Patent Document

[0001]    This application is a divisional of U.S. patent application Ser. No. 14/250,023 filed Apr. 10, 2014 which is incorporated by reference herein. 
     
    
     FIELD OF THE INVENTION 
       [0002]    This invention relates generally to medical imaging, endoprosthesis, and fabrication methods. 
       INCORPORATION BY REFERENCE 
       [0003]    All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. 
       BACKGROUND 
       [0004]    Endoluminal prostheses or endoprostheses are medical devices adapted to be implanted in a human or veterinary patient. Stents are a type of endoprosthesis which are deployed in blood vessel, urinary tract, bile duct, or other bodily lumen to provide structural support and optionally to deliver a drug or other therapeutic agent. Stents are generally cylindrical and function to hold open and sometimes expand a segment of the bodily lumen. Stents are often used in the treatment of atherosclerotic stenosis in blood vessels. Stents are often delivered to a desired location while in a reduced configuration having a smaller diameter than when fully deployed. The reduced configuration allows the stent to be navigated through very small passageways, such as coronary vessels and other bodily lumen. A crimping process is performed to place the stent in a reduced configuration. The stent can be crimped onto a catheter that can then be maneuvered over a guidewire that leads to a region of the anatomy at which it is desired to deploy the stent. The passageway through which the stent is maneuvered is often tortuous, so the stent should be capable of longitudinal flexibility. Once the stent has reached the desired deployment location, the stent is allowed to self-expand or is forcibly expanded by a balloon to an enlarged configuration. After deployment, the stent should maintain its enlarged configuration with minimal recoil back to its reduced configuration. All these functional requirements are taken into account in the structural design of a stent. 
         [0005]    In addition to the foregoing functional requirements, it is also important for a stent to have the capability of being visualized to determine whether the stent has been properly maneuvered to the desired location and to confirm that the stent has properly deployed. Various imaging techniques, such as fluoroscopy and optical coherence tomography, may be used to obtain an image of the stent. Fluoroscopy uses X-rays while optical coherence tomography uses optical radiation. 
         [0006]    Compared to metal stents, stents that have a polymeric substrate can be difficult to image due to their radiotranslucent and optically translucent properties. Structural features adjacent to the stent, such as parts of the anatomy and the catheter which carries the stent, can obscure the stent and make it difficult to ascertain its position. Radiopaque markers, such as metallic beads or metallic bands, can be embedded within or attached to the polymeric substrate so that the stent can be easily visualized using fluoroscopy. Radiopaque markers are relatively large in relation to the size of the stent substrate and can thereby affect stent function. Thus, stents often have only a few radiopaque markers which are strategically positioned. 
         [0007]    Optical coherence tomography (OCT) has been used to obtain images that show individual stent struts. OCT typically employs near-infrared light which can penetrate through structures, such as biological tissue, which scatter the light. Interferometric analysis of the scattered light is used to generate images which can have a resolution in the order micrometers. International Application Publication No. WO 2010045386 A describes the use of OCT to obtain images in which reflective surfaces of metal stent struts can be identified. However, stent struts having a polymeric substrate are not as reflective as metal substrates. 
         [0008]    OCT has been used to visualize stent struts made of a polymeric substrate. See Gutierrez-Chico et al., “Spatial Distribution and Temporal Evolution of Scattering Centers by Optical Coherence Tomography in the Poly(L-Lactide) Backbone of a Bioresorbable Vascular Scaffold” Circulation Journal, Vol. 76, 343-350 (Feb. 2012). Gutierrez-Chico et al. describe the appearance of “scattering centers” or SC, which is defined as a “focal hyperintense backscattering signal” in the core of the stent strut. All the scattering centers were located exclusively at hinges. In a bench study, there was a complete absence of scattering centers in all regions of stents which were not subjected to crimping. After crimping and deployment, however, there were scattering centers in all hinge regions. Analysis of successive image slices through the hinges of an implanted stent showed that the scattering centers were located at the inner curvature of the hinge. Scattering centers were absent from image slices taken through the outer curvature of the hinge. As compared to the inner curvature of the hinge, parts of the stent which experienced little or no mechanical deformation during crimping and deployment appeared as “black boxes” within a dark field. The black boxes could be identified by a faint outline corresponding to the external surfaces of the stent structure. 
         [0009]    There is a need for an imaging method, stent manufacturing method, and stent which allow for improved OCT imaging that can make it easier to determine where the stent structure begins or ends within a bodily lumen and make it easier to evaluate whether the stent has been properly deployed and is supporting surrounding tissue. 
       SUMMARY 
       [0010]    Described herein are an endoprosthesis, a method of imaging an endoprosthesis, and a method of making an endoprosthesis. 
         [0011]    Various aspects of the invention are directed to a method for imaging an endoprosthesis having a substrate that has been modified by a laser to have voids embedded within the substrate. The voids are sized to increase scattering of optical radiation from within the substrate. The method comprises passing optical radiation across an external surface of the substrate of the endoprosthesis, and obtaining an image by optical coherence tomography (OCT) processing of light that has been scattered by the voids from within the substrate. The obtained image includes an image signal corresponds to an interior substrate portion having the voids. The image signal differentiates the interior substrate portion having the voids from empty space outside of the substrate. 
         [0012]    Various aspects of the invention are directed to a method of making an endoprosthesis. The method comprises modifying a substrate of an endoprosthesis with a laser to form voids embedded within the substrate. The voids are sized to scatter optical radiation from within the substrate so as to produce an optical coherence tomography (OCT) image that distinguishes an interior region of the substrate from empty space outside of the substrate. 
         [0013]    Various aspects of the invention are directed to an endoprosthesis comprises a plurality of radially deformable rings. Each ring comprises a polymeric substrate, and a plurality of voids is embedded within at least a portion of the substrate. The voids are sized to scatter optical radiation that has passed across an external surface of the substrate to produce an optical coherence tomography (OCT) image that distinguishes an interior region of the substrate from empty space outside of the substrate. 
         [0014]    The features and advantages of the invention will be more readily understood from the following detailed description which should be read in conjunction with the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0015]      FIG. 1  is a perspective view showing an endoprosthesis being modified to increase its ability to reflect and scatter light from within the substrate of the endoprosthesis. 
           [0016]      FIG. 2  is a perspective view showing another endoprosthesis being modified to increase its ability to reflect and scatter light from within the substrate. 
           [0017]      FIG. 3  is a perspective view showing the endoprosthesis of  FIG. 2  after being deployed in a lumen. 
           [0018]      FIG. 4  is a cross-section view showing the endoprosthesis of  FIG. 3  while deployed in the lumen. 
           [0019]      FIGS. 5 and 6  are simulated optical coherence tomography (OCT) images of a stent, such as the endoprosthesis in  FIG. 4 . 
           [0020]      FIGS. 7-9  are cross-section showing a substrate after being modified to have voids that increase light scattering from within the substrate, 
           [0021]      FIG. 10  is a plan view showing a hinge of an endoprosthesis through which the cross-sections of  FIGS. 7-9  may be taken. 
           [0022]      FIG. 11  is a perspective view showing an endoprosthesis that can be modified to increase its ability to reflect and scatter light from within the substrate. 
           [0023]      FIGS. 12A and 12B  are photographs showing an endoprosthesis, in crimped and deployed states, that can be modified to increase its ability to reflect and scatter light from within the substrate. 
       
    
    
     DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS 
       [0024]    As used herein, an endoprosthesis is a device that can be implanted in a human or veterinary patient. Examples of such devices include without limitation self-expandable stents, balloon-expandable stents, stent-grafts, grafts (e.g., aortic grafts), heart valve prosthesis (e.g., artificial heart valves), vascular graft, and shunts. 
         [0025]    Referring now in more detail to the exemplary drawings for purposes of illustrating embodiments of the invention, wherein like reference numerals designate corresponding or like elements among the several views, there is shown in  FIG. 1  endoprosthesis  10  in the form of a tube without fenestrations. The tube can be made by extruding or molding polymeric material, or the tube can be made by rolling a sheet of polymeric material. The tube has polymeric substrate  12 . The term “substrate” refers to the structural support material. After endoprosthesis  10  is implanted in a patient, the strength of substrate  12  allows the endoprosthesis to provide support to surrounding tissue or perform any other intended function. Optionally, substrate  12  may be covered by a relatively thin coating from which a drug or other therapeutic agent may be released into a patient. 
         [0026]    As will be discussed in more detail below, when an optical coherence tomography (OCT) technique is used, optical radiation is emitted toward polymeric substrate  12 . External surfaces of the endoprosthesis scatter the light due to a change in the index of refraction between the external surface and a fluid (i.e., air or liquid) adjacent to the external surface. External surfaces include luminal surface  14  and abluminal surface  16 . The term “luminal surface” refers to the radially inward facing surface or the surface that faces toward central passageway or lumen  18  of endoprosthesis  10 . The term “abluminal surface” refers to the radially outward facing surface or the surface that faces away from central lumen  18 . The light scattered from external surfaces can provide an OCT image that shows an outline of the external surfaces. As used herein, the term “OCT image” is an image that is produced using an OCT technique. 
         [0027]    Laser modifying device  20  is used to modify substrate  12  to increase its ability to reflect and scatter light from within substrate  12 . The modification creates changes in the index of refraction within substrate  12 . After the modification, optical radiation from an OCT technique will penetrate through the external surfaces and then be reflected and scattered from within the substrate, such that an OCT image can show an image signal from inside the substrate that would normally not be present. 
         [0028]    As shown in  FIG. 2 , endoprosthesis  10  can be a stent in the form of tubular scaffold. The tubular scaffold is a tube with fenestrations  22 . The term “fenestrations” refers to holes or gaps through the wall of the tube. Endoprosthesis  10  includes a plurality of radially deformable rings  24 . Each ring  24  comprising a series of ring struts  26 . Each ring strut  26  is connected by hinge  28  to adjacent ring strut  26 . Ring struts  26  and hinges  28  are constructed of polymeric substrate  12 . The strength and elasticity of substrate  12  allows endoprosthesis  10  to be crimped to a reduced configuration, deployed to an enlarged configuration, and then provide support to surrounding tissue. Each ring  24  is connected by hinges  28  (further identified with the letter “A”) to adjacent ring  24 . All hinges  28  are configured to bend during crimping and deployment of endoprosthesis  10 . During crimping and deployment, hinges  28  mechanically deform to allow a change in overall outer diameter  30  of each ring  24 . End rings  24  (further identified with the letter “E”) are located at opposite ends of endoprosthesis  10 . 
         [0029]    Fenestrations  22 , ring struts  26 , and hinges  28  can be formed during an injection molding process using a mold having a cavity with a shape that corresponds to the shape of the fenestrations, ring struts, and hinges. Molten polymeric material can be injected into the mold to form the scaffold of  FIG. 2 . After the polymeric material has been cooled and hardened, the tube can be removed from the mold and then laser modifying device  20  can be used to modify substrate  12 . 
         [0030]    Alternatively, fenestrations  22 , ring struts  26 , and hinges  28  can be formed by cutting away material from a tube of polymeric material. Optionally, the tube of polymeric material can be made by extruding a polymer through a die to form a precursor tube. The precursor tube can be radially expanded by a blow molding process to induce polymer molecule chains to have a preferential orientation that provides desirable structural characteristics. Blow molding can be performed as described in U.S. Publication No. 2011/0066222 A1. After blow molding, material is cut away from the radially expanded tube to form the scaffold of  FIG. 2 . Cutting can be performed as described in U.S. Publication No. 2007/0283552 A1. Cutting can be performed using a mechanical knife, a cutting laser device, or other device. After material is cut away from the radially expanded tube to form ring struts  26  and hinges  28 , laser modifying device  20  can be used to modify substrate  12  to increase the ability of the substrate to reflect and scatter light from within the substrate. In further embodiments, the modification process using laser modifying device  20  can be performed at a time between completion of blow molding and the start of cutting. 
         [0031]    In another alternative, fenestrations  22 , ring struts  26 , and hinges  28  can be formed by cutting away material from a flat sheet of polymeric substrate material, which is then rolled to form the scaffold of  FIG. 2 . Cutting can be performed using a mechanical knife, a cutting laser device, or other device. After material is cut away from the flat sheet, laser modifying device  20  can be used to modify substrate  12  to increase the ability of the substrate to reflect and scatter light from within the substrate. Alternatively, the modification process using laser modifying device  20  can be performed before material is cut away. 
         [0032]    As mentioned above, a cutting laser device can be used to cut away material to form fenestrations  22 , ring struts  26 , and hinges  28 . The cutting laser device is adjusted to cut entirely through the wall thickness of the tube. The cutting laser device can be a femtosecond laser modifying device which is controlled in terms of power, pulse duration, pulse repetition rate, wavelength, focus, and other laser device variables in order to remove material and cut completely through the substrate material. As discussed in U.S. Publication No. 2011/0307050 A1, the laser device variables can be set such that there is minimal disruption to the substrate material below the surface being cut. 
         [0033]    Laser modifying device  20  can be a femtosecond laser modifying device, which can be the same laser device which was used to cut away material or a different laser device. In order to modify the interior of substrate  12  to increase light reflection and scattering from within the substrate, laser modifying device  20  is controlled in terms of power, pulse duration, pulse repetition rate, wavelength, focus, and other variables so as not to cut entirely through the substrate material. Settings for the laser device variables used to modify the interior of substrate  12  are different than settings used to cut entirely through the substrate material to produce fenestrations  22 , ring struts  26  and hinges  28 . To modify the interior of substrate  12 , the laser device variables are controlled to produce tiny gas-filled voids below the surface of substrate  12 . The laser modifying device can focus one or more laser beams onto a region below an external surface of substrate  12  to induce a nonthermal and photochemical process that breaks chemical bonds in the region below the external surface, which results in the gas-filled voids. Due to translucency of the substrate material, the external surface above the gas-filled voids can remain in place and undamaged. In some instances, the external surface above the gas-filled voids can remain in place with some alteration but still cover over the gas-filled voids. During the modification process, cool air may be blown onto the external surface to prevent or minimize disruption of the external surface. 
         [0034]    The gas-filled voids can have a diameter or interior dimension that is greater than 1 μm, greater than 2 μm, or greater than 3 μm. Although the term “diameter” is used to describe the size of the gas-filled voids, it should be understood that the gas-filled voids can be irregularly shaped, ellipsoid in shape, or spherical in shape. The gas-filled voids can have any enclosed shape. The term “enclosed shape” means that the void does not open to an external surface of substrate  12 . Voids having the aforementioned diameters can be located at a depth below the external surface nearest the void, the depth being more than 2 μm, more than 10 μm, or more than 30 μm. Each void within substrate  12  provides an interface between gas and polymer, which is also referred to as a gas-polymer interface. The gas-polymer interface corresponds to a change in the index of refraction between gas and polymer, which causes light radiation passing through the external surface to scatter upon reaching the voids. In an OCT technique, the scattered light is processed to produce an OCT image having an increase in image signal intensity from within substrate  12  as compared to a region of the substrate that does not have gas-filled voids. 
         [0035]      FIG. 2  shows endoprosthesis  10  before it has been crimped to a reduced configuration. After laser modifying device  20  is used to modify substrate  12 , endoprosthesis  10  can be crimped onto a catheter so that endoprosthesis  10  has a reduced configuration, and then deployed to an enlarged configuration within a blood vessel or other bodily lumen. 
         [0036]    Alternatively, laser modifying device  20  can be used to modify substrate  12  after it has been crimped onto a catheter. The laser beam can be carefully controlled, such as by use of a feedback camera, to avoid the catheter beneath the substrate. After the substrate  12  is modified to have gas-filled voids, endoprosthesis  10  can be deployed within a blood vessel or other bodily lumen. 
         [0037]      FIG. 3  shows endoprosthesis  10  after substrate  12  has been modified using laser modifying device  20  and after endoprosthesis  10  has been deployed with lumen  40 . For example, after the interior of substrate  12  has been modified to have gas-filled voids, a catheter can be used to maneuver endoprosthesis  10  to a desired location while endoprosthesis  10  is in a reduced configuration. When at the desired location, endoprosthesis  10  is allowed to expand or is forcibly expanded to an enlarged configuration. Abluminal surfaces  16  of endoprosthesis  10  provide support to lumen walls  42  which are shown in cross-section. Lumen walls  42  can be, for example, the walls of a blood vessel or other bodily lumen. 
         [0038]      FIG. 4  shows a length-wise slice of endoprosthesis  10  of  FIG. 3 . Polymeric substrate  12  of endoprosthesis  10  was modified to have gas-filled voids before endoprosthesis  10  was deployed in lumen  40 . The slice shows the entire longitudinal length  11  of endoprosthesis  10 . The small rectangles  44  are schematic representations of ring struts  26  and hinges  28  intersected by the slice. Catheter  50  is inserted through central lumen  18  of endoprosthesis  10 . Catheter  50  has a fiber optic wire that is configured to emit light radially outward, such as in the direction of arrow  46 , toward endoprosthesis portions  44 . The light passes through the external surfaces of endoprosthesis portions  44  and lumen wall  42  and is reflected and scattered from within endoprosthesis portions  44  and lumen wall  42 . The fiber optic wire of catheter  50  is configured to sense the light scattered by endoprosthesis portions  44  and lumen wall  42 . While emitting light and sensing scattered light, catheter  50  can be rotated about its axis, such as in the direction of arrow  52 , and simultaneously pulled axially, such as in the direction of arrow  54 . Rotation and pulling allow light to be scattered and then sensed from the entire longitudinal length  11  of endoprosthesis  10  and from the entire circumference of each ring  24 . 
         [0039]    Catheter  50  is coupled to a processor, which is schematically represented by box  56 . Processor  56  is configured to apply interferometric processing to the scattered light sensed by catheter  50  to generate image data representative of endoprosthesis  10  and lumen wall  42  that surrounds endoprosthesis  10 . The image data can be used to generate a plurality of images, each image being a circumferential slice taken at a different position along longitudinal length  11  of endoprosthesis  10 . For example, one of the images can be that of a circumferential slice at plane  59  to show a stent ring at middle segment  15  of endoprosthesis  10 . Other images can be that of circumferential slices at planes  58  and  60  to show end rings  24 E at opposite end segments of endoprosthesis  10 . The opposite end segments are distal end segment  13  and proximal end segment  17  of endoprosthesis  10 . The image data can also be used to generate a three-dimensional image of endoprosthesis  10 . 
         [0040]    Catheter  50  and processor  56  can be configured for OCT imaging. In which case, catheter  50  can be configured to emit infrared light that passes through the external surfaces of endoprosthesis portions  44  and lumen wall  42 . As used herein, the term “infrared light” encompasses any wavelength from a nominal red edge of the visible spectrum at 700 nanometers (nm) to 1 mm. The infrared light can be short wavelength infrared (1.4 to 3 μm wavelength), near-infrared light (0.75 to 1.4 μm wavelength), mid-infrared light (6 to 8 μm wavelength), or other infrared wavelengths. Selection of wavelength can depend on the specific polymeric substrate material of endoprosthesis  10  and the desired depth through tissue at which an image is to be taken. 
         [0041]    Catheter  50  can be configured to sense the near-infrared light (or other light wavelength mentioned above) that was scattered from within endoprosthesis portions  44  and lumen wall  42 . Processor  56  can be configured to apply OCT processing techniques to the scattered light sensed by catheter  50  to generate image data representative of endoprosthesis  10  and lumen wall  42 . Image data for the entire longitudinal length of the endoprosthesis can be obtained by rotating and pulling catheter  50  as previously described. 
         [0042]      FIG. 5  shows a simulated OCT image showing a circumferential slice of one or more stent rings  24  of endoprosthesis  10  of  FIGS. 3 and 4  deployed in lumen  40 . Image signals, which appear light in color in  FIG. 5 , represent regions from which light was scattered after the light was emitted from a central region of lumen  40  represented generally by a “+” mark. The substrate material of the stent ring has not been modified to increase the ability of the substrate to reflect and scatter light from within the substrate. Thus, portions of substrate  12  intersected by the slice have image signals (appearing as a light color rectangle) that identify the external surfaces of substrate  12 . The absence of an image signal from within substrate  12  causes the area within the substrate to appear dark in the OCT image. The color of the interior region within substrate  12  is that same as that of the empty space at the center of lumen  40 . Structures within lumen wall  42  surrounding the endoprosthesis scatter light and thus provide a ring-shaped image in which the strength of the image signal fades or becomes weaker with increasing distance from the OCT light source near the “+” mark. 
         [0043]      FIG. 6  shows a simulated OCT image showing a circumferential slice of one or more stent rings  24  of endoprosthesis  10  of  FIGS. 3 and 4 . The OCT image is similar to that of  FIG. 5  except substrate  12  has been modified to increase the ability of the substrate to reflect and scatter light from within the substrate. Thus, portions of substrate  12  in the slice have image signals (appearing as a light color rectangle) that identify the external surfaces of substrate  12 , and they also have image signals within substrate  12  that causes the area within the substrate to appear bright. The image signal intensity from the interior of substrate  12  in  FIG. 6  is greater than that in  FIG. 5 . Also, the region within substrate  12  is much brighter than the empty space at the center of lumen  40 . In  FIG. 6 , the increase in brightness from within substrate  12  can help distinguish endoprosthesis structures from the empty space and from surrounding lumen walls  42 . 
         [0044]    In some embodiments, middle segment  15  of endoprosthesis  10  has not been modified by laser modifying device  20  in the manner described above. Substrate  12  in the middle segment does not have gas-filled voids that increase the ability of the substrate to reflect and scatter light from within the substrate. End segments  13  and  17  of endoprosthesis  10  have been modified by laser modifying device  20  to have gas-filled voids that increase the ability of the substrate to reflect and scatter light from within the substrate. In these embodiments, the simulated OCT image of  FIG. 5  may represent a circumferential slice taken through plane  59  in  FIG. 4 , and the simulated OCT image of  FIG. 6  may represent circumferential slices taken through planes  58  and  60  in  FIG. 4 . 
         [0045]    In other embodiments, end segments  13  and  17  of endoprosthesis  10  have not been modified by laser modifying device  20  in the manner described above. Substrate  12  in end segments  13  and  17  do not have gas-filled voids that increase the ability of the substrate to reflect and scatter light from within the substrate. Middle segment  15  of endoprosthesis  10  has been modified by laser modifying device  20  to have gas-filled voids that increase the ability of the substrate to reflect and scatter light from within the substrate. In these embodiments, the simulated OCT image of  FIG. 5  may represent circumferential slices taken through planes  58  and  60  in  FIG. 4 , and the simulated OCT image of  FIG. 6  may represent a circumferential slice taken through plane  59  in  FIG. 4 . It is possible to modify substrate  12  in end rings  24 E exclusively to help determine where the endoprosthesis structure begins and ends when implanted in lumen  40 . 
         [0046]    In yet other embodiments, substrate  12  throughout longitudinal length  11  of endoprosthesis  10  has been modified by laser modifying device  20  to have gas-filled voids that increase the ability of the substrate to reflect and scatter light from within the substrate. In these embodiments, the simulated OCT image of  FIG. 6  may represent circumferential slices taken through planes  58 ,  59 , and  60  in  FIG. 4  and anywhere else along longitudinal length  11  of endoprosthesis  10 . 
         [0047]    As discussed above, substrate  12  can be modified to have gas-filled voids in order to distinguish some longitudinal segments (e.g., end segments) from other longitudinal segments (e.g., a middle segment). Also, substrate  12  of one or more rings  24  can be modified to have gas-filled voids in ring struts  26  but not modified to have gas-filled voids in hinges  28  so as not to affect the elasticity and strength of the hinges. Further, substrate  12  throughout longitudinal length  11  of endoprosthesis  10 , except hinges  28 , can be modified by laser modifying device  20  to have gas-filled voids that increase the ability of the substrate to reflect and scatter light from within the substrate. As discussed below, substrate  12  can also be modified to distinguish a surface of the endoprosthesis (e.g., abluminal surface) from another surface of the endoprosthesis (e.g. luminal surface). 
         [0048]      FIG. 7  shows a cross-section of a portion of substrate  12  which has been modified by laser modifying device  20  to have gas-filled voids  70  that increase the ability of the substrate to reflect and scatter light from within the substrate. Gas-filled voids  70  have a non-uniform spatial density as viewed in the illustrated cross-section of substrate  12 . As used herein, “spatial density” refers to the total number of voids per unit area. For example, spatial density can be measured in terms of the total number of voids per 1000 μm 2 . The spatial density decreases with increasing distance from abluminal surface  16 . The spatial density is greater in area  72  adjacent to abluminal surface  16  of the endoprosthesis as compared to area  74  adjacent to luminal surface  14 . Areas  72  and  74  are interior substrate portions. The greater spatial density in area  72  corresponds to a greater number of gas-polymer interfaces in area  72 , which results in a greater scattering of light and thus a greater OCT image signal that could enhance visualization of abluminal surface  16 . 
         [0049]      FIG. 8  shows a cross-section of a portion of substrate  12  which has been modified by laser modifying device  20  to have gas-filled voids  70  that increase the ability of the substrate to reflect and scatter light from within the substrate. The spatial density increases with increasing distance from abluminal surface  16 . The spatial density of gas-filled voids  70  is greater in area  74  as compared to area  72 . The greater spatial density in area  74  could enhance visualization of luminal surface  14 . 
         [0050]    A greater spatial density can be created in a preferred area (either area  72  or  74 ) by controlling laser modifying device  20  to create more gas-filled voids in the preferred area. For example, laser modifying device  20  can be configured to focus energy in the preferred area instead of another area of substrate  12 . Also, laser modifying device  20  can be arranged to emit a laser beam that enters substrate  12  from one of the external surfaces (abluminal surface  16  or luminal surface  14 ) that is closest to the preferred area. 
         [0051]      FIG. 9  shows a cross-section of a portion of substrate  12  which has been modified by laser modifying device  20  to have gas-filled voids  70  that increase the ability of the substrate to reflect and scatter light from within the substrate. The spatial density of gas-filled voids  70  in area  72  is about the same as that in area  74  so that there is a substantially uniform spatial density. The terms “about the same” and “substantially uniform” mean that the number of gas-filled voids in area  72  can be within plus or minus 20% of the number of gas-filled voids in area  74 . The substantially uniform spatial density can be created by controlling laser modifying device  20  to create about the same number of gas-filled voids in areas  72  and  74 . For example, laser modifying device  20  can be configured to focus about the same amount of energy in areas  72  and  74 . Also, laser modifying device  20  can be arranged to emit a laser beam that enters substrate  12  from one of the external surfaces (abluminal surface  16  or luminal surface  14 ) and then, at a later time, emit a laser beam that enters substrate  12  from the opposite external surface. 
         [0052]    In  FIGS. 7-9 , the illustrated cross-sections of substrate  12  can be that of ring strut  26 , hinge  28  or any other part of endoprosthesis  10 , such as link strut  27  of  FIGS. 11 and 12B . The illustrated cross-section can be a longitudinal cross section, similar in orientation to the substrate cross-sections shown in  FIG. 4 . The illustrated cross-section can be circumferential cross sections, similar in orientation to the substrate cross-sections shown in  FIG. 6 . 
         [0053]    The cross-sections of  FIGS. 7-9  show luminal surface  14  and abluminal surface  16  which face in opposite directions. Side surfaces  76  and  78  connect luminal surface  14  to abluminal surface  16 . Gas filled voids  70  are encapsulated within substrate  12 . Gas filled voids  70  are sealed within luminal surface  14 , abluminal surface  16 , and side surfaces  76  and  78 . Gas filled voids  70  are not necessarily illustrated to scale. Gas-filled voids  70  can have a diameter or interior dimension that is greater than 1 μm, greater than 2 μm, or greater than 3 μm. Gas-filled voids  70  can be located at a depth beyond the external surface nearest the void, the depth being greater than 2 μm, greater than 10 μm, greater than 30 μm, greater than 50 μm, or not greater than 50 μm. For example, gas-filled voids  70  can be located at depths greater than 2 μm, greater than 10 μm, greater than 30 μm, or greater than 50 μm from any one or more of luminal surface  14 , abluminal surface  16 , side surface  76 , and side surface  78 . As further example, there can be gas-filled voids at depths up to 50 μm but not greater than 50 μm as measured from any one of luminal surface  14 , abluminal surface  16 , side surface  76 , and side surface  78 . 
         [0054]    Side surfaces  76  and  78  can be formed by a laser cutting device which cuts entirely through a sheet or tube of polymeric substrate material to form fenestrations  22 , ring struts  26 , hinges  28 , and other parts of endoprosthesis  10 . In some embodiments, area  72  is an area of substrate  12  adjacent to abluminal surface  16  and which extends from one side surface  76  to the opposite side surface  78 . Area  74  is an area of substrate  12  adjacent to luminal surface  14  and which extends from one side surface  76  to the opposite side surface  78 . The distance from side surface  76  to opposite side surface  78  is referred to as the width of the cross-section. 
         [0055]    Optionally, coating  80  can be applied on an external surface of substrate  12 , such as by spraying, dipping, or other method. Gas-filled voids  70  are sealed within coating  80 . Coating  80  may include a polymeric coating material. Coating  80  may also include a drug or other type of therapeutic agent carried by the polymeric coating material. Substrate  12  may be modified to have gas-filled voids before or after coating  80  is applied on substrate  12 . To avoid damage to substances in coating  80 , substrate  12  is preferably modified by laser modifying device  20  to have gas-filled voids before coating  80  is applied on substrate  12 . 
         [0056]    Referring to  FIG. 10 , the illustrated cross-sections of  FIGS. 7-9  can be a slice through plane  81  at inner curvature  82  of hinge  28 . The illustrated cross-sections of  FIGS. 7-9  can be a slice through plane  84  at outer curvature  86  of hinge  28 . Geometric central axis  88  separates inner curvature  82  from outer curvature  86 . Geometric central axis  88  is centered between side surfaces  90  and  92 . 
         [0057]    It is to be understood that that the structural pattern for endoprosthesis  10  is not necessarily limited to what is depicted in  FIGS. 2 and 3 . The structural pattern refers to the arrangement, and orientation of rings and of the various struts, hinges, and other structural elements. The structural pattern can be any of the stent patterns described in U.S. Pat. Nos. 7,476,245 and 8,002,817. The stent can have virtually any stent pattern suitable for a polymer substrate. 
         [0058]    Referring to  FIG. 11 , endoprosthesis  10  can have a strut pattern having radially deformable rings  24  connected to each other by link struts  27 . Opposite ends of link struts  27  meet hinges  28  of adjacent rings  24 . Substrate  12  of link struts  27  can be modified to have gas-filled voids  70  in the manner described above in  FIGS. 7-9  and in the same manner described above for any part of the endoprosthesis of  FIGS. 3 and 4 . 
         [0059]      FIGS. 12A and 12B  show photographs of endoprosthesis  10  having radially deformable rings  24  which are interconnected by link struts  27  similar to the scaffold shown in  FIG. 11 . Substrate  12  of endoprosthesis  10  is made of poly(L-lactic acid) which was extruded to form a precursor tube, then radially expanded by blow molding, and then cut using a laser cutting device to form the scaffold. In  FIG. 12A , the scaffold has been crimped to a reduced configuration on a balloon catheter. In  FIG. 12B , the scaffold has been forcibly expanded to an enlarged configuration in which the inner diameter of each ring  24  is 3.5 mm. Expansion is accomplished by inflation of balloon  96  of the catheter. Compared to ring struts  26  and link struts  27 , it is the hinges  28  that perform most of the bending and flexing needed to allow the diameter of endoprosthesis  10  to be reduced during crimping and enlarged during subsequent expansion. As can be seen in  FIGS. 12A and 12B , ring struts  26  and link struts  27  remain substantially straight during crimping and expansion. Substrate  12  can be modified to have gas-filled voids before or after being crimped on a catheter. During the modification process, the optical translucency of substrate  12  allows energy from laser modifying device  20  to pass across the external surface of the substrate and induce a process that breaks chemical bonds in the region below the external surface, which results in the gas-filled voids within the substrate. Substrate  12  of endoprosthesis  10  can be modified to have gas-filled voids in ring struts  26 , link struts  27 , and hinges  28 . Alternatively, substrate  12  of endoprosthesis  10  can be modified to have gas-filled voids in ring struts  26  and link struts  27  but not modified to have gas-filled voids in hinges  28  so as not to affect the elasticity and strength of the hinges. During an OCT imaging process, the optical translucency of the substrate allows light directed toward the substrate to pass across the external surface of the substrate and be scattered by gas-filled voids. Scattering of light from within the substrate increases the image signal of the endoprosthesis structure. 
         [0060]    In any of the above embodiments, substrate  12  is made of a material that is not metal. In any of the above embodiments, substrate  12  is made of a polymeric substrate material that can be penetrated by near-infrared light (or other light wavelength mentioned above) used in an OCT technique. The polymeric substrate material can be bioresorbable. 
         [0061]    As used herein, the terms “biodegradable,” “bioabsorbable,” “bioresorbable,” and “bioerodable” are used interchangeably and refer to materials that are capable of being completely degraded, eroded, and/or dissolved when exposed to bodily fluids such as blood and can be gradually resorbed, absorbed, and/or eliminated by the body. The processes of breaking down and absorption of the polymer can be caused by, for example, hydrolysis and metabolic processes. 
         [0062]    The polymeric substrate material can be poly(lactic acid) or a polymer based on poly(lactic acid). Polymers based on poly(lactic acid) include graft copolymers, block copolymers, such as AB block-copolymers (“diblock-copolymers”) or ABA block-copolymers (“triblock-copolymers”), and mixtures thereof. Examples of polymeric substrate materials include without limitation poly(lactide-co-glycolide), poly(glycolic acid), poly(glycolide), poly(L-lactic acid), poly(L-lactide) (PLLA), poly(D,L-lactic acid), and poly(caprolactone) (PCL) copolymers. As a further example, substrate  12  can be made from a PLLA/PCL copolymer. 
         [0063]    The coating that is optionally applied on substrate  12  can include a polymer, examples of which include without limitation ethylene vinyl alcohol copolymer (commonly known by the generic name EVOH or by the trade name EVAL), poly(butyl methacrylate), poly(vinylidene fluoride-co-hexafluororpropene) (e.g., SOLEF 21508, available from Solvay Solexis PVDF, Thorofare, N.J.), polyvinylidene fluoride (otherwise known as KYNAR, available from ATOFINA Chemicals, Philadelphia, Pa.), ethylene-vinyl acetate copolymers, and polyethylene glycol. 
         [0064]    The coating that is optionally applied on substrate  12  can include a drug or other therapeutic agent, examples of which include without limitation sirolimus (rapamycin), everolimus, zotarolimus, Biolimus A9, AP23572, tacrolimus, pimecrolimus and derivates or analogs or combinations thereof. The therapeutic agent can be an antiproliferative, antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic, antiallergic, or antioxidant substance. 
         [0065]    The methods described above for modifying substrate  12  to have gas-filled voids to facilitate OCT imaging can be applied to a polymeric substrate in various implantable medical devices, such as pacemaker electrodes, and catheters. 
         [0066]    While several particular forms of the invention have been illustrated and described, it will also be apparent that various modifications can be made without departing from the scope of the invention. It is also contemplated that various combinations or subcombinations of the specific features and aspects of the disclosed embodiments can be combined with or substituted for one another in order to form varying modes of the invention. Accordingly, it is not intended that the invention be limited, except as by the appended claims.

Technology Category: 3