Patent Description:
Most endovascular procedures require the use of flexible catheters, for example, to deliver contrast injection, to deliver implantable devices, perform vascular procedures, or to aspirate. Due to the tortuous nature of the vasculature, it is important for catheters to be flexible enough to travel through vessels without excessive force. However, there is generally a trade-off between the features of catheter diameter, trackability, flexibility, and kink resistance. An increase in catheter diameter tends to increase its stiffness, which lowers its trackability and may dangerously increase vascular sheer forces. An increase in flexibility tends to increase the tendency of the catheter to kink as it is pushed through the vasculature, which limits the catheter to vessels with gentle curves. In general, a decrease in wall thickness increases flexibility and allows access to more tortuous vessels, there being a trade-off between flexural stiffness and kink resistance.

<CIT>) describes a flexible inner liner for the working channel of an endoscope.

<CIT> discloses a catheter having a nonuniform axial-stiffness comprising an inner liner defining a longitudinally extending and generally uniform bore; a non-uniform axial-stiffness outer jacket defining a longitudinally tapered outer surface, and a reinforcement layer encapsulated between the inner liner and the non-uniform axial-stiffness outer jacket.

The invention is directed towards providing a catheter with improved properties for desired flexural stiffness and flexibility, to thereby allow use in difficult locations such as where there are significant curves and small dimensions in the patient vessels.

The invention provides a catheter as set out in claim <NUM>.

A catheter has a jacket defining a lumen and a helical support. The catheter has a proximal portion and a distal portion the distal portion having for at least some of its length a corrugated outer surface. A transition portion provides an optimum transition in flexural stiffness by way of features of the jacket including geometry of jacket corrugations, or overlapping tubular layers. The distal end of the distal portion may in some examples have an extension of liner material folded over to provide a particularly soft tip. In other examples the liner is terminated before the distal tip. The catheter is particularly suited to an aspiration device with a flow restrictor and the distal portion distal of the flow restrictor. An aspiration system may employ the catheter with a pump which dynamically applies negative or positive pressure to optimally aspirate a clot.

In one aspect we describe a catheter comprising a jacket defining a lumen and comprising a helical support in jacket material along at least some of its length, the catheter comprising at least a proximal portion and a distal portion, said distal portion having for at least some of its length a corrugated outer surface. The catheter comprises a transition portion between said proximal portion and said distal portion. The transition portion preferably has a corrugated outer surface in which at least some corrugations of the corrugated outer surface have a smaller depth and/or width than corrugations of the surface of the distal portion.

Although not forming part of the invention, we Weal so describe a method of manufacturing a catheter, wherein the jacket is formed in at least some regions by positioning a membrane over a helical structure, applying heat so that the membrane reflows such that it forms around the helical structure, winding a tensioned cinch wire around the outside of the membrane such that it forces membrane material into grooves between each loop of the helical structure, heat setting the membrane to fix the corrugations in place, and unwinding the tensioned cinch wire leaving the corrugations behind.

The jacket may include fluoropolymers and said fluoropolymers may be bonded with each other and/or with other polymers at bonding interfaces. Chemical treatment may be applied at said interfaces using an etching solution. The etched fluoropolymer may be coated with a thin layer of urethane such as Chornoflex, and on the application of heat, this layer flows and acts to tie the fluoropolymer to a second etched fluoropolymer layer or to a different polymer layer.

In one aspect, the method comprises providing the helical support within a polymer jacket which is bonded to a liner to form a base assembly, placing an outer liner which will not bond to the polymer jacket over the jacketed coil, winding the cinch wire in a helix onto the outside of the outer liner under tension thereby imparting a corrugate geometry, heating to reflow or anneal the material to set said material into the corrugate geometry, cooling the assembly, removing the cinch wire, and peeling off the outer liner.

We also describe an aspiration device comprising a catheter of any embodiment described herein and a flow restrictor, in which the distal portion is distal of the flow restrictor. The catheter may comprise a transition portion between said proximal portion and said distal portion, and at least part of said transition portion extends distally of the flow restrictor.

The flow restrictor may comprise a balloon, and the balloon is arranged to inflate to block blood flow before aspiration of a clot into the catheter distal portion. Alternatively, it may be used to block blood flow before precise delivery of an embolic agent to region of the vasculature, tumour, or organ.

Length of the distal portion is in one case suited to reach specific anatomical locations, such as the distal internal carotid artery, terminus of the internal carotid artery, proximal MI, distal MI, proximal M2, distal M2, basilar, or vertebral vessels, wherein the flow restrictor remains in or proximal of the C1 segment of the ICA.

We also describe a method of use of an aspiration device of any embodiment, the method comprising steps of deploying the aspiration device in a patient's blood vessel, navigating the distal portion to a clot in the vessel, causing the flow restrictor to block blood flow, applying a vacuum to the catheter so that the clot is aspirated into the distal portion.

We also describe an aspiration system comprising a catheter of any embodiment, a pump linked with the catheter proximal portion, and a controller arranged to vary aspiration pressure during aspiration of a clot. The system may comprise a lumen pressure senor and the controller is configured to vary aspiration pressure according to sensed pressure within the catheter lumen. The system may comprise a lumen fluid flow sensor, and the controller is configured to vary aspiration pressure according to sensed fluid displacement in the lumen.

The controller may be configured to improve the efficiency of aspiration by preventing clogging of the catheter, and/or to promote maceration and deformation of a clot to enable it to travel through the lumen.

We also describe methods of use of an aspiration system of any embodiment, in which the controller varies aspiration pressure during aspiration of a clot. There may be a lumen pressure senor and the controller varies aspiration pressure according to sensed pressure within the catheter lumen. There may be a lumen fluid flow sensor, and the controller varies aspiration pressure according to sensed fluid displacement in the lumen. Preferably, the controller improves efficiency of aspiration by preventing clogging of the catheter, and/or promotes maceration and deformation of a clot to enable it to travel through the lumen. Also, the controller may provide a vacuum or a positive pressure based on measured pressure, and change direction hence altering the pressure and fluid displacement.

The controller may have defined upper and lower limits of pressure or displacement to decide whether to apply a vacuum or pressurize, and/or it may cause the catheter to cyclically ingest and if required expel, at least some of a clot, whereby there is deformation of the clot to improve efficiency of aspiration and prevent clogging of the catheter. The controller may begin to draw some vacuum so that a negative pressure is measured and in the absence of an occlusion or partial occlusion of the catheter tip, this will be a nominal reading, representing free-flow of fluid through the catheter, and once the catheter is advanced and engaged with the clot, an increase in the vacuum is observed.

The controller may increase a vacuum to ingest more of a clot and reverse at a low limit of pressure defined such that during vacuum, a portion of the clot has been aspirated but not so much that the clot has become irreversibly clogged and the lower limit of vacuum can be set above a full vacuum pressure to prevent ingestion of too large a clot that could clog the catheter.

For example, in methods of operation of the aspiration system the controller may set the low limit between -<NUM>-HG and -<NUM>-Hg, preferably between -<NUM>-HG and -<NUM>- Hg, more preferably between -<NUM>-HG and -<NUM> mrn-Hg, and more preferably between -<NUM> mrn-HG and -<NUM>-Hg; and it may cause direction of fluid displacement of the pump to be reversed thereby increasing the pressure measured, and unloading a clot.

The invention will be more clearly understood from the following description of some embodiments thereof, given by way of example only with reference to the accompanying drawings in which only <FIG> illustrate all features of the invention, and in which:.

Various embodiments are depicted in the accompanying drawings for illustrative purposes, and should in no way be interpreted as limiting the scope of the embodiments. Furthermore, various features of different disclosed embodiments can be combined to form additional embodiments, which are part of this disclosure.

"Jacket" is the wall of the catheter, and these terms are interchangeable. It may be corrugated in all or some regions along the length (longitudinal direction). It may include any or all of a helical support (or "coil") surrounded by jacket material, and an inner liner. The inner liner, where present, defines the lumen, but otherwise the other jacket material defines the lumen. A liner where present, may be terminated at some location in the catheter.

"Tubular layer" is a layer of material of the jacket.

"Pushability" is understood as the transfer of force and/or displacement applied at a proximal portion of a catheter, along a length of the catheter, to a more distal portion of the catheter. The higher the flexural stiffness the greater the pushability.

"Corrugate" is a rib and recess geometry on the outer surface of the catheter, most often in a spiral pattern.

"Distal" means further from a clinician in use, closer to a catheter tip in the longitudinal direction, and "proximal" means closer to the clinician.

<FIG> illustrates an example of a highly flexible, kink resistant catheter <NUM>. The catheter <NUM> includes a distal portion <NUM>, a proximal portion <NUM>, a central lumen <NUM> and a reinforcing structure such as a helical support <NUM> that runs the length of the catheter. The proximal portion and/or a transition between the distal portion and the proximal portion can in various examples include any of the corresponding features of the catheters described in <CIT>, titled "HIGH FLEXIBILITY, KINK RESISTANT CATHETER SHAFT". The inner tubular layer and/or the outer tubular layer can include PTFE, ePTFE, electrospun PTFE, silicone, latex, TecoThane, nylon, PET, Carbothane (Bionate), SIBS, Tecoflex, Pellethane, PGLA, or Kynar, Polyethylene and cyclic olefin copolymers, PEEK.

The inner and outer tubular layers (<FIG>) in at least the distal portion can be formed from a single section of material or a number different sections of similar or different material. In this example the outer tubular layer <NUM> of the distal portion is formed from a polyurethane (e.g. Pellethane 80AE) and the inner tubular layer <NUM> is formed from ePTFE and/or PTFE.

In this case the catheter jacket comprises an inner liner <NUM> and an outer tubular later <NUM> with a helical support <NUM>. The highly flexible distal portion <NUM> (left side) of the catheter is created by forming corrugations <NUM> into the outer surface of the outer tubular layer <NUM>. The helical support <NUM> is encapsulated between the corrugations of the outer tubular layer <NUM> and the outside of the smooth inner tubular layer <NUM> as shown in <FIG>. The formation of a corrugated wall structure during bending provides flexibility while reducing the likelihood of kinking. The corrugated outer surface can also decrease resistance when the outer surface of the catheter contacts a vessel wall. The depth of the corrugations may be tailored to provide a desired variation in stiffness along the length of the catheter as shown in <FIG>.

As shown in <FIG> a parameter "D" is depth of a corrugation and a parameter "W" is the width of a corrugation. The width is not the distance from peak to peak, rather it is the effective width of the valley. In effect for many examples this is provided during manufacture by tightening a cinch wire around a tubular layer, heat treating, and removing the cinch wire to provide the corrugated surface. The width W is approximately the diameter of the cinch wire in this case. The depth D is not necessarily uniform because the pressure applied by the cinch wire may vary along the length of the catheter thereby forming deeper indentations in some locations than in others.

<FIG> shows a cross section through a wall of a catheter tip <NUM>, having an inner layer <NUM>, a helical coil support structure <NUM>, an outer layer <NUM> with a corrugated surface <NUM>. The depth A of the corrugations on the left hand side is greater than the depth B on the right hand side. The section with the lower corrugation depth B may function as a transition region before a tip (left hand side) with more flexibility.

In the examples of <FIG> and <FIG> the coil is embedded in the jacket; being constrained from movement relative to the surrounding jacket material.

Additionally, pitch, or corrugation width variations may be used to control the flexibility locally in the corrugated region. Also, flexibility may be set during manufacture by choosing some length of the coil to be embedded in the jacket or to be floating, the region with the floating coil being more flexible. Where the coil is floating it is in the context of the jacket tubular layers being attached in the spaces between corrugation rubs, such as a jacket tubular layer to an inner liner.

The outer tubular layer can extend at least a length of the highly flexible distal portion or extend beyond the distal portion for some distance along the proximal (midsection) length or extend the entire length of the catheter as shown in <FIG> and <FIG> (which shows the catheter of <FIG> in its full length). Extending the outer tubular layer at least some length beyond the highly flexible distal portion of the catheter allows for a controlled stiffness transition between the distal and proximal portions of the catheter and for the formation of a robust joint between the outer tubular layer and any additional outer jacket materials. Again, flexibility may be set during manufacture by choosing some length of the coil to be embedded in the jacket or to be floating, as is the case for any of the examples described with reference to <FIG> or <FIG>.

To form the corrugations in a tubular membrane, the membrane can first be positioned over the helical reinforcing structure. On the application of heat, the outer tubular membrane will reflow such that it forms around the helical structure. A tensioned wire can then be wound around the outside of the tubular membrane such that it forces portions of the membrane into the grooves between each loop of the supporting helical structure. The tubular membrane can then be heat set to fix the corrugations in place. After this process the tensioned wire may be unwound leaving the corrugations behind.

The inner tubular layer can extend into the proximal portion of the catheter to provide an uninterrupted lumen and to join or improve the joint strength between the highly flexible distal portion of the catheter and the proximal portion of the catheter. The diameter of the inner tubular layer can be constant (e.g. smooth surface). The inner tubular layer may form at least part of or the entirety of the liner as shown in <FIG>. The inner tubular layer can be made from a low friction material such as ePTFE or PTFE.

As explained above, the outer tubular layer of at least the distal portion is formed from a polyurethane (e.g. Pellethane 80AE) and the inner tubular layer is formed from an ePTFE and/or PTFE liner. It is necessary to attach these layers together and this is not easily achieved as fluoropolymers do not form strong bonds with other materials.

To facilitate bonding between fluoropolymers (e.g. ePTFE and PTFE) and between fluoropolymers and other polymers such as polyurethanes (e.g. Pellethane) the outer or bonding surface of the fluoropolymer(s) may be chemically treated using a sodium-based etching solution such as FluoroEtch. The etching solution removes fluorine atoms from the surface of the fluoropolymer and prepares it for bonding.

The etched fluoropolymer can then be coated with a thin layer of urethane, such as ChronoFlex. On the application of heat, this thin ChronoFlex layer flows and acts to tie the fluoropolymer to a second etched fluoropolymer layer or to a different polymer layer as shown in <FIG>. This embeds the coil.

This diagram shows part of the cross-section of a catheter at its distal portion <NUM>. This includes a liner <NUM> of ePTFE or PTFE, a tie layer <NUM> of urethane or FEP tape or FEP powder. Also, there is a Nitinol™ coil <NUM> in an outer jacket <NUM> of ePTFE, or urethane material. The nitinol coil <NUM> is encapsulated between the outer tubular corrugated layer and the smooth inner tubular layer <NUM>. The tie layer <NUM> serves the purpose of attaching the liner <NUM> to the outer jacket material. If the liner is of ePTFE material then it will need to be etched to strip the fluorine atoms so that it will form a better bond with the tie layer.

Again, flexibility may be set during manufacture by choosing some length of the coil to be embedded in the jacket or to be floating, as is the case for any of the embodiments described below with reference to <FIG>.

The ChronoFlex™ tie-layer <NUM> is so thin it does not cause any significant change in wall thickness. An alternative form of tie-layer involves the use of FEP. The fluoropolymer may be sputter coated with a FEP powder which under heat and pressure forms a bond between the coated fluoropolymer layer and a second layer. An ultra-thin FEP tape may also be used in the same application.

The helical support is encapsulated between the corrugations of the outer tubular layer and the smooth inner tubular layer as shown in <FIG>. The inner tubular layer and the outer tubular layer are bonded together in the space between the adjacent loops of the helical support by such mechanisms as a tie-layer. The helical support is bonded within the helical channel formed by the corrugated outer tubular layer, i.e., the helical support is molecularly or physically attached to the outer tubular layer. The helical support may also be bonded to the outside surface of the smooth inner tubular layer. The distal portion of the catheter retains highly flexibility and kink resistance because of the advantages inherent in a corrugated outer structure and using materials of appropriate stiffness and thickness.

In the present configuration, the pitch of the helical support may vary over the length of the catheter to influence the flexural stiffness of the catheter. For example, the helical support could have a different pitch at the proximal loops compared to the distal loops.

If the outer tubular layer of the distal portion of the catheter is formed from a fluoropolymer such as ePTFE or PTFE and the outer tubular layer of the proximal portion is formed from a different polymer then achieving a good bond, especially one that resists delamination during tracking, can be difficult. This may be overcome by sandwiching the outer layer of the proximal portion of the catheter between the inner and outer tubular layers of the distal portion of the catheter as shown in <FIG>.

<FIG> shows a portion <NUM> of a catheter, having an inner lumen <NUM> with a liner, an outer layer <NUM> of Pellethane 80AE material, and Nitinol coils <NUM>. On the right hand side the catheter has a smooth outer surface <NUM>, and distally in a transition section there are corrugations <NUM> with a small depth, and more distally deeper corrugations <NUM> for more flexibility. The arrangement of having a transition section between proximal and distal sections may be referred to as a "sandwich arrangement".

If the inner tubular layer of the distal portion of the catheter is formed from a different material or different section of material from that of the inner tubular layer of the proximal portion then the tubular layers can be joined by creating a small slit or window in one tubular layer and pulling a spliced length of the other tubular layer through it as shown in <FIG>. The helical support is then wound around the outside of these layers thus keeping them together.

<FIG> shows a catheter section <NUM> with a proximal end <NUM>, a transition section <NUM>, and a distal tip <NUM>, and a spliced proximal layer <NUM> with a window <NUM>.

In various examples the helical support is physically attached by being constrained or embedded in the catheter wall to move with its surrounding wall material. Such embedding might be achieved at an interface between the coil and solely the jacket material, or combination of an interface of the jacket material and the inner liner.

The embedding can be achieved by a very tight fit between the coil and the surrounding material. Generally, there is no gap between the surrounding wall material and the coil. Due to the three-dimensional geometry of the coil, when within a surrounding material, it is unable to move independently.

Due to the manufacturing technique in which the material may be moulded around the coil, there is no play between the coil and jacket, meaning it cannot move independently. That is to say, the coil is immovable without concurrent movement or deformation the surrounding jacket material. This lack of play, and tightness of fit means there is an interfacial friction between the coil and surrounding material, further providing constraint, and meaning the coil and surrounding material must move together.

In other examples the coil may be floating, that is to say there is not a tight fit between the material in the jacket and the helical coil. In these instances, there is some play between the helical support and the jacket. This is particularly the case where the jacket material surrounding the helical support is comprised of ePTFE. In this instance, even in the presence of a relatively tight geometric fit, the material is quite supple and may allow movement of the helical support relative to the ePTFE.

In general, the following are some preferred parameter ranges for aspects of the catheter.

For at least some of the length of the catheter the width of the corrugate is no more than <NUM>% of the pitch of the corrugate.

For at least some of the length of the catheter the width of the corrugate is between <NUM>% and <NUM>% of the pitch of the corrugate, and more preferably the width of the corrugate is between <NUM>% and <NUM>% of the pitch of the corrugate.

For at least some of the length of the catheter the width of the corrugate is between <NUM>% and <NUM>% of the pitch of corrugate.

For at least some of the length of the catheter the width of the corrugate is at least <NUM>% of the jacket thickness.

At the most distal region of the distal portion the width of the corrugate it at least <NUM>% of the jacket thickness.

At the most distal region of the distal portion the width of the corrugate it at least <NUM>% of the wall thickness and the depth of the corrugate is at least <NUM>% of the wall thickness.

The ratio of the width of the corrugate to the depth of the corrugate is at least <NUM> in at least one region of the catheter.

In the examples described below the coil may be either embedded or floating in some or all regions of the catheter, unless stated otherwise.

Referring again to the construction of the catheter structure, we achieve a catheter with a highly flexible distal tip, to ensure that a smooth transition in flexural stiffness and pushability is achieved between the flexible distal portion and the proximal portion of the catheter, which may be of more conventional construction. A smooth transition prevents areas of stress and strain concentration within the catheter shaft. Such areas have potential for kinking of the catheter, delamination of layers of material, and/or of damage to key bonds within the catheter.

Bench testing demonstrates the large difference between the stiffness of a conventional catheter tip design and a highly flexible corrugated design. Smoothly bridging of this gap presents a technical challenge.

<FIG> shows force measured at a <NUM> displacement in a <NUM>-point bend test of a conventional catheter design (<NUM>. 80A urethane jacket over a <NUM>. 005in NiTi coil <NUM>. 018in (<NUM>) pitch over on a <NUM>. 001in (<NUM>) PTFE Liner), and highly flexible corrugated ePTFE design (inner and outer <NUM>. 002in (<NUM>) wall ePTFE <NUM>/cm<NUM> density, with a <NUM> in (<NUM>) NiTi coil, <NUM> in (<NUM>) pitch.

It should be appreciated that while very good catheter shaft flexibility allows the catheter to navigate extremely tortuous bends at low force and reduced potential for vessel damage, it can also lead to some compromise in pushability. For clarity, pushability is understood as the transfer of force and/or displacement applied at a proximal portion of a catheter, across a length of the catheter, to a more distal portion.

Catheter flexibility may limit the transfer of a displacement applied at a proximal portion of the catheter to a distal portion of the catheter. This implies a portion of the displacement is absorbed through global deformation of the catheter as shown in <FIG> shows behaviour of a conventional catheter under compression when pushed against restriction. In this instance the length of the catheter <NUM> has not changed. In general, it is this type of shortening which occurs in catheters of conventional construction.

<FIG> shows behaviour of a corrugated catheter <NUM> under compression when pushed against restriction. In the case of a corrugated outer jacket with a thin inner and outer tubular layer, the deformation may be accommodated by the catheter wall. The inner and or outer tubular layers of the catheter can deform locally, particularly in the recess meaning the overall length is reduced. Some of the global deformation of the catheter as shown in <FIG> would also be expected.

This soft compressive behaviour is advantageous at the distal tip as the catheter tip is limited in its ability to move forward causing vessel damage or dissection. However, in cases in which the distal tip is very long, some increased pushability in the proximal portion of the tip may be preferable to allow the physician to navigate the catheter distally and proximally as intended.

In one configuration one or more regions of varying pushability and flexibility are present within the catheter tip comprised of one or more of the regions of a rib and recess construction. <FIG> shows in a catheter <NUM> use of progressively more flexible or less pushable sections of catheter wall <NUM> within the distal tip, distally of a proximal portion <NUM>. In one configuration the most flexible region is on the distal tip of the catheter.

These regions of increased/decreased pushability/flexural stiffness are achieved by a number of features such as embedding of the helical support, alterations to the inner and outer tubular layers (wherein the helical support may or may not be floating between the inner and outer tubular layers), or the use of an in-fill material.

The change in the stiffness or pushability via the transition region may be gradual change or via multiple steps. Where it is stepped or gradually changed it may be achieved by having a particular tubular layer terminated, or by a change to the degree of corrugation or a change in material.

It is envisaged that any or all of these approaches may be combined on some or all of the catheter shaft. Examples are as follows:.

In one configuration the helical support is embedded by being bonded to the outer jacket, of for example ePTFE material. This has the effect of stiffening the catheter wall construction, when compared to a floating helical support, thus reducing the flexibility and increasing the pushability.

In one configuration, in a catheter portion <NUM> the helical support <NUM> is embedded in a matrix <NUM> of continuous porous flexible material such as ePTFE. The outer wall has corrugated surface, as shown in <FIG>. An inner tubular layer, or liner <NUM>, as shown in <FIG>, may not be required.

While ePTFE provides a very soft flexible material in the catheter construction it is also compressible due to its porosity. Furthermore, when used as a thin tubular layer which deforms easily locally, macro pushability can be compromised if an area of the catheter becomes impeded particularly if the distal tip meets a resistance. To improve pushability while maintaining high flexibility, an incompressible flexible material may be used for embedding instead of a porous material such as ePTFE. This means it can accommodate deformation more readily than materials which are not porous.

The corrugations allow localised deformation, while a region of continuous incompressible material ensures the efficient transfer of axial force and displacement along the length of the catheter. By reducing the depth of the corrugations, and correspondingly increasing the thickness of the continuous material, the pushability of the catheter can be increased, while the flexibility is reduced. This may be described as a corrugated jacket design.

In one example the inner tubular layer is comprised of ePTFE. In one configuration the helical support is transposed from the inner liner such that it is not exposed to the liner. This is to prevent movement or debonding of the helical support, and to prevent it placing local stress or strain on the liner of the catheter. The corrugation geometry may be of semi-circular, U-shaped groove, V-shaped, or square groove.

In one configuration the width of the corrugate at the surface of the catheter is at least <NUM>% of the wall thickness of the wall. Preferably, in at least one section the width of the corrugate at the surface of the catheter is at least <NUM>% of the wall thickness at the wall. Preferably, in at least one region of the distal tip, the width of the corrugate at the surface of the catheter is at least <NUM>% of the wall thickness at the wall.

In one example the corrugate depth is between <NUM>% and <NUM>% of the catheter wall thickness. In one configuration the corrugate depth is at least <NUM>% of the catheter wall thickness in at least one section of the catheter.

In one example, the corrugate depth varies along the corrugated region of the catheter from a larger depth distally to smaller depth proximally. In one example, the corrugate width varies along the corrugated region of the catheter from a larger depth distally to smaller depth proximally.

In another example, the corrugate depth varies from a larger depth distally to smaller depth proximally, while the width is substantially constant along the length of the corrugated section of the catheter.

In one example the corrugate represents the impression of a circular helical wire wound from a depth and width of no impression, i.e. no corrugate, to a depth of at least <NUM>% of the wall thickness. It should be appreciated in that instance that the width of the corrugate is varying from <NUM> to a maximum width equivalent to the diameter of the helical wire, or impression which remains following removal of the helical wire.

It should be appreciated that a tensile force on the wound cinch helical wire is required to create the corrugations. For example, a <NUM>. 005in <NUM> Stainless Steel circular cross section wire at 1N tension wound at a force 1N, on a <NUM>. 006in wall thickness 80A jacket with an ID of <NUM>. 088in will achieve a <NUM>-<NUM>% depth of corrugation. (<NUM> inch corresponds to <NUM>) Increasing the tension to 1N tension wound at a force 7N will achieve a <NUM>-<NUM>% depth of corrugation. Varying levels of force will induce different degrees of corrugation. It should be appreciated that corrugations of high depth D as shown in <FIG> will allow the catheter section to flex at a relatively low force. This is because the global bending of the catheter is actually concentrated within the recess of the corrugate.

However, if the corrugation has a very low width, even very deep and numerous corrugations will have a limit to the degree of bending the catheter can accommodate. This is because adjacent corrugations will start to touch one another. Therefore, the flexural stiffness will be low until the adjacent corrugations contact one another, or "bottom-out", at which point the flexure stiffness will increase. Bending will then be accommodated by deformation of the rest of the catheter wall (and no longer primarily within the recesses).

This bottoming-out means the catheter shaft has a lower limit of bend-radius which it can achieve via deformation within the recess. Further bending deformation beyond the bottoming-out limit is achievable but is not accommodated by deformation at the recess of the corrugation; it is accommodated by pressing adjacent corrugations against one another. This is generally at a very high force compared to the deformation which occurs at lower bend radii while the deformation is focused in the recess.

The width of the corrugate should be controlled so as to be large enough to accommodate sufficient deformation within the recess to reach the desired lower limit of bend-radius at relatively low force of bending. This is important as physicians generally wish to be able to navigate catheters at low forces so that the potential for vessel damage is reduced, and the catheters are not deforming the vessels in order to travel forward.

While the width and depth of the corrugation contribute to the flexural stiffness of the catheter, the width can dominate the lower limit of bend-radius to which the catheter can deform. Accordingly, a larger corrugate width enables a lower bend radius at a low force of bending.

Consider the example of an <NUM>. 088in ID (<NUM>) catheter with a wall thickness of <NUM>. 006in (<NUM>) with an <NUM>. 005in (<NUM>) diameter Nitinol helical support of <NUM>. 018in pitch embedded in 80A, over an ePTFE Liner. A sample with a <NUM>. 004in (<NUM>) corrugate width and <NUM>. 006in corrugate depth will yield a force in 3pt bending of <NUM>. 05N at <NUM> deflection, and a bottom out bend radius of <NUM>. A sample with a <NUM>. 007in (<NUM>) corrugate width and <NUM>. 006in corrugate depth will yield a similar force in 3pt bending but bottom out bend radius of <NUM>.

In order to allow a large catheter to enter the cerebral vessels safely, and to accommodate lower radii bends such as those of the carotid siphon, the width of the corrugate should be of a minimum value relative to the pitch and or wall thickness.

In one example the width of the corrugate is no more than <NUM>% of the pitch of the corrugate (same as the pitch of the helical support). Preferably the width of the corrugate is between <NUM>% and <NUM>% of the pitch of the corrugate. More preferably the width of the corrugate is between <NUM>% and <NUM>% of the corrugate. More preferably the width of the corrugate is between <NUM>% and <NUM>% of the corrugate.

In one example the width of the corrugate is at least <NUM>% of the wall thickness. Preferably the width of the corrugate is at least <NUM>% of the wall thickness. In one example at the most distal section of the tip the width of the corrugate it at least <NUM>% of the wall thickness.

In one example at the most distal section of the tip the width of the corrugate it at least <NUM>% of the wall thickness and the depth of the corrugate is at least <NUM>% of the wall thickness.

In another example the corrugate represents the impression of a circular helical wire wound from a depth and width of no impression, i.e. no corrugate, to a depth of at least <NUM>% of the wall thickness.

In one configuration, the inner tubular layer (liner) terminates in a region proximal to the distal end of the catheter. This will further reduce the stiffness of the catheter for a corrugated or uncorrugated configuration. In this instance, particularly in the case wherein the catheter wall is comprised of a material such as a silicone, urethane or pebax, the region without a liner may be tacky. In one example the region of inner lumen of the catheter without a liner has hydrophilic or hydrophobic coating to improve lubricity. This is shown in <FIG> for a catheter portion <NUM> having a helical support <NUM> embedded in an outer jacket <NUM>, and in which an inner liner <NUM> extends for part of this length but terminates before the distal end (left side).

In one example the un-lined section is at least <NUM> in length, preferably at least <NUM> in length.

The termination of the liner is advantageous in allowing a more flexible section of the catheter. However, this can also form a sudden change in flexural stiffness and potential location for kinking or high stress or strain. This may be managed using a change in corrugation parameters, or by skiving the liner. In another example, the termination of the liner is a skive, or angular cut.

In one configuration a section of the un-lined jacket material adjacent to the liner proximally is less corrugated than the section of unlined jacket distally and proximally. This may be achieved by decreasing the depth of the corrugation. In another configuration a corrugated section of the lined jacket adjacent to the unlined jacket has a longer pitch than the section of unlined jacket distally and proximally.

In one configuration the helical support is transposed from the inner liner such that it is not exposed to the inner lumen of the catheter as shown in <FIG>, having a helical support <NUM> in an outer jacket <NUM>. This is to prevent pop-out the helical support into the catheter lumen during bend of the catheter. In one example the distance from the inner lumen to the helical support is at least <NUM>.

Referring to <FIG>, in a catheter portion <NUM> there is a helical support <NUM>, and an outer jacket <NUM> and an inner liner <NUM>. The outer jacket <NUM> has a proximal part <NUM> without corrugations, distal part <NUM> with corrugations. The inner liner <NUM> terminates proximally of the distal end at <NUM>. This is an example of a configuration in which the most distal section of the distal tip is comprised of a corrugated jacket without a liner, a more proximal section is corrugated and contains a liner, at least one section even more proximally is more corrugated, and at least one section even more proximally again is un-corrugated. In one example all sections of the jacket are of the same material durometer. In one example the material is urethane of durometer 80A. In another example more proximal jackets are of a stiffer urethane or pebax are present.

The liner is comprised of ePTFE. In a more proximal section of the shaft, the liner may transition to PTFE. In one example this transition takes place in a more stiff durometer material than that of the jacket of the corrugated distal tip.

In one example, a catheter portion <NUM> has a liner <NUM>, a helical support <NUM>, and an outer jacket <NUM> as for the catheter portion <NUM>. However, in this case there is an outer tubular layer <NUM> added to the outside of the corrugated structure which embeds the helical support to further increase the stiffness of a section of the catheter proximally of the distal end, as shown in <FIG>. This layer may be of the same or different material as the material used to encapsulate the helical support. Materials of higher stiffness such as PET or Nylon pr PEEK or other polymer can be used in this instance without significantly adding to the profile. In one example a layer of PET is added which has a thickness of <NUM> or less, preferably <NUM> or less, and more preferably <NUM> or less.

In order to manufacture a corrugated polymer jacketed catheter section a number of approaches may be taken. The following steps may be used as shown in <FIG>:.

An in-fill material may also be used to manage flexibility and increase pushability, and where it is used it embeds the coil. <FIG> shows a catheter portion <NUM> with a liner <NUM>, a coil <NUM> and inner and outer tubular layers <NUM> and <NUM> respectively and in-fill for increased stiffness.

In one example the material is used only to partially fill the space around the helical support as shown in <FIG>. In another example the in-fill material completely fills the helical channel around the helical support between the inner and outer tubular layers. In yet another example the in-fill material is melted to form a layer of material on all surfaces within the helical channel.

In one example the outer and inner tubular layer are comprised of ePTFE or PTFE, and the in-fill material is PET, PEEK or FEP.

The helical channel may be formed using a helically wound wire (cinch wire) placed temporarily on the outside of the outer tubular layer. To permanently form the helical channel, the construction may then be heated such that the in-fill layer melts to flow between the helical support, the outer tubular layer, and the inner tubular layer. Upon cooling and removal of the helically wound cinch wire on the outer tubular layer, the corrugate configuration is maintained, and an adhesive chemical bond is achieved between the components via the in-fill material.

In one configuration the in-fill material may be a polyurethane, pebax, PET, silicone, latex, TecoThane, Nylon, PET, Carbothane, SIBS, Tecoflex, Pellethane, PGLA or Kynar, Polyethylene and cyclic olefin copolymers, PEEK.

In one configuration the inner tubular layer and outer tubular layer of ePTFE are bonded to one another via sintering. It must be appreciated that in the case of a fluoropolymer, and in particular ePTFE or PTFE for use as the inner and outer tubular layers, the temperature required for the sintering can exceed <NUM>. In this instance it may be preferable to use materials for in-fill with a high processing and degradation temperatures such as PET, FEP, or PEEK. Other materials such as urethane or pebax will degrade at lower temperature and are not suitable.

As PET is a relatively stiff material it can be introduced in small volumes to stiffen the corrugate structure without significant impact on catheter profile or completely filling of the helical channel. This may provide regions of floating and of embedded coil.

In one configuration an increase in the pushability or stiffness is achieved by changing the thickness of one or both of the tubular layers. An increase in thickness increases the intrinsic stiffness of the wall. It also means a reduction in the available space for localised material bending and deformation. Therefore, the flexibility may be reduced. Furthermore, as the thickness increases the axial cross-sectional area along the axis of transmission of force and displacement along the catheter increases.

In one example, both the inner and outer tubular layer thickness are increased, as shown in <FIG> for the catheter portion <NUM> as compared to the catheter portion <NUM>. In the catheter portion <NUM> there is an inner liner <NUM>, a coil <NUM> and an outer tubular layer <NUM>. In the catheter portion <NUM> there is a thicker inner liner <NUM>, a coil <NUM>, and a thicker outer tubular layer <NUM>. In another example the inner tubular layer thickness alone is increased. In yet another example the outer tubular layer thickness alone is increased.

In another configuration the total outer tubular wall thickness may be altered by the addition of one or more layers of the same material. Referring to <FIG> a catheter portion <NUM> has a liner <NUM>, an outer jacket layer <NUM> underneath a coil <NUM>, and two layers <NUM> and <NUM> outside the coil <NUM>.

The total inner tubular layer wall thickness may be increased by the addition of one or more layers.

These layers may be of the same or different materials. In the case of ePTFE, the combined thickness of the inner tubular layers in an unconstrained configuration may be between <NUM> to <NUM>, preferably between <NUM> and <NUM>.

In one configuration the inner and outer tubular layers are comprised of multiple layers of ePTFE, wherein there is at least one layer between an outer tubular layer and an inner tubular layer. The total thickness of (for example, ePTFE) tubular layers which are comprised of one or more layers may be between <NUM> to <NUM>, preferably between <NUM> and <NUM>. The density of the material (again, such as ePTFE) may be approximately <NUM>/cm<NUM>. Increasing or decreasing the density of the material will necessitate a bigger or smaller wall thickness to achieve the same effect.

In another example the inner tubular layer thickness is constant along the length of the tip, but the outer tubular layer thickness is larger in at least one region. In another example the outer tubular layer thickness is increased proximally at least once along the length of the catheter tip.

In order to achieve a controlled change in stiffness of the distal tip, multiple layers may be overlapped to achieve a precise level of stiffness as shown in <FIG> in which an additional outer layer <NUM> is present for part of this catheter portion. This principle may be used for any number of layers, to achieve a desired variation in stiffness. Similarly, single thicker layers may be used proximally, connected to a thinner layer more distally to achieve the same effect.

In one example the tip has one outer tubular layer of <NUM> to <NUM> across the length of the tip. A second additional outer tubular layer of thickness <NUM> to <NUM> is present in a region more proximally. A third additional outer tubular layer of thickness <NUM> to <NUM> is present in a region even more proximally. A fourth additional layer of thickness <NUM> to <NUM> is present in a region even more proximally.

In one example the distal tip comprises an outer tubular layer of <NUM> across the length of the tip. A second additional outer tubular layer of thickness <NUM> is present in a region more proximally. A third additional outer tubular layer of thickness <NUM> is present in a region even more proximally. A fourth additional layer of thickness <NUM> is present in a region even more proximally.

In one configuration the tubular layers are bonded to one another. The bond may be present across the entire interface of the tubular layers. Alternatively, the bond may only be present at recesses of the corrugations, in the area where the inner and outer tubular layer are in contact. In yet another example, the bond is present between the layers at the rib and recess regions of the corrugations. In another example the material of the inner or outer tubular layer may be changed to one with a higher stiffness to increase the stiffness of the wall.

It should be noted that some variation in the thickness of the tubular layers may be present locally following bonding of inner and outer tubular layers, or their constituent layers, due to the use of local compression (pressure) to ensure a strong bond between tubular layers. This is particularly so with ePTFE because it is a porous compressible material. This localised compression may reduce the wall thickness in that area.

To evaluate a subset of the embodiments described above, 8F catheter samples of inner diameter <NUM>. 088in were built and tested in a Three Point Bend Test. The force at a <NUM> displacement was measured using a 50N Load Cell on a Zwick Roel tensile test machine. The distance between the supports was <NUM>. Clear changes in stiffness were achievable using the various configurations outlined above.

It can be appreciated that the embodiments described above can be used to alter the stiffness of the catheter wall as desired. For comparison, a 6F Microvention Sofia Plus catheter indicated for use in neurovasculature is included. <FIG> shows results of <NUM>-point bend tests to evaluate stiffness of various embodiments described above.

In the neurovasculature, when entering delicate vessels such as M1, M2, ICA, vertebral and basilar arteries, an atraumatic tip of critical importance. It is preferable that the distal tip has a minimum length of its most flexible section such that the catheter tip will deflect or absorb deformation rather than causing vessel damage.

In one example the distal and flexible sections of the catheter of corrugate rib and recess design is a minimum of <NUM> in length and is comprised of inner and outer tubular layers in a corrugate configuration, with a floating helical support within a helical channel. In one embodiment for an 8F catheter distal tip, the force in <NUM>-point bend test, for a span of <NUM>, at <NUM> deflection, should not exceed <NUM>.

As shown in <FIG>, in one configuration, the distal-most end <NUM> of the distal portion is finished by inverting an inner tubular layer <NUM> over the helical support to form a continuous element.

Referring to <FIG>, in another example, in a distal end <NUM> the softness of the distal tip end is improved by extending inner and outer tubular layers <NUM> and <NUM> beyond the last coil of the helical support.

As shown in <FIG>, in a distal portion <NUM> an inner tubular layer <NUM> is inverted at the distal end <NUM> to return as a continuous element. Inner and outer tubular layer are comprised of the same piece of material and are continuous. An extension of ePTFE at the end <NUM> of the corrugated section is present to improve tip softness. Preferably, an extension beyond the last coil is between <NUM> and <NUM>. More preferably the extension beyond the last coil is between <NUM> and <NUM>. The distal portion <NUM> also has an outer tubular layer <NUM> terminating before the distal end <NUM>, and a concentric further outer tubular layer <NUM> around the layer <NUM> for part of the length of the layer <NUM>. This staggered overlapping arrangement provides a transition portion with stepped changes in flexural stiffness.

<FIG> shows a catheter distal portion <NUM> with an inner liner <NUM> which extends out at the distal tip to form an extension. In this case there are also overlapping staggered outer tubular layers <NUM> and <NUM>.

In the catheter <NUM> two or more layers are achieved by using the same piece of material inverted and returned along the length or a portion of the catheter. In one instance two pieces of ePTFE are used to achieve one inner tubular layer, and three outer corrugated tubular layers.

In the catheter <NUM> additional layers are added discretely. In another example, a combination of inverted continuous layers and discrete layers is used. The proximal portion of the catheter (shown un-corrugated) may be corrugated or un-corrugated.

PTFE material is a relatively stiff material compared to eTPFE and so is therefore preferable to avoid the use of PTFE as an inner tubular layer (liner) particularly in areas which will be subject to significant bending during passage through tortuous vessels. In one example, as shown in <FIG> , in a catheter <NUM> having a proximal end <NUM> and an intermediate portion <NUM> an inner tubular layer is of ePTFE material and this extends along the entire length of the catheter including a distal end <NUM>, where it is bent back to be continuous with the outer tubular layer.

In the present invention, the inner tubular layer is ePTFE in a distal portion and PTFE in a more proximal portion of the catheter as shown in <FIG> for a catheter <NUM> having a proximal end <NUM>, an intermediate portion <NUM>, a distal portion <NUM>. There is a transition region <NUM> in which the outer jacket a layer is merged into and joined with an outer jacket of PTFE material in the intermediate portion and the transition region. The transition from ePTFE to PTFE may be achieved by a "butt" joint, in which the inner tubular layers of PTFE and ePTFE are in contact without overlap.

In another embodiment, a transition from inner tubular layer of ePTFE to PTFE occurs in a region of the catheter which is not subject to significant bending during use. In one configuration the device dimensions are suitable for placement in the neurovasculature, including M2, M1 and distal internal carotid arteries. Preferably, the transition from ePTFE to PTFE occurs proximal to the petrous segment of the ICA. In one configuration, the transition from an ePTFE to PTFE inner tubular layer occurs between <NUM> and <NUM> from the distal end of the catheter, preferably between <NUM> and <NUM> from the distal end, and more preferably at least <NUM> from the distal end.

In one configuration, the transition from inner tubular layer of ePTFE to PTFE occurs in a region proximal to a region of the catheter of rib and corrugation recess. In another configuration the transition from inner tubular layer of ePTFE to PTFE occurs proximal to the most flexible region of a rib and recess corrugate design, but still within a region of stiffer rib and recess corrugate design.

In one embodiment the proximal region of rib and recess corrugate has an outer tubular layer comprised of a polymer material, as shown in <FIG>. In one configuration the polymer material is a urethane or pebax. In one embodiment the polymer material is 80A urethane. <FIG> shows a catheter <NUM> having a proximal end <NUM>, an intermediate portion <NUM>, a distal portion <NUM>, and a transition region <NUM>. An ePTFE inner tubular layer (liner) <NUM> transitions to a PTFE jacket <NUM> in the intermediate portion within a corrugated section of the distal tip. A lap joint is used in which the PTFE tubular layer <NUM> is concentric within the ePTFE tubular layer <NUM>.

In another embodiment the transition from ePTFE to PTFE may be achieved via a "lap" joint wherein there is overlap of the tubular layers of ePTFE and PTFE. In one configuration the overlap between the PTFE and ePTFE is between <NUM> and <NUM> in length. The use of an overlap increases the area of interface for bonding thus improving the bond strength.

In one embodiemnt, for a distance the ePTFE is concentric within the PTFE, as shown in <FIG>. In this diagram a catheter <NUM> has a proximal end <NUM>, and intermediate portion <NUM>, and a distal portion <NUM>. An inner liner <NUM> is bent over at the distal end to form part of the outer jacket of the distal portion <NUM>. At a transition region between the intermediate portion <NUM> and the distal portion <NUM> the inner liner <NUM> is within a tube of PTFE material <NUM> with an overlap length of at least <NUM>, preferably at least <NUM>. The tubular layer <NUM> extends proximally within a jacket material <NUM> in the intermediate portion <NUM>. This provides a configuration with an ePTFE inner tubular layer (liner) transitions to PTFE within a corrugated section of the distal tip. A lap joint is used in which the ePTFE tubular layer <NUM> is concentric within the ePTFE tubular layer.

In one example, a maker comprised of a helical coil of Platinum is present on the distal tip.

In one example, the helical support may be comprised of a radiopaque material such as Platinum wire. In another example, to leverage the super elastic properties of Nitinol with radiopacity, the helical support may be comprised of drawn Nitinol tubing filled (such as Nitinol#<NUM> DFT, Fort Wayne Metals) with Platinum or other radiopaque material. This would allow the physician to observe the distal tip behaviour under x-ray through the procedure. In one embodiment the helical support tube is comprised of at least <NUM>% Platinum. <FIG> shows such an arrangement in which a catheter portion <NUM> has a radiopaque helical coil <NUM> around which there is a coating <NUM>, and there is a tubular layer <NUM> over the outer jacket.

In one configuration, the radiopacity of the distal tip is further enhanced via a region in which the helical support pitch is reduced such that an area of greater density of radiopacity is achieved.

<FIG> shows catheters with radiopaque markers <NUM> at various positions along its length.

Advantages and novel aspects are that allow the physician to ensure that more stiff regions the catheter are not placed in more delicate region of the vasculature. For example, a proximal marker at the start of the flexible distal tip can be used to define the region of the proximal catheter which should not be placed beyond the cervical C1 segment of the internal carotid artery. An intermediate marker can further be used to differentiate the end of a region of intermediate flexibility which should not be placed before, within, or beyond the cavernous segment C4. The region between the intermediate marker and distal marker establishes the region of highest flexibility which is suitable for placement in the C4-C7 regions of the internal carotid artery, and more distal vessels.

In one example, in which the device is suitable for placement in the neurovasculature, the distal flexible tip length is at least <NUM>, and the un-lined distal section is at least <NUM> in length. In another embodiment in which the device is suitable for placement in the peripheral vasculature, the Aspiration Device including the Catheter.

A catheter of any example may be used for example for thrombectomy.

Recent clinical data has demonstrated that use of flow arrest using a balloon guide catheter can improve outcomes during thrombectomy procedures. This is done by:.

The prior art setup of balloon guide catheter in a thrombectomy procedure is shown schematically in <FIG>, with a balloon <NUM> and a tip <NUM>. Balloon guide catheters for use in thrombectomy procedures must facilitate the insertion of a microcatheter, and distal access catheter. In order to do this, the balloon guide must have an inner diameter in the range of 5F or greater. Additionally, the catheter typically has an outer diameter in the range of 8F or 9F.

Existing catheter technology, at the dimensions described above, is extremely stiff. This is due to the catheter materials, design and architecture used. Therefore, the distal tip of the balloon guide catheter cannot be placed beyond the petrous segment. Excessive stiffness means the catheter is not flexible enough to track through the tortuosity of the distal ICA and other target vessels where the clot may be located, and there is a high potential for vessel damage or perforation.

Ideally, the tip of the balloon guide catheter should be as close to the clot as possible. This reduces the distance over which the clot must be dragged from the target vessel to the location of the balloon guide catheter tip. It may also enable the physician to directly aspirate the clot locally as the tip of the catheter can now engage the clot.

In some scenarios, remote aspiration of the clot is being performed using balloon guide catheters, while the balloon is inflated. Remote aspiration is a procedure in which the clot is aspirated without contact of the catheter tip with the clot. This works particularly well in a closed system where alternative flow pathways are not present. The success of this technique is often limited by the fact that the tip of the catheter can be a long distance from the clot.

A balloon catheter, whether used for PTA or embolic protection, is typically of a dual lumen, double layer construction along the length proximal to the balloon. This ensures there are two lumens; one for the passage of guide wires, catheters, or fluids, and one lumen for inflation. This dual layer construction is not always as flexible as desired, and is prone to kinking.

There is therefore a need for a balloon guide catheter which can provide flow arrest, but which also incorporates a very flexible distal portion which can track through a tortuous vessel, such as the distal ICA or as far as the MI or other vasculature.

In one example a shaft or section with enhanced flexibility compared to the proximal section is present distal to the balloon of a balloon catheter. This flexible section enables the tip of the balloon to be placed more distally in the vasculature. This section of enhanced flexibility may be comprised of the types described in <CIT>, titled "HIGH FLEXIBILITY, KINK RESISTANT CATHETER SHAFT," and <CIT>, titled "HIGH FLEXIBILITY, KINK RESISTANT CATHETER SHAFT", corrugate construction or other design.

This device may be designed so that the distal tip is flexible enough to reach and touch the clot for vacuum aspiration. The part which is distal of the flow restrictor (such as the balloon) includes the distal portion and preferably at least some of the transition portion. There may also be some of the transition portion proximally of the flow restrictor.

The length of this flexible section may vary such that it can reach specific anatomical locations, such as the distal internal carotid artery, terminus of the internal carotid artery, proximal MI, distal MI, proximal M2, distal M2, basilar, or vertebral vessels. This length may also help ensure that that while the tip of the catheter can reach the target vessel, the balloon does not pass the cavernous, or petrous segment of the ICA. Inflation of the balloon beyond these segments can cause vessel damage. The length of the flexible section may be between 1cmn and <NUM>, preferably between <NUM> and <NUM>.

The outer diameter of this flexible tip may differ from the outer diameter of the proximal section of the catheter. In one example the distal section has a larger diameter than the proximal section. In yet another embodiment the outer diameter has a diameter smaller than the diameter of the proximal section of the catheter. Variations such as a taper in the diameter of the distal section may also be used. Differing diameter distal sections can help to ensure access to specific vessels beyond the area to land the balloon.

<FIG> shows a device <NUM> with a flexible distal catheter tip <NUM> extending from a balloon <NUM>, and proximally of which there is a catheter main section <NUM> extending from a Y-piece <NUM>.

<FIG> shows the balloon <NUM> inner layer inflation lumen <NUM> and the balloon outer layer inflation lumen <NUM>.

In one configuration, the outer layer of balloon inflation lumen may of enhanced flexibility while the inner layer of the balloon inflation lumen may be of a conventional construction comprising a single layer material, braided extrusion, coiled extrusion or other construction. These layers are shown schematically in <FIG>, inner layer <NUM> and outer layer <NUM>. In this way the pushability of the catheter may be maintained by the inner layer, while the outer layer mitigates compromise in terms of flexibility. Furthermore this construction will help to prevent kinking, since mechanics dictate that as the ratio of the inner diameter to the outer diameter of a tube increases, kink resistance is reduced. Use of the enhanced flexibility construction for the outer layer, traditionally more prone to kinking will solve this issue.

In another example, a balloon catheter of dual layer construction comprises both inner and outer layer of the balloon inflation lumen of the enhanced flexibility construction. This will represent an ultra-flexible and kink resistant balloon catheter.

In other configurations, the proximal section may utilise other constructions to inflate the balloon such as a single lumen design with a vent hole and teak proof seal, a coaxial lumen or other design.

It should be noted that a balloon guide catheter, with a long distal tip capable of reaching a clot may be used as a thrombectomy device as follows:.

It may be noted that in the above method, the use of a large diameter distal tip, close to that of the target vessel will maximise the potential of complete clot ingestion.

In yet another example, enhanced catheter shaft flexibility and kink resistance may be achieved without additional helical wire support, but instead using a simple tubular construction with a corrugate architecture. The corrugations may be defined as adjacent circular depressions in the wall thickness of the tube, or as a continuous helical depression as shown in <FIG> respectively. In these diagrams the tip has an outer layer <NUM> with corrugations <NUM> (<FIG>) and an outer layer <NUM> with more shallow corrugations for desired flexibility.

The device may be designed so that the distal tip is flexible enough to reach and touch a clot for vacuum aspiration. The typical target vessels are the M1, M2, M3, distal ICA.

The distal tip should be long enough to reach the target vessel, while also ensuring that the balloon does not pass the petrous segment of the internal carotid artery (known as C2). This is because the vessels and surrounding tissue beyond the petrous segment are prone to damage which can have catastrophic consequences.

It is preferable to ensure that the location of the balloon when inflated is within C1 segment of the carotid artery. It is also preferable that the balloon be distal to the external carotid artery to ensure effect flow restriction and or flow reversal. The length of the flexible section may be between <NUM> and <NUM>, preferably between <NUM> and <NUM>.

<FIG> left image shows an Angiogram demonstrating the external carotid, common carotid and internal carotid artery (ICA), including the C1 and C2 segments, and right image shows acceptable positioning of the balloon (<NUM>, in a catheter <NUM> proximal of a distal end <NUM>. It should not be inflated past the C2 segment. The distal tip length of the catheter should be long enough to reach the clot while ensuring safe position within or proximal to the C2 segment of the ICA.

Any or all the examples described above to refine the transition from the stiffness of the proximal portion of the distal tip to the most distal portion may be used.

The proximal shaft must serve two functions and have at least two lumens; one for balloon inflation and a main lumen for delivery of fluids and devices, and for aspiration. The flexible tip only requires one lumen, therefore has potential to have a larger lumen than the proximal section.

In one embodiment the inner diameter of the flexible tip is the same inner diameter as the proximal shaft.

In another example the proximal and distal shaft have the same outer diameter, and the proximal shaft has two concentric lumens, in which the central lumen diameter is less than that of the flexible distal tip as shown in <FIG>. This drawing shows a balloon guide catheter <NUM> with a flexible corrugated distal tip <NUM> and a balloon <NUM>. In this incidence the inner diameter of a proximal shaft lumen <NUM> is less than that of the flexible corrugated distal tip <NUM>. The proximal and distal shafts have the same outer diameter.

In another example the inner diameter of the proximal shaft is the same as that of the flexible distal tip. In yet another example, the outer diameter of the distal tip is smaller than that of the proximal shaft. The distal tip inner diameter may be the same as, or smaller than, the inner diameter of the proximal shaft. <FIG> shows a catheter <NUM> with a balloon <NUM> and a distal portion <NUM> having a smaller outer diameter than the proximal portion <NUM>.

In one configuration, the distal tip is comprised of a flexible corrugate section distally, and a non-corrugated section proximally. <FIG> shows a catheter <NUM> with a non-corrugated proximal region <NUM> of the distal region <NUM>.

In one configuration, as shown in <FIG> for a catheter device <NUM> a radiopaque marker is present at the distal end of the flexible distal tip. Markers are also present immediately distal and or proximal to the balloon to define its location. An additional intermediate distal marker may be present within the distal tip to define a proximal region of increased stiffness unsuitable for placement in distal to the C2 segment of the ICA.

In one configuration, the balloon catheter is suitable for use via direct carotid access. In this case a shorter proximal shaft will improve ergonomics for the physician. In this instance the length of the catheter shaft proximal to the balloon does not exceed <NUM>, and preferably does not exceed <NUM>.

The examples described above enable the physician to place larger bore catheters more distally than has been possible using conventional catheter technology. However, it may not be possible to place a larger catheter in the target vessel due to the vessel diameter being smaller than the catheter itself. In this instance a larger catheter may be used to achieve flow restriction.

In some instances, additional vessels are present which perfuse the treatment area. For example, in the case of the anterior cerebral artery, proximal occlusion using a balloon guide catheter placed in the ICA does not prevent inflow to the target treatment site. This is also a problem in posterior stroke where there are two significant inflow vessels (left vertebral artery and right vertebral artery), and the target treatment site is the basilar artery or posterior communicating artery.

In one example a system is comprised of a "mother" and "daughter" catheter, in which significant flow restriction, or flow arrest, may be achieved by placing or wedging a large bore highly flexible mother catheter in a vessel location proximal to the target treatment site. A smaller daughter catheter may then be passed through the parent catheter to the treatment site. In this instance a proximal balloon for flow restriction is not required. Near occlusion of the vessel, without wedging the catheter, will dramatically reduce flow also. This is shown in <FIG>, in which there is a large catheter <NUM> and a smaller catheter <NUM> for aspiration of a clot <NUM>. Large bore highly flexible catheters can enable the most distal flow arrest possible.

In other instances, such as embolization, flow restriction using a larger bore catheter may also be advantageous. For example, in embolization, where embolization of non-target vessels is a major concern, additional embolization procedures are often used occlude adjacent non-target vessels. Non-target embolization can cause non-target vessel occlusion, or the delivery of a drug to non-target tissue. This may be avoided if a larger bore highly flexible catheter is placed distally in the vessel feeding the target region of delivery of the embolic such that the catheter tip is wedged. Upon injection of the embolic, the wedged condition prevents retrograde flow of the embolic, thus preventing non-target embolization. Furthermore, the pressure gradient within the vessel is a reflection of the proximal injection pressure, rather than the hemodynamic pressure, giving the physician full control of the delivery of the embolic.

<FIG> shows such a configuration, in a catheter <NUM> having a distal portion <NUM>, Left shows the use of a small catheter unable to reach a distal target vessel (right side vessel) during delivery of a drug or embolic and the resulting undesired delivery to a non-target vessel (top left vessel) The right hand diagram shows the use of a method wherein a highly flexible large diameter catheter is chosen to effectively occlude the target vessel, and can be placed beyond the non-target vessel, so delivery of the embolic only occurs to the target vessel. It is preferable that the catheter is wedged in the target vessel.

Furthermore, the distal nature of the vessels targeted in embolization procedures means that often, only microcatheters are capable of entering the vessels today. This limits the type of embolic which can be used (e.g. <NUM> microcoils may need to be used where larger <NUM> coils or a plug would e preferred, or the desired particle becomes clogged in the only microcatheter capable of entering the vessel). The technical success of these procedures (in particular embolization for BPH) is also limited by the inability to place larger support catheters distally.

A corrugated catheter section with or without a transition arrangement may be used as a proximal section of a catheter in order to provide flexibility about a particular bend, for example, as an access sheath to provide controlled flexibility about the iliac arch. The configurations may could also be incorporated into a more flexible a urethral stent design or Foley-style catheter, and for a flexible endoscope of corrugate wall.

The device may be used to block blood flow before precise delivery of an embolic agent to region of the vasculature, tumour, or organ.

Aspiration has been shown to be safe for the retrieval of clots from the cerebral vasculature. However, technique suffers from a number of limitations. In particular, it is frequently the case that the clot cannot be ingested at the target treatment site. This is particularly the case for harder, larger diameter, and longer clots.

If not completely ingested, the physician will attempt to withdraw catheter and attached clot from the patient under continuous vacuum. This manoeuvre carries risk, is time-consuming, and means the physician has lost access to the target vessel.

If following angiography the physician determines that the target region has not been reperfused, additional attempts must be made to retrieve the clot. Up to five attempts, known as passes are typically required. On average two attempts are required. In <NUM>% to <NUM>% of cases, aspiration is not successful after multiple attempts, and physicians will switch to the use of a stent retriever (Almandoz et al. <NUM>; Lapergue et al. <NUM>; Blanc et al. <NUM>; Möhlenbruch et al. This further increases procedural time and cost.

As the physician withdraws the catheter proximally towards the access site (typically femoral or radial artery), there is a likelihood that some or all of the clot may break off. These fragments of clot, are known as emboli. Distal emboli lead to poor reperfusion outcomes when assessed under angiography or other imaging. Poor reperfusion, as defined by the TICI scale, is associated with worse patient outcomes.

Another limitation of the aspiration technology is that it is not always possible to advance the catheter tip to the face of the clot. This is due to the extreme tortuosity which may be present in the patient, meaning that often only small diameter catheters such as microcatheters can reach the clot. Larger bore catheters are known to have a greater potential to aspirate the clot, but are frequently too stiff to navigate to the clot face. In this instance, the physician may use a smaller bore catheter, but is less likely to successfully aspirate the clot.

Depending on internal diameter of the catheter, and properties of the clot (diameter, length, hardness/durometer, elasticity etc.), there is a limit to the amount of clot which can be aspirated into the catheter lumen. At this limit the catheter may be described as being clogged. Large lumen catheters can aspirate more clot than small lumen catheters without becoming clogged. During aspiration, the limit to the amount of clot which can be aspirated may be reached before a complete vacuum is reached. This implies that the application of further vacuum does not necessarily increase the amount of clot which is aspirated once a certain limit is reached. This is shown schematically in <FIG>, showing a catheter tip <NUM> being used to attempt aspiration of a clot <NUM>. As illustrated, there is incomplete aspiration. It is a limitation of existing vacuum technology (vacuum pumps and syringes) that the applied vacuum is not engineered to prevent clogging, or maximise efficiency of aspiration.

Based on the problems outlined above, it is desirable to enable the clot to be ingested at the target site in a single manoeuvre. This will save time, reduce procedural complexity, and minimise potential for clot fragmentation during clot retrieval.

A pump is disclosed, for use in connection with a catheter such as described above in any embodiment, to aspirate clots or other materials from a blood vessel or other region of the body. An aspiration device is shown schematically in <FIG>, having a catheter <NUM>, a guide <NUM>, tubing <NUM>, and a pump and reservoir assembly <NUM>.

The system utilises control and/or, variation of the vacuum pressure and/or, fluid displacement during aspiration to improve the efficiency of aspiration. Variations in pressure and/or fluid displacement at the catheter tip can help achieve the following:.

The pump <NUM> may provide a negative fluid displacement thereby decreasing pressure (enabling a vacuum) or positive displacement, thereby increasing pressure. The pump is connected to a catheter, enabling application of a positive or negative pressure the catheter lumen. The pump incorporates a sensor which measures the pressure in the catheter lumen.

The magnitude of this pressure may be used to decide whether a vacuum or pressurizing signal should be applied to the catheter. Based on the measured pressure, the pump may change direction hence altering the pressure and fluid displacement.

In one example, shown schematically in the form of a state diagram in <FIG>, the pump uses defined upper and lower limits to decide whether to apply a vacuum or pressurize. These limits enable the catheter to cyclically ingest and if required expel, at least some of the clot. This deformation of the clot improves the efficiency of the aspiration, and prevents clogging of the catheter.

For the purposes of explanation, the initial pressure is defined as <NUM> in-Hg in all diagrams before the pump is switched on <FIG>. In reality, a non-zero pressure is present due to blood pressure. This may be in the region of <NUM> to <NUM>-Hg (<NUM>-<NUM> in-Hg).

The pump will continuously measure the pressure within the catheter lumen during the procedure. This measurement will be arterial pressure if the pump is switched off. Once the pump is switched on, and it begins to draw some vacuum a negative pressure will be measured, <FIG>. In the absence of an occlusion or partial occlusion of the catheter tip, this will be a nominal reading, representing free-flow of fluid through the catheter). Once the catheter is advanced and engaged with the clot, an increase in the vacuum is observed, <FIG>.

Initially when switched on the pump applies a vacuum enabling the catheter to ingest some of the clot, <FIG>. While further increases in the vacuum ingest more of the clot, <FIG>, the efficiency of increases in the vacuum pressure in ingesting more clot is reduced, <FIG>. For this reason, the pump will reverse at some Low Limit of pressure, <FIG>. The Low Limit is defined such that during vacuum, a portion of the clot has been aspirated but not so much that the clot has become irreversibly clogged. An important aspect is that the lower limit of vacuum can be set well above the full vacuum pressure of -760mmHg to prevent ingestion of too large a clot that could clog the catheter. In one embodiment, the Lower Limit is set to between -<NUM> rnm-HG and -<NUM>-Hg. In another embodiment the Lower Limit is set to between -<NUM>-HG and - <NUM>- Hg. In another embodiment the Lower Limit is set to between -<NUM>-HG and -<NUM> mrn-Hg. In another embodiment the Lower Limit is set to between -<NUM> mrn-HG and -<NUM>-Hg.

The direction of fluid displacement of the pump is now reversed. Upon reversal, the catheter will begin to pressurize, thereby increasing the pressure measured, <FIG>. As the catheter is pressurized (vacuum is reversed), the load which was applied to ingest the clot will be reduced, thereby unloading the clot, and even allowing some or all of the clot to be pushed distally towards the catheter tip <FIG>. During this loading/unloading the clot is being macerated and accordingly becomes more "free" within the catheter.

The pressure is further increased until a High Limit is reached. In one embodiment this High Limit is defined such that the ingested clot may not be completely expelled from the catheter.

Additional cycling of the clot between the Low Limit and high limit (<FIG>) further macerates the clot enabling a greater amount of the clot to be ingested for the same Low Limit of vacuum (<FIG>), with eventual complete ingestion of the clot, <FIG>.

In one example the High Limit is a negative pressure. In another example, the high limit may be <NUM> mmHg. In yet another preferred example, the High Limit is a positive pressure (<FIG>.

In the absence of a pressure signal from the pump the presence of intra-vascular blood pressure means there is a force present which supports transport of material from the distal tip of the catheter towards the pump. In one example, an initial blood pressure reading may be taken before the procedure is initiated. This reading may be used to calculate the precise High Limit value required. The mean blood pressure, systolic blood pressure, or diastolic blood pressure may be used. A novel aspect of this pump system is the incorporation of feedback into the pump algorithm in order to produce more effective pressure cycling. That is to say, the ability of the pump to measure the condition in the pump (e.g. pressure or fluid displacement), and continue or alter its behaviour.

In one example, the applied pressure signal incorporates an oscillation or "shake" signal. The shake signal implies the application of pulse cycling between two pressure limits as shown in <FIG>. The signal provides acute aspiration of the clot in order to cause deformation and, or, fragmentation of the clot to improve transport through the catheter. Another aspect is the incorporation of rate-based cycling of a negative and positive pressure signal. Oscillating frequencies can be defined that may cause the elastic modulus of a clot to be exceeded, thereby, fragmenting the clot in the catheter and promoting easier transport.

The addition of this oscillation is shown in the form of the state diagram in <FIG>.

In one example the shake signal may be initiated for a predefined number of cycles. In another example, the shake signal may be used until the pressure has returned to blood pressure. In this instance the material in the catheter can effectively flow without significant resistance. In another example, this shake signal may be initiated based on a specific pressure indicative of catheter occlusion or partial occlusion, and terminated based on measurement of pressure within the catheter indicative of free-flow, or partial occlusion.

While the figures generally show a triangular wave form of pressure with respect to time, it should be pointed out that this may not be the case in reality. The graphs are intended to illustrate the directional changes in pressure which are initiated and controlled by the system. For example depending on the clot properties, and speed of activation or reversal of the pump, the signals may be more square, saw-tooth, or sinusoidal in form. Furthermore, the resulting pressure - time relationship may not have any repeating unit at all.

The system may include both an oscillation or shake signal in the vacuum and positive pressurize signals. This is shown schematically in <FIG>. In yet another example, the system my incorporate only a vacuum oscillation.

A range of Lower Pressure and Higher-Pressure limit values may improve efficiency of clot transport compared to static aspiration technology. In one example it is preferable to specify a Lower Pressure limit such that the amount of clot which can be ingested is maximised for a single cycle. In another example, it is preferable that the Lower Pressure limit is specified such that the amount of clot which is ingested in a single cycle is not maximised, but instead represents an intermediate condition between a small amount of clot ingestion and maximum clot ingestion. Real numbers will be added in the future based on experiment.

In another example, the lower limit may be defined in real-time. In one embodiment, a change in the rate of change of the pressure during the vacuum cycle may be used. For example, as the catheter becomes clogged, there is generally a rapid increase in the vacuum pressure. This sudden change in vacuum pressure may be used as a signal to switch the direction of the pump. Similarly, the upper pressure may be defined based on a sudden change in the pressure during the pressurize cycle. In one example this may be defined in order to identify a condition where the catheter is de-clogged.

It should be appreciated that the upper and lower limits may be defined by a combination of rate of change in pressure, or specific pressure value, or a combination of both.

In another configuration, a flow displacement, or flow meter is incorporated. This may be used to define upper and lower limits to establish the direction of the pump (aspiration or vacuum). In one embodiment the flow meter can detect if there is no fluid displacement, which is suggestive of catheter clogging.

In another example, the pump may use positive and negative fluid displacement to alternately infuse and aspirate the catheter. In one example, the ratio of the infuse-to-aspirate cycle may be between <NUM> and <NUM>. Preferably the ratio will between <NUM> and <NUM>, or more preferably between <NUM> and <NUM>.

In one configuration, the pump is a sterile unit, which can be used within the sterile field, or on the patient table adjacent to the patient. This enables the physician to perform all manoeuvres without the requirement of a technician outside the sterile field. The unit may be single use and disposable.

In one configuration, the pump incorporates a peristaltic pump mechanism. This ensures that there is no blood contact with the pump parts. The pump may incorporate a reservoir for collection of aspirate. <FIG> show a pump and components. Shown are a housing connecting a tube, an on-off switch, a battery pack, a pulsatile pump, and a motherboard. The pressure sensor is connected to the tube-lumen, which is connected to the catheter, thereby enabling pressure measurement within the catheter.

In one example the pump incorporates a series of LEDs or indicators. These are intended to provide feedback to the physician based on the catheter tip and clot interaction condition. This is provided by the pressure within the catheter. For example, the pressure range associated with free-flow within the catheter, or partial occlusion, or complete occlusion, aspirating or clogged.

Furthermore, the indicators may be used to indicate to the physician that the pump is in the oscillation or shake condition.

A method is disclosed whereby the physician uses the feedback from the indicators to define the required adjustment of the catheter tip.

Place catheter tip adjacent to the clot. Switch on the pump. If the pump indicates free flow is observed the catheter should be moved distally to further engage the clot. If the catheter is aspirating with partial or complete occlusion the physician waits until the pump has free-flow again. The physic again moves the catheter tip distally to engage the next piece of clot. In this way the entire vessel can be cleaned of clot. In the event that the pump becomes clogged, a signal may be provided to the physician that the traditional catheter withdrawal technique may be appropriate.

The embodiments of the claimed catheter described within this filing are in general aimed at enabling the physician to access regions of the body which provide a challenging anatomy, with highly flexible corrugated catheters. The catheter designs are optimised by way of transitions, and the addition of other elements, such as flow restrictors and a highly effective pump. The ability to make larger catheters while maintaining this type of controlled flexibility enables improved therapy, such as clot removal, embolic delivery to the body.

Claim 1:
A catheter (<NUM>) comprising a jacket defining a lumen and comprising an inner liner (<NUM>) and an outer tubular layer (<NUM>) with a helical support in jacket material along at least some of its length, the catheter comprising at least a proximal portion (<NUM>) and a distal portion (<NUM>), said distal portion having a corrugated outer surface (<NUM>) with corrugations in the outer surface of the outer tubular layer and the helical support is encapsulated between said corrugations and the outside of the inner liner;
wherein the inner liner (<NUM>, <NUM>, <NUM>) defines said lumen, and the inner liner extends between the distal portion and the proximal portion;
wherein the inner liner comprises an ePTFE tubular layer (<NUM>) in the distal portion and a PTFE tubular layer (<NUM>) in the proximal portion, and a transition wherein said inner liner tubular layers are in contact without overlap (<NUM>) or are in contact by a lap joint in which the tubular layers (<NUM>, <NUM>, <NUM>, <NUM>) are concentric.