Patent Document

[0001]    This is a continuation-in-part of allowed U.S. application Ser. No. 10/304,067, filed on Nov. 26, 2002, now U.S. Pat. No. 7,214,237, issued on May 8, 2007, which is itself a continuation-in-part of U.S. application Ser. No. 09/803,641, filed on Mar. 12, 2002, now U.S. Pat. No. 6,485,502, issued on Nov. 26, 2002, the entire disclosures of which applications and patents are incorporated herein by reference. This application also claims the benefit of the filing dates of the following U.S. Provisional Applications: No. 60/412,071, filed Sep. 19, 2002; No. 60/417,408, filed Oct. 9, 2002; and No. ______, filed Nov. 1, 2002. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    This invention relates to medical devices, such as vascular filters to be used in a body lumen, such as a blood vessel, with improved strength and flexibility. A filter according to the invention includes a proximal frame section, a distal section and a flexible thin membrane with perfusion holes of a diameter that allows blood to pass, but prevents the movement of emboli downstream. 
         [0003]    Both sections can be collapsed into a small diameter delivery catheter and expanded upon release from this catheter. The membrane has a proximal entrance mouth, which can be expanded, or deployed, substantially to the same size as the body lumen. It is attached to the proximal frame section, which has the function to keep the mouth of the membrane open and prevent the passing of emboli between the body lumen wall and the edge of the filter mouth. 
         [0004]    In order to have a good flexibility, the membrane is made extremely thin. Normally this would create the risk that the membrane could tear easily, which could cause problems because emboli and pieces of the membrane would then be carried downstream from the filter site. 
         [0005]    U.S. Pat. No. 5,885,258 discloses a retrieval basket for catching small particles, made from a slotted tube preferably made of Nitinol, a titanium nickel shape memory alloy. The pattern of the slots allows expansion of the Nitinol basket and by shape setting (heat treatment in the desired unconstrained geometry) this basket is made expandable and collapsible by means of moving it out or into a surrounding delivery tube. 
         [0006]    In principle, a distal filter is made of such an expandable frame that defines the shape and enables placement and removal, plus a filter membrane or mesh that does the actual filtering work. 
         [0007]    Sometimes the expandable frame and the mesh are integrated and made from a single material, for example Nitinol, as disclosed in U.S. Pat. No. 6,383,205 or US Published Application No. 2002/0095173. These filters do not have a well-defined and constant size of the holes where the blood flows through, because of the relative movement of the filaments in the mesh. This is a disadvantage, because the size of emboli can be very critical, e.g. in procedures in the carotid arteries. Further the removal of such a filter, accompanied by a reduction of the diameter, may be critical because emboli can be squeezed through the mesh openings with their changing geometry. 
         [0008]    A much better control of the particle size is achieved with a separate membrane or filter sheath, which has a well-defined hole pattern with for example holes of 100 microns, attached to a frame that takes care of the correct placement and removal of the filter. 
         [0009]    WO 00/67668 discloses a Nitinol basket that forms the framework of the filter, and a separate polymer sheath is attached around this frame. At the proximal side, the sheath has large entrance ports for the blood and at the distal side a series of small holes filters out the emboli. This system, however, has some major disadvantages. First of all, the closed basket construction makes this filter frame rather rigid and therefore it is difficult to be used in tortuous arteries. At a curved part of an artery, it may even not fit well against the artery wall and will thus cause leakage along the outside of the filter. 
         [0010]    Another disadvantage of such filters is there is a high risk of squeezing-out the caught debris upon removal, because the struts of the framework force the debris back in the proximal direction, while the volume of the basket frame decreases when the filter is collapsed. Further the construction makes it very difficult to reduce the profile upon placement of the filter. This is very critical, because these filters have to be advanced through critical areas in the artery, where angioplasty and/or stenting are necessary. Of course the catheter that holds this filter should be as small as possible then. In the just described filter miniaturization would be difficult because at a given cross section there is too much material. The metal frame is surrounded by polymer and in the center there is also a guide wire. During angioplasty and stenting, the movements of the guide wire will create further forces that influence the position and shape of the filter, which may cause problems with the proper sealing against the artery wall. This is also the case in strongly curved arteries. 
         [0011]    In U.S. Pat. No. 6,348,062, a frame is placed proximal and a distal polymer filter membrane has the shape of a bag, attached to one or more frame loops, forming an entrance mouth for the distal filter bag. Here the bag is made of a very flexible polymer and the hole size is well defined. Upon removal, the frame is closed, thus closing the mouth of the bag and partly preventing the squeezing-out of debris. This is already better than for the full basket design, which was described above, where the storage capacity for debris of the collapsed basket is relatively small. The filter bag is attached to the frame at its proximal end and sometimes to a guide wire at its distal end. Attachment to the guide wire can be advantageous, because some pulling force may prevent bunching of the bag in the delivery catheter. 
         [0012]    It may be clear that it is easier to pull a flexible folded bag through a small diameter hole, than to push it through. However, the deformation of the bag material should stay within certain limits. 
         [0013]    If the filter is brought into a delivery sheath of small diameter, collapsing the frame and pulling the bag into the delivery sheath causes rather high forces on the connection sites of filter to frame and/or guide wire. While the metal parts of the frame slide easily through such a delivery sheath, the membrane material may have the tendency to stick and in the worst case it may even detach from the frame and tear upon placement or during use, because of too much friction, unlimited expansion, crack propagation etc. 
         [0014]    The connection of the filter bag to the frame is rather rigid, because of the method of direct attachment. Additional flexibility, combined with a high strength attachment spot would also be advantageous. 
         [0015]    Methods for making kink resistant reinforced catheters by embedding wire ribbons are described in PCT/US93/01310. There, a mandrel is coated with a thin layer of encapsulating material. Then, a means (e.g. a wire) for reinforcement is deposited around the encapsulating material and eventually a next layer of encapsulating material is coated over the previous layers, including the reinforcement means. Finally the mandrel is removed from the core of the catheter. 
         [0016]    Materials for encapsulating are selected from the group consisting of polyesterurethane, polyetherurethane, aliphatic polyurethane, polyimide, polyetherimide, polycarbonate, polysiloxane, hydrophilic polyurethane, polyvinyls, latex and hydroxyethylmethacrylate. 
         [0017]    Materials for the reinforcement wire are stainless steel, MP35, Nitinol, tungsten, platinum, Kevlar, nylon, polyester and acrylic. Kevlar is a Dupont product, made of long molecular highly oriented chains, produced from poly-paraphenylene terephalamide. It is well known for its high tensile strength and modulus of elasticity. 
         [0018]    In U.S. application Ser. No. 09/537,461 the use of polyethylene with improved tensile properties is described. It is stated that high tenacity, high modulus yarns are used in medical implants and prosthetic devices. Properties and production methods for polyethylene yarns are disclosed. 
         [0019]    U.S. Pat. No. 5,578,374 describes very low creep, ultra high modulus, low shrink, high tenacity polyolefin fibers having good strength retention at high temperatures, and methods to produce such fibers. In an example, the production of a poststretched braid, applied in particularly woven fabrics is described. 
         [0020]    In US Published Application No. 2001/0034197, oriented fibers are used for reinforcing an endless belt, comprising a woven or non-woven fabric coated with a suitable polymer of a low hardness polyurethane membrane, in this case to make an endless belt for polishing silicon wafers. Examples are mentioned of suitable yarns like meta- or para-aramids such as KEVLAR, NOMEX OR TWARON; PBO or its derivatives; polyetherimide; polyimide; polyetherketone; PEEK; gel-spun UHMW polyethylene (such as DYNEEMA or SPECTRA); or polybenzimidazole; or other yarns commonly used in high-performance fabrics such as those for making aerospace parts. Mixtures or blends of any two or more yarns may be used, as may glass fibers (preferably sized), carbon or ceramic yarns including basalt or other rock fibers, or mixtures of such mineral fibers with synthetic polymer yarns. Any of the above yarns may be blended with organic yarns such as cotton. 
       BRIEF SUMMARY OF THE INVENTION 
       [0021]    The present invention provides novel medical devices, such as vascular filters, with improved strength and flexibility and methods for their manufacture. These filters have a proximal frame section and a distal section, which can be collapsed into a small diameter delivery catheter and expanded upon release from this catheter. The proximal section is made as a frame of a relatively rigid material compared to the material of the distal section, for example a metal, and the distal section is provided with a flexible thin membrane, with perfusion holes in filter devices, of a diameter that allows blood to pass, but prevents the passage of emboli. The distal filter membrane has a proximal entrance mouth, which has almost the same size as the body lumen of a patient when the filter is deployed. The membrane is attached to the proximal section, which has the function to keep the mouth of the distal filter open and to prevent the passing of emboli between the body lumen wall and the edge of the filter mouth. 
         [0022]    In order to have a good flexibility and a minimized crossing profile upon delivery, the membrane is made extremely thin. Tearing of the membrane is prevented by embedding in the filter membrane thin filaments of a material with high strength in the longitudinal direction, but high flexibility upon bending. Such a filter membrane with embedded filaments can have extreme flexibility and elasticity in certain directions, combined with limited deformation, high strength and prevention of crack propagation through the membrane material. Further, the filaments can be attached to the proximal frame section in such a way that the connection points act as hinges and as additional safety for the case that the membrane material might come loose from the frame. 
         [0023]    The embedded filaments can include elements that help to give the membrane a desired shape after deployment. 
         [0024]    The surface of the membrane filter may be coated with an additional material that improves the properties, for example the biocompatibility, drugs release or any other desired property, which the membrane itself does not offer. 
         [0025]    The thus reinforced membranes can also be manufactured without holes for use for parts of catheters, inflatable parts, balloon pumps, replacement of body tissues, repair of body parts and functional parts like artificial valves and membranes, where minimal thickness and/or high strength are required. 
         [0026]    Fibers are used not only as reinforcement for the membranes, but are also used as pulling fibers for the extraction the device from a delivery catheter or for retrieval, or retraction, of the device into a removal sheath. The frames can be used in temporary devices like a removable temporary stent, dilator, reamer, occlusion device for main artery or side artery, a housing for a graft, a valve, a delivery platform for drugs, radiation or gene therapy, or any other device that has to be placed and removed after some time. Applications are not restricted to arteries, but are meant for all body lumens. 
         [0027]    Further, the invention provides a method for producing devices such as filters by dipping on a removable mold. According to this method, thin filaments of a material with high strength in the longitudinal direction, but high flexibility upon bending, are embedded in the filter membrane. The fibers are preferably less stretchable than the membrane material. The resulting composite membrane can have extreme flexibility and elasticity in certain directions, combined with limited deformation, high strength and prevention of crack propagation through the membrane material. Another function of the embedded filaments is that they help to give the membrane a desired shape after deployment. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS  
         [0028]      FIGS. 28-31  are side elevational views showing four stages in the fabrication of a first embodiment of a filter according to the present invention. 
           [0029]      FIG. 32  is an elevational view showing a second embodiment of a filter according to the present invention. 
           [0030]      FIGS. 33-35  are side elevational views showing a third embodiment of a filter according to the present invention in three different stages of operation. 
           [0031]      FIG. 35   a  is a detail view of a portion of the third embodiment in the operation stage of  FIG. 35 . 
           [0032]      FIG. 35   b  is a detail view similar to that of  FIG. 35   a  showing a modified version of a component of the embodiment of  FIGS. 33-35 . 
           [0033]      FIGS. 36   a  and  36   b  are detail views of a modified form of construction of a portion of the embodiment of  FIGS. 33-35 . 
           [0034]      FIG. 37  is a side elevational view showing a modified version of the third embodiment and includes an inset illustrating the modification to a larger scale. 
           [0035]      FIG. 38  is a side elevational view showing the filter of  FIG. 37  in a further possible operating stage. 
           [0036]      FIG. 39  is a side elevational view showing a fourth embodiment of a filter according to the present invention. 
           [0037]      FIGS. 40-47  are pictorial views of successive stage is a procedure for treating an obstruction in a carotid artery according to the invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0038]    The advantages of the invention will become more apparent after reference to the following detailed description.  FIGS. 28-39  show filters that can serve as distal filters in the two-filter systems shown in  FIGS. 1-27 . However, the manufacturing techniques described below can also be used in the manufacture of proximal filters. 
         [0039]    In the present specification, filters with improved flexibility and smaller profile are described. Such a filter basically has a proximal frame for expansion and contraction and, attached thereto, a thin filter bag that is made of two basic materials. One material is the highly flexible filter membrane itself, with a pattern of holes for allowing flow of blood particles below a well defined size, and the other material is a reinforcement made of fine fibers with high axial strength but thin enough to be flexible upon bending. The reinforcement is integrated with the membrane to create a composite structure with very flexible membrane areas where the blood is filtered and extremely strong reinforcement fibers that take up excessive forces to prevent the membrane from tearing even in response to pulling forces, and act as flexible hinges at the points of attachment to the proximal frame and/or to a guide wire. All of the fibers disclosed herein can consist of, or include Dyneema® fibers, manufactured by DSM High Performance Fibers, a subsidiary of DSM N.V. These are superstrong polyethylene fibers. The fibers can also be combined with fibers or wires of other materials, such as Nitinol, to help control the expanded shape of the filter 
         [0040]    These fibers can be embedded in the membrane by a dipping or spraying process or they can be attached with glue, stitching, a solvent for the membrane material, heat, welding etc. 
         [0041]    In order to achieve a better connection between the reinforcement fibers and the membrane material, the fibers may first be coated with a material that adheres well to the membrane material, for example with the same material as the membrane. 
         [0042]    The fibers can be made of any strong and tough material, preferably a material with a modulus of elasticity that is higher than that of the surrounding membrane. The fibers can be made of round, flat or different shaped mono-filaments or multi-filaments and can include metal elements, for example titanium or Nitinol, carbon, boron, glass, or polymers, for example ultra high molecular weight polymers with extreme tensile strength and high modulus. 
         [0043]    The fibers not only reinforce the membrane, but also can be used to control the final geometry, prevent crack propagation, act as hinges at the place of attachment to the frame and prevent loss of the membrane or parts of it. 
         [0044]    Because the reinforcement the membrane itself can be made much thinner than known membranes, the crossing profile of the composite filter can be much lower than for a single polymer membrane, even if the reinforcement fibers are thicker than the membrane itself. 
         [0045]    A method according to the invention for making a reinforced filter is carried out by first providing a paraffin mold having the desired shape of the expanded, or deployed, filter bag. Then the mold is covered with a polymer skin, which will subsequently detach easily from the membrane polymer. This paraffin mold, covered with the polymer skin, is dipped in a solution of polymer and solvent until a layer of membrane polymer is created. After that step, the frame is placed around the mold and reinforcement fibers, possibly coated, are then mounted to the frame at the hinge sites and laid over the surface of the mold. Another dipping step in the solution of polymer and solvent ensures full embedding of the fibers into the growing membrane polymer layer. Finally, the perfusion hole pattern is laser drilled into the membrane and the last step is the removal of the paraffin by melting it out in warm water. The polymer skin can then be easily detached from the inside of the filter membrane and pulled out 
         [0046]    With the use of a paraffin mold it is possible to make complicated or very simple designs, because there is no need to remove a relatively large mandrel from the filter after it has been made. This would be complicated if the mandrel was for example a metal or polymer part, which had to be pulled through some openings at the proximal side. 
         [0047]    Paraffin is of course not the only material that can be used for a mold. Any material that can be brought into the desired shape and can be dipped directly or after application an intermediate layer may be used. Examples are meltable materials or materials that easily dissolve in water, like salt or sugar crystals. Other examples are fine grains in a vacuum bag or an inflated balloon which is deflated after dipping. It is also possible, for certain filter embodiments, to use a mold that can be safely removed without being melted, dissolved, or deformed. 
         [0048]    Fibers are also used for enabling the removal of an expandable device by pulling the device into a removal sheath. 
         [0049]    The principles of the disclosed invention become clear from the following description of the figures. Identical parts in different figures are given the same reference number. 
         [0050]      FIG. 28  shows a paraffin mold  401 , made in the desired filter shape. Paraffin is chosen because it can be removed from the filter easily, at a temperature that does not cause degradation of the polyurethane of the filter. 
         [0051]    However, dipping of the paraffin mold directly into the polyurethane has been found to not give the best results. Therefore, paraffin mold is first covered with a thin sheet  402  of polyvinyl alcohol. The polyvinyl alcohol is a thin sheet that can be stretched after wetting with water and pulled tight around the paraffin and then tied together with a small clip or wire  403 . Then, the resulting assembly is dipped a few times in a solution of polyurethane in tetrahydrofuran, thus building a layer of polyurethane of, e.g., 3 microns in thickness at the right side of the dipping line. 
         [0052]      FIG. 29  shows a Nitinol frame  420  made from tubing having an outer diameter of 0.8 mm by laser cutting and shape setting. At the proximal side, which is on the left, the tube end  425  is uncut and still 0.8 mm. in diameter. From there, the tube is cut to form eight longitudinal spokes  426  that end in a zigzag section with struts  427 , where the unconstrained, expanded material of frame  420  lies on a circle having a diameter is 8 mm at its largest point. This frame  420  will, at any size between the maximum diameter and the collapsed size of 0.8 mm diameter, always adapt smoothly to the given geometry of the body lumen, such as an artery. The mold of  FIG. 28  is placed inside this frame and eight reinforcement fibers  428  of, for example, multifilament ultra high molecular weight polymer are attached to the most distal section of the Nitinol frame  420  at points  429 . Fibers  428  can be attached to frame  420  by means of a knot or each fiber can just be run back and forth from the distal tip to the a point  429  and wrapped around the Nitinol frame at point  429 . In the latter case, each fiber  428  will have twice the length shown. 
         [0053]    At the distal end, i.e., the right-hand end, of the assembly, all fibers come together in a guide ring or tube  430 , where they are held in correct position for the further dipping operation. 
         [0054]      FIG. 30  shows the mold with the Nitinol frame and the surrounding fibers after having been dipped several more times until the fibers are well embedded in the polyurethane membrane, for example until the layer of polyurethane is 5 microns thick at places  431  where no reinforcement fibers  428  are present. Of course the thickness at the places  432  where these fibers are present is greater than at places  431 , dependent on the type of fibers and the number of dipping steps. Guide tube  430  of  FIG. 29  is removed after the dipping is finished and the membrane is dry. 
         [0055]      FIG. 31  shows the final filter  440 , with a pattern of holes  441  each 100 microns in diameter, which have been laser drilled between the reinforcement fibers  428 . After drilling of the holes, the central paraffin mold  401  is removed by melting in warm water, which can be at a temperature of 50° C. The polyvinyl alcohol layer is easily released from the polyurethane filter membrane and is removed. Further, the fibers  428  are cut to the correct length at point  442  and attached to a central guide wire  443  in a connector  444  in the form of a nose tip that fits on top of the delivery catheter if the filter is retracted into this catheter before placement into the body lumen of the patient. Note that the polyurethane membrane between the Nitinol struts  427  at the distal end of frame  420  is also removed, in the spaces enclosed by struts  427  and the dipping line, preferably by laser cutting. 
         [0056]    This construction is extremely strong and still very flexible. The 5 micron thick membrane with the reinforcement fibers  428  fits easily in a delivery catheter of only 0.9 mm inner diameter and adapts to all sizes of arteries between 1 and 8 mm diameter. 
         [0057]    The central guide wire  443  extends to the left from connector  444  through the membrane and frame  420 , including the uncut part of tubing  425 . Within connector  444 , fibers  428  are wrapped around, and secured to, guide wire  443 . To remove the filter from a delivery catheter, guide wire  442  is pushed from its proximal end (not shown-to the left in  FIG. 31 ) so that a pulling force is exerted on fibers  428  due to their connection to guide wire  443  in connector  444 . Thus, all tension forces on the distal section of the filter are taken up by the reinforcement fibers  428 . The membrane only has to follow these fibers and unfold as soon as it leaves the catheter. The filter opens because of the elasticity of Nitinol frame  420 . Also the blood pressure in the artery further helps to open the filter like a parachute. Upon bending of the filter there is almost no force needed at the sites where fibers are attached to the Nitinol struts, so these sites act as hinges. Even in strongly curved arteries the filter frame still adapts well to the artery wall and there is almost no blood leakage between the membrane and artery wall. 
         [0058]    The fibers are so well embedded in the polyurethane membrane that in case the membrane detaches from a Nitinol frame strut, the membrane will still have a strong connection to the frame and can be collapsed and removed from the patient safely. 
         [0059]    In case of a tear in the membrane, for example starting from a 100 micron hole, this membrane may tear further, but only until the tear meets a fiber. There the tear will stop, and the membrane can be removed safely and completely as well. Of course this situation is very undesirable and the loss of some entrapped emboli may be the consequence, but at least the removal of the filter itself would not cause problems. 
         [0060]    After a medical procedure has been performed, the Nitinol frame can be collapsed to close the mouth of the filter and entrapped emboli cannot leave this closed filter bag anymore. The hinges guarantee now that the filled bag hangs at the distal end of the removal catheter and still can move easily through curved arteries. 
         [0061]    The reinforcement fibers can be used not only for their high tensile strength. They can also be combined with memory metal wires, or filaments, made, for example, of Nitinol wires that can be shape set to almost any desired shape by heat treatment. Such wires may be embedded in or attached to the membrane to guarantee a smooth folding/unfolding of the membrane. An example is an embedded Nitinol wire that helps to give the mouth of the filter membrane a smooth geometry that fits well to the artery wall. Such a Nitinol wire for shape control can be combined with a more flexible, but stronger, fiber, which is used to protect the membrane against incidental overload, tear propagation or any of the described problems in non-reinforced membranes. 
         [0062]    The orientation and number of the reinforcement fibers is not limited and can vary with the desired application. 
         [0063]    In  FIG. 32  a distal filter  450  is shown, with a conical shaped filter membrane  451 , attached to the same proximal wire frame  420  as in  FIGS. 29-31 . In this example, however, the membrane is not attached directly to the Nitinol frame. It is attached, for example, by guiding a single, long reinforcement fiber  452  from the distal end at an angle with the cone surface until it reaches the Nitinol struts  427  at points  429 , then wrapping fiber  452  around one of these struts at a point  429  and guiding the fiber back to the distal tip with a reverse angle and repeating this operation several times. Arrows in the drawing show how fiber  452  runs back and forth. By this method the use of knots at the fiber-Nitinol connection is redundant and the safety is further increased, because the filter can never detach from the frame. In this embodiment, membrane  451  can also be formed by dipping a suitably shaped mold in a solution of polymer and solvent. 
         [0064]    A guide wire  453  is fastened to fiber  452  at at least one point at the distal end of the filter and extends through the filter to a proximal end thereof (not shown—to the left in  FIG. 32 ). 
         [0065]    The pattern with crossing reinforcement fibers gives the filter membrane different elastic properties and gives the benefit of an improved, but limited axial elasticity. 
         [0066]    The pattern of filter holes, preferably cut by laser, can be made in zones between the fibers to avoid damaging the fibers. 
         [0067]    However, if the pattern of reinforcement fibers is very fine, the holes may just be cut without regard for the locations of these fibers. There will then still be enough reinforcement left, because adjacent crossing, parallel or angled uncut fibers can take over some forces via the embedding material of the membrane itself. 
         [0068]    The conical filter shape has the following advantages. If this filter has a maximum, expanded, diameter of 8 mm and is placed in an artery of 8 mm diameter, all holes will be free from the artery wall and blood can flow through all holes. As soon as particles of debris, like emboli, are entrapped, they will tend to collect at the most distal tip, leaving the more proximal holes open. 
         [0069]    The area of the conical surface of the cone relates to the cross-sectional area of the artery as the length of the cone edge from base to tip relates to the radius of the artery. Preferably, the total surface area of the holes should be at least equal to the cross-sectional area of the artery in order to guarantee an almost undistorted blood flow. This is the case if the ratio of the total surface area of the cone surface to the total hole surface area is smaller than the ratio of the cone surface area to the cross-sectional area of the artery, or, in other words, the total surface are of the holes is at least equal to the cross-sectional area of the artery. 
         [0070]    For an artery having an inner diameter of 8 mm, a total number of 6400 holes each with a 100 micron diameter is needed for the same surface area. Of course, the type of flow through small 100 micron diameter holes is different from the undistorted flow through an open artery. However, because the wall thickness of a reinforced membrane according to the invention can be extremely small, the length of a hole (for example only 5 microns) ensures a much better flow than compared to a 100 micron hole in a thick membrane. 
         [0071]    A filter made in conical shape will also have enough free holes if it is used in arteries with smaller diameter. The holes that touch the artery wall will not contribute to the flow, but the remaining free holes still have the same surface area as the actual cross section of the smaller artery. 
         [0072]    Filters according to this invention are so much more flexible than existing filters that they can be made longer without creating problems in strong curves. Therefore they can have greater storage capacity for emboli. 
         [0073]    If the reinforced membrane and the filter frame are mounted to each other without overlap, as in  FIG. 32 , it may be clear that the collapsed diameter can be made smaller than in the case of, for example,  FIG. 31 . 
         [0074]    Here, at a specific cross section of the Nitinol frame near the attachment points  429 , the Nitinol frame, the membrane, the fibers and a central guide wire  453  all take their part of the available cross section in the delivery sheath. It depends on the demands if this is allowable, or if a design should be chosen without overlap, where frame and membrane are separated by the fiber hinges, thus reducing the size. 
         [0075]    The construction of Nitinol frame  420  has certain advantages. Production of the frame is very simple, the guide wire is kept in the center, and the filter can be pulled out of the delivery sheath by pushing on guide wire  453  from the left to exert a pulling force on fiber  452  and membrane  451 . 
         [0076]    During removal of the filter from an artery, the longitudinal spokes  426  of frame  420  just have to pull the struts  427  of the zigzag section into a removal sheath. 
         [0077]    However, such a frame can also have some disadvantages. In strongly curved arteries the guide wire will bend and it will cause forces that may deform the zigzag struts. Eventually the contact with the wall of the artery is not optimal then, which is undesirable. 
         [0078]    Another disadvantage is that axial movements of the guide wire, for example caused by the angioplasty/stenting procedure can influence the position of the filter. It would be better if the guide wire could move freely over at least a certain axial length plus in radial and tangential directions within the entire cross section of the filter, without exerting any force on the expanded frame. 
         [0079]    In  FIGS. 33-36  an embodiment with such a freely movable guide wire is disclosed. 
         [0080]      FIG. 33  shows a filter  460  that is constructed in such a way that it can be delivered from a delivery sheath by pushing on a guide wire  461  to exert a pulling force on the filter. After completion of use of the filter in a medical procedure, the filter is removed by pulling it into a removal sheath with the aid of guide wire  461 . The pulling forces are applied in both directions by moving guide wire  461  in axial direction relative to the sheath. 
         [0081]    Guide wire  461  runs through the filter and ends at distal section  462 . Fastened to guide wire  461  are stops  463  and  464  that have a larger diameter than the guide wire itself. These stops are connected tightly to the guide wire by any known technique. At the distal tip of filter  460 , a ring  465  is fastened to the filter and guide wire  461  can slide freely through ring  465 , until stop  463  touches ring  465 . 
         [0082]    At the proximal side of stop  464 , a second slide ring  466  is mounted around guide wire  461  to allow guide wire  461  to slide freely therethrough. Slide rings  465  and  466  are given a smooth shape with rounded edges to let the move easily in associated sheaths and in the artery. 
         [0083]    The filter membrane  470  is connected directly to slide ring  465  and reinforcement fibers  471  are also attached tightly to ring  465 . At the other side, reinforcement fibers  471  are connected to an expandable frame  480  at connection points  481 , possibly together with the membrane material itself. 
         [0084]    Expandable frame  480  is provided with points of attachment  482  at its proximal side, which are needed to pull the frame back into a removal sheath, such as sheath  490  in  FIG. 34 . Flexible fibers  483  are connected to these points  482  and run to the proximal slide ring  466 , to which they are securely attached. 
         [0085]    If the guide wire is moved through the filter in the proximal direction, i.e., to the left in  FIGS. 33-35 , stop  464  will move freely over a distance X 1  before it touches slide ring  466 , and fibers  483  become stretched. 
         [0086]    If the guide wire is moved through the filter in the distal direction, i.e., to the right in  FIGS. 33-35 , stop  463  will move freely over a distance X 2  before it touches slide ring  465 . Fibers  483  will hang free than, because there is no axial force on slide ring  466 . This means that, when the filter has been placed in an artery, guide wire  461  can move freely in the cross-sectional area of the filter frame in both radial and tangential directions without exerting any forces on this frame. Further, the guide wire can also move back and forth over a total distance X (=X 1 +X 2 ) in the longitudinal direction relative to the filter, before it influences the shape or axial position of the filter in the artery. Distance X can be changed by choosing the distance between fixed stops  463  and  464 . If one of these stops is removed, distance X is maximized. Of course the distal end section  462  of guide wire  461  must then be long enough to prevent slide ring  465  from disengaging from the guide wire tip. 
         [0087]    With the construction of slide rings  465  and  466  on guide wire  461 , the guide wire can be rotated around its length axis without influencing the position and shape of the filter and its frame. 
         [0088]    All of these degrees of freedom enable the operator to use guide wire  461  for angioplasty/stenting procedures without influencing the shape and position of the distal filter. This is extremely important. 
         [0089]    Further, this design allows the length of Nitinol frame  480  to be shortened and thus it makes the filter more flexible and more easily usable in strongly bent arteries and arteries with limited space for the filter, in view of the high degree of flexibility of membrane  470  and fibers  471  and  483 . In a strongly curved artery, guide wire  461  may even touch the inner wall of frame  480 , without exerting relevant forces on the filter. Even with a strongly bent guide wire, the filter will still maintain its full contact with the artery wall and guarantee a safe functioning of the device for a wide range of artery diameters and geometries. 
         [0090]    As can be seen from a comparison of  FIG. 33  with  FIGS. 31 and 32 , the design of  FIG. 33  gives a much smaller proximal surface of the expanded frame. In  FIGS. 29-32 , the Nitinol spokes  426  and the proximal side of tube section  425  have a certain surface area that reduces blood flow. This surface area is much smaller in  FIG. 33 , because only a few thin fibers  483  are interposed in the blood flow. 
         [0091]    Another advantage is that debris in the blood will less likely adhere to the thin fibers than to the proximal side of parts  425  and  426  of  FIGS. 29-32 . Of course, an additional treatment of these fibers to reduce the tendency of blood cells to adhere thereto is helpful and is a part of this invention as well. The material for these fibers can be of any kind, and they can for example made of the same materials as the reinforcement wires for the filter membrane. 
         [0092]    An example would be a composite fiber made of a Nitinol filament core, surrounded by a multifilament ultra high molecular weight highly oriented polymer. The Nitinol can be used to give some shape control to the wire, for example to prevent adjacent fibers from becoming entangled. The polymer multifilament, besides having high strength and low strain, can have for example anti-thrombogenic agents embedded therein. 
         [0093]    In  FIG. 34  the filter of  FIG. 33  is shown in a stage in which it is being delivered from a delivery sheath  490 . Sheath  490  has a wall  491  and a distal end  492 . At the proximal side of the guide wire  461  a pushing force F is applied in the distal direction, while sheath  490  is being pulled back in the proximal direction, or is being held in place. Stop  463  on guide wire  461  is now in direct contact with slide ring  465 , and force F is transferred by this ring to the reinforcement fibers  471  of the filter membrane  470 . By the resulting pulling force in the filter membrane and fibers  471 , the filter membrane is stretched and this pulling force is transferred to the collapsed frame  480  via connection points  481 . The frame and filter membrane will easily slide out of sheath  490  by this pulling force, followed by the unloaded fibers  483  and slide ring  466 . As can be seen, the proximal section  482  of frame  480 , to which the fibers  483  are attached, is slightly bent inwards to create a conical proximal side of frame  480 . 
         [0094]      FIG. 35  shows the filter in a position to be retracted into a removal sheath  500 . Removal sheath  500  has a wall  493  and a distal end  494 . At distal end  494 , the removal sheath may have a flared end section  495 , as shown in  FIG. 35   a , a chamfered wall  496 , as shown in  FIG. 35   b , or a combination thereof. Distal end  494  must enable the retrieval of the filter into the lumen of sheath  500  by a pulling force, which is applied to the proximal end of guide wire  461  while sheath  500  is being moved in the distal direction or is being held in place. The tapered proximal side  482  of the frame also assists withdrawal of the frame into removal sheath  500 . 
         [0095]    The force F 1 , applied to guide wire  461 , is transferred by stop  464  to slide ring  466 , which distributes the force to fibers  483  that are now pulling on the proximal side  482  of frame  480 . 
         [0096]    The wire ends can be attached by any technique that is available, for example by putting them through respective holes  484  in frame  480 , and securing them by a knot  485  on the inside surface of the frame. The proximal tips  486  of frame  480  have been formed in such a way that they are slightly curved inside with a conical top angle that is larger than the top angle of the cone, described by the stretched fibers  483 , just before the parts  486  enter into removal sheath  493 . This is done to prevent these proximal sections from becoming stuck at the distal end  494  of the removal sheath. 
         [0097]    With the tapered shape of frame  480 , the tension force in fibers  483  will easily make it possible to slide the removal sheath over the frame until it is completely covered by this sheath. Filter membrane  470 , eventually filled with embolic debris, does not have to be pulled into this sheath completely. It can extend from the distal end  494  while the whole device is removed from the artery. 
         [0098]      FIGS. 36   a  and  36   b  are side views of an alternative embodiment  510  of the filter frame, in its expanded and collapsed shapes, respectively. This embodiment is shorter than the embodiment of  FIGS. 33-35 , and, in particular, lacks the distal end portion of the embodiment of  FIGS. 33-35 . In  FIGS. 36   a  and  36   b , frame  510  is composed of struts configured in a zigzag-pattern. Here again the proximal side  512  is curved inwardly with curved tips  516  and it has attachment holes  514  for the fibers. 
         [0099]    The fact that the filter frame is not subjected to a pushing force during deployment from, or retraction into, a sheath enables a further downscaling of the frame struts and thus a miniaturization of the delivery profile of the device. This is also enhanced by the fact that the guide wire does not influence the shape and position of the filter upon angioplasty and stenting, so the frame itself can now also be made lighter. 
         [0100]    In  FIG. 37 , another embodiment of the filter frame  520  is shown. Elongated attachment parts  526  are formed at the proximal side  512  of the frame  520  in order to bring the holes  524  for the attachment of the fibers  483  further away from the expandable and collapsible unit cells of the frame. This increased length helps to achieve a smoother shape upon shape setting, so that these struts will have the desired curvature that is needed to slide easily into the removal sheath. Placement of the attachment holes at the very proximal tip of the frame struts will also help to allow the frame to be pulled back into the removal sheath without the risk of getting stuck at the entrance of this sheath. 
         [0101]    The elongated struts forming frame  520  can be shape set into almost any desirable angle. A part of the struts may be parallel with the length axis of the filter, while another part or parts may be angled inside or outside, as needed for smooth removal of the device. Outside angled tips may even help to anchor the frame in the blood vessel for more axial stability. 
         [0102]      FIG. 38  shows another feature of the present invention. The design of a filter according to the invention with flexible fibers  483  makes it possible to push a tube  530  over guide wire  461  until the distal end  531  of tube  530  reaches deep into the filter. 
         [0103]    The fibers  483  will easily move with distal end  531  of tube  530  and, dependant on the length of these fibers, the most distal position of tube end  531  can be chosen. This positioning of a tube inside or beyond the frame  520  opens the possibility of flushing and/or suction through it in order to move debris either deeper into the distal end of the filter or to suction debris out of the filter. Flushing with certain liquids can also help to make the debris smaller. An additional treatment device can also be inserted through tube  530  inside the filter. This additional treatment device can be any means for inspection, measuring or all kinds of treatments like breaking up of clots by mechanical means, laser, ultrasonics, etc. Also additional retrieval devices may be brought into the filter through tube  530 . Of course, tube  530  may be the same tube as the removal sheath, in order to save components and to reduce operating time. 
         [0104]      FIG. 39  shows another embodiment for the shape of a filter  470 , with an additional reservoir  472  for storage of debris. Because the conical filters of  FIGS. 33-38  have a tip with limited space to store debris, the filter may be filled too soon, which may cause problems with maintaining a satisfactory blood flow through the filter. 
         [0105]    Normally it can be expected that the major part of the debris will collect most distally, leaving the most proximal holes open for blood flow. This can be improved by providing additional reservoir  472 , which is connected to the conical section  473  by a portion  474 . If the diameter of reservoir  472  is half the maximum diameter of the frame, the surface area that remains free for blood flow between the wall of the full reservoir and the artery wall is still 75% of the maximum surface area of the artery. The capacity of reservoir  472  can be chosen so that the closure of filter holes in section  473  by abundant debris is most unlikely. Additional flushing and/or suction as described with references to  FIG. 38 , may further help here. Of course, continuous monitoring of the blood flow beyond the distal end of the filter will give the necessary information if the situation becomes critical and the filter must be removed. 
         [0106]    The shape and diameter of reservoir  472  will be dependent on the expected diameter and geometry of the artery that will be treated. The shape of reservoir  472  can be determined by embedded fibers. The membrane may for example be elastic, while the fibers can have a limited stretchability. Dependent on the pressure inside the reservoir, the diameter of the membrane can be made to vary until it reaches a certain predetermined value, when the embedded fibers reach their strain limit. Such embedded diameter limiting fibers will have a more or less tangential orientation. 
         [0107]    Frames as shown in  FIGS. 33-39  and described above may not only be used in application of filters. They can also be used as a removable temporary stent, dilator, reamer, occlusion device for main artery or side artery, a housing for a graft, a valve, a delivery platform for drugs, radiation or gene therapy, or any other device that has to be placed and removed after some time. Applications are not restricted to arteries, but are meant for all body lumens. 
         [0108]    A filter according to the invention, particularly because of the flexibility of the fibers, allows an element, such as tube  530  of  FIG. 38 , to penetrate into the region enclosed by the membrane structure to apply suction to debris contained in the filter bag either continuously or intermittently. This is particularly applicable to the distal filter of a two filter assembly. The tube can be introduced over a guide wire associated with the filter and can enter the filter with no risk of perforating it. The safety of applying suction to the interior of the filter is ensured by the nature of the material used for the membrane and reinforcing fibers, as described above with reference to  FIGS. 28-29 . Such suction allows the filter to be maintained relatively free of debris and helps to achieve a relative stability in blood flow through the membrane. In addition, the suction element enables the filter to be kept in a relatively empty condition prior to its being closed and withdrawn and prior to the use of a distal retrieval filter. 
         [0109]    Membranes according to the invention can be used, without holes, as skin for grafts, stents, heart valve tissues, etc. 
         [0110]    The following Figures show a device bearing certain similarities to that shown in  FIG. 9  and having components shown in other Figures that have already been described herein. Components and body features identical to those of  FIG. 9  and the other Figures will be identified with the same reference numerals as those used in  FIG. 9 . 
         [0111]    The start of a procedure according to the invention is shown in  FIG. 40 . First, a sheath, or guiding catheter,  68  carrying a surrounding balloon  72  near its distal end is introduced into common carotid artery (CCA)  70  by a conventional angiographic procedure. Balloon  72  is initially deflated. Guiding catheter  68  preferably has a diameter of 8-9Fr (3Fr=1 mm). 
         [0112]    The next step is the introduction of a filter into the external carotid artery. Customarily, the external carotid artery may have a tortuous course and its location is established initially by the use of a combination of a guide wire  600  and a sheath  10 , which may have a diameter of 3Fr. Guide wire  600  can be radiolucent and non-traumatic and can be positioned with the sheath accurately within the external carotid artery. 
         [0113]    After this position has been established, guide wire  600  can be withdrawn and a filter  601  carried by a guide wire  2  having a distal extension  2 ′ is placed in the external carotid artery  66  through sheath  10 . Then sheath  10  is withdrawn to deploy, or expand, filter  601  in order trap any debris from the subsequent angioplasty procedure while allowing at least a limited blood flow past filter  601 . This procedure is shown in  FIG. 41 . Guide wire  2  and extension  2 ′ are each provided with a bead, as shown in  FIG. 41 , to hold filter  601  in place. Filter  601  may be provided with a filter sheet having a pore size of 100 μm. 
         [0114]    At this stage, blood flow is antegrade, i.e., in the normal forward flow direction, in CCA  70 , ICA  64  and ECA  66 . 
         [0115]    Filter  601  preferably has any of the forms shown in attached FIGS.  7  and  28 - 39 . 
         [0116]    Sheath  10  is withdrawn from the patient&#39;s body to assure that space is available in sheath  68  for subsequent insertion of other catheters. 
         [0117]    In the next part of the procedure, as shown in  FIG. 42 , a further guide wire  602  is introduced through sheath  68  into ICA  64 , past the site of obstruction  62  and an angioplasty catheter  604  carrying a stent  606  is introduced over guide wire  602  to bring stent  606  in line with obstruction  62 . For locating the internal carotid and dealing with technical difficulties of intubation this introduction may need to be carried out in exactly the same way as described above with respect to the introduction of filter  601  in ECA  66 . Guide wire  602  can be a hollow guide wire connected to a pressure gauge to allow the pressure in ICA  64  to be monitored. 
         [0118]    Catheter  604  typically carries a stent deployment balloon that is expanded after catheter  604  has been properly positioned, to expand and deploy stent  606  in order to alleviate the blockage caused by obstruction  62 . Initially, the balloon carried by catheter  604  is deflated. 
         [0119]    The blood flow continues to be antegrade. 
         [0120]    Then, as shown in  FIG. 43 , balloon  72  is inflated to block blood flow in CCA  70  around sheath  68 , thereby essentially blocking most or all of antegrade blood flow in arteries  64 ,  66  and  70 . This allows possible retrograde flow in the ICA and/or ECA. If at this time ICA  64  is not completely blocked, some retrograde flow may occur therein and will result in minimal antegrade flow into ECA  66 . The reason for this assumption is that, ordinarily, blood flow, antegrade or retrograde, in an unobstructed ICA is approximately 3 times that into the ECA and the presence of a filter in the ECA would be expected to reduce flow through the ECA further. Hence, although the retrograde flow from the ICA will initially tend to stagnate in the intermediate part of the carotids between the ICA and ECA, one would expect that if flow occurs from the ICA to ECA, it would be minimal. Equally, the argument cant be made that in the presence of a high grade block in ICA  64 , some minimal blood flow can occur from the ECA to ICA which, the presence of a filter, acting as a resistance and being used for this purpose, will tend to negate. 
         [0121]    After inflation of balloon  72  to block blood flow in CCA  70  around sheath  68  (blood flow within sheath is prevented by sealing the proximal end of sheath  68 ), the balloon carried by catheter  604  is expanded to expand and deploy stent  606  in a manner to compress and at least partially disintegrate obstruction  62 . The resulting debris tends to be trapped between filter  601  in ECA  66 , balloon  72  and and the balloon on catheter  602 . 
         [0122]    The balloon carried by catheter  604  is then deflated after stent deployment. It is to be noted that, ordinarily, retrograde flow would cease when CCA  70  is blocked. However, in the apparatus described, upon partial withdrawal of catheter  604 , it can be utilized to perform low grade suction from outside the body of stagnant blood and debris in the area between the ICA, CCA and blocking balloon  72 . Specifically, suction can be applied by a suction device connected to the proximal end of catheter  604 , from a location outside of the patient&#39;s body, as shown in  FIG. 43 . If, for some reason, the suction provided through catheter  604  is inadequate, catheter  604  can be withdrawn completely from the patient&#39;s body and rapidly exchanged with a 6 F, non-tapered sheath inserted over guide wire  602  and advanced to the top of sheath  68 . Controlled suction can then be resumed through that catheter into the suction device until particulate material and clots are evacuated. Furthermore, drugs such as heparin and other antithrombotic agents, for example Bivalarudin, can be introduced into the arteries through that catheter to allow any clots that have formed to be disintegrated. The drugs used can be other than the one mentioned but would need to be capable of clot dissolution. Using this technique of suction would also promote continued retrograde flow and avoid stagnation, and thereby, reduce the possibility of more clots forming. The material that is suctioned can be readily examined under a microscope and analyzed for debris size, content, and character. The reason for using low pressure suction is to prevent collapse of the stent or stents. 
         [0123]    The presence of filter  601  in ECA  66  will markedly diminish retrograde flow and can serve to prevent a flow from ECA to ICA. Thus, it acts as a partial obstruction. For practical purposes, any retrograde flow from ICA  64  to ECA  66  will result in trapping of debris in filter  601 . 
         [0124]    Then, angioplasty stent catheter  604 , or the above-mentioned non-tapered sheath, is withdrawn from the patient&#39;s body and, as shown in  FIG. 44 , a 3Fr sheath  610  is introduced into ICA  64  over guide wire  602  past stent  606 . Guide wire  602  is then withdrawn from the patient&#39;s body and, as shown in  FIG. 45 , a second filter  620 , identical to any of the filters disclosed herein, is introduced through sheath  610  by a procedure identical to that utilized for introducing a filter into the ECA, as described above, after which that sheath is pulled back to carefully deploy filter  620 , using radiological verification beyond the stent, at a location past stent  606  and allow the filter to expand in order to trap any debris that may subsequently flow in the antegrade direction. In this stage, sheath  10  can be reintroduced at least into CCA  70 , as shown in  FIG. 44 . 
         [0125]    Sheath  610  can now be withdrawn or left in. 
         [0126]    After both filters are safely deployed and are stable, antegrade flow is allowed to resume by deflating balloon  72 .  FIG. 46  shows debris captured by filters  601  and  620 . The purpose of the two filters is to protect the cerebral circulation from embolization through either the internal carotid or, less commonly, through the external carotid, both arteries having been shown to have communications with the brain and the eyes. 
         [0127]    If the patient is hemodynamically stable and has no evidence of stroke objectively determined by well known techniques such as transcranial doppler of the brain and clinical evaluation, each filter can be withdrawn using its respective introductory sheath to end the procedure. This is done, as shown in  FIG. 47 , by merely advancing, or reintroducing, sheaths  10  and  610  to capture and thus retract filters  601  and  620 , filter  601  preferably being withdrawn first. Then sheaths  10  and  610  are completely removed from the patient&#39;s body, followed by withdrawal of sheath  68  from the patient&#39;s body. 
         [0128]    According to a further feature of the invention, suction may be applied to ICA  64  through sheath  610  after angioplasty catheter  604  has been withdrawn from the patient&#39;s body, i.e., at the stage shown in  FIG. 44 , when balloon  72  is still inflated, and/or, through sheath  10  after it has been reintroduced at some point following withdrawal of catheter  604 . This provides added assurance of complete removal of debris resulting from the angioplasty procedure. 
         [0129]    Suction can also be applied directly through sheath  68 . 
         [0130]    Introduction of all illustrated components into the arteries can be effected according to conventional techniques through a conventional manifold. 
         [0131]    While the description above refers to particular embodiments of the present invention, it will be understood that many modifications may be made without departing from the spirit thereof. The accompanying claims are intended to cover such modifications as would fall within the true scope and spirit of the present invention. 
         [0132]    The presently disclosed embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims, rather than the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

Technology Category: 1