because the wire is configured to optimise its resonance at desired frequencies and to control the energy delivered from the proximal section to the distal section. This provides for expression of multi-harmonic oscillations in the distal section, which actuate the distal section chaotically over a wide range of frequencies in axial and radial directions resulting in orbital periodic movement, mapping out a substantially uniform ovoidal orbit within a generally cylindrical volume. As the orbital motion of the distal section of the wire is transmitted proximally to the proximal section via a distally-tapered intermediate section of the wire, the proximal section and the intermediate section also oscillate orbitally in consequence.

[0007] Thus, activation via the proximal section of the wire provides for multi-harmonic transmission and activation of the distal section, and consequential activation of the proximal and intermediate sections, along and around the catheter or other lumen that surrounds the or each section of the wire extending within the balloon.

[0008] It is noted that activation of the wire is maximised at intervals along the distal section at points characteristic of antinodes of the activating harmonic. For example, the first antinode is at A / 4, with subsequent antinodes spaced by A / 2, where A is the wavelength of the primary driving frequency. Node locations can be described by (2n+1)A / 4.

[0009] Ultrasonic activation of the wire effects ultrasonic activity in the external membrane of the surrounding balloon by transmission of ultrasonic shockwaves through the liquid medium that inflates and expands the balloon. Where a catheter defines an inner lumen within the balloon, activation of the wire imparts ultrasonic shocks to the wall of the catheter. The resulting vibration of the catheter wall is then communicated though the inflating medium within the balloon to the membrane of the balloon. It is also possible for the active wire to bear against or to impact the surrounding wall of the catheter, hence imparting vibrations directly to the catheter wall.

[0010] Thus, shockwaves resulting from ultrasonic vibration of the wire within the inner lumen of the catheter are communicated or propagated to external surfaces of the balloon by being transmitted through the medium within the balloon. Correspondingly, the membrane of the balloon oscillates with high fidelity such that its movement can be transmitted directly from the balloon into tissues or lesions that are in contact with themembrane. Shockwaves transmitted by movement of the membrane can also cavitate and generate shockwaves in fluid or other structures outside the balloon. Those shockwaves are thereby conveyed into tissues or lesions surrounding the balloon, even if not in contact with the membrane.

[0011] As tissues or lesions may themselves comprise a substantial proportion of fluid, shockwaves emanating from the balloon can generate further cavitation and / or shockwaves in any such fluid incorporated in tissues or lesions. Also, shockwaves can travel through compliant materials of the tissues or lesions themselves.

[0012] In the case of calcified lesions, imparting an acoustic shock to the lesions and supporting tissues causes the calcified material to fracture as it is unable to flex in response to pressure waves passing through. This has been noted as a mechanism for crack propagation and fragmentation in calcified plaque, and thus for effecting lithotripsic breakdown of the calcified component of medial calcification.

[0013] Membranes of angioplasty balloons suitable for use in the invention can be made of high-tensile polymeric materials, such as high-tensile polyamides, urethanes, amides, ethers, esters or ketones, including extended copolymers or composites. The balloon membrane material may be compliant, semi-compliant or non-compliant, examples being latex, silicone rubber, nylon, PET or Pebax (trade mark). However, materials that excessively absorb and dampen transmission of ultrasonic energy are best avoided.

[0014] To maintain an annulus of liquid between the balloon and a surrounding vessel within which cavitation and shockwaves can be generated, the wire can be activated when the balloon has been inflated only partially or otherwise not expanded fully into contact with the vessel wall. Increasing the compliance or flexibility of the membrane of the balloon may also help to provide space between the balloon and the vessel wall in which a liquid medium such as blood can reside and cavitate.

[0015] The effects of the invention include balloon-mediated effects but can also include wire-mediated or direct effects. In relation to balloon-mediated effects, the geometry of the wire results in orbital ultrasonic activity within the inner lumen of the balloon catheter as noted above. That activity is communicated through the inflating liquid of the balloon to the outer surface of the balloon membrane, where it imparts shockwaves in adjacent tissues or lesions.It has been observed that ultrasonically activating the membrane of an angioplasty balloon by activating a wire disposed within the balloon, or within a catheter extending within the balloon, achieves a significant reduction in the force required to dilate a vessel. This is manifested by relatively low inflation pressure required to expand the balloon within the vessel. Consequently, the balloon can expand at lower and safer pressures and can effect more uniform expansion or dilatation of a vessel that surrounds the balloon.

[0016] Whilst dilation of a vessel can be achieved at a lower inflation pressure than in an angioplasty balloon lacking the assistance of ultrasonic activation, the invention may have other benefits at any practical inflation pressure, examples being in the range of 5 ATM to 40 ATM.

[0017] Sustained activation of the wire within a balloon, for example within the inner lumen of a catheter disposed concentrically within the balloon, maintains transmission of vibrations in a rapid and uniform or regular manner along the length of the balloon and around the circumference of the balloon. This promotes formation of shockwaves across the working area of the balloon. Those shockwaves can be transmitted directly into tissues or lesions in contact with the balloon or can produce a proliferation of micro-cavitations than can impart diffuse lithotripsic energy across the entire working area of the balloon.

[0018] The manner in which the distal end of the wire is positioned or constrained within or relative to the balloon or catheter can affect the mode or level of vibrations in the membrane of the balloon. Vibration of the wire can stretch and compress the inner lumen of the catheter radially or longitudinally, for example resulting in expansion and compression of the membrane radially or longitudinally.

[0019] In relation to wire-mediated effects, vibration of the wire can also be exploited by exposing a distal portion of the wire directly to the target vessel. For this purpose, the distal tip of the wire may extend or protrude beyond the distal end of the catheter or balloon so that ultrasonic activation of the distal portion of the wire, thus exposed, creates cavitation within the surrounding blood vessel to transmit shockwaves directly to the target lesion. In this respect, the geometry of the wire optimises lateral transmission at ultrasonic frequencies, thereby effecting local ablation through microcavitation and bubble collapse which then propagates shockwaves through the calcified component of medial plaque.The distal portion of the wire protruding beyond the distal end of the catheter or balloon may include all or part of the distal section. The protruding distal portion may further include all or part of the intermediate section, and may still further include a distal part of the proximal section.

[0020] The ultrasonic frequencies employed to activate the wire produce radial harmonic frequencies that are associated with sonoporation and the potentiation of drug delivery, be it from bolus or scaffold, or from the balloon to the vessel wall during angioplasty. This applies to both balloon-mediated effects and wire-mediated effects. Sonoporation affects the vessel wall by opening up interstitial spaces and cell walls to facilitate transportation of drug macromolecules through the tissue. Cavitation close to the vessel wall can open up inter-cell or endothelial gaps to allow a drug to enter and / or can reduce the particle size of the drug, the better to fit through such gaps.

[0021] Where a catheter wall lies between the wire and the membrane of the balloon, transmission of ultrasonic vibration to the membrane depends upon the ability of the catheter wall to vibrate with such fidelity to the impinging ultrasound as to transmit ultrasonic activity into and through the annular chamber of the balloon. Such transmissions may be capable of producing cavitation within or outside the balloon. However, even if localised transmission does not impart sufficient acceleration to produce cavitation, useful vibration may still be communicated to the membrane through the liquid that inflates the balloon.

[0022] The mechanical properties of the catheter wall determine its efficiency in conveying the desired vibrations to develop a shock field within the balloon around the catheter. These properties include the intrinsic properties of the catheter wall material, such as its elastic response, in addition to its thickness and geometry.

[0023] Effective transmission of vibrations through the catheter wall and into the membrane of the balloon benefits from substantially uniform active transmission around the inner circumference of the catheter wire lumen. Beneficially in this respect, the multiharmonic vibrations producing orbital oscillation of the sections of the wire are such that the wire maps out its activity uniformly around the catheter wire lumen.

[0024] The radial thickness of the annulus between the wire and the wall of the catheter wire lumen will affect the formation and propagation of cavitation mechanisms serving topromote the transmission of the vibrational energy to the membrane of the balloon. To ensure that the lumen around the wire is filled with liquid, the lumen may be closed at its ends and sealed after filling, optionally after being pressurised, or the lumen can be flushed with liquid.

[0025] The design and inflation of the balloon will also influence the manner in which its excitation by the wire can produce cavitational effects. The volume and pressure of the liquid inflation medium, influencing its partial pressure, can also be significant, as cavitation will only occur when local pressure falls below the vapour pressure of the medium. The partial pressures of any gases present and the hydrostatic pressure applied can determine the formation, agglomeration and implosion of cavitation bubbles at their critical partial pressure in the inflation medium and in the surrounding vascular medium. Pressure of the liquid used for inflation may therefore be monitored and controlled. The temperature of the inflation medium and of the surrounding treatment area could also influence cavitation and so may also be monitored and controlled by cooling or heating the liquid used for inflation as appropriate.

[0026] The liquid medium used to inflate the balloon may be chosen to promote cavitation or be more conducive to shockwave travel, acoustic streaming and / or formation of microjets within the balloon. Such media could include contrast fluid, saline fluid, a mixture of contrast fluid with saline fluid, or a liquid containing high concentrations of dissolved gases such as CO2. Liquids that contain or are enriched by stable microbubbles, such as a microbubble-containing contrast agent, can also be used. The viscosity of the inflating medium may also be significant.

[0027] A medium containing microbubbles or otherwise promoting cavitation could be injected through a catheter to fill a blood vessel around an exposed distal portion of the wire that extends distally beyond the catheter. The activated wire may initiate cavitation in that region and the presence of the injected medium can promote bubble development and implosion with a resulting lithotripsy effect. In addition to the lithotripsy effect, the medium and microbubbles could contain a therapeutic agent which is thereby delivered locally more effectively. Microbubbles of CO2or other gases may also have benefits for imaging ultrasound.

[0028] As disclosed in our previous patent applications referenced above, the dimensions and geometry of the wire are chosen to produce lateral activity within an orbit around and along a central longitudinal axis. Various configurations or shapes of the distal sectioncan be employed to maximise pressure fluctuations and hence cavitation. The distal section can also be tailored for directional effect. For example, vibrations can radiate from the wire preferentially in a radial rather than longitudinal direction for an outward or dilatational lithotripsy effect.

[0029] In some examples, the cross-section of at least one section of the wire, such as the distal section, could be non-circular, for example rectangular, square or elliptical, rather than circular. The wire may have contour features such as dimples or a series of necks disposed between enlarged or bulbous sections. The diameter of the wire may have a wave profile, such as a square wave profile, along its length to create localised pockets of pressure fluctuation.

[0030] Other parameters that can amplify or modulate the effect of the vibrating wire on the balloon membrane include: the diameter of the wire versus the inner diameter of the catheter, hence whether a loose or tight fit; the type of fluid that fills the catheter; the configuration of the distal portion of the wire, whether straight, tapered or shaped, for example with a waveform profile extending along its length; and the material of the catheter and its distal tip, whether compliant or rigid, or of PTFE, nylon or braided construction.

[0031] In summary, the invention resides in an endovascular apparatus for performing intravascular treatment. The apparatus comprises: an angioplasty balloon mounted on a catheter, the balloon comprising an inflatable chamber and a membrane that is expandable radially from the catheter by inflation of the chamber; and an ultrasonic waveguide extending along a waveguide lumen of the catheter and disposed radially inward of the membrane of the balloon. The membrane of the balloon could be coated or impregnated with a drug or other therapeutic agent.

[0032] A wall of the waveguide lumen may be disposed at a radial position between the waveguide and the membrane of the balloon. In that case, the wall of the waveguide lumen can seal the inflatable chamber of the balloon from the waveguide lumen. In any case, the inflatable chamber of the balloon may be in fluid communication with the waveguide lumen, whether through an intervening wall of the catheter or otherwise. For example, the waveguide lumen may be interruped in longitudinal alignment with the balloon.A proximal seal may be provided around the waveguide, that seal being arranged to close the waveguide lumen at a proximal location relative to the balloon. A distal seal may also be provided, arranged to close the catheter at a distal location relative to the balloon.

[0033] An exposed distal portion of the waveguide, exemplified by a wire, may extend distally beyond a distal end of the catheter. The wire may comprise a proximal section, a distal section of lesser diameter than the proximal section, and an intermediate section that tapers distally from the proximal section to the distal section. In that case, the exposed distal portion may comprise at least some of the distal section of the wire and optionally also at least some of the intermediate section of the wire extending distally beyond the distal end of the catheter.

[0034] The distal section of the wire may terminate in an enlargement at a distal tip of the wire, and / or may comprise two or more necks in longitudinal series. Successive necks of that series may be of reduced thickness relative to an enlarged portion disposed between the successive necks.

[0035] To promote cavitation, a liquid enriched with microbubbles or dissolved gas may be disposed within the inflatable chamber of the balloon and / or within the waveguide lumen of the catheter.

[0036] The apparatus of the invention may be combined with an actuator that comprises an ultrasonic transducer coupled to the waveguide.

[0037] The inventive concept embraces a corresponding method of intravascular treatment. The method comprises: positioning a catheter-mounted angioplasty balloon at a treatment site in a blood vessel; inflating a chamber of the balloon to expand a membrane of the balloon toward a wall of the vessel; activating an ultrasonic waveguide disposed radially inward of the membrane to generate shockwaves by cavitation in liquid surrounding the waveguide; and transmitting the shockwaves to the membrane to vibrate the membrane. The vessel may be dilated by expanding the membrane.

[0038] The shockwaves can be transmitted to the membrane via an intervening wall of the catheter, for example by transmitting the shockwaves into the chamber by vibrating the wall of the catheter. It is possible to vibrate the wall of the catheter by contact with thewaveguide. It is also possible to transmit shockwaves to the membrane through a body of liquid with which the waveguide and the membrane are both in contact.

[0039] The membrane of the balloon can be expanded into contact with the wall of the vessel, in which case the shockwaves can be transmitted from the membrane into tissue of the vessel or a lesion of the vessel through that contact. It is also possible to transmit the shockwaves from the membrane into tissue of the vessel or a lesion of the vessel through a liquid-filled gap between the membrane and the wall of the vessel. In this respect, additional cavitation shockwaves can be generated outside the membrane by vibration of the membrane. Similarly, additional cavitation shockwaves can be generated within the chamber of the balloon.

[0040] At least a longitudinal section of the waveguide can be activated to express multiharmonic oscillations, the waveguide thereby mapping out ovoidal orbits within a generally cylindrical volume disposed radially inward of the membrane. The waveguide can be activated in a liquid enriched with microbubbles or dissolved gas, and shockwaves can be transmitted to the membrane via a liquid enriched with microbubbles or dissolved gas.

[0041] The method of the invention may further comprise: exposing a distal portion of the waveguide extending distally beyond a distal end of the catheter; by activation of the waveguide, generating shockwaves by cavitation in liquid within the vessel surrounding the exposed distal portion, outside the catheter; and transmitting the shockwaves through that liquid to the wall of the vessel or to a lesion in the vessel. For example, a passage can be excavated in the lesion by activation of the distal portion of the waveguide.

[0042] The method of the invention is apt to be used in an intravascular lithotripsy procedure. The method of the invention can also be used to effect sonoporation by activation of the waveguide to promote distribution, uptake or absorption of drugs or other agents into tissue of the vessel or a lesion of the vessel. The drugs or other agents may be coated on or impregnated into the membrane of the balloon, and / or provided in a flow of liquid along a lumen of the catheter.

[0043] Thus, an endovascular apparatus of the invention comprises an angioplasty balloon mounted on a catheter. The balloon has an inflatable chamber and a membrane that isexpandable radially by inflation of the chamber. An ultrasonic waveguide extending along a waveguide lumen of the catheter is disposed radially inward of the membrane.

[0044] The catheter-mounted balloon is navigated to a treatment site in a blood vessel. The chamber of the balloon is then inflated to expand the membrane toward a wall of the vessel. Ultrasonically activating the waveguide generates cavitation shockwaves in liquid surrounding the waveguide. Energy of those shockwaves is transmitted to the membrane to vibrate the membrane and is thereby transmitted onwards from the membrane to the wall of the vessel or to a lesion in the vessel.

[0045] In order that the invention may be more readily understood, reference will now be made, by way of example, to the accompanying drawings in which:

[0046] Figure 1 is an overview of a system of the invention;

[0047] Figure 2 is a schematic cross-sectional view showing a balloon in the system of Figure 1 inflated in situ to engage a lesion in a blood vessel;

[0048] Figure 3 is a schematic representation of cavitation and shockwaves generated by ultrasonic activation of a wire in the system of Figure 1 ;

[0049] Figure 4 is a schematic view in longitudinal section showing cavitation and shockwaves propagating within and from the balloon;

[0050] Figure 5 is a schematic side view of a wire of the system of Figure 1 , not to scale;

[0051] Figure 6 is a schematic side view of the wire of Figure 5 activated within a balloon in a system of the invention to treat a lesion in a blood vessel;

[0052] Figure 7 is a schematic side view of a variant of the arrangement of Figure 6, in which the wire extends distally beyond the balloon and a catheter supporting the balloon;

[0053] Figure 8 is a schematic side view of the variant of Figure 7 when excavating a lesion in the form of a chronic total occlusion;Figure 9 is a schematic side view of a further variant of the arrangement of Figure 6; and

[0054] Figure 10 is a schematic side view of a variant of the wire of Figure 5, not to scale.

[0055] Referring firstly to Figure 1 of the drawings, a system 10 of the invention for performing IVL is shown here in overview. The system 10 comprises a controller 12 that generates and modulates a high-frequency electrical signal. In this example, a cable 14 conveys the signal from the controller 12 to an actuator 16 that contains a transducer for converting the signal into mechanical vibrations at an ultrasonic frequency of, for example, 40kHz. In other examples, the controller 12 could be integrated into the actuator 16 as a single unit.

[0056] The transducer of the actuator 16 is mechanically coupled to a waveguide, exemplified here by a wire 18, to convey ultrasonic vibrations into and along the wire 18. The transducer can be coupled to the wire 18 by clamping at any of various locations along the length of the wire 18 selected to activate oscillatory motion of the wire 18.

[0057] Consequently, a proximal portion of the wire 18 extends proximally from the actuator 16. The actuator 16 can be arranged to damp vibration of the proximal portion.

[0058] A distal portion of the wire 18 extends distally from the actuator 16 to be inserted into a wire lumen of an intracorporeal balloon catheter 20 via a proximal Iuer22. The Iuer22 may include a seal or employ a haemostasis valve to facilitate sealing around the wire 18 when flushing a lumen of the catheter 20. The catheter 20 includes a distal balloon 24 that can be inflated in situ within the vasculature by an inflation device 26 connected to the luer 22. For this purpose, as is conventional, the catheter 20 can also include a parallel inflation lumen for effecting fluid communication between the inflation device 26 and the balloon 24. An inflation lumen has been omitted from the drawings for simplicity, hence showing only the wire lumen of the catheter 20.

[0059] Specifically, the catheter 20 is introduced into and navigated through the vasculature to position the balloon 24 within a target lesion. The balloon 24 is then pressurised or inflated to be at least partially expanded, preferably to ensure contact between the balloon 24 and the lesion. The wire 18 is placed within a wire lumen of the catheter 20 to extend along and concentrically within the balloon 24. The catheter 20 can be placed in the vasculature with the wire 18 already within the catheter 20, or the wire 18 can be inserted into the catheter 20 after the catheter 20 has been placed in the vasculature.The actuator 16 is coupled to a selected location along the wire 18 and activated to convey ultrasonic energy into the wire 18.

[0060] Figure 2 shows the wire 18 disposed within the lumen of the catheter 20. The balloon 24 surrounds the catheter 20 in substantially concentric relation and has been inflated in situ into contact with a target lesion 28 within a wall of a vessel 30 such as an artery. It will be appreciated that this is a schematic representation of the anatomy and that, for example, the vessel 30 and hence the balloon 24 are unlikely to have perfectly circular cross-sections.

[0061] Figure 3 represents the cavitation mechanism by which vibration of the wire 18 generates shockwaves. Vibration of the wire 18 produces localised pressure differentials by sinusoidal cycles of massive acceleration and deceleration and hence sudden localised pressurisation and decompression. This forms micro-scale zones or regions of cavitation and compression as pressure gradients alternate under the shockwaves produced from movement of, and contact with, the body of the wire 18.

[0062] The localised fluctuating pressure differentials produced by activity of the wire 18 in a body of liquid 34 around the wire 18 allows microbubbles to form where pressure reduces. Streaming assists the microbubbles to coalesce into larger bubbles, and then increased pressure promotes collapse or implosion of those bubbles to produce shockwaves. The bubbles produced by cavitation can be stable enough to coalesce and grow, only to collapse or implode when they grow beyond a sustainable size or when they are acted upon by increased pressure.

[0063] More specifically, as shown in Figure 3, vibration of the wire 18 creates regions 32 of low pressure in a liquid 34 surrounding the wire 18 within the catheter, such as blood. Cavitation is initiated in the liquid 34 when the local pressure is lower than the vapour pressure of the liquid 34, leading to formation and growth of bubbles 36. The bubbles 36 then collapse rapidly inwardly, creating local regions 38 of high pressure that generate shockwaves 40. The shockwaves 40 propagate through the liquid 34 and eventually into the surrounding lesion 28 and the tissue of the vessel 30, disrupting the lesion 28. The shockwaves 40 can travel directly into the lesion 28 and the tissue 28 if a distal portion of the wire 18 is exposed, or can travel indirectly via the catheter 20 and the balloon 24 where the wire 18 is within the catheter 20.Figure 4 represents the active wire 18 as a set of superimposed waveforms, reflecting how the wire 18 vibrates simultaneously with a harmonic waveform at a fundamental frequency, at or near the drive frequency, and also at superharmonic and subharmonic resonant frequencies. When activated, a distal section of the wire 18 moves in a primary longitudinal mode and also laterally with radial and circumferential components. These waveforms interfere with each other, causing combinations or superpositions of the superharmonic and subharmonic waveforms to generate complex undulating movements of the wire 18. Those movements are transmitted proximally from the distal section into other sections of the wire 18, disposed proximally relative to the distal section.

[0064] The complex movement of the wire 18 extending through the catheter 20 within the balloon 24 causes the wire 18 to map out a substantially cylindrical volume whose diameter is substantially greater than the diameter of the wire 18 itself. That volume extends along the length of the catheter 20 within the balloon 24, hence radiating vibrational energy effectively not only into, but also along the length and around the circumference of the balloon 24.

[0065] Figure 4 also shows how energy imparted by the ultrasonically-activated wire 18 propagates radially outwardly in a cascade of shockwaves 40 through the catheter 20 and the balloon 24 to enter any fluid, lesion or tissue that surrounds or lies beside the balloon 24. Firstly, bubbles 36 generated by cavitation produce shockwaves 40 that radiate outwardly from the wire 18 through fluid within the wire lumen of the catheter 20. Those shockwaves 40 impinge on the flexible wall of the catheter 20 and are transmitted from there into fluid within the surrounding annulus of the balloon 24, where further cavitation bubbles 36 and / or shockwaves 40 may be generated in consequence as shown.

[0066] Shockwaves 40 radiating from the fluid within the annulus of the balloon 24 impinge on the flexible membrane of the balloon 24 and are transmitted from there into a lesion and / or vessel disposed radially outside the balloon 24. Transmission of shockwaves 40 into a lesion may be effected by direct contact between the membrane of the balloon 24 and the lesion or via an intervening fluid in any annular space remaining between the balloon and the lesion.

[0067] Figure 5 shows a wire 18 that has a substantially straight-sided proximal section 42 of uniform diameter, a distally-tapering intermediate section 44 and a substantiallystraight-sided distal section 46 that terminates, in this example, with an enlarged, bulbous distal tip 48 at its free end. The enlarged distal tip 48 adds inertia to the wire 18 to define a node for the waveforms that are expressed in the distal section 46. The distal section 46 is otherwise of uniform diameter.

[0068] The actuator 16 is coupled to the proximal section 42 of the wire 18, imparting longitudinal vibrations that are amplified by the tapered intermediate section 44 and expressed in the activated distal section 46 with the aforementioned combinations of longitudinal and lateral motions resulting in orbital oscillation. As noted above, the orbital motion of the distal section 46 is also conveyed proximally along the wire 18 to the intermediate section 44 and the proximal section 42, which also oscillate orbitally in consequence.

[0069] By virtue of the taper of the intermediate section 44 between them, the distal section 46 of the wire 18 has a smaller diameter than the proximal section 42. The taper of the intermediate section 44 is slight and so is greatly exaggerated in these drawings, which are not to scale. The lengths of the proximal section 42, the intermediate section 44 and the distal section 46 shown in the drawings are also not to scale. Their lengths can be chosen to have a longitudinal resonant mode at or near the driving frequency, such as 40 kHz, with strong sub-harmonics at or near 20kHz, 10 kHz or others in the distal section 46.

[0070] Where A is the wavelength of the primary driving frequency, the intermediate section 44 may extend over a multiple of A in length or a fraction of A in length, that fraction preferably having with a numerator of 1 and an even denominator - for example in the sequence 1 / 2, 1 / 4, 1 / 8... - whereas the distal section 46 may have a length of A / 2 or a multiple of A / 2 or a fraction of A / 2, such as A / 4. Typically, the distal section 46, at least, has a circular cross-section but other regular or irregular cross-sectional shapes are possible to allow modulation of axial and / or lateral vibration modes.

[0071] Figure 6 shows the wire 18 of Figure 5 inserted into a catheter 20 extending within and along an angioplasty balloon 24 that has been inflated into contact with a lesion 28 in a vessel 30. In this example, the distal tip of the wire 18 lies within the catheter 20. Activation of the wire 18 generates cavitation and shockwaves 40 in the liquid within the catheter 20 and in the liquid medium that inflates the balloon 24. Those shockwaves act on the lesion 28 via the membrane of the balloon 24, which causes propagation of cracks 50 in, and fragmentation of, calcified plaque of the lesion 28.In Figures 7 and 8, a distal portion of the wire 18 protrudes distally beyond the surrounding catheter 20. In the example shown in Figure 7, the protruding distal portion comprises the entire distal section 46 and at least part of the intermediate section 44 of the wire. In other examples, the protruding distal portion could only comprise the distal section 46 or could further comprise a distal part of the proximal section 42 of the wire 18.

[0072] Consequently, parts of the lesion 28 located distally with respect to the distal tip of the catheter 20 are subject to direct action of shockwaves 40 arising from the cycle of cavitation and bubble collapse generated by activation of the distal portion of the wire 18 exposed within the bloodstream. In these examples, cavitation is promoted by optional injection of a microbubble-containing liquid 52 along a lumen of the catheter 20 to enter the volume in the vessel 30 around the distally-protruding portion of the wire 18.

[0073] Thus, systems of the invention can act on the local portion of a lesion 28, offset longitudinally from a balloon 24, while also acting on other parts of the lesion 28 by transmission of ultrasonic vibration through the inflation medium and the membrane of the balloon 24. Indeed, systems of the invention can also use the activated wire 18 to excavate a lesion 28. In this respect, Figure 8 shows the distal tip of the wire 18 acting on, and excavating a channel through, a portion of a lesion 28 in the form of a chronic total occlusion (CTO). Here, beneficially, the inflated balloon 24 closes the volume around the distally-protruding portion of the wire 18 to confine the injected cavitationpromoting liquid 52 within that volume.

[0074] Turning next to Figure 9, this drawing shows an arrangement in which the catheter 20 is modified to allow the wire 18 to vibrate within the balloon 24 with no intermediate catheter wall disposed between them. Thus, in effect, the membrane of the balloon 24 is incorporated into the wall of the catheter 20 as a more flexible continuation of, or insert into, that wall. The balloon 24 can therefore be inflated via the wire lumen of the catheter 20, without requiring a parallel inflation lumen to do so.

[0075] Here, the wire 18 is in direct opposition to the membrane of the balloon 24 through an open connection between the wire lumen of the catheter 20 and the inflatable chamber of the balloon 24. For this purpose, the wall of the wire lumen of the catheter 20 is partially or wholly terminated, interrupted or cut away within the balloon 24. Moregenerally, fluid communication can be effected between the wire lumen of the catheter 20 and the inflatable chamber of the balloon 24, for example through one or more holes, slits or other openings in the intervening wall of the catheter 20.

[0076] Proximal and distal seals 54 can be provided to maintain pressure of an inflating liquid medium in the balloon 24 as shown Figure 9. The proximal seal 54 accommodates and seals around the wire 18. The distal seal 54 can also accommodate and seal around the wire 18 if the wire 18 protrudes distally from the catheter 20 as shown in Figures 7 and 8. However, in this example, the wire 18 terminates short of the distal end of the catheter 20 and so does not need to penetrate the distal seal 54.

[0077] Finally, Figure 10 shows an alternative configuration of the wire 18 in which the distal section 46 is of non-uniform diameter along its length. Periodic reductions in diameter form necks 56 at longitudinal intervals of As / 2, being half the wavelength of the dominant lateral vibration frequency. These necks 56 act as articulation points along the wire 18, allowing increased amplitude of lateral vibration. The necks 56 may alternate with enlarged portions 58 of relatively increased diameter. Each enlarged portion 58 may be tuned individually to optimise vibration of the wire 18 and consequent generation of pressure fields.

[0078] Many other variations are possible within the inventive concept. For example, the wire 18 and / or the catheter 20 could be moved longitudinally relative to each other in distal and proximal directions, for example by turning a thumbwheel on the actuator 16 that acts on the tubular wall of the catheter 20. The behaviour of the wire 18 can also be influenced by adjusting radial clearance between the wall of the catheter 20 and the wire 18 or by applying a radially inward force from the wall of the catheter 20 around the wire 18, for example using an inflatable collar within the catheter 20.

[0079] The exterior of the balloon 24 could have micro-blades or other sharp formations running along or across its working area in the manner of a scoring angioplasty balloon. Such protruding formations may help to fracture a calcified lesion 28 to which shockwaves 40 are delivered via the balloon 24. In other embodiments, the balloon 24 can have a non-circular profile or surface shaped with contours or relief designed to concentrate stress and thereby assist the process of plaque fracture. Ultrasonic activation of such features can assist transmission of shockwaves and can provide for more effective fragmentation of asymmetric lesions 28 around a vessel 30.The balloon 24 can be coated or impregnated with drugs or other therapeutic agents to be delivered to the lesion 28 or to the tissue of the vessel 30 by contact or proximity. Similarly, drugs or other therapeutic agents can be conveyed in a flow of liquid along the catheter 20 for injection at the treatment site. In each case, activation of the wire 18 can effect sonoporation, using ultrasound to improve the distribution, uptake or absorption of drugs or other agents.

Claims

Claims1. An endovascular apparatus for performing intravascular treatment, the apparatus comprising:an angioplasty balloon mounted on a catheter, the balloon comprising an inflatable chamber and a membrane that is expandable radially from the catheter by inflation of the chamber; andan ultrasonic waveguide extending along a waveguide lumen of the catheter and disposed radially inward of the membrane of the balloon.

2. The apparatus of Claim 1 , wherein a wall of the waveguide lumen is disposed at a radial position between the waveguide and the membrane of the balloon.

3. The apparatus of Claim 2, wherein the wall of the waveguide lumen seals the inflatable chamber of the balloon from the waveguide lumen.

4. The apparatus of Claim 1 or Claim 2, wherein the inflatable chamber of the balloon is in fluid communication with the waveguide lumen.

5. The apparatus of Claim 4, wherein the waveguide lumen is interruped in longitudinal alignment with the balloon.

6. The apparatus of Claim 4 or Claim 5, comprising a proximal seal around the waveguide, the seal being arranged to close the waveguide lumen at a proximal location relative to the balloon.

7. The apparatus of any of Claims 4 to 6, comprising a distal seal arranged to close the catheter at a distal location relative to the balloon.

8. The apparatus of any preceding claim, wherein an exposed distal portion of the waveguide extends distally beyond a distal end of the catheter.

9. The apparatus of any preceding claim, wherein the waveguide is a wire that comprises a proximal section, a distal section of lesser diameter than the proximalsection, and an intermediate section that tapers distally from the proximal section to the distal section.

10. The apparatus of Claim 9 when dependent on Claim 8, wherein the wire has an exposed distal portion comprising at least some of the distal section of the wire and optionally also at least some of the intermediate section of the wire extending distally beyond the distal end of the catheter.

11. The apparatus of Claim 9 or Claim 10, wherein the distal section of the wire terminates in an enlargement at a distal tip of the wire.

12. The apparatus of any of Claims 9 to 11 , wherein the distal section of the wire comprises two or more necks in longitudinal series, successive necks of the series being of reduced thickness relative to an enlarged portion disposed between the successive necks.

13. The apparatus of any preceding claim, wherein the inflatable chamber of the balloon contains a liquid enriched with microbubbles or dissolved gas.

14. The apparatus of any preceding claim, wherein the waveguide lumen of the catheter contains a liquid enriched with microbubbles or dissolved gas.

15. The apparatus of any preceding claim, wherein the membrane of the balloon is coated or impregnated with a drug or other therapeutic agent.

16. The apparatus of any preceding claim, in combination with an actuator that comprises an ultrasonic transducer coupled to the waveguide.

17. A method of intravascular treatment, comprising:positioning a catheter-mounted angioplasty balloon at a treatment site in a blood vessel;inflating a chamber of the balloon to expand a membrane of the balloon toward a wall of the vessel;activating an ultrasonic waveguide disposed radially inward of the membrane to generate shockwaves by cavitation in liquid surrounding the waveguide; andtransmitting the shockwaves to the membrane to vibrate the membrane.

18. The method of Claim 17, comprising transmitting the shockwaves to the membrane via an intervening wall of the catheter.

19. The method of Claim 18, comprising transmitting the shockwaves into the chamber by vibrating the wall of the catheter.

20. The method of Claim 19, comprising vibrating the wall of the catheter by contact with the waveguide.

21. The method of any of Claims 17 to 20, comprising transmitting the shockwaves to the membrane through a body of liquid with which the waveguide and the membrane are both in contact.

22. The method of any of Claims 17 to 21, comprising expanding the membrane into contact with the wall of the vessel, and transmitting the shockwaves from the membrane into tissue of the vessel or a lesion of the vessel through that contact.

23. The method of any of Claims 17 to 21, comprising transmitting the shockwaves from the membrane into tissue of the vessel or a lesion of the vessel through a liquid-filled gap between the membrane and the wall of the vessel.

24. The method of any of Claims 17 to 23, comprising generating additional cavitation shockwaves outside the membrane by vibration of the membrane.

25. The method of any of Claims 17 to 24, comprising generating additional cavitation shockwaves within the chamber.

26. The method of any of Claims 17 to 25, comprising activating the waveguide to express multi-harmonic oscillations, the waveguide thereby mapping out ovoidal orbits within a generally cylindrical volume disposed radially inward of the membrane.

27. The method of any of Claims 17 to 26, comprising activating the waveguide in a liquid enriched with microbubbles or dissolved gas.

28. The method of any of Claims 17 to 27, comprising transmitting the shockwaves to the membrane via a liquid enriched with microbubbles or dissolved gas.

29. The method of any of Claims 17 to 28, comprising:exposing a distal portion of the waveguide extending distally beyond a distal end of the catheter;by said activation of the waveguide, generating shockwaves by cavitation in liquid within the vessel surrounding the exposed distal portion, outside the catheter; andtransmitting the shockwaves through that liquid to the wall of the vessel or to a lesion in the vessel.

30. The method of Claim 29, comprising excavating a passage in the lesion by the activation of the waveguide acting on the distal portion.

31. The method of any of Claims 17 to 30, comprising effecting sonoporation by activation of the waveguide to promote distribution, uptake or absorption of drugs or other agents into tissue of the vessel or a lesion of the vessel.

32. The method of Claim 31 , comprising providing the drugs or other agents coated on or impregnated into the membrane of the balloon.

33. The method of Claim 31 or Claim 32, comprising providing the drugs or other agents in a flow of liquid along a lumen of the catheter.

34. The method of any of Claims 17 to 33, comprising effecting dilation of the vessel by expanding the membrane.

35. The method of any of Claims 17 to 34, wherein the treatment is intravascular lithotripsy.

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