Abstract:
An apparatus for radially centering a treatment region of a brachytherapy catheter in a lumen of a body vessel. The centering apparatus includes a monofilament wire-form that is pre-shaped to have an expanded configuration having multiple lobes arranged in a radially symmetrical staggered sequence along the treatment region of the catheter. The centering apparatus also has a collapsed configuration that is formable about the catheter by drawing apart the ends of the wire-form. This abstract is provided to comply with the rules requiring an abstract which will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. 37 CFR 1.72(b)

Description:
FIELD OF THE INVENTION  
         [0001]    The invention relates to catheters used for localized delivery of therapeutic radiation within a vessel of a patient and, in particular, to a wire-form centering the catheter in the vessel.  
         BACKGROUND OF THE INVENTION  
         [0002]    Stenosis is a narrowing or constriction of a duct or canal. A variety of disease processes, such as atherosclerotic lesions, immunological reactions, congenital abnormalities and the like, can lead to stenoses of arteries or ducts. In the case of stenosis of a coronary artery, this typically leads to myocardial ischemia. Percutaneous transluminal coronary angioplasty (PTCA), the insertion and inflation of a balloon catheter in a coronary artery to affect its repair, is widely accepted as an option in the treatment of obstructive coronary artery disease. In general, PTCA is used to increase the lumen diameter of a coronary artery that is partially or totally obstructed by a build-up of cholesterol fats or atherosclerotic plaque. In PTCA, a coronary guiding catheter provides a channel from outside the patient to the ostium of a coronary artery. Then, a balloon catheter is advanced over a small diameter, steerable guidewire through the guiding catheter, into the artery, and across the stenosis. The balloon is inflated to expand the narrowing. Dilatation of the occlusion, however, can form flaps, fissures and dissections which threaten abrupt reclosure of the dilated vessel or even perforations in the vessel wall. To treat or prevent such sequelae, tubular stents are often placed within the angioplasty site to scaffold the vessel lumen.  
           [0003]    Other invasive vascular therapies include atherectomy (mechanical removal of plaque residing inside an artery), laser ablative therapy and the like. While the stenosis or occlusion is greatly reduced using these therapies, many patients experience a recurrence of the stenosis over a relatively short period. Restenosis, defined angiographically, is the recurrence of a 50% or greater narrowing of a luminal diameter at the site of a prior therapy. Additionally, researchers have found that angioplasty or placement of a stent in the area of the stenosis can irritate the blood vessel and cause rapid reproduction of the cells in the medial layer of the blood vessel, developing restenosis through a mechanism called medial hyperplasia. Restenosis is a major problem which limits the long-term efficacy of invasive coronary disease therapies. Additionally, the rapid onset of restenosis is compounded by the lack of ability to predict which patients, vessels, or lesions will undergo restenosis.  
           [0004]    Although the mechanism of restenosis is not fully understood, clinical evidence suggests that restenosis results from a migration and rapid proliferation of a subset of predominately medially derived smooth muscle cells, which is apparently induced by the injury from the invasive therapy. Such injury, for example, is caused by the angioplasty procedure when the balloon catheter is inflated and exerts pressure against the artery wall, resulting in medial tearing. It is known that smooth muscle cells proliferate in response to mechanical stretch and the resulting stimulation by a variety of growth factors. Also, intimal hyperplasia can contribute to restenosis, stimulated by the controlled therapeutic injury. It is believed that such proliferation stops one to two months after the initial invasive therapy procedure but that these cells continue to express an extracellular matrix of collagen, elastin and proteoglycans. Additionally, animal studies have shown that during balloon injury, denudation of endothelial cells can occur, followed by platelet adhesion and aggregation, and the release of platelet-derived growth factor (PDGF) as well as other growth factors. As mentioned above, this mass of tissue can contribute to the re-narrowing of the vascular lumen in patients who have restenosis. It is believed that a variety of biologic factors are involved in restenosis, such as the extent of the tissue injury, platelets, inflammatory cells, growth factors, cytokines, endothelial cells, smooth muscle cells, and extracellular matrix production, to name a few.  
           [0005]    It has been found that irradiating the blood vessel walls at the treatment site can reduce or prevent hyperplasia. Accurate control over the amount of radiation is important, since insufficient radiation will not prevent restenosis and excessive radiation can further damage the blood vessel or surrounding tissues. To prevent unnecessary radiation beyond the site of the stenosis, it is preferable to introduce a small radiation source into the treated vessel. There are numerous types of radiation catheters for this purpose. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0006]    The present invention will be understood and appreciated more fully from the following detailed description taken in conjunction with the appended drawings in which:  
         [0007]    [0007]FIG. 1 is a plan view of a partial longitudinal cross-section of a catheter according to the invention, with a centering wire expanded against the lumen of a body vessel;  
         [0008]    [0008]FIG. 2 is an elevation view of the embodiment according to the invention shown in FIG. 1;  
         [0009]    [0009]FIG. 3 is a transverse sectional view of a catheter according to the invention, taken on line  3 - 3  of FIG. 1;  
         [0010]    [0010]FIG. 4 is a transverse sectional view of a catheter according to the invention with an alternative embodiment of the centering wire expanded against the lumen of a body vessel;  
         [0011]    [0011]FIG. 5 is a transverse sectional view of a catheter according to the invention with another alternative embodiment of the centering wire expanded against the lumen of a body vessel;  
         [0012]    FIGS.  6 - 14  are isometric views of alternative embodiments of the centering wire according to the invention, shown in the expanded configuration;  
         [0013]    [0013]FIG. 15 is a longitudinal view of the distal portion of a catheter according to the invention, with a centering wire expanded;  
         [0014]    [0014]FIG. 16 is a longitudinal view of the distal end of the catheter embodiment shown in FIG. 15, with the centering wire collapsed;  
         [0015]    [0015]FIG. 17 is a longitudinal view of the distal end of an alternative embodiment of a catheter according to the invention, with the centering wire expanded;  
         [0016]    [0016]FIG. 18 is a longitudinal view of the distal end of the catheter embodiment shown in FIG. 17, with the centering wire collapsed;  
         [0017]    [0017]FIG. 19 is a longitudinal view of the distal end of another alternative embodiment of a catheter according to the invention, with the centering wire expanded. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0018]    An apparatus is provided by the present invention that allows for intraluminal radiation therapy (IRT), also called brachytherapy. Applicant&#39;s invention is useful with any type of brachytherapy catheter that delivers a small diameter radiation source to a targeted body vessel. Such catheters may feature a lumen for temporary insertion of a radioactive source such as a fluid, a wire or a pellet, or the catheter may have an electrically activated radiation source built into a treatment region adjacent its distal end. Regardless of the source of radiation, such catheters benefit from a mechanism to center them within the lumen of the body vessel, thus ensuring uniform exposure of the vessel tissue.  
         [0019]    FIGS.  1 - 3  illustrate a section of body vessel  10  having lumen  15  and brachytherapy catheter  20  extending there through. Catheter  20  may be any type of IRT catheter, such as those described above. Centering wire  30  is mounted about treatment region  22  of catheter  20 , and comprises wire-form  40 , which is shown in an expanded configuration. The term wire-form is used herein to refer to any pre-formed monofilament that exhibits a shape memory. Other centering wire embodiments, in accordance with the invention, may comprise a conjunction of two or more wire-forms, as will be described below. Examples of materials that are useful for wire-forms in the invention are wires made of nitinol (NiTi) or spring temper stainless steel, or filaments made of thermoplastic polymers. Wire-form  40  comprises a series of lobes  50  arranged along its length. Wire-form  40  also has a center line, which extends axially through the center of catheter  20 . To aid in description of the invention, reference will be made to center line  42 . According to the invention, the number of lobes  50  in a wire-form can be selected as desired. Variables affecting the design of a particular wire-form can be related to the length of treatment region  22  that needs to be centered, and to the axial length of lobes  50 . The axial length of lobes  50  can be defined by the chosen lobe shapes, which may be generally semi-elliptical or semi-circular. Lobes  50  may also be U-shaped, having roughly parallel sides and rounded outer ends. Each lobe  50  has starting segment  52  adjacent one side of center line  42 , and ending segment  56 , which is axially displaced from starting segment  52  and is adjacent the opposite side of center line  42 . Lobe  50  extends radially outwardly from starting segment  52  to apex  54 , then continues radially inwardly to ending segment  56 . Because lobe  50  starts and ends on opposite sides of center line  42 , lobe  50  defines generally flat plane  58 , which crosses center line  42  at a slight angle, as shown in FIG. 2. In wire-form  40 , lobes  50  are staggered within a single plane such that wire-form  40  may resemble a sine wave with peaks and valleys that are engageable with lumen  15  of body vessel  10 .  
         [0020]    Wire-form  40 , and other wire-forms in accordance with the invention, are characterized as having multiple lobes  50  arranged in a radially symmetrical staggered sequence along center line  42 . Lobes  50  are termed in a “sequence” because each lobe  50  is formed longitudinally adjacent another lobe  50 . The designation “staggered” means that each lobe  50  extends in a different radial direction from adjacent lobe(s)  50 . In the case of wire-form  40 , which lies generally within a single plane, sequential lobes  50  alternate between 0° and 180° angular positions about center line  42 , as shown in FIG.  3 . The staggered sequence of lobes  50  is also termed “radially symmetrical” because the angular positions of lobes  50  are equally spaced about center line  42 . As discussed above, FIG. 3 shows the radial symmetry of wire-form  40 , in which lobes  50  extend from center line  42  in two directions: 0° and 180°. FIGS. 4 and 5 show the radial symmetry of wire-forms in alternative embodiments of the invention, which are discussed in further detail below. In FIG. 4, lobes  50  extend from center line  42  in three equally spaced directions: 0°, 120° and 240°. In FIG. 5, lobes  50  extend from center line  42  in four equally spaced directions: 0°, 90°, 180° and 270°.  
         [0021]    Centering wire  30  functions to center catheter  20  in the body vessel as follows. With wire-form  40  in its expanded configuration, apexes  54  contact lumen  15 , and the radial symmetry of wire-form  40  tends to retain center line  42  centered in vessel  10 . To restrain catheter  20  about center line  42 , starting and ending segments  52 ,  56  prevent their respective contact points with catheter  20  from moving or bending towards lumen  15 . For example, as can be seen in FIG. 3, wire-form  40  can effectively prevent catheter  20  from moving laterally, or perpendicular to the plane extending through directions 0° and 180°. Starting and ending segments  52 ,  56  contact catheter  20  on alternating opposite sides only, such that each contact point can only deter lateral displacement of catheter  20  in one direction. In this example, contact points on the same side are separated by the length of two lobes  50 . Alternate embodiments of centering wire  30  are presented below, and feature more contact points and closer separation distances therebetween to achieve better centering performance, especially in curved body vessels. To a lesser extent, wire-form  40  can also act to restrain catheter  20  centered within the plane through directions 0° to 180°, shown in FIG. 3. For catheter  20  to move away from center line  42  towards apex  54  of lobe  50  requires starting and ending segments  54 ,  56  to twist out-of-plane, or for catheter  20  to bend laterally through lobe  50 .  
         [0022]    To exemplify the functionality of centering wire  30  and several alternative embodiments, Table 1 shows the angular position of centering lobes  50  for each example. The wire-forms in each of centering wires  30 - 430  are formed in a single plane. The positions (A-E) refer to lobes  50  of each wire-form  40 , in longitudinal sequence. In the first example of Table 1, centering wire  30  comprises wire-form  40  and has been described above.  
         [0023]    The second example in Table 1 is centering wire  130 , which is shown in FIG. 6 and comprises a conjunction of wire-forms  40 ,  140 . Wire-form  140  is formed as a mirror image of wire-form  40 , or it may be considered to have the same shape as wire-form  40  and to be axially displaced by one lobe or by one half-cycle in a sine wave. In centering wire  130 , each starting segment  52  of wire-form  40  is directly on the opposite side of catheter  20  from an ending segment  56  of wire-form  140  Thus, each point of contact between catheter  20  and centering wire  130  can deter lateral displacement of catheter  20  in two opposite directions, with contact points on the same side being axially separated only by the length of one lobe  50 . Each longitudinal sequence position in centering wire  130  has two lobes  50 , arranged directly opposite each other, as indicated in Table 1.  
         [0024]    The third example in Table 1 is centering wire  230 , which is shown in FIG. 7 and comprises a conjunction of wire-forms  40 , 240 . Wire-form  240  has the same shape as wire-form  40  and is angularly displaced 90° there from. In centering wire  230 , each starting segment  52  of wire-form  40  has a starting segment  52  of wire-form  240  displaced 90° there from on catheter  20 . Thus, each point of contact between catheter  20  and centering wire  230  can deter lateral displacement of catheter  20  in two orthogonal directions, with contact points on the same side being axially separated by the length of two lobes  50 . Each longitudinal sequence position in centering wire  230  has two lobes  50 , arranged orthogonally around center line  42 , as indicated in Table 1.  
                                                                                         TABLE 1                           Angular Position (in degrees) of Centering Lobes for       Centering Wires having Wire-Forms in a Single Plane            Centering       Longitudinal Sequence Position            Wire   Wire-Form   A   B   C   D   E                    30   40   0   180   0   180   0       130   40   0   180   0   180   0           140   180   0   180   0   180       230   40   0   180   0   180   0           240   90   270   90   270   90       330   40   0   180   0   180   0           140   180   0   180   0   180           240   90   270   90   270   90           340   270   90   270   90   270       430   40   0   180   0   180   0           440   120   300   120   300   120           540   240   60   240 60   240                  
 
         [0025]    The fourth example in Table 1 is centering wire  330 , which is shown in FIG. 8 and comprises a conjunction of wire-forms  40 ,  140 ,  240 ,  340 . In centering wire  330 , starting segments  52  of wire-forms  40 ,  140 ,  240 ,  340  are equally spaced around catheter shaft  20 . Thus, each point of contact between catheter  20  and centering wire  330  can deter lateral displacement of catheter  20  in four directions, with contact points on the same side being axially separated by only the length of one lobe  50 . Each longitudinal sequence position in centering wire  330  has four lobes  50 ,which are equally spaced around center line  42 , as indicated in Table 1. With its four lobes  50  and four adjacent contact points, centering wire  330  provides a high degree of centering, and constructing this embodiment requires four separate wire-forms  40 ,  140 ,  240 ,  340 .  
         [0026]    The last example in Table 1 is centering wire  430 , which is shown in FIG. 9 and comprises a conjunction of wire-forms  40 ,  440 ,  540 . Wire-forms  440 ,  540  have the same shapes as wire-form  40  and are angularly displaced 120° and 240° there from, respectively. In centering wire  430 , starting segments  52  of wire-forms  40 ,  440 ,  540  are equally spaced around catheter shaft  20 . Thus, each point of contact between catheter  20  and centering wire  430  can deter lateral displacement of catheter  20  in three directions, with contact points on the same side being axially separated by the length of two lobes  50 . Each longitudinal sequence position in centering wire  430  has three lobes  50 ,which are equally spaced around center line  42 , as indicated in Table 1. In each sequence position, the lobes  50  are angularly displaced 60° relative the adjacent position.  
         [0027]    In all of the examples in Table 1, the wire-forms are formed in a single plane. In other alternative embodiments of centering wires, the wire-forms can be formed in multiple planes. In such cases, starting and ending segments  52 ,  56  are wrapped at least partially around center line  42 , and ending segment  56  of one lobe  50  may also be starting segment  52  of an adjacent lobe  50 . Table  2  shows the angular position of centering lobes  50  for alternative embodiment centering wires  530 - 930 , in which all of the wire-forms would be formed in multiple planes.  
         [0028]    The first example in Table 2 is centering wire  530 , which is shown in FIG. 10. Centering wire  530  comprises wire-form  640 , in which axially adjacent lobes  50  are arranged 90° apart. Although lobes  50  are arranged in four staggered, equally-spaced directions, the partial wrapping of starting and ending segments  52 ,  56  around catheter  20  provides a quarter-circle range of centering support at each contact point, as compared to the unidirectional support offered by a single-plane wire-form such as wire-form  40 , discussed above.  
         [0029]    The second example in Table 2 is centering wire  630 , shown in FIG. 11. Centering wire  630  comprises a conjunction of wire-forms  640 ,  740 . Wire-form  740  is similar to wire-form  640 , but it is axially displaced with respect thereto by two lobe positions. As a result, each longitudinal lobe position along centering wire  630  can support a catheter in two opposite directions, either 0° and 180° or 90° and 270°.  
         [0030]    The third example in Table 2 is centering wire  730 , shown in FIG. 12. Centering wire  730  comprises wire-form  840 , in which axially adjacent lobes  50  are arranged 120° apart. In wire-form  840 , lobes  50  are arranged in three staggered, equally-spaced directions, and the partial wrapping of starting and ending segments  52 ,  56  around catheter  20  provides a one third of a circle range of centering support at each contact point with a catheter.  
         [0031]    The fourth example in Table 2 is centering wire  830 , shown in FIG. 13. Centering wire  830  comprises a conjunction of wire-forms  840 ,  940 ,  1040 . Wire-forms  940  and  1040  are similar to wire-form  840 , but they are axially displaced by one and two lobe positions, respectively. As a result, each longitudinal lobe position along centering wire  830  can support a catheter in three equally spaced directions.  
         [0032]    The fifth example in Table 2 is centering wire  930 , shown in FIG. 14. Centering wire  930  comprises a conjunction of wire-forms  640 ,  740 ,  1140 ,  1240 . Wire-forms  1140 ,  1240  are similar to wire-form  640  but they are axially displaced with respect thereto by one lobe position in each axial direction. As a result, each longitudinal lobe position along centering wire  630  can support a catheter in four opposite directions, 0°, 180°, 90° and 270°.  
                                                                                     TABLE 2                           Angular Position (in degrees) of Centering Lobes for       Centering Wires Having Wire-Forms in Multiple Planes                Longitudinal Sequence Position            Example   Wire-Form   A   B   C   D   E                    530   640   0   90   180   270   0       630   640   0   90   180   270   0           740   180   270   0   90   180       730   840   0   120   240   0   120       830   840   0   120   240   0   120           940   120   240   0   120   240           1040   240   0   120   240   0       930   640   0   90   180   270   0           1140   90   180   270   0   90           740   180   270   0   90   180           1240   270   0   90   180   270                  
 
         [0033]    [0033]FIG. 15 shows catheter  20  and centering wire  30 , which is in an expanded configuration. Catheter  20  includes distal treatment region  22 , which is adapted to irradiate a body vessel, as described above. Catheter  20  may be fabricated from typical components such as extruded and/or braided tubes, and may also include tubing or stiffening wires made of metal(s). Specific materials for such components are common knowledge to those of ordinary skill in the field of catheters. Catheter  20  also has shaft  24  and actuator sleeve  26 , which slidably surrounds a proximal portion of shaft  24 . Centering wire  30  has its distal end coupled to the distal end of shaft  24 , and its proximal end is coupled to the distal end of actuator sleeve  26 . Coupling(s) between centering wires and catheter elements may comprise any suitable means, such as adhesives or the sandwiching of wire portions between layers of melt-bonded thermoplastic polymers.  
         [0034]    [0034]FIG. 16 shows catheter  20  and centering wire  30  of FIG. 15 in a collapsed configuration, achieved by drawing actuator sleeve  26  proximally along shaft  24  to draw or stretch apart the proximal and distal ends of centering wire  30 . The collapsed configuration features a low profile suitable for insertion, withdrawal or repositioning of the apparatus within body vessels of a patient. In the collapsed configuration, centering wire  30  may be generally wrapped around shaft  24  because lobes  50  start and end on opposite sides of center line  42 . Transformation between the collapsed and expanded configurations is repeatably reversible, as often as necessary during treatment of the patient. Shape memory of the expanded configuration is set into wire-form  40 , typically by winding the monofilament in a fixture and heating the assembly under conditions of time and temperature suitable for the chosen material.  
         [0035]    [0035]FIG. 17 shows an alternative embodiment of the invention having catheter  20 ′ and centering wire  30 . Catheter  20 ′ includes distal treatment region  22  and shaft  24 ′. Port  28  is an opening through the wall of shaft  24 ′ and is located adjacent the proximal end of distal treatment region  22 . The distal end of centering wire  30  is coupled to the distal end of shaft  24 ′. The proximal end of centering wire  30  is coupled to the distal end of actuator filament  26 ′, which slidably extends through a lumen (not shown) in shaft  24 ′.  
         [0036]    [0036]FIG. 18 shows catheter  20 ′ and centering wire  30  of FIG. 17 in a collapsed configuration, achieved by pulling actuator filament  26 ′ proximally through shaft  24 ′ to draw or stretch apart the proximal and distal ends of centering wire  30 . As it is transformed from the expanded configuration to the collapsed configuration, a proximal portion of centering wire  30  is drawn through port  28  into the lumen of shaft  24 ′.  
         [0037]    [0037]FIG. 19 shows another alternative embodiment of the invention having catheter  20 ″ and centering wire  30 . In catheter  20 ″, port  28  is located proximally of distal treatment region  22  such that, when centering wire  30  is transformed from its expanded configuration to its collapsed configuration, none of its pre-formed lobes needs to be drawn through port  28 . In catheters  20 ′,  20 ″ centering wire  30  and actuator filament  26 ′ may be separate elements that are coupled together, in which case, the coupling between centering wire  30  and actuator filament  26 ′ may always lie inside of shaft  24 ′, or it may always lie outside of shaft  24 ′, or the coupling may pass through port  28  during transformation of centering wire  30  between expanded and collapsed configurations. Alternatively, centering wire  30  and actuator filament  26 ′ may be made as separate portions of a single component. Catheters  20 ,  20 ′ may both feature a locking mechanism (not shown) at the proximal end, which can maintain the relative positions of shaft  24  and actuator sleeve  26 , or shaft  24 ′ and actuator filament  26 ′. Such a locking mechanism can temporarily hold the apparatus in either the expanded or collapsed configurations.  
         [0038]    While catheters  20 ,  20 ′, and  20 ″ are each shown, for simplicity, with centering wires that have only single wire-forms, it is understood from the examples above that two or more wire-forms may be mounted about the distal treatment region of the brachytherapy catheter. In such multi wire-form embodiments, the wire-forms may be mounted to the catheter independently of each other, or they may be joined at one or both ends, which may simplify the attachment between the centering wire and an actuator. As discussed above, multiple wire-form embodiments can provide radial centering in more than one direction, which may be advantageous in treating tortuous body vessels.  
         [0039]    While the invention has been particularly shown and described with reference to the several disclosed embodiments thereof, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention. For example, catheters  20 ,  20 ′, and  20 ″ may be of several types, including over-the-wire (OTW), single operator or rapidly exchangeable (RX), and fixed-wire (FW).