Abstract:
An intravascular radiation delivery system including a catheter, a radiation source disposed in an open-ended lumen in the catheter and a closed-ended sheath surrounding the radiation source so as to prevent blood and other fluids from coming into contact with the radiation source. Preferably, the open-ended lumen is centered in the balloon for uniform radiation delivery. The catheter may include a blood perfusion lumen under the balloon or around the balloon. The open-ended lumen in the catheter may have a reduced diameter adjacent the distal end of the catheter to prevent the radiation source from exiting the lumen. Methods of using the radiation delivery system are also disclosed. 
     An alternative method of delivering radiation to a treatment site inside the vasculature of a patient using a gas-filled balloon catheter and a radiation source disposed in the balloon catheter. The treatment site is exposed to radiation, preferably beta radiation, through the gas-filled balloon.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 08/782,471 filed Jan. 10, 1997 now U.S. Pat. No. 6,234,951, which is a continuation-in-part of co-pending U.S. patent application Ser. No. 08/608,655 filed on Feb. 29, 1996 now U.S. Pat. No. 5,882,290 entitled INTRAVASCULAR RADIATION DELIVERY SYSTEM, the entire disclosure of which are incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION 
     The present invention generally relates to intralumenal devices used to deliver radiation inside a living body. More specifically, the present invention relates to intravascular devices used to deliver radiation inside the vasculature of a patient for therapeutic purposes. Those skilled in the art will recognize the benefits of applying the present invention to similar fields not discussed herein. 
     BACKGROUND OF THE INVENTION 
     Intravascular diseases are commonly treated by relatively non-invasive techniques such as percutaneous translumenal angioplasty (PTA) and percutaneous translumenal coronary angioplasty (PTCA). These therapeutic techniques are well-known in the art and typically involve the use of a balloon catheter with a guide wire, possibly in combination with other intravascular devices. A typical balloon catheter has an elongate shaft with a balloon attached to its distal end and a manifold attached to the proximal end. In use, the balloon catheter is advanced over the guide wire such that the balloon is positioned adjacent a restriction in a diseased vessel. The balloon is then inflated and the restriction in the vessel is opened. 
     Vascular restrictions that have been dilated do not always remain open. For example, the restriction may redevelop over a period of time, a phenomenon commonly referred to as restenosis. Various theories have been developed to explain the cause for restenosis. It is commonly believed that restenosis is caused, at least in part, by cellular proliferation over a period of time to such a degree that a stenosis is reformed in the location of the previously dilated restriction. 
     Intravascular radiation, including thermal, light and radioactive radiation, has been proposed as a means to prevent or reduce the effects of restenosis. For example, U.S. Pat. No. 4,799,479 to Spears suggests that heating a dilated restriction may prevent gradual restenosis at the dilation site. In addition, U.S. Pat. No. 5,417,653 to Sahota et al. suggests that delivering relatively low energy light, following dilatation of a stenosis, may inhibit restenosis. Furthermore, U.S. Pat. No. 5,199,939 to Dake et al. suggests that intravascular delivery of radioactive radiation may be used to prevent restenosis. While most clinical studies suggest that thermal radiation and light radiation are not significantly effective in reducing restenosis, some clinical studies have indicated that intravascular delivery of radioactive radiation is a promising solution to the restenosis enigma. 
     Since radioactive radiation prevents restenosis but will not dilate a stenosis, radiation is preferably administered during or after dilatation. European Patent No. 0 688 580 to Verin discloses a device and method for simultaneously dilating a stenosis and delivering radioactive radiation. In particular, Verin &#39;580 discloses balloon dilatation catheter having an open-ended lumen extending therethrough for the delivery of a radioactive guide wire. 
     One problem associated with the open-ended lumen design is that bodily fluids (e.g., blood) may come into contact with the radioactive guide wire. This may result in contamination of the bodily fluid and require the resterilization or disposal of the radioactive guide wire. To address these issues, U.S. Pat. No. 5,503,613 to Weinberger et al. proposes the use of a separate closed-ended lumen in a balloon catheter. The closed-ended lumen may be used to deliver a radioactive guide wire without the risk of contaminating the blood and without the need to resterilize or dispose of the radiation source. 
     The closed-ended lumen design also has draw backs. For example, the addition of a separate delivery lumen tends to increase the overall profile of the catheter. An increase in profile is not desirable because it may reduce flow rate of fluid injections into the guide catheter and it may interfere with navigation in small vessels. 
     Another problem with both the open-ended and closed-ended devices is that radiation must travel through the fluid filled balloon in order to reach the treatment site. While this is not a problem for gamma radiation, it poses a significant problem for beta radiation which does not penetrate as well as gamma radiation. Beta radiation is considered a good candidate for radiation treatment because it is easy to shield and control exposure. In larger vessels (e.g., 0.5 cm or larger), a fluid filled balloon absorbs a significant amount of beta radiation and severely limits exposure to the treatment site. 
     SUMMARY OF THE INVENTION 
     The present invention overcomes these problems by providing a radiation delivery system that permits the use of an open-ended delivery lumen without the risk of blood contamination and without the need to dispose of or resterilize the radiation source. In addition, the present invention provides a radiation delivery system that permits beta radiation to be delivered through a balloon without a significant decrease in radiation exposure to the treatment site, even in large vessels. 
     One embodiment of the present invention may be described as a catheter having an open-ended lumen, a radiation source disposed in the open-ended lumen of the catheter and a closed-end sheath surrounding the radiation source. The closed-end sheath prevents blood and other fluids from coming into contact with the radiation source so that blood is not contaminated and the radiation source may be reused. The catheter may be a balloon catheter and may include a guide wire disposed in the open-ended lumen of the catheter. The open-ended lumen may be a full-length lumen or a partial-length lumen (e.g., a rapid exchange lumen). Preferably, the lumen is centered in the balloon for uniform radiation delivery. The catheter may also include a blood perfusion lumen under the balloon or around the balloon. The open-ended lumen in the catheter may have a reduced diameter adjacent the distal end of the catheter to prevent the radiation source from exiting the lumen. Alternatively, the closed-end sheath may have a ridge which abuts a corresponding restriction in the open-end lumen of the catheter to prevent the radiation source from exiting the lumen. 
     Another embodiment of the present invention may be described as a method of delivering radiation to a treatment site inside the vasculature of a patient using a the radiation delivery system described above wherein the method includes the steps of (1) inserting the catheter into the vasculature of a patient; (2) inserting the radiation source into the closed-end sheath; (3) inserting the radiation source and the closed-end sheath into the lumen of the catheter such that the radioactive portion is positioned adjacent a treatment site; and (3) exposing the vascular wall to radiation from the radiation source. Alternatively, the sheath may be inserted into the catheter before the radiation source is loaded into the sheath. The method may also include the steps of (4) removing the radiation source from the catheter; and (5) removing the catheter from the patient. The catheter may be inserted into the vasculature over a guide wire and the guide wire may be removed from the catheter prior to exposing the vascular wall to radiation. 
     Yet another embodiment of the present invention may be described as a method of delivering radiation to a treatment site inside the vasculature of a patient using a gas-filled balloon catheter and a radiation source wherein the method includes the steps of: (1) inserting the catheter into the vasculature such that the balloon is adjacent to a treatment site; (2) inserting the radiation source into the catheter such that the radioactive portion is adjacent to the balloon; (3) inflating the balloon with a gas; and (4) exposing the treatment site to radiation from the radiation source through the gas in the balloon. The balloon may be inflated prior to or subsequent to inserting the radiation source. Preferably beta radiation is used, but other radioisotopes may be employed. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a partially sectioned side view of an embodiment of the present invention. 
     FIG. 2 is a cross-sectional view taken at A—A in FIG.  1 . 
     FIG. 3 is a side view of an alternative embodiment of the present invention including a helical-shaped balloon. 
     FIG. 4 is a side view of an alternative embodiment of the present invention including a toroidal-serpentine-shaped balloon. 
     FIGS. 5 a ,  5   b  and  5   c  are partially sectioned side views of an alternative embodiment of the present invention including a rapid-exchange guide wire lumen. 
     FIG. 6 is a partially sectioned side view of an alternative embodiment of the present invention including a perfusion lumen passing through the balloon. 
     FIG. 7 is a cross-sectional view taken at B—B in FIG.  6 . 
     FIG. 8 is a cross-sectioned side view of an alternative sheath of the present invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The following detailed description should be read with reference to the drawings in which similar parts in different drawings are numbered the same. The drawings, which are not necessarily to scale, depict exemplary embodiments and are not intended to limit the scope of the invention. 
     Examples of suitable materials, dimensions, parts, assemblies, manufacturing processes and methods of use are described for each embodiment. Otherwise, that which is conventional in the field of the invention may be implemented. Those skilled in the field will recognize that many of the examples provided have suitable alternatives which may also be utilized. 
     Refer now to FIGS. 1 and 2 which illustrate a radiation delivery system  10  of the present invention. Radiation delivery system  10  includes a catheter  11  having an open-ended lumen  12  extending therethrough. A closed-ended sheath  13  surrounds a radiation source  14  (such as a guide wire) disposed in the open-ended lumen  12 . An after-loader  22  may be connected to the proximal end of the radiation source  14  to advance and retract the radiation source  14  and safely contain it when not in use. 
     The catheter  11  includes an inflatable balloon  15  having an interior  16  which is in fluid communication with an inflation lumen  17 . The catheter  11  illustrated in FIGS. 1 and 2 has a coaxial shaft construction including an inner tube  23  and an outer tube  24 . Other shaft constructions may be employed such as a dual lumen shaft design illustrated in FIG. 6. A manifold  18  is connected to the proximal end of the catheter  11  and includes a guide wire port  19  and a flush port  20  both of which are in fluid communication with the open-ended lumen  12 . The guide wire port may include a toughy-borst (not shown) to seal about the proximal end of the closed-end sheath  13 . The manifold  18  also includes an inflation port  21  which is in fluid communication with the inflation lumen  17  and the interior  16  of the balloon  15 . 
     The closed-end sheath  13  preferably extends to the proximal end of the catheter  11  and may include means for connection to the after-loader  22 . The closed-end sheath  13  may be formed of polyethylene, PTFE coated polyimide or other suitable flexible material. The closed-end sheath  13  may have a length of about 100 to 300 cm depending on the length of the catheter  11 . A wall thickness between 0.0002 and 0.005 inches is preferred to minimize profile and radiation absorption. 
     As included with catheter  11  illustrated in FIGS. 1 and 2, the open-ended lumen  12 , closed-ended sheath  13 , radiation source  14 , after loader  22  and toughy-borst are also included with catheters  31 ,  41 ,  51  and  61  as illustrated in FIGS. 3,  4 ,  5  and  6  respectively. In addition, those skilled in the art will appreciate that the various features of each catheter  11 ,  31 ,  41 ,  51  and  61  may be mixed and matched depending on the desired result. For example, the rapid exchange features of catheter  51  may be incorporated into perfusion catheter  61 , resulting in a perfusion rapid exchange catheter for the delivery of radiation. As another example, the centering balloon  35  or  45  may be contained inside balloon  15  of catheters  11  and  61  to provide a centering function, even in curved vasculature. 
     Refer now to FIGS. 3 and 4 which illustrate alternative radiation delivery catheters  31  and  41 . Alternative catheters  31  and  41  may be used in place of catheter  11  for the radiation delivery system  10  illustrated in FIG.  1 . Except as described herein, the design and use of alternative catheters  31  and  41  is the same as catheter  11 . Alternative catheter  41  may be made as described in co-pending U.S. patent application Ser. No. 08/608,655 which is incorporated herein by reference. Similarly, alternative catheter  31  may be made as described in the above-referenced case except that the balloon  35  is wound in a helical shape rather than a serpentine shape. 
     With reference to FIG. 3, alternative catheter  31  includes a helically-shaped balloon  35  which is wound around the distal end of the catheter  31 . When the helically-shaped balloon  35  is inflated, a helically-shaped perfusion path  36  is defined between the balloon  35 , the shaft  37  and the inside surface of the blood vessel. The blood perfusion path  36  allows blood to flow across the treatment site while the balloon  35  is inflated. In addition, the concentric and flexible helical shape of the inflated balloon  35  maintains the distal portion of the catheter  31  centered in the vessel, even around turns in the vasculature. Having the catheter  31  centered in a vessel permits the uniform distribution of radiation to the treatment site. 
     The distal end of the shaft  37  may include a reduced diameter tip  38  with a corresponding reduced inside diameter open-ended lumen (not visible). The reduced inside diameter permits a conventional guide wire to exit out the distal end of the catheter  31  but prohibits the sheath  13  and radioactive source wire  14  from exiting. This assumes, of course, that the sheath  13  or radioactive source wire  14  is larger than the guide wire. A reduced diameter tip may be included on any of the catheters described herein. 
     With reference to FIG. 4, alternative catheter  41  includes a toroidal-serpentine-shaped balloon  45 . When the serpentine-shaped balloon  45  is inflated, a linear perfusion path  44  is defined between the balloon  45 , the shaft  47  and the inside surface of the blood vessel. The blood perfusion path  44  allows blood to flow across the treatment site while the balloon  45  is inflated. As with the helical balloon described above, the concentric and flexible serpentine shape of the inflated balloon  45  maintains the distal portion of the catheter  41  centered in the vessel, even around turns in the vasculature. Having the catheter  41  centered in a vessel permits the uniform distribution of radiation to the treatment site. A further advantage of the serpentine-shaped balloon  45  is the relative linearity of the perfusion path  44  which tends to minimize resistance to blood flow. 
     Catheter  41  may also include two radiopaque markers  46  to facilitate radiographic placement in the vasculature. The distal end of the shaft  47  may include a reduced diameter tip  48  with a corresponding reduced inside diameter open-ended lumen (not visible). The reduced inside diameter permits a conventional guide wire to exit out the distal end of the catheter  41  but prohibits the sheath  13  and radioactive source wire  14  from exiting. 
     It is also contemplated that both the helical balloon  35  and the serpentine balloon  45  may be covered with an elastomeric sleeve to aid in collapsing the balloon  35 / 45  upon deflation. This sleeve would be connected to the shaft adjacent the proximal and distal ends of the balloon  35 / 45 . It is further contemplated that this sleeve may include perfusion holes both proximally and distally to permit blood perfusion along the perfusion path  36 / 44  defined by the balloon  35 / 45 . If a gas is used to inflate the balloon  35 / 45  in large diameter vessels (e.g., peripheral vasculature), it is preferred to not permit perfusion of blood which would otherwise absorb beta radiation. In such a situation, the sleeve would not include perfusion holes. 
     Refer now to FIGS. 5 a ,  5   b  and  5   c  which illustrate a rapid-exchange embodiment of the present invention. Alternative catheter  51  may be used in place of catheter  11  for the radiation delivery system  10  illustrated in FIG.  1 . Except as described herein, the design and use of alternative catheter  51  is the same as catheter  11 . 
     Rapid-exchange catheter  51  includes an elongate shaft  57  with a manifold  52  connected to the proximal end and a balloon  45  connected to the distal end. Although catheter  51  is shown with a serpentine balloon  45  and a corresponding linear perfusion path  44 , any of the balloon types described herein may be used. 
     The manifold  52  includes a balloon inflation port  53  which is in fluid communication with the balloon  45  via a conventional inflation lumen. A radiation source entry port  54  is also included in the manifold  52 . The entry port  54  communicates with the open-ended lumen and permits the insertion of the sheath  13  and radiation source  14 . The open-ended lumen terminates in a reduced diameter tip  58  which permits a conventional guide wire  56  to exit out the distal end of the catheter  51  but prohibits the sheath  13  and radioactive source wire  14  from exiting. 
     The guide wire  56  enters the shaft  57  at the proximal guide wire tube  55 . The guide wire tube  55  is located near the distal end of the catheter to permit catheter exchange without the need for an extension wire or wire trapping device. As best seen in FIG. 5 c , the guide wire tube  55  has sufficient length such that the guide wire  56  may be pulled back and out of the open-ended lumen. In particular, the distance from the proximal end of the guide wire tube  55  to the distal end of the catheter  51  is less than the length of the guide wire extending outside of the patient&#39;s body. With the guide wire pulled back, the radioactive source wire  14  and the sheath  13  may be inserted into the entry port  54  to the distal end of the catheter  51 . 
     Refer now to FIGS. 6 and 7 which illustrate an alternative perfusion catheter  61 . Alternative catheter  61  may be used in place of catheter  11  for the radiation delivery system  10  illustrated in FIG.  1 . Except as described herein, the design and use of alternative catheter  61  is the same as catheter  11 . 
     Perfusion catheter  61  includes an elongate shaft  67  with a manifold  18  connected to the proximal end and a balloon  16  connected to the distal end. The shaft  67  is a multi-lumen type extrusion including an open-ended lumen  62  and an inflation lumen  63 . Inflation lumen  63  provides fluid communication between the inflation port  21  and the interior of the balloon  16 . Open ended lumen  62  is in communication with entry port  19  for the insertion of a guide wire (not shown) or the radioactive source  14  and sheath  13 . A guide wire extension tube  64  is connected to the distal end of the multi-lumen shaft  67  and rigidly connects to the distal end of the balloon  15 . 
     Catheter  61  includes a series of perfusion ports  65  which are in fluid communication with the distal portion of the open-ended lumen  62 . The perfusion ports  65  permit blood to flow across the treatment site via the open-ended lumen while the balloon  15  is inflated. 
     With reference now to FIG. 8, an alternative sheath  81  is illustrated. Alternative sheath  81  may be used in place of sheath  13  for the radiation delivery system  10  illustrated in FIG.  1 . Except as described herein, the design and use of alternative sheath  81  is the same as sheath  13 . 
     Sheath  81  includes a proximal portion  82  and a distal portion  83 , wherein the proximal portion  82  includes a relatively thicker wall and larger outside diameter. The thicker wall tends to absorb radiation to reduce the amount of unwanted exposure, particularly exposure of the medical personnel. The larger outside diameter of the proximal portion  84  may be used in conjunction with a corresponding restriction in the open-ended lumen  12  of any of the catheters described herein. Specifically, the leading edge or ridge  86  of the proximal portion  82  may abut a mating restriction in the open-ended lumen  12  such that the sheath  81  cannot be advanced beyond that point. The leading edge  86  and the mating restriction in the open-ended lumen serve the same function as the reduced diameter tip described previously and may be used in lieu thereof. In other words, the leading edge  86  and the mating restriction in the open-ended lumen would permit a conventional guide wire  56  to exit out the distal end of the catheter but would prohibit the sheath  81  and radioactive source wire  14  from exiting the distal end of the catheter. 
     The closed-end sheath  81  may include means for connection to the after-loader  22 . The closed-end sheath  81  may be formed of polyethylene, PTFE coated polyimide or other suitable flexible material. The closed-end sheath  81  may have a length of about 100 to 300 cm depending on the length of the catheter  11 . On the distal portion  83 , a wall thickness between 0.0002 and 0.005 inches is preferred to minimize profile and radiation absorption. On the proximal portion  82 , a wall thickness between 0.040 and 1.0 inches is preferred to maximize radiation absorption without significantly compromising profile. The outside diameter of the proximal portion  82  may be greater than the vascular access size on the portion of the sheath  81  that remains outside the body. Once the radiation source is inside the body, the risk of exposure of beta radiation to medical personnel in diminished. 
     Sheath  81  may also include a radiopaque marker  84  to facilitate radiographic placement of the sheath  81  and radioactive wire  14 . Such a radiopaque marker  84  may also be included on sheath  13 . 
     Sheath  81  may also include a series of annular magnets  85 . Magnets  85  may be used to interact with a series of magnets connected to the catheter  11 ,  31 ,  41 ,  51  or  61  or a series of magnets connected to a guide catheter (not shown). This general arrangement is described in more detail in PCT publication WO 95/21566 which is fully incorporated herein by reference. The interacting magnets provide a means to longitudinally control and stabilize the position of the radiation source relative to the patient and treatment site. 
     In practice, catheters  11 ,  31 ,  41 ,  51  and  61  may be used to deliver radiation to the vascular wall in the following manner. After vascular access is established and a guide catheter is in position (if desired), the catheter  11 / 31 / 41 / 51 / 61  is inserted into the patient with the distal portion adjacent the treatment site. If a guide wire is used, the guide wire may be inserted prior to or simultaneously with the catheter. The balloon is then inflated to a low pressure sufficient to center the balloon in the vasculature and prevent movement of the catheter relative to the treatment site. Optionally, the balloon may first be inflated to a higher pressure in order to dilate the treatment site. If desired, the balloon may be inflated with a gas such as nitrogen, carbon dioxide or other non-toxic gas to minimize the absorption of radiation by the inflation media. After dilatation, the balloon is maintained in an inflated state, preferably at a low pressure, to center the catheter in the vascular lumen. The sheath  13  is placed over the radiation wire  14 , preferably ahead of time, and the two are advanced into the open-ended lumen using an after-loader system. Optionally, the sheath  13  is first loaded into the open-ended lumen of the catheter and the proximal end of the sheath is connected to the after-loader, followed by insertion of the radioactive source wire  14 . The toughy-borst is maintained sufficiently loose to allow advancement and may be locked to fully seal about the sheath  13  once the radiation wire  14  and sheath  13  are in the desired position. If a guide wire is used in the open-ended lumen, the guide wire is preferably retracted to permit passage of the radioactive wire  14  and sheath  13 . If a rapid exchange catheter  51  is used, the guide wire is pulled back into the proximal guide wire tube  55 . The vascular wall is then exposed to radiation (preferably beta radiation) for the desired period of time. The radioactive wire  14  and sheath  13  are removed from the catheter  11 / 31 / 41 / 51 / 61  and the catheter is removed from the patient. 
     While the specification describes the preferred embodiments, those skilled in the art will appreciate the spirit and scope of the invention with reference to the appended claims. Claims directed to methods of the present invention may be read without regard as to the order of the steps unless contraindicated by the teachings herein.