Patent Publication Number: US-2013238012-A1

Title: Embolic coils

Description:
TECHNICAL FIELD 
     The invention relates to embolic coils, as well as related methods, devices, and compositions. 
     BACKGROUND 
     Therapeutic vascular occlusions (embolizations) are used to prevent or treat pathological conditions in situ. Embolic coils can be used to occlude vessels in a variety of medical applications. Delivery of embolic coils (e.g., through a catheter) can depend on the size and/or shape of the coils. Some embolic coils include fibers that can, for example, enhance thrombosis at a treatment site. 
     SUMMARY 
     In one aspect, the invention features an embolic coil that includes a wire having a primary shape with a first outer diameter and a second outer diameter that is smaller than the first outer diameter. The embolic coil is configured to fit within the lumen of a subject. 
     In another aspect, the invention features a method of making an embolic coil, the method including forming a wire into a primary shape with a first outer diameter and a second outer diameter that is smaller than the first outer diameter to form the embolic coil. 
     In another aspect, the invention features a medical device that includes a tubular body (e.g., a catheter) with a lumen, and at least one embolic coil (e.g., multiple, embolic coils) disposed within the lumen. The embolic coil includes a Wire that has a primary shape with a first outer diameter and a second outer diameter that is smaller than the first outer diameter. 
     In another aspect, the invention features a method that includes administering at least one embolic coil (e.g., multiple embolic coils) to a subject. The embolic coil includes a wire that has a primary shape with a first outer diameter and a second outer diameter that is smaller than the first outer diameter. 
     In another aspect, the invention features a method of using a medical device that includes a tubular body (e.g., a catheter) with a lumen, and at least one embolic coil (e.g., multiple embolic coils) disposed within the lumen. The embolic coil includes a wire that has a primary shape with a first outer diameter and a second outer diameter that is smaller than the first outer diameter. The method includes inserting the tubular body into the lumen of a subject, and delivering the embolic coil into the lumen of the subject. 
     Embodiments may also include one or more of the following. 
     The embolic coil can have an effective column strength of from 0.005 pound to about 0.05 pound. 
     The first outer diameter can be at most about 0.03 inch (e.g., from about 0.014 inch to about 0.016 inch), and/or the second outer diameter can be at most about 0.025 inch (e.g., from about 0.012 inch to about 0.013 inch). In some embodiments, the difference between the first outer diameter and the second outer diameter can be at most about 0.024 inch (e.g., from 0.001 inch to 0.004 inch). In certain embodiments, the ratio of the first outer diameter to the second outer diameter can be at least about 1.05:1, and/or at most about 1.5:1. For example, the ratio of the first outer diameter to the second outer diameter can be from about 1.05:1 to about 1.5:1. 
     In some embodiments, a region of the wire that has the first outer diameter can have a length of at most about 35 centimeters. In certain embodiments, a region of the wire that has the second outer diameter can have a length of at most about 10 millimeters (e.g., at most about five millimeters). 
     The wire can have a diameter of from 0.001 inch to 0.005 inch (e.g., 0.003 inch), and/or a restrained length of at most about 250 inches. The wire in its primary shape can have a length that is at least about 20 centimeters. The wire can include a metal (e.g., platinum). The wire can have a secondary shape, such as a J, a diamond, a vortex, or a spiral. 
     The embolic coil can include at least one fiber that is attached (e.g., tied) to the wire (e.g., to a region of the wire that has the second outer diameter). The fiber can include polyethylene terephthalate and/or nylon. In certain embodiments, the fiber can have a length of from about 0.5 millimeter to about five millimeters. 
     Forming a wire into a primary shape can include applying a temperature of about 25° C. to the wire and/or winding the wire around a mandrel. The mandrel can have a third outer diameter and a fourth outer diameter that is smaller than the third outer diameter. In some embodiments, the third outer diameter can be at most about 0.03 inch. In certain embodiments, the fourth outer diameter can be at most about 0.025 inch. The mandrel can include stainless steel. The mandrel can have a lubricious coating (e.g., including polytetrafluoroethylene). The mandrel can include a shape-memory material. In some embodiments, the mandrel can be formed of an erodible or dissolvable material (e.g., an erodible or dissolvable polymer, metal, or metal alloy). In certain embodiments, the mandrel can be hollow. 
     The method can further include attaching (e.g., bonding) at least one fiber to the wire (e.g., to a region of the wire having the second outer diameter). In some embodiments, the fiber can be attached to the wire by compressing the fiber between a first winding of the wire and a second winding of the wire. In certain embodiments, the fiber can be adhesive bonded to the wire. 
     Forming a wire into a primary shape can include applying a first tension to the wire to wind a first region of the wire around a mandrel, and applying a second tension to the wire to wind a second region of the wire around the mandrel. The second tension can be greater than the first tension. In some embodiments, the first tension can be from about four grams to about 80 grams (e.g., from about 10 grams to about 80 grams, from about 25 grams to about 29 grams). In certain embodiments, the second tension can be from about 15 grams to about 100 grams (e.g., from about 30 grams to about 40 grams). The difference between the second tension and the first tension can be from about five grams to about 90 grams. 
     The method can further include forming the wire into a secondary shape (e.g., a J, a diamond, a vortex, or a spiral). Forming the wire into a secondary shape cart include applying a temperature of about 1100° F. to the wire and/or winding the wire in its primary shape around a mandrel. The mandrel can be a stainless steel mandrel. In some embodiments, the mandrel can be plated with chrome. 
     The method can further include combining the embolic coil with a pharmaceutically acceptable medium. 
     The medical device can include a pusher wire. In some embodiments, the pusher wire can be disposed Within the lumen of the tubular member or tubular body, and attached to the embolic coil. 
     In some embodiments, the method of administration can be by a catheter. In certain embodiments, the method of administration can be by a device that has an internal opening, and that is configured to fit within a lumen of a subject. The embolic coil can be disposed within the internal opening of the device. 
     The method can further include using a pusher and/or a saline flush to deliver the embolic coil from the device. In some embodiments, the method can be used to treat aneurysms, arteriovenous malformations, traumatic fistulae, tumors, and combinations thereof. In certain embodiments, the method can include embolizing a lumen of a subject. In some embodiments, the embolic coil can be used in a transarterial chemoembolization procedure. Delivering the embolic coil into the lumen of the subject can include detaching (e.g., chemically detaching, electrolytically detaching) the embolic coil from the pusher wire. The embolic coil can be mechanically detached from the pusher wire. In some embodiments, the method can further include withdrawing the embolic coil into the lumen of the tubular body. 
     Embodiments can include one or more of the following advantages. 
     In some embodiments, an embolic coil can exhibit relatively good occlusive properties to when delivered to a location of interest within a subject. This can, for example, allow the embolic coil to be used to occlude a vessel (e.g., to embolize a tumor), treat an aneurysm, treat an arteriovenous malformation, and/or treat a traumatic fistula. 
     In certain embodiments, an embolic coil can have a relatively low likelihood of sticking to the wall of a delivery catheter. This can, for example, reduce the possibility of complications resulting from the embolic coil sticking to the wall of the delivery catheter when the embolic coil is being delivered to a location of interest within a subject. 
     In some embodiments, an embolic coil can have a relatively high effective column strength. This can, for example, allow the embolic coil to be delivered to a location of interest within a subject even if the embolic coil undergoes seine sticking to the wall of the delivery catheter during delivery of the embolic coil. 
     In certain embodiments, an embolic coil can have a relatively low likelihood of sticking to the wall of a delivery catheter, while also exhibiting relatively good occlusive properties when delivered to a location of interest within a subject. 
     In some embodiments, an embolic coil can have a relatively high effective column strength, while also exhibiting relatively good occlusive properties when delivered to a location of interest within a subject. 
     In certain embodiments, an embolic coil can have a relatively low likelihood of sticking to the wall of a delivery catheter, while also having a relatively high effective column strength, so that even if the embolic coil does stick to the wall of the delivery catheter, the coil can be pushed to a sufficient extent to overcome the sticking and deliver the coil from the catheter. 
     In some embodiments, an embolic coil can have a relatively low likelihood of sticking to the wall of a delivery catheter, a relatively high effective column strength, and relatively good occlusive properties when delivered to a location of interest within a subject. 
     Features and advantages are in the description, drawings, and claims. 
    
    
     
       DESCRIPTION OF DRAWINGS 
         FIG. 1A  is a side view of an embodiment of an embolic coil in a delivery device. 
         FIG. 1B  is a side view of the embolic coil of  FIG. 1A . 
         FIGS. 2A-2C  illustrate the delivery of an embodiment of an embolic coil to the site of an aneurysm. 
         FIG. 3A  is a perspective view of an embodiment of an embolic coil. 
         FIG. 3B  is a perspective view of an embodiment of an embolic coil. 
         FIG. 3C  is a perspective view of an embodiment of an embolic coil. 
         FIG. 3D  is a perspective view of an embodiment of an embolic coil. 
         FIG. 4A  is a side view of an embodiment of a process for forming an embolic coil. 
         FIG. 4B  is a side view of an embodiment of a mandrel used in the process shown in  FIG. 4A . 
         FIG. 5A  is a side view of an embodiment of a mandrel. 
         FIGS. 5B and 5C  are illustrations of an embodiment of a process for forming an embolic coil using the mandrel of  FIG. 5A . 
         FIG. 6  is a side view of an embodiment of an embolic coil. 
     
    
    
     DETAILED DESCRIPTION 
     FIG  1 A shows an embolic coil delivery system  8 , which includes a catheter  10  with a lumen  120 . An embolic coil  14 , formed out of a wire  16 , is disposed within lumen  12 . As  FIG. 1B  shows, embolic coil  14  includes regions  20  of relatively large outer diameter and regions  22  of relatively small outer diameter, to which fibers  24  are attached. Regions  20  have an outer diameter “OD 20 ” and a length “L 20 ”, and regions  22  have an outer diameter “OD 22 ” and a length “L 22 ”. Because fibers  24  are attached to wire  16  in regions  22  of relatively snail outer diameter, embolic coil  14  can be accommodated within lumen  12  of catheter  10 , with a relatively low likelihood of substantial contact between fibers  24  and wall  26  of lumen  12 . This can be advantageous, for example, because if fibers  24  come into sufficient contact with wall  26 , then fibers  24  can adhere to wall  26 , which can complicate the delivery of embolic coil  14  from catheter  10  to a treatment site. 
     In general, the design of embolic coil  14  can result in embolic coil  14  having a relatively high effective column strength. The effective column strength of embolic coil  14  is the column strength (the compression load at which embolic coil  14  will buckle) of embolic coil  14  when embolic coil  14  is constrained within lumen  12  of catheter  10 . The presence of regions  20  of relatively large outer diameter in embolic coil  14  can limit the likelihood that embolic coil  14  will buckle, because outer diameter “OD 20 ” of regions  20  can be selected such that regions  20  are relatively close to wall  26  of catheter  10 . Because embolic coil  14  has a relatively high effective column strength, embolic coil  14  can also have good pushability. Thus, even if fibers  24  adhere to wall  26  of lumen  12 , embolic coil  14  may be sufficiently pushable to overcome the adhesion. Furthermore, an embolic coil with a relatively high effective column strength can, for example, be less likely to buckle during deployment from a delivery device than a comparable embolic coil with a relatively low effective column strength. In some embodiments (e.g., embodiments in which outer diameter “OD 20 ” is about 0.012 inch or about 0.035 inch), embolic coil  14  can have an effective column strength of at least 0.005 pound (e.g., at least 0.007 pound, at least about 0.01 pound, at least about 0.03 pound), and/or at most about 0.05 pound (e.g., at most about 0.03 pound, at most about 0.01 pound, at most 0.007 pound). 
     In general, outer diameter “OD 20 ”, the relatively large outer diameter, is selected to provide strength to embolic coil  14 , while also allowing embolic coil  14  to fit within lumen  12  of catheter  10 . In some embodiments, outer diameter “OD 20 ” can be at most about 0.03 inch. In certain embodiments (e.g., for an intermediate-sized embolic coil), outer diameter “OD 20 ” can be from about 0.014 inch to about 0.016 inch (e.g., from about 0.014 inch to about 0.015 inch), In some embodiments (e.g., for a relatively small embolic coil), outer diameter “OD 20 ” can be at most about 0.01 inch. 
     Generally, outer diameter “OD 22 ”, the relatively small outer diameter, is selected to accommodate fibers  24  and to limit the amount of contact between fibers  24  and wall  26  of lumen  12 . In certain embodiments, outer diameter “OD 22 ” can be at most about 0.025 inch. In some embodiments (e.g., for a relatively large embolic coil), outer diameter “OD 22 ” can be from about 0.012 inch to about 0.021 inch (e.g., from about 0.012 inch to about 0.013 inch, from about 0.019 inch to about 0.021 inch). In certain embodiments (e.g., for an intermediate-sized embolic coil), outer diameter “OD 22 ” can be from about 0.01 inch to about 0.012 inch. In some embodiments (e.g., for a relatively small embolic coil), outer diameter “OD 22 ” can be from 0.006 inch to 0.008 inch. 
     Typically, as the difference between outer diameter “OD 20 ” and outer diameter “OD 22 ” increases, longer fibers may be accommodated on embolic coil  14 . In general, as the difference between outer diameter “OD 20 ” and outer diameter “OD 22 ” decreases, the likelihood of kinking by embolic coil  14  may decrease. In embodiments, the difference between outer diameter “OD 20 ” and outer diameter “OD 22 ” typically can be at most about 0.024 inch (e.g., at most about 0.01 inch). For example, the difference between outer diameter “OD 20 ” and outer diameter to “OD 22 ” can be from 0.001 inch to 0.004 inch (e.g., from 0.001 inch to 0.003 inch). 
     Generally, as the ratio of outer diameter “OD 20 ” to outer diameter “OD 22 ” increases, longer fibers may be accommodated on embolic coil  14 . Typically, as the ratio of outer diameter “OD 20 ” to outer diameter “OD 22 ” decreases, the likelihood of kinking by embolic coil  14  may decrease. In some embodiments, the ratio of outer diameter “OD 20 ” to outer diameter “OD 22 ” can be at least about 1.05:1 (e.g., at least about 1.08:1, at least about 1.2:1, at least about 1.25:1, at least about 1.4:1), and/or at most about 1.5:1 (e.g., at most about 1.4:1, at most about 1.25:1, at most about 1.2:1, at most about 1.08:1). In certain embodiments, the ratio of outer diameter “OD 20 ” to outer diameter “OD 22 ” can be from about 1.05:1 to about 1.5:1 (e.g., from about 1.2:1 to about 1.4:1). 
     While lengths “L 20 ” and “L 22 ” can generally be selected as desired, in some embodiments lengths “L 20 ” and “L 22 ” can be selected to achieve certain properties (e.g., effective column strength). In general, as the ratio of “L 20 ” to “L 22 ” increases, the effective column strength of embolic coil  14  increases. Alternatively or additionally, fibers  24  may be more protected from over-exposure to blood during delivery, thereby resulting in a decrease in the occurrence of premature thrombosis. Typically, as the ratio of “L 20 ” to “L 22 ” decreases, the effective column strength of embolic coil  14  can decrease. Generally, as the difference between “L 20 ” and “L 22 ” increases, the effective column strength of embolic coil  14  can increase. In general, as the difference between “L 20 ” and “L 22 ” decreases, the effective column strength of embolic coil  14  can decrease. 
     In some embodiments, length “L 20 ” can be at least about 0.4 centimeter (e.g., at least about one centimeter, at least about two centimeters, at least about five centimeters, at least about 10 centimeters, at least about 20 centimeters, at least about 30 centimeters), and/or at most about 35 centimeters (e.g., at most about 30 centimeters, at most about 20 centimeters, at most about 10 centimeters, at most about five centimeters, at most about two centimeters, at most about one centimeter). For example, length “L 20 ” can be from about 0.4 centimeter to about 20 centimeters (e.g., from about one centimeter to about 20 centimeters, from about five centimeters to about 10 centimeters). 
     In certain embodiments, length “L 22 ” can be at least about 0.5 millimeter (e.g., at least about one millimeter, at least about two millimeters, at least about 2.5 millimeters, at least about three millimeters, at least about four millimeters, at least about five millimeters, at least about eight millimeters), and/or at most about 10 millimeters (e.g., at most about eight millimeters, at most about five millimeters, at most about four millimeters, at most about three millimeters, at most about 2.5 millimeters, at most about two millimeters, at most about one millimeter). For example, length “L 22 ” can be from about one millimeter to about two millimeters. 
     The length of embolic coil  14  when fully extended within lumen  12  of catheter  10  generally can be selected to allow embolic coil  14  to fit within a delivery device such as catheter  10 . In some embodiments embolic coil  14  can be relatively long yet still exhibit good effective column strength so that, for example, even though embolic coil  14  is long, it is sufficiently stiff to be delivered with little or no buckling. In some embodiments, a relatively long embolic coil (which can also exhibit good effective column strength) can be used instead of multiple shorter embolic coils. In some instances, using a single relatively long embolic coil rather than multiple shorter embolic coils can, for example, reduce the time associated with an embolization procedure, increase the efficiency of an embolization procedure, and/or reduce the likelihood of complications associated with an embolization procedure. In certain embodiments, embolic coil  14  can have a fully extended length of at least about 0.5 centimeter (e.g., at least about 2.3 centimeters, at least about five centimeters, at least about 10 centimeters, at least about 15 centimeters, at least about 20 centimeters, at least about 30 centimeters), and/or at most about 40 centimeters (e.g., at most about 30 centimeters, at most about 20 centimeters, at most about 15 centimeters, at most about 10 centimeters, at most about five centimeters, at most about 2.3 centimeters). In certain embodiments, embolic coil  14  can have a fully extended length of from about 0.5 centimeter to about 40 centimeters (e.g., from about 2.3 centimeters to about 30 centimeters, from about five centimeters to about 25 centimeters). 
     As shown in  FIG. 1B , embolic coil  14  is formed of windings of wire  16 , such as windings  17  and  19 . In general, there is little to no space between consecutive windings (e.g. windings  17  and  19 ) of embolic coil  14 . Fibers  24  are tightly fitted between consecutive windings within regions  22  of embolic coil  14 . 
     The pitch of an embolic coil is the sum of the thickness of one winding of wire  16  (e.g., winding  17 ) and the amount of space between that winding and a consecutive winding (e.g., winding  19 ). In some embodiments, embolic coil  14  can have a pitch of at most about 0.01 inch (e.g., about 0.003 inch). Because the windings of embolic coil  14  are flush with each other, the pitch of embolic coil  14  is equal to the diameter of wire  16 . 
     The diameter of wire  16  can be selected, for example, based on the desired properties (e.g., size, strength) and/or applications of embolic coil  14 . In some embodiments, wire  16  can have a diameter of from 0.001 inch to 0.005 inch (e.g., from 0.0015 inch to 0.005 inch, from 0.002 inch to 0.003 inch, from 0.00225 inch to 0.003 inch). In certain embodiments, wire  16  can have a diameter of 0.003 inch. In some embodiments (e.g., embodiments in which embolic coil  14  is used for peripheral vascular applications), wire  16  can have a diameter of at least about 0.004 inch. In certain embodiments (e.g., embodiments in which embolic coil  14  is used for neurological applications), wire  16  can have a diameter of at most about 0.002 inch, Alternatively or additionally, wire  16  can have a restrained length of at most about 250 inches (e.g., at most about 200 inches, at most about 185 inches, at most about 150 inches, at most about 100 inches, at most about 50 inches). 
     Wire  16  can be fainted of for example, one or more metals or metal alloys, such as platinum, a platinum alloy (e.g., a platinum-tungsten alloy), stainless steel, nitinol, and Elgiloy® (from Elgiloy Specialty Metals). 
     Fibers  24  are typically formed of one or more materials that can enhance thrombosis (e.g., at a target site). Examples of materials from which fibers  24  can be made include polyethylene terephthalate (e.g., Dacron®), nylon, and collagen. Fibers  24  can have a length of from about 0.5 millimeter to about five millimeters (e.g., about 2.5 millimeters). In some embodiments, the length of fibers  24  can be selected so that fibers  24  can fit within regions  22  of relatively small outer diameter without bunching up. 
     Embolic coils can generally be used in a number of different applications, such as neurological application and/or peripheral applications. In some embodiments, embolic coils can be used to occlude a vessel, and/or to treat an aneurysm (e.g., an intercranial aneurysm), an arteriovenous malformation (AVM), or a traumatic fistula. In some embodiments, embolic coils can be used to embolize a tumor (e.g., a liver tumor). In certain embodiments, embolic coils can be used in transarterial chemoembolization (TACE). 
       FIGS. 2A-2C  show the use of embolic coil  14  to fill and occlude an aneurysmal sac.  FIG. 2A  shows embolic coil  14 , loaded into lumen  12  of catheter  10 , and a pusher wire  50  disposed outside of catheter  10 . In some embodiments, embolic coil  14  can be disposed within a carrier fluid (e.g., a saline solution, a contrast agent, a heparin solution) while embolic coil  14  is within lumen  12  of catheter  10 . In  FIG. 2B , catheter  10  is delivered into a lumen  51  of a subject, and pusher wire  50  is inserted into lumen  12  of catheter  10 , such that it contacts embolic coil  14 . Pusher wire  50  is then used to push embolic coil  14  out of catheter  10 , into lumen  51 , and toward an aneurysmal sac  52  formed in wall  49  of lumen  51 .  FIG. 2C  shows embolic coil  14  filling aneurysmal sac  52  after embolic coil  14  has been pushed out of catheter  10  by pusher wire  50 . By filling aneurysmal sac  52 , embolic coil  14  helps to occlude aneurysmal sac  52 . This occlusion of aneurysmal sac  52  can be accelerated by fibers  24 , which can enhance thrombosis within aneurysmal sac  52 . An accelerated embolization procedure can benefit the subject by, for example, reducing exposure time to fluoroscopy. 
     In general, embolic coil  14  has a primary shape and a secondary shape. Embolic coil  14  exhibits only its primary shape when embolic coil  14  is fully extended within lumen  12  of catheter  10  (as shown in  FIG. 1A ). As embolic coil  14  exits catheter  10 , however, embolic coil  14  further assumes its secondary shape, which allows embolic coil  14  to fill aneurysmal sac  52 . Typically, the primary shape of embolic coil  14  is selected for deliverability, and the secondary shape of embolic coil  14  is selected for application (e.g., embolization of an aneurysm). 
     As  FIGS. 3A-3D  illustrate, an embolic coil can have any of a number of different secondary shapes, which can depend on the particular application for the embolic coil. For example,  FIG. 3A  shows an embolic coil  100  with a spiral secondary shape, which can be used, for example, to provide a supportive framework along a vessel wall. Alternatively or additionally, an embolic coil with a spiral secondary shape can be used to hold other embolic coils that are subsequently delivered to the target site.  FIG. 3B  shows an embolic coil  110  with a vortex secondary shape, which can be used, for example, to close the center of a target site (e.g., a vessel or an aneurysm) that is to be occluded, and/or to occlude a target site in conjunction with an embolic coil such as embolic coil  100  ( FIG. 3A ). As shown in  FIG. 3C , an embolic coil  120  can have a diamond secondary shape, which, like the vortex secondary shape, can used, for example, to close the center of a target site (e.g., a vessel or an aneurysm) that is to be occluded, and/or to occlude a target site in conjunction with an embolic coil such as embolic coil  100  ( FIG. 3A ).  FIG. 3D  shows an embolic coil  130  with a secondary shape in the form of a J, which can be used, for example, to fill remaining space in an aneurysm that was not filled by other coils. In some embodiments, an operator (e.g., a physician) can hook the curved portion of embolic coil  130  into a coil or coil mass that has already been deployed at a target site, and then shape the straighter portion of coil  130  to fill the target site. 
       FIG. 4A  illustrates a process for forming an embolic coil (e.g., embolic coil  14 ) in its primary shape, and  FIGS. 5A-5C  show a process for forming the secondary shape of the embolic coil. 
     As shown in  FIG. 4A , a coil-forming apparatus  200  includes a mandrel  210  held by two rotatable chucks  220  and  230 . A spool  240  of wire  250  is disposed above mandrel  210 , and is attached to a moving device  260 . To form an embolic coil in its primary shape, chucks  220  and  230  are activated so that they rotate in the direction of arrows A 2  and A 3 , thereby rotating mandrel  210 . Moving device  260  also is activated, and moves spool  240  in the direction of arrow A 1 . The rotation of mandrel  210  pulls wire  250  from spool  240  at a predetermined pull-off angle, and causes wire  250  to wrap around mandrel  210 . As  FIG. 4A  shows, the pull-off angle (α) is the angle between axis PA 1 , which is perpendicular to longitudinal axis LA 1  of mandrel  210 , and the portion  280  of wire  250  between spool  240  and coil  270 . In some embodiments, α can be from about one degree to about six degrees (e.g., from about 1.5 degrees to about five degrees, from about 1.5 degrees to about 2.5 degrees, about two degrees). In certain embodiments, a controller (e.g., a programmable logic controller) can be used to maintain the pull-off angle in coil-firming apparatus  200 . Because mandrel  210  is rotating as it is pulling wire  250  from spool  240 , and because moving device  260  is moving spool  240  in the direction of arrow A 1 , wire  250  forms a coil  270  in a primary shape around mandrel  210 . Coil  270  can be formed, for example, at room temperature (25° C.). 
     Mandrel  210 , also shown in  FIG. 4B , has regions  212  of relatively small outer diameter “OD 212 ” with a length “L 212 ”, and regions  214  of relatively large outer diameter “OD 214 ” with a length “L 214 ”. Because coil  270  is formed by wrapping wire  250  around mandrel  210 , coil  270  has regions of relatively small outer diameter and regions of relatively large outer diameter that correspond to regions  212  and  214  of mandrel  210 . 
     After coil  270  has been formed, chucks  220  and  230 , and moving device  260 , are deactivated, and portion  280  of wire  250 . Mandrel  210  is then released from chuck  220 , and coil  270  is pulled off of mandrel  210 . In some embodiments, mandrel  210  can be coated with a lubricious coating (e.g., polytetrafluoroethylene, such as Teflon®) in one or more sections in order to aid in the removal of coil  270  (e.g., to reduce friction and/or snagging). In certain embodiments, the middle section of mandrel  210  is coated, while the ends of mandrel  210  remained uncoated. In some embodiments, mandrel  210  can be hollow, such that after coil  270  has been formed on mandrel  210 , pressure can be applied to mandrel  210 , causing mandrel  210  to collapse, and thereby making it easier to pull coil  270  off of mandrel  210 . Alternatively or additionally, mandrel  210  may be formed of a shape-memory material, such that the size of mandrel  210  can be decreased by cooling mandrel  210 . In some such embodiments, mandrel  210  can be cooled prior to removal of coil  270 , thereby making it easier to remove coil  270  from mandrel  210 . In certain embodiments, mandrel  210  can be formed of an erodible or dissolvable material (e.g., an erodible or dissolvable polymer, metal, or metal alloy). In some such embodiments, after coil  270  has been formed, mandrel  210  can be eroded or dissolved (e.g., by applying an eroding or dissolving agent to mandrel  210 ), leaving coil  270 . 
     While coil  270  might lose some of its primary shape as it is pulled off of mandrel  210 , coil  270  can generally return to its primary shape shortly thereafter, because of memory imparted to coil  270  during formation. In some embodiments, after coil  270  has been removed from mandrel  210 , one or both of the ends of coil  270  can be heated and melted to form rounder, more biocompatible (e.g., atraumatic) ends. 
     In some embodiments, outer diameter “OD 212 ,” of regions  212  of relatively small outer diameter can be at most about 0.025 inch (e.g., from about 0.012 inch to about 0.013 inch). Alternatively or additionally, length “L 212 ” of regions  212  of relatively small outer diameter can be at most about five millimeters. 
     In certain embodiments, outer diameter “OD 214 ” of regions  214  of relatively large outer diameter can be at most about 0.03 inch (e.g., about 0.015 inch). Alternatively or additionally, length “L 214 ” of regions  214  of relatively large outer diameter can be at most about 35 centimeters. 
     In some embodiments, the difference between outer diameter “OD 214 ” and outer diameter OD 212 ″ can be at most about 0.024 inch (e.g., 0.003 inch). Alternatively or additionally, the ratio of outer diameter “OD 214 ” to outer diameter “OD 212 ” can be from about 1.05:1 to about 1.5:1 (e.g., from about 1.2:1 to about 1.4:1). 
     Mandrel  210  can be formed of, for example, a metal or a metal alloy, such as stainless steel. In some embodiments, mandrel  210  can be formed of one or more polymers, Such as Teflon® (polytetrafluoroethylene) or Delrin® (polyoxymethylene). As described above, in some embodiments, mandrel  210  can be formed of a shape-memory material. An example of a shape memory material is Nitinol. 
     Mandrel  210  can be formed, for example, by a wire extrusion process. In certain embodiments, mandrel  210  can be formed by grinding the mandrel material into the shape of mandrel  210  (e.g., using a centerless grind). In some embodiments, mandrel  210  can be formed by using a lathe and/or laser to cut or ablate sections of the mandrel material (e.g., to form regions  212  of relatively small outer diameter). Alternatively or additionally, mandrel  210  can be formed by etching the mandrel material (e.g., using photochemical etching). In certain embodiments, mandrel  210  can be formed by polymeric or metal injection molding. 
     While mandrel  210  is shown as having relatively sharp edges  211 , in some embodiments, mandrel  210  can have, relatively rounded edges. 
     The tension of mandrel  210  as it is held between chucks  220  and  230  preferably is sufficiently high to avoid vibration of mandrel  210  during the winding process, and sufficiently low to avoid stretching of mandrel  210  during the winding process. In some instances, significant stretching of mandrel  210  during the winding process could cause coil  270  to have a smaller primary shape than desired, and/or could make it relatively difficult to remove coil  270  from mandrel  210 . In embodiments, the tension of mandrel  210  can be from about 100 grams to about 1,000 grams (e.g., from about 300 grams to about 600 grams, from about 400 grams to about 500 grams). For example, the tension of mandrel  210  can be about 506 grams. 
     Wire  250  typically can be wound around mandrel  210  at a tension of from about 10 grams to about 100 grams (e.g., from about four grams to about 50 grams, from about six grams to about 40 grams, from about 22 grams to about 32 grams, about 27 grams). 
     In embodiments, the length of coil  270  in its primary shape and while under tension on mandrel  210  can be from about 10 centimeters to about 250 centimeters (e.g., from about 50 centimeters to about 200 centimeters, from about 130 centimeters to about 170 centimeters, from about 144 centimeters to about 153 centimeters, from about 147 centimeters to about 153 centimeters). For example, the length of coil  270  in its primary shape and while under tension on mandrel  210  can be about 132 centimeters or about 147 centimeters. Coil  270  may recoil to some extent (e.g., by at most about five centimeters) when portion  280  of wire  250  is severed, such that coil  270  will be somewhat smaller once it has been removed from mandrel  210 . In embodiments, coil  270  can have a length of from about five centimeters to about 225 centimeters (e.g., from about 25 centimeters to about 170 centimeters, from about 120 centimeters to about 140 centimeters, from about 137 centimeters to about 140 centimeters) after being removed from mandrel  210 . After coil  270  has been removed from mandrel  210 , coil  270  can be cut into smaller coils. 
     Once coil  270  has been formed in its primary shape, coil  270  can be further shaped into a secondary shape, as shown in FIGS,  5 A- 5 C. 
       FIG. 5A  shows a mandrel  310  used to form the secondary shape of coil  270 . While is mandrel  310  is shaped to form a diamond, other types of mandrels can be used to form other secondary shapes. Mandrel  310  is formed of a diamond-shaped block  320  with grooves  330  cut into its surface. As shown in  FIGS. 5B and 5C , primary coil  270  is wrapped around mandrel  310 , such that coil  270  fills grooves  330 , creating the secondary shape. The ends of coil  270  are then attached (e.g., pinned) to mandrel  310 , and coil  270  is heat-treated at a temperature of from about 100° F. to about 2000° F. (e.g., from about 500° F. to about 1500° F., from about 1010° F. to about 1125° F.) to impart memory to coil  270 . For example, coil  270  can be heat-treated at a temperature of about 1100° F. In some embodiments, the heat treatment of coil  270  can last for a period of from about 10 minutes to about 40 minutes (e.g., about 25 minutes). After being heat-treated, coil  270  is unwrapped from mandrel  310 . The removal of coil  270  from mandrel  310  allows coil  270  to reassume its secondary shape. In some embodiments, after coil  270  has been removed from mandrel  310 , one or both of the ends of coil  270  can be heated and melted to form rounder, more biocompatible (e.g., atraumatic) ends. 
     Mandrel  310  can be formed from, for example, a metal such as stainless steel. In some embodiments, mandrel  310  can be formed of a plated metal (e.g., chrome-plated stainless steel). 
     After coil  270  has been removed from mandrel  310 , fibers can be attached to coil  270 . In some embodiments, coil  270  is stretched prior to attaching fibers, so that coil  270  is in its extended primary shape, and is then loaded onto a fibering mandrel (e.g., a fibering mandrel from Sematool Mold and Die Co., Santa Clara, Calif.). In some embodiments, fibers can be tied to wire  250  and/or wrapped around wire  250 . In certain embodiments, fibers can be snapped in between windings of wire  250  of coil  270 . Alternatively or additionally, fibers can be bonded (e.g., adhesive bonded) to wire  250  of coil  270 . 
     While certain embodiments have been described, the invention is not so limited. 
     As an example, in some embodiments, a coil with a primary shape having regions of relatively small outer diameter and regions of relatively large diameter can be formed by winding a wire around a mandrel with a constant diameter, and varying the tension that is applied to the to wire. For example, a tension of from about 10 grams to about 100 grams (e.g., from about six grams to about 50 grams, from about 30 grams to about 40 grams) can be applied to form regions of relatively small outer diameter, and a tension of from about four grains to about 80 grams (e.g., from about four grams to about 40 grams, from about 25 grams to about 29 grams) can be applied to form regions of relatively large outer diameter. In certain embodiments, the difference between the tension used to form regions of relatively small outer diameter and the tension used to form regions of relatively large outer diameter can be from about five grams to about 90 grams (e.g., from about 20 grams to about 80 grams, from about 30 grams to about 50 grams), 
     As another example, while embodiments have been described in which an embolic coil has two different outer diameters, in certain embodiments, an embolic coil can have more than two (e.g., three, four, five, 10, 15, 20) different outer diameters. For example, an embolic coil can have regions of relatively small outer diameter, regions of intermediate outer diameter, and regions of relatively large outer diameter. 
     As an additional example, while embodiments have been described in which regions of an embolic coil that have the same outer diameter also have the same length, regions of an embolic coil that have the same outer diameter need not have the same length. For example, an embolic coil Can have regions of relatively small outer diameter that have varying lengths. Alternatively or additionally, the embolic coil can have regions of relatively large outer diameter that have varying lengths. 
     As a further example, in some embodiments, consecutive windings of an embolic coil can have a space between them of at most about 0.01 inch (e.g., at most about 0.005 inch, from about 0.001 inch to about 0.005 inch). The space between consecutive windings in an embolic coil can be used, for example, to accommodate a material that enhances thrombosis, such as fibers that enhance thrombosis. 
     As another example, while embodiments have been described in which the pitch of an embolic coil is substantially the same in different regions of the embolic coil, in certain embodiments, the pitch of an embolic coil can differ in different regions of the embolic coil. For example, some regions of an embolic coil can have a pitch of 0.003 inch, while other regions of an embolic coil can have a pitch of 0.004 inch. In some embodiments, an embolic coil can have a region of relatively large outer diameter with a relatively small pitch (e.g., about 0.001 inch), and a region of relatively small outer diameter with a relatively large pitch (e.g., about 0.007 inch). 
     As a further example, while an embolic coil with two different outer diameters has been shown, in some embodiments, an embolic coil can have more than two different outer diameters. For example,  FIG. 6  shows an embolic coil  400 , which is formed out of a wire  402 , and which has multiple windings of different outer diameters. Windings  404  have a relatively small outer diameter “OD 404 ”, windings  406  have an intermediate outer diameter “OD 406 ”, and windings  408  have a relatively large outer diameter “OD 408 ”. Fibers  410  are attached to embolic coil  400  in the area of windings  404 . 
     As an additional example, while a pushable embolic coil has been shown, in some embodiments an embolic coil can alternatively or additionally be a detachable embolic coil. For example, the embolic coil can be temporarily attached to a pusher wire. The embolic coil can be, e.g., mechanically detachable and/or chemically detachable. In some embodiments, the embolic coil can be electrolytically detachable. In certain embodiments, the embolic coil can be a Guglielmi Detachable Coil (GDC) or an Interlocking Detachable Coil (IDC). Detachable embolic coils are described, for example, in Twyford, Jr. et al,, U.S. Pat. No. 5,304,195, and Guglielmi et al., U.S. Pat. No. 5,895,385, both of which are hereby incorporated by reference. 
     As a further example, in some embodiments, a saline flush can be used to deliver an embolic coil from a delivery device. In certain embodiments, the saline flush can be used in conjunction with a pusher wire. 
     As another example, multiple (e.g., two, three, four) embolic coils can be delivered using one delivery device. 
     As an additional example, in some embodiments, a treatment site can be occluded by using coils in conjunction with other occlusive devices. For example, coils can be used with embolic particles such as those described in Raiser et al,, U.S. Published Patent Application No. 2003/0185896 A1, and in U.S. Patent Application Publication No. US 2004/0096662 A1, published on May 20, 2004, both of which are hereby incorporated by reference. In some embodiments, coils can be used in conjunction with one or more embolic gels. Embolic gels are described, for example, in U.S. patent application Ser. No. 10/927,868, tiled on Aug. 27, 2004, and entitled “Embolization”, which is hereby incorporated by reference, 
     Other embodiments are in the claims,