Abstract:
The present invention relates to a catheter that has adjustable stiffness that enables a user to select the stiffness of at least one region of the catheter during insertion and navigation through a body lumen. A preferred embodiment of the invention works in combination with a guidewire to enable placement of the catheter at a position within the vascular system, for example, to enable treatment of a variety of medical conditions. The catheter can include segments that undergo relative movement in response to actuation by the user to adjust the flexibility of the at least one region, preferably located at or near the distal end of the catheter.

Description:
CROSS REFERENCE TO RELATED APPLICATION 
       [0001]    This application claims priority to U.S. Provisional Application No. 61/766,527 filed Feb. 19, 2013 entitled ADJUSTABLE STIFFNESS CATHETER, the entire contents of the above application being incorporated herein by reference. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    The present invention relates to variable stiffness catheters and more specifically relates to devices and methods for accessing tubular structures in the body. Existing catheters commonly use a guidewire to aid in the positioning thereof within body lumens for the purpose of delivering medical devices or therapeutic agents to treat a variety of medical conditions. Often, the delivery path within the lumens or vessels of a mammalian body can include regions under 2 mm in diameter and may require the distal end of the device to undergo turns of 90 degrees or more to reach the region requiring treatment. Many vascular applications involving the treatment of strokes, aneurysms, or embolizations, for example, involve navigation through the turns that are required, while catheters that are too flexible may kink and thereby complicate proper placement within the body. There are also risks of vessel perforation or vasospasm in procedures that are frequently time sensitive. 
         [0003]    Many available catheters have fixed variable stiffness in which the proximal end is stiffer than the distal end. This improves the pushability of the device and also allows the distal end to bend at the required angles. Some devices are made with materials that are preshaped, or alternatively, permit steam shaping of the distal end to improve navigational performance. However, existing devices continue to be limited in the capabilities needed to access small remote locations requiring treatment. Thus, a continuing need exists for improvements in catheter design that enable fast and safe delivery of various treatment options within the mammalian body. 
       SUMMARY OF THE INVENTION 
       [0004]    The invention generally relates to a catheter having adjustable stiffness in which the user can select a level of stiffness to enable navigation within lumens of a mammalian body. A preferred embodiment can include a tubular body with at least two portions or layers that are able to move relative to each other. Relative motion of the two portions of the tubular body changes the stiffness of at least one region of the catheter such that the at least one region can bend at an angle relative to the longitudinal axis of the catheter. In a preferred embodiment, each of the plurality of layers can include segments of different lengths, materials, and/or durometer rating. 
         [0005]    The catheter can include an inner tube and an outer tube that slide relative to each other by manual actuation. The inner tube has a distal portion with a first plurality of spaced regions having a first stiffness. The spaced regions can be separated by a corresponding plurality of spaced segments having a greater stiffness than the spaced regions. These alternating stiff and flexible elements of the inner tube can be moved longitudinally relative to an outer tube that has alternating segments and regions of differing stiffness. This operates to alter the overall state of flexibility of a distal portion of the catheter. An important metric that reflects this flexibility is the minimum radius of curvature of the flexible portion of the catheter that is associated with a selected relative position of the adjustable catheter elements. For preferred embodiments, the minimum radius of curvature is in a range of 2-6 mm and preferably in a range of 3-5 mm. 
         [0006]    A preferred embodiment includes an actuator or switch to change the position of the layers of the tube relative to each other. The actuator can be mounted on a handle positioned at a proximal end of the catheter, which can also include other operative elements to perform selected modes of treatment within the vascular system, for example. The catheter can include a central lumen having a diameter such that a guidewire can slide into the proximal or distal opening of the catheter lumen. 
         [0007]    Thus, preferred embodiments of the present invention provide access to tubular structures in the body with high tortuosity and can be used for accessing vessels that perfuse the central nervous system, the abdomen, the pelvis, the cardiovascular system, the respiratory system, peripheral vessels, the gastrointestinal system, the genitourinary tract and the neurovascular system. The catheter can be inserted into body lumens, or alternatively, by percutaneous entry with an introducer. 
         [0008]    Preferred embodiments of the invention can include a plurality of treatment devices and methods that can be delivered to anatomic sites within the human or animal body. Devices for treatment of the vascular system can include stents, filters and/or balloon devices, for example. Medications can be delivered with the catheter through one or more channels within the catheter or in combination with the above referenced devices. The handle can include one or more side ports to introduce devices and or medications. 
         [0009]    Preferred embodiments of the invention also relate to methods of manufacturing adjustable stiffness catheters. The inner and outer tubes can be made with a coiled or braided structure. A preferred embodiment can include steps of forming annular segments of differing stiffness, arranging the segments in a selected order, and heating the segments to thereby form the inner and outer tubes such that the segments are arranged to provide the desired range of flexibility. 
         [0010]    Other objects and advantages of the present invention will become apparent to the reader, and it is intended that these objects and advantages are within the scope of the present invention. To the accomplishment of the above and related objects, this invention may be embodied in the form illustrated in the accompanying drawings, attention being called to the fact, however, that the drawings are illustrative only, and that changes may be made in the specific construction illustrated and described within the scope of this application. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0011]      FIGS. 1A-1D  are side views of flexible and rigid states, respectively, of preferred embodiments of the present invention; 
           [0012]      FIGS. 2A-2B  are side views of flexible and rigid states of a catheter body in accordance with the present invention; 
           [0013]      FIGS. 2C-2F  illustrate a process of advancing the catheter through a series of branching features of a lumen system to a treatment site; 
           [0014]      FIGS. 3A-3B  are partial cutaway perspective views of an actuator such as a sliding switch to adjust between flexible and stiff states in accordance with the present invention; 
           [0015]      FIGS. 4A-4I  illustrate embodiments of a sliding two-layer system for an adjustable stiffness catheter in accordance with preferred embodiments of the invention; 
           [0016]      FIGS. 4J-4K  illustrate a spring-operated actuator in accordance with certain embodiments of the invention; 
           [0017]      FIGS. 5-9  illustrate sectional views of methods of forming catheters in accordance with preferred embodiments of the invention; 
           [0018]      FIGS. 10-14  are process sequence diagrams of methods for fabricating adjustable stiffness catheters in accordance with preferred embodiments of the invention; 
           [0019]      FIGS. 15A-15B  illustrate side cutaway views of a catheter according to certain embodiments of the present disclosure; 
           [0020]      FIGS. 16A-16C  illustrate side cutaway views of a catheter according to certain embodiments of the present disclosure; 
           [0021]      FIG. 17  illustrate a side view of a catheter including a balloon treatment device according to certain embodiments; 
           [0022]      FIGS. 18A-18C  illustrate side cutaway views of a catheter used to deliver a stent to a treatment site according to certain embodiments of the present disclosure; 
           [0023]      FIGS. 19A-19C  illustrate a method of positioning a second catheter or treatment device using various embodiments of the present invention; 
           [0024]      FIG. 20  illustrates a side cutaway view of a catheter with a handle region according to certain; 
           [0025]      FIGS. 21A-21D  illustrate components of an actuator in a handle region of a catheter according to certain embodiments; and 
           [0026]      FIGS. 22A-22B  illustrate side cutaway views of catheters incorporating lubricious coatings, according to various embodiments. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0027]    Turning now to a description of the drawings, in which similar reference characters denote similar elements throughout the several views,  FIGS. 1A-1D  illustrate a tube  10  with at least two layers  20 , 22  that are able to slide past each other, each of which includes a plurality of segments  12 , 14  and  16 , 18  that can have different lengths, materials, and/or durometer rating. The device  10  can further comprise an actuator such as a mechanical switch, to change the relative positioning of the layers of the tube relative to each other. 
         [0028]    The outer tube layer  22  can have segments  16 , 18  of different lengths, materials, and/or durometer ratings. In the preferred embodiment, the outer layer  22  comprises two alternating segments  16 , 18 , each with its own characteristic length, material(s), and durometer ratings. In some embodiments, the length of the segment with higher durometer rating  18  will be greater than that of the segment with the lower durometer rating  16 . 
         [0029]    Segment materials can comprise (but are not limited to) FEP, PFA, Pebax, polyurethane, nylon, PVC, TPE, polyester. The catheter elements may be formed by methods including, but not limited to, extrusion or casting. Segment or layer reinforcing material may include a metal such as, but not limited to, 304 SS, 316 SS, and/or monofilament materials. 
         [0030]    The segments may be of appropriate length, be made of appropriate material(s), and have any appropriate durometer rating required for a given application. Catheters having lengths ranging from 10 cm to 2 m, and diameters of less than 1 mm to more than 10 mm, can be made in accordance with preferred embodiments of the invention. Small diameter guide catheters can be less than 2 mm in diameter in the distal region and preferably less than 1 mm. 
         [0031]    The outer layer  22  can comprise two types of segments (each with a characteristic length, material composition, durometer rating) that alternate. It can also comprise selected combinations of different segments. The length of the segment with higher durometer rating ( 18 ) can be greater than, equal to, or less than that of the segment with the lower durometer rating ( 16 ). 
         [0032]    The inner tube layer  20  has segments of different lengths, materials, and/or durometer ratings. In the preferred embodiment, the outer layer comprises two alternating segments  12  and  14 , each with its own characteristic length, material(s), and/or durometer ratings. The length of the segment with higher durometer rating ( 12 ) can be greater than that of the segment with the lower durometer rating ( 14 ). The length of segment  12  can equal that of 18 and the length of segment  14  can equal that of 16, for example. 
         [0033]    Segment materials can comprise, but are not limited to, FEP, PFA, pebax, polyurethane, nylon, PVC, TPE, polyester. The catheter may be formed by methods including, but not limited to, extrusion or casting. Segment reinforcing material may include a metal, nitinol, or specifically stainless steel, such as, but not limited to: 304 SS, 316 SS, or can comprise one or more monofilaments. Thus, one or more components of the catheter can comprise a shape memory material. The catheter can include a curved distal tip to assist with steering of the device. 
         [0034]    The inner layer  20  can comprise two types of segments (each with a characteristic length, material composition, durometer rating) that alternate. It may also comprise a combination of any number of different segments. The length of the segment with higher durometer rating ( 12 ) can be greater than, equal to, or less than that of the segment with the lower durometer rating ( 14 ). 
         [0035]    The inner layer  20  can also take the form of a wire instead of a tube where the application does not require a central lumen for a guidewire or to provide a port for insertion of fluids such as a flushing liquid, or for delivery of medication, or to introduce other tools or devices through, or with, the catheter. 
         [0036]    An actuator used for adjusting catheter stiffening can comprise a sliding device that allows the inner and outer layers of the tube to be switched from a position in which segments  12  and  18  are in register and  14  and  16  are in register, to a position in which they are out of register where the segment  12  bridges the gap between adjacent segments  18  ( FIG. 1D ). In the in-register state ( FIG. 1B ), the flexibility of the overall tube is dictated by the less stiff segments  14  and  16 . In the out of-register state, the flexibility of the overall tube is dictated by the more stiff segments  12  and  18 . 
         [0037]    As shown in  FIGS. 2A and 2B , the catheter body  10  can have a flexible region  40  in which segments are registered such that the flexible region  40  can bend along a selected radius of curvature R. The catheter  10  can include a handle  52  mounted at a proximal end that can have a plurality of actuators, buttons, or switches  58  that are operative to change the flexibility of all or a portion of the catheter. A slider element can also be used to advance a guidewire  56  that can be inserted into a central lumen of the catheter. The guidewire  56  can have a distal hook, or “J” shaped distal end, that can allow the user to select one of a plurality of branches of an arterial system. The guidewire can be used with the adjustable catheter to navigate the many branches of the neurovascular system, for example, to deliver treatment or aid in the imaging of a particular treatment site. A fluid source  54  can be used to deliver a fluid such as a contrast agent, a medication, nutrients, electrolytes, blood products, chemotherapy agents or radiotherapy agents, for example. As shown in  FIG. 2B , the catheter in its more rigid state has limited flexibility and is generally aligned along its longitudinal axis  50 . The catheter  10  can include a device  55 , such as a stent or balloon, which can be positioned with the catheter at a treatment site. Fluoroscopic markers  57  can be included to aid in visualization. 
         [0038]    However, as illustrated in the sequence of  FIGS. 2C-2F , the catheter is used to bend in different directions where the more flexible state is used to initiate turns and a more rigid state to advance along more linear regions of a lumen system. Note that the catheter can simply switch back and forth between two states (rigid and flexible) or alternatively, the user can select a level of stiffness from a continuum of available levels depending on the sizes and locations of the second, third, or fourth degree turns that can be encountered, as illustrated in  FIG. 2C . The catheter can be initially stiff upon percutaneous introductions, is adjusted to a flexible state at the first turn ( FIG. 2D ) is made rigid while advancing to the next turn ( FIG. 2E ) and made flexible to initiate the second turn at  FIG. 2F . This process is continued through the third and fourth turns, as needed, to reach the treatment site. 
         [0039]    As shown in  FIGS. 3A-3B , an actuator such as a slider switch device  60  can comprise a base  26  that can slide relative to the outer layer  28  wherein the user can manually engage the slider element  60  that is connected to the outer layer  28  (see  FIGS. 4J-4K , hereinafter, for example). 
         [0040]    The inner and outer layers  20 , 22  of the tube  10  are concentric and can slide past each other in this embodiment. The switch  60  is connected to the two layers  20 , 22  of the tube, with the base connected to the inner layer  20  of the tube, and a slider  60  connected to the outer layer of the tube. This switch  60  allows the outer layer to slide longitudinally over the inner layer. 
         [0041]    The tube  10  is comprised of inner and outer layers  20 , 22 , each consisting of alternating flexible segments of length x and semi-rigid segments of length y. The inner and outer layers  20 , 22  of the tube  10  can comprise either two concentric tubes with differing radii, or a combination of a tube and wire. The alternating segments can be made of materials, have a selected thickness, have a selected tensile strength, and have a selected shear modulus to achieve the desired thickness and radius of curvature required for a given application. The inner and outer layers  20 , 22  will move longitudinally against each other in a controlled manner, via a mechanical switching device. When the alternating stiff and flexible segments of the inner and outer layers of the catheter tube are in register, the catheter tube is in a “relaxed” flexible state. When the segments are out of register, the rigid segments of the inner and outer layers overlap with each other and the catheter tube stiffens to achieve a more rigid state. 
         [0042]    In the preferred embodiment, the tube is a diagnostic microcatheter with walls strong enough to handle high pressure injections of intravascular radio-opaque contrast. The lengths x and y are 1-5 mm, with y&gt;x. The microcatheter is used to navigate second and third order vessels within patients during interventional radiological, cardiac, or surgical procedures.  FIGS. 4A-4I  show different embodiments in which different segments of the two layers comprise different materials, have different lengths, or register in differing combinations to achieve different bending characteristics. As shown in  FIGS. 4J-4K , the proximal end  100  of the catheter can comprise a handle in which a proximal stop  110  can be used with a thumb knob  104  and one or more spring elements  102  to actuate relative movement between the two layers  20 ,  22 . This can be used with a guidewire positioned within central lumen  120  to manipulate the distal end of the catheter through a sequence of turns in which a physician can navigate through interconnected lumens within the body. 
         [0043]    In another preferred embodiment, a catheter layer  200 , shown in  FIG. 5 , can comprise a variable pitch coil  202  mounted on an inner tube or liner  204  and covered with an outer polymer  206  to provide a flexible region  40 , surrounded by stiffer regions  208 ,  210 . Thus, the layer  200  can include a plurality of alternating segments of higher and lower stiffness. A second layer having an identical structure, except with a larger diameter, can be paired with layer  200  which is inserted within the second layer as described herein to form a flexible catheter that can be adjusted so that the alternating flexible and stiff regions can either be aligned with each other, or moved out of alignment, to provide a flexible or more rigid structure, respectively. Note that the stiffness of each segment can be selected by adjusting the pitch, or number of windings, within a given segment. Thus, stiff regions have a greater pitch and flexible regions have a smaller pitch. 
         [0044]    In a preferred method of making a catheter having adjustable stiffness as shown in  FIG. 6 , an inner liner  304  can be mounted with a coil braid  302 . Grinding wheels  310  can form intervals to form alternating stiff and flexible regions. Another preferred method shown in  FIG. 7  first forms a polymer layer  360  around an inner liner  350 . Grinding wheels can form spaces and a second polymer layer  362  can be deposited in the spaces to form a composite structure of alternating segments. 
         [0045]    In  FIG. 8 , another preferred method of fabrication selectively deposits a polymer  402  to form segments on liner  400 . A third polymer layer  404  can be formed and ground with grinding element  420  to form alternating stiff  422  and flexible  424  regions. In  FIG. 9 , stiff  452  and flexible tubes  454  can be positioned along a liner  450  which are then coated with an outer polymer  460  to secure the segments in place. 
         [0046]    Shown in  FIGS. 10-14  are process sequences illustrating steps for fabricating catheters in connection with preferred embodiments of the invention. In  FIG. 10 , the process  500  includes mounting a liner on a mandrel  502 , mounting coil elements with different pitches  504 , bonding these the liner  506 , overlaying additional polymer layers  508 ,  510 , assembling the different layers  512 , and connecting the  514  actuator. 
         [0047]    In the method  600  of  FIG. 11 , a layer is formed on a mandrel  602 , form a braid or coil  604  and bonding thereof to a liner  606 . A second polymer is overlayed  610 , followed by an optional third layer  612 . An outer tube is formed  614  and connected to a handle  616 . A centerless grinding tool can be used to remove portions  608  of material to form segments. In the method  700  of  FIG. 12 , grooves formed by centerless grinding  706 , for example, can be filled with a polymer of lower durometer  708  to form alternating segments of different durometers in a given layer. This is followed by outer catheter fabrication  712  and connection to a catheter hub or handle  714 . In the method  800  of  FIG. 13 , with steps  802  and  804  followed by an overlying layer formed  806  with a third polymer can be formed over adjacent segments of different durometers along with steps  808 ,  810  and  812 . In the method  900  of  FIG. 14 , two polymer layers can be formed  902 ,  904  on the same mandrel and then cut to selected lengths  906  for mounting on a selected liner in alternating fashion  908 . These segments can then be secured in place with a third polymer layer or adhesive or a heat shrink material to secure the segments in place  910 ,  912  and  914 . 
         [0048]    Current vascular catheters and wires generally employ a different technique to engage second- or third-order vessels. A common problem occurs when small tortuous vessels prevent a catheter from being advanced because of sharp turns. This step is often the most time-intensive and unpredictable component of a procedure. Failure to advance is often due to the catheter being too soft and unable to traverse a sharp bend over a wire, or too stiff, causing the catheter and wire to disengage from the target vessel altogether. Ideally, an advancing catheter needs to be flexible when making initial sharp turns, but stiff enough to allow effective advancement into the vessel to obtain enough purchase for either further advancement or deployment of contrast materials, medication, or therapeutic devices. 
         [0049]    The present invention is useful for any application that requires the operator to navigate a tube through a torturous tubular structure in the body. Preferred embodiments comprise vascular microcatheters, which can be used for procedures ranging from thrombolysis of cerebral artery occlusions to the coiling of bleeding mesenteric arteries. However, the invention provides a suitable solution to similar problems found in endoscopic procedures involving the GI and GU tracts as well as solving problems that frequently occur in cardiac procedures involving intravascular ultrasound catheters. Finally, simple and robust variable-stiffness catheters may also be in industrial applications involving drilling and exploration. 
         [0050]    The catheters of the present disclosure can be used in a variety of different diagnostic and therapeutic procedures. For example, in certain embodiments, the catheters of the present disclosure can be used to sample or delivery fluids to selected anatomic sites. Examples of various diagnostic and therapeutic procedures that may be performed using fluids delivered or obtained through the catheters can include adrenal vein sampling: (e.g., sampling blood from several veins surrounding the adrenal glands in order to determine levels of aldosterone; neurovascular (including carotid, cerebral, and spinal vessels) diagnostic or therapeutic procedures; injection of thrombolytics to break up clots for ischemia treatment; contrast or MR angiography used to identify peripheral vascular disease and plan for future surgical intervention; catheter-based imaging of mesenteric artery to detect or rule out aneurysm, thrombosis, ischemia, or to locate the source of gastrointestinal bleeding; detection of portal hypertension and cirrhosis; imaging of the celiac artery to detect or rule out aneurysm, thrombosis, ischemia, or to locate the source of gastrointestinal bleeding; confirmation or detection of vascular anatomy and patency of hepatic vasculature prior to surgical intervention, for example for liver transplant; catheter-based delivery of contrast for gastric, pancreaticoduodenal, spenic, renal, thoracic, intercostal, coronary, or pulmonary angiography catheter-based delivery of contrast into biliary tree for imaging the biliary network; selective catheter angiogiography to identify anastomoses for percutaneous transluminal angioplasty (PTA) or surgical repair and/or selective catheter angiography to identify anastomoses for PTA or surgical repair; catheter-based injection of contrast agents for imaging lymph vessels to detect cancer metastasis; and/or injection of radiocontrast agents into the urinary tract for diagnostic imaging 
         [0051]    In other embodiments, solids can be delivered using the devices of the present disclosure. As discussed further below, smaller solid agents can be delivered directly by removing the guidewire and then introducing the agents through the microcatheter. For larger agents, however, the inner layer  20  may be removed to increase the inner diameter of the system. The devices of the present disclosure can be used to deliver embospheres (20 μm to 2000 μm, or 0. 0008″ to 0. 008″), coils (0.01″ to 0.4″), gelfoam (variable, typically ˜0.25″), or mechanical thrombectomy devices (stentrievesr). At the 3 French OD scale, agents up to 0.018″ can be delivered without removing the inner catheter, and for larger agents the inner layer may be removed. As examples, the devices of the present disclosure can be used for neurovascular aneurysm coiling, including aneurysms within the circle of Willis, cerebral arteries (posterior, anterior, and middle, up to 2nd order branches), and spinal vessels (aneurysm sizes 2-20 mm); transhepatic arterial chemoembolization (same requirements as hepatic arteries) for tumors; coiling or embolization of hepatic arteries; embolization of gastric artery to prevent aneurysm rupture or to cut off blood supply to a portion of the stomach producing the hormone ghrelin, which can lead to decreased feeding and weight loss in obese individuals; splenic artery coiling/embolization for aneurysms or pseudoanuerysms (aneurysm sizes 5-20 mm); gastroduodenal arterial coiling (aneurysm sizes 3-15 mm) for pseudoaneuryms; superior mesenteric artery embolization/coiling for aneurysms/pseudoaneurysms; mesenteric artery branch embolization/coiling for small bowel bleeding; colonic (right, middle, left) artery branch embolization or coiling for GI bleeding; rectal artery branch embolization or coiling for bleeding; uterine artery branch embolization or coiling (for uterine fibroids, uterine bleeding); pulmonary arterial embolization for treatment of pulmonary arteriovenous malformations, aneurysm, or bleeds; and lymphatic or thoracic duct coiling to prevent leakage of lymphatic fluids into the thoracic duct by selectively blocking the leaking vessels. 
         [0052]    The devices of the present disclosure can further be used to deliver various therapeutic agents or therapies. As examples, the devices can be used for venous sclerosing treatments to selectively deliver sclerosing agents or fiber optic lasers to specific varicose veins in order to target their dissolution. Furthermore, the devices can be used to retrieve objects within a body lumen, include stents, thrombotic filters, unwanted foreign bodies, or instruments accidentally dislodged during surgical or radiological procedures. 
         [0053]    In addition, in certain embodiments, the devices of the present disclosure can be fitted with a camera to be placed into a vessel or other cavity in order to image the area in question. Since cameras must fit within the inner diameter of the assembly (or the inner diameter of the outer catheter), these procedures may require slightly larger catheter systems, perhaps up to 5 French. Visualization using optical cameras may be employed in GI/Biliary applications imaging of the esophagus, stomach, and proximal small bowel; colonoscopy; ERCP (endoscopic retrograde cholangiopancreatography); laparoscopic procedures; mediastinoscopy; rhinoscopy, otoscopy; laryngoscopy; bronchoscopy; neurosurgical scoping; urological procedures; cystoscopy; ureteroscopy; prostatectomies; colposcopy; hysteroscopy; falloposcopy; and arthroscopy or visualization of any joint or musculoskeletal structure. In addition, the devices of the present disclosure may be used to drain or place tubes in various anatomic sites including, urinary catheters; urethral or bladder catheters; percutaneous nephrostomy tubes; abdominal/pelvic cavity tubes; general drains for abscesses or fluid collections; chest tubes; thoracostomy tubes; devices for paracentesis or thoracentesis; neurological devices; and ventriculostomy devices. 
         [0054]    The devices of the present disclosure can be used in a variety of angioplasty or stenting procedures, including, but not limited to carotid stenting or angioplasty; vertebral artery stenting or angioplasty; spinal artery angioplasty; peripheral vascular stenting or angioplasty (lower or upper extremity); superior mesenteric artery stenting or angioplasty; celiac stenting or angioplasty; hepatic artery stenting or angioplasty; arteriovenous graft angioplasty; vascular anastomoses stenting or angioplasty (hepatic artery, vein, portal vein, renal artery, mesenteric artery anastomoses for transplants); biliary ballooning or stenting; pancreatic duct ballooning or stenting; esophageal ballooning or stenting; duodenal ballooning or stenting; colonic ballooning or stenting; and urinary tract stenting or ballooning 
         [0055]    A variety of different sizes and configurations of devices can be selected depending on the specific clinical application. It should be appreciated that the specific size and configuration may vary based on patient-specific factors, clinical situations, and/or clinician preference. Table 1, however, provides typical specifications for various applications, including an expected radius of curvature that the device should obtain for effective use. The presently disclosed devices provide advantages in that they can be produced with a range of sizes and shapes to provide systems for treatment of many different anatomic sites and conditions, and can be scaled to allow for a desired radius of curvature, which may be a critical factor in determining whether or not the device can reach a target site. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Typical device specifications. 
               
             
          
           
               
                   
                 Req. 
                 Req. 
                 Min. 
                   
               
               
                 Type of 
                 catheter 
                 tip 
                 radius of 
                 Vessel 
               
               
                 vessel/technique 
                 size 
                 length 
                 curvature 
                 diameter 
               
               
                   
               
             
          
           
               
                 Adrenal vein sampling 
                 2-4 
                 Fr 
                 3-5 
                 cm 
                 3 mm 
                 2-7 mm 
               
               
                 Neurovascular 
                 1.5-4 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 Upper and lower 
                 1.5-6 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 extremity 
               
               
                 Mesenteric artery 
                 2-4 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 Celiac trunk 
                 3-5 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 Hepatic arteries/veins 
                 2-4 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 Gastric arteries 
                 2-4 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 Pancreaticoduodenal 
                 2-4 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 arteries 
               
               
                 Splenic arteries 
                 2-4 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 Renal arteries or veins 
                 2-4 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 Thoracic or intercostal 
                 2-4 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 arteries 
               
               
                 Pulmonary arteries and 
                 2-6 
                 Fr 
                 1-5 
                 cm 
                 5 mm 
               
               
                 veins 
               
               
                 Coronary arteries 
                 1.5-3 
                 Fr 
                 0.5-5 
                 cm 
                 3 mm 
               
               
                 Arterial anastomoses 
                 2-4 
                 Fr 
                 1-10 
                 cm 
                 3 mm 
               
               
                 Bile duct anastomoses 
                 2-10 
                 Fr 
                 1-15 
                 cm 
                 5 mm 
               
               
                 Bile duct 
                 2-8 
                 Fr 
                 1-10 
                 cm 
                 3 mm 
               
               
                 cholangiogram 
               
               
                 Bowel anastomoses 
                 4-16 
                 Fr 
                 5-20 
                 cm 
                 10 mm  
               
               
                 Lymphangiography 
                 1.8-4 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 Urinary tract imaging 
                 2-10 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 AV graft angioplasty 
                 2-5 
                 Fr 
                 1-10 
                 cm 
                 5 mm 
               
               
                 EGD 
                 4-20 
                 Fr 
                 5-20 
                 cm 
                 5 mm 
               
               
                 Colonoscopy 
                 4-25 
                 Fr 
                 5-20 
                 cm 
                 5 mm 
               
               
                 Bronchoscopy 
                 2-4 
                 Fr 
               
               
                 Cytoscopy/ureteroscopy 
                 4-12 
                 Fr 
               
               
                 Hysteroscopy 
                 2-5 
                 Fr 
               
               
                 Falloposcopy 
                 1.5-4 
                 Fr 
               
               
                 Urethral catheter 
                 8-20 
                 Fr 
               
               
                 Percutaneous 
                 4-15 
                 Fr 
               
               
                 nephrostomy 
               
               
                 General drains 
                 4-40 
                 Fr 
                 1-10 
                 cm 
               
               
                 Paracentesis 
                 4-8 
                 Fr 
               
               
                   
               
             
          
         
       
     
         [0056]      FIGS. 15A-22B  provide additional details illustrating how the devices of the present disclosure may be used in various clinical situations.  FIGS. 15A-15B  illustrate side cutaway views of a catheter  10  according to certain embodiments of the present disclosure. As shown, the catheter  10 , comprises inner layer  20  and outer layer  22 . In addition, the catheter  10  can comprise a guidewire  56  disposed within a lumen of inner layer  20 . In certain embodiments, to deliver therapeutic or diagnostic agents, the guidewire  56  may be removed, thereby providing sufficient surface area within the catheter for effective flow of the agents. Alternatively, as discussed above, the inner layer  20 , may be removed, as illustrated in  FIGS. 16A-16C . As such, the lumen  150  will have an even greater cross-sectional area, which may be desirable for delivery of solid materials or for insertion of devices such as balloons or stents. 
         [0057]    As discussed previously, the devices of the present disclosure can be used for therapeutic interventions, including balloon dilation and/or stenting.  FIG. 17  illustrates a side view of a catheter including a balloon treatment device according to certain embodiments; and  FIGS. 18A-18C  illustrate side cutaway views of a catheter used to deliver a stent to a treatment site according to certain embodiments of the present disclosure. As shown, the devices  10  ( FIG. 17 ) can include a balloon dilation device  170  positioned on a portion thereof, or alternatively, a separate balloon catheter may be advanced over a guidewire positioned using the catheters described herein, or may be passed through a lumen of the catheters described herein. Furthermore, a stent or other therapeutic device can be passed through a lumen of the disclosed catheters after optionally removing the inner layer and/or guidewire and inserting a secondary catheter  184  carrying a stent  180  and deployment device  182 , as shown in  FIGS. 18A-18C . 
         [0058]    In some embodiments, the devices of the present disclosure can be used to access a desired anatomic site, and then to place a secondary catheter or treatment device. For example,  FIGS. 19A-19C  illustrate a method of positioning a secondary catheter or treatment device using various embodiments of the present invention. As shown in  FIG. 19A , a device  10  can be deployed to a desired anatomic site, and may include a guidewire  56 . After positioning the device  10  at the desired site, the catheter  10  may be removed, leaving only the guidewire  56  in place. Subsequently, a secondary device configured for a particular therapeutic or diagnostic application, but perhaps unable to be navigated to the desire site on its own, will be passed over the positioned guidewire  56 , thereby allowing positioning of the secondary catheter  11  or treatment device. 
         [0059]    As noted above, the devices of the present disclosure can include a handle region  57 , which can provide a variety of different structures and functional control for a clinician.  FIG. 20  illustrates a side cutaway view of a catheter with a handle region  57  according to certain. And  FIGS. 21A-21D  illustrate components of an actuator in a handle region  57  of a catheter according to certain embodiments. As shown, the handle  57  can include a button  210 , which can be attached to a cam  220 , and cam follower  224 . Further, as illustrated in  FIGS. 21A-21D , the cam follower  224  can move along a path from an extended position  FIG. 21B-21D , to a retracted position ( FIG. 21A ). As such, the cam follower  224 , which is operably attached to at least one of the inner and outer layers  20 , 22  provides longitudinal movement of the layers  20 , 22  relative to one another. Furthermore, the inner and out layers are held in either an in register or out of register position relative to one another, similar to the mechanism used to hold a “click pen” in an extended or retracted position. 
         [0060]    In addition,  FIG. 20  illustrates various other components of the devices of the present disclosure. As noted above, the devices can be used to deliver fluid, e.g., for therapeutic or diagnostic applications, and the handle may include one or more fluid ports  230 , 232 . In addition, the devices can include one or more radiopaque markers  260 , 270  on either or both of the inner or outer layers  20 , 22 , thereby allowing visualization of the catheters during use, and assisting in determining if the catheter is in a stiffer or flexible state. 
         [0061]      FIG. 20  further illustrates a space  240  between the inner and outer layers  20 , 22 . The space  240  may vary based upon the particular clinical use and dimensions of the device. However, the space  240  should be sized to allow the devices to bend at a high radius of curvature without producing excessive frictional contact between the layers  20 , 22 . In various embodiments, the space is 1-50 microns, or 30-70 microns, on all sides of the inner layer. 
         [0062]    In various embodiments, in order to allow ease of movement through lumens, and in order to provide for movement of the inner and out layer  20 , 22  relative to one another, even during large bends, the surfaces of the layers may be treated to reduce the friction between various components. For example,  FIGS. 22A-22B  illustrate side cutaway views of catheters incorporating lubricious coatings  23 , according to various embodiments. When rounding multiple tortuous bends with the catheter assembly, the increased area of direct contact between the two catheter layers  20 , 22  (due to pressing of the inner catheter against the one side of the outer catheter&#39;s inner surface) can generate friction that prevents shifting between the flexible and stiff states by restricting the movement of the inner catheter relative to the outer catheter. Accordingly, lubricioius coatings  23  may be used in order to reduce the coefficient of friction between the inner and outer catheter, and between the outer catheter and the anatomic sites such as blood vessel walls. The lubricating coatings  23  will be applied to the outer surface of the inner catheter, the outer surface of the outer catheter, and/or the inner surface of the outer catheter. Generally, the coatings  23  will be applied and cured prior to assembly of the inner catheter, outer catheter, and handle into a finished device. 
         [0063]    In various exemplary embodiments, the coatings  23  may be made of the from a variety of materials include a PTFE liner added on top of a mandrel (to coat inner surface of catheter) or on top of the catheter while on a mandrel (to coat outer surface of catheter), a hydrophilic synthetic polymer network that is applied by dip or brush coating and cured to the catheter surface by heat treatment, a hydrophilic synthetic polymer network that is applied by dip or brush coating and cured to the catheter surface by UV treatment, a hydrophilic synthetic polymer network that is applied by gaseous activation of the catheter surface and subsequent grafting onto catheter surface by polymer from aqueous solution, and/or hydrophilic natural polymer network (such as those based on hyaluronic acid) that is bonded to a base coat layer attached to the catheter surface. Further, although the coatings  23  can have a variety of sizes and material properties, exemplary coatings may have a thickness between 1 and 10 micrometers and a coefficient of friction between 0.005 and 0.03, or a reduction of up to 90% compared to uncoated coefficients of friction. Compatible with pebax base materials, and with common methods of sterilization (EtO, gamma irradiation, etc.). 
         [0064]    What has been described and illustrated herein is a preferred embodiment of the invention along with some of its variations. The terms, descriptions and figures used herein are set forth by way of illustration only and are not meant as limitations. Those skilled in the art will recognize that many variations are possible within the spirit and scope of the invention in which all terms are meant in their broadest, reasonable sense unless otherwise indicated. Any headings utilized within the description are for convenience only and have no legal or limiting effect.