Devices and methods for repairing and rapidly healing internal body structures using photobiomodulation therapy

Abstract

In some embodiments, the distal end of a catheter can be positioned within a body cavity (e.g., a space filled with CSF) of a subject near a target region of tissue (e.g., brain tissue) to be treated. The catheter can include a catheter body and a light emitter configured to emit light asymmetrically and at a non-zero angle relative to a central axis of the catheter body. The light can be emitted from the light emitter at a non-zero angle and asymmetrically relative to the central axis of the catheter body toward the target region of tissue.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and benefit of U.S. Provisional Patent Application No. 63 / 407,546, filed September 16, 2022, entitled "Devices and Methods for Repair and Rapid Healing of Internal Body Structures Using Photobiomodulation Therapy," and U.S. Provisional Patent Application No. 63 / 483,962, filed February 8, 2023, entitled "Devices and Methods for Repair and Rapid Healing of Internal Body Structures Using Photobiomodulation Therapy," the disclosures of each of which are incorporated herein by reference in their entireties.

[0002]

[0002] This application is related to U.S. patent application Ser. No. 15 / 976,199, filed May 10, 2018, entitled "Devices and Methods for Repair of a Selected Blood Vessel or Part Thereof and Rapid Healing of Injured Internal Body Cavity Walls," which claims priority to and benefit of U.S. provisional patent application Ser. No. 62 / 508,690, filed May 19, 2017, entitled "Devices and Methods for Repair of a Selected Blood Vessel or Part Thereof and Rapid Healing of Injured Internal Body Cavity Walls," the disclosures of each of which are incorporated herein by reference in their entireties.

[0003] Technical Field

[0003] The present disclosure relates generally to systems, devices, and methods for therapeutic intervention in blood vessels and other body lumens or cavities. [Background technology]

[0004] background

[0004] The embodiments described herein generally relate to the application of therapeutic light energy to cellular elements to induce a healing response, such as modulating blood flow (e.g., reducing flow or completely halting flow) to a selected blood vessel or portion thereof.

[0005]

[0005] Delivery of photobiomodulation (PBM) therapy involves applying low-level energy of coherent or non-coherent (e.g., LED) light selected from a range of wavelengths to target tissue. To aid absorption of the light energy within the target tissue, the light energy can optionally be applied in conjunction with a photosensitizer (e.g., administered intravenously or topically), such as sodium fluorescein, erythrosine B, or rose bengal dye. For example, the photosensitizer can be absorbed onto the endothelial luminal surface of an injured artery, and light energy can be applied to the endothelial luminal surface to induce a healing response.

[0006] A mechanistic explanation for the healing response to incident light is that light-sensitive cellular chromophores, such as cytochrome c oxidase (unit IV of the mitochondrial respiratory chain), absorb incident photons, which dissociate inhibitory nitric oxide from the enzyme, increasing electron transport, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. Another hypothesis proposes that light-sensitive ion channels may be activated, allowing calcium to enter the cell. After the initial photon absorption event, multiple signaling pathways are activated via reactive oxygen species, cyclic adenosine monophosphate (AMP), nitric oxide (NO), and calcium ions (Ca2+), leading to the activation of transcription factors. These transcription factors may increase the expression of genes involved in protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, and antioxidant enzymes. Stem and progenitor cells appear to be particularly susceptible to PBM.

[0007]

[0007] Known approaches to treating nerve regeneration disorders using PBM primarily rely on non-invasive transcutaneous and transosseous delivery of light energy. Therefore, delivery of light energy to target tissues is limited to wavelength ranges that can penetrate soft and hard tissues. Due to attenuation, much greater energy densities (i.e., energy per unit area) than are needed in the target tissue are typically applied. Additionally, the light energy density on the target tissue typically cannot be well controlled to be relatively uniform (i.e., maintained within a range of energy density values ​​high enough to be therapeutically effective and low enough not to damage the target tissue).

[0008] Additionally, patients with chronic subdural hematoma (cSDH) present with a wide range of symptoms of varying severity. These can range from headache, isolated seizures, cognitive decline, stroke-like symptoms such as numbness, and facial asymmetry to aphasia, weakness, paralysis, altered mental status, and death. Current research suggests that cSDH results from initial damage to the dural border cell layer on the inner surface of the dura mater, a thick membrane covering the brain, which then ruptures, allowing cerebrospinal fluid and blood to leak into the space between the ruptured cell layer and the rest of the dura mater. In some patients, the initial damage to the dural border cell layer cannot be repaired, stimulating a cycle of hyperfibrinolysis, inflammation, angiogenesis, and the resulting development of subdural neoplasia.

[0009] For patients with moderate or severe symptoms, surgical drainage via burr hole or craniotomy is typically the standard of care. Surgical drainage improves neurological status through decompression of intracranial material and prevents further progression in patients with extensive cSDH. In addition, minimally invasive clinical trials are evaluating the benefits of medial medial artery (MMA) embolization. In this procedure, a microcatheter is placed into the MMA or its branches, and embolic agents such as polyvinyl alcohol particles, detachable coils, or liquid embolic agents, e.g., Onyx, Squid, Phil, or cyanoacrylate, are injected or introduced into the MMA to cut off the blood supply to the inflamed dura and halt the inflammatory cycle. Embolization can be performed alone or as an adjunct to surgical decompression for the treatment of cSDH.

[0010] However, a major problem with surgical drainage is recurrence. Previous studies have reported a recurrence rate of approximately 10–30% and a mortality rate of 4% after surgical drainage. Complications of minimally invasive microcatheter medial artery embolization, related to inadvertent occlusion of critical branches, include stroke, bleeding, blindness, and facial nerve paralysis. Other problems associated with MMA embolization include recurrence of cSDH and lack of clinical improvement.

[0011]

[0011] Therefore, there is a need for systems, devices, and methods that can more effectively treat target tissues using PBM, particularly for the treatment of diseases and repair of injuries affecting degenerative disorders of the brain and spinal cord, and target tissues contained in or accessible through large synovial joints. Summary of the Invention [Means for solving the problem]

[0012] summary In some embodiments, a distal end of a catheter can be positioned within a body cavity (e.g., a space filled with CSF) of a subject near a target region of tissue (e.g., brain tissue) to be treated. The catheter can include a catheter body and a light emitter configured to emit light asymmetrically and at a non-zero angle relative to a central axis of the catheter body. The light can be emitted from the light emitter to the target region of tissue asymmetrically and at a non-zero angle relative to the central axis of the catheter body. [Brief explanation of the drawings]

[0013] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1] 1 is a schematic block diagram of a system according to one embodiment. [Figure 2A]

[0014] FIG. 2 is a schematic diagram of a light scatterer in the system of FIG. 1. [Figure 2B] FIG. 2 is a schematic diagram of a light scatterer of the system of FIG. [Figure 2C] FIG. 2 is a schematic diagram of a light scatterer of the system of FIG. [Figure 3A]

[0015] FIG. 2 is a schematic diagram of a fluid conduit and inner body for the optical conduit of the system of FIG. 1. [Figure 3B] 2 is a schematic diagram of a fluid conduit and inner body for the light conduit of the system of FIG. 1. [Figure 3C] 2 is a schematic diagram of a fluid conduit and inner body for the light conduit of the system of FIG. 1. [Figure 3D] 2 is a schematic diagram of a fluid conduit and inner body for the light conduit of the system of FIG. 1. [Figure 4A]

[0016] FIG. 2 is a schematic diagram of a spacing member of the system of FIG. 1. [Figure 4B] 2 is a schematic diagram of a spacing member of the system of FIG. 1. [Figure 4C] 2 is a schematic diagram of a spacing member of the system of FIG. 1. [Figure 4D] 2 is a schematic diagram of a spacing member of the system of FIG. 1. [Figure 4E] 2 is a schematic diagram of a spacing member of the system of FIG. 1. [Figure 4F] 2 is a schematic diagram of a spacing member of the system of FIG. 1. [Figure 4G] 2 is a schematic diagram of a spacing member of the system of FIG. 1. [Figure 5A]

[0017] FIG. 2 is a schematic diagram of an imager of the system of FIG. 1. [Figure 5B] FIG. 2 is a schematic diagram of an imager of the system of FIG. [Figure 6]

[0018] FIG. 2 is a schematic diagram of a mesh tube that can be used with the system of FIG. 1. [Figure 7A]

[0019] FIG. 2 is a schematic diagram of an occlusion device that can be used with the system of FIG. 1. [Figure 7B] 2 is a schematic diagram of an occlusion device usable with the system of FIG. 1. [Figure 8]

[0020] FIG. 2 is a schematic diagram of an introducer that can be used with the system of FIG. 1. [Figure 9]

[0021] 1 is a flowchart illustrating a method, according to one embodiment. [Figure 10]

[0022] FIG. 1 is a schematic diagram of a kit containing elements of a system for use in a method, according to one embodiment. [Figure 11A]

[0023] 1 is a schematic illustration of an apparatus and method for treating an aneurysm in a blood vessel, according to one embodiment. [Figure 11B]

[0023] FIG. 1 is a schematic diagram of an apparatus and method for treating an aneurysm in a blood vessel, according to one embodiment. [Figure 11C]

[0023] FIG. 1 is a schematic diagram of an apparatus and method for treating an aneurysm in a blood vessel, according to one embodiment. [Figure 11D]

[0023] FIG. 1 is a schematic diagram of an apparatus and method for treating an aneurysm in a blood vessel, according to one embodiment. [Figure 11E]

[0023] FIG. 1 is a schematic diagram of an apparatus and method for treating an aneurysm in a blood vessel, according to one embodiment. [Figure 12A]

[0024] 1 is a schematic illustration of an apparatus and method for treating an aneurysm at a blood vessel bifurcation, according to one embodiment. [Figure 12B]

[0024] FIG. 1 is a schematic diagram of an apparatus and method for treating an aneurysm at a blood vessel bifurcation, according to one embodiment. [Figure 12C]

[0024] FIG. 1 is a schematic diagram of an apparatus and method for treating an aneurysm at a blood vessel bifurcation, according to one embodiment. [Figure 12D]

[0024] FIG. 1 is a schematic diagram of an apparatus and method for treating an aneurysm at a blood vessel bifurcation, according to one embodiment. [Figure 12E]

[0024] FIG. 1 is a schematic diagram of an apparatus and method for treating an aneurysm at a blood vessel bifurcation, according to one embodiment. [Figure 13]

[0025] 1 is a schematic illustration of an apparatus and method for treating fusiform aneurysms in a blood vessel, according to one embodiment. [Figure 14]

[0026] 1 is a schematic illustration of a device and method for occluding a blood vessel, according to one embodiment. [Figure 15]

[0027] 1 is a schematic illustration of a device and method for embolizing a malformation in a blood vessel, according to one embodiment. [Figure 16]

[0028] 1 is a schematic diagram of an apparatus and method for treating cavernous malformations, according to one embodiment. [Figure 17A]

[0029] 1 is a schematic illustration of a device and method for treating a joint, for example, a knee joint capsule. [Figure 17B]

[0030] FIG. 17B is an enlarged side view of the device of FIG. 17A. [Figure 17C] FIG. 17C is an end view of the device of FIG. 17B. [Figure 17D]

[0031] 17B is a side view of an alternative embodiment of a device suitable for use in a method for treating a joint such as that shown in FIG. 17A. [Figure 17E] FIG. 17B is an end view of an alternative embodiment of a device suitable for use in a method for treating a joint such as that shown in FIG. 17A. [Figure 17F]

[0032] FIG. 17B is a side view of yet another alternative embodiment of a device suitable for use in a method of treating a joint such as that shown in FIG. 17A. [Figure 17G] FIG. 17B is an end view of yet another alternative embodiment of a device suitable for use in a method of treating a joint such as that shown in FIG. 17A. [Figure 17H]

[0033] 17B is an end view of an alternative embodiment of a device suitable for use in a method for treating a joint such as that shown in FIG. 17A. [Figure 18A]

[0034] 1A-1D are various schematic diagrams of the human brain, spinal cord, parts of the associated CSF spaces, and other related body parts. [Figure 18B]

[0034] Various schematic diagrams of the human brain, spinal cord, parts of the associated CSF spaces, and other related body parts. [Figure 19]

[0034] Various schematic diagrams of the human brain, spinal cord, parts of the associated CSF spaces, and other related body parts. [Figure 20]

[0034] Various schematic diagrams of the human brain, spinal cord, parts of the associated CSF spaces, and other related body parts. [Figure 21]

[0035] 1 is a schematic block diagram of a system, according to one embodiment. [Figure 22A]

[0036] 1 is a schematic diagram of a cross section of a portion of a system, according to one embodiment. [Figure 22B]

[0037] 22B is a schematic diagram of a cross section of a portion of the system of FIG. 22A, including an optical scatterer, a reflective surface portion, and a radiopaque marker having two protrusions. [Figure 22C]

[0038] FIG. 22B is a schematic diagram of a radiopaque marker of the system of FIG. 22A. [Figure 22D]

[0039] FIG. 22C is a schematic diagram of a radiopaque marker of the system of FIG. 22B. [Figure 22E]

[0040] FIG. 22B is a schematic diagram of a cross section of a portion of the system of FIG. 22A including an imaging conduit and a reflective surface portion. [Figure 22F]

[0041] 22D is a schematic diagram of a cross section of a portion of the system of FIG. 22A including the end cap and radiopaque marker shown in FIG. 22D. [Figure 23A]

[0042] 1 is a schematic diagram of a cross section of a portion of a system, according to one embodiment. [Figure 23B]

[0043] 1 is a schematic diagram of a cross section of a portion of a system, according to one embodiment. [Figure 24A]

[0044] 1A-1C are schematic cross-sectional views of various spacing members according to one embodiment. [Figure 24B]

[0044] FIG. 1 is a schematic diagram of cross sections of various spacing members according to one embodiment. [Figure 24C]

[0044] FIG. 1 is a schematic diagram of cross sections of various spacing members according to one embodiment. [Figure 24D]

[0044] FIG. 1 is a schematic diagram of cross sections of various spacing members according to one embodiment. [Figure 24E]

[0044] FIG. 1 is a schematic diagram of cross sections of various spacing members according to one embodiment. [Figure 24F]

[0044] FIG. 1 is a schematic diagram of cross sections of various spacing members according to one embodiment. [Figure 24G]

[0044] FIG. 1 is a schematic diagram of cross sections of various spacing members according to one embodiment. [Figure 24H]

[0045] FIG. 1 is a schematic diagram of a perspective view of a spacing member, according to one embodiment. [Figure 24I]

[0045] FIG. 1 is a schematic diagram of a cross-sectional view of a spacing member according to one embodiment. [Figure 25]

[0046] 10A-10C are schematic cross-sectional views of various expansion configurations of a spacing member, according to one embodiment. [Figure 26A]

[0047] 1 is a schematic diagram of a cross section of a portion of a system in a first configuration, according to one embodiment. [Figure 26B]

[0047] FIG. 1 is a schematic diagram of a cross section of a portion of a system in a second configuration, according to one embodiment. [Figure 27]

[0048] 1 is a schematic diagram of a cross section of a portion of a system, according to one embodiment. [Figure 28]

[0049] 1 is a schematic diagram of a cross section of a portion of a system, according to one embodiment. [Figure 29]

[0050] 1 is a schematic diagram of a cross section of a portion of a system, according to one embodiment. [Figure 30]

[0051] 1 is a schematic diagram of a cross section of a portion of a system, according to one embodiment. [Figure 31]

[0052] 1 is a schematic diagram of a cross section of a portion of a system, according to one embodiment. [Figure 32]

[0053] 1 is a schematic diagram of a cross section of a portion of a system, according to one embodiment. [Figure 33]

[0054] 1 is a flowchart illustrating a method, according to one embodiment. [Figure 34]

[0055] 1 is a schematic diagram of an apparatus and method for treating a stroke region of the brain, according to one embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0014] Detailed Description

[0056] Disclosed are systems and methods suitable for effectively treating blood vessels, including cerebral, coronary, and peripheral vessels, for aneurysms or other malformations (such as arteriovenous malformations and dural malformations), for vascular occlusion to drain tumor vessels, and for treating varicose veins and spider veins to exclude them from circulation. The systems and methods can also be used to treat ulcers in the lining of body cavities, such as gastric ulcers, parenchymal tumors, such as brain tumors and liver tumors, and non-vascular lesions of other soft tissues of the body, bleeding vasculature in arteries or veins (not via endovascular access), hemorrhoidal bleeding, esophageal varices, spider angiomas, joint bleeding, amyloidogenic diseases, lymphangiomas, cartilage damage, joint inflammation, such as rheumatoid arthritis, synovial joint inflammation, and traumatic joint injury, bone repair, renal tumors, and inflammatory diseases, such as fibrosis, pulmonary bronchopulmonary bleeding, myocardial injury, carotid artery disease, neurodegenerative diseases, and splenomegaly.

[0015]

[0057] The disclosed system includes a catheter device that may include a catheter body having a distal end and a proximal end, and a light emitter disposed at the distal end of the catheter body and configured to emit light. A fluid conduit is disposed within the catheter body, extending from the proximal end to the distal end of the catheter body. The fluid conduit has an inlet at the proximal end of the catheter body and is connectable to a fluid source, and an outlet at the distal end and configured to discharge fluid from the source through the conduit and out the distal end. A spacing member is disposed at the distal end of the catheter body and is reconfigurable from a collapsed configuration to an expanded configuration. In the expanded configuration, the spacing member is disposed around the light emitter to maintain the light emitter approximately centered within the spacing member relative to at least one axis of the spacing member. The spacing member is at least partially transparent and / or semi-transparent to light emitted from the light emitter. The device is configured such that the distal end of the catheter body is at least partially inserted into a body lumen having an inner wall, the spacing member is positioned in an expanded configuration within the body lumen, fluid is expelled into the body lumen, and light is emitted from the light emitter to illuminate the inner wall of the body lumen.

[0016]

[0058] In some embodiments, a method includes placing a distal end of a catheter within a blood vessel of a subject adjacent to a region of the blood vessel wall to be treated. The distal end of the catheter is positioned at the center or proximal end of the treatment region. The catheter includes a light emitter configured to emit light, a fluid conduit outlet coupled to a fluid source, and a spacing member reconfigurable from a collapsed configuration to an expanded configuration. The spacing member may be at least partially transparent and / or semi-transparent to the light emitted from the light emitter and porous to fluid discharged from the fluid outlet. The spacing member may be transitioned to the expanded configuration when placed at the treatment position. When in the expanded configuration, the spacing member may be disposed around the light emitter to maintain the light emitter approximately centered within the spacing member relative to at least one axis of the spacing member. The method further includes placing the spacing member approximately centered within the blood vessel lumen. Fluid is discharged into the blood vessel from the fluid conduit outlet, diluting blood within the blood vessel with the fluid. Light is irradiated from the light emitter through the diluted blood in the blood vessel lumen and onto the region of the blood vessel wall to be treated.

[0017]

[0059] In some embodiments, the distal end of a catheter can be positioned within a body cavity (e.g., a space filled with CSF) of a subject near a target region of tissue (e.g., brain tissue) to be treated. The catheter can include a catheter body and a light emitter configured to emit light asymmetrically and at a non-zero angle relative to a central axis of the catheter body. The light can be emitted from the light emitter at a non-zero angle and asymmetrically relative to the central axis of the catheter body toward the target region of tissue.

[0018]

[0060] In some embodiments, a system includes a catheter body; an optical conduit at least partially disposed within the catheter body; a light emitter disposed at a distal end of the optical conduit and configured, when disposed within a patient's body cavity near a target tissue region, to emit a first portion of light received through the optical conduit asymmetrically and at a non-zero angle relative to a central axis of the optical conduit such that the first portion is transmitted to the target tissue region at a first intensity and to emit a second portion of the light received through the optical conduit distal to the light emitter; and a light scatterer coupled to the light emitter and configured to diffuse the second portion of the light such that the second portion of the light is transmitted to a non-target tissue region at a second intensity that is lower than the first intensity.

[0019]

[0061] In some embodiments, the system includes a catheter body, an optical conduit, and a light emitter. The optical conduit can be at least partially disposed within the catheter body. The light emitter can be disposed at a distal end of the optical conduit and configured to emit light asymmetrically and at a non-zero angle relative to a central axis of the optical conduit such that the light is transmitted to the target region of tissue when the light emitter is disposed within a patient's body cavity near (e.g., adjacent to) the target tissue region.

[0020]

[0062] In some embodiments, a system includes a catheter body defining a working channel, an inner body translatable within the working channel and including a light emitter at a distal end of the inner body, and a spacing member. The spacing member can be coupled to the inner body proximal to the light emitter and configured to transition between a collapsed configuration and an expanded configuration. The spacing member can have a conical shape in the expanded configuration to define a conical space within which the light emitter is at least partially disposed, and the spacing member can be configured to maintain the light emitter approximately centered relative to a central axis of the spacing member when in the expanded configuration within a body lumen or between opposing walls of a body cavity.

[0021]

[0063] As shown schematically in FIG. 1, treatment system 100 can include a catheter 110 that can be operably coupled to other devices or systems including a light source LS, a fluid source FS, and an image display ID, and can be used in combination with other devices including a mesh tube MT, an occlusion device OD, and an introducer (not shown in FIG. 1), and with compositions such as a photochemical agent PA.

[0022]

[0064] The catheter 110 may have an elongate catheter body 120 having proximal and distal ends suitable for insertion into a body lumen or cavity BL, such as a blood vessel, adjacent a treatment region TR of the body lumen or cavity BL. The catheter body 120 may define an internal working channel 124 through which other components of the catheter 110 may be positioned and moved. Thus, in some embodiments, the catheter body 120 may be inserted into a patient, such as by being delivered over a guidewire through the patient's vasculature until the distal end is positioned adjacent the treatment region TR. The guidewire may then be removed, and other components of the catheter 110 may be delivered through the working channel 124 until their distal ends are positioned in the treatment region TR in appropriate operative relationship with the distal end of the catheter body 120. In other embodiments, some or all of the other components of the catheter 110 may be disposed within and / or coupled to the catheter body 120 before the catheter 110 is inserted into the patient and its distal end is delivered to the treatment region TR.

[0023]

[0065] The catheter 110 includes a light emitter 130 that is disposed at the distal end of the catheter body 120 when the catheter 110 is configured for use. The light emitter 130 may optionally be optically coupled to a light source LS by a light conduit 132 that may be disposed within the catheter body 120, for example, within the working channel 124, and that extends from the proximal end to the distal end of the catheter body 120.

[0024]

[0066] The catheter 110 also includes a fluid conduit 140, which may be disposed within the catheter body 120 and extends from an inlet 144 at the proximal end of the catheter body 120 to an outlet 142 at the distal end of the catheter body 120. The fluid conduit 140 may be coupled to a fluid source FS at the inlet 144.

[0025]

[0067] The catheter 110 can also include a spacing member 150 disposed at the distal end of the catheter body 120. Depending on the implementation of the spacing member 150, the spacing member 150 can be attached to the distal end of the catheter body 120 and actuated by fluid through the fluid conduit 140. In some embodiments, the spacing member 150 is coupled to or integrally formed with another component of the catheter 110. For example, the spacing member 150 can be formed with or coupled to an inner body 148 (e.g., as described with respect to FIG. 3D ), which can now function as a spacing member actuator 152 disposed within the catheter body 120. The spacing member actuator 152 extends from the proximal end to the distal end of the catheter body 120 and can be used to transform the spacing member 150 between a collapsed configuration and an expanded configuration.

[0026]

[0068] The catheter 110 may also include an imager 160 coupled to the distal end of the catheter body 120. The imager 160 may be disposed within the catheter body 120 and optically coupled to an image display ID by an imaging conduit 162, which may extend from the proximal end to the distal end of the catheter body 120.

[0027]

[0069] Each component of the treatment system 100 can be implemented in a variety of ways. In applications in which the catheter 110 is used for intravascular access to a treatment region TR of a body lumen BL, the catheter 110 can be implemented as a conventional intravascular catheter, including its structure and materials, its ability to steer or not steer or bend its distal end, its ability to be deliverable over a guidewire, and can include user controls and accessories at its proximal end. In some embodiments, a guidewire (not shown) can be disposed within the working channel 124 of the catheter body 120. In other embodiments, for example, where the catheter body 120 may be relatively large, the catheter body 120 can include a dedicated guidewire lumen separate from the working channel 124. The proximal portion of the catheter body 120 can be stiffer than the distal portion to provide sufficient rigidity for a user to push the catheter body 120 over a guidewire and through a lumen, e.g., the vasculature. A more flexible distal portion can facilitate navigating the catheter body 120 through, for example, a tortuous vasculature. The catheter body 120 can be introduced into a body lumen BL, such as a blood vessel, via an incision or other percutaneous technique to access the vascular cavity. In some applications, the catheter 110 may be used to directly access the treatment region TR rather than through a subject's vascular system and may be implemented accordingly. For example, if the catheter 110 is used to directly access the treatment region TR through soft tissue, the catheter 110 can be implemented as a relatively rigid needle inserted through a trocar.

[0028]

[0070] The light emitter 130 may be implemented in any known suitable structure for emitting light of a desired wavelength and intensity from the distal end of the catheter 110 to the treatment region TR in the body lumen BL. In some embodiments, the light emitter 130 may simply be the end of an optical fiber, which may serve as an optical conduit 132 for transmitting light from a light source LS that can be coupled to the proximal end of the catheter 110. The light source LS may be any suitable light source of a desired wavelength and intensity, and may be a source of coherent light, such as a laser (pulsed or continuous wave), or a source of incoherent light (such as xenon or halogen light and an appropriate bandpass filter). In other embodiments, the light emitter 130 may be a relatively compact light source, such as a light-emitting diode (LED) or laser diode, located at the distal end of the catheter 110, with power provided by electrical leads extending from the proximal end of the catheter 110 through the catheter body 120 to the light source. In an alternative embodiment, the LED or laser diode may be located at the proximal end of the catheter 110.

[0029]

[0071] To generate a desired distribution of light in the treatment region TR, i.e., a distribution different from the distribution generated by the light source LS, in some embodiments, a light scatterer 136 (see, e.g., FIG. 2A ) is operatively associated with the light source LS to scatter light from the light source LS across the treatment region TR. In some embodiments, the light scatterer 136 may be implemented as a convex end cap on the distal tip of the light conduit 132, e.g., an optical fiber, as shown schematically in FIG. 2A . The end cap may include light-scattering particles, shown as circular regions 138 in FIG. 2A . Such particles may be, for example, titanium dioxide. Other light-scattering materials (high refractive index of approximately 2.5) or refractive structures, such as diffraction gratings, may also be used.

[0030]

[0072] As shown schematically in FIG. 2B , the light emitter 130 extends from the distal end of the catheter body 120, and the end cap and light-scattering particles diffuse and distribute light emitted from the distal tip of the optical fiber 132 around the sides of the tip and end cap to illuminate the treatment region TR, which in this example is the surface of an aneurysm. The light distribution pattern can be tailored to the shape of the treatment region TR to create a relatively uniform energy density on the surface of the treatment region TR and avoid areas of excessively high energy density, or “hot spots.” For example, in the embodiment shown in FIG. 2B , the distribution is approximately spherical to correlate with the approximately spherical shape of the aneurysm that forms the treatment region TR. In other embodiments, such as that shown in FIG. 2C , rather than a convex end cap, the light scatterer 136 can be implemented as a cylindrical tip that scatters light only radially, but not axially, thereby providing a light distribution that better correlates to the cylindrical shape of the treatment region TR, such as the wall of a body lumen such as a blood vessel.

[0031]

[0073] In other embodiments, described in more detail below with reference to FIG. 4E, the light scatterer 136 may be spaced apart from the light emitter 130 and instead be coupled to or form part of another structure, such as a spacing member 150.

[0032]

[0074] The fluid conduit 140 may be implemented with any known suitable structure for conveying a fluid, such as saline, through the catheter 110 to be discharged at the distal end of the catheter body 120. The fluid may provide for dilution, visualization, and / or cooling. For example, as shown schematically in FIGS. 3A and 3B , the fluid conduit 140 may be an annular conduit defined between the catheter body 120 and an inner body 148. The inner body 148 may provide a lumen or passageway within which other structures, such as an optical conduit 132, may pass through the catheter body 120. In the embodiment shown in FIGS. 3A and 3B , the inner body 148 is a braided reinforcement or overwrap for the optical fiber 132 to protect the delicate optical fiber and to provide a stiffer composite structure for distal delivery of the optical fiber and associated scattering elements 136 through the catheter body 120. The inner body 148 also supports the optical scatterers 136 on its distal end. In this embodiment, the fluid conduit 140 is substantially the annular space remaining within the working channel 124 of the catheter body 120 around the inner body 148. In other embodiments, the fluid conduit 140 may be arranged laterally rather than concentrically around another structure, such as the light conduit 132. As shown generally in FIG. 3A , the outlet 142 may simply be configured as an opening in the annular distal end of the fluid conduit 140. In other embodiments, other geometric dimensions or configurations may be employed, for example, to direct the flow of dilution fluid laterally relative to the axis of the catheter body 120, to constrict the flow to reduce flow velocity, to accelerate flow velocity, etc.

[0033]

[0075] The inner body 148 in Figures 3A and 3B is shown in more detail in Figure 3C. The inner body 148 has a distal portion 148A and a proximal portion 148B of different structures. The proximal portion 148B may be formed as a solid tubular structure, such as a hypotube, occupying a majority of the length of the inner body 148, e.g., 1 meter, while the distal portion 148A may be formed as a braid or coil occupying a small portion of the length of the inner body 148, e.g., approximately 25 cm. As described above, the inner body 148 includes a central lumen capable of receiving an optical conduit, such as an optical fiber 132, and a distal tip on which optical scatterers 136 may be mounted. This structure provides a relatively rigid structure that allows the inner body 148 to be pushed distally through the working channel 124 of the catheter body 120, while the flexible distal portion 148A can be easily navigated into and through tortuous body lumens BL. This embodiment is suitable for use with a catheter in which the spacing member 150 is coupled to the catheter body 110, as shown in Figures 4D-4G, described below. In an alternative embodiment, shown in Figure 3D, the spacing member 150 is integrally formed with or otherwise attached to the distal end 148A of the inner body 148, as described in more detail below with reference to Figure 4C.

[0034]

[0076] The spacing member 150 can be implemented with a variety of structures and materials to provide the desired functionality. The primary function of the spacing member 150 is to maintain a minimum spacing between the light emitter 130 and the treatment region TR, i.e., to prevent the light emitter 130 from being placed too close to the treatment region TR so that the light energy density of the light emitter 130 does not exceed an acceptable upper limit. For example, it may be desirable for the spacing member 150 to keep the light emitter 130 relatively centered within the body lumen BL, while still maintaining a relatively uniform spacing between the light emitter 130 and the treatment region TR. These related functions can be achieved in a variety of ways. For example, in some embodiments, as shown in FIG. 4C , the light emitter 130 and spacing member 150 can be fixed relative to each other, and both can be moved to a desired working position through the working channel 124 of the catheter body 120. In other embodiments, as shown in FIGS. 4D and 4E , the spacing member 150 can be fixed relative to the catheter body 120, and the light emitter 130 can be movable relative to both.

[0035]

[0077] As shown schematically in FIG. 4A , when the spacing element 150 has a shape or geometric dimension that is substantially symmetrical about the longitudinal axis LA of the catheter body 120 and the light emitter 130 is positioned substantially on the longitudinal axis LA, the light emitter 130 is positioned substantially centrally within the spacing element 150. When the catheter 110 is positioned within the body lumen BL and the spacing element 150 is in an expanded configuration whose diameter approximates the diameter of the body lumen BL, the light emitter 130 is positioned substantially centrally within the body lumen BL. If the light emitted by the light emitter 130 is then relatively uniformly distributed angularly about the longitudinal axis LA, the light energy density on the treatment region TR will be relatively uniform circumferentially; in other words, the light energy density on the treatment region TR will be between desired upper and lower energy density values. While the shape is schematically shown as ellipsoidal in FIG. 4A , the spacing element 150 may be configured to have any other desired shape, depending, for example, on the shape of the body lumen and / or treatment region. As shown schematically in FIG. 4B, if the body lumen is not tubular, e.g., a blood vessel, but rather has a saccular shape, e.g., an aneurysm, an elliptical or spherical shape may be more appropriate to optimize the center of the light emitter 130 within the body lumen BL.

[0036]

[0078] Another function of the spacing member 150 may be to allow a diluent fluid DF to pass therethrough and into the body lumen BL. For example, as described in more detail below, it may be desirable for the spacing member 150 to be filled with a diluent fluid DF, for example, to replace blood or other body fluid BF and / or to reconfigure or assist in the reconfiguration of the spacing member 150 from a collapsed configuration to an expanded configuration. It may also be desirable for the diluent fluid to dilute and / or replace blood or other body fluid between the spacing member 150 and the treatment region TR and / or body lumen BL. It may also be desirable to use the fluid to expand or otherwise change the geometric size or shape of the treatment region TR and / or body lumen BL. Accordingly, the sidewalls of the spacing member 150 may be porous or permeable to the diluent fluid. 4B, in some embodiments, the proximal end of the spacing member 150 can surround all or a portion of the outlet 142 of the fluid conduit 140, in which case the dilution fluid can enter the interior of the spacing member 150 and the fluid can exit the spacing member 150 (e.g., through a porous or permeable wall of the spacing member 150). In other embodiments, the outlet 142 of the fluid conduit 140 can be located outside the spacing member 150, and it may be desirable to allow the fluid to enter the spacing member 150.

[0037]

[0079] Another function of the spacing member 150 is to expand or otherwise change the geometric size or shape of the treatment region TR and / or body lumen BL mechanically, i.e., by engaging the spacing member 150 with the surface of the treatment region TR and / or body lumen BL.

[0038]

[0080] 4C-4E schematically illustrate several possible configurations of the spacing member 150. In the embodiment shown in FIG. 4C, the spacing member 150 may take the form of a wire cage formed of multiple wires or struts 155 defining multiple openings 157 therebetween through which the diluent fluid discharged by the fluid outlet 142 may pass. The spacing member 150 may be formed of braided wire, laser-cut tubing, or other known structures. The spacing member 150 may be self-expanding, e.g., formed of a shape-memory material such as Nitinol, and may be set or biased to an expanded configuration but retained in a collapsed configuration, e.g., by being placed within the fluid conduit 140 (or working channel 124) of the catheter body 120. Alternatively, the spacing member 150 may be biased to the collapsed configuration and require the application of a force to urge it to the expanded configuration.

[0039]

[0081] In the embodiment shown in FIG. 4D , the spacing member 150 is formed of an elastomeric material and is therefore essentially a balloon. However, rather than being a sealed balloon, it is referred to as a leaky balloon because it includes perforations 157 that allow the passage of diluent fluid. The proximal end of the spacing member 150 is disposed around the fluid outlet 142, so that diluent fluid discharged from the fluid outlet 142 enters the interior of the spacing member 150 and exits through the perforations 157. The diluent fluid can be used to flush the interior of the balloon and expel any air through a bleed channel or tube (not shown) before the light emitter 136 is distally inserted into position within the spacing member 150 through the working channel 124 (not shown) of the catheter body 120. The diluent fluid can also be used to inflate the balloon, i.e., to urge the spacing member 150 from a collapsed configuration (not shown) to the expanded configuration shown in FIG. 4D . As the balloon expands, the perforations 157 expand, thus providing a larger flow area for the diluent fluid to exit the balloon. Thus, the size of the balloon can be controlled by controlling the flow rate and pressure of the diluent fluid exiting fluid outlet 142. After the treatment procedure, the diluent fluid can be withdrawn from the elastic balloon, allowing the spacing member 150 to deform into a collapsed configuration that can be withdrawn from the patient's body.

[0040]

[0082] In the embodiment shown in FIG. 4E, the spacing member 150 is also formed of an elastomeric material and is thus also essentially a balloon. However, in this embodiment, the balloon is sealed, i.e., does not contain perforations as in the previous embodiment. Fluid can be introduced into the body lumen BL through a port (not shown) through the catheter body 120. As in the previous embodiment, the interior of the balloon can be flushed and purged of air, and then inflated by introducing a diluent fluid through the fluid outlet 142, thereby urging the spacing member 150 from a collapsed configuration (not shown) to the expanded configuration shown in FIG. 4E. The size of the balloon can therefore be controlled by controlling the amount of diluent fluid exiting the fluid outlet 142. In this embodiment, the spacing member 150 also provides some or all of the light scattering function in that it includes a layer 135 of light-scattering material on the interior or exterior surface of the spacing member 150 (shown on the interior surface in FIG. 4E). While FIG. 4E also schematically illustrates a light scatterer 136 on the tip of the light conduit 132, in some embodiments, the layer 135 of material on the spacing member 150 may be the only light scatterer. In some embodiments, light scattering may be provided by light scattering particles mixed or suspended in a diluent fluid. In some embodiments, the spacing member 150 may be at least partially transparent and / or semi-transparent to the light emitted from the light emitter 130.

[0041]

[0083] The embodiment shown in Figures 4F and 4G is similar to that shown in Figure 4E, except that spacing member 150 includes a fluid port 158 ​​at its distal end and optical scatterer 136 includes a valve extension 137 at its distal tip. Valve extension 137 can cooperate with fluid port 158 ​​to selectively establish and prevent fluid communication between the body lumen BL and the interior of spacing member 150. For example, the valve extension functions as a closure element, and fluid port 158 ​​of spacing member 150 provides a distal closure surface such that a hermetic seal is formed between a surface of port 158 ​​and a surface of valve extension 137 when valve extension 137 is moved distally. Thus, as shown in Figure 4F, with valve extension 137 positioned within fluid port 158 ​​to fluidly isolate the interior of elastic spacing member 150, fluid ejected from fluid outlet 142 can expand spacing member 150 to a desired configuration. 4G, valve extension 137 can then be withdrawn proximally, thus disengaging from fluid port 158, establishing fluid communication between the interior of spacing member 150 and body lumen BL. Fluid discharged from fluid outlet 142 can then be discharged into body lumen BL via fluid port 158.

[0042]

[0084] The imager 160 may be implemented in any known suitable configuration for collecting images of the treatment region TR or other portions of the body lumen BL. Various imaging modalities may be employed, including optical (in wavelengths including visible, near-infrared, and / or other portions of the spectrum), ultrasound, and optical coherence tomography (OCT). As shown schematically in FIGS. 5A and 5B , the imager 160, which in this example is an optical imager, may include an imaging conduit 162, e.g., an optical fiber. The imager 160 may provide a measure of the optical energy density and, therefore, the total energy applied, applied to the treatment region TR by the light emitter 130 over time. In other embodiments, the imager 160 may enable acquisition of image information from the treatment region TR, such as to aid in positioning the distal end of the treatment system 100 relative to the treatment region TR to assess the condition of the treatment region TR before, during, and after treatment.

[0043]

[0085] The light applied to the treatment region TR, i.e., from the light emitter 130 and optionally by the light scatterer 136, can have a wavelength in the range of 400 nm to 1,100 nm. A convenient and suitable wavelength is 532 nm, which can be produced by readily available and inexpensive lasers and laser diodes. The power of the light applied to the treatment region TR can be in the range of 1 mW to 500 mW, and preferably in the range of 100 mW to 200 mW. The power density of the light applied to the treatment region TR is 1 mW / cm. 2 to 5W / cm 2 in the range of 50 to 500 mW / cm 2 in the range of 175 to 200 mW / cm 2 It can be in the range of

[0044]

[0086] Although the mechanism of action is not well understood, it is believed that application of light of the above wavelengths and intensities may be responsible for activating and / or accelerating hematopoiesis, which causes stem cells to differentiate into blood and vascular cells, followed by rapid conversion of fresh clots into scar tissue and healing of the treated area TR.

[0045]

[0087] The mesh tube MT can be used in combination with the catheter 110 to treat certain indications and anatomical structures. The mesh tube MT can be of various configurations, geometries, sizes, etc., suitable for the desired treatment. Examples of suitable mesh tubes are described in U.S. Patent No. 7,942,925 to Yodfat et al., entitled "Implantable Intraluminal Device and Method of Using Same in Treating Aneurysms," the entire disclosure of which is incorporated herein by reference. One suitable embodiment of the mesh tube MT is shown schematically in FIG. 6 in an expanded configuration in which the mesh tube MT is disposed within a body lumen BL. The mesh tube MT includes multiple filaments of elastic or inelastic biocompatible material, metal, or plastic, extending in a helical, interlacing pattern to define a braided tube. Thus, the first group of filaments MT1 helically extends in one direction, and the second group of filaments MT2 helically extends in the opposite direction, the two groups of filaments interwoven such that the filaments MT1 are above the filaments MT2 at some points, as shown at P1, and below the filaments MT2 at other points, as shown at P2. The filaments MT1 and MT2 thus define a braided tube having a plurality of windows W. The inscribed diameter and length of each window W are W, respectively, in the implanted state (e.g., expanded configuration) of the mesh tube MT. d and W LThese properties depend, among other things, on the number of filaments, the cross-section of the filaments, and the implantation angle "α" at the intersection of the two filament groups MT1 and MT2. The mesh tube MT can be placed across the neck of an aneurysm, along a straight section of the blood vessel, or at or near a branch of the blood vessel, and can function to divert a portion of the blood flow through the vessel away from the aneurysm. The mesh tube MT can also be used to reduce blood flow to selected sections of the blood vessel where blood clotting is desired to be promoted. In some embodiments, the mesh tube MT is detached from the catheter 110 and deployed within the blood vessel. In some cases, blood passing through the mesh tube MT into the aneurysm has a long residence time within the aneurysm, and thus platelets that are activated during their passage into the aneurysm may initiate thrombus formation that is then "trapped" or trapped within the aneurysm. Photoactivation of stem cells significantly accelerates the conversion of thrombus to scar tissue and healing of the condition.

[0046]

[0088] 7A and 7B illustrate the use of an occlusion device OD, which may be used in combination with a catheter 110 in the treatment of certain indications and anatomical structures. As shown schematically in FIG. 7A , the occlusion device OD is positioned within a body lumen BL, such as a blood vessel, and can be moved to an expanded configuration that engages and occludes the inner wall of the body lumen BL, i.e., reduces or prevents the flow of fluid, e.g., blood, through the body lumen BL. In this embodiment, the catheter 110 is shown with its distal end positioned within an aneurysm A upstream of the occlusion device OD. The catheter 110 can thus evacuate fluid into the aneurysm A and dilute the blood therein to a desired dilution ratio without the fluid being carried away through the body lumen BL with the blood, since the body lumen BL is occluded by the occlusion device OD. In the embodiment of FIG. 7A , the distal tip of the catheter 110 is steerable, so the light emitter can be positioned at a desired location within the aneurysm A without the need for a spacing device. As is well known in the art, the occlusion device OD can be deployed in a collapsed configuration for delivery to a desired location within the body lumen BL prior to treatment of the aneurysm A and for withdrawal after treatment is complete, and can be inflated to its expanded configuration to occlude the body lumen BL by inflating the balloon with a fluid. Suitable balloon occlusion devices include, for example, the HyperForm Occlusion Balloon sold by Medtronic.

[0047]

[0089] 7B, occlusion device OD can be an elongated balloon that spans the neck of aneurysm A and "traps" the distal tip of catheter 110. That is, the proximal portion of occlusion device OD can trap a portion of the distal end of catheter 110 against the wall of body lumen BL, thus anchoring catheter 110 in addition to occluding the lumen as in the previous embodiment. Suitable elongated balloon occlusion devices include, for example, the HyperGlide Occlusion Balloon sold by Medtronic.

[0048]

[0090] FIG. 8 illustrates an embodiment of an introducer IN that may be used in combination with the catheter 110 to treat certain indications and anatomical structures. The introducer IN has a generally cylindrical body B with a tapered distal portion DP, a proximal end PE, a central lumen extending through the body B, and a slot SL communicating with the central lumen. The introducer IN can facilitate the introduction of the inner body 148 into the catheter 110. For example, an incision or cutdown can be made in the patient's skin at the site where the catheter 110 is to be introduced into the patient's body. The catheter 110 is then inserted into the patient's body through a standard introducer sheath. A standard hemostasis valve is then attached to the proximal tip of the catheter 110. The tip of the tapered distal portion DP can be inserted into the hemostasis valve, and the introducer IN can be pushed through the hemostasis valve. When the distal end of the introducer IN is in the desired position, the distal end of the inner body 148 can be inserted into the lumen of the introducer IN at the proximal end PE and pushed through the lumen and out the distal tip of the introducer IN into the desired portion of the patient's anatomy, e.g., the body lumen BL. Alternatively, the distal end of the inner body 148 can be pre-loaded into the lumen of the introducer IN.

[0049]

[0091] A method for treating a treatment region TR of a body lumen, particularly a portion of the lumen wall of a blood vessel, is shown schematically in FIG. 9. At 202, any photochemical agent can be administered to the subject (e.g., patient) to be treated. For example, a light energy absorber or biochemical thrombolytic agent can also be utilized within the selected portion of the blood vessel to be treated, including the neck and full thickness of the malformation. In some cases, a photochemical agent, such as erythrosin B or rose bengal, can be injected into the treatment region of the blood vessel prior to irradiation to enhance light absorption by the vessel wall and accelerate the photochemical reaction. The agent can be administered intravenously (IV) (i.e., systemically) or locally within the blood vessel (or aneurysm or malformation) to be treated, either via catheter 110 or via a separate microcatheter. An optically translucent or transparent field is then established before light energy is applied thereto.

[0050]

[0092] At 204, a catheter (e.g., catheter 110) can be inserted into a blood vessel of a subject, and the distal end of the catheter can be positioned adjacent to or near a region of the blood vessel wall to be treated. In some embodiments, before inserting the catheter into the blood vessel, a guidewire can be inserted into the blood vessel and positioned near the treatment region. The catheter can then be inserted over the guidewire (e.g., the lumen of the catheter can be received over the guidewire) and moved along the guidewire to the desired location in the treatment region.

[0051]

[0093] At 206, the spacing member (e.g., spacing member 150) and light emitter 130 (e.g., light emitter 130 with light scatterers 136) of catheter 110 can be extended from the distal end of the lumen of catheter 110, and the spacing member can be deformed into an expanded configuration around the light emitter. The spacing member can prevent contact between the light emitter and the vessel wall and ensure centering of the light emitter within the vessel so that uniform distribution of photon energy flux to the surrounding vessel wall can be achieved. At 208, the spacing member can be positioned approximately centrally within the vessel to be treated.

[0052]

[0094] At 210, fluid can be ejected from the outlet of the fluid conduit of the catheter 110 and into the blood vessel to dilute the blood within the vessel. For example, saline injection can be initiated to establish a transparent or translucent optical field within the treatment region of the blood vessel. At 212, light energy can be emitted from the light emitter of the catheter through the diluted blood and onto the wall of the blood vessel. The light energy can initiate and / or accelerate clotting of blood within the treatment region, while the spacing member can prevent emboli resulting from the clotting from traveling downstream through the blood vessel. In some cases, the spacing member can be detached from the delivery system and permanently left in place at the treatment site for protection. After treatment, the catheter can be removed from the blood vessel.

[0053]

[0095] FIG. 10 is a schematic diagram of a kit according to one embodiment. As described above, the treatment system 100 can be provided as a kit including one or more components that perform various functions for treating the treatment region TR. In some embodiments, the KIT can be a single-use set of disposable components. In some embodiments, the KIT can include the catheter 110 disposed within kit packaging, such as a sterile package used to protect the catheter 110 from contamination during shipping and storage. In some embodiments, the kit packaging can include an outer package and one or more inner sterile packaging components for containing and protecting one or more of the KIT components. The catheter 110 can include a catheter body 120 having a working channel 124, a light emitter 130, and a fluid conduit 140, for example, as described above. The KIT can also optionally include one or more of the following components that can be used in combination with the catheter 110: an occlusion device OD, a light source LS, a fluid source FS, a photochemical agent PA, a mesh tube MT, an introducer IN, a spacing member 150, an imager 160, and / or instructions for use IFU. In some embodiments, the KIT may include multiple types of spacing members (e.g., 150), for example, to allow a user (e.g., a physician) to select an appropriate spacing member 150 for a particular treatment. In some embodiments, the KIT may include multiple types of light emitters (e.g., 130), for example, to allow a user (e.g., a physician) to select an appropriate light emitter 130 (e.g., having various types of light scatterers 136, etc.) for a particular treatment. Each of the components of the KIT may be disposed in one or more sterile kit packages.

[0054]

[0096] 11A-11E illustrate various approaches for using a treatment system such as that described above to treat an aneurysm located laterally off the sidewall of a blood vessel. The treatment system embodiments and specific components illustrated and described with respect to FIGS. 11A-11E may be configured the same as or similar to, and may include the same or similar features as, corresponding components of system 100 described above. As noted above, the illustrated systems and components may be used to treat aneurysms using, for example, light energy.

[0055]

[0097] In the treatment procedure shown in FIG. 11A , a treatment system includes a catheter 210, the distal end of which is positioned within an aneurysm A laterally offset from the sidewall of a blood vessel BV. The catheter 210 can include any of the features described above, the details of which are omitted from FIG. 11A for simplicity. For example, a spacing member 250, located at the distal end of the catheter body 224, can be implemented using any of the options described above, including a porous balloon, a non-porous balloon, a wire cage, etc. The spacing member 250 can be transformed using any of the techniques described above between a collapsed configuration (not shown) during delivery to the treatment site and an expanded configuration (shown in FIG. 11A ) during the treatment procedure. The spacing member 250 can be used to maintain a minimum spacing between the light emitter 230 and the wall of the aneurysm A to be treated. With the light emitter 230 and spacing member 250 positioned within the aneurysm A, the light emitter 230 can be activated to emit the desired light energy to treat the aneurysm A. Optionally, fluid (e.g., saline) can be introduced into the treatment area as described above. Optionally, immediately after treating (e.g., irradiating) aneurysm A with light emitted from light emitter 230, an intra-aneurysmal implant, such as one or more coils, a Woven EndoBridge (WEB) device, or any other intra-aneurysmal implant, can be placed within aneurysm A, using the system in one of the configurations shown in Figures 11A, 11D, and / or 11E. Alternatively, after light treatment and withdrawal of the distal end of catheter body 224 from aneurysm A, spacing member 250 can be detached from catheter body 224 and left within aneurysm A.

[0056]

[0098] In the technique shown in FIG. 11B , a catheter 210 is used in combination with a mesh tube 246. The mesh tube 246 may be formed and configured the same as or similar to the mesh tube MT described with respect to FIG. 6 . The mesh tube 246 may be positioned within a blood vessel BV outside an aneurysm A so as to extend across (i.e., straddle) the opening of the aneurysm A. The mesh tube 246 may be deployed in a contracted or collapsed configuration and transformed into an expanded configuration within the blood vessel BV. In this embodiment, the catheter 210 is inserted between the wall of the blood vessel BV and the mesh tube 246 before expanding the mesh tube 246. The mesh tube 246 is then expanded to hold or trap the catheter 210 against the wall of the blood vessel BV during treatment with the light emitter 230. A transparent or translucent light field may be established by introducing fluid (e.g., saline) into the treatment area, and light energy may then be applied by the light emitter 230 to irradiate the treatment target blood vessel wall and initiate or accelerate clotting of blood within the aneurysm. Mesh tube 246 can prevent emboli resulting from clotting from migrating into the blood vessel. Mesh tube 246 can also function to divert a portion of the blood flow through blood vessel BV away from aneurysm A.

[0057]

[0099] The technique shown in FIG. 11C is similar to the technique shown in FIG. 11B , except that the catheter 210 is used in combination with a mesh tube 246′, which may be formed and configured the same as or similar to the mesh tube MT described with respect to FIG. 6 . The mesh tube 246′ may be positioned within a blood vessel BV outside the aneurysm A so as to extend across (i.e., straddle) the opening of the aneurysm A. In this technique, the catheter 210 is inserted through the lumen defined by the mesh tube 246′, and the mesh tube 246′ is inflated at the treatment location before being inserted into the aneurysm through the sidewall of the mesh tube 246′. The mesh tube 246′ may function to divert a portion of the blood flow through the blood vessel BV away from the aneurysm A. The mesh tube 246′ may also help maintain the position of the catheter 210 relative to the aneurysm A during treatment with the light emitter 230. As described above, fluid may be injected into the treatment area, and light energy may be applied by the light emitter 230.

[0058]

[0100] In the procedure shown in FIG. 11D , catheter 210 is used in combination with occlusion device 254. Occlusion device 254 may be formed and configured the same as or similar to occlusion device OD described above with reference to FIGS. 7A and 7B . For example, occlusion device 254 may be an inflatable balloon that can be transformed between a collapsed configuration for delivery to a treatment location within blood vessel BV and an expanded configuration as shown in FIG. 11D . Occlusion device 254 may be positioned within blood vessel BV in a collapsed configuration to extend across (i.e., straddle) the opening of aneurysm A and deployed within the blood vessel outside aneurysm A. Catheter 210 is inserted between the wall of blood vessel BV and occlusion device 254, after which occlusion device 254 is transformed into its expanded configuration so that occlusion device 254 holds or traps catheter 210 against the wall of blood vessel BV. Fluid (e.g., saline) may be introduced into the treatment area to establish a transparent or translucent optical field, and then light energy may be applied by light emitter 230 to illuminate the treatment target vessel wall and initiate or accelerate clotting of blood within aneurysm A. During light treatment, the occlusion device 254 prevents emboli resulting from clotting from migrating into the blood vessel BV. The occlusion device 254 can also obstruct blood flow within the blood vessel during treatment of the aneurysm A.

[0059]

[0101] In the approach shown in FIG. 11E, catheter 210′ ​​has a steerable distal end portion and can therefore be used without spacing member 250. The distal end portion of catheter 210′ ​​is positioned within aneurysm A as described with respect to FIG. 11A, with light emitter 230 positioned approximately centered within aneurysm A by steering control of the distal end portion. In this illustration, catheter 210′ ​​is used in combination with occlusion device 254′. Occlusion device 254′ can be formed and configured the same as or similar to occlusion device OD described above with respect to FIGS. 7A and 7B. For example, occlusion device 254′ can be an inflatable balloon that can be transformed between a collapsed configuration for delivery to a treatment location within blood vessel BV to an expanded configuration shown in FIG. 11E.

[0060]

[0102] In this technique, the occlusion device 254' is deployed in a collapsed configuration within the blood vessel BV to a position downstream of the aneurysm A to block blood flow through the blood vessel BV, and then inflated to secure the occlusion device 254 within the blood vessel distal to the aneurysm A. A catheter 210' is inserted between the inflation conduit of the occlusion device 254' and the wall of the blood vessel BV, and the distal end portion is manipulated so that the light emitter 230 is approximately centered within the aneurysm A. A fluid (e.g., saline) can be introduced into the treatment area to establish a transparent or translucent light field, and light energy can then be applied by the light emitter 230 to illuminate the treatment target vessel wall and initiate or accelerate clotting of blood within the aneurysm A. During light treatment, the occlusion device 254 prevents emboli resulting from the clotting from migrating downstream within the blood vessel BV.

[0061]

[0103] 12A-12E illustrate various techniques for using a treatment system such as those disclosed above to treat an aneurysm located at a bifurcation in a blood vessel. The treatment system embodiments and specific components illustrated and described with respect to FIGS. 12A-12E may be configured the same as or similar to, and may include the same or similar features as, corresponding components of system 100 described above. The illustrated systems and components may be used to treat aneurysms, for example, using light energy, as described above.

[0062]

[0104] In the treatment procedure shown in Figure 12A, a treatment system includes a catheter 310, the distal end portion of which is positioned within an aneurysm A located at a bifurcation BF of a blood vessel BV. Catheter 310 can include any of the features described above, the details of which are omitted from Figure 12A for the sake of simplicity.

[0063]

[0105] For example, the spacing member 350 located at the distal end of the catheter body 324 can be implemented using any of the options discussed above, including a porous balloon, a non-porous balloon, a wire cage, etc. The spacing member 350 can be transformed using any of the techniques discussed above between a collapsed configuration (not shown) for delivery to the treatment location and an expanded configuration (shown in FIG. 12A) during treatment. The spacing member 350 can be used to maintain a minimum distance between the light emitter 330 and the wall of the aneurysm A to be treated.

[0064]

[0106] Catheter 310 is inserted into blood vessel BV, and the distal end portion of catheter 310, including spacing member 350 and light emitter 330, is positioned within aneurysm A. Spacing member 350 is deformed to its expanded configuration, and fluid is injected to establish a transparent or translucent light field. Light energy is then applied by light emitter 330 to initiate and / or accelerate coagulation of blood in the treatment area. Spacing member 350 may also prevent emboli resulting from the coagulation from migrating downstream into the blood vessel.

[0065]

[0107] In the approach shown in FIG. 12B , catheter 310 is used in combination with mesh tubes 346 and 347 to further prevent emboli from migrating into the blood vessel during treatment. Mesh tubes 346 and 347 not only function as a filter to prevent emboli from migrating into the blood vessel, but can also function as a scaffold for vascular remodeling after photon therapy. Mesh tubes 346 and 347 may be formed and configured the same as or similar to mesh tube MT described with reference to FIG. 6 . Mesh tube 346 includes a first portion positionable within blood vessel BV outside aneurysm A and a second portion extending into bifurcation B1 of blood vessel BV. Similarly, mesh tube 347 includes a first portion positionable within blood vessel BV outside aneurysm A that engages mesh tube 346 and a second portion extending into bifurcation B2 of blood vessel BV. Mesh tubes 346 and 347 can be delivered in a collapsed configuration and transformed into an expanded configuration at the treatment location. In this embodiment, mesh tubes 346 and 347 collectively define an elongated space within blood vessel BV, terminating at the opening of the aneurysm. The distal end portion of catheter 310 can be inserted between the vessel wall and the elongated space defined by mesh tubes 346 and 347, effectively becoming “trapped” between the vessel wall and the mesh tubes. Spacing element 350 and light emitter 330 can be inserted into aneurysm A, spacing element 350 can be inflated within aneurysm A, and fluid can be injected to establish a transparent or translucent light field. Light energy is then applied by light emitter 330 to initiate and / or accelerate blood clotting in the treatment area. The mesh tubes and spacing element 350 also help prevent emboli resulting from clotting from migrating downstream into the blood vessel.

[0066]

[0108] The technique shown in FIG. 12C is similar to the technique shown in FIG. 12B , except that in this figure, catheter 310 is used in combination with mesh tubes 346′ and 347′, which may be formed and configured the same as or similar to mesh tube MT described with respect to FIG. 6 . Mesh tube 346′ includes a first portion positionable within blood vessel BV outside aneurysm A and a second portion extendable within bifurcation B1 of blood vessel BV. Similarly, mesh tube 347′ includes a first portion positionable within blood vessel BV outside aneurysm A and a second portion extendable within bifurcation B2 of blood vessel BV. In this embodiment, mesh tubes 346′ and 347′ abut each other within blood vessel BV such that mesh tubes 346′ and 347′ collectively form a generally Y-shape (referred to as a “double-barrel technique”). In this embodiment, catheter 310 is inserted with its distal end portion positioned within aneurysm A before mesh tubes 346′ and 347′ are inserted into blood vessel BV. After catheter 310 is positioned, mesh tubes 346′ and 347′ may be positioned within blood vessel BV and branches B1 and B2 and inflated to hold or trap catheter 310 within the space formed between mesh tubes 346′ and 347′ and the arterial wall. Mesh tubes 346′ and 347′ may function to divert a portion of blood flow through blood vessel BV away from aneurysm A. Mesh tubes 346′ and 347′ may also help maintain the position of catheter 310 relative to the aneurysm during treatment with light emitter 330.

[0067]

[0109] In the procedure of FIG. 12D , catheter 310 is used in combination with a single mesh tube 346″, which may be formed and configured the same as or similar to mesh tube MT described with respect to FIG. 6 . In this embodiment, mesh tube 346″ includes a first portion extending into bifurcation B1 of blood vessel BV and a second portion extending into bifurcation B2. As shown in FIG. 12D , catheter 310 is inserted into the aneurysm, and mesh tube 346″ is then opened to an expanded position, substantially trapping catheter 310 between the arterial wall and mesh tube 346″ with its distal tip within aneurysm A. Mesh tube 346″ may also help maintain the position of catheter 310 relative to aneurysm A during treatment with light emitter 330.

[0068]

[0110] In the approach shown in FIG. 12E , catheter 310 is used in combination with a single mesh tube 346′″, which may be formed and configured the same as or similar to mesh tube MT described with respect to FIG. 6 . Mesh tube 346′″ is generally Y-shaped and includes a middle section positioned within blood vessel BV outside the opening of aneurysm A and two branch sections extending into bifurcation B1 and bifurcation B2 of blood vessel BV. As shown in FIG. 12E , in this embodiment, catheter 310 is inserted into aneurysm A and mesh tube 346′″ is deformed to an open position, essentially “confining” or trapping catheter 310 between the arterial wall and mesh tube 346′″. Mesh tube 346′″ may also help maintain the position of catheter 310 relative to the aneurysm during treatment with light emitter 330.

[0069]

[0111] 13 illustrates the use of a treatment system such as that described above to treat a fusiform aneurysm FA located in the wall of a blood vessel BV near a bifurcation BF. The embodiments and specific components of the treatment system illustrated and described with respect to FIG. 13 may be configured the same as or similar to, and may include the same or similar features as, corresponding components of the system 100 described above. The illustrated system and components may be used to treat a fusiform aneurysm FA using, for example, optical energy, as described above.

[0070]

[0112] As shown in Figure 13, the treatment system includes a catheter 410, which is shown with its distal end portion positioned within a fusiform aneurysm FA located in the sidewall of a blood vessel BV. Catheter 410 can include any of the features described above, the details of which are omitted from Figure 12A for simplicity.

[0071]

[0113] Spacing member 450 can be implemented using any of the options described above, including a porous balloon, a non-porous balloon, a wire cage, etc. Spacing member 450 can be transformed between a collapsed configuration (not shown) and an expanded configuration (shown in FIG. 13 ) using any of the techniques described above. Spacing member 450 can be used to maintain a minimum distance between light emitter 430 and the wall of the fusiform aneurysm FA to be treated. With light emitter 430 and spacing member 450 positioned within the fusiform aneurysm FA, light emitter 430 can be activated to emit a desired light intensity to treat the aneurysm.

[0072]

[0114] In this embodiment, catheter 410 includes an occlusion device 454 coupled to catheter body 420. Occlusion device 454 may be formed and configured the same as or similar to occlusion device OD described above with respect to Figures 7A and 7B. For example, occlusion device 454 may be an inflatable balloon that can be transformed between a collapsed configuration for delivery to a treatment location within blood vessel BV and an expanded configuration as shown in Figure 13. In this embodiment, occlusion device 454 is positioned within blood vessel BV anterior to fusiform aneurysm FA to obstruct or block blood flow through blood vessel BV.

[0073]

[0115] The catheter 410 can also be used in combination with a mesh tube 446, as shown in Figure 13, for example, which may be formed and configured the same as or similar to the mesh tube MT described with respect to Figure 6. In this embodiment, the mesh tube 446 is elongated and shown positioned within a blood vessel BV that traverses a fusiform aneurysm FA with "landing zones" in the arteries on either side of the aneurysm FA. The catheter 410 is inserted through a lumen defined by the mesh tube 446 and remains positioned within the lumen of the mesh tube 446 during treatment of the fusiform aneurysm FA with the light emitter 430.

[0074]

[0116] 14 shows catheter 410 positioned within blood vessel BV illustrating the use of catheter 410 for treatment of the wall of blood vessel BV (e.g., treatment of varicose veins) and the use of occlusion device 454 to occlude blood flow within blood vessel BV during treatment with, for example, light emitter 430. After light treatment with light emitter 430, a device suitable for occluding the blood vessel, such as, for example, one or more thrombogenic coils or other suitable devices described herein, can be placed within blood vessel BV to affect healing.

[0075]

[0117] FIG. 15 shows a catheter 410 positioned within a blood vessel BV to treat a malformation M therein. In FIG. 15, branches BF at the exit of the malformation M indicate potentially multiple exits from the malformation M. In this example, a catheter 410 including an occlusion device 454 coupled to a catheter body 420 is positioned within the blood vessel BV that leads directly into the malformation. The spacing member 450 is transformed into an open position, initiating fluid flow through the flow channel 440. Illumination of the malformation M with light emitted from the light emitter 430 begins to embolize the malformation within the blood vessel BV. Penetration of light into the small, fragile arteries of the malformation M can initiate thrombus formation and subsequent transformation into scar tissue, resulting in the elimination of the malformation M from circulation. Following light treatment with the light emitter 430, a device suitable for occluding the blood vessel, such as one or more thrombus-forming coils or other suitable devices described herein, can be placed within the blood vessel BV to affect healing.

[0076]

[0118] Figure 16 illustrates components of a treatment system such as those described above being used to treat a low-flow malformation, such as a cavernous malformation, within a subject. The embodiments of the treatment system and specific components illustrated and described with respect to Figure 16 may be configured the same as or similar to, and may include the same or similar features as, corresponding components of system 100 described above. As discussed above, the illustrated system and components may be used to embolize the malformation, for example, using optical energy.

[0077]

[0119] As shown in Figure 16, the treatment system includes a catheter 510, with a distal end portion of the catheter 510 shown positioned within the cavernous region CV. The catheter 510 can include any of the features described above, the details of which are omitted from Figure 16 for simplicity. In some embodiments, the catheter 510 can be a blunt needle that is inserted into the lesion over a trocar.

[0078]

[0120] For example, spacing member 550 is disposed at the distal end of catheter body 520 through working channel 524. Spacing member 550 shown in FIG. 16 is constructed the same as or similar to spacing member 150 shown and described with respect to FIG. 4C. More specifically, spacing member 550 includes a plurality of wires or struts defining multiple openings therebetween through which diluent fluid discharged by catheter 410 may pass. Spacing member 550 may be used to maintain a minimum spacing between light emitter 530 and the wall of the treatment area. Any of the other spacing member designs described above may also be used.

[0079]

[0121] In this treatment approach, the catheter 510 is inserted directly into the cavernous malformation through the patient's skin and intervening tissue (e.g., percutaneously) rather than into an artery or vein. For example, the catheter 510 may be introduced into the patient's body via a delivery sheath that is inserted into the body through openings in the patient's body's skin and / or bony structures, such as the skull. In this embodiment, the working channel 524 of the catheter body 520 may be used to introduce or inject fluid from a fluid source (not shown) into the treatment area, i.e., the cavernous area CV. A separate suction device 564 may be used to aspirate (e.g., remove) excess fluid and / or other material from the treatment area. In some embodiments, the catheter 510 may include an aspiration channel incorporated into the catheter body 524. Examples of such embodiments are described below with respect to FIGS. 17A-17H.

[0080]

[0122] 17A-17C illustrate components of a treatment system that may be used to treat, for example, a cavernous malformation or joint, such as the knee capsule KC (FIG. 17A). The treatment system embodiments and specific components illustrated and described with respect to FIGS. 17A-17C may be configured the same as or similar to, and may include the same or similar features as, corresponding components of system 100 described above. The illustrated systems and components may be used to treat a treatment area within the knee capsule KC, for example, using light energy, as described above.

[0081]

[0123] Similar to the previous embodiment of FIG. 16 , as shown in FIGS. 17A-17C , a treatment system is introduced directly (e.g., percutaneously) into a patient's joint (e.g., knee capsule). The treatment system includes a catheter 610 (e.g., a blunt needle), the distal end portion of which is shown positioned within the knee capsule KC. The catheter 610 includes a catheter body 620 defining a lumen 624 through which an inner body 648 is movably disposed. The lumen 624 can also be used to introduce fluid (e.g., saline) into the treatment region from a fluid source (not shown). In this embodiment, the inner body 648 defines a lumen 633 (see FIG. 17C ) that can receive an optical fiber (not shown) coupled to a light emitter 630. A light scattering element can be incorporated into the light emitter 630 and attached to the inner body 648. The light emitter 630 (and the optical fiber) can be coupled to a light source (not shown). Because the fluids within body joints are clear or translucent, there is no need to dilute such fluids with clear fluids, such as saline, in order to allow the light radiation to reach the soft tissue to be treated. Furthermore, no cooling is required when using fully transparent, light-scattering materials, such as diamond dust.

[0082]

[0124] 17D and 17E illustrate another embodiment of a catheter that can provide fluid irrigation and aspiration functions and can be used to treat a joint, such as the knee capsule KC shown in FIG. 17A. The catheter 710 includes a catheter body 720 that defines a lumen 724 through which an inner body 748 is movably disposed. The inner body 748 defines a lumen 733 (see FIG. 17E) that can receive an optical fiber (not shown) coupled to an optical emitter 730. Although not shown, a light scattering element can also be attached to or incorporated into the optical emitter 730. The optical emitter 730 (and optical fiber) can be coupled to a light source (not shown).

[0083]

[0125] In this embodiment, the lumen 724 of the catheter body 720 can also be used to introduce or deliver a fluid, such as saline, from a fluid source (not shown) into the treatment region, e.g., the cavernous malformation or knee joint capsule KC. The fluid can exit the lumen 724 through a distal opening or outlet 742. As previously described, the fluid can provide dilution, visualization, and / or cooling within the treatment region. The catheter body 720 also defines a separate aspiration lumen 766 disposed parallel to the lumen 724. The aspiration lumen can be used to aspirate (e.g., remove) excess fluid from the treatment region, e.g., continuously during treatment or when light treatment is completed.

[0084]

[0126] Figures 17F and 17G illustrate another alternative embodiment of a catheter that can provide fluid irrigation and aspiration functions and can be used to treat a joint or cavernous malformation, such as the knee capsule KC, as shown in Figures 17A and 16, respectively. The catheter 810 includes a catheter body 820 that defines a lumen 824 through which an inner body 848 is movably disposed. The inner body 848 defines a lumen 833 (see Figure 17G) that receives therein an optical fiber (not shown) coupled to an optical emitter 830. Although not shown, a light scattering element can also be attached to or incorporated into the optical emitter 830. The optical emitter 830 (and optical fiber) can be coupled to a light source (not shown).

[0085]

[0127] In this embodiment, the lumen 824 of the catheter body 820 can also be used to introduce or deliver fluid from a fluid source (not shown) into the treatment region, e.g., the cavernous malformation or knee capsule KC. Fluid can exit the lumen 824 through a distal opening or outlet 842. The catheter body 820 also defines an aspiration lumen 866 that can be used to aspirate the treatment region (e.g., remove fluid and / or other matter from the treatment region). In this embodiment, the lumen 824 (used to introduce fluid) and the aspiration lumen 866 are coaxial. Alternatively, the lumen 824 can be used for aspiration, and the lumen 866 can be used to deliver fluid into the treatment region.

[0086]

[0128] In an alternative embodiment shown in Figure 17H, a catheter 810' can include a catheter body 820' defining a lumen 824' that can be used to both deliver fluid to and suction the treatment area. For example, the catheter body 824' can be coupled to a fluid source to deliver fluid to the treatment area. Fluid flow through the lumen 824' can then be terminated, and the catheter body 820' can be coupled to a device for suctioning through the lumen 824'. Alternatively, the lumen 824' can be coupled to a valve that switches between a source of fluid irrigation and a source of suction.

[0087]

[0129] As mentioned above, in some embodiments, a system such as any of the systems described herein can be used to treat a target area (e.g., tissue) accessible from a body cavity. For example, the systems and methods described herein can be used to access a body cavity containing cerebrospinal fluid (CSF) to target brain tissue and / or spinal disc tissue. Additionally, the systems and methods described herein can be used to access a synovial joint cavity filled with synovial fluid to treat a target area of ​​a synovial joint.

[0088]

[0130] In some embodiments, the systems and methods described herein can be used (e.g., using photobiomodulation (PBM)) to treat ischemic stroke, chronic neuropathic pain, and / or brain tissue damage resulting from neurodegenerative disorders. Addressable neurodegenerative disorders include, but are not limited to, Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD-related disorders, prion diseases, motor neuron diseases (MND), Huntington's disease (HD), spinocerebellar ataxia (SCA), spinal muscular atrophy (SMA), traumatic and non-traumatic spinal cord injury, seizure disorders, and neuropsychiatric conditions (e.g., anxiety and depression). Additionally, the systems and methods described herein can be used to induce neuroprotection and to trigger neuroregenerative effects (e.g., for ischemic and hemorrhagic stroke and / or for improving cognitive function). For example, applying PBM to ischemic-damaged brain tissue via a burr hole (BH) or via the CSF space in the acute phase after an ischemic event or in brain tissue that has already suffered a stroke can generate and differentiate new neurons, increase dendritic spine density, foster new neuronal connectivity, and drive neuroplasticity. As another example, to treat chronic, intractable neuropathic pain, PBM can be applied to the thalamus via the CSF space of the third ventricle and to the spinal cord via the anterior and posterior CSF spaces. As another example, to treat movement disorders, PBM can be applied to the deep brain (e.g., the thalamus, subthalamic nucleus, and / or caudate nucleus) via the CSF space of the ventricular system (e.g., the third ventricle and lateral ventricle).

[0089]

[0131] As mentioned above, the CSF space is one of the body cavities and spaces accessible via the methods and systems described herein to treat tissue (e.g., brain tissue). Figures 18A-20 are various schematic diagrams of portions of the human brain, spinal cord, associated CSF spaces, and other related body parts. For example, Figure 18A shows a patient P having a brain B and spinal cord SC. As shown in Figures 18A-20, CSF spaces surround the inner portion of the brain (e.g., filling the ventricles V and central canal CC), the outer portion of the brain B, the brain surface, and the spinal cord SC (e.g., by circulating within the spinal canal). Specifically, CSF spaces surround the brain's convexities, fill fissures (e.g., the Sylvian fissure), include the spinal canal, and include the outer CSF space OCSF, which surrounds the inner brain surface (e.g., filling the basilar cistern, the interventricular cistern IPD, the anterior cerebral cistern PPC, etc.). As shown in Figures 18A, 18B, and 19, the CSF space also includes the internal CSF space (ICSF), which includes the closed ventricular system, a closed CSF space within the brain. The ventricular system includes four ventricles (i.e., two lateral ventricles (LV), the third ventricle (TV), and the fourth ventricle (FV). The third ventricle (TV) is connected to both lateral ventricles (LV) via the interventricular foramina (IVF) (foramen of Monro) and to the fourth ventricle (FV) via the cerebral aqueduct (CA). CSF space continues from the fourth ventricle (FV) into the central canal (CC) within the spinal cord (SC). As shown in Figure 20, the fourth ventricle is connected to the external CSF space (OCSF) (including the spinal canal) and CSF exit sites by the lateral opening (LA) (i.e., the foramen of Luschka, a pair of openings located in the lateral recess of the fourth ventricle) and the central opening (MA) (i.e., the foramen of Magendie).

[0090]

[0132] In some embodiments, the CSF space can be accessed surgically (e.g., via a burr hole or craniectomy). In some embodiments, the CSF space can be accessed minimally invasively (e.g., using a micropuncture kit at the cervical, thoracic, or lumbar level). In some embodiments, an existing access site can be used to access the CSF space. One or more catheters can be guided (e.g., steered on one or more wires) through the access site to a target location (e.g., within the CSF space and / or brain tissue). In some embodiments, the target location can be accessed via the spinal canal. Once at the target location, PBM therapy (e.g., light) can be emitted from one or more catheters toward the target treatment region. For example, an electrical and / or optical delivery device (e.g., a fiber optic device) can be coupled to or inserted through one or more catheters to the target location (i.e., treatment region), and PBM therapy can be delivered from the electrical and / or optical delivery device to a target treatment region (e.g., target tissue) associated with (e.g., aligned with or therapeutically accessible from) the target location. In some embodiments, PBM therapy can be delivered from the distal end of an optical fiber and / or from a miniature LED in an electrical and / or optical delivery device. PBM therapy can be used to stimulate, regenerate, and / or heal brain and / or spinal cord damage and / or prevent further damage, for example, in acute ischemic stroke or traumatic brain injury (TBI) of the brain and spinal cord. PBM therapy can also be used to reduce inflammation and alleviate both acute and chronic neurogenic pain.

[0091]

[0133] In some embodiments, a patient's CSF space can be accessed at any point along the spinal axis for treatment via the CSF space using any of the systems and methods described herein. For example, in some embodiments, the access location can be in the lumbar spine below the back and spinal cord SC. Various exemplary lumbar CSF entry points are designated LEP in FIG. 18A . In some embodiments, the access location to the CSF space can be via a suboccipital approach (designated SEP in FIGS. 18A and 18B ) after fine-gauge needle puncture or at the cervical C1 / C2 level (designated CEP in FIGS. 18A and 18B ) (see, e.g., FIGS. 18A and 19 ). In some embodiments, the CSF space can be directly accessed after creating a burr hole in the patient's head or via craniectomy. Once access to the CSF space is created, in some embodiments, a guide sheath (e.g., a tube) can be temporarily or permanently placed through the access and secured (e.g., aseptically) to the skin. The steerable catheter can then be guided through the guide sheath (e.g., with or without the aid of a guidewire) through an entry point into the CSF space (e.g., anterior to the spinal cord) to a region of interest (i.e., a target location) along the spinal cord SC or the brain surface (e.g., brain convexities, fissures, and / or cisterns) that define the CSF space.

[0092]

[0134] For example, in some embodiments, for treatment via the ventricular system (i.e., the internal CSF space) using the systems and methods described herein, access to the ventricular system can be gained through a burr hole or craniectomy. A guide sheath (e.g., a tube) can be passed through brain tissue into the lateral ventricle LV. In some embodiments, after placement of the sheath as described above, CSF access can be gained by a pathway that travels along the spinal cord SC through the CSF space. A steerable catheter can be guided along or over a guidewire anterior to the spinal cord SC, upwardly through the prepontine cistern PPC and the interpeduncular cistern IPD to the floor of the third ventricle TV. A wire, balloon, mechanical device, and / or laser light can be used to access the third ventricle TV and create a fenestration (also called a window) in the floor of the third ventricle TV (i.e., a ventriculotomy). A catheter, such as one of the catheters of the systems described herein, can then be advanced through the fenestration. In some embodiments, the catheter can be navigated to the target location (e.g., to and through the fenestration) using fluoroscopy and a roadmap generated after dye injection into the CSF space. In some embodiments, the catheter can be navigated to a target location using a segmentation process based on MRI and / or CT images. For example, the catheter can be navigated to a target location (e.g., an area or region) within the ventricular system and adjacent to various deep nuclei involved in neurodegenerative disorders, such as the caudate nucleus, thalamus, and subthalamic nucleus. In some embodiments, once the third ventricle TV is accessed and the steerable catheter is positioned at a target location within the CSF space or advanced into brain tissue, light can be emitted from the catheter to therapeutically treat the target tissue by any of the methods described herein. For example, a fiber optic element can be advanced and / or activated relative to the catheter (e.g., coaxially through a lumen or channel of the catheter) to deliver low-level laser therapy (LLLT) to the target tissue.

[0093]

[0135] In some embodiments, the ventricular system can be accessed by the CSF space posterior to the spinal cord SC via the foramen of Magendi MA or the foramen of Luschka LA to the fourth ventricle FV (see, e.g., dashed lines in Figure 19). The third ventricle TV and the lateral ventricle LV can be accessed directly from the fourth ventricle FV via the cerebral aqueduct CA (i.e., the aqueduct of Sylvius) and the foramen of Monro IVF, respectively.

[0094]

[0136] In some embodiments, the systems and methods described herein can be used to treat patients with chronic subdural hematoma (cSDH). As described above, the pathophysiology involved in cSDH appears to result from initial damage to the dural border cell layer on the inner surface of the dura mater, which ruptures, resulting in the leakage of cerebrospinal fluid and blood into the space between the ruptured cell layer and the remainder of the dura mater. The damaged cells activate inflammatory mediators, including interleukins and other cytokines, and recruit inflammatory cells. This cascade triggers the release of angiogenic growth factors, including vascular endothelial growth factor, cyclooxygenase-2, transforming growth factor-β1, and platelet-derived growth factor, which have been found to be highly concentrated in this fluid. Further inflammatory cells are recruited into the cavity, causing ongoing cellular injury and further stimulating inflammatory cells and angiogenic factors. As mentioned above, the initial damage to the dural border cell layer in some patients cannot be repaired, thus stimulating a cycle of hyperfibrinolysis, inflammation, angiogenesis, and the resulting development of subdural neoplasia.

[0095]

[0137] In some embodiments, PBM can be applied to address this issue related to cSDH using different biological pathways. For example, in some embodiments, the systems and methods described herein can be used to place a light emitter between the inner and outer membranes of the brain, between the neo- and dura mater of the brain, and / or between the dural border cell layer and the remainder of the dura mater (e.g., within the cSDH cavity) and to emit light into the cSDH cavity and / or adjacent tissue regions to treat patients with cSDH. In some embodiments, low-level laser light therapy can be delivered directly into the cSDH cavity, and the photons can dissociate inhibitory nitric oxide from enzymes, resulting in increases in electron transport, mitochondrial membrane potential, and ATP production. In some embodiments, light-gated ion channels can be activated, allowing calcium to enter the cell. Following the initial photon absorption event, reactive oxygen species, cyclic AMP, NO, and Ca2+ can activate numerous signaling pathways, leading to the activation of transcription factors. These transcription factors can increase the expression of genes involved in protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, and antioxidant enzymes. Stem and progenitor cells appear to be particularly susceptible to PBM. In some embodiments, these cellular pathways in the lumen wall and intraluminal fluid can be activated to initiate the recruitment of distant cellular elements to repair (e.g., seal) the lumen. In some embodiments, an optical cable (e.g., as shown in FIG. 4A or FIG. 14) can be used to occlude the MMA through the interaction of light energy with cellular elements in the vessel wall. In some embodiments, such as that shown in FIG. 30, electrical conduits embedded in the optical cable can be used to inflict mild thermal damage to the vessel wall (e.g., without detaching a spacing element, such as spacing element 1150), after which low-level light therapy can optionally be applied to stimulate the patient's repair pathways and induce a damage-repair response.

[0096]

[0138] In some embodiments, a system such as any of the systems described herein can include a catheter device that can include an elongated tubular body and / or optical cable with a distal end, a proximal end, and an optical emitter configured to emit light disposed at the distal end (e.g., of the optical cable). The optical cable can include one or more optical fibers configured to deliver, for example, laser light, and / or one or more electrical wires coupled to light-emitting diodes (LEDs) and / or photodetectors. A spacing member can be disposed at or near the distal end of the optical cable and can be reconfigured from a collapsed configuration to an expanded configuration. In the expanded configuration, the spacing member can be disposed around the optical emitter to maintain the optical emitter approximately centered within the spacing member relative to at least one axis of the spacing member. The spacing member can be at least partially transparent and / or semi-transparent to light emitted from the optical emitter. The catheter device can be configured so that the distal end of the catheter body can be at least partially inserted into a body cavity or lumen having an interior wall, the spacing member can be transitioned to an expanded configuration within the body cavity or lumen (e.g., in contact with the interior wall but without applying sufficient pressure to the interior wall to widen the body cavity or lumen), and light can be emitted from the light emitter to illuminate the interior wall of the body cavity or lumen. In some embodiments, the light emitter can be or have a distal end configured to transmit light in a lateral or sideways trajectory rather than axially along the cable, so that the light emitter can illuminate an area of ​​the interior wall on only one side of the light emitter and / or catheter (e.g., a small arcuate portion relative to the light emitter) rather than illuminating an area around the entire circumference of the light emitter and / or catheter.

[0097]

[0139] In some embodiments, the method includes positioning a distal end of a catheter within a body lumen (also called a passageway) or cavity (e.g., a blood vessel, airway, urinary tract, CSF tract, or other body cavity) of a subject adjacent to a region of the wall of a blood vessel or cavity to be treated. For example, the distal end of the catheter can be positioned within any of the body lumens or cavities described herein using any of the access procedures described herein. The distal end of the catheter can be positioned at the center or proximal end of the target treatment region or area. The catheter can include (e.g., positioned at its distal end) a light emitter configured to emit light, optionally a fluid conduit outlet coupled to a fluid source, optionally a fluid conduit inlet coupled to a fluid sink, and optionally a spacing member reconfigurable from a collapsed configuration to an expanded configuration. The spacing member can be at least partially transparent and / or semi-transparent to the light emitted from the light emitter and porous to the fluid discharged from the fluid outlet. The spacing member can be transitioned to the expanded configuration when positioned at the treatment location. A spacing element can be disposed around the light emitter to maintain the light emitter approximately centered within the spacing element relative to at least one axis of the spacing element when in the expanded configuration. The method can further include disposing the spacing element approximately centered within the vascular or body cavity and / or disposing the light emitter at a predetermined distance from the target tissue based on the diameter of the spacing element in the expanded configuration. In some embodiments, fluid can be ejected into the blood vessel or body cavity through an outlet of the fluid conduit to cool the light emitter. In some embodiments, such as when blood is disposed within the target treatment region or area (e.g., a blood vessel or body cavity), fluid can be ejected into the blood vessel of the body cavity through an outlet of the fluid conduit to dilute the blood with the fluid and establish a translucent or transparent region of light (also referred to as an optical field). In some embodiments, such as when the body fluid within the body cavity is transparent (e.g., CSF fluid), fluid can be ejected from the body cavity through a fluid sink (e.g., proportional to any fluid added through the fluid conduit to maintain the pressure in the body cavity within a threshold range). Light can be emitted from the light emitter through diluted blood (e.g., in a blood vessel lumen) or through an optically transparent fluid (e.g., in a body cavity) to the target tissue (e.g., the region of the wall to be treated).

[0098]

[0140] In some embodiments, as shown generally in FIG. 21 , treatment system 900 can include catheter 910, which can be operably coupled to other devices or systems, including a light source LS, a fluid source FS, a fluid sink FK, and / or an image display ID, and can be used in combination with other devices, such as a mesh tube MT, a helical coil, an occlusion device OD, and an introducer (not shown in FIG. 21 ), and with compositions, such as a photochemical agent PA. Treatment system 900 and its components can be identical or similar in structure and / or function to any of the treatment systems described herein, such as treatment system 100. For example, catheter 910 can be identical or similar in structure and / or function to any of the catheters described herein, such as catheter 110.

[0099]

[0141] The catheter 910 can have an elongated catheter body 920 having a proximal end and a distal end suitable for insertion into a body lumen BL or a body cavity BC. The body lumen BL or a body cavity BC can include, for example, a blood vessel, a synovial joint, or a CSF-filled space near (e.g., adjacent to) or including a treatment region TR of the body lumen BL or a body cavity BC. In some embodiments, as described above, the body lumen BL or a body cavity BC and / or treatment region TR can include a cSDH cavity. The catheter body 920 can define and be movable through an internal working channel 924 through which other components of the catheter 910 can be disposed. Thus, in some embodiments, the catheter body 920 can be inserted into a patient's body until the distal end is positioned adjacent to the treatment region TR. In some embodiments, the distal end of the catheter body 920 can be translated into a patient's body cavity BC (e.g., a CSF-filled cavity) using any of the access locations and access procedures described herein (e.g., described with respect to FIGS. 18A-20 ). For example, in some embodiments, the catheter body 920 can be delivered over a guidewire through the patient's vasculature. The guidewire can be removed, and one or more other components of the catheter 910 can be delivered through the working channel 924 until their distal ends are positioned within the treatment region TR in appropriate operative relationship with the distal end of the catheter body 920 and the target tissue. In other embodiments, some or all of the other components of the catheter 910 can be disposed within and / or coupled to the catheter body 920 after the catheter 910 has been inserted into the patient's body and before its distal end is delivered to the treatment region TR.

[0100]

[0142] The catheter 910 includes a light emitter 930, which is disposed at the distal end of the catheter body 920 when the catheter 910 is configured for use. In some embodiments, the light emitter 930 can be translated to a location distal to the distal end of the catheter body 920 (e.g., via the working channel 924 before or after the distal end of the catheter body 920 is positioned within the target region TR). In some embodiments, the light emitter 930 can be coupled to the distal end of the catheter body 920 before the distal end of the catheter body 920 is positioned within the target region TR. The light emitter 930 can be optically coupled to the light source LS by a light conduit 932, which can be disposed within the catheter body 920 (e.g., within the working channel 924) and can extend from the proximal end to the distal end of the catheter body 920. The light conduit 932 can include, for example, one or more optical and / or electrical cables.

[0101]

[0143] The catheter 910 optionally includes a first fluid conduit 940 disposed within the catheter body 920 and extending from a first inlet 944 at the proximal end of the catheter body 920 to a first outlet 942 at the distal end of the catheter body 920. The first fluid conduit 940 may be coupled to a fluid source FS via the first inlet 944. In some embodiments, the first fluid conduit 940 is defined by the catheter body 920. In some embodiments, the first fluid conduit 940 may be formed as a tube configured to be inserted through a lumen defined by the catheter body 920, such as the working channel 924. In addition to the first fluid conduit 940, the catheter 910 may optionally include a second fluid conduit 941. The second fluid conduit may be disposed within the catheter body 920 and extending from a second inlet 943 at the distal end of the catheter body 920 to a second outlet 945 at the proximal end of the catheter body 920. The second fluid conduit 941 can be coupled to a fluid sink FK via a second outlet 945. Thus, fluid can be supplied from a fluid source FS to a distal region of the catheter 910 via the first fluid conduit 940 and withdrawn from the distal region of the catheter 910 via the second fluid conduit 941 into the fluid sink FK. Thus, optionally, pressure within the treatment region TR (e.g., within the body cavity BC) can be maintained within a certain range (e.g., a safety range) by at least one of supplying and withdrawing fluid from the treatment region TR. The pressure can be maintained to maintain an equilibrium pressure in the treatment region TR (e.g., maintain a natural pressure in the treatment region TR) during the treatment process. When fluid is introduced (e.g., injected) into the treatment region TR from the fluid source FS, for example, to cool the light emitter 930 and / or to dilute the fluid in the treatment region TR (e.g., if the treatment region TR contains blood) to establish a translucent or transparent light region (also referred to as an optical field), fluid can be removed from the treatment region TR (e.g., proportional to any fluid added via the first fluid conduit 940) via the fluid sink to maintain the pressure in the treatment region TR within an equilibrium pressure or threshold range or at the equilibrium pressure of the treatment region TR.

[0102]

[0144] The catheter 910 may also include a spacing member 950 disposed at the distal end of the catheter body 920. The spacing member 950 may be identical or similar in structure and / or function to any of the spacing members described herein. The spacing member 950 may be actuated from an initial configuration to an expanded configuration, in which the spacing member 950 has a larger diameter and / or lateral extent than the initial configuration. The initial configuration may be, for example, a collapsed and / or uninflated configuration. When in the expanded configuration, the spacing member 950 may be configured to center the light emitters 930 relative to at least one axis of the spacing member 950 (e.g., relative to one, two, or three axes of the spacing member 950), center the light emitters 930 relative to opposing walls defining a cavity or passageway of the treatment region TR, and / or maintain the light emitters 930 at a predetermined distance from the target tissue of the treatment region TR (e.g., a predetermined distance from a target portion of the wall). In some embodiments, the spacing member 950 can be formed of a porous material, such as a mesh or a porous balloon, to allow fluid to flow into and out of the spacing member 950. In some embodiments, the spacing member 950 can be formed of a non-porous balloon. In some embodiments, the spacing member 950 can be sufficiently non-porous so that when the spacing member 950 is in an expanded configuration and in contact with the wall defining the treatment region TR, the spacing member 950 can prevent or impede the flow of fluid beyond the spacing member. In some embodiments, the spacing member 950 is sufficiently porous or defines sufficiently large openings so that at least some fluid can flow through the spacing member 950 (e.g., blood or CSF), while some flow and / or particles above a certain size are prevented from flowing through or past the spacing member 950.

[0103]

[0145] In some embodiments, the spacing member 950 can be coupled to the distal end of the catheter body 920 and configured to be actuated (e.g., inflated from an initial configuration to an expanded configuration) by fluid supplied through the first fluid conduit 940. In some embodiments, the spacing member 950 can be coupled to or integrally formed with another component of the catheter 910. For example, the spacing member 950 can be formed with and coupled to an inner body (e.g., inner body 148 described with respect to FIG. 5A ) that can function as a spacing member actuator 952 (e.g., a spacing member actuator that can be the same or similar in structure and / or function as spacing member actuator 152) disposed within the catheter body 920. The spacing member actuator 952 can be translated relative to the catheter body 920 (e.g., extended from the proximal end to the distal end of the catheter body 920 and moved distally) to transition the spacing member 950 between the collapsed configuration and the expanded configuration (e.g., by transitioning from a constrained state disposed in the catheter body 920 and a region distal to the catheter body 920 such that the spacing member 950 can expand into the expanded configuration to which the spacing member 950 can be biased).

[0104]

[0146] In some embodiments, the catheter 910 may also optionally include an imager 960 coupled to the distal end of the catheter body 920. The imager 960 may be disposed within the catheter body 920 and optically coupled to an image display ID by an imaging conduit 962, which may extend from the proximal end to the distal end of the catheter body 920.

[0105]

[0147] Each component of the treatment system 900 can be implemented in a variety of ways. For example, in applications where the catheter 910 is used for intravascular access to a treatment region TR of a body lumen BL, the catheter 910 can be implemented as a conventional intravascular catheter, including its structure and materials, the ability to steer or not steer or bend its distal end, and the ability to be deliverable over a guidewire or not, and can include user controls and accessories at its proximal end. In some embodiments, a guidewire (not shown) can be positioned within the working channel 924 of the catheter body 920. In other embodiments, for example, where the catheter body 920 may be relatively large, the catheter body 920 can include a dedicated guidewire lumen separate from the working channel 924. In some embodiments, the proximal portion of the catheter body 920 can be stiffer than the distal portion to provide sufficient rigidity for a user to push the catheter body 920 over a guidewire and through a lumen, e.g., the vasculature. A more flexible distal portion can facilitate navigating the catheter body 920 through, for example, a tortuous vasculature. The catheter body 920 can be introduced into a body lumen BL, such as a blood vessel, via an incision or other percutaneous technique to access the vascular cavity. In some applications, the catheter 910 may be used to directly access the treatment region TR rather than through the subject's vascular system and may be implemented accordingly. For example, if the catheter 910 is used to directly access the treatment region TR through soft tissue, the catheter 910 may be implemented as a relatively stiff needle inserted through a trocar. In some embodiments, the catheter 910 can be used to access a body cavity BC, such as a CSF space (i.e., a space containing CSF) or a synovial joint space, via any of the access locations and methods described herein. For example, the catheter 910 can be used to access a body cavity BC surgically (e.g., via a burr hole or craniectomy), via a minimally invasive technique such as using a micropuncture kit at the cervical, thoracic, or lumbar level, or using an existing access site.

[0106]

[0148] As described above with respect to light emitter 130, light emitter 930 may be implemented in any known suitable structure for emitting light of a desired wavelength and intensity from the distal end of catheter 910 to a treatment region TR in body lumen BL or BC. For example, in some embodiments, light emitter 930 may simply be the end of an optical fiber, which may serve as an optical conduit 932 for transmitting light from a light source LS that can be coupled to the proximal end of catheter 910. Light source LS may be any suitable light source of a desired wavelength and intensity, and may be a source of coherent light, such as a laser (pulsed or continuous wave), or a source of incoherent light (such as xenon or halogen light and appropriate bandpass filters). In other embodiments, light emitter 930 may be a relatively compact light source, such as a light-emitting diode (LED) or laser diode, located at the distal end of catheter 910, with power provided by electrical leads extending from the proximal end of catheter 910 through catheter body 920 to the light source. In an alternative embodiment, an LED or laser diode can be positioned at the proximal end of the catheter 910 (e.g., configured as a light source LS) and light can be transmitted to the treatment region TR through the light conduit 932 (e.g., reflected by a light emitter 930 positioned at the distal end of the light conduit 932).

[0107]

[0149] To generate a desired distribution of light in the treatment region TR (i.e., a distribution different from that generated by the combination of light source LS and / or light emitter 930), in some embodiments, a light scatterer 936 is operatively associated with light source LS to scatter light from light source LS across the treatment region TR. Light scatterer 936 may be identical or similar in structure and / or function to light scatterers described herein, such as light scatterer 136. For example, as shown schematically with respect to light scatterer 1036 in FIG. 22A , in some implementations, light scatterer 936 may be implemented as a convex end cap on the distal tip of light conduit 932, which may be formed, for example, as an optical fiber. The end cap may include light scattering particles, as illustrated, for example, as circular region 1038 of light scatterer 1036 in FIG. 22B . Such particles may be, for example, titanium dioxide. Other light scattering materials (e.g., materials with a high refractive index of −2.5) or refractive structures, such as diffraction gratings, may also be used.

[0108]

[0150] During use, the distal end of the catheter 910 can be positioned within a body cavity BC or body lumen BL of a subject near (e.g., adjacent to) or within a treatment region TR (e.g., including a target tissue to be treated). The distal end of the catheter 910 can be positioned within the body cavity BC or body lumen BL by any of the access locations, procedures, or devices (e.g., catheters) described herein, such as with respect to Figures 18A-20, and the body cavity BC or body lumen BL can include any of the body cavities or body lumens described herein. The target tissue to be treated can be, for example, any of the target tissues described herein.

[0109]

[0151] The spacing member 950 can be transitioned from an initial configuration to an expanded configuration. For example, the spacing member 950 can be transitioned to the expanded configuration such that the spacing member 950 stabilizes and maintains the light emitter 930 at a particular distance (e.g., a predetermined distance) relative to the target tissue. The spacing member 950 can maintain the light emitter 930 centered within the body lumen BL or between opposing walls defining the body lumen BC.

[0110]

[0152] Optionally, a cooling fluid can be supplied through the catheter body 920 (e.g., via the first fluid conduit 940 or the working channel 924) to cool the light emitter 930. Optionally, a dilution fluid can be supplied through the catheter body 920 (e.g., via the first fluid conduit 940 or the working channel 924) to dilute the fluid in the body cavity BC or body lumen BL to improve transmission of light through the fluid to the target tissue. Optionally, the pressure in the body cavity BC or body lumen BL (e.g., an equilibrium pressure) can be maintained within a certain pressure range by at least one of supplying fluid to the body cavity (e.g., via the first fluid conduit 940) and / or removing fluid from the body cavity (e.g., via the second fluid conduit 941).

[0111]

[0153] The light emitter 930 can be activated to emit light asymmetrically and at a non-zero angle relative to the central axis of the catheter body 920 onto the target tissue. The light emitter 930 can continue to emit light until a therapeutic response or benefit is achieved. In some embodiments, the light emitter 930 can be or have a distal end configured to deliver light in a lateral or sideways trajectory or evenly around the circumference of the light emitter 930, rather than or in addition to an axial direction relative to the light emitter 930 or catheter body 920. The light emitter 930 can illuminate an area of ​​the interior wall on only one side of the light emitter 930 and / or catheter body 920 (e.g., a small arc portion relative to the light emitter 930), rather than illuminating an area around the entire circumference of the light emitter 930 and / or catheter 910, or an area completely distal and axially aligned with the light emitter 930. For example, the light emitter 930 can be configured to emit a laterally directed beam to illuminate a flush area of ​​the interior wall having a length (e.g., arc length) that is less than 5%, 10%, 15%, 20%, 30%, 40%, or 50% of the circumference of the passageway or cavity that the light emitter 930 is placed in. Such an asymmetric, laterally emitted light distribution may better correlate to the shape of the treatment region TR forming the body cavity BC (e.g., the surface of the brain) or the target tissue within the treatment region TR.

[0112]

[0154] In some embodiments, as described above, a system, such as any of the systems described herein, can be configured to emit light (e.g., therapeutic light) laterally and / or asymmetrically relative to a centerline of a catheter or optical conduit such that the system can be used to apply targeted therapeutic light therapy to a treatment region and avoid non-treatment regions (e.g., regions adjacent to the treatment region or target tissue). In some embodiments, as described herein, a system, such as any of the systems described herein, can be configured to emit light (e.g., in the form of a light beam) laterally and / or asymmetrically to target a treatment region (e.g., a primary target treatment region) and to emit light having a second intensity less than the first intensity to a non-target treatment region (e.g., a secondary target treatment region) or not to emit light to a non-target treatment region that may be adjacent to the target treatment region. For example, FIG. 22A is a schematic diagram of a portion of system 1000. System 1000 can be identical or similar in structure and / or function to any of the systems described herein, such as system 900. As shown in FIG. 22A , the system 1000 includes a light conduit 1032 having a distal end forming a light emitter 1030 disposed within a light scatterer 1036 formed as a convex end cap. In some embodiments, the light scatterer 1036 can have a tubular portion and a dome-shaped distal end coupled to the distal end of the tubular portion. The light emitter 1030 can be disposed within the tubular portion and / or the dome-shaped distal end. The light conduit 1032 can be disposed within a working channel of a catheter body 1020, which can be the same as or similar to any of the catheter bodies described herein. In some embodiments, the light conduit 1032 can be included within an inner body, such as any of the inner bodies described herein (e.g., inner body 148 described above), and / or the light emitter 1030 can be mounted on the distal end of such an inner body. Thus, the light conduit 1032 and / or light emitter 1030 may be translatable relative to the catheter body (e.g., beyond the distal end of the catheter body of the system 1000). In some embodiments, the light scatterer 1036 may form an end cap of the inner body, the catheter body 1020, or a portion of the catheter body 1020.As shown in FIG. 22A, the light scatterer 1036 may be coupled to a flexible coil 1049 configured to provide stability to the distal end of the inner body or catheter body 1020, particularly at the interface between the light scatterer 1036 and the catheter body 1020 or inner body.

[0113]

[0155] In some embodiments, rather than including a light scatterer 1036, system 1000 may include a convex end cap having the same overall shape and size as the light scatterers described herein, within which light emitter 1030 may be disposed in a similar manner as described herein with respect to light scatterers, thereby allowing light to be emitted from light emitter 1030 to the target tissue and / or non-target or secondary target tissue regions. For example, such a convex end cap may function to protect light emitter 1030 (e.g., to isolate the light emitter from regions distal to the light emitter), and may optionally not have any light diffusing characteristics or functionality.

[0114]

[0156] 22A , the distal tip of the light conduit 1032 (e.g., the portion forming the light emitter 1030) may be formed as an angled tip. For example, the distal end of the light conduit 1032 may be cut at an angle relative to a central axis A of the light conduit 1032. The light conduit 1032 may be formed as a solid, elongated member such that the angled cut at the distal end causes light traveling from the proximal end of the light conduit 1032 to reflect off the angled distal end of the light conduit 1032 and travel transversely to (e.g., at a non-zero angle relative to) the central axis A, through a portion of the sidewall of the light conduit 1032, in the direction of arrow B, through the light scatterer 1036, and into the treatment region TR. In some embodiments, the angle Z (i.e., the angle of light incidence) between the normal to the distal surface of the light conduit 1032 and / or the optical contact surface at the distal end of the light conduit 1032 and the central axis A (e.g., the acute angle between the central axis A and the normal to the distal surface of the light conduit 1032 as shown in FIG. 22A ) is sufficiently large (e.g., greater than or equal to the critical angle required for total internal reflection) so that all of the light traveling through the light conduit 1032 is reflected from the distal surface and emitted (e.g., in the direction of arrow B) through the portion of the sidewall of the light conduit 1032 facing the distal surface (i.e., facing the proximal side of the distal surface). In some embodiments, the angle Z between the normal to the distal surface of the light conduit 1032 and / or the optical contact surface at the distal end of the light conduit 1032 and the central axis A is small (e.g., less than the critical angle required for total internal reflection). If angle Z is less than the critical angle, a portion of the light traveling through the light conduit 1032 may be emitted distally of the light emitter 1030 (i.e., refracted along the central axis A and / or in a direction extending between the central axis A and the distal surface of the light conduit 1032), and a portion of the light traveling through the light conduit 1032 may be emitted laterally from the light emitter 1030 (e.g., reflected through a sidewall of the light conduit 1032). The light emitted laterally from the light emitter 1030 (e.g., a first portion of the light emitted from the light emitter and received through the light conduit 1032) may have a higher intensity than the light emitted distally (e.g., axially) from the light emitter (e.g., a second portion of the light emitted from the light emitter and received through the light conduit 1032).22E illustrates an embodiment of system 1000 in which light may be dispersed both axially and laterally, with light emitted in the direction of arrow B having a higher intensity than light emitted axially along central axis A and / or light emitted circumferentially or laterally in directions other than the direction of arrow B. In some embodiments, both a first portion and a second portion of light emitted from light emitter 1030 may travel through light scatterer 1036, with the first portion being directed by a first portion of light scatterer 1036 (e.g., a sidewall portion, such as a sidewall of a tubular portion) and the second portion being directed by a second portion (e.g., a distal end portion, such as a dome-shaped distal portion). In some embodiments, the angle of the distal surface of light conduit 1032 and / or the light-contacting surface of the distal end of light conduit 1032 may be formed at or within a critical angle such that light rays passing through light conduit 1032 and reaching the distal end of light conduit 1032 are totally internally reflected and not refracted. For example, in some embodiments, the angle of the distal surface of the light conduit 1032 and / or the light contact surface at the distal end of the light conduit 1032 may be formed at or within a critical angle such that all light rays passing through the light conduit 1032 and reaching the distal end of the light conduit 1032 are reflected along the distal surface. The critical angle is determined by the formula CA=sin. -1 The angle Z between the normal to the distal surface of the optical conduit 1032 and the central axis A can be calculated using the numerical aperture (NA) based on the numerical aperture of the fiber used as the optical fiber of the optical conduit 1032, where CA represents the critical angle and NA represents the numerical aperture. The numerical aperture can be, for example, from 0.1 to 0.5. Thus, in some embodiments, the angle Z between the normal to the distal surface of the optical conduit 1032 and the central axis A can range from about 5.74 degrees to about 30 degrees.

[0115]

[0157] In some embodiments, as mentioned above, the system 1000 can be configured to emit a light beam to apply therapeutic light to a target tissue region while simultaneously dispersing light to secondary tissue regions. Thus, such a system 1000 can provide the combined effect of non-uniform light scattering, which can be more diffuse in peripheral or outer regions of the target treatment region and relatively more focused or intense in a primary (e.g., central) portion of the target treatment region. For example, the light emitter 1030 can emit a first portion of light received via the light conduit 1032 laterally and / or asymmetrically (e.g., in a beam) so that the light is received at the primary target tissue region at a first intensity (e.g., so that the light received at the primary target tissue region has a first power density). The light emitter 1030 can simultaneously emit a second portion of light received via the light conduit 1032 to be received by the secondary target tissue region at a second intensity that is less than the first intensity (e.g., such that the light received at the secondary target tissue region has a second power density that is less than the first power density). The second portion of light emitted from the light emitter 1030 can, for example, travel distally from the light emitter 1030 to interact with (e.g., pass through) one or more light scatterers (e.g., light scatterer 1036) and be scattered by such light scatterers. In some embodiments, the second portion of light scattered by the light scatterer 1036 can be spherically dispersed relative to the light scatterer and / or light emitter 1030 such that the light scatterer and / or light emitter 1030 are surrounded by the secondary target tissue region that receives the second portion of the scattered light. In some embodiments, the secondary target tissue region can include portions of tissue distal and / or proximal to the primary target tissue region, as well as portions of tissue on either side of the primary target tissue region between the proximal and distal ends of the target tissue region (e.g., the secondary target tissue region can optionally surround the periphery of the primary target tissue region). In some embodiments, the secondary target tissue region can include and / or surround the primary target tissue region such that the primary target tissue region also receives a portion of the second portion of light.In some embodiments, system 1000 can include any suitable components described with respect to FIG. 3A and any suitable components described with respect to FIG. 22E , for example, to enable spherical dispersion of light by a diffuser (e.g., light scatterer 136 described with respect to FIG. 3A ) and to enable laterally directed light (e.g., in a beam) by a distal surface of light conduit 1032 (as described with respect to FIG. 22E ). In some embodiments, as shown in FIG. 22B , light emitter 1030 can optionally include a reflective surface portion 1033 disposed at the distal end of light conduit 1032 (e.g., disposed on the angled distal surface of light conduit 1032). Reflective surface portion 1033 can be configured such that all light traveling to the distal end of light conduit 1032 is directed through a sidewall of light conduit 1032 in the direction of arrow B. Reflective surface portion 1033 can be configured to prevent or obstruct light from traveling through the distal end of light conduit 1032. The reflective surface portion 1033 can be, for example, a reflective prism surface. In such embodiments, the light conduit 1032 can be solid or can define a central lumen. Additionally, as shown in FIG. 22B , the light scatterer 1036 can optionally include particles (e.g., shown as circular regions 1038). Such particles can be, for example, titanium dioxide. Other light-scattering materials (e.g., materials with a high refractive index of -2.5) or refractive structures, such as, for example, diffraction gratings, can also be used.

[0116]

[0158] 22A, the system 1000 can optionally include a radiopaque marker 1039 coupled to the light emitter 1030 to allow a user of the system 1000 to determine the position and orientation of the light emitter 1030 prior to applying light from a light source through the light emitter 1030 (e.g., to apply radiation to a treatment region TR). As shown in FIG. 22C, which is a perspective view of the radiopaque marker 1039, the radiopaque marker 1039 can include a base portion 1039B (e.g., a circular base portion) and a protrusion 1039A protruding from a non-central portion of the base portion 1039B. The base portion 1039B can define a central opening such that the light conduit 1032 can be positioned within the central opening of the base portion 1039B. The base portion 1039B may be coupled to the light emitter 1030 such that the protrusion 1039A rests against a portion of the sidewall of the light conduit 1032 along which light is directed from the distal end of the light conduit 1032 during operation of the system 1000. As shown, the protrusion 1039A may be positioned on the light conduit 1032 opposite a portion of the sidewall along which diverging light (represented as a box 1000B surrounding arrow B) is configured to be directed. Thus, when placed within a patient, a user can visualize the position and orientation of the radiopaque marker 1039 using x-ray visualization and determine the position and orientation of the portion of the sidewall along which light is directed based on the position and orientation of the radiopaque marker 1039 (e.g., based on the orientation of the protrusion 1039A relative to the base portion 1039B). If the user determines, based on the position and orientation of the radiopaque marker 1039, that a portion of the sidewall is not properly aligned with the treatment region TR, the user can manipulate the light emitter 1030 (e.g., by rotating and / or translating a portion of the system 1000, such as the light conduit 1032, the inner member, and / or the catheter body) relative to the treatment region TR. The radiopaque marker 1039 can be visualized and manipulated again as necessary until the portion of the sidewall of the light conduit 1032 is properly aligned with the treatment region TR so that light is directed from the light emitter to the treatment region TR. Light can then be delivered to the treatment region TR through the light conduit.

[0117]

[0159] As shown in FIG. 22B , in some embodiments, the system 1000 can optionally include a radiopaque marker 1039X having two protrusions. As shown in FIG. 22D , which is a perspective view of the radiopaque marker 1039X, the radiopaque marker 1039X can include a base portion 1039B and a protrusion 1039A (also referred to as the first protrusion 1039A), as shown and described above with respect to the radiopaque marker 1039 shown in FIG. 22C . In addition, the radiopaque marker 1039X can include an additional protrusion 1039C protruding from an opposite side of the base portion 1039B from the first protrusion 1039A. The second protrusion 1039C can thus be located on or adjacent to the same portion or side of the light conduit 1032 configured to direct divergent light (represented as the box 1000B surrounding the arrow B). 22D , the first protrusion 1039A and the second protrusion 1039C can have different lengths (e.g., the second protrusion 1039C can be shorter than the first protrusion 1039A). Thus, when placed within a patient, a user can use x-ray visualization to visualize the position and orientation of the radiopaque marker 1039X and determine the position and orientation of the portion of the sidewall through which light is directed based on the position and orientation of the radiopaque marker 1039X (e.g., based on the orientation of the first protrusion 1039A relative to the second protrusion 1039C and / or relative to the base portion 1039B). The inclusion of the second protrusion 1039C may allow a user to more precisely direct the output light beam from the light conduit 1032, as compared to the radiopaque marker 1039.For example, a user can rotate the optical conduit 1032 and radiopaque marker 1039 (which may be rigidly coupled) until the first protrusion 1039A overlaps the second protrusion 1039C (e.g., completely overlapping under x-ray visualization when viewing the target area TR from a position aligned orthogonal to a plane that includes the target area TR), which overlap indicates that a portion of the sidewall of the optical conduit 1032 through which light is directed is aligned with or adjacent to the target area TR, and that the system 1000 is oriented to direct light onto the target area TR (e.g., along the beam path in the direction of arrow B in FIG. 22B and represented as box 1000B). Although the systems are described and / or illustrated herein as including radiopaque marker 1039 or radiopaque marker 1039X, any of the systems described herein may include one or the other.

[0118]

[0160] 22E, which is a schematic illustration of a side view of a portion of the system 1000 and a cross-sectional view of the optical conduit 1032, in some embodiments, the optical conduit 1032 can include a set of imaging conduits (e.g., optical fibers) 1062. For example, the optical conduit 1032 can include or be coupled to four imaging conduits 1062. The imaging conduits 1062 can allow light and / or images from the treatment region TR to travel via the imaging conduit 1062 to an image display coupled to the proximal end of the optical conduit 1032, such as an image display ID, so that a user can use the optical conduit 1032 to observe the treatment region TR.

[0119]

[0161] As shown in FIG. 22F, which is a schematic illustration of a side view of a portion of the system 1000 and a cross-section of the light conduit 1032, in some embodiments, the system 1000 can include an end cap 1034 coupled to the distal end of the light conduit 1032 and configured to help direct all light emitted from the light emitter 1030 radially relative to the central axis A of the light conduit 1032. In some embodiments, as shown in FIG. 22F, the end cap 1034 can have a diameter large enough to cover at least the lumen defined by the light conduit 1032 while maintaining an unobstructed optical path for the imaging conduit 1062. In some embodiments, the end cap 1034 can be opaque. In some embodiments, the end cap 1034 can be configured to reflect light through a sidewall of the light conduit 1032 (e.g., in the direction of arrow B). In some embodiments, the end cap 1034 can include a reflective surface (e.g., a reflective prismatic surface) configured to reflect light through the sidewall.

[0120]

[0162] Although the system 1000 is shown as including a light conduit 1032, in some embodiments the light emitter 1030 may include a light emitter, such as an LED or laser diode, disposed at the distal end of the catheter body 120 and configured to reflect off a reflector, such as an end cap 1034 or a reflective surface portion 1033, and emit light that travels transverse to the central axis of the light emitter and / or catheter body 1020.

[0121]

[0163] FIG. 23A is a schematic diagram of a cross section of a portion of system 1100. System 1100 may be identical or similar in structure and / or function to any of the systems described herein. For example, system 1100 may include a catheter 1110 including a catheter body 1120. Catheter body 1120 defines a working channel 1124. System 1100 also includes an inner body 1148 within which an optical conduit 1132 may be disposed. The optical conduit 1132 may extend to or beyond the proximal end of the inner body 1148. A flexible coil 1149 may be included within or disposed within the inner body 1148, which may be identical or similar in structure and / or function to any of the coils described herein. The distal end of inner body 1148 forms a light emitter 1130. A light scatterer 1136 may be disposed over the light emitter 1130. As shown, the light scatterer 1136 can optionally include a light scattering portion 1138 (e.g., including light scattering particles). The system 1100 can optionally include a radiopaque marker 1139 coupled to the light emitter 1130 (e.g., disposed between the light emitter 1130 and a portion of the inner body 1148 proximal to the light emitter 1130) to enable a user of the system 1100 to determine the position and / or orientation of the light emitter 1130. The radiopaque marker 1139 can be any suitable shape or size (e.g., can have a tubular shape and can define one or more openings through which the light conduit 1132 and / or fluid can pass). In some embodiments, the radiopaque marker 1139 can be the same or similar in structure and / or function as the radiopaque marker 1039 described above.

[0122]

[0164] System 1100 includes a spacing member 1150, which can be the same or similar in structure and / or function to any of the spacing members described herein, such as spacing member 150. Spacing member 1150 can be coupled to inner body 1148 and / or light scatterer 1136. For example, in some embodiments, spacing member 1150 can include a neck portion coupled to an outer surface of inner body 1148 along any suitable length of inner body 1148 (e.g., a portion including the radiopaque marker and / or a portion proximal to the radiopaque marker and light emitter 1130, such as a portion having a length of about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or more centimeters proximal to light emitter 1130). In some embodiments, the spacing member 1150 may be coupled to only a portion of the inner body 1148 that includes the radiopaque marker. The spacing member 1150 may be configured to expand between an initial configuration and an expanded configuration (shown in FIG. 23A ). In the expanded configuration, the spacing member 1150 may have a sufficient diameter or lateral extent to allow the spacing member 1150 to contact the opposing body structure (e.g., a lumen or cavity wall). In some embodiments, the spacing member 1150 may be configured to maintain the light emitter 1130 at a particular distance from the target tissue and / or centered between the opposing body structures. Thus, the energy density of the light (i.e., energy per unit area of ​​the cavity or vessel wall) on the target tissue may be controlled to be relatively uniform (i.e., maintained within a range of energy density values ​​high enough to be therapeutically effective and low enough not to damage the cavity or vessel wall). In some embodiments, in the expanded configuration as shown in Figure 23A, the spacing member 1150 can be shaped to define a pocket in which the light emitter 1130 can be at least partially disposed and / or from which the light emitter 1130 can protrude. In some embodiments, the spacing member 1150 can have a larger diameter at its distal end than at its proximal end in the expanded configuration.In some embodiments, the spacing member 1150 can have outer and inner surfaces that taper from a larger diameter at the distal end to a smaller diameter at the proximal end in the expanded configuration, hi some embodiments, the spacing member 1150 can be cone-shaped, cup-shaped, basket-shaped, plunger-shaped, or any other suitable shape in the expanded configuration.

[0123]

[0165] For example, the spacing member 1150 can be biased to the expanded configuration but held in an initial configuration within the working channel 1124 of the catheter body 1120. To transition the spacing member 1150 from the initial configuration to the expanded configuration, the inner body 1148 can be translated distally relative to the catheter body 1120 so that the spacing member 1150 is disposed distally of the distal end of the catheter body 1120 and is unconstrained to expand to the expanded configuration. In some embodiments, the spacing member 1150 can be configured to center the light emitter 1130 (e.g., the tip of the optical fiber forming the light conduit 1132) within a body lumen or cavity in the expanded configuration. In some embodiments, the spacing member 1150 can be configured to expand within a body lumen or cavity to a shape and size such that the spacing member 1150 contacts the wall of the body lumen or cavity to keep the light emitter 1130 a predetermined distance from the wall (e.g., center it within the body lumen or cavity), but does not force the wall away from the light emitter 1130 such that the dimensions (e.g., diameter) of the body lumen or cavity are significantly enlarged or distorted by the spacing member 1150. Additionally or alternatively, in some embodiments, in the expanded configuration, the spacing member 1150 can be used to reduce blood flow past the spacing member 1150. Thus, the spacing member 1150 can be positioned relative to an aneurysm such that the spacing member 1150 reduces blood flow into the aneurysm, thereby increasing the residence time of cellular elements within the treatment region so that the cellular elements receive an adequate dose of radiation. Additionally, reducing blood flow past the spacing member 1150 can help establish a translucent light field within the treatment region. Additionally, spacing member 1150 can be used to temporarily prevent thrombus from leaving the aneurysm during treatment.

[0124]

[0166] In some embodiments, spacing member 1150 can be configured to detach from inner body 1148 and remain (e.g., permanently) within the aneurysm to support the aneurysm after illumination by light emitter 1130. For example, spacing member 1150 can function as a neck-supporting scaffold for building progressive (e.g., reparative) tissue within the aneurysm.

[0125]

[0167] The spacing member 1150 can be releasably coupled to the inner body 1148 by any suitable removable coupling mechanism. For example, FIG. 23B is a cross-sectional schematic diagram of a portion of the system 1100 in which the spacing member 1150 includes or can be coupled to an elongated neck portion 1151 by a sacrificial adhesive 1153 (also referred to herein as a sacrificial adhesive layer 1153). The spacing member 1150 (or a distal expandable portion of the spacing member 1150) can be detached from the elongated neck portion 1151 at the location of the sacrificial adhesive layer 1153. For example, the sacrificial adhesive layer 1153 can be damaged by light emitted from the light emitter 1130. For example, at the end of the treatment phase of light delivery, the light intensity from the light emitter 1130 can be briefly increased to an intensity and for a duration sufficient to damage the sacrificial adhesive layer 1153 so that the spacing member 1150 (or a distal expandable portion of the spacing member distal to the sacrificial adhesive layer 1153) can detach from the elongated neck portion 1151 and remain within the aneurysm when the remainder of the system 1100 is withdrawn from the aneurysm. As shown in FIG. 23B , the sacrificial adhesive layer 1153 can be positioned in contact with and / or circumferentially surround a portion of the light emitter 1130 so that light from the light emitter can contact the sacrificial adhesive layer 1153. Additionally, as shown in FIG. 23B , the sacrificial adhesive layer 1153 can optionally be positioned distal to some or all of the radiopaque marker 1139.

[0126]

[0168] In some embodiments, the spacing member 1150 can include any suitable shape or structure, can be made of any suitable material, and can be formed using any suitable manufacturing method. For example, FIGS. 24A-24G are schematic illustrations of cross-sectional views of various spacing member 1150 embodiments. FIGS. 24H and 24I are perspective and cross-sectional views of another version of the spacing member 1150, according to embodiments. As shown in FIG. 24A, in some embodiments, the spacing member 1150 can be braided from metal (e.g., nitinol) or polymer wire. As shown in FIG. 24B, in some embodiments, the spacing member 1150 can be fabricated by laser cutting a metal or polymer sheet. As shown in FIG. 24C, in some embodiments, the spacing member 1150 can be made of multiple layers. In some embodiments, the multiple layers can be separate layers, each having a perimeter and / or end that differs from those of the other layers. In some embodiments, the multiple layers can be formed by folding one or more layers over each other one or more times. Thus, for example, the distal-most portion of spacing member 1150 can be formed from an intermediate portion of a layer formed by folding the layer over, such that the distal-most portion of spacing member 1150 has a curved and / or continuous distal contact surface rather than including or being formed from a free edge (e.g., a sharp or discontinuous edge) of a layer or material. As shown in FIG. 24D, in some embodiments, spacing member 1150 can be made from a single layer of material.

[0127]

[0169] In some embodiments, the spacing member 1150 can be fabricated as a composite of multiple elements. For example, the spacing member 1150 can include a first element (e.g., a frame) and a second element (e.g., a cover) coupled to the frame and extending partially or completely from the proximal end to the distal end of the spacing member 1150. The first element can be fabricated, for example, by laser cutting a metal or polymer sheet, can be braided from a metal (e.g., nitinol) or polymer wire, or can be hand-wound on a suitable jig in a braided or non-braided format. For example, FIGS. 24E and 24F show a manually-wound first element 1159A, respectively. As shown in FIG. 24F, for example, the second element 1159B can be fabricated from a membranous polymer (e.g., PTFE) and bonded to the first element 1159A. The surface of the membranous second element 1159B can be textured to include micropores of known dimensions, as shown in FIG. 24F, or can include macropores, which have dimensions one or more orders of magnitude larger than the micropores, providing a textured surface to further accommodate hemodynamics and cell growth on the surface, as shown in FIG. 24G. In some embodiments, the macropores can be the same or similar in size as the windows W described above with respect to FIG. 6. In some embodiments, the membranous second element 1159B can include both micropores and macropores, as shown in FIGS. 24H and 24I, which are perspective and cross-sectional side views of one embodiment of the spacing member 1150. Alternatively, in some embodiments, the second element 1159B can be formed as an assembly of polymer fibers, such as an electrospun mesh. Individual fibers can have a microtexture, and the macropores / porosity can be provided by the density and arrangement of the fibers. 24H and 24I, the textured membrane 1159B can provide full or partial surface coverage (e.g., coverage of a first proximal conical portion but not a second portion distal to the first portion) of the spacing member 1150. Thus, the membrane 1159B can extend at least partially from the proximal end to the distal end of the spacing member 1150.

[0128]

[0170] In some embodiments, spacing member 1150 can have any suitable shape in the expanded configuration. For example, FIG. 25 includes schematic illustrations of cross-sectional views of various spacing member 1150 embodiments in the expanded configuration. As shown, each of the spacing members 1150 shown in FIG. 25 has a different geometric configuration. For example, spacing member 1150A can assume a configuration that can reside at the neck of an aneurysm in the expanded configuration (also referred to as the “open position”). As another example, spacing member 1150B can assume a “pear” shape in the open position to expand and conform to the shape of the aneurysm after deployment. As another example, spacing member 1150C can be formed of a continuous layer and configured to function as a neck-bridge device with symmetry that allows for improved stability upon deployment. As another example, spacing member 1150D can assume a generally spherical shape in the open position. The spacing member 1150D can be configured to deploy along the direction of arrow Y such that the spacing member 1150D unfolds from a deployment point at the distal end of the catheter body 1120 and moves proximally (e.g., in a breaststroke fashion) along a curved path toward the proximal portion of the catheter body 1120 (e.g., back toward the proximal side of the aneurysm).

[0129]

[0171] In some embodiments, the spacing member 1150 can be coupled to the inner body 1148 and can be detachable from the inner body 1148 by severing the sacrificial adhesive layer 1153. The light emitter 1130 can be translated relative to the sacrificial adhesive layer 1153 to align the light emitter 1130 with the sacrificial adhesive layer 1153 for severing the sacrificial adhesive layer 1153. For example, FIGS. 26A and 26B are schematic cross-sectional views of a portion of the system 1100 in a first configuration and a second configuration, respectively. As shown, the spacing member 1150 is detachable from the inner body 1148 with the use of the sacrificial adhesive layer 1153. Damaging (e.g., severing) the adhesive layer 1153 is achieved by retracting the light emitter 1130 from a treatment position relative to the adhesive layer 1153 (shown in FIG. 26A ) to a detachment position relative to the adhesive layer 1153 (shown in FIG. 26B ). At the detachment position, the light source coupled to the light emitter 1130 may be activated with sufficient power to decompose (e.g., dissolve) the sacrificial adhesive layer 1153. In some embodiments, the detachment position (e.g., the position of the light emitter 1130 relative to the adhesive layer 1153) can be confirmed prior to activating the detachment process by visualizing the change in the relative positions of the radiopaque markers 1139 and 1156 coupled to the spacing member 1150 and adjacent the adhesive layer 1153 compared to their relative positions at the treatment position.

[0130]

[0172] 27 is a schematic diagram of a system 1100 in which multiple optical fibers 1163 are embedded in an inner body 1148 and arranged around an optical conduit 1132 (e.g., a central optical fiber) that supplies light to the light emitter 1130. The distal end of each of the optical fibers 1163 can all be polished at an angle less than the critical angle (e.g., the angle associated with total internal reflection) so that light emanates from the distal end of the fiber toward the sacrificial adhesive layer 1153. In addition, the polished distal surfaces of the fibers 1163 can optionally be coated with a reflective layer (such as a mirror) to enhance the refraction of light toward the sacrificial adhesive layer 1153. The sacrificial adhesive layer 1153 itself can be mixed with a light-absorbing material to promote the decomposition of the sacrificial adhesive layer 1153 when exposed to light from the fibers 1163. Once detached, retraction of the inner body 1148 can be monitored by observing the change in the position of the radiopaque marker 1139 on the inner body 1148 relative to the position of the marker 1156 on the spacing member 1150. In some embodiments, optical fiber 1163 can be used during the treatment phase to collect scattered light transmitted to the treatment area and transmit it as feedback to the user.

[0131]

[0173] In some embodiments, one or more of the optical fibers 1163, but not all of the optical fibers 1163 surrounding the light conduit 1132, may be elongated and at least partially embedded within the light emitter 1130. For example, FIG. 28 is a schematic diagram of a system 1100 in which optical fiber 1165 of the plurality of optical fibers 1163 extends into the light emitter 1130 (e.g., beyond the radiopaque marker 1139). The optical fiber 1165 can be used as an optical conduit to provide feedback on the amount of power delivered from the light source to the light emitter 1130 and to the treatment area. As before, detachment of the spacing member 1150 can be monitored by observing the change in the position of the radiopaque marker 1139 and the radiopaque marker 1156 relative to one another.

[0132]

[0174] In some embodiments, the spacing member 1150 may not be removably coupled to the inner body 1148, but rather may be removably coupled to an outer body, which may be a separate conduit within which the inner body 1148 may be disposed and translated. The outer body may be, for example, the catheter body 1120 or another tubular body (e.g., a tubular body disposed within the catheter body 1020 and configured to translate relative to the catheter body 1020). For example, FIG. 29 is a schematic cross-sectional view of a portion of a system 1100 in which the spacing member 1150 is removably coupled to the outer body 1185 via a sacrificial bond 1153. As shown in FIG. 29 , the inner body 1148 is encased in a separate outer body 1185. As shown, an optical fiber 1163 capable of transmitting optical energy to the sacrificial bond 1153 may be embedded in the outer body 1185 instead of being located inside the inner body 1148. As shown, the distal end of the optical fiber 1163 may be disposed adjacent to or in contact with the sacrificial bond 1153.

[0133]

[0175] In some embodiments, the system 1100 can include electrical wires (e.g., within the catheter body 1120 or another separate outer conduit) to provide the energy necessary to damage the sacrificial bond 1153. For example, Figure 30 is a schematic diagram of a cross section of a portion of the system 1100 in which electrical wires 1168 are embedded within the outer body 1185 to provide the energy necessary to damage the sacrificial bond 1153. As shown, an insulator 1169 can be included to ensure that all electrical energy passes through the sacrificial bond.

[0134]

[0176] Another feature that can be realized in this embodiment is a feedback system that can indicate the amount of energy delivered to tissue by the light emitter 1130 during a treatment phase by sensing changes in the resistance of the spacing member 1150 and its connected electrical leads 1168 in response to a low-level voltage across it. For example, the spacing member 1150 and its connected electrical leads can function as a variable resistor (or one leg) of a Wheatstone bridge during exposure of the spacing member to light energy.

[0135]

[0177] In some embodiments, the spacing member 1150 can be removably coupled to the inner body and / or outer body via a pressure-rupturable hollow tube. For example, FIG. 31 is a cross-sectional schematic diagram of a portion of a system 1100 in which the spacing member 1150 (also referred to as a “centering mechanism” or “centering member”) is removably coupled to the inner body 1148 via a short length of flexible hollow tube 1180. The hollow tube can be supplied with fluid through a channel 1181 embedded in an outer conduit 1185. When disconnection is desired, the fluid within the channel 1181 and the tube 1180 can be pressurized, causing the tube 1180 to radially expand and disconnect the spacing member 1150 from the inner body 1148. In some embodiments, the tube 1180 can be ruptured to disconnect the spacing member 1150 from the outer conduit 1185.

[0136]

[0178] FIG. 32 is a schematic cross-sectional view of a portion of system 1100 including a separable friction fit between spacing member 1150 (also referred to as a “centering mechanism” or “centering member”) and light emitter 1130 and / or inner body 1148. For example, the neck portion of the spacing member 1150 can include a friction fit portion 1182B (e.g., a circumferential friction fit portion), the conduit 1185 can include a friction fit portion 1182A (e.g., a circumferential friction fit portion), and the light emitter 1130 and / or marker 1139 and / or inner body 1148 can include or function as such a friction fit portion configured so that the outer surfaces of the light emitter 1130 and / or marker 1139 and / or inner body 1148 and the inner surfaces of the spacing member 1150 and conduit 1185 can be tightly fitted together by friction and held in place (e.g., the neck portion of the spacing member 1150 can be coupled to the marker 1139 by a friction fit, and the conduit 1185 can be coupled to the marker 1139 by a friction fit). By pulling the inner body 1148 proximally while preventing movement of the independent conduit 1185 (e.g., holding the conduit 1185 stationary), the friction fit between the light emitter 1130, the marker 1139, and / or the neck portion of the inner body 1148 and the centering member 1150 can be broken. Thus, the inner body 1148 can be retracted and removed, and the independent conduit 1185 can be retracted and removed relative to the centering member 1150, leaving the centering member 1150 in the treatment area. In some implementations, the independent conduit 1185 can be retained in place after the inner body 1148 is fully removed and used as a conduit to access the treatment site where the centering member 1150 is located for further treatment (e.g., fluid delivery and / or suction and / or light therapy). Once treatment is complete, the independent conduit 1185 can be removed.

[0137]

[0179] FIG. 33 is a flowchart illustrating a method 1200 for treating a treatment region in a body cavity. At 1202, a distal end of a catheter can be positioned within a body cavity of a subject near (e.g., adjacent to) a target region of tissue to be treated. The catheter can include, for example, a catheter body and a light emitter. The light emitter can be configured to emit light asymmetrically and at a non-zero angle relative to a central axis of the catheter body. At 1204, optionally, an optional spacing member of the catheter can be transitioned to an expanded configuration within the body cavity. At 1206, optionally, pressure (e.g., equilibrium pressure) within the body cavity can be maintained (e.g., within a certain range) by at least one of supplying fluid to or withdrawing fluid from the body cavity. In some embodiments, supplying fluid to and withdrawing fluid from the body cavity can occur simultaneously. At 1208, light can be emitted from the light emitter onto the target region of tissue asymmetrically and at a non-zero angle relative to the central axis of the catheter body. Although light is described as being emitted asymmetrically, in some embodiments, light can be emitted onto the target region of tissue symmetrically relative to the central axis of the catheter body. Optionally, in some embodiments, the light may be dispersed to areas outside the target area of ​​tissue at an intensity that is less than the intensity of the light emitted into the target area of ​​tissue, as described above.

[0138]

[0180] In some embodiments, the target region can include brain tissue, and the body cavity can be a space adjacent to the brain tissue that contains cerebrospinal fluid. In some embodiments, the body cavity can be a synovial joint cavity. In some embodiments, the target region can include a spinal disc. In some embodiments, the target region can include damaged brain tissue, such as any of the damaged brain tissues described herein. In some embodiments, the target region can include the thalamus, and the distal end of the catheter can be positioned adjacent to the target region by translating the distal end of the catheter through the CSF space of the third ventricle of the subject. In some embodiments, the target region can include the spinal cord, and the distal end of the catheter can be positioned adjacent to the target region by translating the distal end of the catheter through the CSF space anterior to or posterior to the spinal cord. In some embodiments, the target region can be at least one of the thalamus, subthalamic nucleus, or caudate nucleus, and the distal end of the catheter can be positioned adjacent to the target region by translating the distal end of the catheter through the CSF space of the ventricular system. In some embodiments, the target region or body cavity can include the cSDH space.

[0139]

[0181] In some embodiments, the catheter can include a first fluid conduit and a second fluid conduit, and method 1200 can include maintaining a pressure within the body cavity within a range by at least one of supplying fluid to the body cavity via the first fluid conduit or withdrawing fluid from the body cavity via the second fluid conduit. In some embodiments, supplying fluid to and withdrawing fluid from the body cavity can occur simultaneously.

[0140]

[0182] In some embodiments, the catheter can include a light conduit at least partially disposed within the catheter body, the light emitter can be disposed at a distal end of the light conduit, and the light can be configured to be provided to the light emitter via the light conduit. In some embodiments, the light emitter can be formed by a distal end portion of the light conduit, and emitting light includes emitting light through a sidewall of the light conduit.

[0141]

[0183] In some embodiments, the catheter can include a spacing member configured to transition between a collapsed configuration and an expanded configuration. In some embodiments, the spacing member can be configured to prevent contact of the light emitters with tissue walls defining the body cavity (e.g., the target area). In the expanded configuration, the spacing member can be configured to maintain the light emitters approximately centered relative to at least one axis of the spacing member. Method 1200 can include transitioning the spacing member from the collapsed configuration to the expanded configuration within the body cavity such that the light emitters are centered between opposing tissue walls defining the body cavity. In some embodiments, the spacing member is at least partially transparent and / or semi-transparent to light emitted from the light emitters, and emitting light includes emitting light through the spacing member.

[0142]

[0184] In some embodiments, the method includes emitting light at a wavelength in the visible portion of the spectrum. In some embodiments, the method includes emitting light at a wavelength in the near-infrared portion of the spectrum. In some embodiments, emitting light includes emitting light at a power and duration sufficient to deliver a sufficient amount of light energy to the target area of ​​tissue to induce a photochemical effect on the target area of ​​tissue, recruiting stem cells locally and / or remotely and initiating activation, differentiation, and proliferation of cells, including pluripotent stem cells, hematopoietic stem cells, and / or mesenchymal stem cells, hemangioblasts, endothelial progenitor or progenitor cells, neurons and glial progenitor cells, neural stem cells, and / or differentiated cells such as fibroblasts and collagen. In some embodiments, the light is emitted at a wavelength between 400 nm and 1,100 nm. In some embodiments, the light is emitted at a wavelength of, for example, 532 nm. In some embodiments, the power of the light applied to the target area can be in the range of 1 mW to 500 mW. In some embodiments, the power can be in the range of 100 mW to 200 mW. In some embodiments, the power density of the light applied to the target area is 1 mW / cm 2 to 5W / cm 2 In some embodiments, the power density may be in the range of 5 mW / cm 2 to 500mW / cm 2In some embodiments, the power density may be in the range of 50 mW / cm 2 to 500mW / cm 2 In some embodiments, the power density may be in the range of 175 mW / cm 2 to 200mW / cm 2 In some embodiments, the light can be emitted to the target area in a single irradiation or multiple irradiations within a single session, and in a single session or over multiple sessions. In some embodiments, the light emitted from the light emitter can be pulsed. In some embodiments, the energy irradiance to the target area (e.g., the total energy irradiance delivered in a single irradiation session or procedure, or the total cumulative energy irradiance delivered over multiple sessions) can be in the range of 0.05 J / cm. 2 to 250 J / cm 2 In some embodiments, emitting light includes not emitting light onto a non-target region of tissue adjacent to the target region of tissue. In some embodiments, emitting light includes emitting light at a lower intensity (e.g., at a lower power density) onto a non-target region of tissue (e.g., a secondary region) adjacent to the target region of tissue.

[0143]

[0185] In some embodiments, the catheter includes a radiopaque marker coupled to the light emitter, and the method 1200 includes visualizing the radiopaque marker within the body cavity and maneuvering the catheter based on the visualization of the radiopaque marker to adjust at least one of the orientation or position of the light emitter relative to the target region of tissue.

[0144]

[0186] FIG. 34 is a schematic diagram of a treatment system 1300 used to treat a stroke region SR of a subject's brain B, which may be the same as or similar to any of the treatment systems or devices described herein. The stroke region SR may include, for example, stroke-damaged tissue. The embodiments and specific components of treatment system 1300 shown and described with respect to FIG. 33 may be configured the same as or similar to, and include the same or similar features as, corresponding components of any of the systems or devices described herein, such as system 100, system 900, and system 1100 described above. Treatment system 1300 may be used, for example, to treat stroke-damaged tissue with light energy using any of the methods described herein to achieve any of the intended effects or results described herein.

[0145]

[0187] 34 , treatment system 1300 may include catheter 1310, shown with its distal end portion positioned within stroke region SR. Catheter 1310 may include any of the features described above with respect to catheters 110, 910, or 1110, for example. In some embodiments, catheter 1310 may be a blunt needle. In some embodiments, catheter 1310 may be inserted into stroke region SR via a trocar. As shown, a burr hole BH may be formed through the subject's skull SK, and catheter 1310 may be inserted through burr hole BH to position the distal end of the catheter within or near stroke region SR.

[0146]

[0188] The treatment system 1300 can include a light emitter, which can be identical or similar in structure and / or function to any of the light emitters described herein. In some embodiments, the treatment system 1300 can also include an inner body 1348. The inner body 1348 can be identical or similar in structure and / or function to any of the inner bodies described herein. For example, the inner body 1348 can include or be coupled to a light emitter. Additionally, the inner body 1348 can include and / or define a lumen configured to receive a light conduit 1332 (e.g., an optical fiber) coupled to the light emitter. The light emitter (and optional light conduit 1332) can be coupled to a light source (not shown).

[0147]

[0189] The treatment system 1300 may include a spacing member 1350, which may be the same or similar in structure and / or function to any of the spacing members described herein. For example, the spacing member 1350 may be disposable at the distal end of the catheter body 1320 of the catheter 1310 (e.g., via the working channel 1324 of the catheter body 1320). For example, the spacing member 1350 may be deployable to maintain a minimum spacing between the light emitters of the treatment system 1300 and the walls of the treatment region that define the stroke region SR.

[0148]

[0190] 34, a catheter 1310 can be inserted into the stroke region SR through a burr hole BH, as described above. A spacing member 1350 can be deployed by any suitable method described herein. Light can then be emitted from the light emitter by any suitable method described herein to therapeutically target stroke-damaged brain tissue.

[0149]

[0191] In some embodiments, the working channel 1324 of the catheter body 1320 (e.g., a first fluid conduit of the working channel 1324) can be used to introduce or inject a fluid (e.g., saline) from a fluid source (not shown) into the treatment region, i.e., stroke region SR. Because the fluid in the stroke region SR of the brain B is typically transparent or translucent, it may not be necessary to dilute such a fluid with a clear fluid, such as saline, to allow the light irradiation to reach the brain tissue to be treated. The fluid can be used to cool the stroke region SR (e.g., during the application of light from a light emitter). In some embodiments, cooling may not be necessary when a fully transparent light-scattering material, such as diamond dust, is used (e.g., a light scatterer such as any of the light scatterers described herein coupled to the distal end of the inner body 1348 and / or covering the light emitter). The catheter body 1320 can define or include a second fluid conduit for aspirating (e.g., removing) excess fluid and / or other substances from the treatment region (e.g., continuously or intermittently, such as during periods of fluid input by the first fluid conduit). Additionally, fluid delivery by the first fluid conduit and aspiration by the second fluid conduit can be controlled to avoid increasing pressure (e.g., CSF pressure) in the treatment region (e.g., outside of an unsafe pressure range). For example, fluid can be delivered through the first fluid conduit and aspirated through the second fluid conduit at approximately the same flow rate so that pressure in the treatment region remains unchanged or within a safe range during treatment.

[0150]

[0192] While various embodiments have been described above, it should be understood that they have been presented by way of example only, and not by way of limitation. Where the methods described above indicate that certain events occur in a certain order, the order of the certain events may be modified. Additionally, certain of the events may not only be performed sequentially as described above, but may also be performed simultaneously in parallel processes where possible.

[0151]

[0193] While the above-described schematic diagrams and / or embodiments show certain components arranged in a certain orientation or position, the arrangement of the components may be modified. While embodiments have been specifically illustrated and described, it will be understood that various changes in form and detail may be made. Except for mutually exclusive combinations, any portion of the apparatus and / or methods described herein may be combined in any combination. The embodiments described herein may include various combinations and / or subcombinations of the functions, components, and / or features of the different embodiments described.

Claims

1. A catheter body; an optical conduit at least partially disposed within the catheter body; a light emitter disposed at a distal end of the optical conduit, the light emitter configured, when disposed within a patient's body cavity proximate a target tissue region, to emit a first portion of light received through the optical conduit asymmetrically and at a non-zero angle relative to a central axis of the optical conduit such that the first portion is transmitted to the target tissue region at a first intensity, and to emit a second portion of light received through the optical conduit distal to the light emitter; a light scatterer coupled to the light emitter and configured to diffuse the second portion of the light such that the second portion of the light is transmitted to a non-target tissue region at a second intensity that is lower than the first intensity; Including, the system.

2. 2. The system of claim 1, wherein the light emitter comprises a distal end face of the light conduit, the distal end face being positioned at a non-zero angle with respect to a central axis of the light conduit such that a first portion of the light transmitted through the light conduit to the distal end face is reflected by the distal end face through a sidewall of the light conduit and a second portion of the light is transmitted through the distal end face.

3. The system of claim 2 , wherein the light pipe is formed as a solid elongated member.

4. The system of claim 1 , wherein the light scatterer and the light emitter are configured such that the first portion is transmitted through a sidewall of the light emitter to the target tissue region.

5. The system of claim 1 , wherein the light emitter is formed by a distal end portion of the light conduit and is configured to emit the first portion through a sidewall of the light conduit.

6. The system of claim 1 , wherein the non-target tissue region is adjacent to the target tissue region.

7. The system of claim 1 , wherein the light scatterer and the light emitter are configured so that the second portion of the light is diffused by the light scatterer in an axial direction and a lateral direction relative to a central axis of the light scatterer, and the light scatterer and the light pipe are arranged coaxially.

8. The system of claim 7 , wherein the non-target tissue region surrounds the optical scatterer.

9. 10. The system of claim 1, further comprising a spacing member configured to transition between a collapsed configuration and an expanded configuration, wherein in the expanded configuration, the spacing member is configured to be disposed around the light emitter to maintain the light emitter approximately centered relative to at least one axis of the spacing member, and wherein the spacing member is configured to maintain the light emitter centered between opposing tissue walls defining the body cavity in the expanded configuration.

10. The system of claim 9 , wherein the spacing member is at least partially transparent and / or semi-transparent to light emitted from the light emitter.

11. The system of claim 9 , wherein the spacing member is porous to the fluid.

12. 10. The system of claim 9, wherein the spacing member has a conical shape in the expanded configuration so as to define a conical space within which the light emitter is at least partially disposed.

13. 10. The system of claim 9, wherein the spacing member has an open distal end and, in the expanded configuration, defines an interior space within which the light emitter is at least partially disposed, the spacing member including a frame portion and a membrane cover portion.

14. The system of claim 13 , wherein the membrane cover portion covers at least a proximal portion of the frame portion.

15. The system of claim 1 , further comprising a light source coupleable to the proximal end of the light conduit and configured to generate light at a wavelength in the visible portion of the electromagnetic spectrum.

16. The system of claim 15, wherein the light source is configured to generate light having a power between 1 mW and 500 mW.

17. The target tissue area receiving light transmitted from the light source through the light conduit and the light emitter to the target tissue area has a fluence of 5 mW / cm ２ ~500mW / cm ２ 16. The system of claim 15, wherein the light source is configured to generate the light to have a surface power density of

18. a target tissue region receiving the light transmitted from the light source through the light conduit and the light emitter to the target tissue region, the target tissue region receiving a dose of 0.05 J / cm2 relative to the target tissue region; ２ ~150 J / cm ２ 16. The system of claim 15, wherein the light source is configured to generate light such that an energy dose of

19. The system of claim 1 , further comprising a light source coupleable to the proximal end of the optical conduit and configured to generate light at a wavelength between 400 nm and 1,100 nm.

20. A catheter body; an optical conduit at least partially disposed within the catheter body; a light emitter disposed at a distal end of the optical conduit, the light emitter configured, when disposed within a patient's body cavity proximate a target tissue region, to emit light asymmetrically and at a non-zero angle relative to a central axis of the optical conduit such that the light is transmitted to the target tissue region; Including, the system.

21. 21. The system of claim 20, wherein the light emitter is configured to emit the light such that the light is transmitted to the target tissue region and not to non-target tissue regions adjacent to the target tissue region.

22. 21. The system of claim 20, wherein the catheter body defines a first fluid conduit configured to fluidly couple to a fluid source and a second fluid conduit configured to couple to a fluid sink, the first fluid conduit and the second fluid conduit configured to be in fluid communication with the body cavity such that a pressure within the body cavity can be maintained within a predetermined range by at least one of supplying fluid to the body cavity from the fluid source via the first fluid conduit or withdrawing fluid from the body cavity to the fluid sink via the second fluid conduit.

23. 21. The system of claim 20, wherein the light emitter is formed by a distal end portion of the light pipe and is configured to emit light through a sidewall of the light pipe.

24. 21. The system of claim 20, wherein the light pipe is formed as a solid elongated member, and the light emitter comprises a distal end face of the light pipe, the distal end face being positioned at a non-zero angle relative to a central axis of the light pipe such that light transmitted through the light pipe to the distal end face is reflected by the distal end face through a sidewall of the light pipe.

25. 25. The system of claim 24, wherein the non-zero angle at which the distal end face is positioned relative to the central axis of the light pipe is large enough to cause all of the light traveling through the light pipe to be reflected by the distal end face and emitted through the side wall of the light pipe.

26. 21. The system of claim 20, wherein the light emitter includes a distal end surface of the light conduit and a reflective surface portion disposed on the distal end surface, the distal end surface and the reflective surface portion being disposed at a non-zero angle with respect to a central axis of the light conduit such that light transmitted through the light conduit to the distal end surface is reflected by the reflective surface portion through a sidewall of the light conduit.

27. 21. The system of claim 20, further comprising a radiopaque marker coupled to the light emitter to enable visualization of the orientation and position of the light emitter.

28. 21. The system of claim 20, further comprising a spacing member configured to transition between a collapsed configuration and an expanded configuration, wherein in the expanded configuration the spacing member is configured to be disposed around the light emitter to maintain the light emitter approximately centered relative to at least one axis of the spacing member, and wherein the spacing member is configured to maintain the light emitter centered between opposing tissue walls defining the body cavity in the expanded configuration.

29. 30. The system of claim 28, wherein the spacing member is at least partially transparent and / or semi-transparent to the light emitted from the light emitter.

30. 30. The system of claim 28, wherein the spacing member is porous to the fluid.

31. 30. The system of claim 28, wherein the spacing member has a conical shape in the expanded configuration so as to define a conical space within which the light emitter is at least partially disposed.

32. 30. The system of claim 28, wherein the spacing member has an open distal end and defines an interior space within which the light emitter is at least partially disposed in the expanded configuration, the spacing member including a frame portion and a membrane cover portion.

33. The system of claim 32 , wherein the membrane cover portion covers at least a proximal portion of the frame portion.

34. 21. The system of claim 20, further comprising a light source coupleable to the proximal end of the light conduit and configured to generate light at wavelengths in the visible region of the electromagnetic spectrum.

35. 35. The system of claim 34, wherein the light source is configured to generate light having a power between 1 mW and 500 mW.

36. The target tissue area receiving light transmitted from the light source through the light conduit and the light emitter to the target tissue area has a fluence of 5 mW / cm ２ ~500mW / cm ２ 35. The system of claim 34, wherein the light source is configured to generate the light to have a surface power density of

37. a target tissue region receiving light transmitted from the light source through the light conduit and the light emitter to the target tissue region, the target tissue region receiving a dose of 0.05 J / cm2 relative to the target tissue region; ２ ~150 J / cm ２ 35. The system of claim 34, wherein the light source is configured to generate the light such that an energy dose of

38. 21. The system of claim 20, further comprising a light source coupleable to the proximal end of the light conduit and configured to generate light at a wavelength between 400 nm and 1,100 nm.

39. a catheter body defining a working channel; an inner body translatable within the working channel and including a light emitter at a distal end; a spacing member coupled to the inner body proximal to the light emitter, the spacing member configured to transition between a collapsed configuration and an expanded configuration, the spacing member having a conical shape in the expanded configuration to define a conical space within which the light emitter is at least partially disposed, the spacing member configured to maintain the light emitter approximately centered relative to a central axis of the spacing member when in the expanded configuration within or between opposing walls of a body lumen; Including, the system.

40. 40. The system of claim 39, wherein the spacing member is configured to be biased to the expanded configuration, to be held in the collapsed configuration by the catheter body when disposed within the working channel of the catheter body, and to expand when the spacing member is translated distally relative to the catheter body so that it is disposed distally of the catheter body.

41. 40. The system of claim 39, wherein the spacing member is configured to prevent fluid flow from a region distal to the spacing member to a region proximal to the spacing member in the expanded configuration.

42. 40. The system of claim 39, wherein the spacing member is configured to permit fluid flow from a distal region of the spacing member to a proximal region of the spacing member while preventing objects above a size threshold from flowing from the distal region of the spacing member to the proximal region of the spacing member in the expanded configuration.

43. 40. The system of claim 39, wherein the spacing member has a conical shape in the expanded configuration so as to define a conical space within which the light emitter is at least partially disposed.

44. 40. The system of claim 39, wherein the spacing member has an open distal end and defines an interior space within which the light emitter is at least partially disposed in the expanded configuration, the spacing member including a frame portion and a membrane cover portion.

45. 45. The system of claim 44, wherein the membrane cover portion covers a proximal portion of the frame portion.

46. positioning a distal end of a catheter within a body cavity of a subject adjacent a target area of ​​tissue to be treated, the catheter comprising: A catheter body; a light emitter configured to emit light asymmetrically and at a non-zero angle relative to a central axis of the catheter body; and emitting light from the light emitter onto the target region of the tissue asymmetrically and at a non-zero angle relative to the central axis of the catheter body; A method comprising:

47. 47. The method of claim 46, wherein the target region of tissue comprises brain tissue and the body cavity is a space adjacent to the brain tissue that contains cerebrospinal fluid.

48. 47. The method of claim 46, wherein the body cavity is a synovial joint cavity.

49. the catheter including a first fluid conduit and a second fluid conduit; The method comprises: Maintaining pressure within the body cavity within a predetermined range by at least one of supplying fluid to the body cavity via the first fluid conduit or withdrawing fluid from the body cavity via the second fluid conduit.

47. The method of claim 46, further comprising:

50. 47. The method of claim 46, wherein the catheter further comprises an optical conduit disposed at least partially within the catheter body, the light emitter disposed at a distal end of the optical conduit, and configured such that light is provided to the light emitter via the optical conduit.

51. 51. The method of claim 50, wherein the light emitter is formed by a distal end portion of the light pipe, and wherein emitting light includes emitting light through a sidewall of the light pipe.

52. the catheter includes a spacing member configured to transition between a collapsed configuration and an expanded configuration, the spacing member configured to maintain the light emitter substantially centered relative to at least one axis of the spacing member in the expanded configuration; transitioning the spacing member from the collapsed configuration to the expanded configuration within the body cavity such that the light emitter is centered between opposing tissue walls defining the body cavity.

47. The method of claim 46.

53. 53. The method of claim 52, wherein the spacing member is at least partially transparent and / or semi-transparent to the light emitted from the light emitter, and wherein emitting light comprises emitting light through the spacing member.

54. 47. The method of claim 46, wherein emitting light comprises emitting light of a wavelength in the visible region of the electromagnetic spectrum.

55. 47. The method of claim 46, wherein emitting light comprises emitting light at a power and duration sufficient to deliver a sufficient amount of light energy to the target area of ​​the tissue to produce a photochemical effect in the target area of ​​the tissue to recruit stem cells locally and / or remotely and to initiate differentiation, activation, and proliferation of cells, including pluripotent stem cells, hematopoietic stem cells, and / or mesenchymal stem cells, hemangioblasts, endothelial progenitor or precursor cells, and / or differentiated cells such as fibroblasts and collagen.

56. 47. The method of claim 46, wherein emitting light comprises emitting light at a wavelength between 400 nm and 1,100 nm.

57. 47. The method of claim 46, wherein emitting light comprises emitting light at a power between 1 mW and 500 mW.

58. The light emitted is 5 mW / cm ２ ~500mW / cm ２ 47. The method of claim 46, comprising emitting light at a power density of

59. emitting light to a target area of ​​the tissue at a dose of 0.05 J / cm ２ ~250 J / cm ２ 47. The method of claim 46, comprising emitting light to provide an energy dose of

60. 47. The method of claim 46, wherein emitting light comprises not emitting light onto a non-target area of ​​tissue adjacent to the target area of ​​tissue.

61. the catheter includes a radiopaque marker coupled to the light emitter; The method comprises: visualizing the radiopaque marker within the body cavity; manipulating the catheter based on the visualization of the radiopaque marker to adjust at least one of the orientation or position of the light emitter relative to the target region of the tissue; 47. The method of claim 46, further comprising:

62. 47. The method of claim 46, wherein the target area of ​​tissue comprises at least a portion of a chronic subdural hematoma cavity.

63. 47. The method of claim 46, wherein the light is the first portion of light, and emitting comprises axially emitting the second portion of light from the light emitter to a light scatterer such that the second portion of light is dispersed onto a secondary region of tissue adjacent the target region of tissue at a lower intensity than the first portion of light.

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