Patent Publication Number: US-2023149022-A1

Title: Filamentary devices for treatment of vascular defects

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. Application Serial No. 16/816,436, filed Mar. 12, 2020, which claims the benefit of priority under 35 U.S.C. § 119(e) from U.S. Provisional Application Serial No. 62/819,296, filed Mar. 15, 2019, both of which are hereby expressly incorporated by reference in their entireties for all purposes. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     Not applicable. 
    
    
     FIELD OF THE INVENTION 
     Embodiments of devices and methods herein are directed to blocking a flow of fluid through a tubular vessel or into a small interior chamber of a saccular cavity or vascular defect within a mammalian body. More specifically, embodiments herein are directed to devices and methods for treatment of a vascular defect of a patient including some embodiments directed specifically to the treatment of cerebral aneurysms of patients. 
     BACKGROUND 
     The mammalian circulatory system is comprised of a heart, which acts as a pump, and a system of blood vessels which transport the blood to various points in the body. Due to the force exerted by the flowing blood on the blood vessel the blood vessels may develop a variety of vascular defects. One common vascular defect known as an aneurysm results from the abnormal widening of the blood vessel. Typically, vascular aneurysms are formed as a result of the weakening of the wall of a blood vessel and subsequent ballooning and expansion of the vessel wall. If, for example, an aneurysm is present within an artery of the brain, and the aneurysm should burst with resulting cranial hemorrhaging, death could occur. 
     Surgical techniques for the treatment of cerebral aneurysms typically involve a craniotomy requiring creation of an opening in the skull of the patient through which the surgeon can insert instruments to operate directly on the patient’s brain. For some surgical approaches, the brain must be retracted to expose the parent blood vessel from which the aneurysm arises. Once access to the aneurysm is gained, the surgeon places a clip across the neck of the aneurysm thereby preventing arterial blood from entering the aneurysm. Upon correct placement of the clip the aneurysm will be obliterated in a matter of minutes. Surgical techniques may be effective treatment for many aneurysms. Unfortunately, surgical techniques for treating these types of conditions include major invasive surgical procedures which often require extended periods of time under anesthesia involving high risk to the patient. Such procedures thus require that the patient be in generally good physical condition in order to be a candidate for such procedures. 
     Various alternative and less invasive procedures have been used to treat cerebral aneurysms without resorting to major surgery. One approach to treating aneurysms without the need for invasive surgery involves the placement of sleeves or stents into the vessel and across the region where the aneurysm occurs. Such devices maintain blood flow through the vessel while reducing blood pressure applied to the interior of the aneurysm. Certain types of stents are expanded to the proper size by inflating a balloon catheter, referred to as balloon expandable stents, while other stents are designed to elastically expand in a self-expanding manner. Some stents are covered typically with a sleeve of polymeric material called a graft to form a stent-graft. Stents and stent-grafts are generally delivered to a preselected position adjacent a vascular defect through a delivery catheter. In the treatment of cerebral aneurysms, covered stents or stent-grafts have seen very limited use due to the likelihood of inadvertent occlusion of small perforator vessels that may be near the vascular defect being treated. 
     In addition, current uncovered stents are generally not sufficient as a stand-alone treatment. In order for stents to fit through the microcatheters used in small cerebral blood vessels, their density is usually reduced such that when expanded there is only a small amount of stent structure bridging the aneurysm neck. Thus, they do not block enough flow to cause clotting of the blood in the aneurysm and are thus generally used in combination with vaso-occlusive devices, such as the coils discussed above, to achieve aneurysm occlusion. 
     Some procedures involve the delivery of embolic or filling materials into an aneurysm. The delivery of such vaso-occlusion devices or materials may be used to promote hemostasis or fill an aneurysm cavity entirely. Vaso-occlusion devices may be placed within the vasculature of the human body, typically via a catheter, either to block the flow of blood through a vessel with an aneurysm through the formation of an embolus or to form such an embolus within an aneurysm stemming from the vessel. A variety of implantable, coil-type vaso-occlusion devices are known. The coils of such devices may themselves be formed into a secondary coil shape, or any of a variety of more complex secondary shapes. Vaso-occlusive coils are commonly used to treat cerebral aneurysms but suffer from several limitations including poor packing density, compaction due to hydrodynamic pressure from blood flow, poor stability in wide-necked aneurysms, and complexity and difficulty in the deployment thereof as most aneurysm treatments with this approach require the deployment of multiple coils. Coiling is less effective at treating certain physiological conditions, such as wide neck cavities (e.g. wide neck aneurysms) because there is a greater risk of the coils migrating out of the treatment site. 
     A number of aneurysm neck bridging devices with defect spanning portions or regions have been attempted, however, none of these devices have had a significant measure of clinical success or usage. A major limitation in their adoption and clinical usefulness is the inability to position the defect spanning portion to assure coverage of the neck. Existing stent delivery systems that are neurovascular compatible (i.e. deliverable through a microcatheter and highly flexible) do not have the necessary rotational positioning capability. Another limitation of many aneurysm bridging devices described in the prior art is the poor flexibility. Cerebral blood vessels are tortuous, and a high degree of flexibility is required for effective delivery to most aneurysm locations in the brain. 
     What has been needed are devices and methods for delivery and use in small and tortuous blood vessels that can substantially block the flow of blood into an aneurysm, such as a cerebral aneurysm, with a decreased risk of inadvertent aneurysm rupture or blood vessel wall damage. In addition, what has been needed are methods and devices suitable for blocking blood flow in cerebral aneurysms over an extended period of time without a significant risk of deformation, compaction or dislocation. 
     Intrasaccular occlusive devices are part of a newer type of occlusion device used to treat various intravascular conditions including aneurysms. They are often more effective at treating these wide neck conditions, or larger treatment areas. The intrasaccular devices comprise a structure that sits within the aneurysm and provides an occlusive effect at the neck of the aneurysm to help limit blood flow into the aneurysm. The rest of the device comprises a relatively conformable structure that sits within the aneurysm helping to occlude all or a portion of the aneurysm. Intrasaccular devices typically conform to the shape of the treatment site. These devices also occlude the cross section of the neck of the treatment site/aneurysm, thereby promoting clotting and causing thrombosis and closing of the aneurysm over time. 
     These intrasaccular devices are difficult to design for various reasons. For neurovascular aneurysms, these intrasaccular devices are particularly small and any projecting structures from the intrasaccular device can prod into the vessel or tissue, causing additional complications. In larger aneurysms, there is also a risk of compaction where the intrasaccular device can migrate into the aneurysm and leave the neck region. There is a need for an intrasaccular device that addresses these issues. 
     SUMMARY 
     An intrasaccular occlusion device is described that is used to treat a variety of conditions, including aneurysms and neurovascular aneurysms. It is generally beneficial to have some stiffness at a proximal region of an intrasaccular device to promote proper seating of the device at the neck of the aneurysm and to resist migration into the aneurysm. It is also generally beneficial to have high flow-disruption at the proximal or neck-adjacent region of the occlusion device to limit blood flow into the aneurysm. One way to increase flow-disruption at the neck region and to prevent the issue of potential migration is to increase stiffness at the proximal part of the intrasaccular device. The following embodiments incorporate coils, springs, or similar components into a proximal mesh portion of an intrasaccular device to increase stiffness and flow-disruption along the proximal part of an intrasaccular occlusion device. 
     In one embodiment, a device for treatment of a patient’s cerebral aneurysm is described. The device comprises a resilient self-expanding permeable shell including a radially constrained elongated state configured for delivery within a catheter lumen, an expanded state with a longitudinally shortened configuration relative to the radially constrained state, and a plurality of elongate filaments that are woven together to form a mesh and define a cavity of the permeable shell, the expanded state having a proximal and a distal portion, wherein the proximal portion comprises at least one coil or spring like element (e.g., either a helical coil or a complex, three-dimensionally shaped coil) coupled to or incorporated into or with the mesh. 
     In another embodiment, a method for treating a cerebral aneurysm having an interior cavity and a neck is described. The method includes the step of advancing an implant in a microcatheter to a region of interest in a cerebral artery, wherein the implant comprises a resilient self-expanding permeable shell including a radially constrained elongated state configured for delivery within a lumen of the microcatheter, an expanded state with a longitudinally shortened configuration relative to the radially constrained state, and a plurality of elongate filaments that are woven together to form a mesh and define a cavity of the permeable shell, the expanded state having a proximal and a distal portion, wherein the proximal portion comprises at least one coil coupled to the mesh, wherein the implant is in the radially constrained elongated state in the microcatheter. The implant is then deployed within the cerebral aneurysm, wherein the permeable shell expands to the expanded state in the interior cavity of the aneurysm. The microcatheter is then withdrawn from the region of interest after deploying the implant. 
     In another embodiment, a device for treatment of a patient’s cerebral aneurysm is described. The device comprises a resilient self-expanding permeable shell including a radially constrained elongated state configured for delivery within a catheter lumen, an expanded state with a longitudinally shortened configuration relative to the radially constrained state, and a plurality of elongate filaments that are woven together to form a mesh and define a cavity of the permeable shell, wherein the expanded state has a proximal and a distal portion, and wherein the proximal portion includes at least one coil coupled to the mesh. 
     In another embodiment, a method for treating a cerebral aneurysm having an interior cavity and a neck is described. The method includes the step of advancing an implant in a microcatheter to a region of interest in a cerebral artery, wherein the implant comprises a resilient self-expanding permeable shell including a radially constrained elongated state configured for delivery within a catheter lumen, an expanded state with a longitudinally shortened configuration relative to the radially constrained state, and a plurality of elongate filaments that are woven together to form a mesh and define a cavity of the permeable shell, wherein the expanded state has a proximal and a distal portion, and wherein the proximal portion includes at least one coil coupled to the mesh. The implant is then deployed within the cerebral aneurysm, wherein the permeable shell expands to the expanded state in the interior cavity of the aneurysm. The microcatheter is then withdrawn from the region of interest after deploying the implant. 
     In another embodiment, a device for treatment of a patient’s cerebral aneurysm is described. The device comprises a resilient self-expanding permeable shell including a radially constrained elongated state configured for delivery within a catheter lumen, an expanded state with a longitudinally shortened configuration relative to the radially constrained state, and a plurality of elongate filaments that are woven together to form a mesh and define a cavity of the permeable shell, wherein the expanded state has a proximal and a distal portion, and wherein the proximal portion includes one or more stiffening elements to augment a proximal stiffness of the device. 
     In another embodiment, a method for treating a cerebral aneurysm having an interior cavity and a neck is described. The method includes the step of advancing an implant in a microcatheter to a region of interest in a cerebral artery, wherein the implant comprises a resilient self-expanding permeable shell including a radially constrained elongated state configured for delivery within a catheter lumen, an expanded state with a longitudinally shortened configuration relative to the radially constrained state, and a plurality of elongate filaments that are woven together to form a mesh and define a cavity of the permeable shell, wherein the expanded state has a proximal and a distal portion, and wherein the proximal portion includes one or more stiffening elements to augment a proximal stiffness of the device. The implant is then deployed within the cerebral aneurysm, wherein the permeable shell expands to the expanded state in the interior cavity of the aneurysm. The microcatheter is then withdrawn from the region of interest after deploying the implant. 
     In another embodiment, a device for treatment of a patient’s cerebral aneurysm is described. The device comprises a resilient self-expanding mesh including a radially constrained elongated state configured for delivery within a catheter lumen and an expanded state with a longitudinally shortened configuration relative to the radially constrained state, wherein the mesh is formed from a plurality of interwoven elongate filaments that define a cavity therein, the mesh having a plurality of pores and a proximal and a distal portion, and wherein the proximal portion of the mesh includes one or more reinforcing elements, such that a proximal porosity of the mesh is less than a distal porosity of the mesh. 
     In another embodiment, a method for treating a cerebral aneurysm having an interior cavity and a neck is described. The method includes the step of advancing an implant in a microcatheter to a region of interest in a cerebral artery, wherein the implant comprises a resilient self-expanding mesh including a radially constrained elongated state configured for delivery within a catheter lumen and an expanded state with a longitudinally shortened configuration relative to the radially constrained state, wherein the mesh is formed from a plurality of interwoven elongate filaments that define a cavity therein, the mesh having a plurality of pores and a proximal and a distal portion, and wherein the proximal portion of the mesh includes one or more reinforcing elements, such that a proximal porosity of the mesh is less than a distal porosity of the mesh. The implant is then deployed within the cerebral aneurysm, wherein the mesh expands to the expanded state in the interior cavity of the aneurysm. The microcatheter is then withdrawn from the region of interest after deploying the implant. 
     The at least one coil (e.g., either having a helical, or three-dimensional complex shape), stiffening element, or reinforcement element may be coupled to the mesh in numerous ways. The at least one coil, stiffening element, or reinforcement element may be disposed about at least one filament of the mesh or the at least one coil may be woven together with the filaments to form the mesh. The at least one coil, stiffening element, or reinforcement element may have a lumen running therethrough and at least a portion of the filament may be disposed in the lumen. The at least one coil, stiffening element, or reinforcement element may be incorporated into at least about 40% to about 100%, alternatively about 50% to about 90%, alternatively about 40% to about 80% of the proximal portion of the device. 
     The at least one coil, stiffening element, or reinforcement element may be a plurality of coils, stiffening elements, or reinforcement elements. For example, the at least one coil, stiffening element, or reinforcement element may include at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25 coils, stiffening elements, or reinforcement elements. The at least one coil, stiffening element, or reinforcement element may include between about 2 and about 10, about 3 and about 12, about 4 and about 8, about 5 and about 10, or about 5 and about 15. The at least one coil, stiffening element, or reinforcement element may be made from a variety of materials. For example, a shape memory metallic material such as nitinol or stainless steel can be used. Radiopaque materials such as platinum, platinum alloys (e.g., platinum-tungsten), gold, or palladium can be used. Composite materials like drawn filled tubing wires made of a number of materials (e.g., a radiopaque core such as platinum surrounded by a nitinol jacket) to aid in radiopacity can also be used. The at least one coil, stiffening element, or reinforcement element may further have a tertiary coil shape, such as a helical or other three-dimensional shape, wherein the tertiary coil is disposed about a filament of the mesh device. The tertiary shape, e.g., helical shape or 3D shape, increases the overall diameter of the proximal filament around which it is disposed. This increases the effective diameter of the wire in the proximal region of the device. This increase in diameter directly contributes to stiffness based on a stiffness relationship to the diameter of the wire to the fourth power. 
     The proximal portion that includes the at least one coil, stiffening element, or reinforcement element has a stiffness greater than a distal portion of the device that does not include any coils. In one example, the proximal portion of the device that includes the at least one coil may have a radial and/or axial stiffness that is between 1.5 to 3 times the distal portion of the device. 
     The device may also include a hydrogel incorporated into the proximal portion of the permeable shell. The at least one coil, stiffening element, or reinforcement element may be coated with the hydrogel or the hydrogel may be placed within an interior lumen defined by the wound nestings of the coil, stiffening element, or reinforcement element. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    is an elevation view of an embodiment of a device for treatment of a patient’s vasculature and a plurality of arrows indicating inward radial force. 
         FIG.  2    is an elevation view of a beam supported by two simple supports and a plurality of arrows indicating force against the beam. 
         FIG.  3    is a bottom perspective view of an embodiment of a device for treatment of a patient’s vasculature. 
         FIG.  4    is an elevation view of the device for treatment of a patient’s vasculature of  FIG.  3   . 
         FIG.  5    is a transverse cross sectional view of the device of  FIG.  4    taken along lines 5-5 in  FIG.  4   . 
         FIG.  6    shows the device of  FIG.  4    in longitudinal section taken along lines 6-6 in  FIG.  4   . 
         FIG.  7    is an enlarged view of the woven filament structure taken from the encircled portion 7 shown in  FIG.  5   . 
         FIG.  8    is an enlarged view of the woven filament structure taken from the encircled portion 8 shown in  FIG.  6   . 
         FIG.  9    is a proximal end view of the device of  FIG.  3   . 
         FIG.  10    is a transverse sectional view of a proximal hub portion of the device in  FIG.  6    indicated by lines 10-10 in  FIG.  6   . 
         FIG.  11    is an elevation view in partial section of a distal end of a delivery catheter with the device for treatment of a patient’s vasculature of  FIG.  3    disposed therein in a collapsed constrained state. 
         FIG.  12    illustrates an embodiment of a filament configuration for a device for treatment of a patient’s vasculature. 
         FIG.  13 A  illustrates a device for treatment of a patient’s vasculature that includes coils in a proximal area. 
         FIG.  13 B  illustrates a top profile of the occlusive device of  FIG.  13 A . 
         FIG.  14    illustrates a device for treatment of a patient’s vasculature that includes coils and hydrogel in a proximal area. 
         FIG.  15    illustrates a device according to  FIGS.  13 - 15    deployed within an aneurysm. 
         FIGS.  16 A- 16 C  illustrate various configurations of reinforcement elements integrated into a mesh of a device. 
         FIG.  16 D  illustrates an alternative embodiment including additional wires. 
         FIG.  17    is a schematic view of a patient being accessed by an introducer sheath, a microcatheter and a device for treatment of a patient’s vasculature releasably secured to a distal end of a delivery device or actuator. 
         FIG.  18    is a sectional view of a terminal aneurysm. 
         FIG.  19    is a sectional view of an aneurysm. 
         FIG.  20    is a schematic view in section of an aneurysm showing perpendicular arrows which indicate interior nominal longitudinal and transverse dimensions of the aneurysm. 
         FIG.  21    is a schematic view in section of the aneurysm of  FIG.  20    with a dashed outline of a device for treatment of a patient’s vasculature in a relaxed unconstrained state that extends transversely outside of the walls of the aneurysm. 
         FIG.  22    is a schematic view in section of an outline of a device represented by the dashed line in  FIG.  21    in a deployed and partially constrained state within the aneurysm. 
         FIGS.  23 - 26    show a deployment sequence of a device for treatment of a patient’s vasculature. 
         FIG.  27    is an elevation view in partial section of an embodiment of a device for treatment of a patient’s vasculature deployed within an aneurysm at a tilted angle. 
         FIG.  28    is an elevation view in partial section of an embodiment of a device for treatment of a patient’s vasculature deployed within an irregularly shaped aneurysm. 
         FIG.  29    shows an elevation view in section of a device for treatment of a patient’s vasculature deployed within a vascular defect aneurysm. 
     
    
    
     DETAILED DESCRIPTION 
     Discussed herein are devices and methods for the treatment of vascular defects that are suitable for minimally invasive deployment within a patient’s vasculature, and particularly, within the cerebral vasculature of a patient. For such embodiments to be safely and effectively delivered to a desired treatment site and effectively deployed, some device embodiments may be configured for collapse to a low profile constrained state with a transverse dimension suitable for delivery through an inner lumen of a microcatheter and deployment from a distal end thereof. Embodiments of these devices may also maintain a clinically effective configuration with sufficient mechanical integrity once deployed so as to withstand dynamic forces within a patient’s vasculature over time that may otherwise result in compaction of a deployed device. It may also be desirable for some device embodiments to acutely occlude a vascular defect of a patient during the course of a procedure in order to provide more immediate feedback regarding success of the treatment to a treating physician. 
     Intrasaccular occlusive devices that include a permeable shell formed from a woven or braided mesh have been described in US 2017/0095254, US 2016/0249934, US 2016/0367260, US 2016/0249937, and US 2018/0000489, all of which are hereby expressly incorporated by reference in their entirety for all purposes. 
     Some embodiments are particularly useful for the treatment of cerebral aneurysms by reconstructing a vascular wall so as to wholly or partially isolate a vascular defect from a patient’s blood flow. Some embodiments may be configured to be deployed within a vascular defect to facilitate reconstruction, bridging of a vessel wall or both in order to treat the vascular defect. For some of these embodiments, the permeable shell of the device may be configured to anchor or fix the permeable shell in a clinically beneficial position. For some embodiments, the device may be disposed in whole or in part within the vascular defect in order to anchor or fix the device with respect to the vascular structure or defect. The permeable shell may be configured to span an opening, neck or other portion of a vascular defect in order to isolate the vascular defect, or a portion thereof, from the patient’s nominal vascular system in order allow the defect to heal or to otherwise minimize the risk of the defect to the patient’s health. 
     For some or all of the embodiments of devices for treatment of a patient’s vasculature discussed herein, the permeable shell may be configured to allow some initial perfusion of blood through the permeable shell. The porosity of the permeable shell may be configured to sufficiently isolate the vascular defect so as to promote healing and isolation of the defect, but allow sufficient initial flow through the permeable shell so as to reduce or otherwise minimize the mechanical force exerted on the membrane the dynamic flow of blood or other fluids within the vasculature against the device. For some embodiments of devices for treatment of a patient’s vasculature, only a portion of the permeable shell that spans the opening or neck of the vascular defect, sometimes referred to as a defect spanning portion, need be permeable and/or conducive to thrombus formation in a patient’s bloodstream. For such embodiments, that portion of the device that does not span an opening or neck of the vascular defect may be substantially non-permeable or completely permeable with a pore or opening configuration that is too large to effectively promote thrombus formation. 
     In general, it may be desirable in some cases to use a hollow, thin walled device with a permeable shell of resilient material that may be constrained to a low profile for delivery within a patient. Such a device may also be configured to expand radially outward upon removal of the constraint such that the shell of the device assumes a larger volume and fills or otherwise occludes a vascular defect within which it is deployed. The outward radial expansion of the shell may serve to engage some or all of an inner surface of the vascular defect whereby mechanical friction between an outer surface of the permeable shell of the device and the inside surface of the vascular defect effectively anchors the device within the vascular defect. Some embodiments of such a device may also be partially or wholly mechanically captured within a cavity of a vascular defect, particularly where the defect has a narrow neck portion with a larger interior volume. In order to achieve a low profile and volume for delivery and be capable of a high ratio of expansion by volume, some device embodiments include a matrix of woven or braided filaments that are coupled together by the interwoven structure so as to form a self-expanding permeable shell having a pore or opening pattern between couplings or intersections of the filaments that is substantially regularly spaced and stable, while still allowing for conformity and volumetric constraint. 
     As used herein, the terms woven and braided are used interchangeably to mean any form of interlacing of filaments to form a mesh structure. In the textile and other industries, these terms may have different or more specific meanings depending on the product or application such as whether an article is made in a sheet or cylindrical form. For purposes of the present disclosure, these terms are used interchangeably. 
     For some embodiments, three factors may be critical for a woven or braided wire occlusion device for treatment of a patient’s vasculature that can achieve a desired clinical outcome in the endovascular treatment of cerebral aneurysms. We have found that for effective use in some applications, it may be desirable for the implant device to have sufficient radial stiffness for stability, limited pore size for near-complete acute (intra-procedural) occlusion and a collapsed profile which is small enough to allow insertion through an inner lumen of a microcatheter. A device with a radial stiffness below a certain threshold may be unstable and may be at higher risk of embolization in some cases. Larger pores between filament intersections in a braided or woven structure may not generate thrombus and occlude a vascular defect in an acute setting and thus may not give a treating physician or health professional such clinical feedback that the flow disruption will lead to a complete and lasting occlusion of the vascular defect being treated. Delivery of a device for treatment of a patient’s vasculature through a standard microcatheter may be highly desirable to allow access through the tortuous cerebral vasculature in the manner that a treating physician is accustomed. A detailed discussion of radial stiffness, pore size, and the necessary collapsed profile can be found in US 2017/0095254, which was previously expressly incorporated by reference in its entirety. 
     As has been discussed, some embodiments of devices for treatment of a patient’s vasculature call for sizing the device which approximates (or with some over-sizing) the vascular site dimensions to fill the vascular site. One might assume that scaling of a device to larger dimensions and using larger filaments would suffice for such larger embodiments of a device. However, for the treatment of brain aneurysms, the diameter or profile of the radially collapsed device is limited by the catheter sizes that can be effectively navigated within the small, tortuous vessels of the brain. Further, as a device is made larger with a given or fixed number of resilient filaments having a given size or thickness, the pores or openings between junctions of the filaments are correspondingly larger. In addition, for a given filament size the flexural modulus or stiffness of the filaments and thus the structure decrease with increasing device dimension. Flexural modulus may be defined as the ratio of stress to strain. Thus, a device may be considered to have a high flexural modulus or be stiff if the strain (deflection) is low under a given force. A stiff device may also be said to have low compliance. 
     To properly configure larger size devices for treatment of a patient’s vasculature, it may be useful to model the force on a device when the device is deployed into a vascular site or defect, such as a blood vessel or aneurysm, that has a diameter or transverse dimension that is smaller than a nominal diameter or transverse dimension of the device in a relaxed unconstrained state. As discussed, it may be advisable to “over-size” the device in some cases so that there is a residual force between an outside surface of the device and an inside surface of the vascular wall. The inward radial force on a device  10  that results from over-sizing is illustrated schematically in  FIG.  1    with the arrows  12  in the figure representing the inward radial force. As shown in  FIG.  2   , these compressive forces on the filaments  14  of the device in  FIG.  1    can be modeled as a simply supported beam  16  with a distributed load or force as show by the arrows  18  in the figure. It can be seen from the equation below for the deflection of a beam with two simple supports  20  and a distributed load that the deflection is a function of the length, L to the 4 th  power: 
     
       
         
           
             
               
                 Deflection of Beam = 5FL 
               
               4 
             
             / 
             384 
               
             El 
           
         
       
     
     
       
         
           
             where F=force, 
           
         
       
     
     
       
         
           
             L=length of beam, 
           
         
       
     
     
       
         
           
             E=Young’s Modulus, and 
           
         
       
     
     
       
         
           
             l=moment of inertia 
             . 
           
         
       
     
     Thus, as the size of the device increases and L increases, the compliance increases substantially. Accordingly, an outward radial force exerted by an outside surface of the filaments  14  of the device  10  against a constraining force when inserted into a vascular site such as blood vessel or aneurysm is lower for a given amount of device compression or over-sizing. This force may be important in some applications to assure device stability and to reduce the risk of migration of the device and potential distal embolization. 
     In some embodiments, a combination of small and large filament sizes may be utilized to make a device with a desired radial compliance and yet have a collapsed profile which is configured to fit through an inner lumen of commonly used microcatheters. A device fabricated with even a small number of relatively large filaments  14  can provide reduced radial compliance (or increased stiffness) compared to a device made with all small filaments. Even a relatively small number of larger filaments may provide a substantial increase in bending stiffness due to change in the moment of Inertia that results from an increase in diameter without increasing the total cross sectional area of the filaments. The moment of inertia (I) of a round wire or filament may be defined by the equation: 
     
       
         
           
             I =  
             π 
             
               d 
               4 
             
             / 
             64 
           
         
       
     
      where d is the diameter of the wire or filament. 
     Since the moment of inertia is a function of filament diameter to the fourth power, a small change in the diameter greatly increases the moment of inertia. Thus, small changes in filament size can have substantial impact on the deflection at a given load and thus the compliance of the device. 
     Thus, the stiffness can be increased by a significant amount without a large increase in the cross sectional area of a collapsed profile of the device  10 . This may be particularly important as device embodiments are made larger to treat large aneurysms. While large cerebral aneurysms may be relatively rare, they present an important therapeutic challenge as some embolic devices currently available to physicians have relatively poor results compared to smaller aneurysms. 
     As such, some embodiments of devices for treatment of a patient’s vasculature may be formed using a combination of filaments  14  with a number of different diameters such as 2, 3, 4, 5 or more different diameters or transverse dimensions. In device embodiments where filaments with two different diameters are used, some larger filament embodiments may have a transverse dimension of about 0.001 inches to about 0.004 inches and some small filament embodiments may have a transverse dimension or diameter of about 0.0004 inches and about 0.0015 inches, more specifically, about 0.0004 inches to about 0.001 inches. The ratio of the number of large filaments to the number of small filaments may be between about 2 and 12 and may also be between about 4 and 8. In some embodiments, the difference in diameter or transverse dimension between the larger and smaller filaments may be less than about 0.004 inches, more specifically, less than about 0.0035 inches, and even more specifically, less than about 0.002 inches. 
     As discussed above, device embodiments  10  for treatment of a patient’s vasculature may include a plurality of wires, fibers, threads, tubes or other filamentary elements that form a structure that serves as a permeable shell. For some embodiments, a globular shape may be formed from such filaments by connecting or securing the ends of a tubular braided structure. For such embodiments, the density of a braided or woven structure may inherently increase at or near the ends where the wires or filaments  14  are brought together and decrease at or near a middle portion  30  disposed between a proximal end  32  and distal end  34  of the permeable shell  40 . For some embodiments, an end or any other suitable portion of a permeable shell  40  may be positioned in an opening or neck of a vascular defect such as an aneurysm for treatment. As such, a braided or woven filamentary device with a permeable shell may not require the addition of a separate defect spanning structure having properties different from that of a nominal portion of the permeable shell to achieve hemostasis and occlusion of the vascular defect. Such a filamentary device may be fabricated by braiding, weaving or other suitable filament fabrication techniques. Such device embodiments may be shape set into a variety of three-dimensional shapes such as discussed herein. 
     Referring to  FIGS.  3 - 10   , an embodiment of a device for treatment of a patient’s vasculature  10  is shown. The device  10  includes a self-expanding resilient permeable shell  40  having a proximal end  32 , a distal end  34 , a longitudinal axis  46  and further comprising a plurality of elongate resilient filaments  14  including large filaments  48  and small filaments  50  of at least two different transverse dimensions as shown in more detail in  FIGS.  5 ,  7 , and  18   . The filaments  14  have a woven structure and are secured relative to each other at proximal ends  60  and distal ends  62  thereof. The permeable shell  40  of the device has a radially constrained elongated state configured for delivery within a microcatheter  61 , as shown in  FIG.  11   , with the thin woven filaments  14  extending longitudinally from the proximal end  42  to the distal end  44  radially adjacent each other along a length of the filaments. 
     As shown in  FIGS.  3 - 6   , the permeable shell  40  also has an expanded relaxed state with a globular and longitudinally shortened configuration relative to the radially constrained state. In the expanded state, the woven filaments  14  form the self-expanding resilient permeable shell  40  in a smooth path radially expanded from a longitudinal axis  46  of the device between the proximal end  32  and distal end  34 . The woven structure of the filaments  14  includes a plurality of openings  64  in the permeable shell  40  formed between the woven filaments. For some embodiments, the largest of said openings  64  may be configured to allow blood flow through the openings only at a velocity below a thrombotic threshold velocity. Thrombotic threshold velocity has been defined, at least by some, as the time-average velocity at which more than 50% of a vascular graft surface is covered by thrombus when deployed within a patient’s vasculature. In the context of aneurysm occlusion, a slightly different threshold may be appropriate. Accordingly, the thrombotic threshold velocity as used herein shall include the velocity at which clotting occurs within or on a device, such as device  10 , deployed within a patient’s vasculature such that blood flow into a vascular defect treated by the device is substantially blocked in less than about 1 hour or otherwise during the treatment procedure. The blockage of blood flow into the vascular defect may be indicated in some cases by minimal contrast agent entering the vascular defect after a sufficient amount of contrast agent has been injected into the patient’s vasculature upstream of the implant site and visualized as it dissipates from that site. Such sustained blockage of flow within less than about 1 hour or during the duration of the implantation procedure may also be referred to as acute occlusion of the vascular defect. 
     As such, once the device  10  is deployed, any blood flowing through the permeable shell may be slowed to a velocity below the thrombotic threshold velocity and thrombus will begin to form on and around the openings in the permeable shell  40 . Ultimately, this process may be configured to produce acute occlusion of the vascular defect within which the device  10  is deployed. For some embodiments, at least the distal end of the permeable shell  40  may have a reverse bend in an everted configuration such that the secured distal ends  62  of the filaments  14  are withdrawn axially within the nominal permeable shell structure or contour in the expanded state. For some embodiments, the proximal end of the permeable shell further includes a reverse bend in an everted configuration such that the secured proximal ends  60  of the filaments  14  are withdrawn axially within the nominal permeable shell structure  40  in the expanded state. As used herein, the term everted may include a structure that is everted, partially everted and/or recessed with a reverse bend as shown in the device embodiment of  FIGS.  3 - 6   . For such embodiments, the ends  60  and  62  of the filaments  14  of the permeable shell or hub structure disposed around the ends may be withdrawn within or below the globular shaped periphery of the permeable shell of the device. 
     The elongate resilient filaments  14  of the permeable shell  40  may be secured relative to each other at proximal ends  60  and distal ends  62  thereof by one or more methods including welding, soldering, adhesive bonding, epoxy bonding or the like. In addition to the ends of the filaments being secured together, a distal hub  66  may also be secured to the distal ends  62  of the thin filaments  14  of the permeable shell  40  and a proximal hub  68  secured to the proximal ends  60  of the thin filaments  14  of the permeable shell  40 . The proximal hub  68  may include a cylindrical member that extends proximally beyond the proximal ends  60  of the thin filaments so as to form a cavity  70  within a proximal portion of the proximal hub  68 . The proximal cavity  70  may be used for holding adhesives such as epoxy, solder or any other suitable bonding agent for securing an elongate detachment tether  72  that may in turn be detachably secured to a delivery apparatus such as is shown in  FIG.  11   . 
     For some embodiments, the elongate resilient filaments  14  of the permeable shell  40  may have a transverse cross section that is substantially round in shape and be made from a superelastic material that may also be a shape memory metal. The shape memory metal of the filaments of the permeable shell  40  may be heat set in the globular configuration of the relaxed expanded state as shown in  FIGS.  3 - 6   . Suitable superelastic shape memory metals may include alloys such as NiTi alloy and the like. The superelastic properties of such alloys may be useful in providing the resilient properties to the elongate filaments  14  so that they can be heat set in the globular form shown, fully constrained for delivery within an inner lumen of a microcatheter and then released to self expand back to substantially the original heat set shape of the globular configuration upon deployment within a patient’s body. 
     The device  10  may have an everted filamentary structure with a permeable shell  40  having a proximal end  32  and a distal end  34  in an expanded relaxed state. The permeable shell  40  has a substantially enclosed configuration for the embodiments shown. Some or all of the permeable shell  40  of the device  10  may be configured to substantially block or impede fluid flow or pressure into a vascular defect or otherwise isolate the vascular defect over some period of time after the device is deployed in an expanded state. The permeable shell  40  and device  10   generally also has a low profile, radially constrained state, as shown in  FIG.  11   , with an elongated tubular or cylindrical configuration that includes the proximal end  32 , the distal end  34  and a longitudinal axis  46 . While in the radially constrained state, the elongate flexible filaments  14  of the permeable shell  40  may be disposed substantially parallel and in close lateral proximity to each other between the proximal end and distal end forming a substantially tubular or compressed cylindrical configuration. 
     Proximal ends  60  of at least some of the filaments  14  of the permeable shell  40  may be secured to the proximal hub  68  and distal ends  62  of at least some of the filaments  14  of the permeable shell  40  are secured to the distal hub  66 , with the proximal hub  68  and distal hub  66  being disposed substantially concentric to the longitudinal axis  46  as shown in  FIG.  4   . The ends of the filaments  14  may be secured to the respective hubs  66  and  68  by any of the methods discussed above with respect to securement of the filament ends to each other, including the use of adhesives, solder, welding and the like. A middle portion  30  of the permeable shell  40  may have a first transverse dimension with a low profile suitable for delivery from a microcatheter as shown in  FIG.  11   . Radial constraint on the device  10  may be applied by an inside surface of the inner lumen of a microcatheter, such as the distal end portion of the microcatheter  61  shown, or it may be applied by any other suitable mechanism that may be released in a controllable manner upon ejection of the device  10  from the distal end of the catheter. In  FIG.  11    a proximal end or hub  68  of the device  10  is secured to a distal end of an elongate delivery apparatus  111  of a delivery system  112  disposed at the proximal hub  68  of the device  10 . Additional details of delivery devices can be found in, e.g., US 2016/0367260, which was previously incorporated by reference in its entirety. 
     Some device embodiments  10  having a braided or woven filamentary structure may be formed using about 10 filaments to about 300 filaments  14 , more specifically, about 10 filaments to about 100 filaments  14 , and even more specifically, about 60 filaments to about 80 filaments  14 . Some embodiments of a permeable shell  40  may include about 70 filaments to about 300 filaments extending from the proximal end  32  to the distal end  34 , more specifically, about 100 filaments to about 200 filaments extending from the proximal end  32  to the distal end  34 . For some embodiments, the filaments  14  may have a transverse dimension or diameter of about 0.0008 inches to about 0.004 inches. The elongate resilient filaments  14  in some cases may have an outer transverse dimension or diameter of about 0.0005 inch to about 0.005 inch, more specifically, about 0.001 inch to about 0.003 inch, and in some cases about 0.0004 inches to about 0.002 inches. For some device embodiments  10  that include filaments  14  of different sizes, the large filaments  48  of the permeable shell  40  may have a transverse dimension or diameter that is about 0.001 inches to about 0.004 inches and the small filaments  50  may have a transverse dimension or diameter of about 0.0004 inches to about 0.0015 inches, more specifically, about 0.0004 inches to about 0.001 inches. In addition, a difference in transverse dimension or diameter between the small filaments  50  and the large filaments  48  may be less than about 0.004 inches, more specifically, less than about 0.0035 inches, and even more specifically, less than about 0.002 inches. For embodiments of permeable shells  40  that include filaments  14  of different sizes, the number of small filaments  50  of the permeable shell  40  relative to the number of large filaments  48  of the permeable shell  40  may be about 2 to 1 to about 15 to 1, more specifically, about 2 to 1 to about 12 to 1, and even more specifically, about 4 to 1 to about 8 to 1. 
     The expanded relaxed state of the permeable shell  40 , as shown in  FIG.  4   , has an axially shortened configuration relative to the constrained state such that the proximal hub  68  is disposed closer to the distal hub  66  than in the constrained state. Both hubs  66  and  68  are disposed substantially concentric to the longitudinal axis  46  of the device and each filamentary element  14  forms a smooth arc between the proximal and distal hubs  66  and  68  with a reverse bend at each end. A longitudinal spacing between the proximal and distal hubs  66  and  68  of the permeable shell  40  in a deployed relaxed state may be about 25 percent to about 75 percent of the longitudinal spacing between the proximal and distal hubs  66  and  68  in the constrained cylindrical state, for some embodiments. The arc of the filaments  14  between the proximal and distal ends  32  and  34  may be configured such that a middle portion of each filament  14  has a second transverse dimension substantially greater than the first transverse dimension. 
     For some embodiments, the permeable shell  40  may have a first transverse dimension in a collapsed radially constrained state of about 0.2 mm to about 2 mm and a second transverse dimension in a relaxed expanded state of about 4 mm to about 30 mm. For some embodiments, the second transverse dimension of the permeable shell  40  in an expanded state may be about 2 times to about 150 times the first transverse dimension, more specifically, about 10 times to about 25 times the first or constrained transverse dimension. A longitudinal spacing between the proximal end  32  and distal end  34  of the permeable shell  40  in the relaxed expanded state may be about 25% percent to about 75% percent of the spacing between the proximal end  32  and distal end  34  in the constrained cylindrical state. For some embodiments, a major transverse dimension of the permeable shell  40  in a relaxed expanded state may be about 4 mm to about 30 mm, more specifically, about 9 mm to about 15 mm, and even more specifically, about 4 mm to about 8 mm. 
     An arced portion of the filaments  14  of the permeable shell  40  may have a sinusoidal-like shape with a first or outer radius  88  and a second or inner radius  90  near the ends of the permeable shell  40  as shown in  FIG.  6   . This sinusoid-like or multiple curve shape may provide a concavity in the proximal end  32  that may reduce an obstruction of flow in a parent vessel adjacent a vascular defect. For some embodiments, the first radius  88  and second radius  90  of the permeable shell  40  may be between about 0.12 mm to about 3 mm. For some embodiments, the distance between the proximal end  32  and distal end  34  may be less than about 60% of the overall length of the permeable shell  40  for some embodiments. Such a configuration may allow for the distal end  34  to flex downward toward the proximal end  32  when the device  10  meets resistance at the distal end  34  and thus may provide longitudinal conformance. The filaments  14  may be shaped in some embodiments such that there are no portions that are without curvature over a distance of more than about 2 mm. Thus, for some embodiments, each filament  14  may have a substantially continuous curvature. This substantially continuous curvature may provide smooth deployment and may reduce the risk of vessel perforation. For some embodiments, one of the ends  32  or  34  may be retracted or everted to a greater extent than the other so as to be more longitudinally or axially conformal than the other end. 
     The first radius  88  and second radius  90  of the permeable shell  40  may be between about 0.12 mm to about 3 mm for some embodiments. For some embodiments, the distance between the proximal end  32  and distal end  34  may be more than about 60% of the overall length of the expanded permeable shell  40 . Thus, the largest longitudinal distance between the inner surfaces may be about 60% to about 90% of the longitudinal length of the outer surfaces or the overall length of device  10 . A gap between the hubs  66  and  68  at the proximal end  32  and distal end  34  may allow for the distal hub  66  to flex downward toward the proximal hub  68  when the device  10  meets resistance at the distal end and thus provides longitudinal conformance. The filaments  14  may be shaped such that there are no portions that are without curvature over a distance of more than about 2 mm. Thus, for some embodiments, each filament  14  may have a substantially continuous curvature. This substantially continuous curvature may provide smooth deployment and may reduce the risk of vessel perforation. The distal end  34  may be retracted or everted to a greater extent than the proximal end  32  such that the distal end portion of the permeable shell  40  may be more radially conformal than the proximal end portion. Conformability of a distal end portion may provide better device conformance to irregular shaped aneurysms or other vascular defects. A convex surface of the device may flex inward forming a concave surface to conform to curvature of a vascular site. 
       FIG.  10    shows an enlarged view of the filaments  14  disposed within a proximal hub  68  of the device  10  with the filaments  14  of two different sizes constrained and tightly packed by an outer ring of the proximal hub  68 . The tether member  72  may optionally be disposed within a middle portion of the filaments  14  or within the cavity  70  of the proximal hub  68  proximal of the proximal ends  60  of the filaments  14  as shown in  FIG.  6   . The distal end of the tether  72  may be secured with a knot  92  formed in the distal end thereof which is mechanically captured in the cavity  70  of the proximal hub  68  formed by a proximal shoulder portion  94  of the proximal hub  68 . The knotted distal end  92  of the tether  72  may also be secured by bonding or potting of the distal end of the tether  72  within the cavity  70  and optionally amongst the proximal ends  60  of the filaments  14  with mechanical compression, adhesive bonding, welding, soldering, brazing or the like. The tether embodiment  72  shown in  FIG.  6    has a knotted distal end  92  potted in the cavity of the proximal hub  68  with an adhesive. Such a tether  72  may be a dissolvable, severable or releasable tether that may be part of a delivery apparatus  111  used to deploy the device  10  as shown in  FIG.  11    and  FIGS.  23 - 26   .  FIG.  10    also shows the large filaments  48  and small filaments  50  disposed within and constrained by the proximal hub  68  which may be configured to secure the large and small filaments  48  and  50  in place relative to each other within the outer ring of the proximal hub  68 . 
       FIGS.  7  and  8    illustrate some configuration embodiments of braided filaments  14  of a permeable shell  40  of the device  10  for treatment of a patient’s vasculature. The braid structure in each embodiment is shown with a circular shape  100  disposed within a pore  64  of a woven or braided structure with the circular shape  100  making contact with each adjacent filament segment. The pore opening size may be determined at least in part by the size of the filament elements  14  of the braid, the angle overlapping filaments make relative to each other and the picks per inch of the braid structure. For some embodiments, the cells or openings  64  may have an elongated substantially diamond shape as shown in  FIG.  7   , and the pores or openings  64  of the permeable shell  40  may have a substantially more square shape toward a middle portion  30  of the device  10 , as shown in  FIG.  8   . The diamond shaped pores or openings  64  may have a length substantially greater than the width particularly near the hubs  66  and  68 . In some embodiments, the ratio of diamond shaped pore or opening length to width may exceed a ratio of 3 to 1 for some cells. The diamond-shaped openings  64  may have lengths greater than the width thus having an aspect ratio, defined as Length/Width of greater than 1. The openings  64  near the hubs  66  and  68  may have substantially larger aspect ratios than those farther from the hubs as shown in  FIG.  7   . The aspect ratio of openings  64  adjacent the hubs may be greater than about 4 to 1. The aspect ratio of openings  64  near the largest diameter may be between about 0.75 to 1 and about 2 to 1 for some embodiments. For some embodiments, the aspect ratio of the openings  64  in the permeable shell  40  may be about 0.5 to 1 to about 2 to 1. 
     The pore size defined by the largest circular shapes  100  that may be disposed within openings  64  of the braided structure of the permeable shell  40  without displacing or distorting the filaments  14  surrounding the opening  64  may range in size from about 0.005 inches to about 0.01 inches, more specifically, about 0.006 inches to about 0.009 inches, even more specifically, about 0.007 inches to about 0.008 inches for some embodiments. In addition, at least some of the openings  64  formed between adjacent filaments  14  of the permeable shell  40  of the device  10  may be configured to allow blood flow through the openings  64  only at a velocity below a thrombotic threshold velocity. For some embodiments, the largest openings  64  in the permeable shell structure  40  may be configured to allow blood flow through the openings  64  only at a velocity below a thrombotic threshold velocity. As discussed above, the pore size may be less than about 0.016 inches, more specifically, less than about 0.012 inches for some embodiments. For some embodiments, the openings  64  formed between adjacent filaments  14  may be about 0.005 inches to about 0.04 inches. 
       FIG.  12    illustrates in transverse cross section an embodiment of a proximal hub  68  showing the configuration of filaments which may be tightly packed and radially constrained by an inside surface of the proximal hub  68 . In some embodiments, the braided or woven structure of the permeable shell  40  formed from such filaments  14  may be constructed using a large number of small filaments. The number of filaments14 may be greater than 125 and may also be between about 80 filaments and about 180 filaments. As discussed above, the total number of filaments  14  for some embodiments may be about 70 filaments to about 300 filaments, more specifically, about 100 filaments to about 200 filaments. In some embodiments, the braided structure of the permeable shell  40  may be constructed with two or more sizes of filaments  14 . For example, the structure may have several larger filaments that provide structural support and several smaller filaments that provide the desired pore size and density and thus flow resistance to achieve a thrombotic threshold velocity in some cases. For some embodiments, small filaments  50  of the permeable shell  40  may have a transverse dimension or diameter of about 0.0006 inches to about 0.002 inches for some embodiments and about 0.0004 inches to about 0.001 inches in other embodiments. The large filaments  48  may have a transverse dimension or diameter of about 0.0015 inches to about 0.004 inches in some embodiments and about 0.001 inches to about 0.004 inches in other embodiments. The filaments  14  may be braided in a plain weave that is one under, one over structure (shown in  FIGS.  7  and  8   ) or a supplementary weave; more than one warp interlace with one or more than one weft. The pick count may be varied between about 25 and 200 picks per inch (PPI). 
     In order to properly treat aneurysms, proper positioning of an intrasaccular device is important, especially in regard to placement over the neck of the aneurysm. The neck region is where blood flows into the aneurysm and therefore proper seating with respect to the neck is important. Furthermore, proximal stability of the intrasaccular device is important to prevent the device from compacting or otherwise dislodging into the aneurysm. The following embodiments address these issues by utilizing proximal stiffening or reinforcing elements (e.g., coils or springs) to enhance proximal stiffness of the device. 
       FIGS.  13 A and  13 B  illustrate an embodiment of a device  110  comprising a permeable shell  140  for treatment of a vascular defect, such as an aneurysm  160 . The device also includes stiffening or reinforcement elements  122  incorporated into a proximal section  133  of the permeable shell  140 . In some embodiments, these stiffening or reinforcement elements  122  are helical coils that are wound around a portion of the filaments of the device  110 . 
     As seen in  FIG.  15   , the proximal section  133  is intended to sit at or in close proximity to the neck of the aneurysm  160  while the remaining portion of the permeable shell  140  fills the space distal to the neck of the aneurysm  160 . As mentioned previously, it is desirable to increase stiffness at the proximal region  133  of the device  110  to promote proper positioning of the device  110  within the aneurysm. As seen in  FIGS.  13 A and  13 B , the inclusion of coiled wire reinforcement elements  122  in the proximal part of the device is one way to increase stiffness in the proximal section  133 . As described in other embodiments, the occlusive device itself is formed from one or more braided wires that are joined or gathered at proximal and distal ends of the device  110  with hubs or marker bands  66 ,  68 . The coiled wire reinforcing elements  122  can be wound around various sections of the constituent braided wires or filaments  114  of the occlusive device - in other words, the coiled wire elements are directly wound over the filaments  114  of the device itself. 
     The stiffening or reinforcement elements  122  may be made of a variety of materials - for instance, shape memory metallic material such as nitinol or stainless steel. Alternatively, radiopaque material such as platinum, platinum alloy (e.g., platinum-tungsten), palladium, gold, or tantalum can be used - one advantage to a radiopaque material is increased visibility of a proximal region of the device so the physician can better visualize how the proximal end is seated with respect to the neck of the aneurysm. Composite materials such as DFT (drawn-filled tubing) wires can also be used. These DFT materials can incorporate a radiopaque (e.g., tantalum or platinum) core surrounded by a shape memory (e.g., nitinol) jacket - to provide heightened visualization along with shape memory properties. 
     As these reinforcement elements  122  (e.g., coils or springs) serve to enhance proximal stiffness of device  110 , the coiled elements  122  can have their own stiffness values and force values (as a function of stiffness). A coiled element has material properties like a spring, and the “k” value of a spring represents its stiffness. This k value is represented by the following equation: k = Gd 4 /(8nD 3 ), where the variables include G (modulus of rigidity of the material), d (wire diameter of the wire forming the coil or spring), n (number of coils), and D (diameter of the overall coil). Generally, for two similarly designed materials, any change in diameter will have around a 4 th  power exponential difference in associated stiffness. Therefore, for example, the material comprising the coiled elements, wire diameter of the coiled elements, and overall coiled diameter can be customized to promote a desired diameter profile. In some examples, the coiled elements  122  may have a diameter of between 1-3 times the diameter of the wire braid and an associated stiffness of about 1 - 81, 1.2 - 50, 1.25 - 25, or 1.5 - 6 times the rest of the device  110 . 
     In some embodiments, these reinforcement elements  122  are helically configured as a consistent coil (resembling a plurality of nested windings forming a consistent 2-dimensional coiled shape). In some embodiments, these coiled  122  elements are separately wound into a shape-memory heat-set complex, three-dimensional shape. Such three-dimensional shaped coils are described in U.S. Pat. Nos. 6,605,101; 8,066,036; and 9,533,344, all of which are herein incorporated by reference in their entirety for all purposes. 
     The proximal section  133  of the permeable shell  140  may have a length that is about ⅓, alternatively about ¼, of the length of the permeable shell  140  in its expanded state. The proximal section  133  of the permeable shell  140  may comprise the portion beginning at the proximal end  132  and extending to about 20% or less, alternatively about 25% or less, alternatively about 30% or less, alternatively about 33% or less, alternatively about 40% or less of the total length of the expanded state of the device  110 . The proximal section  133  of the permeable shell  140  may comprise the portion beginning at the proximal end  132  and extending to between about 10% to about 40%, alternatively between about 10% and about 30%, alternatively between about 15% and about 40%, alternatively between about 20% and about 40% of the total length of the expanded state of the device  110 . The coiled elements may be incorporated into at least about 20%, alternatively at least about 30%, alternatively at least about 40%, alternatively at least about 50%, alternatively at least about 60%, alternatively at least about 70%, alternatively at least about 80%, alternatively at least about 90%, alternatively at least about 100% of the proximal section. The coiled elements  122  may be incorporated into between about 20% and about 90%, alternatively between about 30% and 80%, alternatively between about 40% and 70%, alternatively between about 50% and 80%, alternatively between about 30% and 90% of the proximal section. 
     The proximal section  133  (which utilizes the stiffening or reinforcement elements  122 ) may contain at least about one coil, alternatively at least about 2 coils, alternatively at least about 3 coils, alternatively at least about 4 coils, alternatively at least about 5 coils, alternatively at least about 6 coils, alternatively at least about 7 coils, alternatively at least about 8 coils, alternatively at least about 9 coils, alternatively at least about 10 coils. The proximal section may contain between about 2 and about 10, alternatively between about 3 and about 12, alternatively between about 4 and about 8, alternatively between about 5 and about 10, and alternatively between about 5 and about 15 coils. 
       FIG.  13 B  shows a top view profile of the occlusive device including the coiled reinforcement elements  122 . The coiled elements can be added to the braid in a variety of patterns. For instance, the coiled elements  122  can be incorporated into the entire proximal section  133  of the braid. The coiled elements are like miniature springs that are assembled over the wire braid before the hubs or marker bands (see elements  66 ,  68  of  FIG.  6   ) are attached. The coiled reinforcement elements  122  can be placed over the constituent wires comprising the braid, for instance, directly over one or more wire sections of the braid.  FIGS.  16 A- 16 C  show various configurations for how a coiled reinforcement element  122  can be integrated into a braid or mesh of the occlusive device. In  FIG.  16 A , the coiled reinforcement element  122  sits over, disposed about, adjacent to, or otherwise associated with at least a portion of one of the constituent filaments or wires  114  (in a 1:1 relationship) comprising the device  110  mesh. In this configuration, different constituent wires of the mesh could utilize their own distinct coiled reinforcement element  122 .  FIG.  16 B  shows an alternative configuration, whereby each coiled reinforcement elements  122  sits over, disposed about, adjacent to, or otherwise associated with a plurality of constituent wire or filament  114  elements forming the braid. In  FIG.  16 C , each coiled reinforcement element  122  sits over, disposed about, adjacent to, or otherwise associated with two or more filament  114  elements forming the braid, however they are placed in between various filament intersection points and are therefore spaced out to more of a degree. 
     The reinforcement elements  122  can be secured to the wire braid of the device  110  in a number of ways. For instance, before the hubs or marker bands  66 ,  68  (e.g., shown in  FIG.  6   ) are assembled on both side of the device (prior to all the ends of the device being secured, meaning the ends of the device  110  are open so that the reinforcement elements  122  can be placed over the wire or filaments of the device  110 ), the coiled elements are placed over one or more constituent filaments of the device  110  mesh or braid (e.g., see  FIGS.  16 A- 16 C ). In one embodiment, these coiled reinforcement elements  122  are freely floating and are not directly affixed to the wires of the device braid. In one embodiment, the coiled elements  122  can be freely floating at one end and fastened at one end or alternatively can be fastened at both ends by epoxy or UV glue, or in some instances, can be laser welded to the original braid wire. 
     The coiled reinforcement elements  122  can be added to all the of the constituent wires of the proximal part of the device braid  110 , only some of the constituent wires, or in a piece-meal manner along some of the proximal part of the device  110 , etc. The placement of the coiled reinforcement elements  122  will affect the stiffness of the device and can be customized based on the size of the occlusive device, the neck region of the treatment site (e.g., aneurysm), overall treatment site dimensions, and the region of the body being treated. 
     Alternative ways to enhance stiffness at the proximal end of the device can also be used. For example, the number of wires and size of the wires in the proximal section of the device can vary compared to the rest of the device to increase the stiffness along this region - i.e., the proximal region can utilize larger wires compared to the rest of the device or a different amount of wires in its constituent braid, which may negate the need to add in a separate reinforcement element  122  to augment stiffness. Furthermore, the use of stiffer, radiopaque material (such as tantalum or drawn-filled tubing (DFT)) can also be used as part of the braid in the proximal section of the device to augment stiffness as well as visualization. In some embodiments, an additional wire can be wound alongside or near the constituent wire/filament of the proximal part of the device  110  braid to selectively stiffen this region. For instance, additional wires or an additional braid can be interwound within the proximal device braid to augment stiffness in this region.  FIG.  16 D  shows an arrangement meant to represent a proximal portion of the device  110 . The thinner wires  114  represent the device braid, and the thicker wires  114  represent one or more separate wires that are placed near the constituent wires or filaments of the braid to selectively stiffen the region. These reinforcement wires can be thicker, thinner, or the same size as the rest of the wire braid, and can be selectively connected to portions of the wire braid to augment stiffness or alternatively are not connected and are just part of the broader braid defining the proximal end of the device  110 . In the context of  FIG.  16 D , the additional wires  214  effectively decrease the porosity or pore space of the illustrated cross section and increase the associated braid density to the additional wires, thereby providing increased resistance to blood flow while also augmenting stiffness due to the additional material. 
     The permeable shell  140  is primarily made of filaments comprising a strong shape memory metallic material, such as nitinol. The permeable shell  140  may be made of wires having a smaller diameter, as compared to devices without coiled elements  122 . The permeable shell may include between about 36 and 72 filaments, alternatively between about 72 and 108 filaments, alternatively between about 108 and 144 filaments. The filaments may have a diameter between about 0.001” and 0.004”, alternatively between about 0.004” and 0.0015”, alternatively between about 0.0004” and 0.001”. The permeable shell  140  may also have filaments with different diameters. The permeable shell may be made of filaments having two different diameters, alternatively three different diameters, alternatively four different diameters, alternatively five different diameters. The permeable shell may also have filaments made with different materials. For instance, the permeable shell may contain filaments made from nitinol and also contain composite (DFT) filaments. 
     As discussed above, the permeable shell and the proximal section of the intrasaccular device  110  have different axial stiffness as the proximal section is configured to be stiffer (via the various embodiments described). By way of example, the proximal section of the intrasaccular device  110  is between 1.0 times to 3 times higher in terms of radial and/or axial stiffness. 
     The proximal portion  133  of the device  110  is stiffer due to the reinforcement elements  122  (and has more occlusive effect, as discussed above), than the distal section  135  of the device  110  (which lacks these reinforcement elements  122 ) - as shown in  FIG.  13 A . The distal section  135  may be soft and deformable. As such, the distal portion  135  retains more flexibility thereby more readily adopting the shape of the target region (e.g., aneurysm 160). The soft distal end  134  and distal region  135  will allow the device  110  to conform to the different shapes of the aneurysm and substantially fill the annular sac (interior cavity of the aneurysm). In some embodiments, the soft distal end  134  and distal region  135  will also allow a smaller number and variety of implant devices  110  with different heights to be manufactured because one device  110   will be able to be used for one aneurysm diameter size but a range of aneurysm heights - thereby lowering manufacturing costs. For instance, a device  110  with an expanded height of 8 mm could fit an aneurysm with a height of between about4 and about 8 mm. The distal portion of the permeable shell may have a smaller or lower radial stiffness that is, for instance, about ⅓ to about ½ the stiffness of the proximal portion of the intrasaccular device  110 . 
     Moreover, as a result of the increased stiffness in the proximal region  133 , there is also a greater anchoring force along the proximal region  133 , which helps to seal the neck region and anchor the occlusive device  110  in place. This mitigates the risk of the occlusion device migrating away from the neck of the treatment location and relocating into the aneurysm sac. The improved anchoring at the neck of the aneurysm allows for universal sizing because other parts of the intrasaccular device  110  can be as soft as possible to fill in the volumetric space of the aneurysm sac. An intrasaccular device  110  with a soft distal end also has the additional benefit of improved safety during deployment. 
     In an alternative embodiment, as shown in  FIG.  14   , a hydrogel can be included in the coils  124  to further augment the occlusion along the proximal section of the device. Hydrogels are sometimes used in other embolic devices (e.g., embolic coils used to occlude a target structure) and are configured to expand upon reaction with blood (typically reacting to pH or the aqueous component of blood), to thereby enhance the occlusion or space-filling effect of a device. The coiled elements along the proximal end of the device can include a hydrogel component, which expands when placed on the treatment site thereby enhancing the occlusive effect of the proximal section of the device. For instance, hydrogel can be coated around the wound wire comprising the coil - meaning the hydrogel radially extends from the wire’s surface upon expansion. Alternatively, one or more sections of the wound configuration forming the nested loops of the coil can utilize hydrogel (i.e., the hydrogel is placed within the coil’s lumen) - this configuration is described in more detail in U.S. Pat. No. 8,377,091, which is hereby incorporated by reference in its entirety. Alternative hydrogel configurations can utilize the hydrogel being placed selectively along the proximal braid structure comprising the occlusion device - for instance, being coated or affixed over particular wire components of the braid or attached to the proximal section of the braid. The hydrogel filaments in one embodiment can be inserted in the miniature springs that are assembled over the proximal region of the intrasaccular device  110 . Alternatively, the hydrogel can be shape set to the reinforcement elements (e.g., springs or coils) and wrapped around the wires located at the proximal end of the device. 
     The use of the coiled elements  122 ,  124 , along with increasing the stiffness of the proximal section, will also augment occlusion along the proximal section because the coiled elements will increase the overall wire thickness along the proximal section. In other words, the greater wire coverage will create a more occlusive barrier to blood flow, thereby also augmenting occlusion along the proximal portion of the device. Similarly, with respect to coiled elements  124 , hydrogel is a biologically compatible material that promotes reendothelialization and will augment the endothelial growth over the neck of the aneurysm, which will eventually close off the aneurysm. Moreover, the expansile state of hydrogel will provide increased resistance to blood flow at the proximal section of the device  110 . 
     The use of the reinforcement elements  122 ,  124 , whether configured as a coil, spring, additional braided wire, or otherwise, effectively increases the stiffness and braid density of the proximal region of the device  110 . These elements also serve to decrease the porosity or “open-space” formed between the wire crossing points of the proximal portion of the device because the additional reinforcement elements  122 ,  124  occupy more space along the device  110 . 
     Some intrasaccular device embodiments may include proximal and distal recesses (e.g., see  FIG.  6   , which utilizes proximal and distal concave sections or recesses at the ends of the braid). The proximal recess would be configured to largely abut the neck of the aneurysm, where the wires comprising the edge of this dimpled, recessed, or concave section disrupt blood flow into the aneurysm. With respect to the embodiments presented above, the reinforcement elements  122  can at least be placed along this proximal dimpled or recessed region to further disrupt blood flow into the aneurysm (e.g., the reinforcement elements  122  would thicken this region presenting more of a barrier to blood entry). These reinforcement elements  122  would also increase the stiffness of this proximal end region, where the reinforcement elements  122  can continue into the rest of the proximal section of the braid (e.g., see  FIG.  13   ) to augment stiffness along a greater proximal portion of the braid. 
     In other embodiments, the ideas presented herein can be used to increase stiffness or augment flow disruption, along a larger portion of the occlusive device. For instance, in a large aneurysm with a particularly wide neck, it may be desirable to augment stiffness along a significant portion or even the entire occlusive device  110  to keep the device in place. As such, a larger portion of the device  110  can utilize the reinforcement structures  122 ,  124 . 
     For some embodiments, the permeable shell  40 ,  140  or portions thereof may be porous and may be highly permeable to liquids. In contrast to most vascular prosthesis fabrics or grafts which typically have a water permeability below 2,000 ml/min/cm 2  when measured at a pressure of 120 mmHg, the permeable shell  40  of some embodiments discussed herein may have a water permeability greater than about 2,000 ml/min/cm 2 , in some cases greater than about 2,500 ml/min/cm 2 . For some embodiments, water permeability of the permeable shell  40  or portions thereof may be between about 2,000 and 10,000 ml/min/cm 2 , more specifically, about 2,000 ml/min/cm 2  to about 15,000 ml/min/cm 2 , when measured at a pressure of 120 mmHg. 
     Device embodiments and components thereof may include metals, polymers, biologic materials and composites thereof. Suitable metals include zirconium-based alloys, cobalt-chrome alloys, nickel-titanium alloys, platinum, tantalum, stainless steel, titanium, gold, and tungsten. Potentially suitable polymers include but are not limited to acrylics, silk, silicones, polyvinyl alcohol, polypropylene, polyvinyl alcohol, polyesters (e.g. polyethylene terephthalate or PET), PolyEtherEther Ketone (PEEK), polytetrafluoroethylene (PTFE), polycarbonate urethane (PCU) and polyurethane (PU). Device embodiments may include a material that degrades or is absorbed or eroded by the body. A bioresorbable (e.g., breaks down and is absorbed by a cell, tissue, or other mechanism within the body) or bioabsorbable (similar to bioresorbable) material may be used. Alternatively, a bioerodable_(e.g., erodes or degrades over time by contact with surrounding tissue fluids, through cellular activity or other physiological degradation mechanisms), biodegradable (e.g., degrades over time by enzymatic or hydrolytic action, or other mechanism in the body), or dissolvable material may be employed. Each of these terms is interpreted to be interchangeable. bioabsorbable polymer. Potentially suitable bioabsorbable materials include polylactic acid (PLA), poly(alpha-hydroxy acid) such as poly-L-lactide (PLLA), poly-D-lactide (PDLA), polyglycolide (PGA), polydioxanone, polycaprolactone, polygluconate, polylactic acid-polyethylene oxide copolymers, modified cellulose, collagen, poly(hydroxybutyrate), polyanhydride, polyphosphoester, poly(amino acids), or related copolymer materials. An absorbable composite fiber may be made by combining a reinforcement fiber made from a copolymer of about 18% glycolic acid and about 82% lactic acid with a matrix material consisting of a blend of the above copolymer with about 20% polycaprolactone (PCL). 
     Permeable shell embodiments  40 ,  140  may be formed at least in part of wire, ribbon, or other filamentary elements  14 ,  114 . These filamentary elements  14  may have circular, elliptical, ovoid, square, rectangular, or triangular cross-sections. Permeable shell embodiments  40  may also be formed using conventional machining, laser cutting, electrical discharge machining (EDM) or photochemical machining (PCM). If made of a metal, it may be formed from either metallic tubes or sheet material. 
     Device embodiments  10 ,  110  discussed herein may be delivered and deployed from a delivery and positioning system  112  that includes a microcatheter  61 , such as the type of microcatheter  61  that is known in the art of neurovascular navigation and therapy. Device embodiments for treatment of a patient’s vasculature  10 ,  110  may be elastically collapsed and restrained by a tube or other radial restraint, such as an inner lumen  120  of a microcatheter  61 , for delivery and deployment. The microcatheter  61  may generally be inserted through a small incision  152  accessing a peripheral blood vessel such as the femoral artery or brachial artery. The microcatheter  61  may be delivered or otherwise navigated to a desired treatment site  154  from a position outside the patient’s body  156  over a guidewire  159  under fluoroscopy or by other suitable guiding methods. The guidewire  159  may be removed during such a procedure to allow insertion of the device  10 ,  110  secured to a delivery apparatus  111  of the delivery system  112  through the inner lumen  120  of a microcatheter  61  in some cases.  FIG.  17    illustrates a schematic view of a patient  158  undergoing treatment of a vascular defect  160  as shown in  FIG.  18   . An access sheath  162  is shown disposed within either a radial artery  164  or femoral artery  166  of the patient  158  with a delivery system  112  that includes a microcatheter  61  and delivery apparatus  111  disposed within the access sheath  162 . The delivery system  112  is shown extending distally into the vasculature of the patient’s brain adjacent a vascular defect  160  in the patient’s brain. 
     Access to a variety of blood vessels of a patient may be established, including arteries such as the femoral artery  166 , radial artery  164 , and the like in order to achieve percutaneous access to a vascular defect  160 . In general, the patient  158  may be prepared for surgery and the access artery is exposed via a small surgical incision  152  and access to the lumen is gained using the Seldinger technique where an introducing needle is used to place a wire over which a dilator or series of dilators dilates a vessel allowing an introducer sheath  162  to be inserted into the vessel. This would allow the device to be used percutaneously. With an introducer sheath  162  in place, a guiding catheter  168  is then used to provide a safe passageway from the entry site to a region near the target site  154  to be treated. For example, in treating a site in the human brain, a guiding catheter  168  would be chosen which would extend from the entry site  152  at the femoral artery up through the large arteries extending around the heart through the aortic arch, and downstream through one of the arteries extending from the upper side of the aorta such as the carotid artery  170 . Typically, a guidewire  159  and neurovascular microcatheter  61  are then placed through the guiding catheter  168  and advanced through the patient’s vasculature, until a distal end  151  of the microcatheter  61  is disposed adjacent or within the target vascular defect  160 , such as an aneurysm. Exemplary guidewires  159  for neurovascular use include the Synchro2® made by Boston Scientific and the Glidewire Gold Neuro® made by MicroVention Terumo. Typical guidewire sizes may include 0.014 inches and 0.018 inches. Once the distal end  151  of the catheter  61  is positioned at the site, often by locating its distal end through the use of radiopaque marker material and fluoroscopy, the catheter is cleared. For example, if a guidewire  159  has been used to position the microcatheter  61 , it is withdrawn from the catheter  61  and then the implant delivery apparatus  111  is advanced through the microcatheter  61 . 
     Delivery and deployment of device embodiments  10 ,  110  discussed herein may be carried out by first compressing the device  10 ,  110  to a radially constrained and longitudinally flexible state as shown in  FIG.  11   . The device  10 ,  110  may then be delivered to a desired treatment site  154  while disposed within the microcatheter  61 , and then ejected or otherwise deployed from a distal end  151  of the microcatheter  61 . In other method embodiments, the microcatheter  61  may first be navigated to a desired treatment site  154  over a guidewire  159  or by other suitable navigation techniques. The distal end of the microcatheter  61  may be positioned such that a distal port of the microcatheter  61  is directed towards or disposed within a vascular defect  160  to be treated and the guidewire  159  withdrawn. The device  10 ,  110  secured to a suitable delivery apparatus  111  may then be radially constrained, inserted into a proximal portion of the inner lumen  120  of the microcatheter  61  and distally advanced to the vascular defect  160  through the inner lumen  120 . 
     Once disposed within the vascular defect  160 , the device  10 ,  110  may then allowed to assume an expanded relaxed or partially relaxed state with the permeable shell  40 ,  140  of the device spanning or partially spanning a portion of the vascular defect  160  or the entire vascular defect  160 . The device  10 ,  110  may also be activated by the application of an energy source to assume an expanded deployed configuration once ejected from the distal section of the microcatheter  61  for some embodiments. Once the device  10  is deployed at a desired treatment site  154 , the microcatheter  61  may then be withdrawn. 
     Some embodiments of devices for the treatment of a patient’s vasculature  10 ,  110  discussed herein may be directed to the treatment of specific types of defects of a patient’s vasculature. For example, referring to  FIG.  18   , an aneurysm  160  commonly referred to as a terminal aneurysm is shown in section. Terminal aneurysms occur typically at bifurcations in a patient’s vasculature where blood flow, indicated by the arrows  172 , from a supply vessel splits into two or more branch vessels directed away from each other. The main flow of blood from the supply vessel  174 , such as a basilar artery, sometimes impinges on the vessel where the vessel diverges and where the aneurysm sack forms. Terminal aneurysms may have a well defined neck structure where the profile of the aneurysm  160  narrows adjacent the nominal vessel profile, but other terminal aneurysm embodiments may have a less defined neck structure or no neck structure.  FIG.  19    illustrates a typical berry type aneurysm  160  in section where a portion of a wall of a nominal vessel section weakens and expands into a sack like structure ballooning away from the nominal vessel surface and profile. Some berry type aneurysms may have a well defined neck structure as shown in  FIG.  19   , but others may have a less defined neck structure or none at all.  FIG.  19    also shows some optional procedures wherein a stent  173  or other type of support has been deployed in the parent vessel  174  adjacent the aneurysm. Also, shown is embolic material  176  being deposited into the aneurysm  160  through a microcatheter  61 . Either or both of the stent  173  and embolic material  176  may be so deployed either before or after the deployment of a device for treatment of a patient’s vasculature  10 . 
     Prior to delivery and deployment of a device for treatment of a patient’s vasculature  10 ,  110 , it may be desirable for the treating physician to choose an appropriately sized device  10 ,  110  to optimize the treatment results. Some embodiments of treatment may include estimating a volume of a vascular site or defect  160  to be treated and selecting a device  10 ,  110  with a volume that is substantially the same volume or slightly over-sized relative to the volume of the vascular site or defect  160 . The volume of the vascular defect  160  to be occluded may be determined using three-dimensional angiography or other similar imaging techniques along with software which calculates the volume of a selected region. The amount of over-sizing may be between about 2% and 15% of the measured volume. In some embodiments, such as a very irregular shaped aneurysm, it may be desirable to under-size the volume of the device  10 ,  110 . Small lobes or “daughter aneurysms” may be excluded from the volume, defining a truncated volume which may be only partially filled by the device without affecting the outcome. A device  10 ,  110  deployed within such an irregularly shaped aneurysm  160  is shown in  FIG.  28    discussed below. Such a method embodiment may also include implanting or deploying the device  10 ,  110  so that the vascular defect  160  is substantially filled volumetrically by a combination of device and blood contained therein. The device  10 ,  110  may be configured to be sufficiently conformal to adapt to irregular shaped vascular defects  160  so that at least about 75%, in some cases about 80%, of the vascular defect volume is occluded by a combination of device  10 ,  110  and blood contained therein. 
     In particular, for some treatment embodiments, it may be desirable to choose a device  10 ,  110  that is properly oversized in a transverse dimension so as to achieve a desired conformance, radial force and fit after deployment of the device  10 .  FIGS.  20 - 22    illustrate a schematic representation of how a device  10 ,  110  may be chosen for a proper fit after deployment that is initially oversized in a transverse dimension by at least about 10% of the largest transverse dimension of the vascular defect  160  and sometimes up to about 100% of the largest transverse dimension. For some embodiments, the device  10 ,  110  may be oversized a small amount (e.g. less than about 1.5 mm) in relation to measured dimensions for the width, height or neck diameter of the vascular defect  160 . 
     In  FIG.  20   , a vascular defect  160  in the form of a cerebral aneurysm is shown with horizontal arrows  180  and vertical arrows  182  indicating the approximate largest interior dimensions of the defect  160 . Arrow  180  extending horizontally indicates the largest transverse dimension of the defect  160 . In  FIG.  21   , a dashed outline  184  of a device for treatment of the vascular defect is shown superimposed over the vascular defect  160  of  FIG.  20    illustrating how a device  10 ,  110  that has been chosen to be approximately 20% oversized in a transverse dimension would look in its unconstrained, relaxed state.  FIG.  22    illustrates how the device  10 ,  110 , which is indicated by the dashed line  184  of  FIG.  21    might conform to the interior surface of the vascular defect  160  after deployment whereby the nominal transverse dimension of the device  10 ,  110  in a relaxed unconstrained state has now been slightly constrained by the inward radial force  185  exerted by the vascular defect  160  on the device  10 ,  110 . In response, as the filaments  14 ,  114  of the device  10 ,  110  and thus the permeable shell  40 ,  140  made therefrom have a constant length, the device  10 ,  110  has assumed a slightly elongated shape in the axial or longitudinal axis of the device  10  so as to elongate and better fill the interior volume of the defect  160  as indicated by the downward arrow  186  in  FIG.  22   . 
     Once a properly sized device  10 ,  110  has been selected, the delivery and deployment process may then proceed. It should also be noted also that the properties of the device embodiments  10 ,  110  and delivery system embodiments  112  discussed herein generally allow for retraction of a device  10  after initial deployment into a defect  160 , but before detachment of the device  10 ,  110 . Therefore, it may also be possible and desirable to withdraw or retrieve an initially deployed device  10  after the fit within the defect  160  has been evaluated in favor of a differently sized device  10 ,  110 . An example of a terminal aneurysm  160  is shown in  FIG.  23    in section. The tip  151  of a catheter, such as a microcatheter  61  may be advanced into or adjacent the vascular site or defect  160  (e.g. aneurysm) as shown in  FIG.  24   . For some embodiments, an embolic coil or other vaso-occlusive device or material  176  (as shown for example in  FIG.  19   ) may optionally be placed within the aneurysm  160  to provide a framework for receiving the device  10 ,  110 . In addition, a stent  173  may be placed within a parent vessel  174  of some aneurysms substantially crossing the aneurysm neck prior to or during delivery of devices for treatment of a patient’s vasculature discussed herein (also as shown for example in  FIG.  19   ). An example of a suitable microcatheter  61  having an inner lumen diameter of about 0.020 inches to about 0.022 inches is the Rapid Transit® manufactured by Cordis Corporation. Examples of some suitable microcatheters  61  may include microcatheters having an inner lumen diameter of about 0.026 inch to about 0.028 inch, such as the Rebar® by Ev3 Company, the Renegade Hi-Flow® by Boston Scientific Corporation, and the Mass Transit® by Cordis Corporation. Suitable microcatheters having an inner lumen diameter of about 0.031 inch to about 0.033 inch may include the Marksmen® by Chestnut Medical Technologies, Inc. and the Vasco 28® by Balt Extrusion. A suitable microcatheter  61  having an inner lumen diameter of about 0.039 inch to about 0.041 inch includes the Vasco 35 by Balt Extrusion. These microcatheters  61  are listed as exemplary embodiments only, other suitable microcatheters may also be used with any of the embodiments discussed herein. 
     Detachment of the device  10 ,  110  from the delivery apparatus  111  may be controlled by a control switch  188  disposed at a proximal end of the delivery system  112 , which may also be coupled to an energy source  142 , which severs the tether  72  that secures the proximal hub  68  of the device  10  to the delivery apparatus  111 . While disposed within the microcatheter  61  or other suitable delivery system  112 , as shown in  FIG.  11   , the filaments  14 ,  114  of the permeable shell  40 ,  140  may take on an elongated, non-everted configuration substantially parallel to each other and a longitudinal axis of the catheter  61 . Once the device  10 ,  110  is pushed out of the distal port of the microcatheter  61 , or the radial constraint is otherwise removed, the distal ends  62  of the filaments  14 ,  114  may then axially contract towards each other so as to assume the globular everted configuration within the vascular defect  160  as shown in  FIG.  25   . 
     The device  10 ,  110  may be inserted through the microcatheter  61  such that the catheter lumen  120  restrains radial expansion of the device  10 ,  110  during delivery. Once the distal tip or deployment port of the delivery system  112  is positioned in a desirable location adjacent or within a vascular defect  160 , the device  10 ,  110  may be deployed out the distal end of the catheter  61  thus allowing the device to begin to radially expand as shown in  FIG.  25   . As the device  10 ,  110  emerges from the distal end of the delivery system  112 , the device  10 ,  110  expands to an expanded state within the vascular defect  160 , but may be at least partially constrained by an interior surface of the vascular defect  160 . 
     Upon full deployment, radial expansion of the device  10 ,  110  may serve to secure the device  10 ,  110  within the vascular defect  160  and also deploy the permeable shell  40  across at least a portion of an opening  190  (e.g. aneurysm neck) so as to at least partially isolate the vascular defect  160  from flow, pressure or both of the patient’s vasculature adjacent the vascular defect  160  as shown in  FIG.  26   . The conformability of the device  10 ,  110 , particularly in the neck region  190  may provide for improved sealing. For some embodiments, once deployed, the permeable shell  40 ,  140  may substantially slow the flow of fluids and impede flow into the vascular site and thus reduce pressure within the vascular defect  160 . For some embodiments, the device  10 ,  110  may be implanted substantially within the vascular defect  160 , however, in some embodiments, a portion of the device  10 ,  110  may extend into the defect opening or neck  190  or into branch vessels. 
     For some embodiments, as discussed above, the device  10 ,  110  may be manipulated by the user to position the device  10 ,  110  within the vascular site or defect  160  during or after deployment but prior to detachment. For some embodiments, the device  10 ,  110  may be rotated in order to achieve a desired position of the device  10  and, more specifically, a desired position of the permeable shell  40 ,  140 ,  240 ,  340 ,  440 , prior to or during deployment of the device  10 ,  110 . For some embodiments, the device  10 ,  110  may be rotated about a longitudinal axis of the delivery system  112  with or without the transmission or manifestation of torque being exhibited along a middle portion of a delivery catheter being used for the delivery. It may be desirable in some circumstances to determine whether acute occlusion of the vascular defect  160  has occurred prior to detachment of the device  10 ,  110  from the delivery apparatus  111  of the delivery system  112 . These delivery and deployment methods may be used for deployment within berry aneurysms, terminal aneurysms, or any other suitable vascular defect embodiments  160 . Some method embodiments include deploying the device  10 ,  110  at a confluence of three vessels of the patient’s vasculature that form a bifurcation such that the permeable shell  40  of the device  10 ,  110  substantially covers the neck of a terminal aneurysm. Once the physician is satisfied with the deployment, size and position of the device  10 ,  110 , the device  10 ,  110  may then be detached by actuation of the control switch  188  by the methods described above and shown in  FIG.  26   . Thereafter, the device  10 ,  110  is in an implanted state within the vascular defect  160  to effect treatment thereof. 
       FIG.  27    illustrates another configuration of a deployed and implanted device in a patient’s vascular defect  160 . While the implantation configuration shown in  FIG.  26    indicates a configuration whereby the longitudinal axis  46  of the device  10 ,  110  is substantially aligned with a longitudinal axis of the defect  160 , other suitable and clinically effective implantation embodiments may be used. For example,  FIG.  27    shows an implantation embodiment whereby the longitudinal axis  46  of the implanted device  10 ,  110  is canted at an angle of about 10 degrees to about 90 degrees relative to a longitudinal axis of the target vascular defect  160 . Such an alternative implantation configuration may also be useful in achieving a desired clinical outcome with acute occlusion of the vascular defect  160  in some cases and restoration of normal blood flow adjacent the treated vascular defect.  FIG.  28    illustrates a device  10 ,  110  implanted in an irregularly shaped vascular defect  160 . The aneurysm  160  shown has at least two distinct lobes  192  extending from the main aneurysm cavity. The two lobes  192  shown are unfilled by the deployed vascular device  10 ,  110 , yet the lobes  192  are still isolated from the parent vessel of the patient’s body due to the occlusion of the aneurysm neck portion  190 . 
     Markers, such as radiopaque markers, on the device  10 ,  110  or delivery system  112  may be used in conjunction with external imaging equipment (e.g. x-ray) to facilitate positioning of the device or delivery system during deployment. Once the device is properly positioned, the device  10  may be detached by the user. For some embodiments, the detachment of the device  10 ,  110  from the delivery apparatus  111  of the delivery system  112  may be affected by the delivery of energy (e.g. heat, radiofrequency, ultrasound, vibrational, or laser) to a junction or release mechanism between the device  10  and the delivery apparatus  111 . Once the device  10 ,  110  has been detached, the delivery system  112  may be withdrawn from the patient’s vasculature or patient’s body  158 . For some embodiments, a stent  173  may be place within the parent vessel substantially crossing the aneurysm neck  190  after delivery of the device  10  as shown in  FIG.  19    for illustration. 
     For some embodiments, a biologically active agent or a passive therapeutic agent may be released from a responsive material component of the device  10 ,  110 . The agent release may be affected by one or more of the body’s environmental parameters or energy may be delivered (from an internal or external source) to the device  10 ,  110 . Hemostasis may occur within the vascular defect  160  as a result of the isolation of the vascular defect  160 , ultimately leading to clotting and substantial occlusion of the vascular defect  160  by a combination of thrombotic material and the device  10 ,  110 . For some embodiments, thrombosis within the vascular defect  160  may be facilitated by agents released from the device  10  and/or drugs or other therapeutic agents delivered to the patient. 
     For some embodiments, once the device  10 ,  110  has been deployed, the attachment of platelets to the permeable shell  40  may be inhibited and the formation of clot within an interior space of the vascular defect  160 , device, or both promoted or otherwise facilitated with a suitable choice of thrombogenic coatings, anti-thrombogenic coatings or any other suitable coatings (not shown) which may be disposed on any portion of the device  10 ,  110  for some embodiments, including an outer surface of the filaments  14  or the hubs  66  and  68 . Such a coating or coatings may be applied to any suitable portion of the permeable shell  40 . Energy forms may also be applied through the delivery apparatus  111  and/or a separate catheter to facilitate fixation and/or healing of the device  10 ,  110  adjacent the vascular defect  160  for some embodiments. One or more embolic devices or embolic material  176  may also optionally be delivered into the vascular defect  160  adjacent permeable shell portion that spans the neck or opening  190  of the vascular defect  160  after the device  10  has been deployed. For some embodiments, a stent or stent-like support device  173  may be implanted or deployed in a parent vessel adjacent the defect  160  such that it spans across the vascular defect  160  prior to or after deployment of the vascular defect treatment device  10 ,  110 . 
     In any of the above embodiments, the device  10 ,  110  may have sufficient radial compliance so as to be readily retrievable or retractable into a typical microcatheter  61 . The proximal portion of the device  10 ,  110 , or the device as a whole for some embodiments, may be engineered or modified by the use of reduced diameter filaments, tapered filaments, or filaments oriented for radial flexure so that the device  10 ,  110  is retractable into a tube that has an internal diameter that is less than about 0.7 mm, using a retraction force less than about 2.7 Newtons (0.6 lbf) force. The force for retrieving the device  10 ,  110  into a microcatheter  61  may be between about 0.8 Newtons (0.18 lbf) and about 2.25 Newtons (0.5 lbf). 
     Engagement of the permeable shell  40 ,  140  with tissue of an inner surface of a vascular defect  160 , when in an expanded relaxed state, may be achieved by the exertion of an outward radial force against tissue of the inside surface of the cavity of the patient’s vascular defect  160 , as shown for example in  FIG.  29   . A similar outward radial force may also be applied by a proximal end portion and permeable shell  40 ,  140  of the device  10 ,  110  so as to engage the permeable shell  40  with an inside surface or adjacent tissue of the vascular defect  160 . Such forces may be exerted in some embodiments wherein the nominal outer transverse dimension or diameter of the permeable shell  40  in the relaxed unconstrained state is larger than the nominal inner transverse dimension of the vascular defect  160  within which the device  10 ,  110  is being deployed, i.e., oversizing as discussed above. The elastic resiliency of the permeable shell  40  and filaments  14  thereof may be achieved by an appropriate selection of materials, such as superelastic alloys, including nickel titanium alloys, or any other suitable material for some embodiments. The conformability of a proximal portion of the permeable shell  40 ,  140  of the device  10 ,  110  may be such that it will readily ovalize to adapt to the shape and size of an aneurysm neck  190 , as shown in  FIGS.  20 - 22   , thus providing a good seal and barrier to flow around the device. Thus, the device  10  may achieve a good seal, substantially preventing flow around the device without the need for fixation members that protrude into the parent vessel. 
     Although the foregoing invention has, for the purposes of clarity and understanding, been described in some detail by way of illustration and example, it will be obvious that certain changes and modifications may be practiced which will still fall within the scope of the appended claims.