Patent Publication Number: US-2005131510-A1

Title: Device for distal protection and treatment of blood vessels

Description:
RELATED APPLICATIONS  
      This application is based on a prior copending provisional application Ser. No. 60/486,178, filed on Jul. 9, 2003, the benefit of the filing date of which is hereby claimed under 35 U.S.C. § 119(e), and is also a continuation-in-part of a prior copending application Ser. No. 10/799,357, filed on Mar. 12, 2004, which itself is based on a prior copending provisional application Ser. No. 60/455,069, filed on Mar. 14, 2003, the benefits of the filing dates of which are hereby claimed under 35 U.S.C. § 119(e) and 35 U.S.C. § 120. 
    
    
     FIELD OF THE INVENTION  
      The present invention generally relates to a method and apparatus for using light to diagnose and treat tissue, and more specifically, to a method and apparatus to diagnose or treat tissue accessible via a cavity, duct, vessel or other body lumen, in connection with a distal protection device.  
     BACKGROUND OF THE INVENTION  
      Photodynamic therapy (PDT) is a process whereby light of a specific wavelength or waveband is administered to tissue, to enable diagnosis or treatment of the tissue. The tissue is rendered photosensitive through the administration of a photoreactive or photosensitizing agent having a characteristic light absorption waveband. In PDT, the photoreactive agent is administered to a patient, typically by intravenous injection, oral administration, or by local delivery to the treatment site. Abnormal tissue in the body is known to selectively absorb certain photoreactive agents to a much greater extent than normal tissue. Once the abnormal tissue has absorbed or linked with the photoreactive agent, the abnormal tissue can then be diagnosed or treated by administering light having a wavelength or waveband corresponding to the absorption wavelength or waveband of the photoreactive agent. The PDT can then cause necrosis of the abnormal tissue.  
      PDT has proven to be very effective in destroying abnormal tissue, such as cancer cells, and has also been proposed for the treatment of vascular diseases, such as atherosclerosis and restenosis due to intimal hyperplasia. In the past, percutaneous transluminal coronary angioplasty (PTCA) has typically been performed to treat atherosclerotic cardiovascular diseases. A more recent treatment based on the use of drug eluting stents has reduced the rate of restenosis in some diseased vessels. As effective as such therapies are, a new form of therapy is needed for treating peripheral arterial disease and more problematic coronary diseases, such as vulnerable plaque, saphenous vein bypass graft disease, and diffuse long lesions.  
      As noted above, the objective of PDT may be either diagnostic or therapeutic. In diagnostic applications, the wavelength of light is selected to cause the photoreactive agent to fluoresce, yielding information about the tissue without damaging the tissue. In therapeutic applications, the wavelength/waveband of light delivered to the tissue treated with the photoreactive agent causes the photoreactive agent to undergo a photochemical reaction with oxygen in the localized tissue, which is believed to yield free radical species (such as singlet oxygen) that cause localized cell lysis or necrosis. The central strategy to inhibit arterial restenosis using PDT, for example, is to cause a depletion of vascular smooth muscle cells, which are a source of neointima cell proliferation (see, Nagae et al.,  Lasers in Surgery and Medicine  28:381-388, 2001). One of the advantages of PDT is that it is a targeted technique, in that selective or preferential delivery of the photoreactive agent to specific tissue enables only the selected tissue to be treated. Preferential localization of a photoreactive agent in areas of arterial injury, with little or no photoreactive agent delivered to healthy portions of the arterial wall, can therefore enable highly specific PDT ablation of arterial tissue.  
      Light delivery systems for PDT are well known in the art. Delivery of light from a light source such as a laser, to the treatment site has typically been accomplished through the use of a single optical fiber delivery system with special light-diffusing tips affixed thereto. Exemplary prior art devices also include single optical fiber cylindrical diffusers, spherical diffusers, micro-lensing systems, an over-the-wire cylindrical diffusing multi-optical fiber catheter, and a light-diffusing optical fiber guidewire. Such prior art PDT illumination systems generally employ remotely disposed high power lasers or solid state laser diode arrays, which are coupled to optical fibers for delivery of light to a treatment site. The disadvantages of using laser light sources include relatively high capital costs, relatively large size, complex operating procedures, and the safety issues that must be addressed when working with high power lasers. Accordingly, there is a substantial need for a light generating system that does not include a laser, and which generates light at the treatment site instead of at a remote point. For vascular applications of PDT, it would be desirable to provide a light-generating apparatus having a minimal cross-section, a high degree of flexibility, and compatibility with a guidewire introduction system, so the light-generating apparatus can readily be delivered to the treatment site through a vascular lumen. Such an apparatus should also deliver light uniformly to the treatment area.  
      For vascular application of PDT, it would further be desirable to provide a light-generating apparatus that is easily centered within a blood vessel, and which is configured to prevent light absorbent material, such as blood, from being disposed in the light path between the target tissue and the apparatus. Typically, an inflatable balloon catheter that matches the diameter of the blood vessel when the balloon is inflated is employed for centering apparatus within a vessel. Such devices also desirably occlude blood flow, enabling the light path to remain clear of obstructing blood.  
      Historically, the saphenous vein has been used to bypass stenotic coronary arteries during a PTCA surgical procedure. Increasing experience with postoperative follow-up of patients after saphenous vein bypass grafting has revealed a significant incidence of saphenous vein graft disease. Vein grafts develop endothelial proliferation as soon as they are placed in arterial circulation and after a few years, tend to develop atherosclerosis with thrombus formation. Vein graft atherosclerosis is often diffuse, concentric, and friable, with a poorly developed fibrous cap. Because of this characteristic, percutaneous interventions in saphenous vein grafts are limited by distal embolization, which can be extremely dangerous to a patient. Several types of catheter systems have been designed to capture atherothrombotic debris that embolize distally during vein graft intervention, where the intervention includes balloon dilation and/or stent placement. A distal protection device typically employs one of two approaches—a distal occlusion with a flow-occlusion balloon, followed by aspiration, and a distal occlusive filter. Neither approach is sufficient by itself. Therefore, it would be desirable to provide additional distal protection, to prevent accelerated vein graft disease, and to prevent distal embolization during interventions.  
     SUMMARY OF THE INVENTION  
      The present invention encompasses light generating devices for illuminating portions of vascular tissue to administer PDT. Each embodiment includes one or more light sources adapted to be positioned inside a body cavity, a vascular system, or other body lumen. While the term “light source array” is frequently employed herein, because particularly preferred embodiments of this invention include multiple light sources arranged in a radial or linear array, it should be understood that a single light source can also be employed within the scope of this invention. Using a plurality of light sources generally enables larger treatment areas to be illuminated. Light emitting diodes (LEDs) are particularly preferred as light sources, although other types of light sources can be employed, as described in detail below. The light source that is used is selected based on the characteristics of a photoreactive agent with which the apparatus is intended to be used, since light of incorrect wavelengths or waveband will not cause the desired reaction by the photoreactive agent. An array of light sources can include light sources that provide more than one wavelength or produce light that covers a waveband. Linear light source arrays are particularly useful to treat elongate portions of tissue within a lumen. Light source arrays used in this invention can also optionally include reflective elements to enhance the transmission of light in a preferred direction. Each embodiment described herein can beneficially include expandable members to occlude blood flow and to enable the apparatus to be centered in a blood vessel.  
      A key aspect of the light generating device of the present invention is that each embodiment is either adapted to be used with, or includes, a distal protection device. Interventions on vessels often results in distal embolization of atherosclerotic debris downstream, which can result in clinically significant events, including myocardial infarction, stroke, and renal failure. Distal protection devices trap blood and suspended debris, enabling removal of such debris before unobstructed flow is restored. Studies relating to the use of distal protection devices indicate such devices reduce the incidence of major adverse cardiac events by as much as 50 percent.  
      The present invention uses at least one of an integrated light source element disposed on a distal end of an intra lumen device, and a substantially transparent hollow shaft disposed on a distal end of an intra lumen device, the hollow shaft being configured to accommodate a separate light source element. When a separate light source element is employed, the separate light source element is advanced through a working lumen in the intra lumen device and into the hollow shaft, after the intra lumen device is properly positioned in a body lumen. Preferably, the present invention also includes a hollow tip disposed distally of the light source element (or of the hollow shaft that is adapted to receive a separate light source element). The hollow tip includes an orifice at its distal end and an orifice on a side surface of the hollow tip, which enable the intra lumen device to be advanced over a guidewire, without the need to extend a guidewire lumen in the light source element (or in the hollow shaft into which a separate light source element will be introduced). A guidewire lumen is preferably included to enable the intra lumen device to be advanced over a guidewire; also preferably included is a flushing and aspiration lumen. The flushing and aspiration lumen enables a flushing fluid to be introduced into an isolated portion of a body lumen and enables the flushing fluid and any debris to be subsequently evacuated (i.e., aspirated) from the isolated portion of the body lumen.  
      In one embodiment of the present invention, a first intra lumen device does not include a distal protection device, but instead, is adapted to be used with existing distal protection devices. The first intra lumen device includes the light source element (or the hollow shaft adapted to accommodate a separate light source element), the hollow tip, the guidewire lumen, and the flushing lumen, all of which were discussed above. The first intra lumen device is adapted to be used with a guide catheter having an occlusion balloon at its distal end, and a distal protection device. A guidewire, distal protection device, and guide catheter are introduced into a body lumen, so that a distal end of the guidewire is disposed beyond the treatment area, the distal protection device is disposed distal of the treatment area, and a distal end of the guide catheter is disposed proximal of the treatment site. The first intra lumen device is advanced into the body lumen until the distal end of the first intra lumen device (including the light source element or the hollow shaft adapted to accommodate a light source element) is disposed adjacent to the treatment area, and between the distal end of the guide catheter and the distal protection device. If a separate light source element is used, the separate light source element is advanced into the hollow shaft adapted to accommodate the separate light source element. The distal protection device and the guide catheter balloon are activated, isolating the treatment area. Flushing fluid is introduced into the isolated area to displace blood that might interfere with light transmission, and the light source element is activated. Flushing fluid can be removed, along with any debris. Normal blood flow is allowed to resume for a period of time, and if required, additional light therapy is administered. The first intra lumen device can then be repositioned to treat other portions of the body lumen, if required. For example, in some cases, the light source element cannot illuminate all of the portion of the body lumen isolated by the guide catheter balloon and the distal treatment device, without being repositioned. A similar embodiment of the first intra lumen device includes a balloon disposed proximal of the light source element (or proximal of the hollow shaft adapted to accommodate a separate light source element), so that the guide catheter is not required to include a balloon.  
      Another embodiment of the present invention includes integrated distal protection devices. In one such embodiment, an outer guide catheter has an occlusion member (such as a balloon) disposed at its distal end, and an inner light emitting catheter. The light emitting catheter includes at least one of a light source element and a substantially transparent hollow shaft, and a hollow tip at its distal end (such that the light emitting catheter can be advanced over a guidewire without requiring a guidewire lumen to be included in the light element portion), as described above. The light emitting catheter further includes a generally light transmissive expandable member substantially encompassing the light source element (or the hollow shaft), so that the light source element can be centered within a body lumen, and so that the expandable member can displace blood that would otherwise block light from reaching the walls of the body lumen (and the target tissue) where the device is disposed. This embodiment further includes a distal protection device formed of a shape memory material that is disposed distal of the light source element. The distal protection device is activated by applying thermal energy to the shape memory material. Either a separate heating element is included, or the shape memory material overlays a portion of the light source element, so heat emitted by the light source element increases the temperature of the shape memory material, causing the distal protection device to deploy.  
      To use this embodiment of an intra lumen device, the guide catheter is positioned proximal of the treatment site, and the light emitting catheter is positioned so that the distal protection device is distal of the treatment site, and the light source element is disposed adjacent to the treatment site. The occlusion member is inflated, and the distal protection device is deployed, thus isolating a portion of the body lumen into which the device is deployed. The expandable member encompassing the light source element is expanded to perform angioplasty (if desired). Flushing fluid is introduced to remove debris, as discussed above. The expandable member is expanded once again, to displace blood that would interfere with light transmission, and the light source element is energized. Flushing fluid is introduced to remove any additional debris. Normal blood flow is allowed to resume for a period of time, and if required, additional light therapy is administered. The light emitting catheter can then be repositioned to treat other portions of the body lumen, if required.  
      Yet another embodiment of an intra lumen device that includes a distal protection device has a first and a second generally toroidal inflatable member (i.e., balloons) disposed at a distal end of the intra lumen device. An impermeable sleeve extends between the two inflatable members, forming a conduit within the sleeve through which blood (or other bodily fluid) is diverted when the inflatable members are inflated. Inflating the inflatable members results in a portion of a body lumen in which the device is disposed being isolated, without interrupting blood flow in the body lumen. The portion of the intra lumen device within the sleeve includes a light source element (or the hollow shaft adapted to accommodate a separate light source element). A light transmissive expandable member encompasses the light source element, as noted above. The intra lumen device includes a flushing lumen adapted to introduce (and remove) flushing fluid in the isolated portion of the body lumen (that portion between the inflatable members and the sleeve). It will be appreciated that the distal most inflatable member functions as a distal protection device. Preferably, the light source element is movable relative to the inflatable members, so that the light source element can be repositioned without deflating and re-inflating the inflatable members.  
      To use this intra lumen device, it is positioned within a body lumen so that a treatment area is disposed between the two inflatable members. The light source element is disposed adjacent the treatment site. The inflatable members are inflated, and the expandable member encompassing the light source element is expanded initially to perform angioplasty, if desired (note that the sleeve must be sufficiently flexible to accommodate this function). Flushing fluid is introduced to remove debris, as indicated above, and to keep the isolated portion free of blood that would interfere with light transmission. The expandable member is expanded once again, sufficiently to occlude blood flow within the sleeve (since the blood flow would interfere with light transmission), and the light source element is energized. Preferably, blood flow is occluded for less than about 50 seconds. Normal blood flow is allowed to resume for a period of time (preferably about 50 seconds), and if required, additional light therapy is administered. Flushing within the isolated portion is continued as needed to remove debris. The light source element can then be repositioned to treat other portions of the body lumen, as required. 
    
    
     BRIEF DESCRIPTION OF THE DRAWING FIGURES  
      The foregoing aspects and many of the attendant advantages of this invention will become more readily appreciated as the same becomes better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings, wherein:  
       FIG. 1A  schematically illustrates a first embodiment of a light-generating device for use with a distal protection device during an intervention;  
       FIG. 1B  schematically illustrates a guide catheter and a distal protection device being deployed in a vessel during an intervention;  
       FIG. 1C  schematically illustrates the light-generating device of  FIG. 1A , the guide catheter of  FIG. 1B , and the distal protection device of  FIG. 1B  being used together during an intervention;  
       FIG. 1D  is a cross-sectional view of the light-generating device of  FIG. 1A ;  
       FIG. 2A  schematically illustrates a second embodiment of a light-generating device for use with a distal protection device during an intervention;  
       FIG. 2B  schematically illustrates a guide catheter and a distal protection device being deployed in a vessel during an intervention;  
       FIG. 2C  schematically illustrates the light-generating device of  FIG. 2A , the guide catheter of  FIG. 2B , and the distal protection device of  FIG. 2B  being used together during an intervention;  
       FIG. 2D  is a cross-sectional view of the light-generating device of  FIG. 2A ;  
       FIG. 3A  schematically illustrates a heart, indicating the position of a saphenous vein graft;  
       FIG. 3B  schematically illustrates a light-generating device with a distal protection device being used for an intervention;  
       FIGS. 3C and 3D  are cross-sectional views of the light-generating device of  FIG. 3B ;  
       FIG. 3E  schematically illustrates an embodiment of a light-generating device that is based on the light-generating device of  FIG. 3B , in which heat from the light-generating device is used to deploy a shape memory material comprising the distal protection device;  
       FIG. 3F  schematically illustrates a light-generating device based on the light-generating device of  FIG. 3B , in which heat from a heating element is used to deploy the shape memory material comprising the distal protection device;  
       FIG. 4A  schematically illustrates another implementation of a light-generating device with a distal protection device, during an intervention;  
       FIG. 4B  is a cross-sectional view of the light-generating device of  FIG. 4A ; and  
       FIG. 4C  is an enlarged view of a portion of  FIG. 4A . 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT  
      Unless otherwise defined, it should be understood that each technical and scientific term used herein and in the claims that follow is intended to be interpreted in a manner consistent with the meaning of that term as it would be understood by one of skill in the art to which this invention pertains. The drawings and disclosure of all patents and publications referred to herein are hereby specifically incorporated herein by reference. In the event that more than one definition is provided herein, the explicitly defined definition controls.  
      Various embodiments of light-generating devices that either incorporate distal protection devices, or are adapted to be used with a distal protection device, are described herein. An objective of administering PDT with the present invention may be either diagnostic, wherein the wavelength or waveband of the light being produced is selected to cause the photoreactive agent to fluoresce, thus yielding information about a target tissue, or therapeutic, wherein the wavelength or waveband of the light delivered to photosensitized tissue under treatment causes the photoreactive agent to undergo a photochemical interaction in the tissue that yields free radical species, such as singlet oxygen, causing the photosensitized tissue lysing or destruction.  
      Referring to  FIG. 1A , a light-generating device  1  comprises a multi-lumen catheter having an elongate flexible body  5 , formed from a suitable biocompatible material, such as a polymer or metal. Light generating device  1  is adapted to be used with prior art distal protection devices, as explained in greater detail below, and includes a distal end  6 , a proximal end  8  (normally disposed outside a body lumen and configured to enable light-generating device  1  to be manipulated), a flushing lumen  12 , a guidewire lumen  14 , an optional working lumen  16 , an optional power lumen  15 , and a light source array  10  (see  FIG. 1D , which shows lumens  12 ,  14 ,  15 , and  16 ). Generally, either a working lumen or a power lumen will be included, as discussed in detail below. The relative configuration of the lumens as shown in  FIG. 1D  is intended to be exemplary, and other configurations can be employed in the alternative. Thus, the relative orientations of the lumens of  FIG. 1D  is not intended to be limiting of the present invention. Furthermore, the lumens shown in  FIG. 1D  are not drawn to scale, and the relative sizes of the lumens shown are exemplary, rather than controlling. These comments, which specifically pertain to the cross sectional view of  FIG. 1D , also apply to the cross sectional views of  FIGS. 2D, 3C ,  3 D, and  4 B.  
      Guidewire lumen  14  enables elongate flexible body  5  to be advanced over a guidewire, and flushing lumen  12  enables a flushing fluid to be introduced into a body lumen proximate distal end  6  of elongate flexible body  5 . Guidewire lumen  14  comprises a hollow conduit of a diameter sufficient to accommodate a guidewire therein and extends between distal end  6  and proximal end  8 . As indicated in  FIG. 1A , the guidewire is disposed externally of light-generating device  1  near a light source array  10 , so that light source array  10  is not required to include a guidewire lumen. Flushing lumen  12  is preferably used to convey saline, or another appropriate fluid (such as heparin, a light scattering medium such as Intralipid, or an optically clear, biocompatible fluid), to displace bodily fluids (such as blood) proximate distal end  6 , when light-generating device  1  is disposed in a body lumen. Such bodily fluids (especially blood) undesirably interfere with the transmission of light from light source array  1  to target tissue. The flushing fluid is introduced into the body lumen via ports  12   a  that are disposed on distal end  6  of elongate flexible body  5 , proximate light source array  10 .  
      Light source array  10  includes one or more LEDs coupled to conductive traces  13  that are electrically connected to leads extending proximally through a power lumen  15  of light-generating device  1 , to an external power supply and control device (not shown). As an alternative to LEDs, other sources of light maybe used, such as organic LEDs, superluminescent diodes, laser diodes, fluorescent light sources, incandescent sources, and light emitting polymers. Light source array  10  is preferably encapsulated in silicone, or another biocompatible polymer, and is coupled to the distal end of elongate flexible body  5 .  
      Optional working lumen  16  is configured to enable an non integrated light source array to be employed. Instead of including integrated light source array  10 , light-generating device  1  can be configured without any integrated light source, so that a separate light source array is advanced to the target area through the working lumen after light-generating device  1  is properly positioned in the body lumen. Of course, if a non integral light source array is used, power lumen  15  is not necessary (the power leads for the separate light source element being disposed in the working lumen) and may thus be omitted. If a separate light source array is used, then a hollow, light transmissive shaft is disposed between tip  11  and ports  12   a  (i.e., if a separate light source array is employed, then reference numeral  10  corresponds to a hollow, light transmissive shaft configured to accommodate a light source array).  
      Distal end  6  of light-generating device  1  includes a hollow tip  11  coupled to a distal end of light source array  10 , (or to the hollow shaft if used in place of light source array  10 ), with an outwardly facing orifice  7   a , as well as a distal orifice  7   b , which enable light-generating device  1  to be advanced over a guidewire  2 . Note that guidewire lumen  14  does not extend into light source array  10 , and thus, the guidewire is disposed external to proximate light source array  10 . To position light-generating device  1  in a body lumen, a guidewire  2  is introduced into an artery (or other body lumen) and advanced until the guidewire is disposed adjacent a treatment area (generally an arterial lesion). Elongate flexible body  5  is then advanced over guidewire  2 , until distal end  6  is adjacent to the treatment area.  
       FIG. 1B  schematically illustrates a prior art distal protection device  19 , such as a PERCUSURGE™ or a ANGIOGUARD™ Filter, that has been advanced through a guide catheter  17 , through aorta  20 , for placement at an anastomosis of a saphenous vein graft  21 . Guide catheter  17  includes an occlusion balloon  18  disposed near a distal end  22  of guide catheter  17 . As shown in  FIG. 1C , light generating device  1  is advanced into saphenous vein graft  21 , until it is disposed between balloon  18  and distal protection device  19 . The guide catheter includes a working lumen that is larger than light-generating device  1 , so that light-generating device  1  is advanced to the treatment site within the working lumen of the guide catheter.  
      Once light-generating device  1  is properly positioned, occlusion balloon  18  is inflated to block blood flow. Saline solution (or an another biocompatible solution that facilitates light transmission) is flushed through flushing lumen  12  of light generating device  1  to displace the blood in saphenous vein graft  21 , thereby facilitating light illumination of target tissue  3 . Distal protection device  19  is activated (i.e., expanded), and light-generating device  1  is energized to illuminate target tissue  3 . Target tissue  3  will preferably have previously been treated with a photoreactive agent, but if the particular photoreactive agent employed is rapidly taken up by target tissue  3 , light generating device  1  can be used to deliver the photoreactive agent through flushing lumen  12 , or through a dedicated drug delivery lumen (not shown).  
      Distal protection device  19  is used to capture atherosclerotic debris that may be generated during the treatment of target tissue  3 . Such debris, if allowed to escape downstream, may result in clinically significant and undesirable events, including myocardial infarction, stroke, and renal failure. As noted above, studies have shown that the use of distal protection devices reduces the incidence of major adverse cardiac events by as much as 50 percent. Light generating device  1  can be moved within saphenous vein graft  21  to enable the light source array to illuminate other target tissue, if the target area extends beyond an area that can be illuminated at one time.  
       FIGS. 2A-2D  schematically illustrate a related embodiment of a light generating device  1   a , which is intended to be used in a fashion similar to that described above, in regard to light-generating device  1 . The difference between light generating device  1  ( FIGS. 1A, 1C , and  1 D) and light generating device  1   a  ( FIGS. 2A, 2C , and  2 D) is that light generating device  1   a  includes a low-pressure compliant occlusion balloon  18   a , and an inflation lumen  24  (see  FIG. 2D ). Accordingly, a guide catheter  17   a  (see  FIGS. 2B and 2C ) is not required to include an occlusion balloon, as is necessary for guide catheter  17  of  FIGS. 1B and 1C . Because the guide catheter is not required to include a balloon, it is possible, but less preferred, for the guide catheter to be smaller than optional working lumen  16  of light-generating device  1   a , so that light-generating device  1   a  is advanced to the treatment site over the guide catheter.  
       FIG. 3A  schematically illustrates a heart  26 , generally indicating the position of a saphenous vein graft  28 , a portion of which is depicted in greater detail in  FIG. 3B . The portion of saphenous vein graft  28  shown in  FIG. 3B  includes treatment areas  29  (typically having lesions or plaque). Yet another embodiment of a light-generating device is shown in  FIG. 3B . Note that while light generating device  1  of  FIGS. 1A-1D , and light generating device  1   a  of  FIGS. 2A-2D  each are intended to be used with a prior art distal protection device, the light generating devices discussed in connection with  FIGS. 3A-3F  include a distal protection member. Referring to  FIG. 3B , a light-generating device  3  includes a guiding catheter  30  and a multi-lumen light-generating catheter  32 . Guiding catheter  30  includes a low pressure occlusion balloon  31  (disposed near the distal end of guiding catheter  30 ). Also, as shown in  FIG. 3C , guiding catheter  30  has a guidewire lumen  30   a , an inflation lumen  30   b  (adapted to enable low pressure occlusion balloon  31  to be selectively inflated), a working lumen  30   c , and an aspiration lumen  30   d . Working lumen  30   c  is configured to accommodate light-generating catheter  32 , so that light-generating catheter  32  can be advanced to a treatment site within the working lumen of guide catheter  30 . Aspiration lumen  30   d  enables a flushing fluid introduced via light-generating catheter  32  (described in detail below) to be removed from the body lumen. However, if desired, the flushing lumen in light generating catheter  32  can be used both to introduce a flushing fluid, and to aspirate the flushing fluid previously introduced, so that aspiration lumen  30   d  is then not required.  
      Light-generating catheter  32  has an elongate flexible body formed from a suitable biocompatible material, such as a polymer or metal. As shown in  FIG. 3D , light-generating catheter  32  also has a plurality of lumens, including a flushing lumen  34 , a guidewire lumen  33   a , an inflation lumen  33   b , and an optional working lumen  33   c.    
      Referring back to  FIG. 3B , flushing medium is introduced into a body lumen into which light-generating catheter  32  is disposed through one or more ports  34   a . Once again, the flushing medium may be saline solution or any other appropriate medium that is suitable to displace the bodily fluids (such as blood) in a body lumen, to facilitate light illumination of the target tissue. Guidewire lumen  33   a  is a hollow conduit of a diameter sufficient to accommodate a guidewire therein, and extends between a distal end of light-generating catheter  32  and a proximal end of light-generating catheter  32 . As indicated in  FIG. 3 , the guidewire is disposed externally of light-generating catheter  32  near a light emitting portion, so that the light emitting portion is not required to include a guidewire lumen. The distal end of light-generating catheter  32  includes a hollow tip  36   a  with an orifice  36   b  that faces toward a wall of the body lumen, and a distal orifice  36   c  (in a configuration similar to that shown in  FIG. 1A  for light generating device  1 ). Orifices  36   b  and  36   c  facilitate the advancement of light-generating catheter  32  over guidewire  2 .  
      Light-generating catheter  32  includes a light source array  37 , which can optionally be coupled to collection optics (not shown). As discussed above in connection with light source array  10  of  FIG. 1A , light source array  37  may include one or more LEDs coupled to conductive traces that are electrically connected to leads extending proximally through a lumen of the light generating catheter to an external power supply and control device (not shown). As an alternative to LEDs, other sources of light maybe used, such as organic LEDs, superluminescent diodes, laser diodes, fluorescent light sources, incandescent sources, and light emitting polymers. Light source array  37  is preferably encapsulated or otherwise covered with a substantially optically transparent (at least with regard to the wavelengths emitted by light source array  37 ) biocompatible polymer, such as silicone. Light source array  37  can be integral to light-generating catheter  32  (in which case, light-generating catheter  32  preferably includes a power lumen to convey the electrical leads that are employed to couple the light source array to an external power supply), or light source array  37  can be a separate component that is advanced to the treatment site using optional working lumen  33   c , after light-generating catheter  32  is properly positioned in the body lumen. If light source array  37  is a separate component, then light-generating catheter  32  includes a transparent hollow shaft  60 , adapted to accommodate light source array  37  (such a shaft is also described above, in connection with  FIG. 1A  and light generating device  1 ).  
      Light-generating catheter  32  also includes an expandable member  38 , for centering the distal end of light-generating catheter  32 , and for either occluding blood flow or for performing angioplasty (or both). Inflation lumen  34  is adapted to selectively control the inflation of expandable member  38 , which is preferably secured to the distal portion of light-generating catheter  32  so as to encompass light source array  37 . Expandable member  38  comprises a suitable biocompatible material, such as, polyurethane, polyethylene, fluorinated ethylene propylene (FEP), polytetrafluoroethylene (PTFE) or PET (polyethylene terephthalate), and preferably, is substantially light transmissive, since light from light source array  37  must freely pass through expandable member  38  to reach the target tissue. Proximal of expandable member  38  and orifice  36   b  is a shape memory filter  39  that traps and removes emboli and/or other debris from the body lumen within which light-generating catheter  32  is being used.  
      Shape memory filter  39  moves between its first and second positions in response to a temperature change, preferably, an increase in temperature. An application of heat increases the temperature of the shape memory material above its transition temperature. The shape memory material memorizes a certain shape at a certain temperature and can be selectively activated to return to its memorized shape by applying heat to the shape memory material so that it is heated above the transition temperature. Preferably the shape memory material is a polymer; such shape memory materials are well known in the art and need not be described herein in detail. The first position of shape memory filter  39  corresponds to an un-deployed configuration, wherein shape memory filter  39  generally conforms to the distal end of the light-generating catheter  32 . The second position of shape memory filter  39  corresponds to a deployed configuration, wherein shape memory filter  39  generally expands outwardly and away from light-generating catheter  32 , until the shape memory filter contacts the walls of the body lumen in which light-generating catheter  32  is deployed, thereby preventing debris from moving past shape memory filter  39 .  
      When light generating device  3  is in use, guiding catheter  30  is introduced into a body lumen and positioned proximal of a treatment area. Then, light-generating catheter  32  is advanced through guiding catheter  30  (and over guidewire  2 , distal of guiding catheter  30 ) until light generating array  37  is disposed adjacent the treatment area. While the light-generating catheter  32  is being advanced over the guidewire to a treatment site, shape memory filter  39  is not deployed. When light-generating catheter  32  is positioned adjacent to the treatment site, shape memory filter  39  is deployed into its second position. Occlusion balloon  31  is inflated, and expandable member  38  is inflated and deflated to perform angioplasty (if desired).  
      Saline solution is then introduced to the isolated portion of the body lumen (i.e., to the portion between occlusion balloon  31  and shape memory filter  39 ) via flushing lumen  34  and removed via aspiration lumen  30   d . As noted above, flushing and aspiration could be carried out using a single lumen, by first flushing and then aspirating through the lumen. The use of a separate flushing lumen and a separate aspiration lumen enable a circulating flow to be achieved, so that more debris can be removed in a shorter time. Flushing not only removes debris, which might get past shape memory filter  39  as light generating catheter  32  is removed, but also maintains a clear light transmission path to the body lumen wall, keeping the portion of the body lumen between balloon  31  and shape memory filter  39  essentially free of blood and debris. Expandable member  38  is then again inflated to facilitate the transmission of light from light source array  37  to the body lumen wall. Preferably, light source array  37  is rotated within catheter  32 , to enable all portions of the lumen walls around the light source array to be illuminated. Alternatively, the light source array can include light sources disposed so that light is emitted outwardly of the light source array through substantially a full 360 degrees of arc.  
      As noted above, shape memory filter  39  is preferably deployed by using heat.  FIGS. 3E and 3F  schematically illustrate different embodiments for applying the required thermal energy to shape memory filter  39 . Each of  FIGS. 3E and 3F  includes a light generating catheter substantially similar to light generating catheter  32 , except for the modification discussed in detail below to enable shape memory filter  39  to be heated by the light source. In each of  FIGS. 3E and 3F , expandable member  38  has been omitted, to reduce the complexity of those Figures.  
       FIG. 3E  schematically illustrates a light generating catheter  32   a  (with the expanding member not shown, as noted above). A light source array  37   a  extends into a hollow tip  36   d . A shape memory filter  39   a  is disposed distal of orifice  36   b , to ensure that the guidewire does not interfere with the filter when it is in the deployed position. In  FIG. 3E , shape memory filter  39   a  is not yet deployed, and part of shape memory filter  39   a  overlays a portion  37   b  of light source array  37   a . Energizing light source array  37   a  produces heat that is absorbed by shape memory filter  39   a , causing the filter to deploy.  
       FIG. 3F  illustrates a related embodiment, in which a heater, rather than the light-generating array, is used to provide the heat that changes the temperature of the shape memory material comprising the filter (the distal protection device). In  FIG. 3F , a light-generating catheter  32   b  is shown. A hollow tip  36   e  includes orifice  36   b , orifice  36   c , and a heating element  35   a . A shape memory filter  39   b  is disposed distal of orifice  36   b , again to ensure that the guidewire does not interfere with the filter when it is in the deployed position. Shape memory filter  39   b  does not overlie light source array  37  in light-generating catheter  32   b . Instead, shape memory filter  39   b  is disposed adjacent to heating element  35   a , so that the heat produced by energizing heating element  35   a  causes shape memory filter  39   b  to deploy. Electrical lead  35   b  couples heating element  35   a  to an external power source (not shown). Preferably, heating element  35   a  is a resistive heating element, such as a nichrome wire, although other types of heating elements can alternatively be employed.  
       FIG. 4A  schematically illustrates another implementation of a light-generating device with an integrated distal protection device, for use during an interventional procedure. Light-generating device  4 , shown disposed in saphenous vein graft  28  (which includes treatment areas  29 ) comprises a multi-lumen catheter  41  having an elongate, flexible body formed from a suitable biocompatible material, such as a polymer or metal. Catheter  41  includes a proximal torus-shaped protection balloon  47 , and a distal torus-shaped protection balloon  48 , coupled with an impermeable exclusion sleeve  49  that extends between balloon  47  and balloon  48 ; sleeve  49  thus defines a conduit  50 . When catheter  41  is disposed in saphenous vein graft  28  (or in another body lumen) and balloons  47  and  48  are inflated, a portion  54  of saphenous vein graft  28  is defined by the walls of saphenous vein graft  28 , sleeve  49 , and balloons  47  and  48 . Portion  54  is isolated from blood flow, which is diverted around portion  54  through conduit  50 , thereby excluding treatment areas  29  (i.e., the lesions) from the vascular lumen, and allowing blood flow to continue during the intervention, which prevents embolization. When inflated, balloons  47  and  48  tend to center the portion of catheter  41  extending between the balloons within the body lumen in which the body lumen catheter  41  is deployed.  
      Catheter  41  also includes a light source array  51 , which is generally consistent with the light source arrays described above. Once again, light source array  51  can be an integral part of catheter  41 , or the light source array can be a separate component advanced through a working lumen after catheter  41  is properly positioned, as discussed above. Again, if the light source array is not an integral component of catheter, then catheter  41  includes a transparent hollow shaft adapted to accommodate the separate light source array, which is introduced into the hollow shaft via a working lumen, also as described above.  
      Catheter  41  preferably includes an expandable member  52  that is adapted to occlude blood flow through conduit  50  and to perform angioplasty (if desired). Preferably, expandable member  52  encompasses light-source array  51  (or the hollow shaft adapted to receive the light source array), and is formed from a suitable biocompatible material, such as, polyurethane, polyethylene, FEP, PTFE or PET. Because expandable member  52  encompasses light source array  51 , the expandable member is formed of a light transmissive material, so that light from light source array can freely pass through the expandable member to reach the target tissue.  
      As shown in  FIG. 4A , light source array  51  and expandable member  52  are disposed within conduit  50 , so that sleeve  49  (which defines conduit  50 ) must also be sufficiently transparent so that light from light source array  51  can freely pass through sleeve  49  to reach target tissue  29 . Further, where expandable member  52  is intended to be used to perform angioplasty, sleeve  49  must be sufficiently large and flexible, to accommodate expandable member  52  in its fully expanded state (i.e., when expandable member  52  is inflated to contact the walls of the body lumen in which catheter  41  is disposed). If it is not necessary to perform angioplasty, expandable member  52  is inflated only enough to securely position the light source array within sleeve  49 . Preferably, sleeve  49  comprises a polymeric material that transmits light of the wavelength or waveband used for the PDT. Preferably, light source array  51  rotatable within catheter  41 , to enable all portions of the lumen walls to be illuminated. Alternatively, the light source array can include light sources disposed so that light is emitted outwardly from the light source array through substantially a full 360 degrees of arc, to fully illuminate the treatment area.  
       FIG. 4B  illustrates the plurality of lumens included in catheter  41 , include a flushing and aspiration lumen  42 , an inflation lumen  43 , which enables expandable member  52  to be selectively inflated and deflated, optional conductive lumens  44 , which accommodate a laser fiber or light emitting diode wire, neither of which are shown, but which can be used in addition to or in place of light source array  51 , a balloon inflation lumen  45 , which enables balloons  47  and  48  to be selectively inflated and deflated (an additional balloon inflation lumen can be incorporated if it is desired to independently control the inflation/deflation of balloons  47  and  48 ), and a guidewire lumen  46 , which accommodates guidewire  2 , to enable catheter  41  to be advanced over the pre-positioned guidewire. Flushing and aspiration lumen  42  is connected to lumen portion  54  through one or more ports  42   a  that pass through sleeve  49 . As described above, the flushing fluid is used to displace blood and debris in portion  54 , and to facilitate illumination of target tissue  29  using light source array  51 . Exemplary suitable flushing fluids include saline solution, and the other flushing fluids noted above. While a working lumen to accommodate a separate light source array is not specifically shown, it should be understood that such a working lumen is readily included in catheter  41  (such working lumens have been indicated in  FIGS. 1D, 2D , and  3 D).  
      To use catheter  41 , guidewire  2  is first introduced into the body lumen to be treated and advanced to just beyond the target tissue. Catheter  41  is then advanced into the body lumen over guidewire  2 , until light source array  51  (or the hollow shaft adapted to receive the light source array) is disposed adjacent to target tissue  29 . Torus-shaped balloons  47  and  48  are then inflated, isolating the portion of the lumen between the balloons. Blood continues to flow through conduit  50 . Expandable member  52  is inflated to perform angioplasty (if desired). Saline solution is then flushed and aspirated through flushing and aspiration lumen  42  to maintain a clear light transmission path to the vessel wall essentially free of blood and debris. Expandable member  52  is again inflated, to displace blood flowing within conduit  50 , which may interfere with the transmission of light from light source array  51 , and to securely position the light source array within sleeve  49 . Light source array  51  is energized, preferably for less than about 50 seconds. During the administration of light to the target tissue, expandable member  52  occludes blood flow in conduit  50 . It is believed that interrupting blood flow for less than about 50 seconds, followed by enabling blood flow to resume for about 50 seconds (to enable the blood to re-perfuse), should obviate problems that are sometimes encountered when blood flow is occluded for longer intervals. Thus, expandable member  52  can be expanded and deflated cyclically, for periods of about 50 seconds each, to administer the desired PDT to a specific target area. Portion  54  (partially defined by balloons  47  and  48 ) may extend beyond the illumination limits of light source array  51 . Preferably, the light source array is then selectively repositioned within portion  54 , without having to move balloons  47  and  48 , to enable the light source array to administer PDT to all target tissue in portion  54 .  
      One structure that enables light source array  51  to be selectively repositioned without moving balloons  47  and  48  is achieved by forming the catheter body between the balloons from a substantially light transmissive polymer material. Light source array  51  is then slidably disposed in a working lumen in the catheter body, so that the light source array can be repositioned as desired. Such working lumens are shown in  FIGS. 1D, 2D  and  3 D. Expandable member  52  is coupled to the light transmissive portion of the catheter body (i.e., the portion of catheter  41  encompassed by sleeve  49 ), so that blood flow through sleeve  49  can be occluded when the light source array is energized.  
       FIG. 4C  illustrates that catheter  41  preferably includes a hollow tip  64 , which is disposed distally of light source array  51  and proximally of balloon  48 . Hollow tip  64  includes a side facing orifice  66  that enables catheter  41  to be advanced over guidewire  2  (i.e., light source array  51  does not include a guidewire lumen, and the guidewire is exposed externally to catheter  41 , proximate light source array  51 ). This configuration is shown in greater detail in  FIGS. 1A, 2A ,  3 E, and  3 F). Alternatively, but not separately shown, light source array  51  includes a guidewire lumen, or guidewire  2  can be withdrawn once balloons  47  and  48  are inflated, so that a separate light source array can be advanced through the guidewire lumen. Balloon  52  has been omitted from  FIG. 4C , to simplify the Figure.  
      Although the present invention has been described in connection with the preferred form of practicing it and modifications thereto, those of ordinary skill in the art will understand that many other modifications can be made to the present invention within the scope of the claims that follow. Accordingly, it is not intended that the scope of the invention in any way be limited by the above description, but instead be determined entirely by reference to the claims that follow.