Patent Application
20100274330
Light activated drug therapy is a process whereby light of a specific wavelength or waveband is administered to tissue, to activate a light activatable drug that has been administered to the tissue. Significantly, only the drug actually exposed to light of the proper wavelength or waveband will be activated; thus, the process is highly selective and highly controllable, simply by controlling where the light is delivered. Light activatable drugs include those that when activated fluoresce, to facilitate a diagnostic function. The diagnostic function is particularly useful where the light activatable drug selectively accumulates at tissue of a certain type. Such selectivity can be enhanced by including a binding agent to the light activatable drug, where the binding agent selectively targets certain types of tissue, such as cancer cells. Light activatable drugs also include those that when activated can result in the destruction of adjacent cells/tissue. The term photodynamic therapy (PDT) is often employed where light of a specific wavelength or waveband is administered to tissue, to enable treatment of the tissue. The term photodynamic diagnosis (PDD) is often employed where light of a specific wavelength or waveband is administered to tissue, to enable a diagnosis of the tissue. In both diagnostic and therapeutic light activated drug therapy, the tissue is rendered photosensitive through the administration of a photoreactive or photosensitizing agent having a characteristic light absorption waveband. In therapeutic light activated drug therapy, 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 accumulate or retain (or otherwise absorb) certain photoreactive agents to a much greater extent than normal tissue. Once the abnormal tissue has taken up the photoreactive agent, the abnormal tissue can then be diagnosed or treated by administering light having one or more wavelengths or wavebands corresponding to the absorption wavelengths or wavebands of the photoreactive agent. Diagnostic light activated drug therapy reveals the location of the photoreactive agent, and hence, the location of the abnormal tissue, generally via a fluorescence signal, and therapeutic light activated drug therapy can be used to cause destruction (via necrosis or apoptosis) of the abnormal tissue.
Light activated drug therapy 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 obstruction of the coronary vasculature. Clinical results of PTCA have been enhanced by integrating one or more bare metal stents to prop open the revascularized vessel. However, restenosis due to vascular tissue proliferation at the site of the intervention often compromises the initial clinical benefit. A more recent treatment based on the use of drug eluting stents has reduced the rate of restenosis in coronary interventions. As effective as such therapies are in the coronaries, a new form of therapy is needed for treating peripheral arterial disease in the lower limbs, where the extent of disease and the challenges posed in this vascular bed are in many cases more demanding than in the coronary vasculature. New therapies are also required to treat more problematic coronary disease, such as unstable or vulnerable plaque, bifurcation disease, saphenous vein bypass graft disease, and diffuse long lesions (whether these occur in either the coronary or peripheral vasculatures).
As noted above, the objective of light activated drug intervention 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 photonic energy within light of the characteristic wavelength/waveband delivered to the tissue is taken up by the photoreactive agent and, through inter-system crossing, this energy is transferred to molecular oxygen in the tissue within which the photoreactive agent is distributed. A highly reactive form of oxygen known as singlet oxygen is formed through this process. Singlet oxygen damages cellular and sub-cellular membranes, causing apoptotic or necrotic cell death, according to the quantities of drug and light in the tissue. The central strategy to inhibit arterial restenosis using light activated drug therapy, for example, is to cause a depletion of vascular smooth muscle cells, which are a source of neointimal cell proliferation. One of the advantages of light activated drug therapy is that it is a targeted technique, in that selective or preferential localization of the photoreactive agent to specific tissue enables only the selected tissue to be treated. Preferential localization of a photoreactive agent in areas of endovascular injury (for example, as caused by plaque debulking procedures such as angioplasty or atherectomy) or atherosclerotic disease, with little or no photoreactive agent being taken up by healthy or uninjured portions of the arterial wall, can therefore enable not only site-specific light activated drug therapy of an individual focal lesion, but also treatment of multifocal lesions within long vascular segments.
Light generating and delivery systems for light activated drug therapy 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. 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 light activated drug therapy 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, significant inefficiencies in coupling light output from the laser and the optical fiber used to deliver light to the treatment site, 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 light activated drug therapy, 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.
For vascular application of light activated drug therapy, 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.
The present invention encompasses light generating devices for illuminating portions of vascular tissue to administer light activated drug therapy (PDT or PDD). 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 activation of the photoreactive agent and will therefore not generate singlet oxygen. An array of light sources can include light sources that provide more than one wavelength or produce light that covers one or more wavebands. 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, even one that follows a tortuous path.
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 in 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 or collect such debris in the blood, enabling its removal 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. Cycles of light therapy/diagnosis interspersed with periods of reperfusion can be used to reduce risk of ischemia in distal tissues caused by interruption in blood flow. 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 the entire 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. Cycles of light therapy interspersed with periods of reperfusion can be used to reduce risk of ischemia in distal tissues caused by interruption in blood flow. 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. Cycles of light therapy interspersed with periods of reperfusion can be used to reduce risk of ischemia in distal tissues caused by interruption in blood flow. 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.
This Summary has been provided to introduce a few concepts in a simplified form that are further described in detail below in the Description. However, this Summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.
Various aspects and attendant advantages of one or more exemplary embodiments and modifications thereto 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:
Exemplary embodiments are illustrated in referenced Figures of the drawings. It is intended that the embodiments and Figures disclosed herein are to be considered illustrative rather than restrictive. No limitation on the scope of the technology and of the claims that follow is to be imputed to the examples shown in the drawings and discussed herein.
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 light activated drug therapy with the present invention may be either diagnostic (i.e., PDD), 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 (i.e., PDT), wherein the wavelength or waveband of the light delivered to photosensitized tissue under treatment causes the photoreactive agent to undergo a photochemical interaction with molecular oxygen in the tissue yielding highly reactive singlet oxygen, causing biological changes in the tissue within which the photoreactive agent is distributed.
Referring to
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
Light source array 10 includes one or more LEDs coupled to conductive traces (not shown) that are electrically connected to conductors 13 extending proximally through a power lumen 15 of light-generating device 1, to an external power supply and control device (not shown). Thus, conductors 13 enable the LEDs to be coupled to a power source. 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 a 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 a tip 11 and ports 12a (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 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 7a, as well as a distal orifice 7b, 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 of and proximate to light source array 10, such that the portion of the guidewire proximate to the light source array is exposed to the body lumen, as indicated in
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 7. Distal protection device 19 is activated (i.e., expanded), and light-generating device 1 is energized to illuminate target tissue 7. Target tissue 7 will preferably have previously been treated with a photoreactive agent, but if the particular photoreactive agent employed is rapidly taken up by target tissue 7, 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 7. 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.
It should be noted that the light source array 10 and hollow tip 11 each have a diameter smaller than that of elongate flexible body 5. Note that as the guidewire extends beyond elongate flexible body 5 to hollow tip 11, the guidewire is parallel to and external of the light source array. The reduced diameter of the light source means that the guide wire does not radially extend into the body lumen beyond elongate flexible body 5. In other words, a cross sectional footprint of the guidewire, the hollow tip, and the light source array are smaller than a cross sectional footprint of elongate flexible body 5. The structures of
Light-generating catheter 32 has an elongate flexible body formed from a suitable biocompatible material, such as a polymer or metal. As shown in
Referring back to
Note that light-generating catheter 32 does not require a guide-wire lumen, as light-generating catheter 32 is advanced through the working lumen of guide catheter 30. If desired, light-generating catheter 32 can incorporate a guide-wire lumen, to enable light-generating catheter 32 to be used independent of a guide catheter.
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
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 33b 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. Distal of expandable member 38 and orifice 36b 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, guide catheter 30 is introduced into a body lumen and positioned proximal of a treatment area. Then, light-generating catheter 32 is advanced through guide catheter 30 (and over guidewire 2, distal of guide catheter 30) until light source 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 30d. 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.
It should be recognized that if desired the distal protection device can be eliminated from the light generating catheters described above.
Referring once again to
Particularly if the treatment area is large enough to require light-generating catheter 32 to be repositioned several times, it will be beneficial to provide a bypass for blood flow occluded by balloon 31. Such a bypass can be implemented by adding a bypass lumen 27 to the distal end of the guide catheter. Such a bypass can also be implemented by configuring balloon 31 to leak, in the sense balloon 31 is configured to ensure that the guide catheter remains fixed in position, without fully occluding blood flow distal of the balloon. In at least one embodiment (see
Another useful modification to the guide catheter and light generating catheter of
Yet another modification to the guide catheter and light generating catheter of
Still another modification to the guide catheter and light-generating catheter of
The array formed of light emitting devices 153 and conductive substrate 155 is disposed between proximal portion 154 and distal portion 152, with each end of the array being identifiable by radio-opaque markers 158 (one radio-opaque marker 158 being included on distal portion 152, and one radio-opaque marker 158 being included on proximal portion 154). Radio-opaque markers 158 comprise metallic rings of gold or platinum. Light-generating apparatus 150 includes an expandable member 157 (such as a balloon) preferably configured to encompass the portion of light-generating apparatus 150 disposed between radio-opaque markers 158 (i.e., substantially the entire array of light emitting devices 153 and conductive substrate 155). As discussed above, expandable member 157 enables occlusion of blood flow past distal portion 152 and centers the light-generating apparatus. Where an expandable member is implemented as a fluid filled balloon, the fluid acts as a heat sink to reduce a temperature build-up caused by light emitting devices 153. This cooling effect can be enhanced if light-generating apparatus 150 is configured to circulate the fluid through the balloon, so that heated fluid is continually (or periodically) replaced with cooler fluid. Preferably, expandable member 157 ranges in size (when expanded) from about 2 mm to 10 mm in diameter. Preferably such expandable members are less than 2 mm in diameter when collapsed, to enable the apparatus to be used in a coronary vessel. Those of ordinary skill will recognize that catheters including an inflation lumen in fluid communication with an inflatable balloon, to enable the balloon to be inflated after the catheter has been inserted into a body cavity or blood vessel, are well known. While not separately shown, it will therefore be understood that light-generating apparatus 150 (particularly proximal portion 154) includes an inflation lumen. When light emitting devices 153 are energized to provide illumination, expandable member 157 can be inflated using a radio-opaque fluid, such as Renocal 76™ or normal saline, which assists in visualizing the light-generating portion of light-generating apparatus 150 during computerized tomography (CT) or angiography. The fluid employed for inflating expandable member 157 can be beneficially mixed with light scattering material, such as Intralipid, a commercially available fat emulsion, to further improve dispersion and light uniformity.
Light-generating apparatus 150 is positioned at a treatment site using a guidewire 151 that does not pass through the portion of light-generating apparatus 150 that includes the light emitting devices. Instead, guidewire 151 is disposed external to light-generating apparatus 150—at least between proximal portion 154 and distal portion 152. Thus, the part of guidewire 151 that is proximate light emitting devices 153 is not encompassed by expandable member 157. Distal portion 152 includes an orifice 159a, and an orifice 159b. Guidewire 151 enters orifice 159a, and exits distal portion 152 through orifice 159b. It should be understood that guidewire 151 can be disposed externally to proximal portion 154, or alternatively, the proximal portion can include an opening at its proximal end through which the guidewire can enter the proximal portion, and an opening disposed proximal to light emitting devices 153, where the guidewire then exits the proximal portion.
The length of the linear light source array (i.e., light emitting devices 153 and conductive substrate 155) is only limited by the effective length of expandable member 157. If the linear array is made longer than the expandable member, light emitted from that portion of the linear array will be blocked by blood within the vessel and likely not reach the targeted tissue. As described below in connection with
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 the 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 transparent 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 the light source array can freely pass through the expandable member to reach the target tissue.
As shown in
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 in the coronary circulation. 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
Portion 62 in an enlarged view in
Because the light source arrays of the present invention are intended to be used in flexible catheters inserted into blood vessels or other body passages, it is important that the light source arrays be relatively flexible, particularly where a light source array extends axially along some portion of the catheter's length. Clearly, the longer the light source array, the more flexible it must be. Light source array 180 (
External bond wires can increase the cross-sectional size of an LED array, and are prone to breakage when stressed.
Turning now to
In
Once light emitting devices 222 have been inserted into compartments 221 and electrically coupled to conductive core 224, a second electrical conductor 226, such as a flexible conductive substrate or a flexible conductive wire, is longitudinally positioned along the exterior of guidewire 220, and electrically coupled to each light emitting device 222 using suitable electrical connections 228, such as conductive adhesive 223 as (illustrated in
As already noted above, using a plurality of expandable members enables a linear light source array that is longer than any one expandable member to be employed to illuminate a treatment area that is also longer than any one expandable member.
Referring to the cross-sectional view of
Once multi-lumen catheter 230 is positioned within blood vessel 237 so that a target area is disposed between expandable member 233a and expandable member 233d, inflation lumen 232a is first used to inflate expandable member 233a. Then, the flushing fluid is introduced into blood vessel 237 through port 238. The flushing fluid displaces blood distal to expandable member 233a. After sufficient flushing fluid has displaced the blood flow, inflation lumen 232b is used to inflate expandable members 233b and 233c, thereby trapping the flushing fluid in portions 237a, 237b, and 237c of blood vessel 237. The flushing fluid readily transmits light of the wavelength(s) used in administering PDT, whereas if blood were disposed in portions 237a, 237b, and 237c of blood vessel 237, light transmission would be blocked. An alternative configuration would be to provide an inflation lumen for each expandable member, and a flushing port disposed between each expandable member. The expandable members can then be inflated, and each distal region can be flushed, in a sequential fashion.
A preferred flushing fluid is saline. Other flushing fluids can be used, so long as they are non-toxic and readily transmit light of the required wavelength(s). As discussed above, additives can be included in flushing fluids to enhance light transmission and dispersion relative to the target tissue. Working lumen 236 is sized to accommodate light emitting guidewire 235, which can be fabricated as described above. Multi-lumen catheter 230 can be positioned using a conventional guidewire that does not include light emitting devices. Once multi-lumen catheter 230 is properly positioned and the expandable members are inflated, the conventional guidewire is removed and replaced with a light emitting device, such as an optical fiber coupled to an external source, or a linear array of light emitting devices, such as LEDs coupled to a flexible conductive substrate. While not specifically shown, it will be understood that radio-opaque markers such as those discussed above can be beneficially incorporated into light-generating apparatus 231 to enable expandable members 233a and 233d to be properly positioned relative to the target tissue.
Still another embodiment of the present invention is light-generating apparatus 241, which is shown in
Light-generating apparatus 241 is based on an elongate and flexible multi-lumen catheter 240 that includes light emitting array 246 (including a plurality of light sources 246a) and a plurality of expandable members 242a-242d. Light emitting array 246 preferably comprises a linear array of LEDs. As noted above, while four expandable members are shown, more or fewer expandable members can be employed, with at least two expandable members being particularly preferred. The materials and sizes of expandable members 242a-242d are preferably consistent with those described above in conjunction with multi-lumen catheter 230. The walls of multi-lumen catheter 240 proximate to light emitting array 246 are formed of a flexible material that does not substantially reduce the transmission of light of the wavelengths required to activate the photoreactive agent(s) with which light-generating apparatus 241 will be used. As indicated above, biocompatible polymers having the required optical characteristics can be beneficially employed, and appropriate additives can be used. Preferably, each expandable member is constructed of a material and inflated using a fluid that readily transmit light of the required wavelength(s).
Referring to the cross-sectional view of
It should be recognized that in any of the embodiments disclosed above wherein a first expandable member is disposed proximal of the light source or light source array, and a second expandable member is disposed distal of the light source/array, activating the first and second member will isolate a region of the vessel proximate the light source/array. The photoreactive drug can then be administered into the region between the first expandable member and the second expandable member, thereby increasing photoreactive drug uptake in tissue surrounding the region, while limiting introduction of the photoreactive drug to other portions of a patient's body. This aspect of the invention can be implemented even where one of the expandable members only partially occludes blood flow (i.e., where that expandable member is primarily an anchoring member, as opposed to an occlusion member), so long as the blood flow naturally moves from the anchoring member to the other expandable member.
Although the concepts disclosed herein have been described in connection with the preferred form of practicing them and modifications thereto, those of ordinary skill in the art will understand that many other modifications can be made thereto within the scope of the claims that follow. Accordingly, it is not intended that the scope of these concepts in any way be limited by the above description, but instead be determined entirely by reference to the claims that follow.
This application is a continuation of a copending patent application Ser. No. 12/101,069, filed on Apr. 10, 2008, which itself is a continuation-in-part of a patent application Ser. No. 10/888,572, filed on Jul. 9, 2004, which itself is based on a prior copending provisional application, Ser. No. 60/486,178, filed on Jul. 9, 2003, the benefit of the filing dates of which is hereby claimed under 35 U.S.C. §119(e) and 35 U.S.C. §120. patent application Ser. No. 10/888,572 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 benefit of the filing dates of which is hereby claimed under 35 U.S.C. §119(e) and 35 U.S.C. §120. This present application is further a continuation-in-part of a copending patent application Ser. No. 11/834,572, filed on Aug. 6, 2007, the benefit of the filing date of which is hereby claimed under 35 U.S.C. §120.
| Number | Date | Country | |
|---|---|---|---|
| 60486178 | Jul 2003 | US | |
| 60455069 | Mar 2003 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12101069 | Apr 2008 | US |
| Child | 12831159 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 10888572 | Jul 2004 | US |
| Child | 12101069 | US | |
| Parent | 10799357 | Mar 2004 | US |
| Child | 10888572 | US | |
| Parent | 11834572 | Aug 2007 | US |
| Child | 10799357 | US |
