WO2008086376A2

WO2008086376A2 - Therapeutic devices for the treatment of varicosity

Info

Publication number: WO2008086376A2
Application number: PCT/US2008/050545
Authority: WO
Inventors: Zihong Guo; Nicholas Yeo; Phil Burwell; Ignacio Cespedes; Wade Watters
Original assignee: Light Sciences Oncology, Inc.
Priority date: 2007-01-08
Filing date: 2008-01-08
Publication date: 2008-07-17
Also published as: WO2008086376A3

Abstract

The present invention provides methods and devices for treating varicosities, including varicose veins, by administering therapeutic energy. In one embodiment, energy is delivered to the interior of a vessel using a catheter containing an energy emitting source, thereby causing ablation of the vessel without damage to surrounding tissue. The methods of the invention may further include the use of a photosensitizer that binds to the interior of the vessel wall or a chromophore, both of which generate localized thermal damage to the interior vessel wall without harming surrounding tissue. In another embodiment, the present invention provides less invasive methods of treating varicosities, which include introducing a heat-activated glue, photosensitizer solution, or heatable liquid into a vessel being treated and administering light from an external source sufficient to activate the glue to close the vessel, activate the photosensitizer to damage the vessel, or heat the liquid to damage the vessel.

Description

THERAPEUTIC DEVICES AND METHODS OF USE THEREOF FOR THE

TREATMENT OF VARICOSITY

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit under 35 U. S. C. § 119(e) of U.S. Provisional Patent Application No. 60/879,466 filed January 8, 2007, where this provisional application is incorporated herein by reference in its entirety.

BACKGROUND

Technical Field The present invention relates to the treatment and prevention of varicosity and other venous disorders. In particular, the present invention provides methods and systems for using energy to treat varicosity, including one or more varicose veins.

Description of the Related Art Varicose veins are estimated to affect up to 60% of all American adults and the incidence of their occurrence increases with age. As the population demographics shift to increasing age, the absolute number of affected individuals will certainly increase. It is estimated that 41 % of American women will have varicose veins in the fifth decade, rising to 72% in the seventh decade. For men, 24% are estimated to have varicose veins in their 40s, increasing to 43% by the seventh decade.

Varicose veins are abnormally enlarged and tortuous vessels that result when veins become incompetent. If the thin flaps of the venous valves of a vein no longer meet in the midline, the vein may fail to properly function and may therefore be incompetent. These types of valve failures allow blood to flow in a retrograde, or reflux, direction. Superficial venous reflux introduces elevated intravascular pressure into veins that are intended to function at a relatively low-pressure. This abnormally high pressure progressively promotes various vascular problems, such as vein distention, dilation, and tortuosity. Since the superficial veins lack muscle support and reside close to the surface of the skin, they become visible with increased intravascular pressure. The condition is further aggravated by the weakening of the affected vein's walls. Varicose veins are often present in the back of the calf or on the inside of the leg between the groin and ankle. Veins that are often affected include, but are not limited to, those shown in Figure 1. Figure 1 shows an epigastric vein 50, sapheno-femoral junction 52, the great saphenous vein 54 (superficial system), femoral vein 58, and small saphenous vein 60 (superficial system).

Great saphenous vein (GSV) reflux is a common underlying cause of varicose veins. Traditional treatment of GSV reflux has been surgical removal of the GSV. Although surgical ligation and stripping of the GSV under general anesthetic has been frequently performed, it is associated with significant perioperative morbidity. Nevertheless, it is estimated that around one million vein-stripping procedures are conducted each year in the U.S. and Europe.

In an attempt to reduce morbidity and improve recovery time, several minimally invasive techniques have been developed as alternatives to these types of surgical procedures. Endovenous laser treatment (ELT) and radiofrequency ablation (RFA) are two minimally invasive techniques enabling large amounts of energy to be delivered to the target vessel, thereby heating the diseased vein to a target temperature threshold around 85-100° C. The heat causes modification of the vein's collagen structure and promotes fibrosis leading to reduction in size of the vein and, ultimately, its collapse. Successful varicose vein treatment often requires permanent damage to the tunica intima (endothelium and underlying connective tissue). Collateral damage to the perivenous tissues (i.e., beyond the tunica external) is avoided. Tumescent anesthesia is, therefore, injected along the track of the vein being treated to create a heat-sink, thereby mitigating the risk of collateral thermal effects, particularly if the skin is less than 0.5 cm above the vein being treated. Various tissue layers in blood vessel walls are shown in Figure 2. Figure 2 shows a valve 70, the endothelium of the tunica interna (intima) 72, connective tissue 74 (elastic and collagenous fibers), tunica media 76, and tunica externa 78 (adventitia). One of the major limitations of ELT is the need to precisely correlate energy delivery with vein diameter to ensure the thermal threshold temperature is achieved through the depth of the tunica intima. The difficulty of this task is exacerbated by hydrostatic pressure from the tumescent anesthesia, which often causes the vein to collapse fully or partially. EFT and RFA often use a catheter-delivered device to transmit energy to the vein. The devices are delivered through a delivery catheter delivered over a guidewire to a point 1-2 cm below the saphenofemoral junction (SFJ). The energized device is then manually pulled back through the target vein. The literature points to this manual pull-back procedure as being a tedious part of the procedure for the operator. Also, in the case of pulsed laser delivery, manual pull-back can introduce positioning inaccuracy.

RFA devices are often in the form of a bipolar, high-frequency electrosurgical device deployed as an array of electrodes that create a 6-8 mm long thermal footprint on the vessel surface. The array of electrodes is pulled back at a speed of 2.5-3 cm/min. Manual compression is applied to the groin. The vein is exsanguinated before the pull-back procedure, either by compression or saline infusion. The device incorporates a complicated temperature feedback circuit for adjusting power in an attempt to maintain an even vein wall temperature. An impedance feedback provides an indication of the adequacy of juxtaposition between the electrodes and the vein wall.

Unfortunately, these types of RFA devices may be prone to malfunctions, need complicated calibrations, and not result in desired wall temperatures.

In ELT devices, energy from the ELT fiber is delivered either pulsed (pulse duration 1-3 seconds with fiber pull-back in 3-5 mm increments every 2 seconds) or continuously with constant pull-back at a speed of 1-3 mm/s. The literature suggests continuous delivery is preferred. Treatment time, i.e., thermal delivery time, for a 30 cm GSV is typically 10 min for RFA, 2.5 min for pulsed ELT, and 1.5 min for continuous ELT. Overall procedure time is approximately 50-60 min. Following ELT or RFA, the leg is bandaged and graduated compression is applied to maintain the vein in a collapsed state while the fibrotic process continues to obliterate the vein.

Particular contraindications for the use of either ELT or RFA include: (1) significant venous tortuousity that prevents catheter deployment within the target vein; (2) veins > 12 mm in diameter; and (3) superficial veins that are too prominent, i.e., <0.5cm from the skin surface, where the risk of thermal injury to the skin is too great. In addition, it was has been found that 36 of 63 (57%) of patients screened for potential treatment of venous insufficiency using the VNUS radiofrequency closure catheter were excluded because of either varicose tortuosity or large veins. Accordingly, there is clearly an unmet need for alternative treatment of varicosity, which avoids some of the undesirable side-effects associated with vein-stripping and permits treatment of veins having significant tortuosity or a superficial location, such that ELT and RFA cannot be used.

BRIEF SUMMARY In some embodiments, a method of treating a varicosity is provided. The method comprises inserting a catheter into a varicose blood vessel, wherein the catheter comprises a deployable photonic delivery device inside its distal tip. The photonic delivery device is deployed from inside the catheter. Light is administered from the photonic delivery device to the interior of the varicose blood vessel, wherein the wavelength of the light and the duration of administration is sufficient to cause destruction of the vessel.

In some other embodiments, a method of treating a varicosity in a patient comprises providing a photosensitizer to the interior of a varicose vessel in the patient, wherein a portion of the photosensitizer binds to cells on the interior of the vessel wall. Light is administered to the skin of the patient generally over the area of the varicose vessel. As used herein, the term "over" is broadly construed to include, without limitation, adjacent to or above in place or position. The light is administered at a wavelength that activates the photosensitizer, thereby damaging the vessel. In yet other embodiments, a method of treating a varicosity in a patient comprises providing a photoactivatable tissue glue to the interior of a varicose vessel in a patient. Light is administered to the skin of the patient generally over the area of the varicose vessel, wherein the light is administered at a wavelength that activates the tissue glue. The vessel is physically compressed during or following light administration, thereby closing the vessel. In some embodiments, the light activated damage can lead to closure of the varicosity without damage to the surrounding tissue in which the photosensitizer is not present.

In some embodiments, a method of treating a varicosity in a patient comprises providing an energy absorbing chromophore to the interior of a varicose vessel in the patient. Light is administered to the skin of the patient generally over the area of the varicose vessel, wherein the light is administered at a wavelength that activates the chromophore, thereby heating and damaging the cells lining the interior of the vessel. The vessel is physically compressed during or following light administration, thereby causing closure of the vessel.

In some embodiments, a method of treating a varicosity in a patient is provided. The method comprises performing non-invasive real-time imaging to identify a varicosity in a patient and administering light through the skin of the patient to the varicosity identified by the imaging. The light is administered from an array of directional energy sources at a wavelength that causes energy absorption by the varicosity, whereby the accumulation of energy at the varicosity is sufficient to cause closure of the varicosity and surrounding tissues are not irreversibly damaged.

In yet other embodiments, a method of treating a varicosity comprises providing a bio-absorbable, double-sided bio-adhesive tape comprising a pressure-sensitive matrix comprising a photosensitizer or photosclerosant to the interior of a varicosity, administering pressure to the varicosity, and administering light to the varicosity, at a wavelength that activates the photosensitizer or photosclerosant, thereby causing closure of the vessel. In some embodiments, a method of treating a varicosity comprises introducing a catheter comprising a distal compliant balloon containing a heatable liquid medium into a varicose vessel and administering heat to the liquid sufficient to increase the temperature of the liquid to a level sufficient to cause permanent damage to the interior of the vessel. In yet other embodiments, a device adapted for the treatment of varicosities comprises a catheter, a guidewire, and a light source. The catheter is sized for insertion into a blood vessel and comprises a lumen and a distal tip having a proximal end. The guidewire is sized to be received and extend through the lumen of the catheter. The light source is located in the lumen adjacent to the distal tip of the catheter, wherein the light source is deployable from the distal tip of the catheter.

The light source can include, without limitation, one or more light emitters, such as LEDs (e.g., edge emitting LEDs, surface emitting LEDs, organic LEDs, super luminescent LEDs), laser diodes, and the like. An exemplary light emitter can emit appropriate wavelength(s) or waveband(s) suitable for treating the patient, with or without using a treatment agent. If a treatment agent (e.g., a photoreactive or photosensitive agent) is utilized, the light emitters may emit radiation wavelength(s) or waveband(s) that correspond with, or at least overlap with, the wavelength(s) or waveband(s) that excite or otherwise activate the agent. Photosensitive agents can often have one or more absorption wavelengths or wavebands that excite them to produce substances which damage, destroy, or otherwise treat target tissues of the patient. The photosensitive agents and light emitters can be selected to achieve the desired interaction. In some embodiments, a method of treating a varicosity in a patient is provided. The method includes providing a photosensitizer or conjugate thereof to an interior of a varicose vessel in the patient. The conjugate can be complex formed by the photosensitizer and a targeting agent and/or receptor in the tissue or it can be photosensitizer linked/bounded to a targeting agent, target on a cell {e.g., a receptor), and the like. A portion of the photosensitizer can bind to cells on the interior of the varicose vessel. Light is administered to a region of the patient's skin generally over the varicose vessel. In some embodiments, the light is administered at a wavelength that activates the photosensitizer, thereby damaging the vessel.

Photosensitizer can be removed from the target site. In some embodiments, the method includes removing at least some unbound photosensitizer from the interior of the varicose vessel prior to the administration of light. For example, the varicose vessel can be flushed with a fluid, such as saline. In other embodiments, the unbound photosensitizer can be flushed using normal body functioning, such as normal blood flow. In some embodiments, for example, the light administration can be performed a sufficient amount of time (e.g., 10 minutes) after providing the photosensitizer to ensure that a sufficient amount of the unbound photosensitizer is flushed away. The photosensitizer can be flushed away to minimize or limit the risk of damage to surrounding tissue caused by the presence of photosensitizer not bound to the varicose treatment target.

The present invention provides novel devices and methods for treating varicosity. The invention also provides novel systems useful in carrying out the methods of the present invention.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS In the drawings, identical reference numbers identify similar elements or acts. The sizes and relative positions of elements in the drawings are not necessarily drawn to scale. For example, the shapes of various elements and angles are not drawn to scale, and some of these elements are arbitrarily enlarged and positioned to improve drawing legibility. Figure 1 is a schematic depiction of a human leg showing certain veins.

Figure 2 is a longitudinal cross-sectional view of a typical blood vessel showing layers of the vessel wall. Figure 3 is a schematic of a treatment system positioned in a subject, wherein the treatment system includes an endovenous photoablative device, according to one illustrated embodiment.

Figure 4 is a schematic of a treatment system positioned in a subject, wherein the treatment system includes an endovenous photoablative device, according to one illustrated embodiment.

Figure 5 is a schematic of an endovenous therapy system positioned in a blood vessel, wherein the therapy system includes a light activatable device and photoreactive agent.

Figures 6A and 6B are schematics of an endo-exovenous therapy system that includes a photo curing tissue glue and an exovenous light activating device, according to one illustrated embodiment.

Figure 7 is a schematic of an exovenous therapy system that includes a chromophore and a light device, according to one illustrated embodiment. Figure 8 is a schematic of a transcutaneous therapy system that includes a color-flow duplex Doppler ultrasonography-guided energy delivery device, according to one illustrated embodiment.

Figure 9 is a schematic of a device that includes a bifurcated light source, according to one illustrated embodiment. Figure 10 is a schematic of a system that includes a catheter comprising a distal compliant balloon containing a heatable liquid medium, according to one illustrated embodiment.

Figure 11 is a schematic of a system that includes an occlusion balloon catheter and an outlet/inlet for medium of elevated temperature, according to one illustrated embodiment. Figure 12 is a schematic of a treatment system ready for delivering energy to a vessel in a subject, according to one illustrated embodiment.

Figure 13 is a schematic of a catheter of a treatment system positioned within a vessel, according to one illustrated embodiment.

Figure 14 is a partial cross-sectional view of a retraction mechanism of a treatment system, according to one illustrated embodiment.

Figure 15 is a side eievational view of a cooling mechanism between a light source and a target vessel, according to one illustrated embodiment.

DETAILED DESCRIPTION

In the following description, certain specific details are set forth in order to provide a thorough understanding of various disclosed embodiments. However, one skilled in the relevant art will recognize that embodiments may be practiced without one or more of these specific details, or with other methods, components, materials, etc. In other instances, well-known structures associated with light emitters, light emitting diodes, lasers, catheters, guide wires, and controllers have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments. Unless the context requires otherwise, throughout the specification and claims which follow, the word "comprise" and variations thereof, such as, "comprises" and "comprising" are to be construed in an open, inclusive sense, that is as "including, but not limited to."

Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Further more, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

In various embodiments, the present invention provides, without limitation, methods of treating varicosities. A varicosity is an enlarged and tortuous vein, artery, or lymphatic vessel, including, e.g., a varicose veins and a varix. A varicose vein is a vein that is permanently dilated, and a varix is an abnormally enlarged or twisted blood vessel or lymphatic vessel. In certain embodiments, varicosities treated according to the invention are medically relevant or pathological conditions, such as, e.g., GSV. In other embodiments, the methods of the invention are used for primarily cosmetic purposes, e.g., in the treatment of spider veins. The methods of the invention may be used to treat a variety of different veins, arteries, and blood vessels, including but not limited to those shown in Figure 1. The methods, devices, and systems of the invention may be used to treat varicosities located anywhere within a patient, including, e.g., a leg. Patients may be any animal, but are typically humans or other mammals.

In certain embodiments, the present invention provides methods of treating varicosities comprising administering photoablative light to the interior of the varicose vessel. These methods may be practiced using the photoablative devices and systems described herein or known in the art. In other embodiments, methods of the present invention comprise providing a photoreactive agent or a chromophore to the interior of the vessel and then administering light at a wavelength that activations the photoreactive agent or chromophore, resulting in damage to the interior of the vessel that leads to ablation or permanent closure of the vessel. The present invention also includes a method comprising contacting the interior of a varicose vessel with a heated solution, which causes thermal damage to the interior of the vessel. Accordingly, in various embodiments, the present invention provides devices, methods, apparatus, and systems for light and/or heat treatment that damages or ablates blood vessels and is, therefore, useful in the treatment of varicosities, including, without limitation, varicose veins. Some methods disclosed herein may offer one or more advantages over prior art methods, such as surgery, ELT, and RFA. First, they do not require vein stripping, which is associated with significant surgical risks and a long recovery time. In addition, they accommodate variations in vessel diameter and, therefore, may be used to administer consistent light throughout a vessel having a varying diameter by, for example, maintaining the distance between the light source and the interior surface of the vessel. This avoids the need to accurately modulate the energy to compensate for varying vessel diameter. Also, in certain embodiments, the methods and devices of the present invention utilize a photon generating light source, which provides procedural cost economies over prior art devices. Another advantage of the methods of the present invention is that since they are able to localize light or heat delivery to the interior of the vessel wall, without substantially affecting surrounding tissue, they do not require the use of tumescent anesthesia. The following description of specific embodiments of the present invention is provided to exemplify various aspects of the invention and its uses. As will be understood by the skilled artisan, the methods, devices, and systems of the invention specifically exemplified herein may be adapted to achieve the same or substantially similar results, and such routine adaptions are within the scope of the present invention.

Photoablation methods and devices

Embodiments disclosed herein may provide methods, devices, and systems for the photoablation of varicosities, including an endovenous photoablative device and related methods of use thereof. Accordingly, the invention includes a method that comprises providing a light source to the interior of a varicose vessel using a catheter. Light is administered by the light source to the interior of the treated vessel, thereby generating heat sufficient to cause the vessel or a portion thereof to ablate, degrade, die, or undergo apoptosis. Exemplary methods may be practiced using a catheter that either itself includes a light source or through which a light source can be inserted. In various embodiments, the catheter is inserted into the vessel being treated. The light source is then deployed from within the catheter, or inserted through the catheter, the end result being that the light source is located outside of and at the distal end of the catheter, where it can be used to administer light to the interior of the vessel. In particular embodiments, the light source comprises two or more branches, which when deployed from the catheter, spread out to contact the interior wall of the vessel. In one embodiment, the branches may spread to accommodate vessels having diameters of about 3 mm to about 20 mm. Alternatively, the catheter may be transparent to the light, so that the light source does not need to extend beyond the catheter. The light source can deliver light through the transparent catheter to the target site. Light can be administered at a wavelength appropriate to generate thermal injury to the interior of the vessel.

In one embodiment, the light is administered to various regions of the vessel at subsequent times. A variety of different devices and procedures may be used to accomplish this. For example, the light source may be initially provided to the distal region of the vessel and then pulled-back through the vessel so as to administer light throughout the vessel. The light source may be attached to or otherwise associated with the catheter, which is pulled-back through the vessel. Alternatively, the catheter may be transparent and the light source may be pulled back through this transparent catheter. In particular embodiments, the catheter and/or light source are pulled-back through the vessel (or catheter) using an automated pull-back device, which ensures that the rate of pull-back is consistent.

In certain embodiments, the light source is a photon delivery device for delivering energy (e.g., light/radiation energy, thermal energy, combinations thereof, or other suitable energy) to a treatment site. In some embodiments, the photon delivery device may comprise one or more light sources, such as emitting elements, that generate one or more wavelengths that may cause thermal damage, e.g., 800 nm -1400 nm or, in particular embodiments, 810 nm, 940 nm, 980 nm, 1064 nm, or 1320 nm. In certain embodiments, a light source comprising multiple elements, such as light emitting diodes (LEDs), may be present within a transparent catheter or on the exterior of a catheter. The elements of the light source may be activated sequentially, e.g., from the distal end to the proximal end of the vessel, thereby achieving the same or similar effect as if the light source was pulled-back through the vessel. A current can be delivered to activate the light source. The activated light source generates and emits light. Once the current is stopped, the light source is deactivated and stops generating and emitting light. In a different embodiment, light is administered to the entirety of the vessel being treated at the same time. In various embodiments, the interior of the vessel wall is heated to a temperature of at least 40, 50, 60, 70, 80, 100, 110, 120, 130, 140, or 150° C. The methods of the present invention may further include, in some embodiments, at least partially closing the passageway in the vessel by, for example, collapsing or compressing the vessel wall. In some embodiments, the blood vessel is mechanically collapsed or compressed by applying pressure, via vacuuming, and/or by any other suitable method for at least the thermal relaxation time or for a time sufficient to allow the apposed walls of the blood vessel to couple together. The apposed walls of the blood vessel may be coupled together via a permanent weld.

The methods of the present invention may also include excluding blood flow from the region of the vessel being treated with light. This may be accomplished using tourniquets at one or both the distal end and/or proximal end of the vessel being treated, or by use of a balloon catheter. In one embodiment, blood is removed from the vessel being treated prior to administration of light so as to allow the light to reach the interior vessel wall without interference from the blood. Methods of the present invention may further include monitoring the collapse of the vessel and/or verifying the post-procedural effect using an external light measuring device or photometer such as a position sensing detector (PSD) or a charge coupled device (CCD). In one particular embodiment, the method of the invention is used for eradication of incompetent GSV. The systems for performing the methods can be adapted for a single use. Single-use systems can include one or more non-rechargeable power supplies that provide sufficient power for a single treatment. In some embodiments, the system includes a housing that lacks access to an internal power supply or remote charging capabilities to as to prevent recharging. After the treatment, the system is conveniently discarded.

The system may also be packaged to maintain its sterility. For example, a kit may comprise the system for energy delivery and a container of a photoreactive agent, both contained in packaging. The container can contain a single dose or a plurality of doses of the photoreactive agent. A schematic diagram of an endovenous device and system, including optional components, that may be used to practice this method, is shown in Figure 3. In certain embodiments, the system includes a catheter and a console, which may be single-use and disposable, or multi-use. The console contains a power supply (e.g., battery) and also a pull-back mechanism for removing the light source during treatment. The power source may be linked to a power controller and a light source, which may be a photonic delivery device. In certain embodiments, the pull-back mechanism may be an automated engine or a guide for manual pull-back. Typically, the photonic delivery device is deployable from inside the distal tip of the catheter, such that it accommodates variation in vein diameter, e.g., 3-20 mm, during pull-back. The photonic delivery device comprises one or more light emitting elements, and these, or any other light source used, generate one or more of the wavelengths typically used in ELT, e.g., 810 nm, 940 nm, 980 nm, 1064 nm, or 1320 nm, or any wavelength within the range of 800-1400 nm. In other embodiments, blue light, e.g., about 410 nm to about 475 nm, is used to achieve heating on the primary surface of the vessel. In one embodiment, a balloon is mounted on the catheter with the light source inside the balloon, which is used to exclude blood from the light path. In a related embodiment, a cuff and ball is located within the distal tip of the catheter body, and a small pump is used to remove blood from the catheter tip and create a void ahead of the catheter. In another embodiment, the system includes a photometer or external light-measuring device.

The deployable endovenous photoablative devices of the present invention accommodate vein diameter variation, thereby maintaining the distance between the energy source and the vein surface, thus avoiding the need to precisely modulate the energy delivered. The critical thermal threshold for successful ablation is this maintained within the tunica intima. In contrast, in practice, energy delivered from the ELT laser fiber is not adjusted during pull- back, and the electrode array in RFA will only accommodate up to 10 mm veins. In addition, automated pull-back improves procedural efficiency and accuracy. The use of automated pull-back with a device capable of accommodating vein diameter variation allows the consistent application of uniform energy, either light or thermal energy, throughout the vessel being treated.

The invention further provides an endovenous photoablative device that includes additional refinements as compared to the device described above. In one embodiment, this device is adapted for the treatment of tortuous varicosities. This device is particularly useful, since more than 30% of patients considered for minimally-invasive eradication of incompetent GSV have significant tortuosity that precludes the use of ELT or RFA.

The present invention, therefore, includes methods of treating tortuous varicosities that are substantially similar to those methods described supra. According to these methods, the PTD device or other light source is contained within the distal tip of a highly flexible catheter (in contrast to the lack of flexibility in ELT and RFA devices), which is inserted into the tortuous vessel. In particular embodiments, the PTD or other light source is located in the catheter, and/or extendible out of the catheter. In one embodiment, the distal tip of the catheter contains a flow-deployable component, e.g., an opening leaflet or parachute, that enables the catheter to be advanced, e.g., 'floated,' down the tortuous vein under pressure (e.g., hydrostatic pressure) and, in some embodiments, navigated to just below the saphenofemoral junction (SFJ) during ultrasound. A cable may be coupled to the flow-deployable component. A user can use the cable to control operation (e.g., deployment, recapture, and the like) of the flow-deployable component. Recapture of the flow deployable component then enables the catheter to be withdrawn in normal fashion along the vein. A schematic of this device and method is provided in Figure 4.

Treatment methods and devices Light therapy is a process whereby light of a specific wavelength or waveband is directed toward target cells, tissues, or biological structures that have been rendered photosensitive through the administration of a photo- reactive, photo-initiating, or photosensitizing agent. This photo-reactive agent has a characteristic light absorption waveband and is commonly administered to a subject via intravenous injection, oral administration, or by local delivery to the treatment site. In the context of the treatment of varicosity, once the photo- reactive agent has distributed to the internal vessel wall, the varicosity can then be treated by exposing the vessel wall to light of an appropriate wavelength or waveband that substantially corresponds to the absorption wavelength or waveband of the photo-reactive agent. The wavelength of light delivered to the vessel treated with the photo-reactive agent causes the agent to undergo a photochemical reaction with oxygen in the localized targeted cells, to yield free radical species (such as singlet oxygen), which cause localized cell lysis or necrosis, resulting in ablation or closure of the vessel. In one embodiment, the present invention provides methods, devices and systems for the treatment of vessels. In various embodiments, the light is delivered from within the vessel or from outside the patient's body. These methods may be used to treat a variety of disorders, including, but not limited to, tortuous varicosities, superficial varicosities, and venous insufficiency arising from GSV incompetence. In general, these methods and systems result in energy deposition into the wall of the vessel being treated sufficient to damage the vessel without exposing adjacent tissues to thermal injury. The methods involving exogenous light delivery are particularly advantageous, since they are non-invasive and can be used to replace both invasive surgical vein- stripping and minimally invasive catheter ablation techniques. The exogenous methods described herein are particularly well-suited for the treatment of varicose veins, including spider veins and other superficial varicosities, since these methods provide for the elimination of varicosities without surgical or catheter intervention within minimal risk of collateral damage to perivenous tissues or skin.

In one embodiment, a method of the present invention comprises delivering an appropriate dose of a photosensitizer to a vessel in a patient, and generating light inside the treated vessel once the photosensitizer has bound to the interior of the vessel. In particular embodiments, the photosensitizer is administered systemically, e.g., intravenously in a peripheral vein, e.g., in the arm. In other embodiments, the photosensitizer is administered locally directly into the lumen of the varicose vessel or region thereof to be treated.

In specific embodiments, the region of the vessel to be treated is flushed with a substance, e.g., with saline, prior to providing the photosensitizer or prior to generating light inside the vessel, i.e., activating the photosensitizer. The flush removes light-absorbing blood from the region, thereby permitting use of a light source that illuminates the vessel wall with a wavelength of light that (1) excites the photosensitizer, (2) does not penetrate to any significant extent into the adventitia of the vessel, and/or (3) does not cause damage to normal arterial endothelium within the region of treatment. In one embodiment, the photosensitizer is administered in the substance used to flush the treated vessel or region thereof. Accordingly, in particular embodiments, the substance used for flushing comprises a photosensitizer. It is understood that the photosensitizer may, therefore, be administered prior to or during flushing. In addition, an additional flushing may be performed after administration of flushing substance comprising photosensitizer, e.g., with a substance such as saline lacking photosensitizer, in order to remove excess photosensitizer.

In other embodiments, including those wherein a light emitter is juxtaposed directly against the vessel wall being treated, there is no need to flush the blood or fluid from the vessel prior to the administration of light.

In accordance with the present invention, the photosensitizer is excited by light of a wavelength that secures good photonic energy distribution in the intima of the treated vessel. However, the activating wavelength and optical power are chosen such that the light's irradiance, as it transmits through the vessel, is attenuated substantially below the threshold at which the generation of singlet oxygen creates irreversible damage to tissue surrounding the vessel. This dictates a wavelength parameter that can be used to select an appropriate photosensitizer. In various embodiments, the light used for activation of the photosensitizer is coherent or non-coherent light. In certain embodiments of the present invention, the light wavelength is in the range of from about 410 to about 475 nm. In one embodiment, the light wavelength is in the range of 410 to 475 nm. Thus, photosensitizers having an excitation wavelength within this range are suitable for use. Photosensitizers excited by light in this wavelength range can be advantageous, because violet-blue light is highly scattered and energy is rapidly attenuated during transmission. Thus when violet-blue light is generated within the lumen of the vessel being treated it provides strong activation of the photosensitizer in the intima but is attenuated before reaching the adventitial layer of the vessel. In particular embodiments of the invention, the photosensitizer is mono-N-aspartyl chlorin e6 (Talaporfin Sodium), which is strongly excited by light having a wavelength in the 410-415 nm range. Other photosensitizers having excitation wavelengths within the specified ranges may also be used, as long as they also meet other criteria set forth herein. Useful photosensitizers may be selected, using the criteria set forth herein, from those listed in U.S. Patent No. 6,800,086, columns 6-20, which is fully incorporated herein by reference. In preferred embodiments, photosensitizers are water- soluble.

In one embodiment, methods of the present invention utilize photosensitizers that, upon delivery, rapidly distribute to the vessels to be treated to minimize intervention time. Nonetheless, other photosensitizers that are not so readily dispersed within the vessel tissue are also useful. In certain embodiments, photosensitizers can be standard dyes known in the art or derivatives made through linkage to macromolecular targeting carriers {e.g., growth factors, microspheres, liposomes, peptides, antibodies, or lipoproteins). In various embodiments, the light source is a laser light source, or a non-laser light source, or a coherent light source, or a non-coherent light source, as long as the wavelength of light emitted meets the criteria set forth herein, and it has sufficient energy to supply an effective light dose to carry out the energy delivery procedure within the period of time for the procedure. According to these methods, the presence of the photoreactive agent acts an energy concentrator avoiding collateral damage to other tissues, since there is no photosensitizer there, nor is the light alone of sufficient intensity to create thermal damage. In the context of exovenous energy therapy, where the activation wavelength is of a wavelength not highly absorbed by the intervening tissue, activation energy may be applied at a "minimally thermal" level to allow directed thermal energy to the target vessel wall. The resultant combined thermal/photodynamic effect may allow shortened treatment times and enhanced efficacy. As used herein, the term "energy therapy" is broadly construed to include without limitation, methods employing energy to treat or alleviate various conditions, diseases, disorders, symptoms, or other conditions. The type of energy can be selected based on the desired physiological response. For example, light therapy is a type of energy therapy suitable for destroying, contracting, or otherwise effecting vascular vessels.

Related devices and systems for energy ablative methods of the invention comprise a photosensitizer, which typically is a water-soluble photosensitizer with a high affinity for venous endothelium. They further comprise a feature {e.g., a port) used infuse the photosensitizer in solution into the vessel being treated, such as a needle or other delivery device. For exovenous treatment, a system may further include a light source, such as, e.g., a flexible LED array providing activated wavelength light that can be draped over the area where varicosities are present. For endovenous treatment, a system may further include a light source that may be delivered via catheter, including any of those described supra.

In one embodiment, the invention includes a method of treating a varicosity or venous insufficiency, comprising providing a photoreactive agent to the interior of a vessel being treated, and then delivering energy from outside the body so as to activate the photoreactive agent in the vessel, causing it to damage, kill, or induce apoptosis of the vessel wall, without causing damage to intervening tissue, since the activating energy is itself delivered at sub-thermal toxicity levels. In one embodiment, a photoreactive agent that binds the endothelial surface of the vessel wall is used. In one embodiment, the photoreactive agent is Talaporfin Sodium.

In one embodiment, the photoreactive agent (also called a photosensitizer) is provided to a patient in an aqueous solution. The photoreactive agent in solution may be instilled into a vessel that is occluded by pressure, e.g. , a tourniquet, at either side of the target segment for treatment. The solution may be provided by any mean available, including, e.g., by injection using a needle and syringe, through an injection port. After a sufficient time for the agent to bind the endothelial surface, the instilled solution is withdrawn or flushed from the vessel, leaving the photosensitizer on the surface of the vessel and a fluid that is transparent to the activation wavelength, such as saline, in the vessel. The instilled solution is removed to avoid attenuation of light by photosensitizer in the vessel lumen that would reduce the intensity of light reaching the side of the vessel that is distal to the light source. A secondary benefit is that the photosensitizer does not enter the systemic circulation after occlusion is released. In one embodiment, the instilled solution is expelled via the injection port using external compression on the vessel. Following incubation of the vessel with the photoreactive agent and removal of the photoreactive agent solution, light of the appropriate wavelength to activate the photoreactive being used is directed onto the skin generally over the site of the vessel being treated. The treated vessel may be physically compressed using standard procedures after light activation. The compression may be provided, e.g., by a light emitting pressure anvil or roller that will provide activation concurrently.

According to this procedure, sufficient reactive species, e.g., singlet oxygen, is generated from the photoreactive agent during light activation to irreversible damage the intima tunica, and the vessel undergoes a fibrotic healing process that obliterates the lumen.

In another related embodiment, the invention provides an endovenous therapy system similar to the exovenous system described above, except that the light source is provided from the interior of the vessel, where it is placed using a catheter. In particular embodiments, the catheter comprises an injection and/or ejection port, which may be used to provide the photosensitizer to the vessel, and/or may be used to flush the vessel. The catheter may further comprise one or more balloon to occlude the end of the region of the vessel being treated. One embodiment of such a system is shown in Figure 5. This system comprises a catheter and a light-emitting source, such as an LED.

Methods of the invention may be practiced in a localized region of a vessel, or, alternatively, entire vessels or regions thereof may be treated.

Photoactivatable Tissue Glue

In another related embodiment, the present invention provides a method and system for treating varicosities, which comprises providing an inactive tissue glue to the interior of a vessel, and administering light having a wavelength that activates the tissue glue, thereby adhering the opposing walls of the vessel to each other. The light is administered from outside the body, using any suitable source, such as a flexible LED array providing activated wavelength light that can be draped over the area where varicosities are present. The vessel may subsequently be compressed or flattened, leading to a permanent closure without prospect of re-canalization.

In certain embodiments, the tissue glue is administered in a foam to prevent its migration beyond the intended vessel. Such a foam composition also allows subsequent compression of the vessel with minimal extrusion of glue beyond the treated vessel. In yet another related embodiment, the glue comprises a photosensitizing agent, which creates a "photosclerosant" effect coupled with the adhesive effect of the glue. One embodiment of this method and system is depicted in Figure 6. A variety of photoactivatable tissue glues have been described in the art and can be used according to this method of the present invention. These include, e.g., photolabile hydrogels and photoactive cross-linking agents.

Heating Agent Therapy

The invention also provides methods of treating a varicosity that comprise administering a heating agent, such as an energy absorbing heating agent (e.g., a chromophore), to the interior of a vessel being treated, and administering energizing light of an appropriate wavelength to activate the chromophore through the skin to the underlying target tissue. The energy is taken up by the dye and heats the tunica intima to a temperature that results in vessel damage and eventual destruction, without heating the surrounding tissue. As used herein, the term "destruction" includes, but is not limited to, the act of completely destroying the target site or feature, causing a reduction in varicosity, and/or causing so much damage to the target site or feature that it cannot be repaired or no longer exists. For example, the heating agent can cause the reduction in varicosity to improve the aesthetic appearance of the subject. The vessel is typically subsequently compressed, leading to a permanent closure without prospect of re-canalization. A schematic of this method is provided in Figure 7.

Heating agents useful according to this method include, e.g., those specific for blood vessels endothelial lining. Specific examples of chromophores include, without limitation, one or more of the following: Cy 5.5 (tricarbocyanine group), ICG (indocyanine green), Alexa Fluor 680, Alexa Fluor 700, and metallic nanoparticles. Chromophores may be liquid dyes. The exogenous chromophore is delivered either as a bolus injection, or conjugated with a ligand antibody specific to an endothelial cell receptors (e.g., von

Willebrand factor). The exogenous chromophore contributes to the local light or energy absorption within the targeted vessel, facilitating the use of lower light exposure and minimizing the risk of damage to surrounding tissue. Additionally, the fluorescence properties of the same exogenous chromophores provide a capability to monitor vessels during treatment.

The invention further provides devices and systems for performing this method. In one embodiment, a system comprises a biocompatible chromophore, e.g., a liquid dye, a means to infuse the dye into a vessel to be treated, and a light source, e.g., a flexible LED array providing light energy that can be draped or positioned over the area being treated.

Transcutaneous therapy system

In another embodiment, the invention provides a method of treating a varicosity using ultrasonography-guided energy delivery, e.g., using a color-flow duplex Doppler ultrasonography (CDDU). This method uses vessel imaging information to focus spatial delivery of transcutaneous ablative energy from multiple sources outside the body.

According to this method, non-invasive imaging, e.g., color-flow duplex Doppler ultrasonography (CDDU), is performed to evaluate venous flow and identify an incompetent vessel, such as the GSV and associated branches or tributaries. Energy is then administered from outside the patient to the identified incompetent vessels, using multiple light or energy sources, each providing a sub-threshold energy beam directed toward the CDDU-identified target vessel. The accumulation of energy in the target exceeds the threshold for thermal effects that cause vessel closure, whereas the surrounding tissues are exposed to sub-threshold temperatures and are spared irreversible damage. The treatment process is continued along the length of the vessel until ultrasonography imaging confirms cessation of blood flow through the vessel. Following ultrasound energy delivery, the treated vessel may be compressed, e.g., mechanically or by vacuuming of the vessel. In certain embodiments, a translucent cooling mechanism is applied to the skin surface during energy delivery to minimize thermal damage to the skin.

Bioadhesive tape comprising photosensitizer

The present invention further includes a method of treating a varicosity comprising delivering to the vessel a bio-absorbable, double-sided bio-adhesive tap containing a pressure-sensitive photoreactive drug or photo- sclerosant eluting matrix. In one embodiment, the tape is delivered using a catheter, and in particular embodiments, blood is removed from the vessel prior to delivery of the tape to the vessel. In some embodiments, the tape is an adhesive tap with a coating made, in whole or in part, of the photoreactive drug. In some embodiments, the tape is an adhesive tape having impregnated photoreactive drug.

Liquid Heating Therapies

The present invention further includes methods of treating varicosities comprising contacting the interior of the vessel with a heat source comprising a heatable liquid, and administering heat to the interior of the vessel by heating the heatable liquid, thereby increasing the temperature at the surface of the interior of the vessel to at least around 85-100° C. The heat causes modification of the vessel's collagen structure and promotes fibrosis leading to reduction in size and, ultimately, its collapse. The requirement for successful varicose vein treatment is permanent damage to the tunica intima (endothelium and underlying connective tissue).

In certain embodiments, the heatable liquid is provided to the vessel using a catheter comprising a heating element and a balloon containing the heatable liquid. The catheter is inserted into the vessel being treated, the heating element is then activated, e.g., using a linked power supply and a dose of thermal energy sufficient to heat the liquid within the balloon to a temperature sufficient to damage the vessel is administered to the heatable liquid. The catheter is then pulled-back through the vessel, at a rate of movement controlled to provide adequate energy for successful ablation of the vessel being treated. In certain embodiments, pull-back is performed using an automated pull-back device. An external light measuring device may be used to monitor the amount of light provided to the vessel, monitor collapse of the vessel, or monitor the post-procedural effect. Following heat administration, the treated vessel may be compressed, e.g., mechanically or by vacuuming of the vessel.

Devices and Systems for Treatment of Varicosities

The present invention further includes devices and systems useful in practicing the methods of the present invention. In certain embodiments, the present invention includes devices and/or systems that have one or more of the following features: a catheter, which may include a balloon or other means to occlude blood from the treatment site, and which allows other devices to be placed through and beyond it to the treatment site; some means to apply a liquid flush to the vessel being treated to flush out blood or other fluid from the vessel at the treatment site, for example, an injection port coupled to a flushing port; and a light emitter that emits light of a wavelength to injure the interior of the vessel being treated or to activate a photosensitizer. In one embodiment, a light treatment system for treatment of varicosities possesses all of these features. In another embodiment, the present invention provides a system useful for practicing a method of the present invention. In one embodiment, the system includes a catheter sized for insertion into blood vessels to be treated with light activated treatment. The catheter includes an inflatable proximal occlusion balloon and a lumen. The lumen can be adapted to allow delivery over a guidewire into the vessel and for other intervention utilities including, e.g., inflation of the balloon, flushing, and delivery of a photosensitizer. In one embodiment, the system also includes a photosensitizer, e.g., one having peak energy absorption in the violet-blue sector of visible light ranging from about 41 Onm to about 475nm. The system includes an endovascular light-generating module chosen for its output wavelength to match the excitation wavelength of the photosensitizer. The light-generating module is sized for insertion into the lumen of the catheter to deliver light to the vessel wall at the required energy dose for therapeutic activation of the photosensitizer. Further, in various embodiments, the system includes such ancillaries as may be necessary or desirable in the interventional suite or such other location as the treatment may be performed.

The invention provides additional devices, apparatus, and systems that can be used, e.g., to practice the methods of the present invention. Particular embodiments of these are shown in Figures 3-11.

Figure 3 illustrates an embodiment of a light treatment system 100 comprising a catheter 106 that includes a light source 104. The illustrated light source 104 is a photonic delivery device in the form of a lightbar positioned within a blood vessel 110. When an electrical current is provided to the light source 104, the activated light source 104 generates and outputs electromagnetic waves.

In certain embodiments, the system 100 further includes a controller 108 operably coupled to the light source 104. The controller 108 can include a power supply 109 (illustrated in phantom) that provides power to the light source 104. The power supply 109 can be one or more batteries capable of delivering a sufficient amount of power to operate of the light source 104. As used herein, the term "power supply" includes, but is not limited to, one or more lithium batteries, chemical battery cells, super- or ultra-capacitors, fuel cells, secondary cells, thin film secondary cells, button cells, lithium ion cells, zinc air cells, nickel metal hydride cells, paper batteries (e.g., POWER PAPER®), printed power sources, and the like. The power supply 109 may be rechargeable or non-rechargeable. If the light source 104 or the entire light treatment system 100 is disposable, the power supply 109 can be non- rechargeable. In some embodiments, the power supply 109 is hermetically sealed in a housing 111. Accordingly, the controller 108 may lack access to recharge the power supply 109 or induction recharge capability. If the catheter 106 or the entire treatment system 100 is reusable, the power supply 109 can be rechargeable.

The system 100 may further comprise an external light measuring device 102. The external light measuring device 102 can be adapted to detect the amount of light transmitted out of the skin of the patient. The light therapy procedure can be adjusted based on feedback from the light measuring device 102.

In use, the catheter 106 is guided into position in the vessel 110. An illustrated distal end 114 of the catheter 106 is proximate the region of vessel 110 to be treated. The light source 104 is deployed from inside the distal tip 114 of the catheter 106. For example, the light source 104 can be moved distally out from a delivery sheath 117 of the catheter 106. The light source 104 is then activated using the controller 108 to deliver a dose of energy (e.g., either light energy or thermal energy, or both), while the catheter is moved relative to the vessel 110. In some embodiments, the light source 104 is pulled- back through the vessel 110 at rate of movement controlled to provide adequate energy for successful ablation of the vessel 110. The light source 104 can continuously or intermittently output energy while moving through the vessel 110. In certain embodiments, the catheter 106 is pulled proximally through the vessel 110 using an automated pull-back device. The external light measuring device 102 may be used to monitor the amount of light provided to the vessel 110, monitor collapse of the vessel 110, and/or monitor the post- procedural effect, if any. Following light administration, the treated vessel 110 may be compressed, e.g., mechanically or by vacuuming of the vessel. Figure 4 illustrates an embodiment of a light treatment system 200 that is generally similar to the light treatment system 100 in Figure 3, except as detailed below. The light treatment system 200 comprises a flexible catheter 202 comprising a light source 210, illustrated in the form of a photonic delivery device. In the illustrated embodiment, a distal tip 209 of the flexible catheter 202 comprises a deployable component 206 movable between a collapsed configuration and an expanded configuration (illustrated). The deployable component 206 permits insertion of the catheter 202 into a tortuous vessel, even a highly tortuous vessel. The deployable component 206 can be operably linked to another component, such as an actuation element 204. The actuation element 204 can be used to control operation of the deployable component 206.

The deployable component 206 of Figure 4 can be adapted to deploy using blood flow through the vessel 208. The illustrated deployable component 206 includes a plurality of struts 214 connected to an umbrella- shaped membrane 216. The struts 214 can be biased outwardly to expand, alone or in combination with the blood flow, the membrane 216. For a low- profile delivery configuration, the struts 214 and membrane 216 can be collapsed inwardly. Once the deployable component 206 is positioned in the vessel 208, the plurality of struts 214 can move radially outward to open the membrane 216. The catheter 202 can then float through the vessel 208 to a desired position. In some embodiments, distally flowing blood can provide sufficient forces to cause expansion of the deployable component 206. If blood pools in the vessel 208, the struts 214 can deploy the membrane 216.

Other types of deployable members can also be used. Exemplary deployable members include, but are not limited to, leaflets, parachutes, radially expandable occlusion devices, and the like. The type and configuration of the deployable member can be selected based on the treatment to be performed.

The actuation element 204 can be a stylet, push/pull rod, cable, or guidewire, or combinations thereof. If the deployable component 206 is retained in a longitudinally-extending working lumen 221 upon entry into the subject, the actuation element 204 can be sufficiently rigid to push the deployable component 206 out of the catheter 202. If the deployable component 206 is outside of the distal tip 209 upon entry into the subject, the actuation element 204 can be cable used to retract the deployable component 206.

In use, the flexible catheter 202 can be guided into position in the vessel 208, after deployment of the deployable component 206, which facilitates insertion of the catheter 202 into the tortuous vessel 208. The actuation element 204 can be operated to move the deployable element 206 inwardly and/or outwardly a desired amount to permit distal and/or proximal movement of the distal tip 209. The photonic delivery device 210 may be deployed from inside the distal tip 209 of the catheter 202, and the deployable component 206 is recaptured using the attached actuation element 204, enabling the catheter to be withdrawn in normal fashion through the vessel. The deployable component 206 can be pushed out of the lumen 221 using the actuatation element 204. When the actuation element 204 is moved proximally, the struts 214 and the umbrella-shaped membrane 216 can be drawn into the lumen 221.

The photonic delivery device 210 is activated using an external power supply to deliver a dose energy, while the catheter 202 containing the photonic delivery device 210 is pulled-back through the vessel 208, at a dose and rate of movement controlled to provide adequate energy for successful ablation of the vessel 208. In certain embodiments, pull-back is performed using an automated pull-back device operably coupled to the catheter 202. An external light measuring device may be used to monitor the amount of light provided to the vessel 208, monitor collapse of the vessel 208, or monitor the post-procedural effect. Following light administration, the treated vessel 208 may be compressed, e.g., mechanically or by vacuuming of the vessel.

Figure 5 illustrates an embodiment of a light treatment system 300 that includes a photosensitizer 308. The illustrated photosensitizer 308 is along a section 307 of a vessel 309 adjacent a light source 304. In some embodiments, the endothelium or the entire vessel 309 can be sensitized by the photosensitizer 308. The system 300 includes a catheter 302 comprising the light source 304. The system 300 may further comprise a power source 306 operably linked to the light source 304.

In use, the catheter 302 is guided into position in the vessel 309. The patient is treated with a dose of the photosensitizer 308. The photosensitizer 308 may be administered in an aqueous solution to the vessel being treated, e.g., via an injection port 313 located in the catheter 302. After sufficient time has elapsed for the photosensitizer 308 to bind to cells on the vessel wall, the instilled solution is withdrawn or flushed from the vessel 309, leaving the photosensitizer 308 bound on the surface of the vessel 309 and a fluid that is transparent to the activation wavelength, such as saline, in the vessel. The light source 304 is deployed from inside the distal tip of the catheter 302 and activated using an external power supply 306 to deliver a dose of light at the activation wavelength of the photosensitizer 308, while the catheter 302 containing the light source 304 is pulled-back through the vessel 309, at a rate of movement controlled to provide adequate energy for activation of the photosensitizer 308. In certain embodiments, pull-back is performed using an automated pull-back device operably coupled to the catheter 302. Following light administration, the treated vessel may be compressed, e.g., mechanically or by vacuuming of the vessel. Figure 6A illustrates an embodiment of a light treatment system

400 that includes a light-activatable coupler 402 in the form tissue glue and an external activation device 403 for transcutaneous^ activating the glue 402. The external device 403 includes a light source 404. The system may further comprise a power source 407 (illustrated in phantom) operably linked to the light source 404.

The glue 402 can include, without limitation, one or more adhesives, bonding agents, binders, photosentizers, medicants, fillers, and the like. The composition of the glue 402 can be selected based on the therapy to be performed. To perform light therapy, for example, the glue 402 can include both an adhesive and at least one photosensitizer. Energy from the device 403 can activate the glue 402 or the photosensitizer, or both. The glue 402 may be activated to keep a vessel 409 in the collapsed state (either a fully collapsed state or a partially collapsed state). In some embodiments, for example, the glue 402, when activated, may cross-link, cure, polymerize, or otherwise couple to the inner surface 415 of the vessel 409 together. The glue 402 may be in the form of a gel, paste, fluid, and/or foam (e.g., a low density foam, a medium density foam, or a high density foam). The external device 403 can be in the form of a flexible patch suitable for delivering energy to a desired internal target site. The external device 403 may be one of the patches disclosed in U.S. Patent No. 6,096,066 (the '066 patent). This reference is incorporated by reference in its entirety. The '066 patent discloses various types of flexible patches having a plurality of light sources {e.g., LEDs) that may be adapted to activate at least one constituent of the glue 402. The external device 403 in the form of a conformable patch can overlay the target site to direct energy towards the glue 402.

In use, the light-activatable tissue glue 402 is inserted into the vessel 409 being treated, e.g., by injection. One or both ends of the section of the vessel 409 being treated may be occluded by pressure, e.g., tourniquet, to prevent the glue 402 from dispersing beyond the section of the vessel 409 being treated. Plugs, balloon, or other occluding devices can be employed. In some embodiments, the glue 402 may have a viscosity sufficiently high to prevent the glue 402 from spreading to untargeted regions of the vessel 409.

In certain embodiments, the tissue glue 402 is a foam, which allows subsequent compression of the vessel 409 with minimal extrusion of glue 402 beyond the treated section. Figure 6B shows a treated section 431 of the vessel 409 in a collapsed state. The patient is treated with a dose of light from the external device 403 over the area being treated, i.e., externally through the skin, using a wavelength suitable for activating the tissue glue 402 and for a time sufficient to activate at least one constituent of the tissue glue 402. In another embodiment, the tissue glue 402 comprises a photosensitizer and an adhesive, and the treated vessel is treated with light of a wavelength and time sufficient to activate the adhesive or the photosensitizer, or both. Following light administration, the treated vessel may be compressed, e.g., mechanically or by vacuuming of the vessel.

In some embodiments, the light-activatable coupler 402 is an adhesive tape that can be delivered using a catheter 437 (illustrated in the form of a delivery catheter). The adhesive tape can include, without limitation, a bio- absorbable, double-sided bio-adhesive tape comprising an adhesive, such as a pressure-sensitive matrix comprising a photosensitizer or photosclerosant. Once the tape 402 is pushed out of the catheter 437 and into the vessel 409, opposing inner surfaces of the vessel 409 can be brought together against the tape 402.

Figure 7 illustrates an embodiment of a light treatment system 500 that includes an energy absorbing agent 502 and an external light source 504, illustrated in the form of a patch 505 having a plurality of light emitters 507a-d. The energy absorbing agent 502 can be a heating agent that interacts with light from the light source 504 to provide localized heating. The tissue treated with the heating agent 502 can be elevated to a target temperature {e.g., a temperature suitable for destroying tissue) while adjacent non-treated tissue is kept at a lower temperature, thereby preventing irreversible damage of the non- treated tissue.

The heating agent 502, in some embodiments, can absorb at least a portion of the emitted light and is heated as a result of such absorption. The heating agent 502 can be a natural or synthetic substance, including, without limitation, one or more chromophores. Exemplary chromophores include, without limitation, dyes, inks, carbon particulates, and the like in the form of gels, pastes, foams, solutions, and the like. In some embodiments, the heating agent 502 can coat an inner surface 509 of a vessel 511 and can absorb light so as to heat the vessel 511. In some embodiments, the heating agent 502 can include one or more glues, drugs (e.g., a photoreactive agent), and/or a light absorptive heating agent. Glue can help collapse the vessel 511 and the light absorptive heating agent can heat and destroy the wall of the vessel 511.

In use, the heating agent 502 is introduced into the vessel 511 being treated, e.g., by injection. One or both ends of the section of the vessel 511 being treated may be occluded by pressure, e.g., tourniquet, to prevent the heating agent 502 from dispersing beyond the section of the vessel 511 being treated. The patient is treated with a dose of light from the light source 504 positioned over the area being treated, i.e., externally through the skin, using a wavelength suitable for interacting with the heating agent 502 and for a time sufficient to cause desired heating of the interior of the vessel 511. Following light administration, the treated vessel 511 may be compressed, e.g., mechanically or by vacuuming of the vessel 511.

Figure 8 illustrates an embodiment of a light treatment system 600 that includes a non-invasive imaging modality able to provide real-time vessel flow information. The illustrated light treatment system 600 includes a noninvasive imaging system 602 comprising an imaging element 606. The imaging system 602 can comprise software that interfaces with the imaging element 606 to provide real-time, spatial coordination between vessel flow artifacts and the application of directional therapeutic energy. The light treatment system 600 can be in the form of an ultrasonography system, and the imaging element 606 can be an ultrasound energy delivery scan head. The imaging element 606 may also include, without limitation, one or more energy sources, such as light sources, ultrasound devices, cooling devices, and the like. Thus, the imaging element 606 can provide both imaging and energy (e.g., ablative energy) for treating vessels of interest.

In use, vessel imaging information obtained using the imaging system 602 is used to focus spatial delivery of transcutaneous ablative energy. The imaging system 602 can be used to position a plurality of energy sources outside of the subject's body such that transcutaneous^ delivered energy is directed toward the vessels of interest. Imaging (e.g., color-flow duplex Doppler ultrasonography (CDDU)) may be performed to evaluate venous flow for the purpose of identifying and evaluating incompetence in vessels, such as the GSV and associated branches or tributaries. Energy is then administered to the identified incompetent vessels using a spatial array of energy sources 608 deployed around the target vessel, with each providing a sub-threshold energy beam directed toward the CDDU-identified target vessel. The accumulation of energy in the target exceeds the threshold for thermal effects that cause vessel closure, whereas the surrounding tissues are exposed to sub-threshold temperatures and are spared irreversible damage. The treatment process is continued along the length of the vessel until ultrasonography imaging confirms cessation of blood flow through the vessel. Following ultrasound energy delivery, the treated vessel may be compressed, e.g., mechanically or by vacuuming of the vessel. In certain embodiments, a translucent cooling mechanism is applied to the skin surface during energy delivery to minimize thermal damage to the skin.

Figure 9 illustrates an embodiment of a light treatment system 700 including an expandable light source 704 and a delivery sheath 702. The expandable light source 704 is movable between a collapsed delivery configuration and an expanded illumination configuration. The system 700 may further comprise a power source operably linked to the light source 704. The illustrated sheath 702 can cover and surround the light source 704, thereby keeping struts 709a, 709b, 709c (collectively 709) collapsed during insertion into a vessel 721. The sheath 702 can be moved proximally relative to the struts 709 to deploy the struts 709. The illustrated expandable light source 704 includes a hub 707 and the plurality of elongate struts 709 rotatably coupled to the hub 707. The struts 709a, 709b, 709c have distal ends 711a, 711b, 711c, respectively, that can be moved outwardly in the radial direction to position light emitters with respect to the vessel 721. The proximal ends 713a, 713b, 713c (collectively 713) of the respective elongate struts 709a, 709b, 709c are coupled to the hub 707. Hinges, pivots, flexible connectors, or other suitable structures can rotatably couple the proximal ends 713 to the hub 707.

Each of the elongate struts 709 can carry at least one light emitter 715. The light emitters 715 can be configured to emit light having one or more wavelengths in the red spectrum and/or infrared spectrum. In the illustrated embodiment, each of the elongate struts 709 carries three light emitters 715. It is contemplated that any number of light emitters can be coupled to each of the struts 709a, 709b, 709c. The number, types, and positions of the light emitters 715 can be selected to produce evenly or unevenly distributed light rays. The elongate struts 709 can be self-expanding for convenient deployment. In some self-expanding embodiments, the struts 709 are biased radially outward. During delivery, the delivery sheath 702 restrains, inhibits, or otherwise limits self-expansion of the elongate struts 709. Once moved out of the delivery sheath 702, the struts 709 rotate outwardly to their expanded configurations.

The light source 704 can be made, in whole or in part, of one or more shape memory materials, which can move the light source 704 between the collapsed and expanded configurations when activated. Shape memory materials may include, for example, a shape memory alloy {e.g., NiTi), a shape memory polymer, or other suitable materials. These materials can be transformed from a first preset configuration to a second preset configuration when activated. The shape memory material can be activated by an external energy source (e.g., an ultrasound energy source, a thermal energy source, etc.), internal heating elements (e.g., resistive heating elements), and the like. In some embodiments, the light source 704 is a furcated tube having laser cut sections defining the branched struts 709.

Alternatively or additionally, the light source 704 may be expanded using any of a variety of expansion techniques involving enlargement structures (such as an inflatable balloon), mechanical expansion techniques (such as a pullwire assembly), and the like. It is contemplated that shape memory materials can be used in combination with these expansion techniques.

In use, the sheath 702 and the covered light source 704 are inserted into the vessel being treated. The struts 709 are deployed from inside a distal tip 719 of the sheath 702 by pulling back the sheath 702. The lumen walls of the delivery sheath 702 restrain the elongate struts 709 until the light source 704 is delivered out of the delivery sheath 702 and self-expands. After expansion, the light source 704 is activated, e.g., using a linked power supply, to deliver a dose of light or thermal energy through the light emitters 715, while the sheath 702 and light source 704 are pulled-back through the vessel 721 , at a dose and rate of movement controlled to provide adequate energy for successful ablation of the section of the vessel being treated. In some embodiments, the light source 704 is generally centered within the vessel 721 as the outwardly biased struts 709 cam along an inner surface 727 of the vessel 721.

In certain embodiments, pull-back is performed using an automated pull-back device operably coupled to the sheath 702 and/or light source 704. An external light measuring device may be used to monitor the amount of light provided to the vessel 721 , monitor collapse of the vessel 721 , or monitor the post-procedural effect. Following light administration, the treated vessel 721 may be compressed, e.g., mechanically or by vacuuming of the vessel.

Figure 10 illustrates an embodiment of a heat treatment system 800 including a catheter 802 and a heating element 810 (shown in phantom). In the illustrated embodiment, the heating element 810 is operably linked to a controller 804. The system 800 further includes a guidewire 806 for positioning the catheter 802. The catheter 802 further comprises a distal compliant balloon 812 containing a heatable medium 808. The heating element 810 can be used to regulate the temperature of the heatable medium 808 and ultimately the temperature of the compliant balloon 812. In some embodiments, the controller 804 can provide power to the heating element 810 such that the heating element 810 generates thermal energy to the heatable medium 808, thereby heating the medium 808 to a desired temperature. The heating element 810 can be an electrically powered device (e.g., one or more resistive heating elements, positive thermal coefficient elements, light emitters, combinations thereof, and the like) within the balloon 812, as depicted, or it may be outside the patient and operably linked to the balloon 812 to provide thermal energy to the medium 808. For example, the medium 808 can be heated outside of the patient in the controller 804 and then delivered through the catheter 802 into the balloon 812.

In use, the catheter 802 is inserted into the vessel 811 being treated using the guidewire 806. Once the catheter 802 is positioned, the heating element 810 is activated, e.g., using the controller 804, to deliver a dose of thermal energy sufficient to heat the medium 808 and balloon 812 to a temperature sufficient to damage the vessel 811. The catheter 802 is pulled- back through the vessel 811 at a rate of movement controlled to provide adequate energy for successful ablation of the vessel 811. In certain embodiments, pull-back is performed using an automated pull-back device operably coupled to the catheter 802. If the catheter 802 includes a light source, an external light measuring device may be used to monitor the amount of light provided to the vessel, monitor collapse of the vessel, or monitor the post-procedural effect. Following heating of the vessel 811 , the treated vessel 811 may be compressed, e.g., mechanically or by vacuuming of the vessel. Figure 11 illustrates an embodiment of a heat treatment system 900 including a distal catheter 902 and a proximal catheter 904. The distal catheter 902 extends from the proximal catheter 904 and includes a distal occluder 910. The proximal catheter 904 includes a proximal occluder 912. Each of the distal and proximal occluders 910, 912 are in the form of expandable balloons that can cooperate to isolate a section of a vessel 920. For example, each of the distal and proximal occluders 910, 912 can form a fluid tight seal with the vessel 920 to define a closed section 921. A heated medium (represented by arrows) can be delivered out of the heat treatment system 900 into the closed section 921.

The distal catheter 902 can include an inflation lumen extending proximally from an inflation port 930 for inflating the occluder 910 and a delivery lumen extending proximally from an inlet port 932 for delivering the heated medium into the closed section 921 of the vessel 920. The medium can be drawn out of the closed section 921 via an outlet port 936. To achieve a generally uniform temperature distribution of the vessel 920 along the closed section 921 , the medium can be circulated through the closed section 921 via the inlet and outlet ports 932, 936.

The outlet port 936 can be in the distal catheter 902 or the proximal catheter 904. In some embodiments, including the illustrated embodiment of Figure 11 , the outlet port 936 is positioned in the proximal catheter 904. A return lumen extends proximally from the outlet port 936 through the proximal catheter 904.

In use, the heat treatment system 900 can be positioned in the vessel 920. The occluders 910, 912 can be expanded until suitable seals are formed with the vessels 920 to define the closed section 921. A heated medium is then delivered through the inlet port 932 into the sealed closed section 921 of the vessel 920. The heated medium can be at an elevated temperature suitable eliciting a desire response, such as destruction of the wall of the vessel 920. After treating the vessel 920, the occluders 910, 912 can be deflated for removal of the heat treatment system 900.

Figure 12 illustrates a treatment system 1000 including a catheter 1002 and a controller 1004. The controller 1004 is an automated pull-back device that includes a retraction mechanism 1010 (illustrated in phantom) adapted to regulate a length of the catheter 1002 therefrom. A user input device 1020 can be positioned along the controller 1004 such that a user can conveniently increase or decrease the length of the catheter 1002 before, during, or after the therapy procedure. Referring to Figure 13, after the catheter 1002 is positioned within a targeted vessel 1030, the controller 1004 can move the catheter 1002 and its activatable element 1040 through a lumen 1050 of the vessel 1030. In some embodiments, including the illustrated embodiment of Figure 13, the controller 1004 moves the catheter 1002 proximally (indicated by the arrow 1060) at a desired rate. As the catheter 1002 is pulled back through the vessel 1030, the element 1040 can emit an adequate amount of energy to successfully treat at least a portion of the vessel wall. As noted above, in certain embodiments, movement of the catheter 1002 is performed before and/or during compression of the vessel 1030.

The controller 1004 can remain generally stationary with respect to the patient while the catheter 1002 is moved through the vessel 1030. The controller 1004 of Figures 12 and 13 can be fixedly coupled to the skin 1032 of the subject. In some embodiments, a coupling element 1035 is sandwiched between a housing 1033 of the controller 1004 and the skin 1032. In some embodiments, the coupling element 1035 is a double-sided adhesive sheet adhered to a lower surface of the housing 1033 and the skin 1032 so as to limit or substantially prevent relative movement between the controller 1004 and the subject. In other embodiments, the coupling element 1035 is an adhesive gel compressed between the housing 1033 and the skin 1032. Other devices and systems can also be employed to position the controller 1004 with respect to the subject. For example, one or more restraining straps can secure the controller 1004 to the subject.

Figure 14 illustrates the retraction mechanism 1010 including a retraction mechanism housing 1050 and a reel system 1060 disposed within the housing 1050. The reel system 1060 includes a shaft 1072, a reel 1070 rotatable about the shaft 1072, and a motor 1080 that drivingly engages the shaft 1072. To retract the catheter 1002, the reel 1070 can be rotated (indicated by the arrow 1080) about the shaft 1072 to wind the catheter 1002 about an inner drum of the reel 1070. The reel 1070 can be rotated in the opposite direction to extend the catheter 1002. In this manner, the catheter 1002 can be controllably pulled into or extended from the controller 1004.

Referring again to Figures 12 and 13, a user can use the input device 1020 to increase or decrease the speed at which the element 1040 is moved through the vessel 1003. In some embodiments, the controller 1004 can be programmed to move the catheter 1002 at a particular rate based upon one or more parameters determined by a physician based on, for example, the lumen diameter of the vessel 1003, wall thickness of the vessel 1003, and the like. A temperature control mechanism can control the temperature of the patient's skin. Figure 15 shows a light treatment system 1100 including a translucent cooling mechanism 1110 applied to the subject's skin 1112 during the administration of light for activating an agent 1113. The illustrated cooling mechanism 1110 is sandwiched between a light source 1120 and the skin 1112. The light source 1120 includes light emitters 1121 a-e capable of emitting light rays that can be transmitted through the translucent cooling mechanism 1110.

The cooling mechanism 1110 can be made, in whole or in part, of a transmissive material, such as an optically clear polymer material, plastic material, resin, and the like. A plurality of spaced apart cooling channels 1122 extend through a main body 1123 of the cooling mechanism 1110. A chilled fluid {e.g., chilled water) can flow through the channels 1122 to keep the cooling mechanism 1110 at or below a target temperature to minimize, limit, or substantially prevent unwanted heating of the skin 1112. Without the cooling mechanism 1110, excessive heat generated by the light emitters 1121 a-e may burn or damage the skin 1112 or nearby tissues.

In some embodiments, the main body 1123 comprises one or more peltier devices. Peltier devices are solid state components which become hot on one side and cool on an opposing side, depending on the direction of current passed through the devices. Accordingly, by simply selecting the direction of current passed through the devices, the peltier devices can be employed to cool an engagement surface 1137 of the main body 1123 for contacting the skin 1112 to a target temperature before, during, or after the light therapy procedure. Other types of heating/cooling elements can also be employed. The present invention further includes other devices and systems for practicing methods of the invention, such as one of those described above. It will be clear to those of average skill in the art that the embodiment of a catheter shown, and other catheters that perform the same functions, may require ancillary equipment such as a power supply for the light emitters and for their movement along the guidewire where that form of the invention is practiced. Within the environment where treatment with this invention will be administered, the power supply may be, for example, from disposable or rechargeable batteries of any kind or powered by electricity. Certain embodiments of the present invention will also require a flushing and/or evacuation pump for the solutions used to flush the vessel. Further, a balloon control device for inflation and deflation may also be required for certain embodiments of the present invention. In various embodiments, systems of the present invention comprise one or more of these components, in addition to the catheter device. Preferably, but not necessarily, these are all integrated into a single mobile unit with a control panel to facilitate use in an operating room environment. The single mobile unit can include a handheld controller with a control panel in the form of a touch screen, key board, or other input device. During the procedure, the unit can be mounted a stand, the patient, or other suitable mounting location. The catheter can be integrated into the controller to prevent unwanted separation during use.

In one embodiment, a system of the present invention comprises a catheter sized for insertion into a blood vessel, the catheter comprising an inflatable balloon and a lumen; a guidewire sized to be received and extend through the lumen of the catheter; and a light source located in the lumen of the catheter to deliver light to tissue, wherein the light is delivered at an excitation wavelength that is close to an excitation wavelength of a photosensitizer. In one embodiment, the system further comprises a substance delivery system for providing a substance to the tissue, the substance delivery system including a delivery tube extending through the lumen of the catheter. The catheter may, therefore, include a port for discharging the substance into the blood vessel. In certain embodiments, the substance is used for flushing the region of a vessel being treated, while in related embodiments, the substance is used to deliver a photosensitizer to a region of a vessel being treated. Accordingly, in particular embodiments, the substance is saline or saline in combination with an amount of a photosensitizer. In one particular embodiment, a system of the present invention comprises a catheter sized for insertion into blood vessels to be treated with energy therapy, the catheter comprising an inflatable balloon and a lumen sized to contain a guidewire; a photosensitizer having an excitation wavelength in the range from about 410 to about 475nm; a light source sized for insertion into the lumen of the catheter to deliver light to tissue containing a concentration of the photosensitizer, the light source providing light in the excitation wavelength of the photosensitizer; and a saline flush system for delivery of flushing liquid to blood vessels to be treated, the flush system comprising a saline delivery tube sized for insertion into the lumen of the catheter. In one embodiment of a system of the present invention, the balloon of the catheter comprises fluid exit ports for deflation of the balloon, and fluid inlet ports for successive re-inflation of the balloon during stages of a energy treatment procedure.

In particular embodiments of systems and methods of the present invention, the light source is a source of laser light. In additional embodiments, the photosensitizer is Talaporfin Sodium or its derivatives, verteporfin or its derivatives, or rostaporfin or its derivatives.

The above description of illustrated embodiments, including what is described in the Abstract, is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Although specific embodiments of and examples are described herein for illustrative purposes, various equivalent modifications can be made without departing from the spirit and scope of the invention, as will be recognized by those skilled in the relevant art. The teachings provided herein of the invention can be applied to various light transmission devices and/or systems, not necessarily the light transmission systems generally described above. The various embodiments described above can be combined to provide further embodiments.

All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications, and non-patent publications referred to in this specification and/or listed in the Application Data Sheet, including U.S. Patent Nos. 6,958,498; 6,784,460; 6,661 ,167; and 6,445,011 ; U.S. Publication No. 2005/0228260; U.S. Provisional Patent Application No. 60/879,466; International Patent Application Nos. PCT/US2005/032851 and PCT/US01/44046; U.S. Patent Application Serial No. 11/323,319, U.S. Patent Application Serial No. 11/357,358, U.S. Provisional Patent Application No. 60/640,382; and U.S. Provisional Patent Application No. 60/879,508 are incorporated herein by reference, in their entirety. Aspects of the invention can be modified, if necessary, to employ aspects, features, and concepts of the various patents, applications, and publications to provide yet further embodiments of the invention.

These and other changes can be made to the invention in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the invention to the specific embodiments disclosed in the specification and the claims, but should be construed to include all light transmission systems that operated in accordance with the claims. Accordingly, the invention is not limited by the disclosure, but instead its scope is to be determined entirely by the following claims.

Claims

1. A method of treating a varicosity, comprising: inserting a catheter into a varicose blood vessel, wherein said catheter comprises an activatable photonic delivery device inside a distal tip of the catheter, the photonic delivery device adapted to generate and emit light; deploying said photonic delivery device from inside the catheter; and administering light from the photonic delivery device to an interior of the varicose blood vessel, wherein a wavelength of the light and a duration of administration are sufficient to cause destruction of the varicose blood vessel.

2. The method of claim 1 , wherein the administration of light comprises delivering a current to the photonic delivery device to activate the photonic delivery device in situ.

3. The method of claim 1 , wherein the photonic delivery device comprises one or more light emitting diodes (LEDs) and/or laser dies.

4. The method of claim 1 , further comprising longitudinally moving the catheter along a lumen of the blood vessel during the administration of light.

5. The method of claim 1 , further comprising moving the catheter through the blood vessel using an automated device.

6. The method of claim 1 , further comprising moving the catheter through the blood vessel using a retraction mechanism while administering the light.

7. The method of claim 1 , wherein the wavelength is in a range of about 800 nm to about 1400 nm.

8. The method of claim 1 , further comprising moving a deployable component at the distal tip from a collapsed configuration to an expanded configuration while the distal tip is within the varicose blood vessel.

9. A method of treating a varicosity in a patient, comprising: providing a photosensitizer or conjugate thereof to an interior of a varicose vessel in the patient, wherein a portion of the photosensitizer or conjugate thereof binds to cells on the interior of the varicose vessel; and administering light to a region of the patient's skin generally over the varicose vessel, wherein the light is administered at a wavelength that activates the photosensitizer or conjugate thereof, thereby damaging the vessel.

10. The method of claim 9, further comprising removing unbound photosensitizer or conjugate thereof from the interior of the varicose vessel prior to the administration of light.

11. The method of claim 9, further comprising occluding opposing ends of a section of the varicose vessel prior to providing the photosensitizer or conjugate thereof to the interior of the vessel, wherein said section is damaged by the photosensitizer or conjugate thereof activated by the administered light.

12. The method of claim 9, further comprising physically compressing the vessel during or following the administration of light.

13. The method of claim 9, wherein the photosensitizer or conjugate thereof is water soluble.

14. The method of claim 9, wherein the light is administered at a wavelength within a range of about 410 nm to about 475 nm.

15. The method of claim 9, wherein the photosensitizer is Talaporfin Sodium or derivatives thereof.

16. The method of claim 9, wherein the administered light used for activation of the photosensitizer or conjugate thereof is coherent light or non-coherent light.

17. A method of treating a varicosity in a patient, comprising: providing a photoactivatable tissue glue to an interior of a varicose vessel in a patient; administering light to a region of skin of the patient generally over the varicose vessel, wherein the light is administered at a wavelength that activates the tissue glue; and physically compressing the varicose vessel during and/or following the administration of light so as to close the vessel.

18. The method of claim 17, wherein the photoactivatable tissue glue is a foam.

19. The method of claim 17, wherein the photoactivatable tissue glue includes a photosensitizer.

20. A method of treating a varicosity in a patient, comprising: providing an energy absorbing heating agent to an interior of a varicose vessel in the patient; administering light to a region of skin of the patient adjacent the varicose vessel, wherein the light is administered at a wavelength that is absorbed by the heating agent such that the heating agent causes sufficient heating to damage cells lining the interior of the vessel; and physically compressing the vessel during and/or following administration of light, thereby causing at least partial closure of the vessel.

21. The method of claim 20, further comprising occluding opposing ends of a section of the vessel prior to providing the heating agent to the interior of the vessel so as to capture the heating agent between the opposing ends during the administration of light.

22. The method of claim 21 , wherein occluding the opposing ends includes inflating a pair of spaced apart balloons in the vessel.

23. A method of treating a varicosity in a patient, comprising: performing non-invasive, real-time imaging to identify a varicosity in a patient; and transcutaneous^ administering light to the varicosity identified by the imaging, wherein the light is administered from an array of directional energy sources and is at a wavelength that causes energy absorption by the varicosity such that a sufficient amount of energy is accumulated at the varicosity to cause closure of the varicosity and surrounding tissues are not irreversibly damaged.

24. The method of claim 23, wherein the real-time imaging is performed by ultrasonography.

25. The method of claim 23, further comprising applying a translucent cooling mechanism to the patient's skin such that the administered light passes through the translucent cooling mechanism and then to the varicosity.

26. A method of treating a varicosity, comprising: providing a bio-absorbable, double-sided bio-adhesive tape comprising a pressure-sensitive matrix comprising a photosensitizer or photosclerosant to an interior of a varicosity; administering pressure to the varicosity; and administering light to the varicosity at a wavelength that activates the photosensitizer or photosclerosant, thereby causing closure of the varicosity.

27. The method of claim 26, wherein the tape is provided using a catheter.

28. A method of treating a varicosity, comprising: introducing a catheter comprising a distal compliant balloon into a varicose vessel; and administering heat to a flowable medium in the balloon sufficient to increase a temperature of the flowable medium to a level sufficient to cause permanent damage to an interior of the varicose vessel.

29. The method of claim 28, wherein the heat is administered using a energizable thermal device within the catheter.

30. The method of claim 28, wherein the heat is administered using an external heat source that generates heat that is transferred to the distal balloon.

31. The method of claim 28, further comprising conducting thermal energy from the flowable medium to a portion of the interior of the vessel contacting the balloon.

32. The method of claim 28, further comprising circulating the flowable medium within the balloon while thermal energy is transferred from the flowable medium to the interior of the vessel.

33. A device adapted for treatment of varicosities, comprising: a catheter sized for delivery through a blood vessel, the catheter comprising a lumen and a distal tip; and an expandable light source dimensioned and configured to be positioned in the lumen of the catheter, wherein said light source is deployable out of the lumen and the distal tip of the catheter when the light source is expanded from a collapsed configuration to an expanded configuration.

34. The device of claim 33, wherein the expandable light source includes at least one light emitter adapted to generate and emit light.

35. The device of claim 33, wherein the expandable light source includes a frame that is movable radially between a first configuration and a second configuration, the frame carries an array of light emitters that moves outwardly as the frame moves from the first configuration to the second configuration.

36. The device of claim 33, wherein the expandable light source is movable from a first position within the lumen of the catheter to a second position outside of the lumen of the catheter and in closer proximity to a wall of the blood vessel.

37. A system for treating varicosity, comprising: a device of claim 33; and a power source electrically coupled to the light source, the power source capable of providing sufficient power to the light source to energize at least one light emitter of the light source.

38. The system of claim 37, wherein the catheter includes an external controller and a main catheter body extending proximally from the distal tip to the controller, the external controller including the power supply.

39. The system of claim 37, further comprising a photosensitizer.

40. The system of claim 39, wherein the photosensitizer has an excitation wavelength in a range from about 410 nm to about 475 nm.

41. The system of claim 39, wherein the photosensitizer is selected from Talaporfin Sodium and its derivatives.

42. The system of claim 39, wherein the photosensitizer is selected from a group consisting of verteporfin and its derivatives, and rostaporfin and its derivatives.

43. A system for treating a varicosity in a subject, comprising: a catheter system including a main body and a distal tip coupled to the main body, the distal tip including an energy delivery device; and an external controller including a retraction mechanism connected to the main body, the retraction mechanism operable to retract the catheter system while the distal tip is within a varicose vessel and emits energy to contract and/or destroy the varicose vessel.

44. The system of claim 43, wherein the external controller is coupleable to skin of the subject to fix the external controller with respect to the subject while the retraction mechanism moves the distal tip through the varicose vessel.

45. The system of claim 43, wherein the retraction mechanism moves the distal tip at a rate less than about 3 cm/min when the retraction mechanism is powered.

46. The system of claim 43, wherein the energy delivery device includes at least one photonic delivery device.

47. The system of claim 43, wherein the external controller includes a power supply electrically coupled to the retraction mechanism, the power supply capable of providing a sufficient amount of power to the retraction mechanism such that the retraction mechanism moves the distal tip at a generally constant speed through the varicose vessel.