Light delivery system and method for photosensitizer-assisted photodynamic therapy

Abstract

A photodynamic therapy light delivery system can comprise a light source and a light delivery catheter, including an expandable distal section, to be advanced to a treatment area in a closed state, and to be expanded to form a flow channel, and configured to have an outer compliant portion to compliantly press against the treatment area; wherein the space between the blood flow channel and outer portion of the catheter can be filled with a balloon, inflated with a fluid transparent or translucent at the treatment wavelengths; a shaft and a proximal section, together configured to advance the expandable distal section to the treatment area, and to receive the light from the light source at the proximal section and to forward the light to the expandable distal section; and side-emitting optical fibers, positioned in the expandable distal section, to receive the light and to illuminate the treatment area.

Description

Atorney Docket No. 67555-703601LIGHT DELIVERY SYSTEM AND METHOD FOR PHOTOSENSITIZER-ASSISTED PHOTODYNAMIC THERAPYCROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 681,015, filed August 8, 2024, which application is incorporated herein by reference in its entirety for all purposes.TECHNICAL FIELD

[0002] Broadly, this invention refers to methods and systems for photodynamic therapy, more specifically to methods and devices for delivering light to a target tissue area to enable photodynamic therapy of the target tissue area.BACKGROUND

[0003] Inflammatory diseases and disorders are conditions in which an abnormal or otherwise dysregulated inflammatory response causes cellular damage and contributes to the etiology or severity of disease. Examples of inflammatory diseases in blood vessels include aneurysms, vasculitis, and other vascular diseases. Chronic inflammatory diseases are characterized by infiltration of immune cells and damage of tissue. Abdominal aortic aneurysm (AAA) is a disease of chronic inflammation that results in the degradation of extracellular matrix proteins (ECM) in the wall of the abdominal aorta. ECM is a major structural component of blood vessel walls. As a result of ECM degradation, the aortic wall weakens, leading to the dilation of the vessel wall and, if left untreated, an increased likelihood of rupture with associated high risk of death. The inner diameter of atypical abdominal aorta is around 15 mm. AAA can lead to this diameter expanding up to 50 mm, typically at a rate of about 3-4 mm / year over about ten years. It is characterized by immune cell infiltration into the vascular wall that causes a protease-mediated degradation of the ECM and changes in the composition of collagen and elastin.

[0004] Regulating immune cell infiltration and maintaining the integrity of the ECM by attenuating protease activity is critical to slowing the growth of aortic aneurysms. However, attempts to target ECM proteases by drugs are limited by the fact that the targeted enzymes play crucial functional roles in several tissues as well as in physiological processes.Atorney Docket No. 67555-703601

[0005] For this reason, other therapeutic approaches have been used to treat AAA. Surgical repair of the abdominal aorta has been performed to repair the aortic aneurysm, often with reinforcement using synthetic graft material. The procedure is the surgical standard for an abdominal aortic aneurysm repair but is associated with an extensive healing period and risk of surgical complications. A less-invasive method is the endovascular implantation of stent grafts to exclude the aneurysm from blood pressure to slow or stop its growth. The procedure has lower surgical risks and a faster healing period, but is not without its own risks, including leakage of the stent graft into the aneurysm, damage to the vessel wall, collapse or migration of the implant, and other post-procedural complications.

[0006] Photodynamic therapy (PDT) has the potential to strengthen the aortic wall without the morbidity of major abdominal surgery or risks associated with a stent graft implantation. PDT involves the administration of a photosensitizer dye which can be activated by light to modulate cellular function. PDT has been shown to increase collagen crosslinking, to lower endothelial activation, and to inhibit smooth-muscle cell migration. Notably, cross-linked collagen increases resistance to protease degradation. All these changes have the potential to act synergistically and protect against aortic aneurysms while maintaining ECM integrity. Studies using riboflavin as a photosensitizer and UV-A light PDT (with wavelengths in the 320- 400 nm range, such as 350 nm) have shown that the mechanical strength of adventitial collagen can be increased in porcine aortic walls. Although promising, riboflavin cannot be directly adapted for AAA because it relies on the application of potentially harmful and low-penetrating UV-A light.

[0007] For all the above reasons, there is a need for new PDT strategies that selectively target sites of inflammation while reducing the side effects associated with light therapy. There is also a need for devices and methods to selectively activate photosensitizer dyes in the region of an abdominal aortic aneurysm. Preferably the devices and methods can be employed using endovascular techniques to minimize the associated procedure complications and healing period.SUMMARY

[0008] In order to address the above needs, a photodynamic therapy (PDT) system has been developed that involves the administration of a photosensitizer dye, which is then locally activated by light using a non-harmful wavelength to modulate cellular function in vascular tissue. The PDT induces localized elastin and collagen crosslinking and promotes local immune suppression. Cross-linked collagen increases resistance to protease degradation. All theseAtorney Docket No. 67555-703601 changes have the potential to act synergistically and protect against aortic aneurysms while maintaining ECM integrity. The here-described PDT uses light at a wavelength that penetrates through oxygenated blood, with a photosensitizer excitation maximum matching the optimum wavelength range of 640-680 nm. An example of such photosensitizers is methylene blue. Further, a polypeptide is conjugated to the photosensitizer that selectively binds to sites of inflammation within the body and is therefore suitable to selectively accumulate the drug to the target tissue.

[0009] The PDT system described herein includes a photosensitizer which can be administered systemically, and a PDT light delivery system comprising a light source of appropriate wavelength and power and a light delivery catheter to deliver light to the treatment site to activate the photosensitizer at the treatment site. Important design principles of this PDT system include the following.

[0010] 1. Blood absorbs light very strongly. Therefore, there is a danger that a substantial fraction of the illumination by the PDT system gets absorbed by the blood in the aorta and does not reach the treatment area. However, it was recognized that the light absorption coefficient of oxygenated blood has a sharp minimum around the wavelength of 660 nm. Therefore, it was recognized that the PDT system should generate its light with a wavelength that approximately matches the minimum of the light absorption coefficient of oxygenated blood in the aorta around 660 nm. With such a design, the illumination will traverse the residual amount of blood that is potentially between the PDT system and the aortic wall with minimal absorption and most of it will reach the treatment area.

[0011] 2. Naturally, the wavelength of the illumination delivered by the PDT system should also approximately match the activation wavelength of the photosensitizer. Therefore, the photosensitizer should be selected so that its activation wavelength is also close to 660 nm. Methylene blue has been identified as such a “wavelength matched” photosensitizer. Other photosensitizer compounds with wavelength-matched absorption can be utilized as well.

[0012] 3. To avoid attenuation of light in the blood between the catheter and the aorta wall, the design of the PDT system should be such that the surface that emits the illumination should be as close as possible to the treatment area - the aorta wall. Preferably, the light-emitting surface should be able to achieve a direct contact with a large fraction of the treatment area. One way to achieve this is that the PDT system employs a compliant balloon that is soft enough to adapt to even an uneven inner wall of the aortic aneurysm so that the balloon contacts the inner wall of the aneurysm over a large fraction of the aneurysm and minimizes the distance toAtorney Docket No. 67555-703601 the aortic wall where it does not achieve a direct contact. Other expanding structures that do not employ a balloon but still achieve good contact with the treatment area can also be used.

[0013] 4. The design of the PDT system should also be such that the treatment light is delivered to the treatment area with an intensity as close as possible to a uniform intensity, within a tolerable range, so that the effect of the treatment is consistent over the entire aneurysm.

[0014] 5. Blocking the blood flow in the main aorta for the duration of the PDT even for a short period (and certainly for the tens of minutes of the PDT) would cause hemodynamic pressure elevation as well as deprive essential organs from vital oxygen and is thus medically unacceptable. Therefore, the PDT system needs to allow sufficient flow of blood during the photodynamic therapy.

[0015] Embodiments address the above challenges and design principles with the following designs. In some embodiments, a photodynamic therapy (PDT) light delivery system can comprise a light source, to generate light for the photodynamic therapy; and a light delivery catheter, including an expandable distal section, to be advanced to a treatment area in a closed state, and to be expanded to form a flow channel, and configured to have an outer compliant portion to compliantly press against the treatment area; a shaft and a proximal section, together configured to advance the expandable distal section to the treatment area, and to receive light from the light source at the proximal section and to forward the light to the expandable distal section; and side-emitting optical fibers, positioned in the expandable distal section, to receive light and to emit it uniformly onto the treatment area.

[0016] In some embodiments of the PDT light delivery system, the expandable distal section can comprise an inner tubular portion that includes an expandable scaffold, to expand when an introducer sheath is withdrawn; and an expandable tubular inner layer around the scaffold, to form the flow channel when expanded by the scaffold; wherein the outer compliant portion includes an outer layer, sealed together with the inner layer to form an inflatable balloon to compliantly press against the treatment area when inflated.

[0017] In some embodiments, a photodynamic therapy (PDT) light delivery system may comprise a light source, to generate light for the photodynamic therapy; and a light delivery catheter, including an expandable distal section, to be advanced to a treatment area in a closed state, and to be expanded to form a flow channel, and to have an outer compliant portion to compliantly press against the treatment area; and side-emitting optical fibers, positioned in the expandable distal section, to receive the light and to emit it onto the treatment area. To enable approximately uniform side emission, side-emitting optical fibers include light scatterers,Atorney Docket No. 67555-703601 characterized by a scattering coefficient S(x) that depends on x, a longitudinal coordinate along a side-emitting zone of the side-emitting optical fibers. In some embodiments, the scattering coefficient S(x) can be increasing with x in order to compensate for decreasing light power inside the fiber and thus to provide an approximately uniform illumination along the sideemitting zone.

[0018] In some embodiments, a method of applying a photodynamic therapy (PDT) with a PDT light delivery system to a treatment area can comprise the steps of: (a) exposing the treatment area to a photosensitizer agent; (b) accessing the treatment area with an introducer sheath; (c) advancing a light delivery catheter, having a closed expandable distal section, a shaft, and a proximal section, in the introducer sheath so as to align the expandable distal section with the treatment area; (d) withdrawing the introducer sheath; (e) expanding the closed distal section to form a flow channel and to have an outer compliant portion press compliantly against the treatment area; (f) delivering a PDT illumination to the treatment area via sideemitting optical fibers, positioned in the expanded distal section; and (g) ceasing the illumination, collapsing the expanded distal section by advancing the introducer sheath, and withdrawing the light delivery catheter through the introducer sheath.BRIEF DESCRIPTION OF THE DRAWINGS

[0019] FIG. 1 shows a schematic drawing of a photodynamic therapy (PDT) light delivery system 100 comprising a light source 110 and a light delivery catheter 120, with an introducer component 130.

[0020] FIGS. 2A-B show an embodiment of the expandable distal section 200 of the light delivery catheter 120.

[0021] FIGS. 3A-E show the expandable distal section 200 of FIG. 2 in a compressed state.

[0022] FIG. 4 shows the expandable distal section 200 of FIG. 2 in an expanded state.

[0023] FIG. 5 shows the expandable distal section 200 of FIG. 2 in an expanded and inflated state.

[0024] FIG. 6 shows an alternate embodiment of the expandable distal section 200, in an expanded state.

[0025] FIG. 7 shows the expandable distal section 200 of FIG. 6 in an expanded and inflated state.Atorney Docket No. 67555-703601

[0026] FIG. 8 shows another embodiment of the expandable distal section 200, in an expanded state.

[0027] FIGS. 9A-E show an embodiment of a scaffold 215 in a collapsed state, in an expanded state, and in a sequence of intermediate states.

[0028] FIG. 10 shows an alternate embodiment of the scaffold 215, in an expanded state.

[0029] FIG. 11 shows another alternate embodiment of the scaffold 215, in an expanded state.

[0030] FIGS 12A-C show a multi-cage embodiment of the scaffold 215.

[0031] FIG. 13 shows an alternate embodiment of the expandable distal section 200 with a covered scaffold 215, in an expanded state.

[0032] FIGS. 14A-B show another, multi-balloon embodiment of the expandable distal section 200, in an expanded and inflated state.

[0033] FIG. 15 shows yet another alternate embodiment of the expandable distal section 200, in an expanded and inflated state.

[0034] FIG. 16 shows an embodiment of a mechanically expandable distal section 200, in an expanded state.

[0035] FIG. 17 shows another embodiment of the expandable distal section 200 with a helical wire structure 290, in an expanded state.

[0036] FIG. 18 shows another embodiment of the expandable distal section 200 with an expandable braided structure 294, in an expanded state.

[0037] FIGS. 19A-E show several embodiments of the side-emitting optical fiber 230.

[0038] FIGS. 20A-B show additional embodiments of the side-emitting optical fiber 230.

[0039] FIG. 21 shows an alternate light delivery system with a cluster of LEDs 510 integrated into the expandable distal section 200.

[0040] FIG. 22 is a graph showing the wavelength dependent absorption spectrum of oxygenated blood.

[0041] FIG. 23 is a graph showing the growth of an aortic diameter in an animal study with and without the application of the present photodynamic therapy method.

[0042] FIG. 24 shows an abdominal aortic anatomy including an aneurysm.

[0043] FIGS. 25A-H show an embodiment of the method 500.

[0044] FIGS. 26A-B show an alternate embodiment of the method 500.

[0045] FIGS. 27A-E show yet another embodiment of the method 500.

[0046] FIG. 28 shows a sonodynamic therapy system 600.Atorney Docket No. 67555-703601

[0047] FIGS. 29A-B show sonodynamic therapy systems 600 for abdominal aortic aneurysm and cerebral aneurysm.DETAILED DESCRIPTION

[0048] To address the above medical needs, a PDT system has been developed based on the above-described design principles. The details of the photosensitizer of the PDT system have been disclosed in the related co-pending application “Methods And Composition For A Photosynthesizer Conjugated Polypeptide And Therapeutic Applications Thereof’ to Daniel M. Schwartz et al.; serial number: PCT / US2024 / 016154, filed on 2 / 16 / 2024, which application is hereby incorporated by reference in its entirety.

[0049] FIG. 1 shows a schematic of a photodynamic therapy (PDT) light delivery system 100, comprising: a light source 110, to generate light for the photodynamic therapy; and a light delivery catheter 120, including an expandable distal section 200, to be advanced to a treatment area in a closed state, and to be expanded to form a flow channel, and configured to have an outer compliant portion to compliantly press against the treatment area; a shaft 300 and a proximal section 400, together configured to advance the expandable distal section 200 to the treatment area, and to receive light from the light source 110 at the proximal section 400 and to forward the light to the expandable distal section 200; and side-emitting optical fibers 230, positioned in the expandable distal section 200, to receive the light and to emit illumination onto the treatment area. In embodiments of the PDT light delivery system 100 the flow channel 220 after expansion can have a diameter between 5 mm and 15 mm. The PDT light delivery system 100 may also include an introducer 130 to introduce the light delivery catheter 120 in a constrained configuration into an introducer sheath and from there into the vasculature of the patient. In one embodiment, the PDT light delivery system 100 is configured to deliver light to an abdominal aortic aneurysm (AAA) site to enable a PDT treatment of the AAA.

[0050] The proximal section 400, and the optical fibers 230 within can be coupled to the light source 110 via a fiber connector (or light cable) 115, through optical couplers 410a-b. The light source 110 can be configured to generate light with sufficient power that is delivered by the light delivery catheter 120 to activate the photo-sensitizer dye that has been previously delivered to the treatment area. This generated light is “wavelength-matched” in the sense that the absorption coefficient of oxygenated blood shows a (local) minimum in the 600 nm - 700 nm range, and the light source 110 is built to generate light with a wavelength approximately matching this minimum, for the reasons described below.Atorney Docket No. 67555-703601

[0051] The introducer component 130 may be used to facilitate inserting the light delivery catheter 120 into a procedural introducer sheath in a collapsed state. Alternately, the introducer component 120 can serve as the introducer sheath.

[0052] Embodiments of the PDT light delivery system 100 differ from traditional and existing stents in function and in design in several important ways.

[0053] 1. Unlike other catheters, the PDT light delivery system 100 applies light onto the treatment area, as part of a photodynamic therapy (PDT). The PDT light delivery system 100 is capable of applying light efficiently to the treatment area in spite of the strong light absorption in blood because at least of the followings. (1.1) The method of using this PDT light delivery system 100 involves applying a photosensitizer which was chosen because its activation wavelength approximately coincides with the sharp minimum of the light absorption spectrum of blood. (1.2) The PDT light delivery system 100 uses a light source to illuminate the treatment area with light whose wavelength also matches this blood absorption minimum, because light with this wavelength can traverse the distance from the expandable distal section 200 to the aortic wall with minimal absorption loss, and there can activate the photosensitizer efficiently. In this sense this PDT light delivery system 100 and therapy can be called “wavelength-matched”. (1.3) The structure and design of the PDT light delivery system 100 positions its light emitting surface in contact with, or at least very close to the inner wall of the aneurysm. This makes the distance to be traversed in blood close to zero, where the two are in direct contact, and at most, around a millimeter - much closer than the light penetration depth in oxygenated blood, shown in FIG. 22.

[0054] 2. Unlike most catheters, the PDT light delivery system 100 does not block blood flow. This makes it a very promising candidate for applications in the abdominal aorta, where stopping the blood flow beyond 10-20 seconds is medically unacceptable. In this sense, this system can be called a flow-through, or non-blocking PDT light delivery system 100.

[0055] 3. Unlike all other catheters, the PDT light delivery system 100 has an inverted structure. In the PDT light delivery system 100, a stent-like wire structure is inside the balloon and expands the balloon, whereas in typical catheters, the balloon is inside the stent and expands the wire structure of the stent.

[0056] 4. Unlike previous catheter-based treatments of aneurysm, whose goal is to implant a stent, the PDT light delivery system 100 is collapsed and retracted at the end of the procedure, and no stent is left behind. The PDT light delivery system 100 is a treatment system, not an implanting system.Atorney Docket No. 67555-703601

[0057] 5. Unlike some catheters that apply light to implants or to a mesh that is intended to stay in the aneurysm, the PDT light delivery system 100 applies light to photo-induce crosslinking in the aortic tissue itself.Light Delivery Catheter Embodiments

[0058] For the treatment of AAA, the light delivery catheter is configured to be positioned in the AAA and allow sufficient flow of blood through the aorta during the PDT treatment, in the event that the PDT treatment involving aortic occlusion lasts longer than about 30 minutes. A normal abdominal aorta lumen for an adult is about 15 mm on average. Depending on the treatment time as well as the blood pressure and hemodynamic requirements of the patient, sufficient flow can be accomplished by a central channel 220 though the expandable distal section 200 of a diameter between 5 and 15 mm, or less in some cases. The expandable distal section 200 can be in a constrained, closed, or collapsed configuration during introduction into the patient through an introducer sheath; then in an expanded configuration to stabilize the light delivery catheter 120 at the treatment site; and in an expanded and inflated configuration to conform to the wall of the AAA, when the outer compliant portion 204 is fully deployed. The light delivery catheter 120 includes a central lumen configured to accept a guidewire such as an .035” OD (outer diameter) guidewire to allow for endovascular access and placement of the light delivery catheter 120 over a guidewire.

[0059] FIG. 2A shows an embodiment of the photodynamic therapy (PDT) light delivery system 100 in more detail, wherein the expandable distal section 200 comprises an inner tubular portion 202 that includes an expandable scaffold 215 and an expandable tubular inner layer 208 around the scaffold 215, to form the flow channel 220 when expanded by the scaffold 215; and the outer compliant portion 204 with an outer layer 212, sealed together with the inner layer 208 to form an inflatable balloon 205 to compliantly press against the treatment area when inflated. This PDT light delivery system 100 also includes the side-emitting optical fibers 230, positioned in the expandable distal section 200, to receive the light and to emit illumination onto the treatment area; and the shaft 300 and the proximal section 400. For brevity, the closed expandable distal section 200 and the expandable distal section 200 will be simply referred to as the distal section 200. In this embodiment, the expansion of the expandable distal section 200 takes place in two stages: the expansion of the scaffold 215 and the inner layer 208 to form the flow channel 220; and the inflation of the balloon 205 to compliantly press against the treatment area. In later embodiments, these two stages unfoldAtorney Docket No. 67555-703601 together as the expansion of the outer compliant portion 204 simultaneously forms the flow channel and presses against the treatment area.

[0060] In some exemplary embodiments, the treatment area can be an aneurysm, and the PDT light delivery catheter 120 can illuminate the inner wall of the aneurysm. However, the PDT light delivery catheter 120 can be used to administer photodynamic therapy to other tissues within the human body, such as to aneurysms in other areas, as the brain. The PDT light delivery system 100 can be used even for non-artery -based applications, such as for pulmonary PDT treatments. For specificity, the description of the embodiments of the PDT light delivery system 100 will use mostly the example of abdominal aortic aneurysm. However, with natural modifications and adaptations, the PDT light delivery system 100 can be used for the just referenced other medical applications.

[0061] The inner layer 208 can be formed from a higher durometer, low compliance, or non-compliant material that is expanded by the expandable scaffold structure. Example materials for the inner layer 208 can be nylon, polyester, polyethylene, or Pebax, but analogous materials can be used as well. The outer layer 212 can be formed from a thin, lower durometer material such that it can be expanded by filling the balloon 205 with a low pressure inflation fluid 213 so as to minimize the force on the aneurysm wall when the outer layer 212 compliantly presses against the aneurysm wall. Example materials for the outer layer 212 are silicone rubber, elastomeric polyurethane, thermoplastic elastomers, blends thereof, or other appropriate materials. The inner layer 208 and the outer layer 212 can be sealed together tightly in a waterproof manner to form a balloon 205 that is capable to contain and accommodate the inflation liquid 213 to expand the outer layer 212.

[0062] The light delivery catheter 120 can further include side-emitting optical fibers 230a, 230b, . . ., collectively referred to simply as optical fibers 230, to generate illumination towards the aneurysm wall. As discussed later, the optical fibers 230 can run along the entire length of the shaft 300 and become side-emitting only once they entered the expandable distal section 200. Only one optical fiber 230a is shown in FIG. 2A, but embodiments can have two, three, four, or more such optical fibers. As described below, these optical fibers 230 may enter the light delivery catheter 120 at the proximal section 400, may run the entire length of the shaft 300, eventually reaching and entering the expandable distal section 200. They are side-emitting in the sense that they side-emit light only, or dominantly, in their part which is inside the balloon 205 of the expandable distal section 200. The side-emitting optical fibers 230 can be positioned on the outer wall of the inner layer 208, either directly affixed to, integrated into it, or loosely running along.Atorney Docket No. 67555-703601

[0063] In operation, the balloon 205 of the expandable distal section 200 is inflated to press the outer layer 212 against the aneurysm wall so as to expel the highly absorbing blood from between the side-emitting optical fibers 230 and the aneurysm wall. After inflation, the largest fraction of the area of the outer layer 212 achieves direct contact with the aneurysm wall, so that there is no blood left between them, and thus the illuminating light can reach the aneurysm wall without getting absorbed by blood. In the remaining smaller fraction of the area, the separation between the outer layer 212 and the aneurysm wall, filled by blood, can increase up to a couple mm. However, since a wavelength-matched light is emitted by the optical fibers 230, the absorption by the blood that fills this separation is quite limited and still most of the illumination reaches the aneurysm wall.

[0064] The balloon 205 can be inflated by pumping inflation fluid 213 into it, using a syringe or another inflation device. This inflation fluid 213 can be chosen to be transparent at the PDT light wavelength, matched to the blood absorption minimum and the photosensitizer activation wavelength, thus allowing the light of the side-emitting optical fibers 230 to reach the aneurysm wall with minimal loss. In other embodiments, the fluid can be translucent but scattering light at the PDT wavelength. In such embodiments, the light generated by the discrete optical fibers 230 is spread more evenly across the aneurysm wall. In embodiments with either transparent or translucent inflation fluid 213, the spatial, or angular distribution of the illumination light can be further homogenized by making the outer surface of the inner layer 208 reflecting, to form a reflecting surface 235. Light from the optical fibers 230 that is not directed radially outward will be reflected by this reflecting surface 235 towards and through the outer layer 212, eventually towards the aneurysm wall. Embodiments of the expandable distal section 200 that are filled with a translucent inflation fluid 213 and / or have a reflecting surface 235, generate an illumination light with an advantageously high spatial and / or angular homogeneity.

[0065] FIG. 2B shows the expandable distal section 200 after it has been inserted, advanced to the treatment area and inflated to contact the aneurysm wall. This embodiment utilizes four optical fibers 230a-d. The light rays emitted from these optical fibers 230a-d show the effect of the reflecting surface 235: the reflecting surface 235 redirects originally inward propagating light to propagate radially outward, towards the targeted aneurysm wall.

[0066] FIG. 2A shows that the expandable distal section 200 also includes the expandable scaffold 215. In some embodiments, the expansion scaffold can be formed from a nitinol tube with a cut pattern. This cut pattern can be, for example, a staggered or aligned set ofAtorney Docket No. 67555-703601 longitudinal cuts. In some embodiments, the expandable scaffold 215 can include at least one of struts, spokes, expandable circular wires, a set of longitudinal wires, wire meshes, a stentlike structure, a series of linked zig zag rings, a braided structure, a ring-link structure, and a mesh. Any of these expandable scaffolds 215 can be formed, at least partially, from nitinol. The nitinol wires or mesh can be heat-set into the expanded shape. The heat-setting can be performed in the range of 100 C-1,000 C, in some cases in the range of 300 C-500 C, for example around T=400 C. Stainless steel can also be used. Other scaffold embodiments, materials, and configurations are described later.

[0067] The preparation for the photodynamic therapy can involve the following steps for the expandable distal section 200. First is the inserting and advancing the expandable distal section 200 of the light delivery catheter 120 to the treatment site. Second is the expanding the expandable scaffold 215 to expand the inner layer 208 of the expandable distal section 200 to create and to maintain the flow channel 220 for the blood flow (F). Atypical (inner) diameter (ID) of this flow channel 220 after expansion is between 5 mm and 15 mm, preferably between 8 mm and 15 mm. As described among the design principles, forming this flow channel 220 is crucial to provide uninterrupted blood flow and maintain a safe arterial blood pressure for the vital organs during the PDT procedure. Forming such a large cross section flow channel 220, or blood flow lumen 220, allows the PDT to retain at least 50% of the flow cross section of a typical aorta after the inner layer 208 has been expanded. In some embodiments, 75% or even 90% of the regular aorta flow cross section may be retained.

[0068] Third is inflating the balloon 205 to expel blood from between the outer layer 212 and the aneurysm wall, or at least minimize the amount of blood in that space. Doing so eliminates, or minimizes, the absorption of the PDT illumination by blood. The expansion and the inflation can be performed in either order, or in parallel.

[0069] The inflation of the balloon 205 is performed by providing, or pumping in the inflation fluid 213 through one or more inflation lumens 275 which have a distal fluid connection to the interior of the balloon 205 via inflation arms 225a and 225b. At their proximal end, the inflation lumens are connected at the catheter proximal section 400 to an inflation connection which can be attached to an inflation device. Many suitable inflation systems are known and do not need to be detailed here. Finally, as described later, scaffold shaft 240 can provide the means by which the expandable scaffold 215 is controlled and manipulated.

[0070] Some embodiments of the light delivery catheter 120 are deliverable using standard endovascular methods and accessories, including introduction over a guidewire and through an introducer sheath 120 into the vasculature. Preferentially, the access site can be in the femoralAtorney Docket No. 67555-703601 artery and the light delivery catheter 120 can be advanced in a retrograde direction to the abdominal aorta. The sheath size through which the catheter can be delivered can be 14 F (0.182” OD) or less; in some embodiments 10 F (0.130” OD) or less, in yet other embodiments 8 F (0.104” OD) or less. Here the unit “F” stands for “French”, the widely used unit of length characterizing the diameter of catheters. 1 French stands for 1 / 3 mm. Accordingly, 3 F=1 mm. OD stands for “outer diameter”. Below, ID will stand for “inner diameter”. Inches will be denoted by ”. In some embodiments, the size of the guidewire can be 0.035”, requiring a guidewire lumen of 0.038” to 0.040” inner diameter ID. A guidewire distal tip is typically rounded, tapered, or otherwise atraumatic to the vasculature as the light delivery catheter 120 is advanced to the target treatment site. The light delivery catheter 120 can be sized to be able to treat aneurysms as little as 30 mm diameter x 8 cm in length, or as large as 50 mm in diameter x 15 cm in length.

[0071] FIG. 3A shows a side view of the light delivery catheter 120 in a compressed state, before expansion; FIG. 3B shows the informative “B” cross section of the expandable distal section 200; while FIG. 3C shows the cross section “C” of the shaft 300 in this pre-deployed, compressed state. The optical fibers 230a-b can be positioned along the length of light delivery catheter 120, from the proximal section 400 along the shaft 300, and terminate between the inner layer 208 and outer layer 212. The number of optical fibers 230 can be two or more. The higher the number of the optical fibers 230, the more uniform the spatial, or angular distribution of the PDT illumination. The optical fibers 230 can be positioned or affixed on the outer surface of the inner layer 208, or on its inner surface if the inner layer 208 is transparent. In some embodiments, they can be integrated into the inner layer 208 itself. In some cases, they may not be attached to the inner layer 208; rather, the optical fibers 230 can be just positioned proximate to the inner layer 208. The expandable scaffold 215 can be connected at its proximal end to a scaffold shaft 240. The scaffold shaft 240 can be positioned in a central lumen of catheter shaft 300.

[0072] The outer layer 212 of the balloon 205 is transparent, or clear, at least at an operating wavelength of the illumination, so that the illumination light can propagate from the optical fibers 230 to the treatment area, such as the aneurysm wall, with no, or minimal loss. The inner layer 208 may be clear, translucent, or opaque. The inner layer 208 may also be reflective, or has a reflective surface 235, for the operating light wavelength, either with a reflective coating, or with a reflective additive in the polymer, so as to reflect and redirect the illumination outward, towards the aneurysm wall, or treatment area. This design increases the power of the illumination and makes its angular distribution more homogeneous.Atorney Docket No. 67555-703601

[0073] In an embodiment, the optical fibers 230 are positioned inside the inner layer 208, between the inner layer 208 and the scaffold 215, and not within the inflatable balloon 205. In this embodiment, both the inner layer 208 and outer layer 212 are clear, or transparent, so as to allow the light to travel from the optical fibers 230 through both layers 208 and 212 to the aneurysm wall.

[0074] FIGS. 3A-C show the expandable distal section 200 in a compressed configuration, used while the light delivery catheter 120 is being advanced to the treatment area, before the expandable distal section 200 is expanded at the targeted treatment area. FIG. 3A shows a side view of the expandable distal section 200 and a portion of shaft 300. FIG. 3B shows cross section “B” through the expandable distal section 200, and FIG. 3C shows cross section “C” through the shaft 300. As seen most clearly in FIG. 3B, in the constrained configuration the scaffold 215 is compressed into a relatively small diameter configuration, and the balloon 205 is deflated, with the inner layer 208 and the outer layer 212 furled around the scaffold 215 as flaps 250a and 250b. FIG. 3B shows two flaps 250a and 250b of the balloon 205 in a deflated state and furled in a helical or chiral pattern around the collapsed or compressed scaffold 215. The flaps 250a and 250b can also be wrapped towards each other. In alternate embodiments, the collapsed scaffold 215 could be situated on one side of the deflated balloon 205, so that the deflated balloon 205 forms only a single flap 250, furled helically around the compressed scaffold 215. In yet other embodiments, the deflated balloon 205 could have three or more flaps, furled helically around the compressed scaffold 215. In all of these embodiments, the expandable distal section 200 is compressed by folding the balloon 205 into one or more wraparound flaps 250. As described later, these flaps 250 inflate and expand into one or more lobes when the expandable distal section 200 is expanded.

[0075] FIG. 3C shows the “C” cross section of the shaft 300 that has a main lumen 260 that houses the scaffold shaft 240. The interior of the scaffold shaft 240 forms a center lumen 270 that is configured to accept a guidewire, for example an .035” or .038” guidewire, so as to allow guidewire-assisted advancement of the light delivery catheter 120 to the treatment area, such as the aneurysm.

[0076] The main lumen 260 is surrounded by the shaft 300. This shaft 300 can include the one or more optical fibers 230a-b, and one or more inflation lumens 275a-b. The optical fibers 230a-b and the inflation lumens 275a-b can be co-housed, or the optical fibers 230a-b can be inside the inflation lumens 275a-b, or they can be formed separately in the wall of the shaft 300. The inflation lumens 275a and 275b are fluidly connected inflation arms 225a and 225b, respectively. The inflation arms 225a-b flexibly connect the shaft 300 to the expandable distalAtorney Docket No. 67555-703601 section 200: they start at their connection to the distal end of the inflation lumens 275a-b, and movably extend to terminate inside the balloon 205. The flexibility and loose connectivity of the inflation arms 275a-b allows them to maintain the fluid connection between the inflation lumens 275a-b and the interior of the balloon 205 when the inner layer 208 is expanded by the scaffold 215. Among others, this requires an extra length to accommodate the radial expansion of the scaffold 215. Thereby, the one or more inflation lumens 275a-b that have a distal fluid connection to the balloon 205 via the one or more inflation arms 225a-b, are configured to inflate the outer layer 212 with the inflation fluid 213.

[0077] The one or more inflation lumens 275a-b also have a proximal fluid connection to an inflation device via an inflation connector 433 of the proximal section 400. FIG. 1 shows an embodiment where the proximal section 400 has the inflation connector 433 to connect the inflation lumen(s) 275a-b to an inflation device (not shown) such as a syringe, a balloon inflation device, or some other, well-known equivalent. The inflation connector 433 can be a female Luer connector, a fluid line terminating in a female Luer connector or any other type of connector that mates with an inflation device.

[0078] A function of the inflation device, the inflation connector 433, the inflation lumens 275 and the inflation arms 225 is to facilitate the inflating the inflatable balloon 205 with a translucent, or light-dispersive (inflation) fluid 213. The illuminating light generated by the optical fibers 230 has a narrower spatial, or angular distribution, and thus would not illuminate the treatment area sufficiently homogeneously. Therefore, the PDT is more effective if the illumination is made more homogeneous, more dispersed. This is a function that a dispersive fluid 213 can perform well. Such dispersive fluids 213 do not absorb, or only minimally absorb the illumination. However, they repeatedly scatter and thus disperse the illumination generated by the optical fibers, and therefore, by the time the illumination reaches the outer layer 212 and thus the treatment area, its spatial and angular distribution is more homogenized. Some embodiments can use a light-dispersive fluid 213 that includes at least one of a lipid solution, an intralipid, and an oil solution.

[0079] FIG. 3C also shows that portions of the optical fibers 230a-b may be housed in the inflation lumens 275a-b, as shown, or the shaft 300 may contain separate lumens for the optical fibers 230a-b. If the optical fibers 230a-b are housed in the inflation lumens 275a-b, then the optical fibers 230 can continue in the inflation arms 225a-b to reach the interior of the balloon 205. In alternate embodiments, where the optical fibers 230a-b are in separate lumens of the shaft 300, the optical fibers 230a-b can be positioned in separate flexible inflation arms (notAtorney Docket No. 67555-703601 shown), reaching the interior of the balloon 205 that way. In either embodiment, the optical fibers 230a-b can be on the inside of these connecting arms.

[0080] FIG. 1 also shows that at the proximal section 400, the optical fibers 230a-b can be coupled, or connected, to the light source 110 via optical couplers 41 Oa-b and light cables 115a- b. Alternately, the optical fibers 230 can extend continuously from the distal section 200 all the way to the light source 110 with no intermediary connect! ons / couplers 410 and / or or connector cable 115. If the optical fibers 230a-b are positioned in the inflation lumens 275a-b, the optical fibers 23 Oa-b can travel through a seal component or adhesive to the optical couplers / connectors 410a-b to fluidly separate the inflation connector 433 from the optical couplers / connectors 410a-b. The optical coupler / connector 410 may include a fiber splitter to connect multiple optical fibers 230a-d to the light source 110 through a single light cable 115. Alternately, the optical coupler / fiber connector 410 in the catheter 120 may include a fiber splitter to combine multiple light cable 115a-b to a single optical fiber 230. In some light delivery catheters 120, the shaft 300 itself may carry only this single optical fiber 230 along its length, which is coupled to a fiber splitter only at its distal end where it connects to the expandable distal section 200 to feed light into multiple optical fibers 230a-d within the balloon 205. The optical coupler / fiber connector 410 may be an integral part of the light delivery catheter 120, or it may be a separate component. Alternately, the optical fibers 230 can extend directly from the light source 110 to the distal section 200 without the intermediary optical coupler 410, or light cable 115. In this embodiment, the light fibers 230 may extend quite a distance beyond the working length of the light delivery catheter 120 so as to be able to connect to the light source 110 some distance away from the operating table.

[0081] The embodiment shown in FIGS. 3A-C depict the distal section 200 with the scaffold 215 positioned inside the furled balloon 205 during catheter positioning. FIGS. 3D-E show another embodiment, where the scaffold 215 is not positioned inside the inner layer 208 of balloon 205. Rather, the scaffold 215 is positioned proximal relative to the furled balloon 205, in a compressed state in the main lumen 260 of the shaft 300 during catheter positioning. A tubular inner member 277 is also positioned inside the main lumen 260 of shaft 300, extending from the proximal compressed scaffold 215 through inside of the distal furled balloon 205, so that an inner member tapered tip 279 at its end is distal to the balloon 205, as shown. Once the expandable distal section 200 with the balloon 205 is positioned at the treatment area, the scaffold 215 can be advanced, or slid, over the inner member 277 and positioned in the flow channel 220 of the balloon 205. As it will be described in relation to FIG. 27B, this flow channel 220 maybe only partially opened, for example, by the oncomingAtorney Docket No. 67555-703601 blood flow. From here, the expansion of the scaffold 215 and the inflation of the inner balloon 205 can proceed analogously to that of the embodiment of FIGS. 3A-C. (In this embodiment, the proximal scaffold 215 can be still thought of as being part of the expandable distal section 200.) Since the inner member 277 has a smaller outer diameter (OD) than the compressed scaffold 215, the furled balloon 205 can be furled with a tighter diameter, and thus this embodiment has a smaller delivery profile than the embodiment depicted in FIG 3A. This smaller delivery profile makes the procedure of advancing and positioning the light delivery catheter 120 with this “proximal scaffold-distal balloon” design easier.

[0082] FIG. 4 shows the expandable distal section 200 of the embodiments of either FIG 3A or FIG. 3D in an intermediate state of expansion, or deployment. Here, the parts of the inner tubular portion 202: the expandable scaffold 215 and the inner layer 208 have already been expanded. The outer compliant portion 204 is not shown for clarity. As shown, the scaffold 215 extends past the ends of the inner layer 208 and the entire balloon 205, which can be called interchangeably an inflation structure 205. There are at least two reasons for this. When the scaffold 215 is expanded from its compressed, or closed state, its length shortens, while at the same time the length of the inner layer 208 does not, or just minimally so. Therefore, the scaffold 215 can expand the entire inner layer 208 properly, if in its compressed state the scaffold 215 is longer that the inner layer 208. Second, there is a benefit of the ends of the scaffold 215 extending past the inner layer 208 even in the expanded state: this allows the scaffold 215 to be positioned and anchored in the aorta past the aneurysm. Doing so stabilizes the expandable distal section 200 in place during the inflation process and during the photodynamic therapy itself. In these embodiments, the inflatable balloon 205 and therefore the light from the optical fibers 230 reaches the entire treatment area of the aneurysm, from the transition section from the normal aorta to the aneurysm segment, the body of the aneurysm, and the transition section from the aneurysm back to the normal segment. In some designs, the scaffold 215 can extend past the inner layer 208, or the inflation structure at its distal end only. In yet other designs, the scaffold 215 can be flush at both ends of the inflation structure, of inner layer 208.

[0083] The expanded diameter of the scaffold 215 can be as large as the aorta itself, or it can be smaller than the aorta. A primary function of expanding the scaffold 215 is to form and to maintain the flow channel 220 for blood flow during the PDT treatment. As described earlier, in some cases, the inner diameter of the expanded scaffold 215 can be in the 5 mm - 15 mm range. In addition, if the diameter of the expanded scaffold 215 is as large as that of the pre- PDT aorta, then the scaffold 215 will anchor the expandable distal section 200 firmly in theAtorney Docket No. 67555-703601 aorta, in which case the subsequent inflation of the outer layer 212 of the balloon 205 can be minimal. In other PDT protocols, the scaffold 215 expands the inner layer 208 to a diameter less than that of the aorta. In such protocols the distant section 200 can be primarily stabilized by inflating the balloon 205 via its outer layer 212.

[0084] FIG. 5 shows the expandable distal section 200 in its expanded and inflated state at the treatment area. Of the constituents of the balloon 205, the inner layer 208 has been expanded by the scaffold 215, and the outer layer 212 has been expanded by filling it up with inflation fluid 213. In some embodiments, the inner layer 208 has higher durometer than the durometer of the outer layer 212. Example materials for the inner layer 208 include nylon, mylar, polyester, polyethylene, or Pebax, but analogous materials can be used as well. Example materials for the outer layer 212 include Pebax, silicone rubber, elastomeric polyurethane, thermoplastic elastomers, blends thereof, or other appropriate materials. This is why during the expansion, the higher durometer inner layer 208 remains wrapped around the expandable scaffold 215, while the softer, low durometer, compliant outer layer 212 keeps expanding when inflated with inflation fluid 213. Because of this compliant, softly elastic characteristics of the outer layer 212, a low pressure is already sufficient to inflate the balloon 205 to appose the majority or all of the aortic aneurysm wall. And even where the outer layer 212 does not achieve direct contact with the aneurysm wall, it gets very close to it, achieving a separation as small as 0.1 mm - 1 mm. Light delivery catheters 120 that require low expansion pressure are desirable to minimize the force exerted on the aneurysm wall. In an embodiment, the pressure required to inflate the balloon 205 can be less than 1 psi. In another embodiment, the pressure required to inflate the balloon 205 can be between 1 and 5 psi, or between 1 and 3 psi.

[0085] As already mentioned, the scaffold 215 shortens somewhat when expanding from a collapsed / compressed state to an expanded state, whereas the inflation structure 205, or balloon 205, which unfurls when expanding and inflating from a collapsed state to an expanded state, does not shorten. To accommodate this difference of shortening of these two components, the scaffold 215 is only partially attached to the inner layer 208. The scaffold 215 can be unattached to the inner layer 208 at its distal end, at its proximal end, or along the entire length. For example, the scaffold 215 may extend past the distal end of the inner layer 208 by a first distance when in a collapsed state, and then extend past the distal end of the inner layer 208 by a second, shorter distance when expanded. Given that their attachment is only partial, or in some cases they are not attached at all, during expansion an outer surface of the scaffold 215 is moving relative to the inner layer 208, in some embodiments the inner layer 208 can be made of a lubricious material, or a low friction material. In related embodiments, the inner layer 208Atorney Docket No. 67555-703601 can be made of a non-compliant or semi-compliant material such as nylon 12, low-density polyethylene (LLDPE), or a thermoelastic elastomer that may include polyamide and poly ether backbone blocks, an example being Pebax, or analogous materials. In some embodiments, the inner layer 208 may have a low friction additive or coating to reduce the friction further. In an embodiment, the inner layer 208 may have reinforcing ribs, rods, or other structural elements built into the material or affixed to the material to maintain its length while the scaffold 215 expands and shortens.

[0086] As noted above, the diameter of the scaffold 215 in the expanded state is preferably large enough to create the flow channel 220 to enable adequate blood flow during a PDT treatment. In an embodiment, the scaffold 215 can expand to an inner diameter in the range 8 to 15 mm. The scaffold 215 may be slightly flattened or compressed when the balloon 205 is being inflated with inflation fluid 213, but still has enough radial and structural strength to maintain an adequate cross section for the flow channel 220. This adequate cross section is maintained by the scaffold 215 even at maximum inflation of the outer layer 212 and in aortic blood pressure conditions.

[0087] In embodiments, the balloon 205 is sized and compliant enough to cover a range of aneurysm sizes up to a maximum size of approximately 50 mm in diameter and 6 cm in length. In an embodiment, the entire light delivery catheter 120 can be configured in a range of sizes to address aortas and aortic aneurysms of different sizes. The balloon 205 will vary in inflated diameter to match the anatomy of the patient and clinical requirements of the procedure.

[0088] In the embodiments of the light delivery catheter 120, the balloon 205 comprises the inner layer 208 and the outer layer 212, which are hermetically sealed together at both ends to for the balloon 205 in a watertight manner to safely accommodate the inflation fluid 213. The seal could be an adhesive seal, a thermal seal or a weld. The seal could also comprise a tie layer of material which could be thermally welded to both inner and outer layer materials. The inflation arms 225a-b can enter the balloon 205 at the proximal seal, and are themselves sealed, either with thermal bonding, adhesive, or some combination.

[0089] FIGS. 6-7 show that in a variation, the distal seal can be formed with the distal edge of the outer layer 212 folded over and then sealed to the inner layer 208. Visibly, the distal end of the outer layer 212 is folded over to form outer layer distal fold 280. The distal fold 280 is folded over and sealed to the inner layer 208. FIG. 6 shows this embodiment in the expanded but uninflated state. FIG. 7 shows the same embodiment after the balloon 205 and its outer layer 212 were inflated. FIG. 7 shows that the distal seal is not taking up room on the distal edge. This embodiment therefore increases the contact area of the inflated outer layer 212 withAtorney Docket No. 67555-703601 the aneurysm wall, and thus increases the treatment area that is exposed to light without increasing the length of the expandable distal section 200.

[0090] In yet another alternate embodiment, the inner layer 208 and the outer layer 212 of the balloon 205 are formed from a single material layer, which is just folded at the distal end, and thus requires sealing only at the proximal end in a hermetic, watertight manner. The inflation arms 225 that enter the balloon 205 at this proximal seal are sealed as well. An advantage of this embodiment is that one less seal is required to form the balloon 206. However, in some natural embodiments the same material is used for both the inner layer 208 and the outer layer 212. In other embodiments, optionally a suitable coating can be used only for the inner layer portion 208, e.g. to make it reflective to form the reflective surface 235.

[0091] The previous embodiments were described to have a straight edge at their proximal end. In some other embodiments, the proximal end of the balloon 205 may be shaped to make retraction of the expandable distal section 200 into the introducer component 120 or introducer sheath smoother. FIG. 8 shows such an embodiment, where the inner layer 208 and outer layer 212 of the balloon 205 form a V-shaped proximal edge 218 that reduces resistance against the retraction of the expandable distal section 200 and thus makes the completion of the PDT much smoother. In addition, the inner layer 208 and outer layer 212 of the balloon 205 can form one or more balloon arms 226a-b to align with, or even to incorporate the inflation arms 225a-b. The inflation arms 225a-b may terminate at the proximal end of the balloon arms 226a-b, or may continue up the balloon legs 226a-b to enter the main inflation balloon 205, as shown. In this embodiment, the seal between the inner layer 208 and the outer layer 212 may extend along the balloon arms 226a-b, so that they do not inflate. Other configurations of the balloon 205 are possible to facilitate the attachment to the catheter shaft 300, the furling or unfurling of the flaps 250a-b, the retraction into the sheath, or other design features.

[0092] In the embodiments described above, the materials of the inner layer 208 and the outer layer 212 are selected to provide the needed performance characteristics. The compliant outer layer 212 of the ballon 205 may be made from silicone rubber, elastomeric polyurethan, thermoplastic elastomers, blends thereof, or other appropriate materials. The wall thickness should be as thin as possible while still providing the required mechanical integrity, so as to keep the inflation pressure low. The material of the outer layer 212 should be largely transparent or clear at the operation wavelength of the illumination, around 600-700 nm. As already mentioned, the inner layer 208 does not have to be compliant, and can be made from polymers such as nylon, polyethylene, LLDPE, Pebax, or other appropriate materials.Atorney Docket No. 67555-703601

[0093] FIGS. 9A-B show an embodiment of the scaffold 215 and scaffold shaft 240 in isolation, to better illustrate their details. FIG. 9A shows the scaffold 215 in the collapsed or constrained state, and FIG. 9B shows the scaffold 215 in the expanded state. The length LI of the scaffold 215 in the collapsed, or compressed, configuration is longer than the length L2 of the scaffold 215 in the expanded configuration. In this embodiment, the scaffold 215 is an expandable tube with cut pattern 215-10 that is expandable to the desired diameter. The cut pattern also creates two or more struts 215-12, which connect the expandable tube with cut pattern 215-10 to a solid uncut tube 215-14 on the proximal end of scaffold 215. If the expandable tube with cut pattern 215-10 is made of nitinol, then optionally it can be heat set to the desired expanded diameter. In other embodiment, the scaffolding 215 can be made of stainless steel. The cut pattern in the compressed state can be parallel lines of repeating longitudinal cuts, where the cuts in neighboring lines are shifted by about a half period. When expanded, this cut pattern expands into a sequence of zig zag rings attached at some or all peaks to valleys of the adjacent ring, as shown. The dimensions of the zig zag struts can be selected to provide the radial force or pressure that is needed to expand the inner layer 208. Another consideration is to minimize the shortening of the pattern cut expandable tube 215-10. The links connecting peaks to valleys may be short straight bridges, or may have a continuous undulating shape to create some flexibility between rings. Other embodiments of the expandable scaffolding 215 may include struts, spokes, expandable circular wires, a set of longitudinal wires, wire meshes, a stent-like structure, a series of linked zig zag rings, a braided structure, a ring-link structure, and a mesh.

[0094] The scaffold 215 may be continuous with the scaffold shaft 240. In other words, the scaffold shaft 240 may be formed from the same nitinol tube as the scaffold 215. Alternately, the scaffold 215 can be constructed from one tube and the scaffold shaft 240 from another tube of the same or different material. For example, the scaffold 215 may be made of nitinol and the scaffold shaft 240 may be made of stainless steel. In an embodiment, the scaffold 215 can be mechanically attached to the scaffold shaft 240, for example with a puzzle piece shape on the proximal end of the uncut tube 215-14, and a negative of the puzzle piece shape cut into the distal end of the scaffold shaft 240. Alternately, the scaffold 215 may be swaged, welded, soldered, or otherwise attached to the scaffold shaft 240.

[0095] FIGS. 9A-B further show that the scaffold shaft 240 itself may have a pattern of slits to improve its flexibility, without compromising its mechanical characteristics. The pattern of slits may vary along the length of the scaffold shaft 240 or may disappear altogether in theAtorney Docket No. 67555-703601 proximal segment, such that it is more flexible in the distal segment and more rigid in the proximal segment. Alternately, the scaffold shaft 240 can be a solid length of tubing.

[0096] FIGS. 9C-E show a cross-sectional view of stages of expanding the scaffold 215 in an embodiment. The PDT light delivery catheter 120 can include a scaffold assembly 216 comprising the scaffold 215 and a scaffold restraining sleeve 217. This scaffold assembly 216 can be advanced through the shaft 300 to the treatment area where it can be expanded as part of the expandable distal section 200. One of the purposes of the restraining sleeve 217 is to keep the scaffold 215 in the collapsed, or compressed, configuration during delivery of the light delivery catheter 120 to the target site, or treatment area, as shown in FIG. 9C. When the collapsed scaffold 215 reaches the treatment area, the restraining sleeve 217 can be pulled proximally with respect to the scaffold 215. This causes the self-expanding scaffold 215 to open, either driven by its internal elastic forces, or by a pulling external force. FIG. 9C shows the scaffold 215 in its initial, compressed state; FIG. 9D shows it in an intermediate state when the restraining sleeve 217 is partially withdrawn and the scaffold 215 is partially expanded and deployed; and FIG. 9E shows the final state when the restraining sleeve 217 sleeve is completely pulled back to completely expose the scaffold 215, at which stage the scaffold 215 opens up to its fully expanded configuration.

[0097] An advantage of the scaffold assembly 216 is that because it is in a restrained configuration in the light delivery catheter 120, it can move independently with respect to the balloon 205 as it is not continually exerting an outward force on the balloon 205. Thus, when the light delivery catheter 120 is in its delivery configuration, the scaffold assembly 216 can be positioned proximally to the balloon 205, completely in the central lumen 270 of the catheter shaft 300. Once the light delivery catheter 120 is positioned with the balloon 205 at the treatment area, or target site, the scaffold assembly 216 can be advanced into the central channel of the balloon 205, and then expanded by pulling back the restraining sleeve 217. By making the scaffold 215 positionable independently from the balloon 205, it allows the balloon 205 to be furled to a smaller diameter in the delivery configuration, as the balloon 205 does not have to furl around the scaffold 215, but rather, can be furled around a smaller diameter guidewire lumen. This configuration also allows the scaffold 215 which may shorten on expansion to expand easily without interfering with the balloon layers 208 and 212.

[0098] The balloon 205 can include the side-emitting optical fibers 230 as seen, for example, in FIG. 2. In the delivery configuration of the light delivery catheter 120, where the scaffold 215 is not inside the balloon 205, but, rather, proximal to it; when the balloon 205 is first positioned in the treatment area, it may be advantageous to include features which exert aAtorney Docket No. 67555-703601 slight outward force on the inner layer 208 that forms the flow channel 220, so that the expandable distal section 200 does not rely on blood flow alone to open up the flow channel 220. For example, spring wires which are shaped to expand outward may be adhered to the inner layer 208 of balloon 205. Alternatively, these spring wires may be included in connection with the side-emitting optical fibers 230. Other means may be added to balloon 205 to urge the flow channel 220 to open up for the blood flow.

[0099] FIG. 10 depicts an alternate embodiment of the scaffold 215: an expandable braid 215-20. The expandable braid 215-20 of the scaffold 215 can be a braided wire construction from two or more braided wires 215-22. The shown embodiment has four braid wires 215-22- 1 . . . 215-22-4 in the expandable braid 215-10. The braid wires 215-12 may have looped ends on one or both ends, to reduce trauma to the vessel wall during advancement and placement, expansion, and removal of the device. Struts 215-24 connect the expandable braid 215-20 to a proximal braid end 215-26. In an embodiment, the struts 215-24 can be extensions of the braid wires 215-22. In an alternate embodiment, the struts 215-24 can be separate wires, attached by being looped or otherwise interwoven with the expandable braid 215-10, or alternately welded, soldered, or otherwise attached to the expandable braid 215-20. In yet another embodiment, the struts 215-24 can be formed from a cut pattern of a tube of the scaffold 215. The proximal braid-end 215-26 is attached to scaffold shaft 240, by mechanical attachment, welding, swagging, soldering, or other attachment means.

[0100] FIG. 11 shows yet another alternate embodiment of the scaffold 215. This expandable tube 215-30 can be made of nitinol, with an asymmetric cut pattern 215-32. Struts 215-34 can connect the expandable tube 215-30 to a proximal end 216-36. The proximal end 215-36 canbe attached to the scaffold shaft240, by mechanical attachment, welding, swagging, soldering, or other attachment means, or is continuous with the scaffold shaft 240.

[0101] FIG. 12 illustrates that some cylindrical, embodiments of the scaffold 215, e.g. the ones illustrated in FIGS. 9-11 may not have sufficient radial resistance, or strength, to sustain a stable flow channel 220 during the PDT. FIGS. 12A-C show a multi-cage scaffold 215 that can sustain a higher outward pressure, or radial force. The multi-cage scaffold 215 can include a series of expandable sections, or (expandable) cages, 215-40-1 ... 215-40-n, each with three or more struts that expand outward from a central shaft when the multi-cage scaffold 215 is shortened, or actuated. (Here n is the number of cages: in FIG. 12A, n=2). FIG. 12A shows the multi-cage scaffold 215 in a collapsed state, and FIG. 12B shows the multi-cage scaffold 215 in its expanded state. From the distal end, the shown embodiment has a scaffold tip 215- 41, a first cage 215-40-1, and a second cage 215-40-2, pairwise separated by a first cageAtorney Docket No. 67555-703601 connector 215-42-1, ending in scaffold proximal end 215-43. Each cage 215-40 can comprise three or more cage struts 215-44 that extend from a distal end of the cage 215-40 to a proximal end of the cage 215-40. In FIG. 12B each cage, e.g. 215-40-1, has six cage struts, e.g. 215-44- 1 (not individually labeled for brevity). Some embodiments of the scaffold 215 may include only one cage, others, more than two.

[0102] The cages 215-40 may be formed by laser cutting a single tube with sets of parallel longitudinal slits to form the cage struts 215-44, the sets being pairwise separated by a cage connector 215-42. This slit tube can be then heat set in the expanded configuration, as shown in FIG. 12B. The multi-cage scaffold 215 can be expanded, or actuated, by the following mechanism, for example. The proximal-most cage 215-40-n can be attached to a scaffold shaft 215-45, by mechanical attachment or by welding, soldering, or other attachment means. Alternately the scaffold shaft 215-45 can be continuous with the tubing from which the cages 215-40 were formed. The cages 215-40 can be expanded by pulling the distal actuator tip 215- 46 towards the scaffold proximal end 215-43 via an internal actuator 215-47, which can either extend all along the center of the expandable distal section 200 and along the scaffold shaft 215-45, as shown, or can have a separate but attached proximal section in the scaffold shaft 215-45. This internal actuator 215-47 can be positioned inside the scaffold shaft 215-45 and through the cages 215-40 to extend out to the distal actuator tip 215-46. The distal actuator tip 215-46 may be fixedly attached to distal end of the distalmost cage 215-40-1. With this design, pulling the internal actuator 215-47 proximally with respect to the scaffold shaft 215-45 pulls the actuator tip 215-46 in a proximal direction, as shown. This shortens the scaffold 215 and thus forces the cages 215-40 to expand, their cage struts 215-44 to buckle radially outward. This is performed during the deployment and expansion of the expandable distal section 200. Another step of the overall photodynamic therapy PDT is the withdrawal of the expandable distal section 200 at the end of the PDT. This involves pushing the internal actuator 215-47 distally with respect to scaffold shaft 215-45 and the scaffold proximal end 215-43, which pushes the actuator tip 215-46 distally and thus lengthens the scaffold 215 and collapses the cages 215-40.

[0103] In an embodiment, the cages 215-40 can be heat set in a very slightly open configuration as depicted in FIG. 12A, so as to predictably expand outward when the scaffold 215 is shortened, and to collapse when the pulling tension on the internal 215-47 is released, or it is pushed distally. In this embodiment, the scaffold 215 can be in the collapsed configuration without requiring external constraint, and be independently advanced and expanded without restraining sleeve 217, as described in reference to FIGS. 9C-E.Atorney Docket No. 67555-703601

[0104] In an embodiment, hinge features can be included in the struts to create specific bend points. The hinge features may be cut-outs in the sides of the struts to create a short segment of thinner struts.

[0105] This scaffold design was described as being able to exert higher outward pressure or force than some of the other scaffolds. One of the reasons for this is because this scaffold 215 has the cage struts 215-44, which have angled sections that radially point toward the center of the scaffold 215. These radial sections transfer the radially inward pressure from the aneurysm wall and the inflation of the balloon 205 onto the center of the scaffold, as can be verified by considering the geometry of how the force vectors balance each other. This is less true for some of the previous scaffold designs, since some of those are purely cylindrical, which lack radially angled structures, and thus are less well suited for such a radial force transfer. An aspect of these multi-cage scaffold 215 designs is that the angled sections of the cage struts 215-44 are within the flow channel 220. Nevertheless, there is sufficient cross section to support a sufficiently strong blood flow.

[0106] FIG. 12C shows a related feature of the multi-cage scaffold 215. As just described, the multi cage designs means that this scaffold does not have an uninterrupted cylindrical surface. Therefore, between the cages, for example, between cages 215-40-1 and 215-40-2, and at the two ends, the inner layer 208 does not have a firm support, and therefore is likely to protrude into the flow channel 220, narrowing its cross section. However, as illustrated in FIG. 12C, this narrowing protrusion by the inner layer 208 is only limited because the inner layer 208 is non-compliant, and thus not “stretchy”, and its mechanical strength prevents it from narrowing the flow channel 220 too much. Therefore, in this design, a sufficient channel cross section for blood flow F may still be maintained for the PDT. As before, in one variation of this embodiment, the cages 215-44 can be heat set in the expanded configuration.

[0107] All the scaffold embodiments of FIGS. 2-12 can open up and expand spontaneously from their closed state when the withdrawal of the introducer sheath releases their compressed elastic energies. Thus, they do not need the dedicated actuator system 215-45 / 46 / 47. However, another class of scaffolds 215 may not be made of heat-set nitinol and thus does not expand spontaneously. These scaffolds 215 may be made of non-heat-set nitinol, stainless steel or any kind of plastic. For the multi-cage scaffold of FIGS. 12A-C, the above actuator-based design 215-45 / 46 / 47 is well suited to cause this scaffold to expand. For completeness, modified versions of the other scaffolds of FIGS. 2-11 with closed ends on both ends may also use this actuator design. For example, referencing FIGS. 9A-E, the distal end of the scaffold 215 can include an uncut tube section corresponding to proximal scaffold tip 215-41 of FIGS. 12A-B.Atorney Docket No. 67555-703601Similarly, the braided scaffold of FIG. 10 may include a distal braid end corresponding to the proximal braid end 214-26. In general, these embodiments may include an actuator tip at their distal end; and an internal actuator, configured to pull the actuator tip in a proximal direction, thereby causing the scaffold 215 to expand radially outward, in a similar fashion to that depicted in FIGS. 12A-B.

[0108] FIG. 13 shows yet another alternate embodiment of the scaffold 215. In this design, the expandable distal section 200 of catheter 120 is comprised of the scaffold 215 with an inner membrane covering 215-51, and optionally an outer membrane covering 215-52, and the outer compliant layer 212. The inner membrane covering 215-51 and the optional outer membrane covering 215-52 can be adhered to the scaffold 215 in a similar fashion to the cover layer of covered stents or stent grafts. The scaffold 215 may be a nitinol cut tube design, braided wire, or other wire stent design. The membrane covering 215-51 and 215-52 may be expanded polytetrafluoroethylene (ePTFE), polyurethane, or other suitable polymer material. The inner membrane covering 215-51 and the outer membrane covering 215-52 may sandwich the scaffold 215. The outer compliant layer 212 is adhered to one or both membrane coverings 215-51 and 215-52 to create the sealed inflatable component balloon 205. In an embodiment, the membrane coverings 215-51 and the optional 215-52, and the outer layer 212 can extend past the scaffold 215 on either end to create a firm seal.

[0109] FIGS. 14A-B show yet another embodiment of photodynamic therapy (PDT) light delivery system 100, wherein the expandable section 200 again comprises the inner tubular portion 202 that includes the expandable scaffold 215; and the outer compliant portion 204 includes a set of inflatable compliant balloons 205-1,... 205-4, together 205-n, wherein a peripheral region 205p of each balloon 205-n compliantly presses against the treatment area when the balloon 205-n is inflated, and a central region 205c of each balloon 205-n presses against the scaffold 215, thereby contributing to the formation of the flow channel 220. In these embodiments, the central region 205c can be viewed as belonging to both or shared by the inner tubular portion 202 and the outer compliant portion 204. In these embodiments, the sideemitting optical fibers 230 are positioned within the inflatable compliant balloons 205-n.

[0110] The shown embodiment of the expandable distal section 200 has four inflatable compliant balloons 205-1, ..., 205-4, each balloon having an optical fiber 230-1,... 230-4, respectively. The expandable scaffold 215 can be any embodiment of the scaffold 215, described in relation to FIGS. 1-13 and the corresponding preceding sections, which, therefore, serve as a written description of possible embodiments of the present scaffold 215 as well. For example, the expandable scaffold 215 can be cylindrical as in FIGS. 4-11, or multi-cage, as inAtorney Docket No. 67555-703601FIGS. 12A-C. Analogously, the inflatable compliant balloons 205-n can be any of the balloons 205 described in FIGS. 1-13. For example, the central portion 205c of each compliant balloon 205 can optionally have a reflective surface like the reflective surface 235 of the inner layer 208 in FIG. 2B; and analogously, the peripheral portion 205p of these same compliant balloons 205-n can be transparent for the illumination from the optical fibers 230, as are the embodiments of the outer layer 212 in FIGS. 1-13. Also, each compliant balloon 205-n can be connected via an inflation arm (not shown) to one or more inflation lumens in shaft 300. The compliant balloons 205-n may be fluidly connected to a single inflation device, or the compliant balloons 205-n may be inflated separately to optimally appose an aneurysm, which may be advantageous in the cases of an asymmetrical or otherwise irregularly shaped aneurysm. In the latter case, the proximal section 400 of the light delivery catheter 120 will have multiple connectors to inflation devices, one for each compliant balloon 205-n.

[0111] FIG. 15 shows yet another embodiment of a light delivery PDT system 100. Several of its components again can be analogous to those previously described in FIGS. 1-14, and thus need not be detailed here. The expandable distal section 200 of this system is different in the sense that it does not have a separate scaffold 215 and tubular inner layer 208. Instead, the expandable distal section 200 again comprises an inner tubular portion 202, but that includes a set of inflatable tubular scaffold balloons 215tsb, to form the flow channel 220 when inflated; the outer compliant portion 204 includes an inflatable compliant outer balloon 205, formed by an outer layer 212 and the set of inner tubular scaffold balloons 215tsb, to compliantly press against the treatment area when inflated. The side-emitting optical fibers 230 can be positioned in the inflatable compliant outer balloon 205.

[0112] As before, this expandable distal section 200 includes many elements that are identical or analogous to previously described elements, some analogously numbered, and thus need not be repeated here. For example, the outer layer 212 can again be made of Pebax, silicone rubber, elastomeric polyurethane, thermoplastic elastomers, blends thereof, or other appropriate materials, as described before.

[0113] In this expandable distal section 200, the previous functions of the inner layer 208 and the scaffold 215 are integrated into the inner tubular scaffold balloons 215tsb that are non- compliant or have low compliance, and thus can receive a substantial amount of inflation pressure, in some embodiments in the 5-20 atm range without increasing in size, so as to provide a high level of radial force / pressure with a controlled expansion of the expandable distal section 200. On the other hand, the compliant outer layer 212 is inflated separately at a lower pressure to inflate the outer layer 212 to appose the aneurysm wall. One or more innerAtorney Docket No. 67555-703601 inflation arms 225i can be fluidly connected to one or more inflation lumens 275i in the shaft 300 (not shown) to inflate the inner tubular scaffold balloons 215tsb. A separate set of outer inflation arms 225 (or 225o to distinguish from the inner inflation arms 225i) can be fluidly connected to one or more separate inflation lumens 275 in the shaft 300, to inflate the inflatable outer balloon 205 at a lower pressure, to appose the outer layer 212 to the wall of the aneurysm. As such, the deployment of the expandable distal section 200 involves inflating the inner tubular scaffold balloons 215tsb with a higher pressure, and then deploying the outer compliant portion 204 by inflating the compliant outer balloon 205, optionally through different, dedicated inflation arms 225i and 225(o) with a lower pressure. This structure of the inflatable outer balloon 205 has the advantage of not shortening when expanded. An alternate construction to the inner tubular scaffold balloons 215tsb is two sheets of non-compliant or low compliance material, or a single folded sheet, which is heat sealed in a series of long channels to essentially create the analogous set of inner tubular scaffold balloons 215tsb.

[0114] FIG. 16 shows yet another embodiment of the light delivery catheter 120 and the expandable distal section 200. In this embodiment a flow channel 220 for perfusion is within a distal shaft portion 300d itself at the center of the expandable distal section 200. In this embodiment, the outer compliant portion 204 includes an inflatable compliant outer balloon 205, or simply balloon 205 that comprises the inflatable outer layer 212 to appose the aneurysm wall. Therefore, the deployment of the expandable distal section 200 in this embodiment does not involve the expansion of an inner scaffold 215: the distal shaft portion 300d is already in a large diameter state that forms the flow channel 220. The deployment of the expandable distal section 200 only involves deploying the outer compliant portion 204 by inflating the compliant outer balloon 205. As before, one or more optical fibers 230 can be positioned within the inflatable balloon 205.

[0115] A differentiating aspect of this embodiment is the introduction of one or more shaft holes 310 in a proximal shaft portion 300p, proximal to the balloon 205. As shown, this design allows blood flow, as indicated by the arrow F, into the flow channel 220 at the distal shaft portion 300d on the distal end of the expandable distal section 200, through the distal shaft portion 300d in the center of the balloon 205, into the proximal shaft portion 300p, to which it is fluidly connected, and out the perfusion shaft hole, or holes 310 of the proximal shaft portion 300p when the balloon 205 is inflated. The distal shaft portion 300d can have a large enough diameter for its flow channel 220 to allow for sufficient blood flow. In an embodiment, a diameter of the flow channel 220 can be 5 mm or greater, 8 mm or greater, or 10 mm or greater. In some embodiments, the distal shaft portion 300d in the center of the balloon 205 may beAtorney Docket No. 67555-703601 expandable mechanically or by inflation. As this version has such a large inner diameter, the light delivery catheter 120 may be delivered with an inner dilator component (not shown) over a guidewire.

[0116] In another class of embodiments of the PDT light delivery catheter 120, the outer compliant portion 204 of the expandable distal section 200 can include a mechanically expandable structure rather than an inflatable structure, such as a helical wire structure, a braided mesh, or a scaffold that supports the side-emitting optical fibers 230 such that the sideemitting optical fibers 230 are expanded to the treatment area when the outer compliant portion 204 is expanded. The optical fibers 230 can be brought either in direct contact with the aneurysm wall, or expanded close to it. These embodiments can be balloonless, and thus the expansion of the expandable distal section 200 may not include expanding an inner tubular portion 202, or inflating an outer compliant balloon 205. Instead, the expansion of the expandable distal section 200 only involves deploying the outer compliant portion 204 by expanding the above mechanically expandable structure of the outer compliant portion 204. In these embodiments, the blood flow through the flow channel 220 is a blood flow through either a pre-formed flow channel 220 (FIG. 17), or through the mechanically expandable structure itself (FIG. 18), or through a combination thereof (FIG. 17). This class of designs allows a freer, less obstructed perfusion of blood through the aorta, as there is no inflation structure or balloon 205 taking up a portion of the lumen of the aorta.

[0117] FIG. 17 shows a balloonless embodiment of the expandable distal section 200 of the PDT light delivery catheter 120, that includes a helical wire structure 290 as the outer compliant portion 204, and optionally a pre-formed flow channel 220. The helical wire structure 290 includes one or more helical wires 292 that supports one or more side-emitting optical fibers 230 that are integrated with, or attached to the helical wire 292. The gap between the neighboring turns of the helical wire 292 can be configured to provide enough light density to the aortic wall to have the intended therapeutic effect. In an embodiment, the gap between neighboring can be between 1 mm and 3 mm.

[0118] In some embodiments, in the collapsed configuration, the helical wire structure 290 can be stretched out in a smaller diameter but longer pitch helix, or in a straight configuration, along a lumen in the catheter shaft 300. The expansion of the expandable distal section 200 involves the deployment of the outer compliant portion 204 by expanding the helical wire structure 290 to appose the aneurysm wall. This can be achieved by pushing the proximal end(s) of the helical wire structure 290 distally while the shaft 300 is simultaneously rotated. The combination of these two actions can expand and deploy the helical wire structure 290 to moveAtorney Docket No. 67555-703601 the side-emitting optical fibers 230 close to the aneurysm, or even into contact with it. Alternately, the distal end of the helical wire structure 290 can be attached to an inner member of the shaft 300, and the proximal end attached to an outer member of the shaft 300. In this embodiment, the outer member can be moved distally with respect to the inner member to shorten and thereby expand the helical wire structure 290. The wire may be radiopaque, so that the user, doctor, or operator may visually monitor and control the expansion configuration of the helical wire structure 290 via fluoroscopy during this procedure step.

[0119] FIG. 18 shows yet another embodiment of the expandable distal section 200 that includes an expandable braided wire structure 294, comprising two or more helical braided wires 296 as the outer compliant portion 204. The side-emitting optical fibers 230 can be attached across several braided wires 296. Other braided wires 296 can be bare wires to secure the structural robustness of the expandable braided structure 294. The distal end of the braid wires 296 can be attached to an inner shaft member 3 OOi, and the proximal end to an outer shaft member 300o. The expandable braided structure 294 can be expanded and deployed by moving the proximal outer shaft member 300o distally with respect to the inner shaft member 3 OOi to shorten and expand the expandable braided structure 294. As before, the braid wires 296 may be radiopaque, so that the user may visually monitor and control the expansion configuration of the helical braid wires 296 on fluoroscopy during this procedure step. The flow channel 220 in this embodiment is through the expandable braided structure 294.

[0120] The number of braid wires 296 and the density of the braid pattern in the expanded configuration are selected to ensure a sufficient density of light to the aortic wall to produce the intended therapeutic effect. In an embodiment, the gap between the braid wires can be between 1 mm and 3 mm.

[0121] In a variation of this embodiment, the braid wires 296 can all be structural wires in the sense that the optical fibers 230 are not attached along the individual wires. Instead, the optical fibers 230 can be attached across several braid wires 296 such that when the expandable braided structure 294 is expanded, the optical fibers 230 are pressed against the aortic wall. The optical fiber 230 may be arranged helically on the outside of the expandable braided structure 294, or may be arranged in an alternate fashion which allows it to remain on the outside of the expandable braided structure 294 when the braid shortens and expands. Alternately, there can be slack in the optical fibers 230 so that as the expandable braided structure 294 is expanded, the optical fibers 230 are drawn out of the shaft 300, and as the expandable braided structure 294 is collapsed, the optical fibers 230 are pulled back. An actuation mechanism on the proximal section 400 can be configured to coordinate theAtorney Docket No. 67555-703601 expansion and collapse of the expandable braided structure 294 with the fiber length exposed in the expandable distal section 200 of the catheter.

[0122] The embodiments of the PDT light delivery systems 100 described in FIGS. 1-18 can share some technical features. For example, in any of the designs, the catheter shaft 300 can include at least one polyethylene, nylon, polyurethane, polyether ether-ketone (PEEK), Pebax, and a combination thereof. In others, the catheter shaft 300 may include a stainless steel hypotube, or braid or coil reinforcement.

[0123] Some embodiments of the PDT light delivery system 100 which include an expandable scaffold can also include a restraining sleeve, to keep the expandable tubular scaffold 215 compressed until the expandable distal section 200 reaches the treatment area during insertion, and to be pulled back thereafter, such as restraining sleeve 217 as shown in FIGS. 9C-E. This restraining sleeve can be reinforced with at least one of fibers, wires, and a metal ribbon, in a braided or coil format between layers of polymer. In other embodiments, the expandable scaffold 215 may not require a restraining sleeve 217 but is instead mechanically actuated to expand, rather than being heat set in the expanded configuration.

[0124] Some designs of the PDT light delivery system 100 can include a guidewire lumen to allow a guidewire and a distal tip at the end of the guidewire, to guide the insertion of the light delivery catheter 120 and the expandable distal section 200.

[0125] Finally, some designs of the PDT light delivery system 100 can utilize radiopaque markers, positioned to denote a location of a distal end of the expandable distal section 200, and / or a proximal end of the expandable distal section 200, or some other characteristic structural feature. Using such radiopaque markers enables the operating doctor to determine the location or position of the inserted expandable distal section 200 with high precision with respect to the treatment area such as an abdominal aortic aneurysm, via fluoroscopic imaging the location of these radiopaque markers. The radiopaque markers may be attached to the scaffold 215, with swagged, glued, welded, or mechanically crimped radiopaque components. Alternately or additionally, the inflatable balloon 205 may have radiopaque components at its distal and proximal ends, glued, heat sealed, encased, or otherwise bonded to the inner layer 208 and or the outer layer 212.Optical Fibers and Light Source Embodiments

[0126] The PDT light delivery system 100 generates the treatment light in the light source 110. This light is then coupled via optical fibers 230 along the length of the light delivery catheter 120 all the way to the distal section 200. In some embodiments, this light can beAtorney Docket No. 67555-703601 coupled via a light cable 115 into the optical couplers 410 of the proximal section of the light delivery catheter 120. Once in, the treatment light propagates through the shaft 300 to the expandable distal section 200 via optical fibers 230. As quantified below, the intensity of the treatment light is bracketed by the following: The intensity has to be high enough to activate the photosensitizer at the treatment area within the time constraints of the treatment, yet low enough to avoid any clinical harm, such as thermal damage.

[0127] The light in the shaft 300 propagates in the optical fibers 230. A primary function of the proximal portion of these optical fibers 300 is to enable the propagation of the light to the expandable distal section 200 with as little loss and emission as possible. In contrast, the function of these same optical fibers 300 changes in the expandable distal section 200, where their role is to emit the treatment light from their side, so that the treatment light is delivered from the optical fibers 230 onto the treatment area. Because of this function, the distal sections of the optical fibers 230 are side-emitting. The light is coupled out of the side-emitting optical fibers in a controlled manner to spread, distribute and disperse the treatment light as uniformly as possible onto the treatment area, which is in many cases the aneurysm wall of an AAA. The following sections describe different designs for coupling the light out of the expandable distal section 200 onto the treatment area. While much of the description will concentrate on a single side-emitting optical fiber 230, the expandable distal section may contain several such sideemitting optical fibers 230, in some embodiments two, three, or four, in a quest to illuminate the treatment area as uniformly as possible.

[0128] FIG. 19A, top section shows a schematic of an individual elongated optical fiber 230 that includes a fiber cladding 231 around a fiber core 232. The proximal section of the optical fiber 230 is running along the shaft 300, typically in a dedicated or shared lumen. In this proximal section, repeated near-total reflections at the interface of the fiber core 232 and the fiber cladding 231 keep the light inside the optical fiber 230, making it propagate forward. Once the optical fiber 230 reaches the expandable distal section 200, its function changes to coupling the light out of the fiber and onto the treatment area. This is achieved by forming a side-emitting zone 233 on the sides of the optical fiber 230, turning this section of each fiber into a side-emitting optical fiber 230. This coupling out the light can be achieved by several different designs, including adding diffusors or scatterers to the fiber core 232, or along the interface of the fiber core 232 with the fiber cladding 231 to scatter light through the side walls of the optical fiber 230 in the side-emitting zone 233. There are many different embodiments of scatterers. They can be, for example, nanoparticles or suitable diameter, various precipitates, chemical inhomogeneities, bubbles formed in the glass, or any kind of roughening, cuts,Atorney Docket No. 67555-703601 scrapings on the core-cladding 232-231 interface. Given the wide variety of possible scatterers, it is natural to characterize them through their shared characteristics: their scattering coefficient S(x). The intensity of the coupling out of the light is controlled by this scattering coefficient S(x), which can be tuned in several different ways, including varying the density of the scatterers, varying the size of the scatterers, varying their scattering cross section, varying the degree of surface roughness of the core-cladding 232-231. Varying one or more of these factors makes scattering coefficient S(x) vary along x, a longitudinal coordinate along a side-emitting zone 233 of the side-emitting optical fiber 230.

[0129] The middle graph in FIG. 19A shows a side-emitting optical fiber 230 (which sometimes will be simply referred to as fiber 230 for brevity) that has a uniform scattering coefficient S(x) along the side-emitting zone 233. The bottom graph of FIG. 19A shows that the emitted illumination intensity I(x) in this fiber 230 is non-uniform. The intensity I(x) is decreasing along x of the distal side-emitting zone 233, because this fiber 230 scatters out a constant fraction of a light whose intensity decreases along the length of the distal side-emitting zone 233 due to the light loss to the side emission. As it is well known, scattering out a spatially constant fraction induces the Lambert-Beer exponentially decaying profile: I(x)=Io exp(-ax). This fiber design 230 therefore applies a decaying, non-uniform light intensity to the treatment area, which may cause a decaying, non-uniform cross-linking effect within the treatment area. As such, this profile may be less desirable, for treatments that prefer a more uniform emitted illumination intensity.

[0130] FIG. 19B shows an improved design, where a back-reflecting mirror, or reflector 234 is added at the end of the fiber 230. The middle graph of FIG. 19B shows that this fiber 230 still has a uniform scattering coefficient S(x), often created by using a uniform scatterer density. The bottom graph of FIG. 19B shows that the mirror / reflector 234 sends back the light that reached the end of the fiber 230, instead of releasing it or absorbing it. The total intensity of the light is the sum of the forward propagating intensity and the reflected intensity, as shown. This back-propagating light increases the internal light intensity close to the distal end of the fiber 230, where the intensity was the lowest in the reflector-less design of FIG. 19A. For this reason, the addition of the reflector 234 makes the light distribution, and therefore the emitted light intensity I(x) along the length of the fiber more uniform, as shown by the total intensity profile in the bottom graph of FIG. 19B.

[0131] FIG. 19C shows an embodiment of the fiber 230 in which the scatterer density, or scattering coefficient S(x) is rising along the side-emitting zone 233 of the optical fiber 230. This feature can be achieved by modifying the size or density of the scattering features in theAtorney Docket No. 67555-703601 optical fiber 230. This variation is shown as a function of x in the middle graph of FIG. 19C. The bottom graph of FIG. 19C indicates that in this design an increasing fraction of the decreasing amount of light is being scattered out by the increasing scattering coefficient S(x) with increasing x. Harnessing and controlling these competing effects has the potential of making the emitted illumination intensity I(x) more and more homogeneous.

[0132] FIG. 19D shows a particular implementation of this idea. In this design, the x dependence of the scattering coefficient S(x) is approximately a reciprocal function with a singularity close to, but beyond the distal end of the side-emitting zone 233 of the optical fiber 230. In formula:

[0133] where the parameter L* is greater than L, the length of the side-emitting zone 233 of optical fiber 230. The left graph of FIG. 19D shows such a reciprocal x dependence for S(x). Straightforward calculations show that in this embodiment, the light propagating inside the fiber 230 is attenuated approximately linearly, i.e. its power, or intensity, follows the form P(x) = Po- kx, as shown in the right graph of FIG. 19D. Since the emitted illumination intensity I(x) is proportional to the derivative of the propagating power density P(x): such alinearly decaying P(x) light intensity inside the optical fiber 230 produces a constant emitted illumination intensity I(x) outside the fiber 230: TZTI =K.(2)

[0134] An emitted illumination intensity I(x) that is approximately constant can be particularly useful to provide an approximately uniform treatment light for the treatment area, such as the aneurysm wall. Other embodiments of the fiber 230 can have other scatterer densities S(x) that follow some other function of x that rises towards the expandable distal section 200 of the fiber 230. In general, the scattering coefficient S(x) approximately following a particular function is meant in an inclusive manner. In some embodiments, S(x) can deviate from the specified functions on average by up to 20%. Another way S(x) can approximate the specified function is that its maximum deviation does not exceed 30%, in some cases 20%, in some cases 10%. Other reasonable definitions of S(x) approximately following a function can also be used.

[0135] FIG. 19E shows a further embodiment, in which the optical fiber 230 again has a mirror, or reflector 234 at its distal end. This design is motivated by the improvement such a reflector gave to the design of FIG. 19A, leading to the design of FIG. 19B. Straightforward calculations show that in such fibers, a constant side emitted illumination intensity I(x) can beAtorney Docket No. 67555-703601 achieved (as shown in the bottom graph of FIG. 19E) if the x dependence of the scattering coefficient S(x) is approximately a rounded reciprocal function with a singularity approximately at the distal end of the side-emitting zone 233, as approximately illustrated in the middle graph of FIG. 19E. In formula:

[0136] In this mirror design, the scatterer coefficient S(x) varies less than in the design of without a mirror of FIG. 19C, and hence this design is easier to manufacture.

[0137] The scattering effect may be achieved by several different designs. The scatterers, or diffusors can be created by adding scattering centers into the core 232 of the fiber 230 with or without longitudinally varying density, depending on the embodiment. The scattering centers may comprise altering the refractive index of the core 232, adding impurities in the core material, adding surface texture to the outer surface of the core, and / or adding discontinuities in the fiber cladding layer 231, as well as the previously listed techniques.

[0138] In some embodiments, instead of the density of the scatterers, the size of the scattering centers can be varied, because larger scattering centers scatter more. In these embodiments the intensity of the side-emitted light can be controlled by a varying size of the scatterers along the side-emitting zone 233 of fiber 230.

[0139] These scatterers can be created by varying the optical density of the fiber core 232. In some cases, this can be achieved by using focused laser pulses to generate mircovacuoles or other variations within the fiber core 232.

[0140] The designs of FIGS. 19C-E can be realized, for example, by using scatterers that are scattering centers added into the cores 232 of the optical fibers 230 with an increasing density towards the distal end of the optical fibers 230. In an alternative design, the scatterers are scattering centers added into the cores 232 of the optical fibers 230 with an increasing size towards the distal end of the optical fibers 230.

[0141] In other designs, the side emission can be achieved by modifying the core / clad interface to suppress the total internal reflection, and instead to decouple the light from the fiber core 232. In these designs, the modification of the interface can vary along the optical fiber 230 to tailor the light emission profile to the design needs, such as to ensure an approximately constant emitted light intensity. One beneficial feature of creating side-emitted light via interface modification is that this method can create fibers which emit only into a limited spatial angle, such as into a 180 degree angle, because the core / cladding 232 / 231 interface was modified only on one side of the optical fiber 230. Fibers 230 with such limitedAtorney Docket No. 67555-703601 spatial emission send all their light radially outward, toward the treatment area. In contrast, in designs where the side-firing is uniform, or isotropic, up to a half of the illumination is emitted radially inward, toward the flow channel 220. In such embodiments of the light delivery catheter 120, this light can be reflected back towards the treatment area by including a reflecting surface 235. In some cases, the inner layer 208 itself can be made of a reflective material, in other cases, it can have a mirror coating, or a metallic reflective film. In yet other designs, one side of the surface of the optical fiber 230 can be coated with a reflective coating that reflects the light towards the other side of the fiber 230. In these designs, the coated side of the fiber 230 can be oriented towards the inner layer 208, in order to direct the light reflected from it radially outward.

[0142] FIG. 20A shows a fiber 230 with a fiber core 232 that contains a set of stepped variations 236 of the refractive index along a side-emitting section 233. These “refractive index steps” 236 are angled relative to the longitudinal fiber axis, for example at 45 degrees, or at other angles exceeding the range of the total internal reflection angles. These refractive index steps 236 can be optically “written” into the fiber 230 using UV or femtosecond light sources. These index variations, or steps, 236 can also form a (Bragg-) grating structure to diffract the light away from the angles of total internal reflection, and thereby to decouple the light through the side walls of the fiber 230, thus forming the side-emitting zone 233.

[0143] To compensate for light attenuation along the side-emitting zone 233 of the fiber 230, in some designs, the density of the side-emitting refractive index steps 236 can increase along x, the length of the fiber. This design is similar conceptually to that of FIGS. 19C-E.

[0144] FIG.20B shows that in some embodiments, the planes of the refractive index steps 236 might also be rotated by a suitable angle along the axis of the fiber 230 to create a specific rotational emission profile for the illumination. In the left panel, the shown two sets of these planar refractive index steps 236 have the same angulation relative to the axis of the fiber 230 but have different rotational angle 1 and angle 2 normal to the axis of the fiber 230. The right panel shows that the planar refractive index steps 236 with different rotational angles have different, rotated emission profiles. This is a design approach to convert the anisotropic emission profiles of the planar refractive index steps 236 towards a more isotropic angular illumination profile. In some designs, the refractive index steps can form bent surfaces instead of planes.

[0145] In any of the above optical fiber embodiments, the material of the fiber core 232 may be glass, or may be a suitable polymer such as Polymethyl Methacrylate Polymer (PMMA). The fiber cladding 231 surrounding the core is a material of lower index ofAtorney Docket No. 67555-703601 refraction, such as a fluorinated polymer EPTE or PTFE, so that the light in the non-sideemitting section of fiber 230 is not dispersed.

[0146] In any of the above the above optical fiber-based designs, the light delivery catheter 120 can be connectable to a laser diode, an LED, an array of laser diodes, or to any other light source that can function as the light source 110, via an optical coupler(s) 410a-b of its proximal section 400. Alternately, the optical fibers 230 may extend beyond the proximal section 400 to couple directly to the light source 110. In some embodiments, the catheter shaft 300 can include a single optical feed-fiber to feed the light of the light source from the optical couplers 410 to the one or more side-emitting optical fibers 230 of the expandable distal section 200 through a distal fiber coupler or a fiber splitter. In other embodiments, the catheter shaft 300 can include multiple lumens that can accommodate non-side-emitting proximal portions of the sideemitting optical fibers 230 of the expandable distal section 200. The lumens can be fiber lumens, dedicated to the optical fibers 230; or can be the inflation lumens 275 in FIG. 3C, which can also accommodate these optical fibers 230.

[0147] The light source can be operated either in a continuous wave (CW), or in a pulsed mode. The pulse length can vary from seconds down to nanoseconds.

[0148] In an embodiment, the laser diode, or in general the light source 110, can produce light at a wavelength and power suitable for PDT. For example, the light source 110 can produce light at a wavelength in the 640-680 nm range, or more specifically in the 655-665 nm range, for reasons discussed later. The light source 110 can have a power in the 0.5-20 W range, in some designs in the 0.5-5 W range. The illumination intensity on the treatment area can be in the 1-300 mW / cm2range, in some cases in the 3-100 mW / cm2range, in some cases in the 10-30 mW / cm2range. In some embodiments multiple lasers might be used.

[0149] Advantageously, in such designs, the power transmitted to the expandable distal section 200 from the optical couplers 410 through the optical fibers 230 is already in the form of light, so there is no heat generation in the expandable distal section 200 itself as a byproduct of light generation. This is to be contrasted with designs where the light sources themselves, such as microLEDS, are positioned within the expandable distal section 200. These embodiments convert electric energy into light in the expandable distal section 200, which process unavoidably generates heat, which can induce undesirable side effects.

[0150] In some embodiments, the laser diode can be controlled by a laser console. Such a laser console can enable the adjustment and monitoring of the laser power, the pulse length, and the illumination time to comply with the specific needs of the PDT. The laser console might also have an integrating sphere detector to validate power delivery of the specific light deliveryAtorney Docket No. 67555-703601 catheter 120 before inserting it into the patient. The console also might have a fiber breakage or damage detector included, that monitors light reflecting back from the fiber or the coupler itself.

[0151] Some designs can have an optical coupler 410 at the proximal section 400 to be releasably coupled to the light source 110, and within it, the laser diode. The optical coupler 410 can be a subminiature assembly, or SMA, connector. In other designs, the optical coupler 410 can include ceramic ferrule guided connectors, which are also used in the telecommunications industry. This optical coupler 410 can couple the light of the light source 110 into the proximal section 400 and from there into either the optical feed fiber or into the bundle of optical fibers 230. In an embodiment, the optical coupler 410 connects directly to the light source 110. In an alternate embodiment, the optical coupler 410 connects to the intermediary light cable 115, which then connects to the light source 110.

[0152] In another embodiment of light delivery system 100, the light is not transmitted via optical fibers 230 through the light delivery catheter 120 from the external light source 110. Rather, as shown schematically in FIG. 21, the light source is a string or cluster of small or microLEDs 510-n, affixed to the expandable distal section 200. The cluster of LEDs 510 can be organized into LED strings. As before embodiments of this PDT catheter 100 can include an expandable distal section 200, to be advanced to a treatment area in a compressed state, a shaft 300 and a proximal section 400, together configured to advance the expandable distal section 200 to the treatment area; the expandable distal section 200 including an inner tubular portion 202 to form a flow channel 220 when expanded; an outer compliant portion 204 to compliantly press against the treatment area when expanded; and a cluster of LEDs 510-n, supported by the inner tubular portion 202 or the outer compliant portion 204, to illuminate the treatment area with the light.

[0153] In some embodiments of the PDT light delivery system 100, the cluster of LEDs 510-n can include strings of LEDs, powered through electric wiring positioned in the shaft 300, and optionally affixed to the inner tubular portion 202. These embodiments have many similarities and analogies to the designs described in relation to FIGS. 2-16, any one of which can be naturally imported or adapted for these present embodiments. FIG. 21 shows a scheme of a simple design, where the cluster of LEDs 510 is a set of linear LED strings 510, attached to the inner layer 208, possibly along linear wires of the underlying scaffolding 215. In this figure, the outer compliant layer 212 is not shown, to more clearly illustrate the LED position on the inner layer 208.Atorney Docket No. 67555-703601

[0154] In other embodiments, the outer compliant portion 204 can include a wire structure; and the cluster of LEDs 510-n can be affixed, at least partially, to this wire structure. These embodiments can be analogous to those described in FIGS. 17-18, whose details can be adapted for this present embodiment. In some embodiments, the wire structure can be analogous to the helical wire structure 290 of FIG. 17, or the expandable braided structure 294 of FIG. 18. Accordingly, the cluster of LEDs 510-n can be formed and positioned in a twisted or helical manner; in yet other embodiments as a set of expandable LED loops, or any other one dimensional or two-dimensional pattern. In embodiments, where the cluster of LEDs 510- n includes LED strings, then these strings can be aligned with the struts, or wires, of the expandable distal section 200 of FIGS. 16-17. Some embodiments can use microLED arrays. The structure of these designs is very analogous to the designs of FIGS. 17-18, with the change that the strong-cluster of the LEDs 510 takes over the role of the side-emitting optical fibers 230 in those Figures. For this reason, it is not necessary to repeat those descriptions.

[0155] The LEDs 510 are connected to a power source via the electrical wiring 520, which run down the length of catheter shaft 300 to connect to the external power source. It is noted that the LED energy conversion efficiency is typically only 20% or less. Therefore, the light generation in this embodiment in the expandable distal section 200 is accompanied by a substantial amount of heat generation. However, the flow channel 220 in the presented catheter design functions as an efficient heat sink as it is able to carry heat away efficiently and disperse the heat to lower, acceptable levels. The central blood flow in the proposed catheter design can act as an efficient coolant.

[0156] Returning to considerations that apply to all the embodiments described in FIGS. 1-21, FIG. 22 shows the absorption coefficient of oxygenated blood. Broadly, as mentioned before, blood is a very efficient absorber of light. This poses a challenge for the efficacy of the PDT if parts of the outer compliant portion 204 did not achieve contact with the treatment area and are thus separated from the treatment area by a blood-filled space, with a thickness possibly reaching a few mm. In such cases, a substantial fraction of the emitted illumination gets absorbed by the blood, the thicker the space, the larger the absorption. However, it is also noted that the blood light absorption coefficient has a minimum around the wavelength of 660 nm. Noting that the vertical axis is logarithmic, this minimum is quite sharp. With this recognition, the PDT light delivery system 100 disclosed here overcomes this design challenge by implementing at least the following design principles, as already outlined above.

[0157] 1. The illumination generated by the PDT light delivery system 100 has a wavelength that approximately matches the minimum of the light absorption coefficient ofAtorney Docket No. 67555-703601 oxygenated blood around 660 nm. Light at this wavelength can traverse blood for several millimeters with minimal absorption. As such, even if parts of the outer compliant layer 212 are unable to make direct contact with the aneurysm wall, and thus the outer layer 212 is separated from the aneurysm wall by a space of 1-2 mm that is filled with blood, most of the illuminating light, emitted through the outer compliant layer 212, will still reach the treatment area or the aneurysm wall because of the low absorption.

[0158] 2. The embodiments of the light delivery catheter 120 employ a compliant outer layer 212 which is conformable to the varying and irregular shape of the aneurysm in order to minimize or eliminate the distance the illumination has to travel in a blood-filled region to reach the aortic wall to be treated.

[0159] In detail, the first principle is implemented by the PDT light delivery system 100 having a light source which can emit the illumination with a wavelength in the 500-2,000 nm range. In some embodiments, this wavelength is in the 600-800 nm range. In some embodiments, this wavelength is in the 640-680 nm range. The same can be expressed by saying that the side-emitting optical fibers 230 operate at a wavelength in the range of 500- 2,000 nm; or 600-800 nm; or 640-680 nm. Alternately, in the case of the embodiment of FIG. 21, the LEDs 510 operate at a wavelength in the range of 500-2,000 nm; or 600-800 nm; or 640-680 nm. Put in yet another way, the light source 110 can have an operating wavelength that is within 100 nm of a minimum of a light absorption coefficient of oxygenated blood.

[0160] The efficiency of the photodynamic therapy can be further enhanced by the PDT light delivery system 100 generating an illumination with a wavelength that is within 100 nm of an activating wavelength of a photosensitizer of the photodynamic therapy. In some embodiments, the illumination wavelength can approximately match the activating wavelength of the photosensitizer of a photodynamic therapy (PDT). These twin principles can be implemented by the light delivery system 100 emitting an illumination close to 660 nm, while the PDT utilizing a photosensitizer whose activation wavelength is also around 660 nm. As mentioned earlier, an example of such a photosensitizer is methylene blue. The biologies of the photosensitizer and the selectively binding polypeptide conjugated to it have been described in great detail in the incorporated co-pending application “Methods And Composition For A Photosynthesizer Conjugated Polypeptide And Therapeutic Applications Thereof’ to Daniel M. Schwartz et al.; serial number PCT / US2024 / 016154, filed on 2 / 16 / 2024.

[0161] In light of the above, the PDT will be particularly efficient and useful, if the PDT light delivery system 100 uses the “matching wavelength” in a vicinity of 660 nm, that matches two impactful wavelengths: the wavelength of the absorption minimum of oxygenated blood;Atorney Docket No. 67555-703601 and the activation wavelength of the used photosensitizer. In the case of methylene blue as a photosensitizer, both of these wavelengths are within the 640 nm to 680 nm range, more specifically in a vicinity of 660 nm. Therefore, the PDT using a light source 110 with a wavelength in this 640 nm to 680 nm range can be called using a “matching wavelength.” Put in other words, the PDT light delivery system 100 can advantageously operate at the “matching wavelength” in the sense that an operating wavelength of the light source 110 of the PDT light delivery system 100, a minimum of a light absorption coefficient of oxygenated blood, and an activation wavelength of a photosensitizer of the PDT can be all within a 50 nm range in embodiments.

[0162] Here, it is mentioned that preliminary animal experiments using methylene blue as photosensitizer and a PDT light delivery system operating with a light of wavelength about 660 nm showed encouraging early results. The graph of FIG. 23 illustrates these results, showing that the percentage growth of an aortic diameter in animal models has been greatly slowed down by the administration of the PDT. After about 60 days animals who were not treated with the PDT following the above design principles had a 5% larger aortic diameter, which was still increasing. In contrast, the PDT-treated animals had an aortic diameter, which grew only 2% and then stopped growing after about 40 days.Photodynamic Therapy Methods

[0163] Embodiments of the method 500 to use the light delivery system 100 in a photodynamic therapy procedure (PDT) will be described next. FIG. 24 depicts a schematic of an abdominal aortic aneurysm. The abdominal aorta Ao, the section of aorta in the abdomen below the diaphragm, terminates into a bifurcation of the common right and left iliac arteries (RIA and LIA, respectively) which perfuse the lower limbs. Major side branches from the Ao, the right and left renal arteries RRA and LRA, perfuse the kidneys. Other side branches not shown perfuse other organs and tissue beds. In a patient with an abdominal aortic aneurysm, a weakened section of aorta wall starts to bulge out, causing an abdominal aortic aneurysm AAA. As the disease progresses, the bulge enlarges, increasing the risk of a catastrophic rupture.

[0164] FIGS. 25A-H depict the steps of the procedure 500 utilizing the PDT light delivery system 100 in a photodynamic therapy procedure to treat AAA. FIG. 25A shows that the first step of the procedure 500 is 510: exposing the treatment site to a photosensitizer agent. This photosensitizer agent can be methylene blue, or any of the analogous agents described in the incorporated copending application. The exposure may be done systemically via intravenousAtorney Docket No. 67555-703601 injection of the agent, or topically, locally via a catheter inserted through the procedural access site.

[0165] In preparation for the next steps, the PDT light delivery system 100 can be prepared by connecting the light delivery catheter 120 to the light source 110 via a light cable 115 and the optical coupler 410.

[0166] FIG. 25B shows that the next step 520 is accessing the treatment area with a long introducer sheath 501 with a tapered dilator 502, over a guidewire 503. The distal end of the introducer sheath 501 can be positioned past the AAA, in a normal aorta segment, either above or below the renal arteries depending on the location of the aneurysm. The tapered dilator 502 is then removed while the guidewire 503 can remain in place. The accessing typically involves inserting the introducer sheath 501 into an access site at a femoral artery or a carotid artery, and advancing the introducer sheath 501 over the guide wire 503, headed by the taped dilator 502.

[0167] FIG. 25C shows that the next step 530 is inserting the light delivery catheter 120, that has the closed expandable distal section 200, the shaft 300, and the proximal section 400, into the introducer sheath 501, and advancing it over the guidewire 503 so as to align the expandable distal section 200 with the treatment area. In embodiments in which the expandable distal section 200 requires a restraint to remain in a closed state, the introducer component 130 may be used to insert the expandable distal section 200 in a compressed state into the introducer sheath 501. Even in embodiments where the expandable distal section 200 is closed without needing compression, such as in FIGS. 15-18, an introducer component 130 may be desirable to protect the expandable distal section 200 as it is inserted through the hemostasis valve of the introducer sheath 501. Once the expandable distal section 200 is inserted into the introducer sheath 501 with the help of the introducer component 130, the body of the introducer sheath 501 keeps the expandable distal section 200 in the closed, or compressed, state. In this step, the light delivery catheter 120 can be advanced until the distal tip of the light delivery catheter 120 is aligned with the expandable distal end of the introducer sheath 501. As a variant, the light delivery catheter 120 can be advanced so as to align its closed expandable distal section 200 with the treatment area. The expandable distal section 200 and the distal end of the introducer sheath 501 may have radiopaque markers to aid either of these alignment process under fluoroscopy.

[0168] FIGS. 25D-E show that the next step can be withdrawing, or retracting, 540 the introducer sheath 501; and expanding 550 the closed distal section 200 to form a flow channel 220 and to have an outer compliant portion 204 press compliantly against the treatment area.Atorney Docket No. 67555-703601The blood flow through the aorta is maintained during the PDT by forming the flow channel 220. In some embodiments, this expanding step 550 can include expanding the inner tubular portion 202 of the expandable distal section 200 by causing a closed expandable scaffold 215 to expand, that is surrounded by an expandable tubular inner layer 208, thereby forming the flow channel 220. In a typical embodiment where the closed expandable scaffold 215 is closed by compression, the withdrawing step 540 and the expanding step 550 unfold simultaneously. In such cases, “expanding the distal section” can simply include allowing the closed expandable scaffold 215 to expand, driven by its own compressed elastic pressure. In this case, the light delivery catheter 120 can remain in place, and the closed scaffold 215 can expand on its own as the introducer sheath 501 is retracted.

[0169] Alternately, in embodiments where the closed scaffold 215 is not compressed, the “expanding the distal section” and “expanding the inner tubular portion” can include mechanical actuation by the user. For example, in FIG. 12B, the introducer sheath 501 can be pulled back, and then the user can operate the actuator system 215-47. . . 215-47 to expand the distal section 200 as described earlier. In some cases, the internal actuator 215-47 can be used to pull the actuator tip 215-46 proximally, thereby making the cage struts 215-44-1 and 215- 44-2 buckle radially outward. In yet other embodiments, e.g. in the embodiment of FIG. 15, the “expanding the distal section” can involve inflating the tubular scaffold balloons 215tsb.

[0170] In this step 550, the scaffold 215 can be at least one of at least one of struts, spokes, expandable circular wires, wire meshes, a stent-like structure, a series of linked zig zag rings, a braided structure, a ring-link structure, an asymmetric scaffold, and a mesh. In the embodiments of FIGS. 4-9, the scaffold 215 can be a nitinol tube with a longitudinal cut pattern, heat set to an expanded configuration, and then compressed into the closed distal section, in which case the expanding the distal section involves simply the expansion of the scaffold, caused by letting the heat-set nitinol tube expand.

[0171] In some embodiments, like that of FIGS. 12A-C, the scaffold 215 can comprise the actuator tip 215-46 at its distal end; and the internal actuator 215-47, configured to pull the actuator tip 215-46 in a proximal direction, thereby causing the scaffold 215 to expand radially outward. In the shown embodiment, the scaffold 215 is a multi-cage scaffold with expandable cages 215-40; and each cage 215-40 includes a set of cage struts 215-44. In alternate embodiments, the scaffold of FIGS. 4-11 can also involve an actuator mechanism and can get expanded by operating this actuator mechanism.

[0172] Once the introducer sheath 501 has been fully pulled back and the expandable distal section 200 is in the expanded state, as shown in FIG. 25E, accurate positioning of the distalAtorney Docket No. 67555-703601 section 200 with respect to the aneurysm can be confirmed on fluoroscopy. The position of the expanded distal section 200 may be adjusted if necessary. Minor adjustments may not require collapse of the expanded distal section 200, but for larger adjustments, the expanded distal section 200 may need to be re-collapsed for example by re-advancing the introducer sheath 501 that mechanically collapses the scaffold 215, and then re-expanded after it was moved into its new, adjusted position.

[0173] FIG. 25F shows that in balloon-based embodiments, e.g. those in FIGS. 2-16, the next step 552 can be inflating an inflatable balloon 205 of the outer compliant portion 204, formed from an outer layer 212, sealed together with the inner layer 208, to compliantly press against the treatment area. The inflation can be accomplished by pumping the fluid from an inflation device into the inflatable balloon 205 through inflation lumens 275. The inflation fluid may be a clear fluid such as saline. The inflation fluid may also contain a fluid with light dispersion / scattering properties, such as a lipid solution like intralipid, which may be advantageous in transmitting an even amount of light through the fluid to the aorta wall. The inflation fluid may also contain a contrast agent, so the balloon inflation may be monitored on fluoroscopy to confirm placement and adequate inflation of the balloon with respect to the aneurysm. In the embodiment of FIG. 3, the inflatable balloon 205 can be folded into one or more wrap-around flaps 250 when the expandable distal section 200 is closed.

[0174] In embodiments where there are multiple inflation connectors and multiple inflation lumens 275, for example when the distal section 200 has separate independently inflatable compliant balloons 205-1 . . .4, as in FIGS. 14A-B, multiple inflation devices may be connected. In these embodiments, the expanding the inner tubular portion 202 of the expandable distal section 200 can again include causing the closed expandable scaffold 215 to expand that is surrounded by an expandable tubular inner layer 208, thereby forming the flow channel 220. In addition, the expanding step 550 can include inflating the set of inflatable compliant balloons 205-1...4, wherein a peripheral region 205p of each balloon compliantly presses against the treatment area, and a central region 205c of each balloon presses against the scaffold, thereby contributing to the formation of the flow channel 220. Alternately, the multiple inflation lumens 275 may be combined together and coupled to a single inflation connector.

[0175] In the embodiment of FIG. 15, the expandable distal section 200 can include expanding the inner tubular portion 202 of the expandable distal section 200 by inflating a set of inflatable tubular scaffold balloons 215tsb, to form the flow channel 220; and inflating the compliant outer balloon 205, formed by the outer layer 212 and the set of inner tubular scaffold balloons 215tsb, to compliantly press against the treatment area.Atorney Docket No. 67555-703601

[0176] FIGS. 17-18 show balloonless embodiments of the distal section 200, which do not necessarily have a compliant balloon 205 and an inner tubular portion 202. As such, the PDT method 500 does not involve an inflating step 552. Instead, in these embodiments, the expanding step 550 can include expanding the outer compliant portion 204 of the expandable distal section 200 that includes one of a wire structure, a mesh, and a scaffold that supports the side-emitting optical fibers 230 such that the side-emitting optical fibers 230 are expanded close to the treatment area when the distal section 200 is expanded.

[0177] The wire structure, mesh, or scaffold of these embodiments of the outer compliant portion 204, can be similar or analogous to the scaffolds 215 of the inner tubular portion 202. In the embodiment of FIG. 17, the outer compliant portion 204 is a helical wire structure 290; and the side-emitting optical fibers 230 are attached along the helical wire 292 of the helical wire structure 290. In the embodiment of FIG. 18, the outer compliant portion 204 includes an expandable braided structure 294 that includes a set of helical braid wires 296 in a braid pattern; and the side-emitting optical fibers 230 are attached across the braid wires 296.

[0178] FIG. 25G shows that once the distal section 200 is inflated and the a majority of the surface of the outer layer 212 of the balloon 205 achieved contact, or near contact, with the aneurysm wall, the next step 560 includes delivering a PDT illumination to the treatment area via the side-emitting optical fibers 230, positioned in the expanded distal section 200. This step 560 includes generating the light with the light source 110; coupling the generated light into the proximal section 400 of the light delivery catheter 120; and forwarding the light through the shaft 300 to the side-emitting fibers 230 of the expanded distal section 200. In the balloonbased embodiments of FIGS. 2-16, the light emitted by the side-emitting fibers 230 propagates through the dispersive fluid with minimal or no loss, then it is transmitted through the typically transparent outer layer 212 and reaches the aneurysm wall.

[0179] Some embodiments of the delivering step 560 may include operating the light source with a power in a range of 0.5-20 W. In some embodiments, the delivering 560 can include operating the light source 110 so that the side-emitting optical fibers 230 emit the illumination with an intensity on the treatment area in a range of 1-300 mW / cm2.

[0180] In some cases, a fraction of the outer layer 212 of the balloon 205 may not achieve direct contact with the aorta / aneurysm wall, either due to limited compliance of the inflatable balloon, the irregularity and / or size of the aneurysm, or some other cause. The separation of the outer layer 212 and the aneurysm wall may be as little as a few tenth of a millimeter, or as much as more than 1 mm. As discussed in relation to FIG. 22, blood absorbs light very strongly. Therefore, if the emitted light is forced to traverse a blood-filled region, its intensity may dropAtorney Docket No. 67555-703601 precipitously, and thus the PDT illumination may not achieve its therapeutic goal. However, it has been noted that the absorption spectrum of oxygenated blood has a sharp minimum around a wavelength of 660 nm. Therefore, in embodiments of the PDT illumination system 100 whose light source is operated to emit the PDT illumination with a wavelength in the 600-800 nm range, in some cases in the 640-680 nm range, the illumination will suffer only minimal damping even if it has to traverse a non-contact region filed with blood up to 1 mm - 2 mm thick, and thus the PDT illumination will still achieve the intended medical effect on the photosensitizer in the treatment area. The highest efficiency can be reached with photosensitizers whose activation wavelength is also in a vicinity of 660 nm. Such PDT illumination systems 100 may be called operating at a matched wavelength.

[0181] For completeness it is mentioned that a suitably uniform spatial distribution of the illumination can be achieved with optical fibers 230 which can be characterized by a scattering coefficient S(x) that is rising along the optical fibers 230, as described in great detail in relation to FIGS. 19A-E, and 20A-B

[0182] If the device did not contact the entire aneurysm during this treatment, for example if the aneurysm was longer that the balloon was able to inflate to, the device may be repositioned to the location previously unexposed or underexposed to the light and the previous steps repeated at the new site.

[0183] The delivering of the illumination step 560 is accompanied by heat generation. Helpfully, during the presently described PDT system 100, the expandable distal section 200 is positioned in the aorta without blocking the flow of blood. This blood flow can very effectively dissipate the buildup of thermal energy generated by the light. In embodiments, where the blood flow is not enough to keep the temperature of the expanded and lit distal section 200 at a safe temperature, the distal section 200 may be kept cool by cooling the inflation fluid. If needed, the inflation fluid may be circulating to be continuously kept cool. Alternately, the balloon 205 may be periodically deflated during the procedure and reinflated with newly cooled fluid as required to keep the distal section 200 in the acceptable temperature range while completing the PDT procedure.

[0184] FIG. 25H shows that once the PDT illumination of the aneurysm has been completed, the light delivery catheter 120 can be fully removed from the introducer sheath 501 to complete the procedure. In some detail, step 570 of the method 500 may include 570ci - ceasing the illumination; 570ce - collapsing the expanded distal section 200 by advancing the introducer sheath 501; and 570w - withdrawing the light delivery catheter 120 through the introducer sheath 501. In the balloon-based embodiments of FIGS. 2-16, the step 570 mayAtorney Docket No. 67555-703601 include deflating the balloon 205. In embodiments, where the scaffold 215 was initially closed by compressing an elastically strained scaffold, the advancing the sheath 501 can be sufficient to collapse the expanded distal section 200. In embodiments, where only actuation, and not compression was used, e.g. for the scaffold closing and opening, as in FIGS. 12A-C, and for closing and opening the outer compliant portion 204 as in FIGS. 17-18, the collapsing step 570ce can simply include collapsing by using the corresponding actuation mechanism. For the structures of FIG. 12, 17 and 18, the collapsing step 570ce can include pushing distally the internal actuator 215-47 so that the actuator tip 215-46 moves distally, thereby collapsing the cages 215-40 in FIG. 12; or rewinding the helical wire 292 in FIG. 17, or deflating the tubular scaffold balloons 215tsb, as in FIG. 15.

[0185] FIGS. 26A-B show a complementary embodiment of the method 500. In this method the steps are the catheter is positioned in the AAA from a superior direction towards the bifurcation, for example from a carotid artery access site. FIG. 26A shows this access orientation, with and introducer sheath S and dilator D being advanced across the AAA over a guidewire GW from the superior direction and into an iliac artery. Similar to the previous method, the catheter is advanced through the sheath to be positioned across the aneurysm. The sheath is retracted to expose the distal end, which is then expanded and then inflated. FIG. 26B shows the expandable distal section 200 of the device in an expanded and inflated configuration with the light activated on to perform a PDT of the AAA.

[0186] FIGS. 27A-E show yet another embodiment of the method 500 that is directed to the use of “proximal scaffold-distal balloon” embodiment of the light delivery catheter 100 shown in FIGS. 3D-E. Step 510, the exposing the treatment area to a photosensitizer agent; and step 520, accessing the treatment area with an introducer sheath 501 may proceed as before. FIG. 27A shows that step 530 in this embodiment includes advancing the light delivery catheter 120, having an expandable distal section 200 with a proximal closed scaffold 215 and a distal inflatable balloon 205, a shaft 300, and a proximal section 400, in the introducer sheath 501 so as to align the inflatable balloon 205 with the treatment area. Sometimes “aligning with the treatment area” is described as “positioning across the aneurysm”. Also, for brevity, the furled distal inflatable balloon 205 sometimes will be simply referred to as furled distal balloon 205, or simply as distal balloon 205. Once the distal section 200 is positioned as desired at the treatment site, step 540 again includes withdrawing the introducer sheath 501 to expose the distal section 200 to blood flow.

[0187] FIG. 27B shows step 550 again includes expanding the distal section 200. But in this embodiment, the expanding step 550 involves additional steps as follows. In this “proximalAtorney Docket No. 67555-703601 scaffold-distal balloon” design, the furled distal inflatable balloon 205 becomes unconstrained when the introducer sheath 501 is withdrawn. Building on this aspect, the next step 554 is allowing the oncoming blood flow to open the distal inflatable balloon 205 of the outer compliant portion 204, formed by sealing an inner layer 208 and an outer layer 212 together, to form a partial flow channel 220. In embodiments, where the distal balloon 205 is furled, then this step 554 involves the unfurling of the furled distal balloon 205. As shown, while the central lumen of the distal ballon 205 gets opened up by the oncoming blood flow, the distal balloon 205 itself, formed by the inner layer 208 and the outer layer 212, remains uninflated. The flow channel 220 is partial in the sense that its diameter is smaller than the fully formed flow channel 220 of the previous embodiments. This is primarily caused by the fact that the scaffold 215 has not been expanded within, and thus did not push the inner layer 208 outward yet.

[0188] FIG. 27C shows that the step 554 of unfurling the distal balloon 205 can be followed by step 556: advancing the closed proximal scaffold 215, still in its collapsed configuration, into the newly formed flow channel 220 of the inflatable distal balloon 205.

[0189] FIG. 27D shows that once the closed scaffold 215 has been successfully advanced into, and aligned with, the balloon 205, the next step 558 can be expanding the scaffold 215 and the inner layer 208 with it to widen the partially opened flow channel 220. This scaffold expansion can be active, e.g. using an actuator mechanism like those in FIGS. 12 A-B, or passive, e.g. relying on the elastic forces of a nitinol tube with a cut pattern that has been heatset and compressed, like that in FIGS. 9A-E.

[0190] FIG. 27E shows that after the expanding step 558, the method 500 can proceed as before. In particular, it can continue with the previously described step 552 of inflating the inflatable balloon 205 of the outer compliant portion 204, formed to compliantly press against the treatment area. The inflatable balloon 205 can be constructed by sealing together the outer layer 212 and the inner layer 208. This can be followed by step 560: delivering a PDT illumination to the treatment area via the side-emitting optical fibers 230, positioned in the expanded distal section 200.

[0191] These steps can be followed by step 570 (not shown): ceasing the illumination, collapsing the expanded distal section 200 by advancing the introducer sheath 501, and withdrawing the light delivery catheter 120 through the introducer sheath 501.Sonodynamic therapy system and method

[0192] An alternative to the PDT to effect crosslinking of aneurysmal vessels can be a sonodynamic therapy (SDT). SDT employs a sonosensitizer in a tissue that is activated byAtorney Docket No. 67555-703601 ultrasound to generate reactive oxygen species. Current application of SDT is largely directed at killing cancer cells. However, in a sonodynamic therapy system 600, the SDT-generated reactive oxygen species can be also used to accomplish crosslinking of aneurysms to prevent rupture. Remarkably, several photosensitizers can be also used as effective sonosensitizers. Example of these dual use sensitizers include: 5-aminovulinic acid, methylene blue, protoporphyrin IX, verteporfm, BODIPY (boron-dipyrromethene), and others. The advantage of SDT over PDT is that the activating energy source, the ultrasound source, can be administered non-invasively.

[0193] FIG. 28 shows a conceptual embodiment of a sonodynamic therapy system 600. In a high-level description, an SDT system 600 can include an ultrasound source 610, to generate ultrasound; an ultrasound focusing system 620, to receive the generated ultrasound and to focus the ultrasound 630 to a treatment area that has been treated with a sonosensitizer that generates reactive oxygen species upon activation by the ultrasound, wherein the ultrasound source 610 is configured to generate ultrasound with a frequency and an intensity that is suitable to activate the sonosensitizer. The SDT system 600 can be controlled by a controller 640. The controller 640 may include an ultrasound imaging system as well, to assist the targeting of the focused ultrasound 630 onto the target, or treatment area.

[0194] FIG. 29A shows that the focused ultrasound 630 can be applied trans-abdominally to cause crosslinking in aortic aneurysms. FIG. 29B shows that the focused ultrasound 630 can be applied trans-cranially to cause crosslinking in cerebral aneurysms. In this case, the SDT system 600 may utilize one or more ultrasound sources 610 and ultrasound focusing systems 620. These can be arranged on a head mount 650.

[0195] Alternatively, the ultrasound can be administered via an ultrasound delivery catheter, which generates intravascular ultrasound. In this embodiment of the SDT system 600, the absorption by blood is less critical than in the case of the earlier-described PDT, where light must pass through a thin column of blood at the margin of the inflated balloon 205. In this SDT system 600, where the sonosensitizer is activated by the ultrasound delivery catheter, it may not be necessary to inflate, or even to have, the balloon 205 to appose the wall of the aneurysm, because the oxygenated blood does not have a high absorbance for ultrasound, and thus ultrasound can readily pass from the ultrasound delivery catheter through the blood column to the treatment area.

[0196] As can be appreciated, these methods of PDT with the light delivery system can be accomplished with any combination of light delivery catheter, light fiber, and light source embodiments disclosed herein. These devices, systems and methods of PDT may also beAtorney Docket No. 67555-703601 utilized in aneurysms other than the abdominal aorta, for example the thoracic aorta, to strengthen the tissue in a similar manner. The light delivery system disclosed herein may also be used to perform PDT in other tissue accessible with catheters, with other light-activated therapeutic agents.

[0197] While this document contains many specifics, these should not be construed as limitations on the scope of an invention or of what may be claimed, but rather as descriptions of features specific to particular embodiments of the invention. Certain features that are described in this document in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a subcombination or a variation of a subcombination.

Claims

Atorney Docket No. 67555-703601CLAIMSWhat is claimed is:

1. A photodynamic therapy (PDT) light delivery system, comprising: a light source, to generate light for the photodynamic therapy; and a light delivery catheter, including an expandable distal section, to be advanced to a treatment area in a closed state, to be expanded to form a flow channel, and configured to have an outer compliant portion to compliantly press against the treatment area; a shaft and a proximal section, together configured to advance the expandable distal section to the treatment area, and to receive the light from the light source at the proximal section and to forward the light to the expandable distal section; and side-emitting optical fibers, positioned in the expandable distal section, to receive the light and to illuminate the treatment area.

2. The PDT light delivery system of claim 1, wherein: the flow channel after expansion has a diameter between 5 mm and 15 mm.

3. The PDT light delivery system of claim 1, wherein: the expandable distal section comprises an inner tubular portion that includes an expandable scaffold, to expand when an introducer sheath is withdrawn; and an expandable tubular inner layer around the scaffold, to form the flow channel when expanded by the scaffold; and the outer compliant portion includes an outer layer, sealed together with the inner layer to form an inflatable balloon to compliantly press against the treatment area when inflated.

4. The PDT light delivery system of claim 3, wherein: the side-emitting optical fibers are affixed to the inner layer or positioned proximate to the inner layer.

5. The PDT light delivery system of claim 3, wherein: the outer layer is essentially transparent at an operating wavelength of the illumination.Atorney Docket No. 67555-7036016. The PDT light delivery system of claim 3, wherein: the inner layer is reflective at an operating wavelength of the illumination.

7. The PDT light delivery system of claim 3, wherein: the balloon is folded into one or more wrap-around flaps when the distal section is compressed.

8. The PDT light delivery system of claim 3, the shaft comprising: one or more inflation lumens that have a distal fluid connection to the balloon via one or more flexible inflation arms, to inflate the outer layer with inflation fluid.

9. The PDT light delivery system of claim 8, wherein: the one or more inflation lumens have a proximal fluid connection to an inflation device via an inflation connector of the proximal section.

10. The PDT light delivery system of claim 8, wherein: the inflatable balloon is inflated by filling it up with a translucent fluid through the inflation lumens.

11. The PDT light delivery system of claim 10, the translucent fluid comprising: at least one of a lipid solution, an intralipid, and an oil solution.

12. The PDT light delivery system of claim 8, wherein: the one or more inflation lumens include the optical fibers.

13. The PDT light delivery system of claim 3, wherein: the optical fibers are coupled to optical couplers at the proximal section, configured to be coupled to the light source.

14. The PDT light delivery system of claim 3, wherein: the optical fibers run along the shaft and are coupled into the distal section via flexible inflation arms.Atorney Docket No. 67555-70360115. The PDT light delivery system of claim 3, wherein: the expandable scaffold is longer than the inner layer in its compressed state or in its expanded state.

16. The PDT light delivery system of claim 3, wherein: the inner layer has a higher durometer than the outer layer.

17. The PDT light delivery system of claim 3, wherein: a pressure to inflate the balloon is between 1 psi and 5 psi.

18. The PDT light delivery system of claim 3, wherein: the scaffold is only partially attached to the inner layer.

19. The PDT light delivery system of claim 3, the inner layer comprising: a lubricious material, a low friction material, nylon, linear low-density polyethylene (LLDPE), or a thermoplastic elastomer.

20. The PDT light delivery system of claim 3, the outer layer comprising: silicone rubber, elastomeric polyurethan, thermoplastic elastomers, or blends thereof.

21. The PDT light delivery system of claim 3, wherein: the inner layer and the outer layer are hermetically sealed together to form the balloon in a watertight manner.

22. The PDT light delivery system of claim 3, wherein: the inner layer and the outer layer are formed from the same material; folded at a distal edge; and hermetically sealed together at a proximal edge to form the balloon in a watertight manner; and optionally the inner layer is coated with a reflective coating.

23. The PDT light delivery system of claim 3, wherein: the balloon of the distal section has a V-shaped proximal edge, to reduce resistance against a retraction of the distal section.Atorney Docket No. 67555-70360124. The PDT light delivery system of claim 3, the expandable scaffold comprising: a tube with a cut pattern.

25. The PDT light delivery system of claim 24, wherein: the cut pattern includes parallel lines of repeating longitudinal cuts; wherein the cuts in neighboring lines are shifted by about a haff period.

26. The PDT light delivery system of claim 3, the expandable scaffold comprising: an expandable braid, including a set of braided wires.

27. The PDT light delivery system of claim 3, the expandable scaffold comprising: an expandable nitinol tube, with an asymmetric cut pattern.

28. The PDT light delivery system of claim 3, the expandable scaffold comprising: at least one of struts, spokes, expandable circular wires, a set of longitudinal wires, wire meshes, a stent-like structure, a series of linked zig zag rings, a braided structure, a ring-link structure, and a mesh.

29. The PDT light delivery system of claim 3, wherein: the expandable scaffold is formed from stainless steel or from optionally heat-set nitinol.

30. The PDT light delivery system of claim 3, wherein: the scaffold is a multi-cage scaffold with expandable cages; each cage including a set of cage struts.

31. The PDT light delivery system of claim 30, wherein: the expandable cages are formed from a tube with sets of parallel longitudinal slits, the sets pairwise separated by a cage connector.

32. The PDT light delivery system of claim 30, comprising: an actuator tip at a distal end of the multi-cage scaffold; and an internal actuator, configured to pull the actuator tip in a proximal direction, thereby causing the cage struts to buckle radially outward.Atorney Docket No. 67555-70360133. The PDT light delivery system of claim 3, wherein: the scaffold is a covered stent.

34. The PDT light delivery system of claim 1, wherein: the expandable distal section comprises a proximal expandable scaffold, to expand when an introducer sheath is withdrawn; and a distal inflatable balloon, formed by sealing together an expandable tubular inner layer and an outer layer, to compliantly press against the treatment area when inflated; wherein the proximal expandable scaffold can be slid into the distal inflatable balloon, after the flow channel is partially opened.

35. The PDT light delivery system of claim 1, wherein: the expandable distal section comprises an inner tubular portion that includes an expandable scaffold; and the outer compliant portion includes a set of inflatable compliant balloons, wherein a peripheral region of each balloon compliantly presses against the treatment area when the balloon is inflated, and a central region of each balloon presses against the scaffold, thereby contributing to the formation of the flow channel; and the side-emitting optical fibers are positioned within the inflatable compliant balloons.

36. The PDT light delivery system of claim 35, wherein: the central region of each balloon is reflective on the inside.

37. The PDT light delivery system of claim 1, wherein: the expandable distal section comprises an inner tubular portion that includes a set of inflatable tubular scaffold balloons, to form the flow channel when inflated; the outer compliant portion includes an inflatable compliant outer balloon, formed by an outer layer and the set of inner tubular scaffold balloons, to compliantly press against the treatment area when inflated; and the side-emitting optical fibers are positioned in the inflatable compliant outer balloon.Atorney Docket No. 67555-70360138. The PDT light delivery system of claim 37, wherein: the inner tubular scaffold balloons are inflated with a higher pressure than the compliant outer balloon, optionally through different, dedicated inflation arms.

39. The PDT light delivery system of claim 1, wherein: the expandable distal section includes a flow channel within a distal shaft portion; the outer compliant portion includes an inflatable compliant outer balloon, formed by an outer layer and the inner tubular portion, to compliantly press against the treatment area when inflated; wherein a proximal shaft portion includes one or more shaft holes, fluidly connected to the flow channel of the distal shaft portion; and the side-emitting optical fibers are positioned in the inflatable compliant outer balloon.

40. The PDT light delivery system of claim 1, wherein: the outer compliant portion of the expandable distal section comprises one of a wire structure, a mesh, and a scaffold that supports the side-emitting optical fibers such that the side-emitting optical fibers are expanded close to the treatment area when the distal section is expanded.

41. The PDT light delivery system of claim 40, wherein: the PDT light delivery system is balloonless; and the flow channel is through the wire structure, mesh, or scaffold.

42. The PDT light delivery system of claim 40, wherein: the outer compliant portion is a helical wire structure; and the side-emitting optical fibers are attached along the wire of the helical wire structure.

43. The PDT light delivery system of claim 42, wherein: a gap between neighboring turns of the helical wire structure is between 1 mm and 3 mm.

44. The PDT light delivery system of claim 42, wherein: a proximal end of the helical wire structure is attached to the shaft; and the helical wire structure is configured to be expanded by rotating the shaft, or moving the proximal end distally.Atorney Docket No. 67555-70360145. The PDT light delivery system of claim 40, wherein: the outer compliant portion includes an expandable braided structure that includes a set of helical braid wires in a braid pattern; and the side-emitting optical fibers are attached across several braid wires.

46. The PDT light delivery system of claim 1, the catheter shaft comprising: at least one polyethylene, pebax, nylon, polyurethan, polyether ether-ketone (PEEK), and a combination thereof.

47. The PDT light delivery system of claim 1, the catheter shaft comprising: a stainless steel hypotube.

48. The PDT light delivery system of claim 1, comprising: a restraining sleeve, to keep the expandable tubular scaffold compressed until the distal section reaches the treatment area during insertion, and to be pulled back thereafter.

49. The PDT light delivery system of claim 48, wherein: the restraining sleeve is reinforced with at least one of fibers, wires, and a metal ribbon, in a braided or coil format between layers of polymer.

50. The PDT light delivery system of claim 1, comprising: a guidewire and a distal tip at the end of the guidewire, to guide the insertion of the light delivery catheter and the distal section.

51. The PDT light delivery system of claim 1, comprising: radiopaque markers, positioned to denote a location of at least one of a distal tip, a distal end of the expandable distal section, and a proximal end of the expandable distal section.

52. The PDT light delivery system of claim 1, the side-emitting optical fibers comprising: scatterers that define a scattering coefficient S(x) that depends on x, a longitudinal coordinate along a side-emitting zone of the side-emitting optical fibers; wherein the scattering coefficient S(x) is rising along the side-emitting zone.Atorney Docket No. 67555-70360153. The PDT light delivery system of claim 1, wherein: the light source is operable with a power in a range of 0.5-20 W.

54. The PDT light delivery system of claim 1, wherein: the light source is operable so that the optical fibers emit the illumination with an intensity on the treatment area in a range of 1-300 mW / cm2.

55. The PDT light delivery system of claim 1, wherein: the light source emits the illumination with a wavelength in the 600-800 nm range.

56. A photodynamic therapy (PDT) light delivery system, comprising: a light source, to generate light for the photodynamic therapy; and a light delivery catheter, including an expandable distal section, to be advanced to a treatment area in a closed state, and to be expanded to form a flow channel, and to have an outer compliant portion to compliantly press against the treatment area; and side-emitting optical fibers, positioned in the expandable distal section, to receive the light and to emit it onto the treatment area by scatterers, characterized by a scattering coefficient S(x) that depends on x, a longitudinal coordinate along a side-emitting zone of the side-emitting optical fibers.

57. The PDT light delivery system of claim 56, wherein: the scattering coefficient S(x) is approximately constant along the side-emitting zone.

58. The PDT light delivery system of claim 57, wherein: the side-emitting optical fibers include reflectors at their distal end.

59. The PDT light delivery system of claim 56, wherein: the scattering coefficient S(x) is increasing with x in order to compensate for decreasing light power inside the fiber along the side-emitting zone.Atorney Docket No. 67555-70360160. The PDT light delivery system of claim 59, wherein: the scattering coefficient S(x) is approximately a reciprocal function with a shifted singularity close to, but beyond the distal end of the side-emitting zone:where L*>L, a length of the optical fiber.

61. The PDT light delivery system of claim 59, wherein: each side-emitting optical fiber includes a reflector at its distal end.

62. The PDT light delivery system of claim 61, wherein: the scattering coefficient S(x) is approximately a rounded reciprocal function with a singularity approximately at the distal end of the side-emitting zone:

63. The PDT light delivery system of claim 59, wherein: the scatterers are scattering centers added into cores of the optical fibers with an increasing density towards the distal end of the optical fibers.

64. The PDT light delivery system of claim 59, wherein: the scatterers are scattering centers added into cores of the optical fibers with an increasing size towards the distal end of the optical fibers.

65. The PDT light delivery system of claim 56, wherein: the scatterers are scattering centers formed by applying focused laser pulses to cores of the optical fibers.

66. The PDT light delivery system of claim 56, wherein: the scatterers are modifications of a fiber core / fiber cladding interface.

67. The PDT light delivery system of claim 66, wherein: the modifications of the fiber core / fiber clad interface are limited to a side of the optical fiber.Atorney Docket No. 67555-70360168. The PDT light delivery system of claim 56, the optical fibers comprising: a set of tilted refractive index steps in their cores.

69. The PDT light delivery system of claim 68, wherein: planes of the tilted refractive index steps are rotated along the optical fibers.

70. The PDT light delivery system of claim 56, wherein: the light source includes one of a laser diode and a light emitting diode (LED).

71. The PDT light delivery system of claim 56, wherein: the light source is operable in one of a continuous wave mode or a pulsed mode, with a pulse length in the range of seconds to nanoseconds.

72. The PDT light delivery system of claim 56, wherein: the light source is operable with a power in a range of 0.5-20 W.

73. The PDT light delivery system of claim 56, wherein: the light source is operable with a power in a range of 0.5-5 W.

74. The PDT light delivery system of claim 56, wherein: the light source is operable so that the side-emitting optical fibers emit the illumination with an intensity on the treatment area in a range of 1-300 mW / cm2.

75. The PDT light delivery system of claim 56, wherein: the light source is operable so that the optical fibers emit the illumination with an intensity on the treatment area in a range of 3-100 mW / cm2.

76. The PDT light delivery system of claim 56, wherein: the light source emits the illumination with a wavelength in the 600-800 nm range.

77. The PDT light delivery system of claim 56, wherein: the light source emits the illumination with a wavelength in the 640-680 nm range.

78. The PDT light delivery system of claim 56, wherein:Atorney Docket No. 67555-703601 the light source emits the illumination with a wavelength that is within 100 nm of a minimum of a light absorption coefficient of oxygenated blood.

79. The PDT light delivery system of claim 56, wherein: the light source emits the illumination with a wavelength that is within 100 nm of an activating wavelength of a photosensitizer of the photodynamic therapy.

80. The PDT light delivery system of claim 56, wherein: the PDT light delivery system operates at a matching wavelength in the sense that an operating wavelength of the light source of the PDT light delivery system, a minimum of a light absorption coefficient of oxygenated blood, and an activation wavelength of a photosensitizer of the PDT are all within a 50 nm range.

81. The PDT light delivery system of claim 56, the light delivery catheter comprising: a shaft and a proximal section, together configured to advance the expandable distal section to the treatment area, and to receive the light from the light source at the proximal section and to forward the light to the expandable distal section.

82. The PDT light delivery system of claim 81, wherein: light from the light source is coupled into the proximal section of the light delivery catheter via a releasable optical coupler; wherein the optical coupler is one of a subminiature assembly connector, and a ceramic ferrule guided connector.

83. The PDT light delivery system of claim 81, wherein: the shaft includes an optical feed-fiber, to feed the light of the light source to the side-emitting optical fibers in the expandable distal section.

84. The PDT light delivery system of claim 81, wherein: the shaft includes lumens that accommodate non-side-emitting proximal portions of the sideemitting optical fibers of the expandable distal section.Atorney Docket No. 67555-70360185. The PDT light delivery system of claim 81, wherein: the expandable distal section comprises an inner tubular portion that includes an expandable scaffold, to expand when an introducer sheath is withdrawn; and an expandable tubular inner layer around the scaffold, to form the flow channel when expanded by the scaffold; and the outer compliant portion includes an outer layer, sealed together with the inner layer to form an inflatable balloon to compliantly press against the treatment area when inflated.

86. The PDT light delivery system of claim 85, wherein: the scaffold is a multi-cage scaffold with expandable cages; each cage including a set of cage struts.

87. A photodynamic therapy (PDT) light delivery system, comprising: a light delivery catheter, including an expandable distal section, to be advanced to a treatment area in a compressed state, a shaft, and a proximal section, together configured to advance the expandable distal section to the treatment area; the expandable distal section including an inner tubular portion to form a flow channel when expanded; an outer compliant portion to compliantly press against the treatment area when expanded; and a cluster of LEDs, supported by the inner tubular portion or the outer compliant portion, to illuminate the treatment area with the light.

88. The PDT light delivery system of claim 87, the cluster of LEDs comprising: strings of LEDs, powered through electric wiring positioned in the shaft, and optionally affixed to the inner tubular portion.

89. The PDT light delivery system of claim 87, wherein: the outer compliant portion includes a wire structure; and the cluster of LEDs is affixed, at least partially, to the wire structure.Atorney Docket No. 67555-70360190. A method of applying a photodynamic therapy (PDT) with a PDT light delivery system to a treatment area, the method comprising: exposing the treatment area to a photosensitizer agent; accessing the treatment area with an introducer sheath; advancing a light delivery catheter, having a closed expandable distal section, a shaft, and a proximal section, in the introducer sheath so as to align the expandable distal section with the treatment area; withdrawing the introducer sheath; expanding the closed distal section to form a flow channel and to have an outer compliant portion press compliantly against the treatment area; delivering a PDT illumination to the treatment area via side-emitting optical fibers, positioned in the expanded distal section; and ceasing the illumination, collapsing the expanded distal section by advancing the introducer sheath, and withdrawing the light delivery catheter through the introducer sheath.

91. The method of claim 90, the exposing comprising: delivering the photosensitizer agent intravenously, or topically via a surface of the PDT light delivery system.

92. The method of claim 90, the accessing the treatment area comprising: inserting the introducer sheath into an access site at a femoral artery or a carotid artery; and advancing the introducer sheath over a guide wire, headed by a taped dilator.

93. The method of claim 90, the formation of the flow channel comprising: expanding an inner tubular portion of the expandable distal section by causing a closed expandable scaffold to expand that is surrounded by an expandable tubular inner layer, thereby forming the flow channel.

94. The method of claim 93, wherein: the scaffold is at least one of struts, spokes, expandable circular wires, wire meshes, a stentlike structure, a series of linked zig zag rings, a braided structure, a ring-link structure, an asymmetric scaffold, and a mesh.Atorney Docket No. 67555-70360195. The method of claim 93, wherein: the scaffold is a nitinol tube with a longitudinal cut pattern, heat set to an expanded configuration, and then compressed into the closed distal section; and the expansion of the scaffold is caused by letting the heat-set nitinol tube expand.

96. The method of claim 93, wherein: the scaffold comprises an actuator tip at its distal end; and an internal actuator, configured to pull the actuator tip in a proximal direction, thereby causing the scaffold to expand radially outward.

97. The method of claim 93, wherein: the scaffold is a multi-cage scaffold with expandable cages; and each cage includes a set of cage struts.

98. The method of claim 93, the expanding the closed expandable distal section comprising: inflating an inflatable balloon of the outer compliant portion, formed from an outer layer, sealed together with the inner layer, to compliantly press against the treatment area.

99. The method of claim 98, the inflating comprising: pumping a translucent fluid into the inflatable balloon through inflation lumens, wherein the translucent fluid is at least one of a lipid solution, an intralipid, and an oil solution.

100. The method of claim 98, the inflating comprising: tracking a degree of direct contact between the inflatable balloon and the treatment area; and inflating the inflatable balloon until a predetermined degree of direct contact has been achieved.

101. The method of claim 98, wherein: the inflatable balloon is folded into one or more wrap-around flaps when the expandable distal section is closed.Atorney Docket No. 67555-703601102. The method of claim 90, the formation of the flow channel comprising: allowing an oncoming blood flow to open a distal inflatable balloon of the outer compliant portion, formed by sealing an inner layer and an outer layer together, to form a partial flow channel; advancing a closed proximal scaffold into the newly formed partial flow channel of the distal inflatable balloon; and expanding the closed scaffold, and the inner layer with it, to widen the partial flow channel.

103. The method of claim 102, the expanding the closed expandable distal section comprising: inflating the inflatable balloon to compliantly press against the treatment area.

104. The method of claim 90, the expanding the expandable distal section comprising: expanding an inner tubular portion of the expandable distal section by causing a closed expandable scaffold to expand that is surrounded by an expandable tubular inner layer, thereby forming the flow channel; and inflating a set of inflatable compliant balloons, wherein a peripheral region of each balloon compliantly presses against the treatment area, and a central region of each balloon presses against the scaffold, thereby contributing to the formation of the flow channel.

105. The method of claim 90, the expanding the expandable distal section comprising: expanding an inner tubular portion of the expandable distal section by inflating a set of inflatable tubular scaffold balloons, to form the flow channel; and inflating a compliant outer balloon, formed by an outer layer and the set of inner tubular scaffold balloons, to compliantly press against the treatment area.

106. The method of claim 90, the expanding the expandable distal section comprising: expanding the outer compliant portion of the expandable distal section that includes one of a wire structure, a mesh, and a scaffold that supports the side-emitting optical fibers such that the side-emitting optical fibers are expanded close to the treatment area when the distal section is expanded.Atorney Docket No. 67555-703601107. The method of claim 106, wherein: the outer compliant portion is a helical wire structure; and the side-emitting optical fibers are attached along the helical wire of the helical wire structure.

108. The method of claim 106, wherein: the outer compliant portion includes an expandable braided structure that includes a set of helical braid wires in a braid pattern; and the side-emitting optical fibers are attached across braid wires.

109. The method of claim 90, the delivering the PDT illumination comprising: generating the light with a light source; coupling the generated light into the proximal section of the light delivery catheter; and forwarding the light through the shaft to the side-emitting fibers of the expandable distal section.

110. The method of claim 109, the generating step comprising: operating the light source with a power in a range of 0.5 W-20 W.

111. The method of claim 109, the generating step comprising: operating the light source so that the side-emitting optical fibers emit the illumination with an intensity on the treatment area in a range of 1-300 mW / cm2.

112. The method of claim 109, the generating step comprising: operating the light source to emit the illumination with a wavelength in the 600-800 nm range.

113. The method of claim 109, the generating step comprising: operating the light source to emit the illumination with a wavelength in the 640-680 nm range.

114. The method of claim 109, wherein: the side-emitting optical fibers comprise scatterers that define a scattering coefficient S(x) that depends on x, a longitudinal coordinate along a side-emitting zone of the side-emitting optical fibers; and the scattering coefficient S(x) is rising along the side-emitting zone.Atorney Docket No. 67555-703601115. The method of claim 109, wherein: each side-emitting optical fiber includes a reflector at its distal end; and the scattering coefficient S(x) is approximately a rounded reciprocal function with a singularity approximately at the distal end of the side-emitting zone:

116. A sonodynamic therapy (SDT) system, comprising: an ultrasound source, to generate ultrasound; and an ultrasound focusing system, to receive the generated ultrasound, and to focus the ultrasound to a treatment area that has been treated with a sonosensitizer that generates reactive oxygen species upon activation by the ultrasound; wherein the ultrasound source is configured to generate ultrasound with a frequency and an intensity that is suitable to activate the sonosensitizer.

117. The SDT system of claim 116, wherein: the sonosensitizer is also a photosensitizer.

118. The SDT system of claim 117, wherein: the sonosensitizer is selected from the group of 5-aminovulinic acid, methylene blue, protoporphyrin IX, verteporfm, and BODIPY (boron-dipyrromethene). and others.

119. The SDT system of claim 116, wherein: the ultrasound source and the ultrasound focusing system is configured to apply ultrasound trans-abdominally, to cause crosslinking in aortic aneurysms.

120. The SDT system of claim 116, wherein: the ultrasound source and the ultrasound focusing system is configured to apply ultrasound trans- cranially, to cause crosslinking in cerebral aneurysms.Atorney Docket No. 67555-703601121. The SDT system of claim 116, wherein: the ultrasound source and the ultrasound focusing system are parts of an ultrasound delivery catheter, configured to be inserted into an aorta, and to be advanced to a treatment area.

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