Optical transmission microcatheter device and method

Abstract

[0003] A light-transmitting microcatheter device and method for intravascular embolization are described herein. A microcatheter device is provided, comprising a working lumen and a mechanically protected waveguide. The working lumen has at least one exit port at a distal end of the working lumen and is configured for intravascular injection of a photoactivated embolic agent (PEA) into a target vessel through the at least one exit port. A mechanically protected waveguide (MPW) is operably connected to the working lumen and configured to emit at least one electromagnetic wave through the at least one exit port for delivery to the target vessel.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 386,279, filed December 6, 2022, the contents of which are incorporated herein by reference. [Technical Field]

[0002]

[0002] The present disclosure relates generally to intravascular microcatheter design. In some aspects, the present disclosure relates to methods for therapeutic embolization by injecting a light-activated embolic or therapeutic agent. [Background technology]

[0003]

[0003] Endovascular embolization is a minimally invasive catheterization procedure aimed at halting local blood flow in the peripheral vasculature to address pathologies including hypervascular tumors, arteriovenous malformations, subdural hematomas, and aneurysms. Affected vessels, often difficult to reach via open surgery from superficial vascular puncture, can be accessed by catheters into which selected flow control devices or medications are deployed. When used as a primary or adjunctive method of disease management, endovascular embolization can significantly reduce perioperative risks and patient recovery time.

[0004]

[0004] Current clinically available embolic devices and agents include mechanical devices such as detachable coils and flow diverters, precipitating liquid polymeric agents, and suspended particulate materials. Metal coils for treating aneurysms are prone to recanalization due to insufficient filling of the aneurysm cavity resulting from device compression. Flow diverters have more recently become a popular option for treating aneurysms, but they are prone to incomplete apposition to the parent artery wall, leading to residual aneurysm perfusion. Flow diverters also require patients to undergo lifelong dual antiplatelet therapy. Uncontrolled coagulation, seen with existing injectable embolic agents such as Onyx (Medtronic™), can result in unintended embolization leading to ischemic episodes and supplemented catheters that can dissect healthy vessels and cause rupture.

[0005] Commercially available neurovascular microcatheters used for endovascular embolization, such as the SL10 (Stryker) and Sceptor XC (Balt), are very thin (typically less than 1 mm in outer diameter) and highly flexible, requiring only approximately 1 gram of force to bend the distal tip. This allows for the deployment of embolic materials to highly complex locations within the neurovascular network. The trade-off between size, navigability, flexibility, and injection pressure is often nontrivial in microcatheter design. Microcatheters are often hindered from obtaining additional features that may be available in larger sizes, such as pull wires for active steering. The limited capabilities of microcatheters beyond injection and balloon occlusion have inhibited the innovation of novel embolic materials. For example, balloon-assisted deployment of the precipitating liquid embolic agent Onyx HD-500 in cerebral aneurysms has seen limited adoption, likely due to a lack of deployment control, and there are several case reports of off-target embolization in the literature.

[0006]

[0006] To minimize reperfusion of the treated vessel or other iatrogenic events, there is a clinical need for devices and methods that enable intravascular embolization with i) precise spatiotemporal control of embolic deployment, ii) a shape that is highly adaptable to various vessel morphologies, and iii) excellent mechanical properties of the embolus without structural compression or fracture. Summary of the Invention

[0007] According to some embodiments, a microcatheter device is provided that includes a working lumen and a mechanically protected waveguide. The working lumen has at least one exit port at a distal end of the working lumen and is configured for intravascular injection of a photoactivated embolic agent (PEA) into a target vessel through the at least one exit port. The mechanically protected waveguide (MPW) is operably connected to the working lumen and configured to emit at least one electromagnetic wave through the at least one exit port for delivery to the target vessel.

[0008]

[0008] In some embodiments, the mechanically protected waveguide is at least partially embedded in the wall of the working lumen, co-extruded within the wall of the working lumen, at least partially separated from the working lumen by at least one barrier, coupled to an outer section of the working lumen, woven into a braided portion of the microcatheter, and / or at least partially disposed within an enclosure separate from the working lumen.

[0009]

[0009] According to some embodiments, the microcatheter device further comprises a pre-hardening region within the microcatheter adjacent to at least one exit port, the pre-hardening region configured to adjust the viscosity of the PEA prior to injection into the target vessel.

[0010] According to some embodiments, the mechanically protected waveguide comprises a multimode optical fiber.

[0011] According to some embodiments, the working lumen comprises a biocompatible material such as nylon, vestamid, pebax, and PTFE.

[0012] According to some embodiments, the mechanically protected waveguide is configured to emit electromagnetic waves into the target vessel and / or pre-hardened region.

[0013] According to some embodiments, the microcatheter device further comprises at least one beam forming element. According to some embodiments, the at least one beam forming element comprises one or more optical components, such as one or more of a lens, a diffuser, a filter, a reflector, and a mask. According to some embodiments, the at least one beam forming element is configured to provide at least one radially emitted light beam for delivery to the pre-cure region.

[0014]

[0014] According to some embodiments, the microcatheter device further includes at least one emitted light beam, including a first beam directed toward the target vessel and a second beam directed toward the pre-cured region.

[0015] According to some embodiments, the at least one beam forming element includes a plurality of beam forming elements configured to provide a plurality of radial beams in a plurality of directions.

[0016] According to some embodiments, the mechanically protected waveguide comprises a fiber Bragg grating (FBG). According to some embodiments, the FBG element is configured to be tuned to a secondary wavelength and to back-reflect light having a second wavelength. According to some embodiments, the FBG is configured to selectively propagate light of a first wavelength in a first direction and light of a second wavelength in a second direction based on the frequency of the electromagnetic wave. According to some embodiments, the first direction is toward at least one exit port and the second direction is a radiation direction.

[0017] According to some embodiments, the microcatheter device further comprises a detachment mechanism configured to detach the coagulated PEA from the distal tip of the microcatheter. According to some embodiments, detachment of the PEA is induced by emitting electromagnetic waves via the MPW at a predetermined wavelength configured to photolyze the crosslinked PEA. According to some embodiments, the detachment mechanism comprises a superhydrophobic coating applied to an outer surface of the distal tip proximate the at least one exit port.

[0018] According to some embodiments, at least a portion of the distal end includes a reflective coating and / or reflective material and is configured to reflect excess light emitted radially outward in a radially inward direction.

[0019] According to some embodiments, the microcatheter device further comprises an optical cavity operably connected to the pre-cured region.

[0020] According to some embodiments, the mechanically protected waveguide comprises an optical fiber configured to guide at least one evanescent wave into physical contact with the PEA.

[0021] According to some embodiments, the optical refractive index can be detected within the PEA. According to some embodiments, the microcatheter further comprises a detection mechanism configured to detect changes in the optical refractive index of the medium surrounding the mechanically protected waveguide.

[0022] According to some embodiments, the microcatheter device further comprises a power injector configured to deliver fluid to the outlet port at a predetermined pressure and determine a change in fluid backpressure, according to some embodiments, the determination of the change in fluid backpressure is performed in real time.

[0023] According to some embodiments, the microcatheter device further comprises a detachable tip. According to some embodiments, the detachable tip is configured to dissolve within the target vessel over a predetermined amount of time (typically within tens to hundreds of seconds). According to some embodiments, the detachable tip is biocompatible.

[0024] According to some embodiments, the distal end of the mechanically protected waveguide is allowed to float freely within the pre-cured region.

[0025] According to some embodiments, the microcatheter device further comprises at least one valve mechanism.

[0026] According to some embodiments, the distal end of the working lumen is tapered. According to some embodiments, the taper is sized to achieve a desired flow rate of the PEA into the target vessel.

[0027] According to some embodiments, the microcatheter device further comprises a solid element inserted into the working lumen.

[0028]

[0028] According to some embodiments, the microcatheter device further comprises at least one additive liner within the pre-cured region, the at least one additive liner configured to limit adhesion of the cured PEA to the inner and / or outer surfaces of the working lumen.

[0029] According to some embodiments, there is provided a method of intravascular embolization comprising introducing a microcatheter device according to any one of the preceding embodiments into a target vessel, injecting a photoactivated embolic agent (PEA) into the target vessel until a desired volume of the target vessel is filled, and subsequently or simultaneously irradiating the PEA disposed within the target vessel with electromagnetic waves at a coagulation wavelength. According to some embodiments, the irradiating comprises irradiating the electromagnetic waves to a pre-cured region.

[0030] According to some embodiments, the method further includes determining whether there has been a malfunction of the microcatheter device prior to emitting the electromagnetic waves at the coagulation wavelength. According to some embodiments, determining whether there has been a malfunction of the microcatheter device includes detecting at least one electromagnetic wave reflected back from the PEA.

[0031] According to some embodiments, the method further comprises removing the microcatheter from the coagulated PEA and the target vessel after emitting electromagnetic waves at the coagulation wavelength. According to some embodiments, removing the microcatheter comprises detaching the microcatheter from the coagulated PEA. According to some embodiments, removing the microcatheter comprises activating a photolysis mechanism.

[0032] According to some embodiments, the method further includes determining a coagulation state of the PEA. According to some embodiments, the determining is performed in real time or near real time. According to some embodiments, the determining includes detecting at least one electromagnetic wave reflected back from the PEA placed in the target vessel.

[0033]

[0033] For a better understanding of the various aspects or embodiments described herein, and to show more clearly how they may be carried into effect, reference will now be made, by way of example only, to the accompanying drawings, in which: [Brief explanation of the drawings]

[0034] [Figure 1a] Several exemplary vascular morphologies suitable for embolization using a light-delivering microcatheter device (100) and a light-activated embolic agent (109) are shown. [Figure 1b] Several exemplary vascular morphologies suitable for embolization using a light-delivering microcatheter device (100) and a light-activated embolic agent (109) are shown. [Figure 1c] Several exemplary vascular morphologies suitable for embolization using a light-delivering microcatheter device (100) and a light-activated embolic agent (109) are shown. [Figure 1d] Several exemplary vascular morphologies suitable for embolization using a light-delivering microcatheter device (100) and a light-activated embolic agent (109) are shown. [Figure 1e]Several exemplary vascular morphologies suitable for embolization using a light-delivering microcatheter device (100) and a light-activated embolic agent (109) are shown. [Figure 1f] Several exemplary vascular morphologies suitable for embolization using a light-delivering microcatheter device (100) and a light-activated embolic agent (109) are shown. [Figure 2a] 1 illustrates an exemplary microcatheter (100) having a working lumen (101) within an exemplary target vessel (200, 203, 204, or 205) for delivery of a photoactivated embolic agent (PEA), according to a non-limiting embodiment. A mechanically protected waveguide (MPW) (102) is embedded in the wall of the working lumen (101). Similarly, according to a non-limiting embodiment, the distal end (134) of the microcatheter has an exit port (113) through which the PEA (109) is injected into the target vessel. [Figure 2b] 1 shows an exemplary embodiment of a microcatheter in which a MPW (102) is configured such that an area within a working lumen (101) is exposed to electromagnetic waves (104), according to a non-limiting embodiment. [Figure 2c] 1 shows an exemplary embodiment in which the MPW (102) actively transmits an electromagnetic wave (104) towards the PEA (109), according to a non-limiting embodiment. [Figure 3a] 1 shows several iterations of how mechanical protection is applied to the MPW (102), according to a non-limiting embodiment. [Figure 3b] 1 shows several iterations of how mechanical protection is applied to the MPW (102), according to a non-limiting embodiment. [Figure 3c] 1 shows several iterations of how mechanical protection is applied to the MPW (102), according to a non-limiting embodiment. [Figure 3d] 1 shows several iterations of how mechanical protection is applied to the MPW (102), according to a non-limiting embodiment. [Figure 3e] 1 shows several iterations of how mechanical protection is applied to the MPW (102), according to a non-limiting embodiment. [Figure 3f] 1 shows several iterations of how mechanical protection is applied to the MPW (102), according to a non-limiting embodiment. [Figure 3g] 1 shows several iterations of how mechanical protection is applied to the MPW (102), according to a non-limiting embodiment. [Figure 3h] 1 shows several iterations of how mechanical protection is applied to the MPW (102), according to a non-limiting embodiment. [Figure 4] A plurality of beam forming elements (105) are shown directing electromagnetic waves (104) through exit ports (113) towards the pre-cure region (103), according to a non-limiting embodiment. [Figure 5] A plurality of beamforming elements (105) are shown directing electromagnetic waves radially inside and / or outside (106) the working lumen, according to a non-limiting embodiment. [Figure 6a] A plurality of beam forming elements (105) are shown directing electromagnetic waves (106 and / or 104) radially inward, outward, and / or in the same direction as the exit port (113), according to a non-limiting embodiment. [Figure 6b] 1 illustrates an example of how multiple beamforming elements (105) can be arranged using MPWs (102), according to a non-limiting embodiment. [Figure 7] shows a fiber Bragg grating (FBG) element (108) positioned between radiating electromagnetic waves (104, 114), according to a non-limiting embodiment. [Figure 8a] 1 shows a microcatheter (100) in accordance with a non-limiting embodiment, in which the cured PEA (111) is fully and / or over-cured to the microcatheter (100) within the target vessel and is not easily removed. [Figure 8b-1] 1 shows a radiation beam intended to soften / melt the cured PEA (116), according to a non-limiting embodiment. [Figure 8b-2] 1 shows softened regions of the cured PEA (117) that allow for separation of the microcatheter (100) and the bonded PEA (115), according to a non-limiting embodiment. [Figure 9] 1 shows an exemplary microcatheter coated at its distal end with a coating or liner (118) that limits bonding between the microcatheter (100) and the cured PEA (111), according to a non-limiting embodiment. This coating can be hydrophobic or hydrophilic. [Figure 10] 1 shows an exemplary microcatheter with a distal tip made of a reflective material (119), according to a non-limiting embodiment. [Figure 11a] 1 shows an exemplary microcatheter that emits electromagnetic waves (104) intended to thicken uncured PEA (109), according to a non-limiting embodiment. [Figure 11b] An exemplary microcatheter is shown in which the PEA (111) is fully cured and the reflected electromagnetic waves from the cured PEA (112) are directed to the MPW (102). [Figure 12] 1 shows an exemplary microcatheter in which the MPW (102) is in direct contact with the PEA (109), according to a non-limiting embodiment. An evanescent wave source (120) is propagating. An evanescent wave (120) and a reflected evanescent wave source are generated (122). [Figure 13] 1 shows a power injector capable of inferring back pressure (123) hydraulically connected to a working lumen (101), according to a non-limiting embodiment. [Figure 14] 1 shows a power injector capable of inferring back pressure (123) hydraulically connected to a working lumen (101), according to a non-limiting embodiment. A fault or leak (124) occurs in the hydraulic system, in this case, within the working lumen (101). [Figure 15] 1 shows an exemplary microcatheter in which the MPW (102) has a fault and / or break (130) along its length, according to a non-limiting embodiment. MPW (102). [Figure 16] 1 shows an exemplary microcatheter having a detachable tip (132) attached to its distal end, according to a non-limiting embodiment. [Figure 17]4 shows a detailed exemplary flow chart (400) of a method in which a PEA is used with a microcatheter, according to a non-limiting embodiment. [Figure 18a] 1 shows an exemplary microcatheter with an outlet relief valve (135) attached to the outlet port of the working lumen, according to a non-limiting embodiment. [Figure 18b] 1 illustrates a scenario in which the PEA is cured into a solid, according to a non-limiting embodiment. Pressure within the working lumen forces the cured PEA through the outlet relief valve (also referred to herein as the outlet port valve). [Figure 19] 1 illustrates a working lumen material acting as a diffuser for electromagnetic waves, according to a non-limiting embodiment. [Figure 20a] Varying the flow rate helps increase the area exposed to the electromagnetic waves, according to a non-limiting embodiment. Shown is an enlarged (137) pre-cure area. [Figure 20b] Varying the flow rate helps increase the area exposed to the electromagnetic waves, according to a non-limiting embodiment. Shown is an enlarged (137) pre-cure area. [Figure 21a] 1 illustrates a non-limiting configuration of a pre-cured region having tapered or narrowed walls resulting in a smaller cross-sectional area at the tip. [Figure 21b] 1 illustrates a non-limiting configuration of a pre-cured region having tapered or narrowed walls resulting in a smaller cross-sectional area at the tip. [Figure 22a] 3A and 3B show simplified exemplary flow charts (300a and 300b) outlining the use of a microcatheter device to deposit PEA, according to non-limiting embodiments. [Figure 22b] 3A and 3B show simplified exemplary flow charts (300a and 300b) outlining the use of a microcatheter device to deposit PEA, according to non-limiting embodiments. [Figure 23] 1 shows an example of multiple MPWs (102) contained within respective channels and terminating at different locations in multiple beam directions, according to a non-limiting embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0035]

[0059] It will be understood that for simplicity and clarity of description, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements or steps. Furthermore, numerous specific details are set forth in order to provide a thorough understanding of the embodiments described herein. However, those skilled in the art will understand that the embodiments described herein may be practiced without these specific details. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the embodiments described herein. Furthermore, this description should not be deemed to be in any way limiting the scope of the embodiments described herein, but rather merely illustrative of implementations of the various embodiments described herein.

[0036]

[0060] Ideally, the existing limitations in clinically available medical devices and materials for endovascular embolization would be addressed by a multifaceted solution that addresses the challenges associated with embolization as well as their applicators (i.e., microcatheters). One solution could be for the embolic material to be stimuli-responsive so that the clotting process can be triggered on demand, while the catheter could have the ability to trigger such a clotting process.

[0037]

[0061] SUMMARY OF THE INVENTION A light-delivering microcatheter device and method for intravascular injection of a light-activated embolic agent are described herein.

[0038]

[0062] The present application generally provides a means of endovascular embolization to cause controlled cessation of local blood flow in association with various vascular diseases. One aspect of the systems and methods described herein relates to a microcatheter design capable of delivering a photoactivated embolic agent (PEA) while simultaneously emitting electromagnetic waves into a target vascular anatomy, such as a target blood vessel, via a mechanically protected waveguide (MPW) and / or within the microcatheter device.

[0039]

[0063] In one aspect, the properties of PEA are such that the material is initially in a flowable liquid state and solidifies to form a soft, elastic solid upon exposure to electromagnetic radiation of a predetermined wavelength (typically 200-600 nm). Thus, one purpose of the light-delivered microcatheter device's ability to emit electromagnetic radiation is to controllably trigger the solidification of PEA to form an embolic plug at a desired location within the diseased vasculature.

[0040]

[0064] According to some embodiments, PEA is a stress-relieving fluid. In its resting state, PEA can exhibit solid-like properties, but can become flowable upon exposure to certain stresses, such as injection pressure across the catheter lumen. In some instances, such properties of PEA can facilitate PEA injection through a microcatheter while simultaneously providing initial resistance to blood flow by regaining its solid-like state once inside the vasculature. This initial resistance to blood flow can improve the effectiveness of light-activated coagulation by preventing material washout. Subsequent light-activated coagulation of PEA is typically irreversible, further stabilizing the injected material in the vascular lumen.

[0041]

[0065] In some embodiments, the microcatheter comprises a working lumen through which the PEA can be delivered to the target vessel using a syringe driven manually or by an infusion pump. The microcatheter is typically guided to the target vessel using a guidewire. The PEA is then injected through the microcatheter and into the target vessel through the microcatheter's exit port. The PEA deposited within the target vessel can be exposed to electromagnetic waves to initiate crosslinking, increasing the PEA's viscosity and elastic modulus, ultimately transforming it into a soft, elastic, solid material. One attribute of the microcatheter is that the waveguide is mechanically protected (MPW); otherwise, the use of accessories such as guidewires and high-pressure hydraulic injection can damage the waveguide and deposit electromagnetic waves in unintended locations.

[0042]

[0066] According to some embodiments, a pre-cured region is included within the distal portion of the microcatheter. Before the PEA exits the microcatheter and enters the target vessel, the pre-cured region can be exposed to electromagnetic waves, which allows the PEA to thicken or coagulate. There are a wide variety of target vessels that the operator may occlude, including, but not limited to, high-flow areas or areas where over-penetration of the vasculature must be avoided due to critical structures downstream. Pre-curing the PEA can better localize embolic deposition by remaining tethered to the catheter tip or by size exclusion when the coagulated mass becomes trapped in the distal vasculature (which is typically smaller in size). For example, if the target vessel is relatively large and has a high blood flow, a PEA with a higher viscosity is typically appropriate, while if the target vessel is relatively narrow and has a low flow rate, a PEA with a lower viscosity or conformal nature is typically recommended. The ability to control provides the operator with a level of control over the PEA.

[0043]

[0067] There are several ways to provide mechanical protection for the contemplated waveguide, including, but not limited to: i) partially embedding the MPW in the working lumen, ii) co-extruding the working lumen wall with the MPW, iii) having a barrier between the working lumen and the MPW, iv) bonding the MPW to the exterior of the working lumen, v) weaving the waveguide between braid layers, vi) being protected separately from the working lumen, and / or vii) partially embedding the MPW in the wall of the working lumen while physically transferring a region into the working lumen, but it is understood that any suitable means or combination of means for mechanically protecting the waveguide is contemplated.

[0044]

[0068] The MPW can be configured in several different ways to emit electromagnetic waves. For example, the electromagnetic waves can be emitted toward the exit port of the microcatheter, through the exit port toward the target vessel, toward the pre-cured region, and / or radially toward the target vessel. This can be achieved by placing the MPW within the working lumen. Additionally, beam-shaping elements (such as micro-optics) can be added anywhere appropriate along the optical path of the MPW (or distal to the MPW) to further help direct the electromagnetic waves toward any of the target regions. The use of beam-shaping elements is typically required for complex beam profiles and directions.

[0045]

[0069] In some embodiments, fiber Bragg gratings (FBGs) are added along the length of the MPW. This addition generally provides a means to select specific electromagnetic waves for specific directions. The FBG is tuned to reflect a specific bandwidth of electromagnetic waves and transmit the rest of the electromagnetic spectrum. An example use of an FBG is to orient the FBG between two different beamforming elements. If a bandwidth is selected that matches the FBG's reflection profile, all beamforming elements proximate the FBG will emit the electromagnetic wave. If the bandwidth does not match the FBG's reflection profile, it will be transmitted. This mechanism generally gives the operator an added sense of control. A foreseeable application is when an operator wants to independently change the input power of the electromagnetic wave at the pre-cured region relative to the input power at the exit port.

[0046]

[0070] According to some embodiments, multiple wavelengths are utilized, where a primary wavelength of electromagnetic radiation crosslinks and thickens or solidifies the PEA. A secondary wavelength can be used to break the crosslinks and liquefy certain types of solidified PEA. This is useful when the PEA adheres to the microcatheter and cannot be retrieved while engaged within the blood vessel. Alternatively, a hydrophobic coating can be applied to the distal end of the microcatheter to prevent strong bonding between the cured PEA and the microcatheter.

[0047]

[0071] According to some embodiments, multiple MPWs are integrated to achieve various electromagnetic energy distributions. For example, in a two-MPW configuration, one MPW can terminate proximal to the pre-cured region and the other MPW can continue to the tip of the catheter. The MPWs in such a configuration can operate sequentially or in unison.

[0048]

[0072] In ideal operation of the pre-curing segment of the catheter, a predetermined level of electromagnetic energy, typically in the range of about 1 to about 1000 mJ of an appropriate wavelength (typically about 200 to about 600 nm), should reliably thicken or solidify the flowable PEA into a soft solid, regardless of variations in injection force that a user may apply during use. In other words, according to some embodiments, the system should be sufficiently insensitive to such input variations so as not to inadvertently release uncured material (in the case of an overly rapid injection) or clog the pre-curing region (in the case of an overly slow injection), either of which could result in procedural complications.

[0049]

[0073] Furthermore, the ability of the pre-hardening zone combined with the electromagnetic energy source to continuously thicken or coagulate the injected PEA may be independent of catheter placement in a given vasculature or local hemodynamics. For example, the catheter tip does not necessarily need to be parallel to the blood vessel, but rather may be directed toward the wall. Such limited catheter positioning may disrupt the flow of PEA from the catheter port and affect the coagulation process.

[0050]

[0074] According to some embodiments, one or more valve mechanisms can be used within the catheter. The valves can be pressure-activated to restrict the passage of uncured PEA until a predetermined pressure differential (typically on the order of one-tenth to several hundred PSI) across a given segment of the catheter is achieved. In one aspect, such a valve mechanism can be used at the distal port of the catheter to release and deposit cured PEA (flowable under high pressure) into the target vasculature while preventing the accidental release of uncured PEA (flowable under low pressure).

[0051]

[0075] To prevent the unintended release of uncured precursor, some embodiments may employ a tapered lumen wall at the distal end of the catheter. Such a tapered wall generally reduces the flow rate of the precursor through the pre-cured region, allowing for greater exposure to electromagnetic energy and ensuring more robust thickening or coagulation. In some embodiments, the tapered wall may also act to reflect the forward firing beam emitted by the waveguide back toward the pre-cured region, further increasing the efficiency of thickening or coagulation.

[0052]

[0076] To increase the crosslinking efficiency within the pre-cured region, a reflective material can be added around the pre-cured region so that the radially radiating electromagnetic waves are reflected toward the pre-cured region. This can also direct a majority of the incident electromagnetic waves toward the exit port (and the target vessel). The reflective material can be made of a radiopaque material.

[0053]

[0077] According to some embodiments, there are back-reflected electromagnetic waves from the uncured PEA. As the PEA transitions from uncured to cured, the optical properties of the back-reflected electromagnetic waves may change. The total power, spectrum, or polarization properties may change based on the state of the PEA. Evaluating these EM wave properties on the back end may help inform the operator of the state of the PEA.

[0054]

[0078] Similar to monitoring the back-reflected electromagnetic waves from the PEA, in some embodiments, the evanescent wave power can be inferred by monitoring the reflected signal from the FBG. This is also an indirect way of informing the operator of the status of the PEA. Further details are provided in the detailed description.

[0055]

[0079] When a PEA is included in a microcatheter's hydraulic system, if the PEA changes from a liquid state to a solid state, this can cause an increase in backpressure in the system. A power injector capable of detecting pressure can be used to infer the viscosity state of the PEA. Conversely, according to some embodiments, if there is a break or failure in the hydraulic system, the backpressure will drop dramatically, which will also be detected by the power injector.

[0056]

[0080] Another failure scenario is when there is a break or defect imposed on the MPW. When a defect is induced in the optical path, the returning electromagnetic waves (known as return loss) increase. Monitoring this for sudden changes is a way to infer whether any damage has occurred to the MPW.

[0057]

[0081] According to some embodiments, the distal portion can have a detachable tip. Detachment methods can include any suitable combination of: physical separation by force, such that a predetermined tear point is destroyed; physical separation by dissolving the predetermined tear point with emitted electromagnetic waves (or secondary electromagnetic waves); or physical separation by dissolving the predetermined tear point with the use of a biocompatible injectable gel specifically designed for dissolution. The detachable tip can be made of a biocompatible material that dissolves while remaining as an implantable device. A non-limiting example of such a material is polyvinyl alcohol (PVA), which is known to dissolve slowly in water and has been micronized and used as a temporary embolic agent.

[0058]

[0082] According to some embodiments, a typical use of the described microcatheter involves guiding the microcatheter to the treatment site using a conventional guidewire. A pre-embolization scan of the disease site is performed using digital subtraction angiography. At this point, the operator can determine what type of viscosity is needed for the PEA to optimally fill the treatment site based on the type of disease. The operator(s) typically select the correct EM wave power for the desired viscosity and inject the PEA accordingly. The operator typically injects the PEA into the disease until it is filled. Using fluoroscopy, the operator can confirm when the treatment site is filled. The operator performs post-injection curing of the PEA by emitting EM waves at the treatment site until the embolic plug solidifies. Several methods for monitoring PEA coagulation are described herein. After coagulation is complete, the operator can remove the microcatheter from the treatment site. According to some embodiments, if removal is difficult due to adhesion between the catheter and the coagulated PEA, the operator can activate the detachment mechanism described herein. According to some embodiments, there are several fault detection methods monitored throughout the use of the microcatheter. Failures include, but are not limited to, a leak from the catheter or a break in the MPW.

[0059]

[0083] Attention is drawn to Figures 1a-1f, which illustrate the use of a light-delivering microcatheter device (100) in combination with a photoactivated embolic agent (PEA) (109, 111) within exemplary vascular morphologies (200, 201, 202), according to non-limiting embodiments. For a given vessel, for example, an operator typically assesses the local vascular morphology, such as nominal blood flow, vessel diameter, and downstream anatomical structures, to determine the optimal injection scheme. Several non-limiting examples are shown in Figures 1a-1f. The first example, shown in Figures 1a and 1b, is of a hypervascular tumor (202), a terminal vasculature composed of capillaries (204). In this case, the PEA (109) is injected into the structure from a larger nutrient artery (203) where the tip of the light-delivering microcatheter device (100) is positioned. Here, throughout Figures 1a-1f, the shaded area represents uncured PEA (109), while the shaded area represents photoactivated and coagulated PEA (111). Due to the inherent rheological properties of PEA (109), which may include shear recovery, material released into the microvasculature is reasonably expected to form a plug up to the injection point. In the example shown in Figure 1b, the operator can choose to first inject precursor PEA (109) into the lesion without electromagnetic radiation (i.e., no thickening or coagulation) to achieve distal penetration. The proximal portion of the injected PEA is then photoactivated (111), generally stabilizing the entire structure. The next example, shown in Figures 1c and 1d, is of an arteriovenous malformation (201), a high-pressure shunt lesion between arteries (205) and veins (206) consisting of multiple interwoven focal vessels (201). In this case, because the structure drains into the venous network (206) rather than distally, excessive penetration of the PEA (109) could potentially cause downstream ischemic events. The operator can address this situation in several ways. One method is to perform a temporary balloon occlusion proximal to the injection point such that the injected PEA (109) is under reduced hemostatic pressure that is driven distally, improving operator control of injection pressure and penetration depth. Another approach is to simply preselect a higher viscosity PEA (109) when injectable through the optically delivered microcatheter device (100) that is more resistant to excessive flow into the distal vasculature.Alternatively, as the PEA (109) enters the vessel, it can be simultaneously injected with a predetermined amount of electromagnetic radiation, thereby thickening or solidifying the PEA (111). This approach can simultaneously benefit from low injection pressure and high occlusion capacity. It should be understood that the effective distribution of uncured PEA (109) and photoactivated PEA (111) occupying the foci (201) can vary significantly depending on the injection technique selected, and Figure 1d represents an exemplary case. For example, if the operator chooses to inject uncured PEA (109) while constantly emitting electromagnetic energy, the entire structure may be composed of photoactivated PEA (111). In the final example of an aneurysm shown in Figures 1e and 1f, the embolic material must be strictly confined within the small aneurysmal space (200) without leakage into the parent artery (250), and the operator may wish to use a balloon catheter (251) for embolization. It can be seen that the photoactivated (having at least some degree of thickening or coagulation) PEA (111) completely fills the aneurysmal space (200) and coagulates therein, so the injection of PEA and the radiation of electromagnetic waves into the aneurysmal sac (200) may be performed sequentially or simultaneously to seal the structure. As shown in Figures 1a-1f, the target vessels may be considered to be, but are not limited to, 200, 203, 204, and 205.

[0060]

[0084] FIG. 2a shows an example of the distal end of a microcatheter device (100) in its simplest form, contained within a target vessel (200, 203, 204, or 205). It comprises a working lumen (101) configured for intravascular injection of a photoactivated embolic agent (PEA) through at least one exit port (113). It also comprises a mechanically connected waveguide (102) operably connected to the working lumen (101) and configured to emit at least one electromagnetic wave through the at least one exit port (113) for delivery to the target vessel (via delivery of electromagnetic wave(s) to the PEA). Not shown in FIGS. 2a-2c for simplicity is a fluid connection for the PEA from a syringe or accessory that can apply pressure to achieve flow of the PEA through the working lumen (101) and out the exit port (113). The exit port (113) is located at the distal end (134) of the working lumen (101). Because the PEA is delivered to a target vascular anatomical structure, such as a target vessel (200, 203, 204, or 205) within the human anatomy, the working lumen (101) is typically of sufficient diameter to accommodate a conventional guidewire used by a surgeon to navigate to the target vessel (200, 203, 204, or 205) and facilitate injection of the PEA. Once the target vessel is navigated, the operator can apply hydraulic pressure to the working lumen (101) to deposit the PEA. Exposure to electromagnetic waves is required to crosslink and coagulate the PEA within the target vessel. The electromagnetic waves are propagated along a waveguide (102), and their transmission is controlled by the operator. Delivering the PEA and / or navigating it with a guidewire through the working lumen would damage an unprotected waveguide. Mechanical protection is provided to the waveguide (102) to limit damage to the waveguide (102). All embodiments of the waveguide (102) described herein have at least some degree of mechanical protection, and therefore the waveguides are referred to as mechanically protected waveguides (MPW) (102).

[0061]

[0085] Figures 2b and 2c show variations of an exemplary microcatheter (100), according to non-limiting embodiments. The MPW (102) is recessed from the distal end (134) to provide a pre-cured region (103) within the microcatheter device (100) between the MPW (102) and the exit port (113) adjacent the exit port (113). Figures 2b and 2c show electromagnetic waves (104) radiating within the pre-cured region (103), toward the exit port (113), and both outside the exit port (113) and into the target vessel. The pre-cured region (103) is configured to help regulate the viscosity of the PEA prior to injection into the target vessel (200, 203, 204, or 205). Recessing the MPW (102) allows for thickening of the PEA (109) in the pre-cured region (103) and before entering the target vessel. Dynamically adjusting the total power of the electromagnetic wave (104) provides the operator with a level of control by controlling the viscosity of the PEA (109) as it enters the target vessel (200, 203, 204, or 205). It is understood that various disease sites require different viscosities. Figure 2b illustrates a scenario in which no PEA is present in the working lumen (101). Figure 2c illustrates uncured PEA (109) within the working lumen.

[0062]

[0086] The MPW (102) may be made from, but is not limited to, multimode optical fiber. Other suitable MPW (102) materials include single-mode optical fiber, glass rods, encased fluid channels, channels encased in reflective materials, or any suitable combination thereof.

[0063]

[0087] Figures 3a-3h illustrate several exemplary methods and degrees of mechanical protection for the MPW (102). Figure 3a illustrates an example in which no additional mechanical protection is provided for the MPW (102). The entire length of the MPW (102) is in physical contact with either the PEA or the guidewire. As a result, there is no protection from the guidewire throughout normal use of the working lumen (101). Figure 3b illustrates an exemplary method of providing mechanical protection in which the MPW (102) is co-extruded with the wall (138) of the working lumen (101). In this method, the MPW (102) is configured to withstand the temperatures required for lumen extrusion. Other methods include, but are not limited to, reflowing the working lumen (101) so that the MPW (102) is positioned or otherwise at least partially embedded within the wall (138). Figure 3c illustrates a secondary lumen (107) within the wall (138) of the working lumen (101). The secondary lumen 107 is large enough to allow the MPW 102 to pass through. In this regard, providing the secondary lumen 107 provides an enclosure, such as enclosure 107a, through which the MPW 102 is disposed at least partially separate from the working lumen. Dual lumen extrusions can be fabricated, allowing the MPW 102 to pass through the secondary lumen 107. Wall clearance between the MPW 102 and the inner diameter of the secondary lumen 107 is typically minimal due to size constraints of the overall microcatheter diameter. Coatings on the inner diameter of the secondary lumen 107, or other enclosures separate from the working lumen, and the MPW 102 can be used to help guide the MPW 102 throughout the entire length of the working lumen 101 manufacturing process. Reflow processes, the addition of adhesives, or heat shrinking are examples of methods for securing the MPW 102 within the working lumen 101 to prevent independent translation during manufacturing or use. Figure 3d shows the MPW (102) adhered to the outer wall of the working lumen (101). Attachment to an outer section of the working lumen (101), such as outer wall (138), also serves to create mechanical separation (and therefore at least some degree of mechanical protection) between the PEA and / or guidewire.Various methods can be used to attach the additional wall to the wall, including, but not limited to, heat shrinking the additional wall, using adhesives, or reflowing. In the exemplary embodiment shown in Figures 3b-3d, the PEA and / or guidewire generally do not come into direct contact with the MPW (102), further reducing the possibility of failure. Figure 3h depicts another exemplary embodiment of mechanical protection in which the MPW (102) is woven into the braided portion (139) and / or coiled layer of the microcatheter. The presence of braids (139) and / or coiling within microcatheters is common and may interfere with the MPW (102). However, according to some embodiments, the MPW may also be woven between various braids (139) or coiled layers. Another embodiment of mechanical protection is to embed the MPW (102) in a separate working lumen (101), intended for use in conjunction with the microcatheters described herein. In Figures 3e and 3f, the MPW (102) is adhered to and protected by the secondary lumen (107). Specifically, with respect to the pre-cured region, at least a portion of the MPW (102) shown in Figures 3e and 3f has the ability to float within the working lumen (101) to allow deposition of the electromagnetic wave (104) at the center of the working lumen (101). When a solid element (such as a guidewire) is inserted into the working lumen (101), the MPW (102) has the freedom to re-center the secondary lumen (107) within the pre-cured region (103).

[0064]

[0088] Figure 3g shows another exemplary mechanism for mechanical protection for the MPW (102), in which the MPW has the ability to retract or move into the secondary lumen (107) while the solid element is inserted into the working lumen (101). Once the solid element is reinserted, the MPW (102) can be returned to the working lumen.

[0065]

[0090] The working lumen (101) of the microcatheter may be constructed of a biocompatible material. Examples of suitable biocompatible materials are nylon, VESTAMID™, PEBAX™, and polytetrafluoroethylene (PTFE). Any suitable biocompatible material is contemplated.

[0066]

[0091] The MPW (102) can be configured to emit electromagnetic waves (104) in various directions (see, e.g., FIG. 6). According to some embodiments, the electromagnetic waves (104) can be emitted toward the exit port (113), through the exit port (113) toward a target vessel, such as target vessel (200, 203, 204, or 205), toward the pre-cured region (103), and / or radially toward the target vessel. These locations may be referred to herein (without limitation) as target regions. According to some embodiments, the MPW (102) can be physically oriented and secured in place using, for example, either adhesive epoxy or reflow techniques.

[0067]

[0092] Additionally, at least one beam-forming element (e.g., micro-optic) (105) can be added at any suitable location along the optical path length of the MPW (102) to further assist in directing the electromagnetic wave (104) to any of the target regions. The MPW (102) emits light based on a numerical aperture (NA). Adding a beam-forming element (105) can help provide the ability to further direct the light to the target region(s). More complex beam profiles and directions may require the use of multiple beam-forming elements (105). Figure 4 shows an example of a beam-forming element (105) used to expand the electromagnetic wave to achieve coverage within the pre-cure region (103) and toward and through the exit port (113). In this illustration, the orientation of the MPW (102) includes a position where the MPW (102) is recessed, thereby achieving better coverage within the pre-cure region (103). Alternatively conceptualized, the MPW (102) can be oriented further into the working lumen (101), which also increases the size of the pre-cured region (103). The beam-forming element (105) can be mechanically attached to the MPW (102) or can be physically separated from the MPW (102), so long as the electromagnetic wave (104) is affected by the beam-forming element (105).

[0068]

[0093] The exemplary microcatheter shown in FIG. 5 also utilizes beam-forming elements. However, the electromagnetic waves are directed toward the pre-cured region and / or radially outward. Examples of suitable beam-forming elements (105) for directing the electromagnetic waves in one or more directions include, but are not limited to, a prism or a folding mirror operably coupled to a focusing or defocusing component. According to some embodiments, at least one beam-forming element comprises one or more optical components, such as one or more of a lens, a diffuser, a filter, a reflector, a prism, a folding mirror, and a mask. Any suitable beam-forming element or combination thereof is contemplated.

[0069]

[0094] 6a also shows a beam forming element (105) whereby the electromagnetic waves (104 and 106) are directed for delivery toward the pre-cured region (103), toward an exit port (113), toward the target vessel, and / or radially (at least one radially emitting beam is provided for delivery to the pre-cured region). In addition to prisms, folding mirrors, focusing / defocusing elements, and / or beam splitters, predetermined splitting ratios can be used to optimize crosslinking in the PEA (109).

[0070]

[0095] According to some embodiments, the at least one beam forming element is configured to provide at least a first emitted light beam directed toward the target vessel and a second emitted light beam directed toward the pre-cured region (see, e.g., FIG. 6a).

[0071]

[0096] According to some embodiments, the at least one beam forming element includes multiple beam forming elements configured to provide multiple radial emitted light beams in multiple directions (see, e.g., FIG. 6b).

[0072]

[0097] According to some embodiments, the MPW (102) comprises a fiber Bragg grating (FBG). FIG. 7 shows an FBG (108) disposed along the length of the MPW (102). The FBG (108) is a device configured to reflect a specific bandwidth of electromagnetic radiation while allowing the remainder of the electromagnetic radiation spectrum to be transmitted. According to some embodiments, the FBG is tuned to a secondary wavelength and configured to back-reflect light having the second wavelength. For example, the FBG (108) can be configured to reflect the λ2 spectrum. As the λ2 radiation propagates through the MPW (102), most of it is typically reflected and exits the MPW (102) as a secondary curing wavelength (114). According to some embodiments, the FBG is configured to selectively propagate light of a first wavelength in a first direction and light of a second wavelength in a second direction based on the frequency of the electromagnetic radiation. For example, if an electromagnetic wave of spectrum λ1 (such as an electromagnetic wave in the ultraviolet range) is propagated and its spectral profile does not overlap with λ2, it will typically pass through the FBG (108) and propagate in a different direction than the secondary curing wavelength (114). If the microcatheter is configured with a back-end laser capable of providing both λ1 and λ2, the FBG (108) can provide a means of non-uniformly distributing the total amount of emitted electromagnetic wave (104, 114) in various directions (104 is a non-limiting example of light directed in a first direction toward the exit port, and 114 is a non-limiting example of light directed in a second direction of emission, or vice versa). Furthermore, if the back-end laser has the ability to select λ1 and / or λ2, the operator has the ability to select which emitted electromagnetic wave (104 or 114) to propagate to the PEA (109). The filter mechanism presented here is not limited to FBG with spectral filter components. Any suitable spectral components are contemplated in place of or in combination with the FBG.

[0073]

[0098] According to some embodiments, the microcatheter (100) further comprises a detachment mechanism configured to detach the solidified PEA from the distal end of the microcatheter. Figures 8a-8b-2 illustrate a detachment mechanism that uses a photolytic wavelength (116) to dissolve the cured PEA (111), releasing the adhered microcatheter (100) from the cured PEA (115). Figure 8a illustrates a microcatheter embedded and adhered within the fully cured PEA (111). A portion of the fully cured PEA (115) unintentionally adheres to the microcatheter (100), and upon removal of the microcatheter (100), the PEA (111) is released from the target vessel. According to some embodiments, PEA detachment is induced by emitting electromagnetic waves via the MPW at a predetermined wavelength configured to photolyze the crosslinked PEA (e.g., via a photolysis mechanism operably connected thereto). Figure 8b-1 shows a photolysis wavelength (116) that is a different spectrum than the electromagnetic waves (104, 106, and / or 114) used to cure the PEA. Figure 8b-2 shows the results of the photolysis wavelength (116) being able to decompose the cured PEA (115) back into uncured PEA (117). This frees the implanted microcatheter (100) from the cured PEA (115). The photolysis wavelength (116) can also be directed in multiple directions as needed.

[0074]

[0099] According to some embodiments, the detachment mechanism includes a superhydrophobic coating applied to the exterior surface of the distal end proximate at least one exit port. Figure 9 illustrates an exemplary mechanism for reducing the occurrence of a microcatheter (100) becoming embedded in cured PEA (111), according to a non-limiting embodiment. A portion of the microcatheter's distal end (134) that is expected to become unintentionally embedded in cured PEA (111) is coated with a hydrophobic coating (118). The portion of the distal end (134) may also include a pre-cured region (103). Those skilled in the art will generally understand that such hydrophobic coatings may include, but are not limited to, silica-based materials and fluoropolymers. The hydrophobic coating generally reduces the likelihood of contact between the PEA (111) and the microcatheter (100) material. The majority of commercially available microcatheters typically have a hydrophilic coating along their entire length to facilitate insertion into the body when wet. However, according to some embodiments, typically only the most distal end of the microcatheter (100) (e.g., the distal end of the working lumen and the outer surface of the distal end of the microcatheter) may be hydrophobic so as not to interfere with the hydrophilic coating required for the majority of the microcatheter. Additionally, the coating (118) may be of a type of material that does not adhere to the key interface elements of the uncured and cured PEA (109, 111). The coating may be applied to a material, or the entire area may be comprised of said coating.

[0075]

[0100] According to some embodiments, at least a portion of the distal end of the working lumen includes a reflective coating and / or reflective material configured to reflect excess light emitted radially outward in a radially inward direction. Figure 10 shows a non-limiting embodiment in which an optical reflector (119) is applied around a portion of the pre-cured region (103). The optical reflector (119) acts as an optical cavity in which electromagnetic waves (104, 106, 114, or 116) exiting the pre-cured region (103) are reflected radially inward back toward the pre-cured region (103). This helps ensure higher efficiency within the pre-cured region (103), directing more electromagnetic waves (104, 106, 114, or 116) toward the exit port (113). One example of an optical reflector (119) is a metallic material, such as a radiopaque marker band. Other suitable modes of achieving an optical cavity operatively connected to the pre-cured region include, but are not limited to, coating the inner surface of the lumen with a reflective metallic coating, such as gold, chromium, and platinum, via a process such as vapor deposition.

[0076]

[0101] Attention is now drawn to Figures 11a and 11b. In Figure 11a, a microcatheter has injected PEA (109) into a target vessel. Electromagnetic waves (104) are transmitted to the PEA (109) to induce hardening or viscosity changes. Reflected electromagnetic waves from the uncured PEA (110) are directed back to the MPW (102). Within the backend (not shown), an electromagnetic wave sensor can generate baseline readings based on either power, spectrum, or polarization. Figure 11b shows the state of the fully cured PEA (111) and the reflected electromagnetic waves from the cured PEA (112) directed to the MPW (102). Within the backend (not shown), the electromagnetic wave sensor compares the measurement to the baseline reading, providing an indication of relative hardening to the operator. Observation of the PEA (109 or 111) state can also be applied to detect dissolution of the PEA (111) during removal of a stuck microcatheter. The observed properties included back-reflected power, polarization state, and wavelength.

[0077]

[0102] According to some embodiments, the MPW comprises an optical fiber element configured to direct at least one evanescent wave into physical contact with the PEA. According to some embodiments, the optical refractive index can be detected within the PEA. FIG. 12 shows an exemplary embodiment of an MPW (102), a portion of which is in physical contact (133) with the PEA (109). The MPW (102) can transmit a wavelength characteristic of an evanescent function known as the evanescent wave source (121). When a small portion of the MPW (102) is exposed to the PEA (109), the evanescent wave phenomenon causes leakage of the evanescent wave source (121) into the PEA (109). The leaked portion is the evanescent wave (120). The strength of the evanescent wave is directly related to the optical refractive index of the PEA (109) with which it is in physical contact (133). This embodiment also includes an embedded FBG (108) or other optical fiber element specifically configured to reflect the electromagnetic waves of the evanescent wave source (120). The intensity of the reflected evanescent wave source (122) is directly correlated to the intensity of the evanescent wave (120). Thus, as the intensity of the evanescent wave (120) increases, the intensity of the reflected evanescent wave source (122) decreases, and vice versa. Assuming that the evanescent wave (120) is related to the refractive index of the PEA (109), a measurement of the relative intensity of the reflected evanescent wave source (122) and the known evanescent wave is an indication of the refractive index of the PEA (109). A possible characteristic of the PEA (109) is its refractive index variation based on its viscosity and / or its curing state.

[0078]

[0103] According to some embodiments, the microcatheter (100) further comprises a detection mechanism (140) configured to detect changes in the optical refractive index of the medium surrounding the mechanically protected waveguide for measuring the changed optical power, polarization state, and / or wavelength.

[0079]

[0104] According to some embodiments, the microcatheter (100) further comprises a power injector configured to deliver fluid to the outlet port at a predetermined pressure and determine changes in the fluid backpressure. Figure 13 shows an exemplary configuration of a microcatheter hydraulically attached to a power injector (123) capable of detecting the backpressure of the PEA (109, 111). The power injector (123) can inject the PEA (109) at a given rate and internal pressure of the system. As the PEA transitions from its uncured state (109) to its cured state (111), the power injector (123) applies the same force to the hydraulic system. If the internal pressure rises above a certain relative threshold, this typically indicates some kind of blockage within the microcatheter or solidification at the distal end of the working lumen (101). This is an indirect way of detecting the viscosity of the PEA (109, 111), which can then be reported to the operator. Another exemplary configuration is shown in Figure 14, where a breach or leak (124) is introduced somewhere within the hydraulic system, including the working lumen (101). The breach causes a sudden drop in internal pressure, which the power injector (123) can typically detect and report to the operator. According to some embodiments, the determination of the change in fluid backpressure occurs in real time or near real time.

[0080]

[0105] Attention is now directed to Figure 15 for an example of detecting a fault scenario within the MPW (102). An electromagnetic wave (104) propagates within the MPW (102), and a small amount of back-reflected electromagnetic wave (131) can be detected along the same line. When any defect or break (130) is introduced into the MPW (102), a reflection point is created. The intensity of the back-reflected electromagnetic wave (131) increases in intensity. Monitoring the relative increase in the intensity of the back-reflected electromagnetic wave (131) can indicate a break (130) in the MPW (102).

[0081]

[0106] Another exemplary embodiment of the described microcatheter device is where the distal end of the microcatheter is detachable from the working lumen, as shown in FIG. 16. In a scenario where the PEA has fully cured (111), the distal end (134) of the microcatheter is encapsulated and cannot be easily removed. The distal portion can have a detachable tip (132). Several methods for enabling tip detachment from the microcatheter include physical separation by force, such that a predetermined tear point is destroyed; physical separation by dissolving the predetermined tear point with emitted electromagnetic waves; and physical separation by dissolving the predetermined tear point with the use of a biocompatible injectable gel specifically designed for dissolution, either individually or in any suitable combination. Furthermore, the detachable tip (132) remains within the cured PEA (111) and subsequently within the target vessel. The detachable tip (132) is made of or otherwise includes a biocompatible material that naturally dissolves over time in the presence of blood flow. According to some embodiments, the detachable tip is configured to dissolve within the target vessel over a predetermined amount of time.

[0082]

[0107] According to some embodiments, the distal end of the MPW is free to float within the pre-cured region, as further described below.

[0083]

[0108] According to some embodiments, the microcatheter (100) further comprises at least one valve mechanism, as further described below.

[0084]

[0109] In some embodiments, the distal end of the working lumen is tapered. This increases the local resistance to PEA flow and therefore reduces the PEA flow rate under constant pressure conditions (such as when an operator applies a constant force to the syringe plunger). Combined with the implementation of a pre-curing region, this localized flow rate reduction increases the exposure time to the EM energy emitted by the MPW, thereby improving thickening / coagulation efficiency and preventing the accidental release of uncured PEA into anatomical structures.

[0085]

[0110] According to some embodiments, the microcatheter (100) further comprises a solid element inserted into the working lumen, such as a guidewire.

[0086]

[0111] 22a and 22b illustrate two non-limiting methods 300a and 300b of endovascular embolization using the microcatheter device described herein. In the first case, the operator typically begins by performing the endovascular navigation necessary to reach the target vessel. Once the catheter is properly positioned within the target vessel, the operator injects the PEA without yet turning on the EM energy source. Then, once the target vessel is sufficiently filled with uncured PEA, the operator enables the EM energy source to radiate through the distal region of the microcatheter device, coagulating the PEA. In the second case, the operator similarly performs the endovascular navigation necessary to reach the target vessel. Once optimal positioning of the microcatheter device is confirmed, the operator activates the electromagnetic energy source simultaneously with the time of PEA injection so that the PEA thickens or coagulates as it exits through the distal region of the microcatheter device. The first method 300a may be referred to as a sequential approach, and the second method 300b may be referred to as a simultaneous or simultaneous approach. Sequential approaches may typically be preferred when local blood flow is relatively low and / or when maximum penetration and conformability of the PEA to the treatment site is desired (such as in hypervascular tumors containing many capillaries). Simultaneous approaches, in which the PEA thickens or solidifies upon injection, reduce conformability of the PEA to various blood vessels, but may be preferred when there are critical downstream structures and the PEA must not excessively penetrate the treatment site, risking ischemia of critical structures (such as arteriovenous malformations).

[0087]

[0112] Attention is now directed to Figures 17, 22a, and 22b, which illustrate flowcharts of methods 300a, 300b, and 400 of endovascular embolization using the microcatheter devices described herein, according to non-limiting embodiments. The following description of methods 300a, 300b, and 400 will provide a further understanding of the devices described herein. However, it should be understood that methods 300a, 300b, and / or 400 can be modified and need not function exactly as described herein relative to each other, and such modifications are within the scope of the present embodiments. For example, methods 300a, 300b, and / or 400 need not be performed in the exact order shown, unless otherwise indicated. Similarly, various blocks may be performed in parallel rather than sequentially. Accordingly, elements of methods 300a, 300b, and 400 are referred to herein as "blocks" rather than "steps."

[0088]

[0113] Attention is now directed to Figure 22a. In block 301a, a microcatheter device, such as microcatheter device 100, is introduced into a target vascular anatomical structure, such as a target blood vessel (200, 203, 204, or 205). In block 302a, a PEA (109) is injected into the target vascular anatomical structure until a desired volume of the target vascular anatomical structure is filled. In block 303a, after injection, at least one electromagnetic wave is irradiated onto the PEA positioned in the target vascular anatomical structure at one or more coagulation wavelengths of the PEA.

[0089]

[0114] According to some embodiments, prior to emitting at least one electromagnetic wave at at least one coagulation wavelength, method 300a further includes determining whether there has been a malfunction of the microcatheter device (e.g., as described above). According to some embodiments, this determination block includes sensing at least one electromagnetic wave reflected back from the MPW.

[0090]

[0115] According to some embodiments, the method 301a further includes removing the microcatheter from the coagulated PEA and the target vascular anatomical structure after emitting at least one electromagnetic wave at a coagulation wavelength (Block 303a). According to some embodiments, removing the microcatheter includes detaching the microcatheter from the coagulated PEA. According to some embodiments, removing the microcatheter includes activating a photolysis mechanism.

[0091]

[0116] According to some embodiments, the method 300a further includes determining a coagulation state of the PEA. According to some embodiments, the determining is performed in real time or near real time (typically with a latency of less than 1 second) using emission of at least one electromagnetic wave to the PEA (Block 303a). According to some embodiments, the determining includes detecting at least one electromagnetic wave back-reflected from the PEA positioned in the target vascular anatomy.

[0092]

[0117] Method 300b (FIG. 22b) shares the act of block 301a (introducing a microcatheter into the target vascular anatomical structure). However, in block 302b, a PEA is injected into the target vascular anatomical structure while (simultaneously) emitting at least one electromagnetic wave of one or more coagulation wavelengths to coagulate the PEA in either the pre-cure region or the target vascular anatomical structure. Optionally, in block 303b, at least one electromagnetic wave is emitted to further coagulate the PEA disposed in the target vascular anatomical structure. Similar to method 300a, method 300b further includes determining a coagulation state of the PEA. For example, determining the coagulation state of the PEA can be performed in real time or near real time using emission of at least one electromagnetic wave to the PEA (blocks 302b and 303b). According to some embodiments, determining includes detecting at least one electromagnetic wave reflected back from the PEA disposed in the target vascular anatomical structure.

[0093]

[0118] Referring again to FIG. 17 and the individual blocks comprising method 400, typical use of a microcatheter typically involves guiding the microcatheter to the treatment site using a conventional microguidewire, which may be further guided by a larger-gauge support catheter (block 401). Once the treatment site is reached, a pre-embolization scan is typically performed using digital subtraction angiography (block 402). Digital subtraction angiography provides local vessel size / diameter, blood flow velocity, downstream vascular structures, and the presence or absence of critical structures. Based on prior knowledge of the anatomy and observations made during digital subtraction angiography, the operator first determines whether the PEA injection will be performed using a coordinated method or a sequential method, which alters the timing of electromagnetic energy emission relative to the timing of injection. Based on such factors affecting local fluid dynamics, the operator can then determine how much thickening or coagulation is required for the PEA to optimally fill the treatment site (target vascular anatomy) (block 403). The operator(s) then determine and select the correct electromagnetic force output for the desired viscosity (block 404). For the sequential approach, the selected EM force output is nominally 0. The operator injects PEA into the treatment site until it fills (block 405). The operator can use live fluoroscopy or additional digital subtraction angiography to confirm when the treatment site fills and repeat or continue the injection as needed (block 406). Note that at any point during the injection, the operator can choose to change the electromagnetic force output based on fluoroscopic feedback (blocks 407 and 408). Thus, the operator could initially begin the injection using a sequential approach (i.e., no electromagnetic energy emitted simultaneously during PEA injection), but then decide to allow electromagnetic energy emission midway through the injection to thicken or coagulate the injected PEA. This situation could occur, for example, if the operator observes excessive PEA washout due to high blood flow.Once the treatment site is filled with the desired amount of PEA, the operator decides whether to perform post-injection curing (block 409). If post-injection curing is deemed necessary, the operator can determine and select the correct electromagnetic power and duration. Post-injection curing is then performed by activating the electromagnetic energy source while maintaining the microcatheter position within the blood vessel such that the distal end of the microcatheter device is in physical contact with the deposited PEA, as confirmed by fluoroscopy (block 410). Note that several methods for monitoring PEA coagulation, such as evanescent wave detection with an integrated FBG, are described herein using several embodiments not shown in this flowchart. After coagulating the PEA, the operator can slowly retract the microcatheter device from the treatment site and sense whether there is resistance to removal, for example, due to adhesion between the coagulated PEA and the microcatheter tip (block 411). If the microcatheter device is difficult to remove (e.g., if the PEA is observed to detach when pulling on the microcatheter device), the operator can activate the detachment mechanism described herein (block 412). Once deemed safe by the operator, the microcatheter device is retracted and completely removed from the body, ending the treatment (block 413). Note that digital subtraction angiography can be performed at any point throughout the course of treatment if deemed necessary by the operator to further evaluate the vasculature at the treatment site and / or to confirm the integrity of the deposited PEA (not depicted in the flowchart). There may be several fault detection mechanisms that are monitored throughout the use of the microcatheter but are not mentioned in the flowchart. These include, but are not limited to, monitoring for catheter burst by syringe pump injection force sensing, and MPW breakage detection by detecting back-reflected light and its power, polarization state, and wavelength.

[0094]

[0119] Figures 18a and 18b illustrate a non-limiting embodiment of an integrated outlet relief valve (135) for controllably pressurizing the pre-cure region and restricting the flow of PEA (109). Such a mechanism can be employed to ensure consistent thickening / coagulation of the injected PEA (109) and limit the accidental release of uncured PEA (109), which could result in non-target embolization. Figure 18a illustrates a pre-cure region configuration of a microcatheter device with the outlet valve (135) in a closed state. The outlet relief valve is configured to open when a predetermined relief pressure (typically on the order of a tenth to several hundred PSI) is reached within the pre-cure region. With the outlet relief valve (135) closed, the flow of PEA (109) within the pre-cure region is stagnated, increasing the time a given volume of PEA (109) is exposed to the electromagnetic energy (102). Once sufficient thickening or solidification of the PEA (109) within the pre-cured region (103) is achieved, the cured PEA (111) can be released into the target vessel by simply applying enough pressure to open the outlet relief valve (135). The outlet relief valve can be closed again, and the process can be repeated multiple times over the course of treatment.

[0095]

[0120] 19 shows an exemplary configuration for diffusing the electromagnetic wave (104) through the working lumen (101). Diffusing the electromagnetic wave (104) is beneficial because it allows for more efficient absorption from the uncured PEA (109) over a controlled distance, compared to configurations with a forward firing scheme, regardless of electromagnetic energy absorption by the PEA. The working lumen (101) can be doped with scatterers, or materials selected to scatter the emitted electromagnetic wave (104) and act as an optical diffuser.

[0096]

[0121] Figures 20a and 20b show non-limiting configurations of the working lumen (104) in which the pre-cured region (103) is widened. Having a widened pre-cured region (137) effectively increases the cross-sectional area under a constant flow regime, such as when the injection is driven by an injection pump, and reduces the flow rate of the uncured PEA (109). The reduced flow rate increases the time the electromagnetic wave (104) has to be absorbed by the uncured PEA (109), thus enabling a faster coagulation rate. In scenarios where fully cured PEA (111) is being ejected from the exit port (113), the widened pre-cured region (137) is designed such that the cured PEA (111) has a desired shape (e.g., a wider diameter). Figure 20a shows a configuration in which the enlarged pre-cured region (137) is positioned concentrically with the working lumen (101) with the MPW (102) off-center, while Figure 20b shows the enlarged pre-cured region (137) having an inner diameter that is positioned concentrically with the MPW (102).

[0097]

[0122] Figures 21a and 21b show non-limiting configurations of the pre-cure region (103) with tapered walls (141) that, in contrast to Figures 20a and 20b, result in a smaller cross-sectional area at the tip. The tapered walls (141) effectively increase the flow resistance within the pre-cure region (103), pressurizing it and reducing the flow rate of uncured PEA (109) when the injection is driven under a constant pressure regime, such as when performing steady manual injection. Figure 21a shows a tapered pre-cure region (103) configuration with the MPW (102) off-center, while Figure 21b shows a tapered pre-cure region (103) with the MPW (102) positioned concentrically within the pre-cure region (103). Both tapered designs illustrated in Figures 20a-21b can help achieve more robust and consistent thickening / clotting and reduce the occurrence of accidental release of uncured PEA 109, which can result in non-target embolization. The choice of design can depend on factors including, but not limited to, whether the injection is volume-controlled or pressure-controlled.

[0098]

[0123] FIG. 23 shows an example of multiple MPWs housed within respective channels and terminated at various locations to allow for multiple beam directions, according to a non-limiting embodiment. In this particular example, one of the MPWs (102) terminates immediately proximal to the pre-curing region (103), and an additional MPW (142) extends to the tip of the microcatheter device. According to a non-limiting embodiment, either the MPW (102) or the MPW (142) can be activated individually, or both can be activated simultaneously. To highlight one use case, an operator may initially desire to perform an injection of PEA while simultaneously coagulating the PEA by emitting electromagnetic energy (104) through the MPW (102) positioned to efficiently irradiate the pre-curing region (103). Once the injection is complete and the treatment site is filled, the operator may further desire to strengthen the injected PEA by further performing post-injection curing by emitting electromagnetic energy (143) through the MPW (142) positioned to effectively irradiate the intravascular space near the tip of the microcatheter device.

[0099]

[0124] Those skilled in the art will recognize that many more alternative embodiments and modifications are possible, and that the above examples are merely illustrative of one or more embodiments. Accordingly, the scope should be limited only by the appended claims.

[0100]

[0125] interpretation It will also be understood that for purposes of this application, the terms "at least one of X, Y, and Z" or "one or more of X, Y, and Z" may be interpreted as X only, Y only, Z only, or any combination of two or more items X, Y, and Z (e.g., XYZ, XYY, YZ, ZZ).

[0101]

[0126] In this application, a component may be described as being "configured" or "enabled" to perform one or more functions. Generally, a component configured or enabled to perform a function is understood to be a component that is configured to perform a function, or enabled to perform a function, or suitable to perform a function, or adapted to perform a function, or operable to perform a function, or capable of performing a function.

[0102]

[0127] Furthermore, components in the present application may be described as being "operably connected," "operably coupled," etc. to other components. It is understood that such components are connected or coupled to one another to perform certain functions. It is also understood that "connected," "coupled," etc. as described in the present application include direct and indirect connections between components.

[0103]

[0128] References in this application to "one embodiment," "one embodiment," "one implementation," "one variation," etc. indicate that the described embodiment, implementation, or variation may include a particular aspect, feature, structure, or characteristic, but not all embodiments, implementations, or variations necessarily include that aspect, feature, structure, or characteristic. Moreover, such phrases may, but do not necessarily, refer to the same embodiment referenced elsewhere in this specification. Furthermore, when a particular aspect, feature, structure, or characteristic is described in connection with an embodiment, it is within the knowledge of one of ordinary skill in the art to affect or connect such module, aspect, feature, structure, or characteristic to other embodiments, whether or not explicitly described. In other words, any module, element, or feature can be combined with any other element or feature in different embodiments unless there is an obvious or inherent incompatibility or unless specifically excluded.

[0104]

[0129] It is further noted that the claims may be drafted to exclude any optional element. Accordingly, this statement is intended to serve as a predicate for use of exclusive terms such as "solely," "only," and the like in connection with the recitation of claim elements or the use of a "negative" limitation. The terms "preferably," "preferably," "preferably," "optionally," "may," and similar terms are used to indicate that a stated item, condition, or step is an optional (but not essential) feature of the invention.

[0105]

[0130] The singular forms "a," "an," and "the" include plural referents unless the context dictates otherwise. The term "and / or" means any one of the items, any combination of the items, or all of the items with which this term is associated. The phrase "one or more" is readily understood by those of ordinary skill in the art, particularly when read in the context of its use.

[0106]

[0131] The term "about" can refer to a variation of ±5%, ±10%, ±20%, or ±25% of the specified value. For example, "about 50" percent can have a variation of 45-55% in some embodiments. For integer ranges, the term "about" can include one or two integers greater than and / or less than the recited integers at either end of the range. Unless otherwise indicated herein, the term "about" is intended to include values ​​and ranges near the recited range that are equivalent in terms of the functionality of the composition or embodiment.

[0107]

[0132] As will be understood by those skilled in the art, for all purposes, particularly with respect to providing a written description, all ranges recited herein also encompass any and all possible subranges and combinations thereof, as well as the individual values, particularly integer values, that make up the range. The recited ranges include each specific value, integer, decimal, or identity within the range. Any recited range can be readily recognized as fully descriptive and allows for division of the same range into at least equal halves, thirds, quarters, fifths, or tenths. As a non-limiting example, each range described herein can be readily broken down into a lower third, middle third, upper third, etc.

[0108]

[0133] Also, as will be understood by those skilled in the art, all terms such as "up to," "at least," "greater than," "less than," "more than," "greater than or equal to," etc. are inclusive of the recited numbers, and such terms refer to ranges that can subsequently be broken down into subranges as described above. Similarly, all ratios set forth herein also include all subratios that fall within the broader ratio.

Claims

1. a working lumen having at least one exit port at a distal end of the working lumen, the working lumen configured for intravascular injection of a photoactivated embolic agent (PEA) into a target vessel through the at least one exit port; a mechanically protected waveguide (MPW) operably connected to the working lumen and configured to emit at least one electromagnetic wave through the at least one exit port for delivery to the target vessel.

2. the mechanically protected waveguide is at least partially embedded in the wall of the working lumen; co-extruded into the wall of the working lumen; at least partially separated from the working lumen by at least one barrier; coupled to the outer section of the working lumen; woven into the braided portion of the microcatheter; and / or The microcatheter device of claim 1 , wherein the microcatheter device is at least partially disposed within an enclosure separate from the working lumen.

3. 3. The microcatheter device of claim 1, further comprising a pre-hardening region within the microcatheter adjacent to the at least one exit port, the pre-hardening region configured to adjust the viscosity of the PEA prior to injection into the target vessel.

4. The microcatheter device of any one of claims 1 to 3, wherein the mechanically protected waveguide is a multimode optical fiber.

5. The microcatheter device of any one of claims 1 to 4, wherein the working lumen comprises a biocompatible material such as nylon, vestamid, pebax, or PTFE.

6. The microcatheter device of any one of claims 1 to 5, wherein the mechanically protected waveguide is configured to radiate the electromagnetic waves to the target vessel and / or the pre-hardened region.

7. The microcatheter device according to any one of claims 1 to 6, further comprising at least one beam forming element.

8. 8. The microcatheter device of claim 7, wherein the at least one beam-forming element comprises one or more optical components such as one or more of a lens, a diffuser, a filter, a reflector, and a mask.

9. 9. The microcatheter device of claim 7 or 8, wherein the at least one beam forming element is configured to provide at least one radially emitted light beam for delivery to the pre-cured region.

10. and further comprising at least one luminous beam, said at least one luminous beam comprising: a first beam directed at the target vessel; A microcatheter device according to any one of claims 7 to 9, further comprising: a second beam directed toward the pre-hardened region.

11. 11. The microcatheter device of claim 7, wherein the at least one beam forming element comprises a plurality of beam forming elements configured to provide a plurality of radial beams in a plurality of directions.

12. The microcatheter device of any one of claims 1 to 11, wherein the mechanically protected waveguide comprises an FBG.

13. 13. The microcatheter device of claim 12, wherein the FBG is tuned to a secondary wavelength and configured to back-reflect light having the second wavelength.

14. 12. The microcatheter device of claim 1, further comprising a fiber Bragg grating (FBG) element configured to selectively propagate light of a first wavelength in a first direction and light of a second wavelength in a second direction based on the frequency of the electromagnetic wave.

15. 15. The microcatheter device of claim 14, wherein the first direction is toward the at least one exit port and the second direction is a radial direction.

16. The microcatheter device of any one of claims 1 to 13, further comprising a detachment mechanism configured to detach the solidified PEA from the distal end of the microcatheter.

17. 17. The microcatheter device of claim 16, wherein the detachment of the PEA is induced by emitting electromagnetic waves via the MPW at a predetermined wavelength configured to photodegrade the crosslinked PEA.

18. 17. The microcatheter device of claim 16, wherein the detachment mechanism comprises a hydrophobic or superhydrophobic coating applied to an exterior surface of the distal end proximate the at least one exit port.

19. 19. The microcatheter device of any one of claims 1 to 18, wherein at least a portion of the distal end includes a reflective coating and / or reflective material configured to reflect excess light emitted radially outward in a radially inward direction.

20. The microcatheter device of any one of claims 2 to 19, further comprising an optical cavity operably connected to the pre-cured region.

21. 21. The microcatheter device of any one of claims 1 to 20, wherein the mechanically protected waveguide comprises a fiber optic element configured to direct at least one evanescent wave into physical contact with the PEA.

22. The microcatheter device according to any one of claims 1 to 21, wherein the optical refractive index can be detected by PEA.

23. 23. The microcatheter device of claim 22, further comprising a detection mechanism configured to detect a change in the optical refractive index of a medium surrounding the mechanically protected waveguide.

24. 24. The microcatheter device of claim 1, further comprising a power injector configured to supply fluid to the outlet port at a predetermined pressure and determine a change in backpressure of the fluid.

25. 25. The microcatheter device of claim 24, wherein the determination of changes in the fluid backpressure occurs in real time.

26. The microcatheter device of any one of claims 1 to 25, further comprising a detachable tip.

27. 27. The microcatheter device of claim 26, wherein the detachable tip is configured to dissolve within the target vessel over a predetermined amount of time.

28. 28. The microcatheter device of claim 27, wherein the detachable tip is biocompatible.

29. The microcatheter device of any one of claims 3 to 28, wherein the distal end of the MPW is free-floating within the pre-hardened region.

30. The microcatheter device of any one of claims 1 to 29, further comprising at least one valve mechanism.

31. The microcatheter device of any one of claims 1 to 30, wherein the distal end of the working lumen is tapered.

32. 32. The microcatheter device of claim 31, wherein the taper is sized to achieve a desired flow rate of the PEA in the target vessel.

33. The microcatheter device of any one of claims 1 to 32, further comprising a solid element inserted into the working lumen.

34. 34. The microcatheter device of any one of claims 3 to 33, further comprising at least one additive liner within the pre-cured region, the at least one additive liner configured to limit adhesion of the cured PEA to the inner and / or outer surface of the working lumen.

35. Introducing the microcatheter device according to any one of claims 1 to 28 into a target blood vessel; injecting a photoactivated embolic agent (PEA) into the target vessel until a desired volume of the target vessel is filled; After the injecting step or simultaneously with the injecting step, irradiating the PEA placed in the target blood vessel with electromagnetic waves at a coagulation wavelength; A method of endovascular embolization comprising:

36. 36. The method of claim 35, wherein the radiating step comprises radiating the electromagnetic waves at the pre-cured area.

37. 37. The method of claim 35 or 36, further comprising determining whether there has been a malfunction of the microcatheter device prior to emitting the electromagnetic waves at the coagulation wavelength.

38. 38. The method of claim 37, wherein determining whether there has been a malfunction of the microcatheter device comprises sensing at least one electromagnetic wave reflected back from the PEA.

39. 39. The method of any one of claims 35 to 38, further comprising the step of removing the microcatheter from the coagulated PEA and the target vessel after emitting the electromagnetic waves at the coagulation wavelength.

40. 40. The method of claim 39, wherein removing the microcatheter comprises detaching the microcatheter from the coagulated PEA.

41. 41. The method of any one of claims 35 to 40, further comprising determining the coagulation state of the PEA.

42. 42. The method of claim 41, wherein the determining step is performed in real time or near real time.

43. 43. The method of claim 41 or 42, wherein the determining step comprises detecting at least one electromagnetic wave reflected back from the PEA positioned within the target vessel.

44. 41. The method of claim 40, wherein removing the microcatheter comprises activating a photolysis mechanism.

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